bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative NMR study on the impact of point mutations on protein stability of Pseudomonas mendocina lipase
Authors: Sibille Nathalie , Favier Adrien , Azuaga Ana I. , Ganshaw Grant , Bott Richard , Bonvin Alexandre M.J.J. , Boelens Rolf , van Nuland Nico A.J. 
Published: July 2006

AbstractIn this work we compare the dynamics and conformational stability of Pseudomonas mendocina lipase enzyme and its F180P/S205G mutant that shows higher activity and stability for use in washing powders. Our NMR analyses indicate virtually identical structures but reveal remarkable differences in local dynamics, with striking correspondence between experimental data (i.e., 15N relaxation and H/D exchange rates) and data from Molecular Dynamics simulations. While overall the cores of both proteins are very rigid on the pico‐ to nanosecond timescale and are largely protected from H/D exchange, the two point mutations stabilize helices α1, α4, and α5 and locally destabilize the H‐bond network of the β‐sheet (β7–β9). In particular, it emerges that helix α5, undergoing some fast destabilizing motions (on the pico‐ to nanosecond timescale) in wild‐type lipase, is substantially rigidified by the mutation of Phe180 for a proline at its N terminus. This observation could be explained by the release of some penalizing strain, as proline does not require any “N‐capping” hydrogen bond acceptor in the i+3 position. The combined experimental and simulated data thus indicate that reduced molecular flexibility of the F180P/S205G mutant lipase underlies its increased stability, and thus reveals a correlation between microscopic dynamics and macroscopic thermodynamic properties. This could contribute to the observed altered enzyme activity, as may be inferred from recent studies linking enzyme kinetics to their local molecular dynamics.
Crystal structures of saposins A and C
Authors: Ahn Victoria E. , Leyko Paul , Alattia Jean‐René , Chen Lu , Privé Gilbert G. 
Published: July 2006

AbstractSaposins A and C are sphingolipid activator proteins required for the lysosomal breakdown of galactosylceramide and glucosylceramide, respectively. The saposins interact with lipids, leading to an enhanced accessibility of the lipid headgroups to their cognate hydrolases. We have determined the crystal structures of human saposins A and C to 2.0 Å and 2.4 Å, respectively, and both reveal the compact, monomeric saposin fold. We confirmed that these two proteins were monomeric in solution at pH 7.0 by analytical centrifugation. However, at pH 4.8, in the presence of the detergent C8E5, saposin A assembled into dimers, while saposin C formed trimers. Saposin B was dimeric under all conditions tested. The self‐association of the saposins is likely to be relevant to how these small proteins interact with lipids, membranes, and hydrolase enzymes.
Characterization of the native and fibrillar conformation of the human Nα‐acetyltransferase ARD1
Authors: Sánchez‐Puig Nuria , Fersht Alan R. 
Published: July 2006

AbstractARD1 (arrest‐defective protein 1), together with NAT1 (N‐acetyltransferase protein 1), is part of the major Nα‐acetyltransferase complex in eukaryotes responsible for α‐acetylation of proteins and peptides. Protein acetylation has been implicated in gene expression regulation and protein–protein interaction. We characterized the native folded and misfolded conformation of hARD1. Structural characterization of native hARD1 using size exclusion chromatography, circular dichroism, and fluorescence spectroscopy shows the protein consists of a compact globular region comprising two thirds of the protein and a flexible unstructured C terminus. In addition, hARD1 forms protofilaments under physiological conditions of pH and temperature, as judged by electron microscopy and staining with the dyes Congo red and thioflavin T. The process is accelerated by thermal denaturation and high protein concentrations. Limited proteolysis of aggregated hARD1 revealed a resistant fragment whose sequence matched a region contained within the acetyl transferase domain.
Circular dichroism spectroscopy of tertiary and quaternary conformations of human hemoglobin entrapped in wet silica gels
Authors: Ronda Luca , Bruno Stefano , Viappiani Cristiano , Abbruzzetti Stefania , Mozzarelli Andrea , Lowe Kenneth C. , Bettati Stefano 
Published: July 2006

AbstractThe relative contributions to changes in visible and near UV circular dichroism spectra of hemoglobin of heme ligation and tertiary and quaternary conformational transitions were separated by exploiting the slowing down of structural relaxations for proteins encapsulated in wet, nanoporous silica gels. Spectral signatures, previously assumed to be characteristic of T and R quaternary states, were demonstrated to be specific to different tertiary conformations. The results support the view that ligation and allosteric effectors can modulate the structural and functional properties of hemoglobin by regulating the equilibrium between the same tertiary species within both quaternary states.
Structure of the angiogenesis inhibitor ovalicin bound to its noncognate target, human Type 1 methionine aminopeptidase
Authors: Addlagatta Anthony , Matthews Brian W. 
Published: July 2006

AbstractMethionine aminopeptidases (MetAPs) remove the initiator methionine during protein biosynthesis. They exist in two isoforms, MetAP1 and MetAP2. The anti‐angiogenic compound fumagillin binds tightly to the Type 2 MetAPs but only weakly to Type 1. High‐affinity complexes of fumagillin and its relative ovalicin with Type 2 human MetAP have been reported. Here we describe the crystallographic structure of the low‐affinity complex between ovalicin and Type 1 human MetAP at 1.1 Å resolution. This provides the first opportunity to compare the structures of ovalicin or fumagillin bound to a Type 1 and a Type 2 MetAP. For both Type 1 and Type 2 human MetAPs the inhibitor makes a covalent adduct with a corresponding histidine. At the same time there are significant differences in the alignment of the inhibitors within the respective active sites. It has been argued that the lower affinity of ovalicin and fumagillin for the Type 1 MetAPs is due to the smaller size of their active sites relative to the Type 2 enzymes. Comparison with the uncomplexed structure of human Type 1 MetAP indicates that there is some truth to this. Several active site residues have to move “outward” by 0.5 Å or so to accommodate the inhibitor. Other residues move “inward.” There are, however, other factors that come into play. In particular, the side chain of His310 rotates by 134° into a different position where (together with Glu128 and Tyr195) it coordinates a metal ion not seen at this site in the native enzyme.
Food web structure and mercury transfer in two contrasting Ugandan highland crater lakes (East Africa)
Authors: Campbell L. , Hecky R. E. , Dixon D. G. , Chapman L. J. 
Published: July 2006

AbstractVolcanic crater lakes scattered throughout western Uganda are important local sources of water and fish. Two representative but contrasting crater lakes near the Kibale National Park were sampled in 2000; the hyper‐eutrophic Lake Saka, which is highly affected by agricultural practices, and the mesotrophic Lake Nkuruba that is still surrounded by intact forest. The food web structures in these two lakes were assessed using stable nitrogen (δ15N) and carbon (δ13C) isotope analyses, and the mercury (THg) transfer patterns were quantified. The δ15N results indicate that food webs in both lakes are abbreviated, with only one to two trophic levels from primary consumers. The Lake Saka biota had distinctively enriched δ13C values compared with those in Lake Nkuruba, which may be due to 12C‐limited phytoplankton blooms in this lake. In Lake Nkuruba, two introduced tilapiine species and the introduced guppy Poecilia reticulata fed predominantly upon invertebrates and decomposed terrestrial plant material. In Lake Saka, the introduced Nile perch Lates niloticus appeared to occupy the top trophic position, but stable isotope values of the endemic haplochromine cichlids exclude those as Nile perch prey items. THg was found to biomagnify through the food web, reaching highest concentrations in P. reticulata in Nkuruba, which tended to be higher than for L. niloticus in Saka, suggesting increased bioavailability of THg in Nkuruba. Maximum THg concentrations in fish never approached WHO recommended guidelines (200 ng g−1) designed to protect at‐risk groups.
Interaction risk with proton pump inhibitors in general practice: significant disagreement between different drug‐related information sources
Authors: Trifirò Gianluca , Corrao Salvatore , Alacqua Marianna , Moretti Salvatore , Tari Michele ,   UVEC group,, Caputi Achille P. , Arcoraci Vincenzo 
Published: July 2006

AimsTo compare information on drug–drug interactions (DDIs) reported on two standard drug‐related information sources (Summary of Product Characteristics and Drugdex system by Micromedex), by assessing the prevalence and predictors of potential DDI with proton pump inhibitors (PPIs) in general practice.MethodsFrom the ‘Caserta‐1’ Local Health‐Service database, 156 general practitioners (GPs) were recruited. From more than 180 000 individuals registered on their lists, we selected patients receiving co‐prescription of PPI and medications at interaction risk, according to the Italian Summary of Product Characteristics (SPC) of PPI and Drugdex information, during the year 2003. Thereafter, we carried out a regression analysis to identify the predictors of co‐prescription at interaction risk with PPI, on the basis of the two information sources. A number of analyses were performed to evaluate agreement on DDI information between the SPC of PPI and Drugdex.ResultsAccording to SPC and Drugdex, 324 (3.0%) and 958 (9.0%) patients, respectively, received co‐prescriptions of PPI and potentially interacting medications during the study period. PPI users’ age, type of medication and number of other drug prescriptions per month were independent predictors of receiving co‐prescriptions at interaction risk, when considering only Drugdex. With regard to potential DDIs with PPI, a significant disagreement (P < 0.0001) between the two drug‐related information sources, was shown through agreement analyses.ConclusionsPotential DDIs with PPI are a common health issue in general practice. Estimates of prevalence and predictors of potential DDIs with PPI significantly changes according to the drug information source being used.
Developing a global approach to the theory and practice of young people leaving state care
Authors: Pinkerton John 
Published: July 2006

ABSTRACTThis paper argues that globalization, although needing to be recognized as a highly complex phenomenon and a contested concept, should become part of the debate about improving the life chances of young people leaving care. Understanding globalization is essential to developing the effective strategies of engagement and resistance needed to address the social exclusion of these young people. Consideration is given to the considerable difficulties faced in moving from that general recognition to a sufficiently nuanced view of the impact of globalization on care leaving required as the basis for action. Existing approaches to promoting international exchange and understanding are discussed and a conceptual model presented as the means to start the work of identifying how the needs of care leavers are assessed and met in different national contexts. It is suggested that by identifying patterns of cross‐national similarities and differences, it will become possible to understand and to engage with the processes and institutions of globalization. An international theoretical and practice agenda are proposed appropriate to the present early stage in ensuring that globalization works for and not against the interests of care leavers.
Research Review: Young people leaving care
Authors: Stein Mike 
Published: July 2006

ABSTRACTThis paper reviews the international research on young people leaving care. Set in the context of a social exclusion framework, it explores young people’s accelerated and compressed transitions to adulthood, and discusses the development and classification of leaving care services in responding to their needs. It then considers the evidence from outcome studies and argues that adopting a resilience framework suggests that young people leaving care may fall into three groups: young people ‘moving on’, ‘survivors’ and ‘victims’. In concluding, it argues that these three pathways are associated with the quality of care young people receive, their transitions from care and the support they receive after care.
Nitrogen‐regulated effects of free‐air CO2 enrichment on methane emissions from paddy rice fields
Authors: ZHENG XUNHUA , ZHOU ZAIXING , WANG YUESI , ZHU JIANGUO , WANG YULONG , YUE JIN , SHI YI , KOBAYASHI KAZUHIKO , INUBUSHI KAZUYUKI , HUANG YAO , HAN SHENGHUI , XU ZHONGJUN , XIE BAOHUA , BUTTERBACH‐BAHL KLAUS , YANG LIANXIN 
Published: July 2006

AbstractUsing the free‐air CO2 enrichment (FACE) techniques, we carried out a 3‐year mono‐factorial experiment in temperate paddy rice fields of Japan (1998–2000) and a 3‐year multifactorial experiment in subtropical paddy rice fields in the Yangtze River delta in China (2001–2003), to investigate the methane (CH4) emissions in response to an elevated atmospheric CO2 concentration (200±40 mmol mol−1 higher than that in the ambient atmosphere). No significant effect of the elevated CO2 upon seasonal accumulative CH4 emissions was observed in the first rice season, but significant stimulatory effects (CH4 increase ranging from 38% to 188%, with a mean of 88%) were observed in the second and third rice seasons in the fields with or without organic matter addition. The stimulatory effects of the elevated CO2 upon seasonal accumulative CH4 emissions were negatively correlated with the addition rates of decomposable organic carbon (P<0.05), but positively with the rates of nitrogen fertilizers applied in either the current rice season (P<0.05) or the whole year (P<0.01). Six mechanisms were proposed to explain collectively the observations. Soil nitrogen availability was identified as an important regulator. The effect of soil nitrogen availability on the observed relation between elevated CO2 and CH4 emission can be explained by (a) modifying the C/N ratio of the plant residues formed in the previous growing season(s); (b) changing the inhibitory effect of high C/N ratio on plant residue decomposition in the current growing season; and (c) altering the stimulatory effects of CO2 enrichment upon plant growth, as well as nitrogen uptake in the current growing season. This study implies that the concurrent enrichment of reactive nitrogen in the global ecosystems may accelerate the increase of atmospheric methane by initiating a stimulatory effect of the ongoing dramatic atmospheric CO2 enrichment upon methane emissions from nitrogen‐poor paddy rice ecosystems and further amplifying the existing stimulatory effect in nitrogen‐rich paddy rice ecosystems.
Global warming and excess nitrogen may induce butterfly decline by microclimatic cooling
Authors: WALLISDEVRIES MICHIEL F. , VAN SWAAY CHRIS A.M. 
Published: July 2006

AbstractGlobal warming may explain the current poleward shift of species distributions. However, paradoxically, climatic warming can lead to microclimatic cooling in spring by advancing plant growth, an effect worsened by excess nitrogen. We suggest that spring‐developing but thermophilous organisms, such as butterflies hibernating as egg or larva, are particularly sensitive to the cooling of microclimates. Using published data on butterfly trends in distribution, we report a comparatively greater decline in egg–larva hibernators in European countries with oceanic climates and high nitrogen deposition, which supports this explanation. Furthermore, trends in abundance from a nationwide butterfly monitoring scheme reveal a 63% decrease over 13 years (1992–2004) for egg–larva hibernators in the Netherlands, contrasting with a nonsignificant trend in adult–pupa hibernators. This evidence supports the hypothesis that these environmental changes pose new threats to spring‐developing, thermophilous species. We underline the threat of climate change to biodiversity, as previously suggested on the basis of mobility, habitat fragmentation and evolutionary adaptation, but we here emphasize a different ecological axis of change in habitat quality.
Gametocytocidal activity in antimalarial drugs speeds the spread of drug resistance
Authors: Hastings Ian M. 
Published: July 2006

SummaryObjective  Antimalarial drugs kill the asexual parasites responsible for causing disease and some, notably chloroquine and the artemisinins, also kill the sexual transmission stages known as gametocytes. It is invariably argued by malariologists that gametocytocidal activity is beneficial because it reduces the rate at which resistance evolves by ‘reducing the transmission of resistant parasites’. This seems dubious from a population genetics perspective, where intuition would lead to the opposite conclusion. The objective was to reconcile these differing views.Methods  The effect of gametocytocidal drug activity was quantified mathematically and calibrated using field data.Results  It appears to be a robust result that gametocytocidal activity actually promotes the spread of resistance through a population; the underlying reason is that gametocytocidal activity reduces transmission of drug‐sensitive forms to a greater extent than the drug resistant, thereby increasing the spread of the latter. The increased rate of spread of resistance is quantified and appears to be small providing drug coverage is moderate or low.Conclusions  Citing reduced spread of resistance as a justification for deploying gametocytocidal antimalarials is unjustified; the deliberate use of a gametocytocidal antimalarial at high coverage to reduce transmission may ultimately be counterproductive through its rapid promotion of drug resistance.Keywords  Plasmodium falciparum malariadrug resistancecombination therapygametocytocidal
Patterns of species richness for vascular plants in China's nature reserves
Authors: Zhao Shuqing , Fang Jingyun 
Published: July 2006

ABSTRACTExplaining the heterogeneous distribution of biodiversity across the Earth has long been a challenge to ecologists and biogeographers. Here, we document the patterns of plant species richness for different taxonomic groups in China's nature reserves, and discuss their possible explanations at national and regional scales, using vascular plant richness data coupled with information on climate and topographical variables. We found that water deficit, energy and elevation range (a surrogate of habitat heterogeneity) represent the primary explanations for variation in plant species richness of the nature reserves across China. There are consistent relationships between species richness and climate and habitat heterogeneity for different taxonomic vascular plant groups at the national scale. Habitat heterogeneity is strongly associated with plant richness in all regions, whereas climatic constraints to plant diversity vary regionally. In the regions where energy is abundant or water is scarce, plant richness patterns were determined by water and habitat heterogeneity, whereas in the region with low energy inputs, water interacting with energy, and habitat heterogeneity determined its species richness pattern. Our results also suggest that energy variables alone do not represent the primary predictor of plant richness.
Museum collections, species distributions, and rarefaction
Authors: Solow Andrew R. , Roberts David L. 
Published: July 2006

ABSTRACTBiological specimens in museums and herbaria are sometimes used to compare the geographical distribution of different species. In doing so, it is necessary to account for differences in the numbers of specimens. We show how rarefaction can be used for this purpose. Rarefaction is a simple mathematical method originally designed to compare species richness in communities that differed in the number of sampled individuals. We present an example involving two Phragmipedium orchid species. In this case, rarefaction suggests that the apparent difference in range can be explained by the difference in the numbers of specimens.
Head and neck blocks in children: an anatomical and procedural review
Authors: SURESH SANTHANAM , VORONOV POLINA 
Published: July 2006

SummaryChildren undergo a variety of neurosurgical, otorhinolaryngology and plastic surgery procedures to the head and neck. Although opioids are utilized for pain control, they are associated with adverse side effects including postoperative nausea and vomiting, respiratory depression, somnolence and itching. The utilization of peripheral nerve blocks provides analgesia while reducing the need for opioids. This review will provide a summary of a variety of commonly used head and neck nerve blocks in children with a brief anatomical and technical summary.
Ultrasound‐guided umbilical nerve block in children: a brief description of a new approach
Authors: DE JOSE MARIA BELEN , GÖTZENS VICTOR , MABROK MAGED 
Published: July 2006

SummaryBackground : The most popular peripheral nerve blocks used in umbilical hernia repair are rectus sheath block and paraumbilical block. However, multiple anatomic variations have been described and some complications may occur. Ultrasonographic guidance of peripheral nerve blocks has reduced the number of complications and improved the quality of blocks. This case series describes a new ultrasound‐guided puncture technique of the 10th intercostal nerve in pediatric umbilical surgery.Methods : Ten children (age range: 2–5 years) scheduled for umbilical hernia repair were included. Following the induction of general anesthesia, the ultrasonographic anatomy of the umbilical region was studied with a 10‐MHz linear probe. An ultrasound‐guided peripheral block of the 10th intercostal nerve in the lateral edge of both rectus abdominis muscles (RMs) was performed (total of 20 punctures). Surgical conditions, intraoperative hemodynamic parameters, and postoperative analgesia by means of the modified CHEOPS scale were evaluated.Results : Umbilical anatomy was clearly identified by ultrasound in all cases. The epigastric vessels were identified – above the umbilicus – within the depth of the muscular mass of the RM. The spread of local anesthetic was ultrasound‐controlled in all cases. However, the intercostal nerve could not be visualized. All blocks were effective during the surgery. Postoperative analgesia was only required in two children in the second postoperative hour. There were no complications.Conclusions : Ultrasound guidance enables performance of an effective umbilical block in the lateral edge of RM. Further studies should be carried on to visualize the intercostal nerve and to compare this technique with the classical ones.