bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noncanonical interactions between serum transferrin and transferrin receptor evaluated with electrospray ionization mass spectrometry
Authors: Leverence Rachael , Mason Anne B. , Kaltashov Igor A. 
Published: April 2010

The primary route of iron acquisition in vertebrates is the transferrin receptor (TfR) mediated endocytotic pathway, which provides cellular entry to the metal transporter serum transferrin (Tf). Despite extensive research efforts, complete understanding of Tf-TfR interaction mechanism is still lacking owing to the complexity of this system. Electrospray ionization mass spectrometry (ESI MS) is used in this study to monitor the protein/receptor interaction and demonstrate the ability of metal-free Tf to associate with TfR at neutral pH. A set of Tf variants is used in a series of competition and displacement experiments to bracket TfR affinity of apo-Tf at neutral pH (0.2–0.6 μM). Consistent with current models of endosomal iron release from Tf, acidification of the protein solution results in a dramatic change of binding preferences, with apo-Tf becoming a preferred receptor binder. Contrary to the current models implying that the apo-Tf/TfR complex dissociates almost immediately upon exposure to the neutral environment at the cell surface, our data indicate that this complex remains intact. Iron-loaded Tf displaces apo-Tf from TfR, making it available for the next cycle of iron binding, transport and delivery to tissues. However, apo-Tf may still interfere with the cellular uptake of engineered Tf molecules whose TfR affinity is affected by various modifications (e.g., conjugation to cytotoxic molecules). This work also highlights the great potential of ESI MS as a tool capable of providing precise details of complex protein-receptor interactions under conditions that closely mimic the environment in which these encounters occur in physiological systems.
Atrial fibrillation in heart failure is associated with an increased risk of death only in patients with ischaemic heart disease
Authors: Raunsø Jakob , Pedersen Ole Dyg , Dominguez Helena , Hansen Morten Lock , Møller Jacob Eifer , Kjærgaard Jesper , Hassager Christian , Torp‐Pedersen Christian , Køber Lars ,   on behalf of the EchoCardiography and Heart Outcome Study (ECHOS) investigators
Published: April 2010

AimsThe prognostic importance of atrial fibrillation (AF) in heart failure (HF) populations is controversial and may depend on patient selection. In the present study, we investigated the prognostic impact of AF in a large population with HF of various aetiologies.Methods and resultsWe included 2881 patients admitted to hospital with symptoms of worsening HF over a 4‐year period (2001–2004), all patients were participants in the Echocardiography and Heart Outcome Study (ECHOS). Patients were followed for up to 7 years for all‐cause mortality stratified according to heart rhythm (sinus rhythm, paroxysmal, or chronic AF) and according to the presence of ischaemic heart disease (IHD). During follow‐up, 1934 patients (67%) died. In HF patients with a history of IHD, chronic AF was associated with an increased risk of death [hazard ratio (HR) 1.44; 95% confidence interval (CI): 1.18–1.77; P < 0.001). In contrast, in patients without IHD, chronic AF was not associated with an increased mortality risk (HR 0.88; 95% CI: 0.71–1.09; P = 0.25). There was significant interaction between the aetiology of HF and the prognostic importance of chronic AF (Pinteraction = 0.003).ConclusionIn patients with HF, AF is associated with an increased risk of death only in patients with underlying IHD.
A simulated archival tagging programme for albacore (Thunnus alalunga) in the Northeast Atlantic, including an analysis of factors affecting tag recovery
Authors: Cosgrove Ronan , Arregi Igor , Brophy Deirdre , Arrizabalaga Haritz , Ortiz de Zarate Victoria , Griffin Nigel 
Published: April 2010

Abstract
Cosgrove, R., Arregi, I., Brophy, D., Arrizabalaga, H., Ortiz de Zarate, V., and Griffin, N. 2010. A simulated archival tagging programme for albacore (Thunnus alalunga) in the Northeast Atlantic, including an analysis of factors affecting tag recovery. – ICES Journal of Marine Science, 67: 1216–1221. An archival tagging programme in the Northeast Atlantic would assist in testing the hypothesis that subpopulations of juvenile albacore exist within the region and provide important information on fish behaviour in relation to environmental variables. No information was available, however, on the ability of juvenile albacore to carry costly implanted archival tags, or on rates of tag recovery. A simulated archival tagging study on albacore using simulated or “dummy” archival tags was therefore carried out in the Bay of Biscay from 2005 to 2008. In all, 353 fish were tagged and released, and 9 fish (2.55%) were recaptured. A comprehensive ICCAT database of conventionally tagged fish in the Northeast Atlantic was also analysed to determine whether optimal conditions at the time of release could be identified and used to boost recovery rates in future tagging programmes. A binary logistic regression model using a response variable with two possible outcomes, recaptured or not recaptured, was developed, then tested on two datasets to deal with association between variables. Effort and fishing gear were significant in the first dataset, and length class and fishing gear in the second. The last two factors can be manipulated, and a recapture rate of >5% was predicted if derived optimal tagging conditions are followed in future tagging programmes.
Antibodies to CBir1 Are Associated With Glycogen Storage Disease Type Ib
Authors: Davis Michael K , Valentine John F , Weinstein David A , Polyak Steven 
Published: April 2010

ABSTRACTObjectives:Glycogen storage disease (GSD) type Ib is a congenital disorder of glycogen metabolism that is associated with neutropenia, neutrophil and monocyte dysfunction, and an inflammatory bowel disease (IBD) that mimics a Crohn disease phenotype. The enteric microflora is implicated in the pathogenesis of IBD; however, its role in the development of GSD‐associated IBD is unknown. Antibody reactivity to Saccharomyces cerevisiae antibodies (ASCA), Escherichia coli outer membrane porin C (anti‐OmpC), and bacterial flagellin (anti‐CBir1) have been associated with Crohn disease in the general population, but they have an undetermined association in children and adults with GSD‐Ib. Our goal was to examine the association of ASCA, anti‐OmpC, and anti‐CBir1 with the clinical features of GSD‐Ib enterocolitis.Patients and Methods:A retrospective review identified 19 patients with GSD‐Ib with or without a known diagnosis of enterocolitis. Radiographic, endoscopic, and serologic data were collected and assays for ASCA, anti‐OmpC, and anti‐CBir1 obtained.Results:Seven patients had combined radiographic, endoscopic, and histologic evidence of intestinal inflammation; the majority had ileocolonic involvement. Seventeen of 19 (89%) patients had elevated anti‐CBir1 levels (6/7 in the IBD group and 11/12 in the no clinical evidence of IBD group). Thirteen of 19 (68%) had elevated anti‐OmpC levels (5/7 in the IBD group and 8/12 in the no clinical evidence of IBD group). Eleven of 19 (58%) patients had elevated ASCA IgA levels (4/7 in the IBD group and 7/12 in the no clinical evidence of IBD group).Conclusions:Nearly all of the patients with GSD‐Ib had elevated anti‐CBir1 levels. The antibody did not differentiate those with and without a diagnosis of GSD‐Ib‐associated IBD. Seroreactivity to flagellin may represent immune dysfunction rather than active enterocolitis in this patient population. Long‐term follow‐up of the group without known IBD is required to determine whether these antibodies can predict intestinal inflammation.
Gastric Emptying Time of Oral Contrast Material in Children and Adolescents Undergoing Abdominal Computed Tomography
Authors: Berger‐Achituv Sivan , Zissin Rivka , Shenkman Ze'ev , Gutermacher Michael , Erez Ilan 
Published: April 2010

ABSTRACTObjectives:Considering the hazards of pulmonary aspiration of oral contrast material (OCM) during general anesthesia, we investigated the gastric emptying time (GET) of OCM in children and adolescents undergoing abdominal computed tomography (CT).Patients and Methods:Included in the study were 101 consecutive patients ages 3.1 to 17.9 years (mean age 12.2 ± 3.3 years), who underwent contrast‐enhanced abdominal CT for suspected acute appendicitis (n = 90), abdominal trauma (n = 10), or suspected ileus (n = 1). Oral iodinated ioxithalamate was given for bowel opacification. Background data (age, sex, weight, chronic diseases, and medication intake), time of initiation and completion of OCM, and time of CT scanning were recorded. To estimate the GET of OCM, CT images were reviewed to examine whether the stomach was empty or full of OCM at the time of imaging.Results:The Kaplan‐Meier curve showed that 75% of the patients had OCM in the stomach 48 ± 5.2 minutes after its completion, 50% after 74 ± 7.9 minutes, and 25% after 135 ± 32.5 minutes; 1 patient still had OCM after 162 minutes. Except for the length of time taken to drink the contrast material (≤90 minutes was associated with slower empting of the stomach; log rank, P = 0.03), GET of OCM was not correlated with sex (P = 0.16), age (P = 0.15), weight (P = 0.13), or type of diagnosis (P = 0.41).Conclusions:Given the variability of GET of OCM and if clinically feasible, we advocate waiting at least 3 hours between completion of OCM ingestion and general anesthesia induction.
Iron, Zinc, and Copper Nutritional Status in Children Infected With Helicobacter pylori
Authors: Janjetic Mariana A , Goldman Cinthia G , Balcarce Norma E , Rua Eduardo Cueto , González Andrea Beltrán , Fuda Julián A , Meseri Emiliano I , Torti Horacio E , Barrado Julieta , Zubillaga Marcela B , López Laura B , Boccio José R 
Published: April 2010

ABSTRACTObjective:Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children.Patients and Methods:A cross‐sectional study was carried out in 395 children (4–16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the 13C‐urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors.Results:Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori–positive and 8.9% and 11.0% of the H pylori–negative children, respectively. There was no association between H pylori infection and anemia (odds ratio = 1.54 [95% confidence interval [CI] 0.73%–3.24%]) or ID (odds ratio = 1.35 [95% CI 0.67–2.70]). Crude β coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori–infected children had an increase of 9.74 μg/dL (95% CI 2.12–17.37 μg/dL) in copper concentrations.Conclusions:This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.
Postoperative Outcome of Colectomy for Pediatric Patients With Ulcerative Colitis
Authors: Patton Dana , Gupta Neera , Wojcicki Janet M , Garnett Elizabeth A , Nobuhara Kerilyn , Heyman Melvin B 
Published: April 2010

ABSTRACTBackground:Few studies have reported on the surgical outcomes of colectomy in pediatric patients with ulcerative colitis (UC).Patients and Methods:We conducted a retrospective chart review of all pediatric patients diagnosed with UC who underwent colectomy at UCSF between 1980 and 2005 to identify early (within 30 days) and later complications of surgery.Results:Complete medical records were available for 31 patients [12.4 ± 3.3 (range 6–19) years] with UC who underwent colectomy at UCSF Children's Hospital. Total colectomy with ileal pouch anal anastomosis (IPAA) was performed in 21 of the 31 patients (12 without diverting ileostomy). Five of the 31 patients had an initial colectomy with IPAA and J‐pouch performed later; 4 had an initial subtotal colectomy for urgent indications. Only one of 31 had IPAA with S‐pouch. The median number of early postoperative complications was 1.0; 4 required additional surgery to treat complications. The most common early complications were small intestinal obstruction in 6 (19%) and wound infection in 4 (13%). Preoperative medications included corticosteroids in 25 (81%), 6‐mercaptopurine/azathioprine in 10 (32%), and 5‐aminosalicylates in 19 (61%). Medication exposure was not related to postoperative complications. Late complications included pouchitis in 12 (39%), anastomotic, anal, or rectal strictures in 5 (16%), and fistulas in 5 (16%); 1 (3%) was subsequently diagnosed as having Crohn disease.Conclusions:Postcolectomy morbidity is common among pediatric patients with UC. Preoperative medications were not associated with postoperative complications. Investigations to determine preoperative factors affecting surgical outcomes and long‐term satisfaction following this surgery in a large pediatric cohort are needed.
Detection and correction of underassigned rotational symmetry prior to structure deposition
Authors: Poon Billy K. , Grosse-Kunstleve Ralf W. , Zwart Peter H. , Sauter Nicholas K. 
Published: April 2010

Up to 2% of X-ray structures in the Protein Data Bank (PDB) potentially fit into a higher symmetry space group. Redundant protein chains in these structures can be made compatible with exact crystallographic symmetry with minimal atomic movements that are smaller than the expected range of coordinate uncertainty. The incidence of problem cases is somewhat difficult to define precisely, as there is no clear line between underassigned symmetry, in which the subunit differences are unsupported by the data, and pseudosymmetry, in which the subunit differences rest on small but significant intensity differences in the diffraction pattern. To help catch symmetry-assignment problems in the future, it is useful to add a validation step that operates on the refined coordinates just prior to structure deposition. If redundant symmetry-related chains can be removed at this stage, the resulting model (in a higher symmetry space group) can readily serve as an isomorphous replacement starting point for re-refinement using re-indexed and re-integrated raw data. These ideas are implemented in new software tools available at http://cci.lbl.gov/labelit.
Macromolecular crystal data phased by negative-stained electron-microscopy reconstructions
Authors: Trapani Stefano , Schoehn Guy , Navaza Jorge , Abergel Chantal 
Published: April 2010

The combination of transmission electron microscopy with X-ray diffraction data is usually limited to relatively large particles. Here, the approach is continued one step further by utilizing negative staining, a technique that is of wider applicability than cryo-electron microscopy, to produce models of medium-size proteins suitable for molecular replacement. The technique was used to solve the crystal structure of the dodecameric type II dehydroquinase enzyme fromCandida albicans(∼190 kDa) and that of the orthologousStreptomyces coelicolorprotein.
Structure of dehaloperoxidase B at 1.58 Å resolution and structural characterization of the AB dimer fromAmphitrite ornata
Authors: de Serrano Vesna , D'Antonio Jennifer , Franzen Stefan , Ghiladi Reza A. 
Published: April 2010

As members of the globin superfamily, dehaloperoxidase (DHP) isoenzymes A and B from the marine annelidAmphitrite ornatapossess hemoglobin function, but they also exhibit a biologically relevant peroxidase activity that is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. Here, a comprehensive structural study of recombinant DHP B, both by itself and cocrystallized with isoenzyme A, using X-ray diffraction is presented. The structure of DHP B refined to 1.58 Å resolution exhibits the same distal histidine (His55) conformational flexibility as that observed in isoenzyme A, as well as additional changes to the distal and proximal hydrogen-bonding networks. Furthermore, preliminary characterization of the DHP AB heterodimer is presented, which exhibits differences in the AB interface that are not observed in the A-only or B-only homodimers. These structural investigations of DHP B provide insights that may relate to the mechanistic details of the H2O2-dependent oxidative dehalogenation reaction catalyzed by dehaloperoxidase, present a clearer description of the function of specific residues in DHP at the molecular level and lead to a better understanding of the paradigms of globin structure–function relationships.
Structural analysis of mycobacterial branched-chain aminotransferase: implications for inhibitor design
Authors: Castell Alina , Mille Christian , Unge Torsten 
Published: April 2010

The branched-chain aminotransferase (BCAT) ofMycobacterium tuberculosishas been characterized as being essential to the survival of the bacterium. The enzyme is pyridoxal 5′-phosphate-dependent and belongs to the aminotransferase IIIa subfamily, to which the human BCATs also belong. The overall sequence similarity is high within the subfamily and the sequence identity among the active-site residues is high. In order to identify structurally unique features ofM. tuberculosisBCAT, X-ray structural and functional analyses of the closely related BCAT fromM. smegmatiswere carried out. The crystal structures include the apo form at 2.2 Å resolution and a 1.9 Å structure of the holo form cocrystallized with the inhibitorO-benzylhydroxylamine (Obe). The analyses highlighted the active-site residues Tyr209 and Gly243 as being structurally unique characteristics of the mycobacterial BCATs relative to the human BCATs. The inhibitory activities of Obe and ammonium sulfate were verified in an inhibition assay. Modelling of the inhibitor Obe in the substrate pocket indicated potential for the design of a mycobacterial-specific inhibitor.
Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plantColeus blumeiBenth.
Authors: Janiak Verena , Petersen Maike , Zentgraf Matthias , Klebe Gerhard , Heine Andreas 
Published: April 2010

Hydroxy(phenyl)pyruvate reductase [H(P)PR] belongs to the family of D-isomer-specific 2-hydroxyacid dehydrogenases and catalyzes the reduction of hydroxyphenylpyruvates as well as hydroxypyruvate and pyruvate to the corresponding lactates. Other non-aromatic substrates are also accepted. NADPH is the preferred cosubstrate. The crystal structure of the enzyme fromColeus blumei(Lamiaceae) has been determined at 1.47 Å resolution. In addition to the apoenzyme, the structure of a complex with NADP+was determined at a resolution of 2.2 Å. H(P)PR is a dimer with a molecular mass of 34 113 Da per subunit. The structure is similar to those of other members of the enzyme family and consists of two domains separated by a deep catalytic cleft. To gain insights into substrate binding, several compounds were docked into the cosubstrate complex structure using the programAutoDock. The results show two possible binding modes with similar docking energy. However, only binding modeAprovides the necessary environment in the active centre for hydride and proton transfer during reduction, leading to the formation of the (R)-enantiomer of lactate and/or hydroxyphenyllactate.
Hereditary causes of kidney tumours
Authors: Axwijk Priscilla Helene , Kluijt Irma , De Jong Daphne , Gille Hans , Teertstra Jelle , Horenblas Simon 
Published: April 2010

Eur J Clin Invest 2010; 40 (5): 433–439AbstractBackground  In most cases of renal cell carcinoma there is no family history of renal cancer and no hereditary cause of the disease. Hereditary renal cancer accounts for about 2–4% of cases. Recognition of this subgroup by clinicians is important because of the possibility of severe medical consequences for patients and their relatives.Materials and methods  We review the latest data about different genetic conditions characterized by an increased risk of developing renal cancer and we formulate tools to recognize high‐risk families.Results  In general, a positive family history, young age at diagnosis of renal cancer, multiple and/or bilateral renal tumours and combined occurrence of different histological types of renal tumours should raise suspicion of a hereditary renal tumour syndrome. In addition, the presence of specific extrarenal symptoms in patients could assist in differentiating between tumour syndromes.Conclusions  A detailed medical and family history, along with physical examination are key factors to diagnose hereditary renal cancer syndromes. When a genetic predisposition for renal cancer is suspected, referral to a Family Cancer Clinic is warranted to initiate genetic examination and counselling on preventive options.
Applying systematic conservation planning principles to palustrine and inland saline wetlands of New Zealand
Authors: AUSSEIL ANNE‐GAELLE E. , LINDSAY CHADDERTON W. , GERBEAUX PHILIPPE , THEO STEPHENS R.T. , LEATHWICK JOHN R. 
Published: April 2010

Summary1. Previous attempts to identify nationally important wetlands for biodiversity in New Zealand were based on expert panel opinions because quantitative approaches were hampered by a lack of data. We apply principles of systematic conservation planning to remote sensing data within a geographical information system (GIS) to identify nationally important palustrine and inland saline wetlands.2. A catchment‐based classification was used to divide New Zealand into 29 biogeographic units. To meet representation goals, all wetland classes need to be protected within each unit.3. We mapped current and historic wetlands down to a minimum size of 0.5 ha. Over 7000 current wetlands were mapped using standardised satellite imagery and a collection of point or polygon data. Historical extent was estimated from soil information refined using a digital elevation model. The current extent of wetlands is 10% of the historic extent, which is consistent with previous estimates.4. A classification was produced using fuzzy expert rules within a GIS to identify seven wetland classes: bog, fen, swamp, marsh, pakihi/gumland, seepage and inland saline. Swamps and pakihi/gumland are the most common, but the former has sustained the greatest reduction in area with only 6% of its historical extent remaining. A preliminary field assessment of classification accuracy in the Otago region found only 60% agreement, mainly because of the misclassification of marshes into swamps.5. Wetland condition was estimated using six measures of human disturbance (natural cover, human‐made impervious cover, introduced fish, woody weeds, artificial drainage and nitrate leaching risk) applied at three spatial scales: the wetland’s catchment, a 30‐m buffer around the wetland and the wetland itself. Measures were transformed and combined into a single condition index. More than 60% of remaining wetlands had condition indices <0.5, probably indicating moderate to severe degradation and loss of native biodiversity.6. Sites were ranked within each biogeographic unit using the wetland classification to ensure a representative set of wetland diversity. Rankings were determined by combining condition and complementarity to calculate conservation effectiveness that was then weighted by irreplaceability. Highest ranked sites in each biogeographic unit were usually the largest remaining wetlands that contained multiple wetland classes. This reflects their potential to protect a diverse range of wetland classes and a high proportion of the remaining habitat.