bluuebunny/crossref_metadata_2025 huggingface dataset:
Niemann–Pick type C 1 function requires lumenal domain residues that mediate cholesterol-dependent NPC2 binding
Authors: Deffieu Maika S. , Pfeffer Suzanne R.
Published: November 2011

Niemann–Pick type C1 (NPC1) protein is needed for cellular utilization of low-density lipoprotein-derived cholesterol that has been delivered to lysosomes. The protein has 13 transmembrane domains, three large lumenal domains, and a cytoplasmic tail. NPC1’s lumenally oriented, N-terminal domain binds cholesterol and has been proposed to receive cholesterol from NPC2 protein as part of the process by which cholesterol is exported from lysosomes into the cytosol. Using surface plasmon resonance and affinity chromatography, we show here that the second lumenal domain of NPC1 binds directly to NPC2 protein. For these experiments, a soluble NPC1 lumenal domain 2 was engineered by replacing adjacent transmembrane domains with antiparallel coiled-coil sequences. Interaction of NPC2 with NPC1 lumenal domain 2 is only detected at acidic pH, conditions that are optimal for cholesterol binding to NPC2 and transfer to NPC1; the pH is also appropriate for the acidic environment where binding would take place. Binding to NPC1 domain 2 requires the presence of cholesterol on NPC2 protein, a finding that supports directional transfer of cholesterol from NPC2 onto NPC1’s N-terminal domain. Finally, human disease-causing mutations in NPC1 domain 2 decrease NPC2 binding, suggesting that NPC2 binding is necessary for NPC1 function in humans. These data support a model in which NPC1 domain 2 holds NPC2 in position to facilitate directional cholesterol transfer from NPC2 onto NPC1 protein for export from lysosomes.
Copy number variation detection in whole-genome sequencing data using the Bayesian information criterion
Authors: Xi Ruibin , Hadjipanayis Angela G. , Luquette Lovelace J. , Kim Tae-Min , Lee Eunjung , Zhang Jianhua , Johnson Mark D. , Muzny Donna M. , Wheeler David A. , Gibbs Richard A. , Kucherlapati Raju , Park Peter J.
Published: November 2011

DNA copy number variations (CNVs) play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders. Array comparative genomic hybridization has been used widely to identify CNVs genome wide, but the next-generation sequencing technology provides an opportunity to characterize CNVs genome wide with unprecedented resolution. In this study, we developed an algorithm to detect CNVs from whole-genome sequencing data and applied it to a newly sequenced glioblastoma genome with a matched control. This read-depth algorithm, called BIC-seq, can accurately and efficiently identify CNVs via minimizing the Bayesian information criterion. Using BIC-seq, we identified hundreds of CNVs as small as 40 bp in the cancer genome sequenced at 10× coverage, whereas we could only detect large CNVs (> 15 kb) in the array comparative genomic hybridization profiles for the same genome. Eighty percent (14/16) of the small variants tested (110 bp to 14 kb) were experimentally validated by quantitative PCR, demonstrating high sensitivity and true positive rate of the algorithm. We also extended the algorithm to detect recurrent CNVs in multiple samples as well as deriving error bars for breakpoints using a Gibbs sampling approach. We propose this statistical approach as a principled yet practical and efficient method to estimate CNVs in whole-genome sequencing data.
Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers
Authors: Morris Luc G. T. , Taylor Barry S. , Bivona Trever G. , Gong Yongxing , Eng Stephanie , Brennan Cameron W. , Kaufman Andrew , Kastenhuber Edward R. , Banuchi Victoria E. , Singh Bhuvanesh , Heguy Adriana , Viale Agnes , Mellinghoff Ingo K. , Huse Jason , Ganly Ian , Chan Timothy A.
Published: November 2011

Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma. Targeted agents such as cetuximab and erlotinib are currently used in patients with head and neck squamous cell carcinoma, but, in this disease, the genomic alterations that cause pathway activation and determine response to pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components, and high-resolution genomic copy number assessment. Mutations were found in
PIK3CA
(6%), but no point mutations were observed in other pathway genes such as
PTEN and EGFR
. In contrast, we observed frequent copy number alterations of genes in the pathway, including
PIK3CA
,
EGFR
, protein tyrosine phosphatase receptor S (
PTPRS
), and
RICTOR
. In total, activating genetic pathway alterations were identified in 74% of head and neck tumors. Importantly, intragenic microdeletions of the EGFR phosphatase
PTPRS
were frequent (26%), identifying this gene as a target of 19p13 loss. PTPRS loss promoted EGFR/PI3K pathway activation, modulated resistance to EGFR inhibition, and strongly determined survival in lung cancer patients with activating EGFR mutations. These findings have important implications for our understanding of head and neck cancer tumorigenesis and for the use of targeted agents for this malignancy.
IFN-α and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells
Authors: Le Buanec Hélène , Gougeon Marie-Lise , Mathian Alexis , Lebon Pierre , Dupont Jean-Michel , Peltre Gabriel , Hemon Patrice , Schmid Michel , Bizzini Bernard , Künding Thomas , Burny Arsène , Bensussan Armand , Amoura Zahir , Gallo Robert C. , Zagury Daniel
Published: November 2011

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10–secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-α. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-α and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti–IFN-α Ab immunotherapy in lupus patients.
Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme
Authors: Silva Rafael G. , Murkin Andrew S. , Schramm Vern L.
Published: November 2011

Contributions of fast (femtosecond) dynamic motion to barrier crossing at enzyme catalytic sites is in dispute. Human purine nucleoside phosphorylase (PNP) forms a ribocation-like transition state in the phosphorolysis of purine nucleosides and fast protein motions have been proposed to participate in barrier crossing. In the present study,
13
C-,
15
N-,
2
H-labeled human PNP (heavy PNP) was expressed, purified to homogeneity, and shown to exhibit a 9.9% increase in molecular mass relative to its unlabeled counterpart (light PNP). Kinetic isotope effects and steady-state kinetic parameters were indistinguishable for both enzymes, indicating that transition-state structure, equilibrium binding steps, and the rate of product release were not affected by increased protein mass. Single-turnover rate constants were slowed for heavy PNP, demonstrating reduced probability of chemical barrier crossing from enzyme-bound substrates to enzyme-bound products. In a second, independent method to probe barrier crossing, heavy PNP exhibited decreased forward commitment factors, also revealing mass-dependent decreased probability for barrier crossing. Increased atomic mass in human PNP alters bond vibrational modes on the femtosecond time scale and reduces on-enzyme chemical barrier crossing. This study demonstrates coupling of enzymatic bond vibrations on the femtosecond time scale to barrier crossing.
Time-resolved structural dynamics of thin metal films heated with femtosecond optical pulses
Authors: Chen Jie , Chen Wei-Kan , Tang Jau , Rentzepis Peter M.
Published: November 2011

We utilize 100 fs optical pulses to induce ultrafast disorder of 35- to 150-nm thick single Au(111) crystals and observe the subsequent structural evolution using 0.6-ps, 8.04-keV X-ray pulses. Monitoring the picosecond time-dependent modulation of the X-ray diffraction intensity, width, and shift, we have measured directly electron/phonon coupling, phonon/lattice interaction, and a histogram of the lattice disorder evolution, such as lattice breath due to a pressure wave propagating at sonic velocity, lattice melting, and recrystallization, including mosaic formation. Results of theoretical simulations agree and support the experimental data of the lattice/liquid phase transition process. These time-resolved X-ray diffraction data provide a detailed description of all the significant processes induced by ultrafast laser pulses impinging on thin metallic single crystals.
Hazlitt's contrariness and familiar prose style: lessons on how to be critical
Authors: Halpin David
Published: November 2011

Contrariness of the kind manifest in the literary output and general disposition of the nineteenth century English essayist and journalist, William Hazlitt, has much to teach contemporary intellectuals working in the academy about how better to be critical, offering important lessons
on the necessity for self-consistency and independence of thought and the need more to write for publication in a familiar and accessible conversational style.
The climate of inclusive classrooms: the pupil perspective
Authors: Tetler Susan , Baltzer Kirsten
Published: November 2011

This paper offers insights into learning experiences in inclusive classrooms, gained by giving voices to pupils about their perceptions of themselves and their opinions on classroom climate. A positive response pattern is identified concerning academic and social dimensions of schools,
while the overall picture concerning the dimension of participation is more blurred. The paper argues for further explorations of the concept of educational participation in inclusive settings, not only with a focus upon the psychological classroom climate aspects, but also upon the pedagogical
and didactic processes that constitute the learning conditions for pupils with disabilities included in mainstream classrooms.
Register shifting of an insulin peptide–MHC complex allows diabetogenic T cells to escape thymic deletion
Authors: Mohan James F. , Petzold Shirley J. , Unanue Emil R.
Published: November 2011

In nonobese diabetic (NOD) mice, two sets of autoreactive CD4+ T cells recognize the B:9–23 segment of the insulin B chain. One set, type A, recognizes insulin presented by antigen-presenting cells (APCs). These T cells are highly deleted in the thymus. The second set, type B, does not recognize insulin protein but reacts with soluble B chain peptide. This set is not deleted in the thymus but is activated in the islets of Langerhans. In this study, we examine the specificity of these two types of T cells. The protein-reactive set recognizes the stretch of residues 13–21 of the insulin B chain. The set reactive to peptide only recognizes the stretch from residues 12–20. A single amino acid shift of the B chain peptide bound to I-Ag7 determines whether T cells recognize peptides generated by the processing of insulin, and consequently their escape from thymic purging. Biochemical experiments indicate that peptides bound in the 13–21 register interact more favorably with I-Ag7 than peptides that bind in the 12–20 register. Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus.
Slow-light propagation in a cylindrical dielectric waveguide with metamaterial cladding
Authors: Zhang Qi , Jiang Tian , Feng Yijun
Published: November 2011

Through rigorous analysis of all possible oscillatory guided modes propagating in a dielectric cylindrical waveguide with anisotropic metamaterial cladding, we demonstrate that slow or even stopped electromagnetic wave (or light) can propagate in the waveguide with specially selected parameters of the metamaterial. We propose a linearly tapered cylindrical waveguide which could lead the propagating light to a complete standstill and validate the structure by full-wave simulation based on the finite-difference time-domain method. For practical implementation, we present two possible realizations of the slow-light waveguide structure: one consists of silver and silicon dioxide multilayered thin films as the metamaterial cladding and the other consists of isotropic plasmonic material as the cladding. We demonstrate that slow-light can be supported in the practical structures by theoretical analysis.
Microwave plasma activation of a polyvinylidene fluoride surface for protein immobilization
Authors: Vasile C , Baican M C , Tibirna C M , Tuchilus C , Debarnot D , Pâslaru E , Poncin-Epaillard F
Published: November 2011

Polyvinylidene fluoride (PVDF) was modified by CO2, N2 or N2/H2 plasmas, which permitted the attachment of short carboxyl or amino groups. A variation of the discharge parameters was performed, for their optimization, as well as for minimizing degradation in favour of acidic, amphiphilic or basic functionalization, respectively. The optimum parameters of discharge for CO2, N2 or N2/H2 plasmas were P = 50 W, gas flow rate Q = 16 × 10−8 m3 s−1, exposure time t = 30–60 s, d = 0.1 m, pressure 15 Pa. The new surfaces were characterized by wettability measurements, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), x-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) methods. In a second step, the proteins (triglycine (TG) and protein A) were adsorbed or chemically grafted onto the carboxyl or amino functionalized surface, after EDC/NHS (1-ethyl-3-(-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide) activation of proteins. ATR-FTIR, XPS and AFM investigations confirmed the presence of protein on the surface. The XPS C1s core levels at 286.3 eV (C–N), 288 eV (amide bond) and 298 eV (carboxylic acid), together with variation of the O1s and N1s signals, illustrated the immobilization of proteins. It was established that TG was better attached on surfaces activated with N2/H2 plasma, while protein A was more tightly anchored on CO2, N2 plasma-activated surfaces. The former procedure allowed higher surface densities, while the latter permitted a better chemical control. The results proved that plasma-treated PVDF is a good substrate for protein coating, which can be further used for microorganisms' detection, as evidenced by the immunoassay test.
Spectral super-resolution in metamaterial composites
Authors: Helsing J , McPhedran R C , Milton G W
Published: November 2011

We investigate the optical properties of periodic composites containing metamaterial inclusions in a normal material matrix. We consider the case when these inclusions have sharp corners and, following Hetherington and Thorpe, use analytic results to argue that it is then possible to deduce the shape of the corner (its included angle) by measurements of the absorptance of such composites when the scale size of the inclusions and period cell is much finer than the wavelength. These analytic arguments are supported by highly accurate numerical results for the effective permittivity function of such composites as a function of the permittivity ratio of inclusions to the matrix. The results show that this function has a continuous spectral component with limits independent of the area fraction of inclusions, and with the same limits for both square and staggered square arrays. For staggered arrays where the squares are almost touching, the absorption spectrum is an extremely sensitive probe of the inclusion separation distance and acts like a Vernier scale.
A novel structural position-specific scoring matrix for the prediction of protein secondary structures
Authors: Li Dapeng , Li Tonghua , Cong Peisheng , Xiong Wenwei , Sun Jiangming
Published: November 2011

Motivation: The precise prediction of protein secondary structure is of key importance for the prediction of 3D structure and biological function. Although the development of many excellent methods over the last few decades has allowed the achievement of prediction accuracies of up to 80%, progress seems to have reached a bottleneck, and further improvements in accuracy have proven difficult.

Results: We propose for the first time a structural position-specific scoring matrix (SPSSM), and establish an unprecedented database of 9 million sequences and their SPSSMs. This database, when combined with a purpose-designed BLAST tool, provides a novel prediction tool: SPSSMPred. When the SPSSMPred was validated on a large dataset (10 814 entries), the Q3 accuracy of the protein secondary structure prediction was 93.4%. Our approach was tested on the two latest EVA sets; accuracies of 82.7 and 82.0% were achieved, far higher than can be achieved using other predictors. For further evaluation, we tested our approach on newly determined sequences (141 entries), and obtained an accuracy of 89.6%. For a set of low-homology proteins (40 entries), the SPSSMPred still achieved a Q3 value of 84.6%.

Availability: The SPSSMPred server is available at http://cal.tongji.edu.cn/SPSSMPred/

Contact:  lith@tongji.edu.cn
Physicochemical Properties of Oat Varieties and Their Potential for Breadmaking
Authors: Hüttner Edith K. , Bello Fabio Dal , Zannini Emanuele , Titze Jean , Beuch Steffen , Arendt Elke K.
Published: November 2011

The breadmaking potential of six oat varieties was compared with and related to their physicochemical properties. The most significant differences in the bread characteristics were found in the crumb structure. The varieties Buggy, Energie, and Zorro resulted in good bread quality with an even gas‐cell distribution characterized by a high number of relatively small pores. In contrast, Typhon, Ivory, and Nord 08/311 each had a large hole in the center of the crumb and accordingly poor quality. Breads differed little in specific volume, bake loss, and density. Rheological analysis revealed positive effects of low batter resistance to deformation on oat bread quality. On the basis of the physicochemical characterization, protein and fat contents were identified as key factors responsible for differences observed in bread quality, provided that starch damage and water‐hydration capacity were low. Additionally, high setback and final viscosity, as determined by Rapid Visco Analyser (RVA) analysis, positively affected oat bread quality. High α‐amylase activity was found to influence negatively the breadmaking performance of oats. Overall, protein, fat, dietary fiber content, starch pasting properties, and α‐amylase activity were responsible for the breadmaking properties of oat varieties.
Synthesis of the Flavonoid-Induced Lipopolysaccharide of Rhizobium Sp. Strain NGR234 Requires Rhamnosyl Transferases Encoded by Genes rgpF and wbgA
Authors: Ardissone Silvia , Noel K. Dale , Klement Mitchell , Broughton William J. , Deakin William J.
Published: November 2011

In the presence of flavonoids, Rhizobium sp. strain NGR234 synthesizes a new lipopolysaccharide (LPS), characterized by a rhamnan O-antigen. The presence of this rhamnose-rich LPS is important for the establishment of competent symbiotic interactions between NGR234 and many species of leguminous plants. Two putative rhamnosyl transferases are encoded in a cluster of genes previously shown to be necessary for the synthesis of the rhamnose-rich LPS. These two genes, wbgA and rgpF, were mutated. The resulting mutant strains synthesized truncated rough LPS species rather than the wild-type rhamnose-rich LPS when grown with flavonoids. Based on the compositions of these purified mutant LPS species, we inferred that RgpF is responsible for adding the first one to three rhamnose residues to the flavonoid-induced LPS, whereas WbgA is necessary for the synthesis of the rest of the rhamnan O-antigen. The NGR234 homologue of lpsB, which, in other bacteria, encodes a glycosyl transferase acting early in synthesis of the core portion of LPS, was identified and also mutated. LpsB was required for all the LPS species produced by NGR234, in the presence or absence of flavonoids. Mutants (i.e., of lpsB and rgpF) that lacked any portion of the rhamnan O-antigen of the induced LPS were severely affected in their symbiotic interaction with Vigna unguiculata, whereas the NGRΩwbgA mutant, although having very few rhamnose residues in its LPS, was able to elicit functional nodules.
Heated competition: how climate change will affect non‐native pumpkinseed Lepomis gibbosus and native perch Perca fluviatilis interactions in the U.K.
Authors: Fobert E. , Fox M. G. , Ridgway M. , Copp G. H.
Published: November 2011

Heated and ambient temperature experimental ponds were used to examine competition between introduced pumpkinseed Lepomis gibbosus and native perch Perca fluviatilis in England, U.K., and how these interactions are likely to change under climate warming conditions. Results from three sets of two‐week experiments indicated that in both species and in all sets, growth was faster in heated than in ambient temperature ponds. Growth of both P. fluviatilis and L. gibbosus in sympatry did not differ significantly from that observed in allopatric ponds. Diet analysis indicated that increased resource partitioning occurred when P. fluviatilis and L. gibbosus were reared in sympatry, with P. fluviatilis shifting to a diet higher in microcrustaceans. The results do not support the previous claims of adverse effects of L. gibbosus on P. fluviatilis populations. Under conditions of climate change, however, which have been demonstrated experimentally to enhance L. gibbosus recruitment, this species is expected to become invasive in England, resulting in higher densities that may exert a stronger competitive effect than examined in this study.
Implications of rapid virological response in hepatitis C therapy in the US veteran population
Authors: Hwang E. W. , Thomas I.‐C. , Cheung R. , Backus L. I.
Published: November 2011

Aliment Pharmacol Ther 2012; 35: 105–115

Background  Early predictors of response to hepatitis C virus (HCV) therapy, such as rapid virological response, are valuable for the identification of patients with a higher likelihood of treatment success.

Aim  To identify predictors of rapid virological response in a real world setting.

Methods  Using the VA Clinical Case Registry, we identified patients with HCV mono‐infection, without liver transplantation, who initiated peginterferon (PEG‐IFN) and ribavirin (RBV) in 2007 or 2008 and had HCV RNA testing for RVR. Significant baseline characteristics from genotype specific univariate analyses were used in backwards stepwise models to identify significant independent predictors of RVR.

Results  The final cohort consisted of 2424 patients with genotype 1 (G1), 666 patients with genotype 2 (G2), and 419 patients with genotype 3 (G3). Rapid virological response rates were 15% for G1, 71% for G2 and 57% for G3. Sustained virological response rates were significantly higher in patients with rapid virological response than without, increasing from 18% to 52% in G1, 39% to 71% in G2, and 40% to 60% in G3 (P < 0.0001). A baseline HCV RNA<500 000 IU/mL positively predicted RVR across all genotypes studied. In addition, for G1, Black race, Hispanic ethnicity, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≥0.6, ferritin≥350 ng/mL, LDL<100 mg/dL and diabetes; for G2, BMI≥30 kg/m2, platelets<150 K/μL, LDL<100 mg/dL and the use of PEG‐IFN alfa‐2b; and for G3, AST/ALT≥1.0, all negatively predicted rapid virological response.

Conclusion  We found several novel independent predictors of rapid virological response, including BMI, AST/ALT ratio, ferritin, platelets, LDL, diabetes and type of PEG‐IFN prescribed, which may be useful in guiding treatment decisions in routine medical practice.
The influence of clinical risk factors on pre‐operative B‐type natriuretic peptide risk stratification of vascular surgical patients
Authors: Biccard B. M. , Lurati Buse G. A. , Burkhart C. , Cuthbertson B. H. , Filipovic M. , Gibson S. C. , Mahla E. , Leibowitz D. W. , Rodseth R. N.
Published: November 2011

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre‐operative B‐type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B‐type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre‐operative B‐type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B‐type natriuretic peptide stratification (OR 5.1, 95% CI 1.8–15 for the intermediate class, and OR 25, 95% CI 8.7–70 for the high‐risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B‐type natriuretic peptides.
Protein C, protein S and von Willebrand factor levels correlate with bleeding symptoms: a population‐based study
Authors: ROJNUCKARIN P. , UAPRASERT N. , AKKAWAT B. , SETTAPIBOON R. , NANAKORN T. , INTRAGUMTORNCHAI T.
Published: November 2011

Summary.  Although natural anticoagulant deficiencies are the established causes of thrombosis, their roles in bleeding are not fully studied. The objective is to correlate haemostatic factors with haemorrhagic symptoms quantified by a standardized questionnaire. Adult subjects were recruited from Bangkok and nearby provinces as part of routine health surveys/checkups. The validated MCMDM‐1VWD form was used to assess their bleeding symptoms. At the same time, von Willebrand factor (VWF) activity, free protein S levels and protein C activity were measured. There were 5196 individuals. The mean age was 44.3 years (range 15–99) and 41% were male subjects. The mean bleeding score was −0.28 and 95% of subjects had scores between −2 and +2. The scores were lower in female subjects than in male subjects (−0.35 vs. −0.16, P < 0.001). Bleeding scores correlated negatively with age, VWF and protein C activities (Spearman’s ρ−0.258, −0.091 and −0.098, respectively, all P < 0.001), but did not significantly correlate with protein S levels. Using multivariate analysis, female gender, VWF below 100 IU dL−1, protein C below 100 IU dL−1 and protein S over 150 IU dL−1 significantly related to high (≥3) bleeding scores (adjusted odds ratio 1.95, 1.83, 1.56 and 2.84, P = 0.001, 0.001, 0.039 and 0.017, respectively). These findings may suggest interacting roles of VWF and natural anticoagulants in modifying bleeding symptoms.
Prediction and diagnosis of clinical outcomes affecting restoration margins
Authors: DENNISON J. B. , SARRETT D. C.
Published: November 2011

Summary  The longevity of dental restorations is largely dependent on the continuity at the interface between the restorative material and adjacent tooth structure (the restoration margin). Clinical decisions on restoration repair or replacement are usually based upon the weakest point along that margin interface. Physical properties of a restorative material, such as polymerisation shrinkage, water sorption, solubility, elastic modulus and shear strength, all have an effect on stress distribution and can significantly affect margin integrity. This review will focus on two aspects of margin deterioration in the oral environment: the in vitro testing of margin seal using emersion techniques to simulate the oral environment and to predict clinical margin failure and the relationship between clinically observable microleakage and secondary caries. The many variables associated with in vitro testing of marginal leakage and the interpretation of the data are presented in detail. The most recent studies of marginal leakage mirror earlier methodology and lack validity and reliability. The lack of standardised testing procedures makes it impossible to compare studies or to predict the clinical performance of adhesive materials. Continual repeated in vitro studies contribute little to the science in this area. Clinical evidence is cited to refute earlier conclusions that clinical microleakage (penetrating margin discoloration) leads to caries development and is an indication for restoration replacement. Margin defects, without visible evidence of soft dentin on the wall or base of the defect, should be monitored, repaired or resealed, in lieu of total restoration replacement.
Immunosuppression, liver injury and post‐transplant HCV recurrence
Authors: Ciesek S. , Wedemeyer H.
Published: November 2011

Summary.  Hepatitis C virus (HCV) infection is a major cause for liver transplantation worldwide. Still, HCV re‐infection of the graft occurs in almost all cases. Most liver transplant recipients experience episodes of graft hepatitis associated with fibrosis progression and graft failure. Clinical management of graft hepatitis can be challenging as in addition to rejection and HCV‐induced hepatitis various other factors might be involved including toxic liver injury, steatohepatitis, ischaemic bile duct lesions or infections with other pathogens. Treatment options are often contradictory for different causes of graft hepatitis, and the role of distinct immunosuppressive drugs has been discussed controversially. Corticosteroids increase the infectivity of HCV by altering expression levels of entry factors and other immunosuppressive agents may have diverse effects on HCV replication and fibrosis progression. Interferon alpha‐therapy of hepatitis C shows limited efficacy and tolerability in liver transplant recipients and may also cause rejection. In this review we summarize the current knowledge on mechanisms of liver injury in post‐transplant hepatitis C, discuss the pros and cons of immunosuppressive agents in this specific setting and describe potential novel approaches to prevent HCV reinfection.
AToxoplasma gondiimutant highlights the importance of translational regulation in the apicoplast during animal infection
Authors: Payne T. Matthew , Payne Amanda J. , Knoll Laura J.
Published: November 2011

Toxoplasma gondiiis an obligate intracellular parasite of all warm‐blooded animals. We previously described a forward genetic screen to identifyT. gondiimutants defective in the establishment of a chronic infection. One of the mutants isolated was disrupted in the 3′ untranslated region (3′UTR) of an orthologue of bacterial translation elongation factor G (EFG). The mutant does not have a growth defect in tissue culture. Genetic complementation of this mutant with the genomic locus ofTgEFGrestores virulence in an acute infection mouse model. Epitope tagged TgEFG localized to the apicoplast, via a non‐canonical targeting signal, where it functions as an elongation factor for translation in the apicoplast. Comparisons of TgEFG expression constructs with wild‐type or mutant 3′UTRs showed that a wild‐type 3′UTR is necessary for translation of TgEFG. In tissue culture, theTgEFGtranscript is equally abundant in wild‐type and mutant parasites; however, during an animal infection, theTgEFGtranscript is increased more than threefold in the mutant. These results highlight that in tissue culture, translation in the apicoplast can be diminished, but during an animal infection, translation in the apicoplast must be fully functional.
Probing the mechanistic role of the long α‐helix in subunit L of respiratory Complex I from Escherichia coli by site‐directed mutagenesis
Authors: Belevich Galina , Knuuti Juho , Verkhovsky Michael I. , Wikström Mårten , Verkhovskaya Marina
Published: November 2011

The C‐terminus of the NuoL subunit of Complex I includes a long amphipathic α‐helix positioned parallel to the membrane, which has been considered to function as a piston in the proton pumping machinery. Here, we have introduced three types of mutations into the nuoL gene to test the piston‐like function. First, NuoL was truncated at its C‐ and N‐termini, which resulted in low production of a fragile Complex I with negligible activity. Second, we mutated three partially conserved residues of the amphipathic α‐helix: Asp and Lys residues and a Pro were substituted for acidic, basic or neutral residues. All these variants exhibited almost a wild‐type phenotype. Third, several substitutions and insertions were made to reduce rigidity of the amphipathic α‐helix, and/or to change its geometry. Most insertions/substitutions resulted in a normal growth phenotype, albeit often with reduced stability of Complex I. In contrast, insertion of six to seven amino acids at a site of the long α‐helix between NuoL and M resulted in substantial loss of proton pumping efficiency. The implications of these results for the proton pumping mechanism of Complex I are discussed.
On the edge of parasitoidism: a new Lower Cretaceous woodwasp forming the putative sister group of Xiphydriidae + Euhymenoptera
Authors: KROGMANN LARS , NEL ANDRÉ
Published: November 2011

The fossil woodwasp Cratoenigma articulatagen. et sp.n. (Insecta: Hymenoptera) is described from the Lower Cretaceous Crato formation of Brazil. This fossil cannot be placed in any existing superfamily, but its putative phylogenetic position within Hymenoptera is discussed in detail on the basis of relevant thoracic, abdominal and wing venation characters. These characters are critically evaluated and compared with those of extant and fossil Hymenoptera. The phylogenetic position of C. articulatasp.n. is investigated relative to extant Xyelidae, Tenthredinoidea s.l., Pamphilioidea, Cephidae, Siricoidea, Xiphydriidae, Orussidae and Apocrita, and also to Mesozoic Gigasiricidae, Myrmiciidae, Daohugoidae, Sepulcidae, Anaxyelidae, Paroryssidae and Ephialtitidae. Based on the presence of a synapomorphic transscutal articulation, a plesiomorphic unconcealed mesopostnotum and autapomorphic hindwing venation (cu‐a distinctly basal to fork between M and Cu), C. articulatasp.n. most likely forms the sister group of Xiphydriidae + Euhymenoptera. This would place it well within Unicalcarida, i.e. the clade in which the transition from endophytic to parasitoid lifestyle evolved.
Renal function after tandem high‐dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor
Authors: Lee Soo Hyun , Paik Kyung Hoon , Sung Ki Woong , Son Meong Hi , Yoo Keon Hee , Koo Hong Hoe , Kim Ju Youn , Cho Eun Joo
Published: November 2011

Lee SH, Paik KH, Sung KW, Son MH, Yoo KH, Koo HH, Kim JY, Cho EJ. Renal function after tandem high‐dose chemotherapy and autologous stem cell transplantation in children with Wilms tumor. Pediatr Transplantation 2011: 15: 855–860. © 2011 John Wiley & Sons A/S.

Abstract:  Despite increasing evidence that tandem HDCT and autoSCT might improve the survival of patients with high‐risk solid tumors, patients with Wilms tumor may be at high risk of acute and chronic renal impairment during and after tandem HDCT/autoSCT because they usually have a single kidney. We investigated the feasibility of tandem HDCT/autoSCT in patients with Wilms tumor, focusing on renal function. Six patients with relapsed/progressed Wilms tumor were assigned to undergo tandem HDCT/autoSCT. One patient developed transient ARF during the first HDCT/autoSCT. All other patients underwent the second HDCT/autoSCT as scheduled. Acute renal dysfunction during the second HDCT/autoSCT was transient and manageable. Indicators of glomerular function such as creatinine clearance, serum creatinine, and albumin excretion were in the normal range at three yr after tandem HDCT/autoSCT. Subclinical tubular dysfunctions, such as increased excretion of β‐N‐acetylglucosaminidase and β2‐microglobulin, were identified at one and three yr after tandem HDCT/autoSCT; however, no patient required treatment for these conditions. These results are helpful to consider tandem HDCT/autoSCT as a treatment option in patients with Wilms tumor. Longer duration of follow‐up and close monitoring of tubular function are required if tandem HDCT/autoSCT is indicated in patients with Wilms tumor.
Effect of Dilution Temperature on Boar Semen Quality
Authors: López Rodríguez A , Rijsselaere T , Vyt P , Van Soom A , Maes D
Published: November 2011

Contents

As boar semen is very sensitive to cold shock and changes in temperature during semen processing can have a profound impact on semen quality, the effect of the extender temperature at the time of dilution was investigated in a two‐step dilution protocol for boar semen being processed for liquid storage. Fifteen boars of different breeds and ages from a commercial artificial insemination centre were included. One ejaculate per boar was collected and processed with Beltsville Thawing Solution semen extender. Each ejaculate was diluted (1  :  1) at 30°C, and subsequently, the samples were diluted (30  × 106 sperm / ml) with either preheated extender [29.3°C  ± 0.2°C, group A (GA)] or extender at room temperature [22.7°C  ± 0.6°C, group B (GB)]. Samples were transported to the Faculty of Veterinary Medicine (University of Ghent, Belgium) in two isotherm boxes (one per group), stored at 17°C and investigated for three consecutive days (D0 to D2). At D0, D1 and D2, motility parameters [computer‐assisted semen analysis (CASA)] and the per cent of sperm with intact membrane (% IM) by eosin nigrosin staining were evaluated. At D0 and D2, the % of sperm with intact acrosome (% IA) was studied by Pisum sativum agglutinin staining. The average temperature of the 1 : 1 dilution was 29.4°C ± 1.1°C immediately after extender addition. No significant differences were found between groups for per cent motility [79.3 ± 9.0 for GA and 81.1 ± 9.2 for GB (p = 0.372)], % progressive motility [56.5 ± 13.3 for GA and 58.4 ± 13.8 for GB (p = 0.737)] or any CASA parameter. No differences were found for % IM [85.1 ± 10.7 and 84.5 ± 3.8 for GA and GB, respectively (p = 0.761)] and % IA [72.2 ± 9.4 for GA and 68.3 ± 16.6 for GB (p = 0.792)]. In conclusion, when a two‐step dilution is performed, preheating the extender for the second dilution to match the semen temperature did not result in better semen quality compared to a dilution at a moderate room temperature.
Usefulness of a semi‐quantitative procalcitonin test and the A‐DROP Japanese prognostic scale for predicting mortality among adults hospitalized with community‐acquired pneumonia
Authors: KASAMATSU YU , YAMAGUCHI TOSHIMASA , KAWAGUCHI TAKASHI , TANAKA NAGAAKI , OKA HIROKO , NAKAMURA TOMOYUKI , YAMAGAMI KEIKO , YOSHIOKA KATSUNOBU , IMANISHI MASAHITO
Published: November 2011

Background and objective:  The solid‐phase immunoassay, semi‐quantitative procalcitonin (PCT) test (B R A H M S PCT‐Q) can be used to rapidly categorize PCT levels into four grades. However, the usefulness of this kit for determining the prognosis of adult patients with community‐acquired pneumonia (CAP) is unclear.

Methods:  A prospective study was conducted in two Japanese hospitals to evaluate the usefulness of this PCT test in determining the prognosis of adult patients with CAP. The accuracy of the age, dehydration, respiratory failure, orientation disturbance, pressure (A‐DROP) scale proposed by the Japanese Respiratory Society for prediction of mortality due to CAP was also investigated. Hospitalized CAP patients (n = 226) were enrolled in the study. Comprehensive examinations were performed to determine PCT and CRP concentrations, disease severity based on the A‐DROP, pneumonia severity index (PSI) and confusion, urea, respiratory rate, blood pressure, age ≥65 (CURB‐65) scales and the causative pathogens. The usefulness of the biomarkers and prognostic scales for predicting each outcome were then examined.

Results:  Twenty of the 170 eligible patients died. PCT levels were strongly positively correlated with PSI (ρ = 0.56, P < 0.0001), A‐DROP (ρ = 0.61, P < 0.0001) and CURB‐65 scores (ρ = 0.58, P < 0.0001). The areas under the receiver operating characteristic curves (95% CI) for prediction of survival, for CRP, PCT, A‐DROP, CURB‐65, and PSI were 0.54 (0.42–0.67), 0.80 (0.70–0.90), 0.88 (0.82–0.94), 0.88 (0.82–0.94), and 0.89 (0.85–0.94), respectively. The 30‐day mortality among patients who were PCT‐positive (≥0.5 ng/mL) was significantly higher than that among PCT‐negative patients (log–rank test, P < 0.001).

Conclusions:  The semi‐quantitative PCT test and the A‐DROP scale were found to be useful for predicting mortality in adult patients with CAP.
Breeding biology and incremental benefits of outcrossing for the restoration wildflower, Hedysarum boreale Nutt. (Fabaceae)
Authors: SWOBODA KATHARINE A. , CANE JAMES H.
Published: November 2011

Northern sweetvetch (Hedysarum boreale Nutt.) is an herbaceous perennial legume of the Rocky Mountains, USA, whose seed is desired for rehabilitating degraded plant communities. Through experimental pollinations, the necessity of pollinators was shown by the failure of autogamy, despite stigmas first becoming receptive in the bud in close proximity to the dehiscing anthers. Nonetheless, the species proved to be self‐fertile, initiating as many fruits through selfing as outcrossing. Incremental benefits of outcrossing only later manifested in superior fruit development, seed maturation and seed germination. Farming of H. boreale can yield abundant viable seed if adequately visited by pollinating bees.
Accumulation and attrition of peat soils in the Australian Alps: Isotopic dating evidence
Authors: GROVER SAMANTHA P. P. , BALDOCK JEFFERY A. , JACOBSEN GERALDINE E.
Published: November 2011

Bog peat soils have been accumulating at Wellington Plain peatland, Victoria, Australia for the last 3300 years. Now, dried peat soils are common adjacent to bog peats. The 14C basal age of dried peat is not different from the 14C basal age of bog peat, which supports the theory that dried peat formed from bog peat. A novel application of 210Pb dating links the timing of this change with the introduction of livestock to Wellington Plain in the mid‐1800s. Physical loss of material appears to have been the dominant process removing material as bog peats drained to form dried peats, as indicated by the mass balances of carbon and lead. This research has implications for the post‐fire and post‐grazing restoration of bogs in Victoria's Alpine National Park, and the contribution of peat soils to Australia's carbon emissions.
Unmarked individuals in mark–recapture studies: Comparisons of marked and unmarked southern elephant seals at Marion Island
Authors: OOSTHUIZEN W. CHRIS , DE BRUYN P. J. NICO , BESTER MARTHÁN N.
Published: November 2011

The presence of unmarked individuals is common in mark–recapture study populations; however, their origin and significance in terms of population dynamics remain poorly understood. At Marion Island, southern Indian Ocean, where virtually all southern elephant seal Mirounga leonina pups born annually (1983–2008) were marked in a long‐term mark–resight study, large numbers of unmarked seals occur. Unmarked seals originate either from marker (tag) loss or from immigration. We aimed to identify patterns in the occurrence of marked and unmarked individuals that will allude to the possible origin and significance of the untagged component of the population, predicting that tag loss will add untagged seals to mainly adult age categories whereas migrating untagged individuals will be mostly juveniles. We fitted a generalized linear model using the factors month, year and age‐class to explain the relative abundance of untagged seals (tag ratio) from 1997 to 2009. Site usage of untagged seals relative to tagged seals was assessed using a binomial test. Untagged seals, predominantly juveniles, were present in the highest proportions relative to tagged seals during the winter haulout (tagged seals/total seals less than 0.3) and the lowest proportion (approximately 0.5) during the female breeding haulout, increasing in relative abundance from 1997 to 2009. Untagged seals were distributed evenly across suitable haulout sites while tagged seals displayed high local site fidelity and occurred in greater numbers at or near large breeding beaches. Untagged seals are considered to be mostly migrant seals that disperse from other islands within the southern Indian Ocean and haul out at Marion Island during non‐breeding haulouts in particular. Some of these seals immigrate to the breeding population, which can be a key component of the local population dynamics. We emphasize the need for mark–recapture studies to evaluate the role of the unmarked component of a population, thereby inducing a more confident estimation of demographic parameters from the marked sample.
Expression of matrix metalloproteinases, type IV collagen, and interleukin‐10 in rabbits treated with morphine after lamellar keratectomy
Authors: Ribeiro Alexandre P. , Silva Miguel L. , Araújo Rodrigo L. , Ferrucci Danilo L. , Mineo Tiago , Thiesen Roberto , Bandarra Márcio B. , Laus José L.
Published: November 2011

Purpose  To study the effects of topical administration of 1% morphine on corneal analgesia in rabbits submitted to lamellar keratectomy and to assess the expression of matrix metalloproteinase‐1, metalloproteinase‐2, metalloproteinase‐9 (MMPs), type IV collagen, and interleukin‐10 (IL‐10) during the treatment.

Methods  Morphine group (MG) received 50 μL of topical 1% morphine four times daily, while the control group received saline instead. Corneal touch threshold (CTT) and the wound area were assessed until corneal healing. Corneal samples were processed for routine histology, immunohistochemistry, zymography, and ELISA.

Results  Following keratectomy, CTT increased significantly from 6 to 96 h time points. Mean corneal re‐epithelization rate and scores of leukocyte infiltration did not differ significantly between treatment groups. Immunolabeling pattern for MMP‐1, MMP‐9, and type IV collagen was similar in both treatment groups. In the MG, zymography indicated significantly higher levels of active MMP‐2 on days 6 and 12; and in the latent MMP‐9, on days 3 and 6, and in the active MMP‐9, on day 6. Latent MMP‐2 and MMP‐9, and active MMP‐9 decreased to values close to those of healthy corneas on day 12, but levels of active MMP‐2 remained significantly elevated in the MG. IL‐10 levels measured on days 1–6 were reduced as compared to those of healthy corneal tissue and returned to levels close to those of healthy corneas on day 12.

Conclusion  Topical morphine promoted corneal analgesia for up to 4 days and did not delay corneal re‐epithelization. The re‐establishment of MMPs and IL‐10 to levels close to baseline values at the end of the study and the expression of type IV collagen in both groups reinforce that, with caution, 1% morphine can be used after lamellar keratectomy in rabbits.