bluuebunny/crossref_metadata_2025 huggingface dataset:
CAD‐score: A new contact area difference‐based function for evaluation of protein structural models
Authors: Olechnovič Kliment , Kulberkytė Eleonora , Venclovas Česlovas
Published: February 2013

Evaluation of protein models against the native structure is essential for the development and benchmarking of protein structure prediction methods. Although a number of evaluation scores have been proposed to date, many aspects of model assessment still lack desired robustness. In this study we present CAD‐score, a new evaluation function quantifying differences between physical contacts in a model and the reference structure. The new score uses the concept of residue–residue contact area difference (CAD) introduced by Abagyan and Totrov (J Mol Biol 1997; 268:678–685). Contact areas, the underlying basis of the score, are derived using the Voronoi tessellation of protein structure. The newly introduced CAD‐score is a continuous function, confined within fixed limits, free of any arbitrary thresholds or parameters. The built‐in logic for treatment of missing residues allows consistent ranking of models of any degree of completeness. We tested CAD‐score on a large set of diverse models and compared it to GDT‐TS, a widely accepted measure of model accuracy. Similarly to GDT‐TS, CAD‐score showed a robust performance on single‐domain proteins, but displayed a stronger preference for physically more realistic models. Unlike GDT‐TS, the new score revealed a balanced assessment of domain rearrangement, removing the necessity for different treatment of single‐domain, multi‐domain, and multi‐subunit structures. Moreover, CAD‐score makes it possible to assess the accuracy of inter‐domain or inter‐subunit interfaces directly. In addition, the approach offers an alternative to the superposition‐based model clustering. The CAD‐score implementation is available both as a web server and a standalone software package at http://www.ibt.lt/bioinformatics/cad‐score/. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Thermodynamics of binding by calmodulin correlates with target peptide α‐helical propensity
Authors: Dunlap Tori B. , Kirk Jessime M. , Pena Emily A. , Yoder Meghan S. , Creamer Trevor P.
Published: February 2013

In this work, we have examined contributions to the thermodynamics of calmodulin (CaM) binding from the intrinsic propensity for target peptides to adopt an α‐helical conformation. CaM target sequences are thought to commonly reside in disordered regions within proteins. Using the ability of TFE to induce α‐helical structure as a proxy, the six peptides studied range from having almost no propensity to adopt α‐helical structure through to a very high propensity. This despite all six peptides having similar CaM‐binding affinities. Our data indicate there is some correlation between the deduced propensities and the thermodynamics of CaM binding. This finding implies that molecular recognition features, such as CaM target sequences, may possess a broad range of propensities to adopt local structure. Given that these peptides bind to CaM with similar affinities, the data suggest that having a higher propensity to adopt α‐helical structure does not necessarily result in tighter binding, and that the mechanism of CaM binding is very dependent on the nature of the substrate sequence. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Identification of mycobacterial lectins from genomic data
Authors: Abhinav K. V. , Sharma Alok , Vijayan M.
Published: February 2013

Sixty‐four sequences containing lectin domains with homologs of known three‐dimensional structure were identified through a search of mycobacterial genomes. They appear to belong to the β‐prism II, the C‐type, the Microcystis virdis (MV), and the β‐trefoil lectin folds. The first three always occur in conjunction with the LysM, the PI‐PLC, and the β‐grasp domains, respectively while mycobacterial β‐trefoil lectins are unaccompanied by any other domain. Thirty heparin binding hemagglutinins (HBHA), already annotated, have also been included in the study although they have no homologs of known three‐dimensional structure. The biological role of HBHA has been well characterized. A comparison between the sequences of the lectin from pathogenic and nonpathogenic mycobacteria provides insights into the carbohydrate binding region of the molecule, but the structure of the molecule is yet to be determined. A reasonable picture of the structural features of other mycobacterial proteins containing one or the other of the four lectin domains can be gleaned through the examination of homologs proteins, although the structure of none of them is available. Their biological role is also yet to be elucidated. The work presented here is among the first steps towards exploring the almost unexplored area of the structural biology of mycobacterial lectins. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Solution structure of the SH3 domain of DOCK180
Authors: Liu Xiangrong , Li Fengjuan , Pan Zhu , Wang Wenning , Wen Wenyu
Published: February 2013

DOCK180 family proteins are Rho guanine nucleotide exchange factors. DOCK1‐5 contains an N‐terminal SH3 domain implicated in their autoinhibition. Release of the closed conformation requires the interaction between SH3 and engulfment and cell motility (ELMO). Here, we solved the solution structure of DOCK180 SH3 domain, which shares similar target binding features with the SH3 domain of DOCK2. The conserved N‐terminal extension packs with the SH3 core domain and forms a new target binding site distinct from the canonical “PxxP” site. Our results demonstrate that the bidentate target binding mode of DOCK180 SH3 domain might be a general feature in all DOCK proteins. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Ab initio structure prediction of the antibody hypervariable H3 loop
Authors: Zhu Kai , Day Tyler
Published: February 2013

Antibodies have the capability of binding a wide range of antigens due to the diversity of the six loops constituting the complementarity determining region (CDR). Among the six loops, the H3 loop is the most diverse in structure, length, and sequence identity. Prediction of the three‐dimensional structures of antibodies, especially the CDR loops, is an important step in the computational design and engineering of novel antibodies for improved affinity and specificity. Although it has been demonstrated that the conformation of the five non‐H3 loops can be accurately predicted by comparing their sequences against databases of canonical loop conformations, no such connection has been established for H3 loops. In this work, we present the results for ab initio structure prediction of the H3 loop using conformational sampling and energy calculations with the program Prime on a dataset of 53 loops ranging in length from 4 to 22 residues. When the prediction is performed in the crystal environment and including symmetry mates, the median backbone root mean square deviation (RMSD) is 0.5 Å to the crystal structure, with 91% of cases having an RMSD of less than 2.0 Å. When the prediction is performed in a noncrystallographic environment, where the scaffold is constructed by swapping the H3 loops between homologous antibodies, 70% of cases have an RMSD below 2.0 Å. These results show promise for ab initio loop predictions applied to modeling of antibodies. © 2012 Wiley Periodicals, Inc.
Highly covarying residues have a functional role in antibody constant domains
Authors: Proctor Elizabeth A. , Kota Pradeep , Demarest Stephen J. , Caravella Justin A. , Dokholyan Nikolay V.
Published: February 2013

The ability to generate and design antibodies recognizing specific targets has revolutionized the pharmaceutical industry and medical imaging. Engineering antibody therapeutics in some cases requires modifying their constant domains to enable new and altered interactions. Engineering novel specificities into antibody constant domains has proved challenging due to the complexity of inter‐domain interactions. Covarying networks of residues that tend to cluster on the protein surface and near binding sites have been identified in some proteins. However, the underlying role these networks play in the protein resulting in their conservation remains unclear in most cases. Resolving their role is crucial, because residues in these networks are not viable design targets if their role is to maintain the fold of the protein. Conversely, these networks of residues are ideal candidates for manipulating specificity if they are primarily involved in binding, such as the myriad interdomain interactions maintained within antibodies. Here, we identify networks of evolutionarily‐related residues in C‐class antibody domains by evaluating covariation, a measure of propensity with which residue pairs vary dependently during evolution. We computationally test whether mutation of residues in these networks affects stability of the folded antibody domain, determining their viability as design candidates. We find that members of covarying networks cluster at domain‐domain interfaces, and that mutations to these residues are diverse and frequent during evolution, precluding their importance to domain stability. These results indicate that networks of covarying residues exist in antibody domains for functional reasons unrelated to thermodynamic stability, making them ideal targets for antibody design. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Computationally‐predicted CB1 cannabinoid receptor mutants show distinct patterns of salt‐bridges that correlate with their level of constitutive activity reflected in G protein coupling levels, thermal stability, and ligand binding
Authors: Ahn Kwang H. , Scott Caitlin E. , Abrol Ravinder , Goddard William A. , Kendall Debra A.
Published: February 2013

The cannabinoid receptor 1 (CB1), a member of the class A G‐protein‐coupled receptor (GPCR) family, possesses an observable level of constitutive activity. Its activation mechanism, however, has yet to be elucidated. Previously we discovered dramatic changes in CB1 activity due to single mutations; T3.46A, which made the receptor inactive, and T3.46I and L3.43A, which made it essentially fully constitutively active. Our subsequent prediction of the structures of these mutant receptors indicated that these changes in activity are explained in terms of the pattern of salt‐bridges in the receptor region involving transmembrane domains 2, 3, 5, and 6. Here we identified key salt‐bridges, R2.37 + D6.30 and D2.63 + K3.28, critical for CB1 inactive and active states, respectively, and generated new mutant receptors that we predicted would change CB1 activity by either precluding or promoting these interactions. We find that breaking the R2.37 + D6.30 salt‐bridge resulted in substantial increase in G‐protein coupling activity and reduced thermal stability relative to the wild‐type reflecting the changes in constitutive activity from inactive to active. In contrast, breaking the D2.63 + K3.28 salt‐bridge produced the opposite profile suggesting this interaction is critical for the receptor activation. Thus, we demonstrate an excellent correlation with the predicted pattern of key salt‐bridges and experimental levels of activity and conformational flexibility. These results are also consistent with the extended ternary complex model with respect to shifts in agonist and inverse agonist affinity and provide a powerful framework for understanding the molecular basis for the multiple stages of CB1 activation and that of other GPCRs in general. Proteins 2013; 81:1304–1317. © 2013 Wiley Periodicals, Inc.
Statistical torsion angle potential energy functions for protein structure modeling: A bicubic interpolation approach
Authors: Kim Tae‐Rae , Yang Joshua SungWoo , Shin Seokmin , Lee Jinhyuk
Published: February 2013

A set of grid type knowledge‐based energy functions is introduced for ϕ–χ1, ψ–χ1, ϕ–ψ, and χ1–χ2 torsion angle combinations. Boltzmann distribution is assumed for the torsion angle populations from protein X‐ray structures, and the functions are named as statistical torsion angle potential energy functions. The grid points around periodic boundaries are duplicated to force periodicity, and the remedy relieves the derivative discontinuity problem. The devised functions rapidly improve the quality of model structures. The potential bias in the functions and the usefulness of additional secondary structure information are also investigated. The proposed guiding functions are expected to facilitate protein structure modeling, such as protein structure prediction, protein design, and structure refinement. Proteins 2013. Proteins 2013; 81:1156–1165. © 2013 Wiley Periodicals, Inc.
Structure and function of a TetR family transcriptional regulator, SbtR, from thermus thermophilus HB8
Authors: Agari Yoshihiro , Sakamoto Keiko , Yutani Katsuhide , Kuramitsu Seiki , Shinkai Akeo
Published: February 2013

SbtR is one of the four TetR family transcriptional regulators present in the extremely thermophilic bacterium, Thermus thermophilus HB8. We identified 10 genes controlled by four promoters with negative regulation by SbtR in vitro. The SbtR‐regulated gene products include probable transporters, probable enzymes for sugar or amino acid metabolism, and nucleic acid‐related enzymes. SbtR binds pseudopalindromic sequences, with the consensus sequence of 5′‐TGACCCNNKGGTCA‐3′ surrounding the promoters, and has a proposed 1:1 dimer binding stoichiometry. The X‐ray crystal structure analysis revealed that SbtR comprises either nine or 10 α‐helices and forms a dimer, as in the typical TetR family proteins. Similar to many characterized TetR family regulators, SbtR has a predicted ligand‐binding pocket at the center of each monomer. Interestingly, the SbtR dimer contains an intermolecular disulfide bridge, formed between the Cys164 residues at the entrance of the pocket. The Cys164Ser and Cys164Ala mutant SbtR proteins formed homodimers similar to that of the wild type, but their thermal stabilities were lower by about 8°C, indicating that the disulfide bridge contributes to the thermal stability of the protein. However, altered repression activity of the mutants was not observed in vitro. From these results, we propose that ligand‐binding is essential for SbtR to disengage from DNA, in a similar manner to the other characterized TetR family regulators. The formation and reduction of the disulfide bond might function in controlling the ligand‐binding affinity of this transcriptional regulator. Proteins 2013; 81:1166–1178. © 2013 Wiley Periodicals, Inc.
Interaction of metal chelators with different molecular forms of acetylcholinesterase and its significance in Alzheimer's disease treatment
Authors: Chitra Loganathan , Kumar Chinnadurai Raj , Basha Haleema M. , Ponne Saravanaraman , Boopathy Rathanam
Published: February 2013

The peripheral anionic site (PAS) of acetylcholinesterase (AChE) is involved in amyloid beta (Aβ) peptides aggregation of Alzheimer's disease (AD). AChE exhibits an aryl acylamidase (AAA) activity along with the well known esterase activity. Numerous studies have reported the beneficiary effect of metal chelators in AD treatment. Hence, a comparative study on the effect of metal chelators on both the esterase and AAA activity of AChE globular (G4 and G1) molecular forms was performed. The inhibitory effect of 1,10‐phenanthroline was high towards AChE esterase activity. The corresponding IC50 values for esterase activity of G4 and G1‐form was 190 µM and 770 µM and for AAA activity it was 270 µM and 2.74 mM, respectively. Kinetic studies on both forms of AChE show that 1,10‐phenanthroline inhibits esterase in competitive and AAA activity in non‐competitive manner. Protection studies further revealed that the nature of 1,10‐phenanthroline inhibition on AChE is through its direct binding to protein rather than its metal chelation property. Molecular docking studies shows orientation of 1,10‐phenathroline in the PAS through hydrophobic interactions with the PAS residues (Trp286, Tyr124 and Tyr341) and hydrogen bonding with Phe295. Further molecular dynamics simulation of “hAChE‐1,10‐phenanthroline” complex revealed that both hydrogen and hydrophobic interaction contribute equally for 1,10‐phenanthroline binding to hAChE. Such an interaction of 1,10‐phenanthroline on PAS may hinder “AChE‐Aβ peptide” complex formation. Hence, 1,10‐phenanthroline can act as a lead molecule for developing drug(s) against AD ailment with dual functions namely, anti‐cholinesterase and anti‐amyloid aggregation potency in a single chemical entity. Proteins 2013. Proteins 2013; 81:1179–1191. © 2013 Wiley Periodicals, Inc.
Guest Editorial on Meeting and Mating Across Borders: Union Formation in the European Union Single Market
Authors: de Valk Helga A. G. , Medrano Juan Díez
Published: February 2013

This editorial introduces a special issue and its different contributions. We provide an overarching background for the special issue by situating it in the context of the European Union integration process and through a general discussion of the role of intermarriage in establishing links across borders. The importance of studying union formation, that is, marriages between Europeans in the context of the European Single Market is discussed. We argue that marriages between Europeans can promote the development of trans‐European solidarity ties and may in this regard contribute to European identity formation. This article introduces the goals of the different research pieces in the special issue and outlines the overarching issues that are demonstrated by the papers collectively. We conclude that European binational marriages are still rather rare and that binational European couples are not a homogenous group. Our findings point towards the continued relevance of local geography, migrant history and patterns, as well as cultural and linguistic similarities for partner choice in a unified Europe. We call for a more integrated approach and a clear research agenda setting for the further study of union formation and dissolution in the European single market. Copyright © 2013 John Wiley & Sons, Ltd.
Shift in re‐randomization distribution with conditional randomization test
Authors: Kuznetsova Olga M. , Tymofyeyev Yevgen
Published: February 2013

Proschan, Brittain, and Kammerman made a very interesting observation that for some examples of the unequal allocation minimization, the mean of the unconditional randomization distribution is shifted away from 0. Kuznetsova and Tymofyeyev linked this phenomenon to the variations in the allocation ratio from allocation to allocation in the examples considered in the paper by Proschan et al. and advocated the use of unequal allocation procedures that preserve the allocation ratio at every step. In this paper, we show that the shift phenomenon extends to very common settings: using conditional randomization test in a study with equal allocation. This phenomenon has the same cause: variations in the allocation ratio among the allocation sequences in the conditional reference set, not previously noted. We consider two kinds of conditional randomization tests. The first kind is the often used randomization test that conditions on the treatment group totals; we describe the variations in the conditional allocation ratio with this test on examples of permuted block randomization and biased coin randomization. The second kind is the randomization test proposed by Zheng and Zelen for a multicenter trial with permuted block central allocation that conditions on the within‐center treatment totals. On the basis of the sequence of conditional allocation ratios, we derive the value of the shift in the conditional randomization distribution for specific vector of responses and the expected value of the shift when responses are independent identically distributed random variables. We discuss the asymptotic behavior of the shift for the two types of tests. Copyright © 2013 John Wiley & Sons, Ltd.
Robotic Anderson–Hynes dismembered pyeloplasty: initial experience
Authors: Moreno‐Sierra Jesús , Castillon‐Vela Ignacio , Ortiz‐Oshiro Elena , Galante‐Romo Isabel , Fernandez‐Perez Cristina , Senovilla‐Perez Jose L. , Casado‐Varela Javier , Garde‐Garcia Hector , Chavez‐Roa Cesar , Vera‐Gonzalez Vicente
Published: February 2013

Introduction

The introduction of the da Vinci® robotic system in 2000 has been a new step forward in the treatment of ureteropelvic junction obstruction (UPJO). The aim of this study was to analyse our initial experience with robot‐assisted dismembered Anderson–Hynes pyeloplasty and to perform a bibliographic review on the topic.

Patients and methods

We performed 11 robot‐assisted pyeloplasties between March 2007 and April 2011. UPJO diagnosis was made on clinical presentation and imaging techniques (CT scan and intravenous urography). All patients underwent basal and diuretic isotopic renograms to evaluate the degree of obstruction and impaired renal function. Median follow‐up was 10 (range 1–26) months.

Results

Mean patient age was 38.8 (range 23‐62) years. There were six women (55%) and five men (45%). All cases were primary surgeries. In four patients the cause of UPJO was a crossing vessel; the other seven patients had intrinsic obstruction. One case was associated with extraction of a calyceal lithiasis. Mean operative time was 189.4 min (125‐270 min). Average time from robotic arms docking was 116.5 (range 55–180) min. Average hospital stay was 4.18 (range 2–8) days. Conversion to open or laparoscopic surgery was not necessary in any case and there were no postoperative complications. Postoperative radiological evaluation and renograms showed good results in all cases.

Conclusions

Robotic surgery offers better ergonomics, enhanced three‐dimensional (3D) vision and more precise movements, easing intracorporeal suturing.These advantages make robotic pyeloplasty a reproducible technique that combines the high success rates of open surgery and the benefits of laparoscopic surgery. Copyright © 2013 John Wiley & Sons, Ltd.
FSW of T joints in overlap configuration: process optimization in joining dissimilar aluminium alloys for the aeronautic application
Authors: Ciliberto S. , Astarita A. , Squillace A.
Published: February 2013

The effect of welding parameters on the mechanical properties of friction stir‐welded dissimilar aluminium alloys in overlap joint configuration was studied. Both the welding configuration and the materials chosen were a typical skin‐stringer configuration, widely used for aeronautical fuselage panels. Mechanical properties were evaluated by means of both hoop stress and T‐pull test. Results show that there is a great dependence of the hoop stress resistance from welding parameters; conversely, T‐pull tests do not show the same dependence. The present work demonstrates the suitability of the x in lap configuration for joining dissimilar aluminium alloys. Copyright © 2013 John Wiley & Sons, Ltd.
Growth of Systems‐Centric Systems Engineering graduate programs in the United States and the role of their non‐tenure‐track faculty
Authors: Lasfer Kahina , Pyster Art
Published: February 2013

This study examines the growth of Systems‐Centric Systems Engineering (SCSE) graduate programs in the United States and the status of full‐time non‐tenure‐track faculty (NTTF) members within these programs. Growth is measured by the number of master's and PhD students who graduated from those programs. The annual production of master's degree graduates has grown by a factor of 5 during the period, increasing from 312 in 2001 to 1535 in 2010. Furthermore, the six largest SE programs accounted for more than half of those graduates. The annual production of PhD degrees has risen as well, though not as dramatically. In spite of such growth, less than 50% of SCSE programs hire NTTF, and, among them, the majority of the programs (65%) have four or fewer NTTF. Only 24% of the total faculty employed by SCSE programs in 2010 are NTTF, and most of them (67%) spend the majority of their time teaching; 65% of the respondents identified industrial experience as the most attractive reason for hiring them. Among SCSE programs that produced a high number of master's degree graduates, the ones that started between 2001 and 2005 employed a higher number of NTTF compared to those that started before 2001. The roles of NTTF are compared to those of tenured and tenure‐track faculty (TTTF). This paper concludes with recommendations on how to best use NTTF. ©2013 Wiley Periodicals, Inc. Syst Eng 16
Separation technologies for current and future biorefineries—status and potential of membrane‐based separation
Authors: Jiang Lan Ying , Zhu Jia Ming
Published: February 2013

Biorefinery is one of the most important industries in the modern world, as it provides a variety of products, particularly renewable bioenergy, which is highly vital to human existence (?). Among the separation technologies applied in biorefinery, membrane‐based separation has received great attention in past decades as it is in line with the worldwide move toward higher energy efficiency and lower environmental impact. Analysis of the academic and industrial activities being undertaken reveals that porous membranes like nanofiltration, ultrafiltration, and microfiltration are generally associated with pretreatment and hydrolysis procedures where separation is relied on for recovering value‐added materials with wide range of molecular weight and facilitating follow‐up bioconversion. An emerging field that highly appreciates porous membranes is biodiesel purification. Molecular level separations including gas product separation existing in thermal and anaerobic conversions and liquid alcoholic products recovery in microbial/enzymatic process offer more opportunity to membrane‐based gas separation and pervaporation using dense membranes. Membrane distillation and supported liquid membrane, commonly classed as new generation of membrane technology, show the potential in bioethanol recovery and hydrolysis step, respectively. Nonetheless, their competitiveness is to be confirmed. The function of membrane separation is being pushed further. Bearing in mind the importance of membranes with higher quality in terms of separation efficiency and material stability, we must also be prepared for the challenges deriving from some engineering aspects such as membrane fouling, module design, and process optimization.

This article is categorized under:

Bioenergy > Science and Materials
Selective Policy of No Drain after Pancreaticoduodenectomy Is a Valid Option in Patients at Low Risk of Pancreatic Fistula: A Case‐Control Analysis
Authors: Lim Chetana , Dokmak Safi , Cauchy François , Aussilhou Beatrice , Belghiti Jacques , Sauvanet Alain
Published: February 2013

Background

Abdominal drainage is routinely performed after pancreaticoduodenectomy (PD), but this policy has recently been challenged. The aim of the present study was to assess whether abdominal drainage could be omitted after PD in patients at low risk of pancreatic fistula (PF).

Methods

From 2009 to 2011, 27 consecutive patients underwent PD without abdominal drainage. Their preoperative characteristics and postoperative outcomes were compared to those of 27 matched patients undergoing PD with prophylactic drainage. Patients were matched 1:1 in terms of demographic data, preoperative weight loss, preoperative biliary drainage, surgical indication, and main risk factors of PF (pancreatic texture, main duct size, and body mass index).

Results

Overall morbidity rates (no drainage, 56 % vs. drainage, 70 %; p < 0.4) and operative mortality (1 patient in each group) were similar in both groups. The two groups did not differ significantly in terms of delayed gastric emptying (15 vs. 11 %; p = 0.68), and chylous ascites (4 vs. 15 %; p = 0.35). Radiological or surgical interventions for surgical complications were required in 2 patients (1 in each group). Pancreatic fistula rate (0 vs. 22 %; p = 0.009) and hospital stay (10 vs. 15 days; p = 0.004) were significantly reduced in the no drainage group as compared to the drainage group. The hospital readmission rate was similar in the two groups (no drainage, 3.7 vs. 0 %; p = 0.31).

Conclusions

This study suggests that abdominal drainage should not be considered routinely after PD in patients at low risk of PF. A no drain policy may reduce hospital stay after PD.
Cyclodextrin alleviates neuronal storage of cholesterol in Niemann‐Pick C disease without evidence of detectable blood–brain barrier permeability
Authors: Pontikis Charles C. , Davidson Cristin D. , Walkley Steven U. , Platt Frances M. , Begley David J.
Published: February 2013

Niemann‐Pick type C disease is an inherited autosomal recessive neurodegenerative disorder characterised by the accumulation of unesterified cholesterol and sphingolipids within the endosomal/lysosomal compartments. It has been observed that the administration of hydroxypropyl‐β‐cyclodextrin (HPBCD) delays onset of clinical symptoms and reduces accumulation of cholesterol and gangliosides within neuronal cells. It was assumed that HPBCD exerts its action by readily entering the CNS and directly interacting with neurones and other brain cells to facilitate removal of stored cholesterol from the late endosomal/lysosomal compartment. Here, we present evidence that refutes this hypothesis. We use two well established techniques for accurately measuring brain uptake of solutes from blood and show that there is no significant crossing of HPBCD into the brain. The two techniques are brain in situ perfusion and intraperitoneal injection followed by multi‐time‐point regression analysis. Neither study demonstrates significant, time‐dependent uptake of HPBCD in either adult or neonatal mice. However, the volume of distribution available to HPBCD (0.113 ± 0.010 ml/g) exceeds the accepted values for plasma and vascular volume of the brain. In fact, it is nearly three times larger than that for sucrose (0.039 ± 0.006 ml/g). We propose that this indicates cell surface binding of HPBCD to the endothelium of the cerebral vasculature and may provide a mechanism for the mobilisation and clearance of cholesterol from the CNS.
Transfer of Phenolic Compounds from Olive Mill Wastewater to Olive Cake Oil
Authors: Boudissa Farida , Kadi Hocine
Published: February 2013

The transfer of the phenolic compounds from olive mill wastewater (OMW) to oil extracted under microwave from olive cake (OC) was carried out by using the following operations: mixing of the olive mill wastewater with the olive cake, drying of the mixture and recovery by solvent of the olive cake oil enriched by phenolic compounds. In the first part of this work, we made a screening design using a Hadamard matrix to quickly locate the factors influencing the process. Among five potentially influential parameters, we found that only three were actually active (OMW/OC ratio noted R, mixing velocity of mixture Vm and mixing time Tm). In the second part, fractional factorial design (25−1) was performed to evaluate the effects of five variables (three of them being selected by screening with exposition time Te and radiation power P) and their eventual interactions. The p value (p < 0.05) indicated that R, P,Te, Vm and Tm had significant effects on the response followed by the interaction effects between R‐P, P‐Te, R‐Vm, Te‐Vm, Te‐Tm, and Vm‐Tm. Under optimal conditions, the addition of OMW to OC increased the phenolic compounds content in the oil from 0.04 ± 0.01 to 0.13 ± 0.02 g/L.
Endovascular Therapy for Acute Trauma: A Pictorial Review
Authors: Mirakhur Anirudh , Cormack Richard , Eesa Muneer , Wong Jason K.
Published: February 2013

The traditional role of radiology in the multidisciplinary approach to modern trauma care has been primarily diagnostic and noninvasive. With the advent of more sophisticated and faster imaging equipment, computed tomography has further entrenched its role as the workhorse of trauma imaging. However, the specialty has evolved over the years with various therapeutic techniques now part of the interventional radiology armamentarium. Several of these techniques have become essential for the management of critically ill trauma patients. This article provides an overview of the common imaging findings of vascular and solid organ trauma from head to toe and subsequent endovascular interventions in these critically ill trauma patients.
Effect of intratympanic mitomycin C on the development of cholesteatoma and otitis media in rats
Authors: Melo A A , Caldas Neto S S , Leão F S , Campos A J C
Published: February 2013

Objective:

To determine whether the administration of mitomycin C prevents propylene glycol exposure from inducing middle-ear cholesteatoma and otitis media, in a rat model.

Methods:

Twenty-four Wistar rats underwent intratympanic injections on days 1, 8 and 15, via the tympanic membrane pars tensa, in both the right and left ears. The right ear injection solution contained 50 per cent propylene glycol, gentamicin and saline (0.9 per cent), while the left ear solution contained 50 per cent propylene glycol, gentamicin and mitomycin C. Animals were sacrificed and examined.

Results:

There were statistically significant differences between the control and experimental groups for tympanic bulla mucosal thickness (p = 0.004) but not for tympanic membrane thickness (p = 0.371), otomicroscopic findings (p = 0.262), or the presence of exudate (p = 0.125), fibrosis (p = 1.000) or cholesteatoma (p = 0.687).

Conclusion:

Intratympanic mitomycin C was ineffective in preventing middle-ear cholesteatoma and otitis media in this rat model.
Secondary, profound, sensorineural hearing loss after recovery from haemolytic uraemic syndrome due to enterohaemorrhagicEscherichia coli, and subsequent cochlear implantation, in two Japanese children
Authors: Minami S B , Takegoshi H , Shinjo Y , Kaga K
Published: February 2013

Objectives:

To describe two cases of profound hearing loss secondary to enterohaemorrhagicEscherichia coliinfection, and to report the efficacy of subsequent cochlear implantation.

Results:

The first case was a four-year-old girl admitted to hospital withEscherichia coliO157 infection and haemolytic uraemic syndrome. Mild hearing loss was confirmed five months after discharge, progressing to profound loss three months later. At the age of seven years, she underwent cochlear implantation, with remarkable improvement in speech perception and production. The second case was a three-year-old boy admitted with haemolytic uraemic syndrome caused byEscherichia coliO111 infection. One year after disease onset, profound hearing loss was confirmed. Cochlear implantation at the age of five years produced significant recovery of auditory function.

Conclusion:

This study represents the first published report of secondary hearing loss after recovery from haemolytic uraemic syndrome caused by enterohaemorrhagicEscherichia coli. It indicates that cochlear implantation can restore hearing function in such patients.
Caught on camera: hairy polyp of the posterior tonsillar pillar
Authors: Seng S , Kieran S M , Vargas S O , Mcgill T J
Published: February 2013

Background:

Hairy polyps are rare congenital growths of the head and neck, mainly found in the nasopharynx and oropharynx. They are made up of two germ cell layers: the ectoderm and mesoderm.

Methods:

This paper reports a four-month-old who presented with breathing and feeding difficulties. Clinical examination was unremarkable, but a video taken by the patient's mother on her smartphone showed a mass protruding from the infant's mouth. Laryngoscopy performed in the operating theatre showed that the mass emanated from the left posterior tonsillar pillar.

Results:

The mass was removed transorally with no complications. Pathological examination showed a skin-covered pedunculated structure characteristic of a hairy polyp. The patient's follow up was unremarkable.

Conclusion:

To the best of our knowledge, this is the second English-language case report of a patient with a hairy polyp emanating from a posterior tonsillar pillar. This paper also highlights the growing usage of smartphones by patients to help physicians with their diagnosis and management.
Effects of resource limitation on habitat usage by the browser guild in Hluhluwe-iMfolozi Park, South Africa
Authors: O'Kane Christopher A. J. , Duffy Kevin J. , Page Bruce R. , Macdonald David W.
Published: February 2013

Resource depletion and associated increases in interspecific competition are likely to influence differential habitat usage amongst a guild. We tested some prominent theoretical concepts using observed differences in seasonal habitat use amongst the savanna browser guild (elephant, giraffe, impala, kudu and nyala) in Hluhluwe-iMfolozi Park, South Africa. Herbivore locations (n = 3108) were recorded over 2 y using repeated road transects and, for elephant, GPS collars (187 254 downloads). Densities were calculated using a novel GIS approach designed to be a cost-effective method for annual censuses, but also able to cope with abrupt changes in visibility. Selectivity for (Manly's α) vegetation types, and overlap (Schoener's index) in vegetation type usage were calculated. Resource depletion in the dry season resulted in all members of the guild increasing selectivity for vegetation types (sum of absolute values away from the neutral value for Manly's alpha for the guild: dry seasons 3.97, 5.16; corresponding wet seasons 3.12, 3.68), but decreasing interspecific overlap (80% of Schoener's indices lower in dry season versus wet season). These effects were more marked over the second, more severe, dry season. We found support for the niche overlap hypothesis and the niche compression hypothesis. The Jarman–Bell principle was generally supported, although unexpectedly during the severe dry season elephant showed the most selectivity for vegetation type. The greater the resource depletion, the more relevant interspecific differences in habitat usage become in relation to the differential impacts of guild members.
The Missing Ethics of Mining
Authors: Siegel Shefa
Published: February 2013

In the middle of the 1980s the pastoralists of Essakane, Burkina Faso, were dying. Drought gripped the drylands of West Africa, crippling peoples' semi-nomadic livelihoods of millet farming and goat herding. When rain finally returned after three years, the earth had hardened like concrete and water skimmed across the floodplain, barely penetrating the surface. Without arable land the people faced famine—until they discovered gold. Instead of a disaster area, Essakane transformed into a commercial oasis: a mining town of 10,000 miners and traders where gold is processed and exchanged for food, cloth, spices, and animals.
CURRENCY UNION, FREE-TRADE AREAS, AND BUSINESS CYCLE SYNCHRONIZATION
Authors: De Pace Pierangelo
Published: February 2013

Since the 1970s, the characteristics of international business cycles have changed, and deeper economic integration has modified the features of cross-country comovement. We formally test for correlation shifts in measures of real economic activity and economic/financial integration. In Europe we find some statistically significant evidence of higher correlations for several subgroups of countries following the creation of the EMU in 1999. We detect significantly more pronounced correlations between Mexico and the United States and between Mexico and Canada in North America after the enforcement of the NAFTA in 1994. Results are derived from an econometric framework based on nonparametric iterated stationary bootstrap methods, whose statistical reliability and performance we assess through Monte Carlo simulations.
Community-wide plasmid gene mobilization and selection
Authors: Sentchilo Vladimir , Mayer Antonia P , Guy Lionel , Miyazaki Ryo , Green Tringe Susannah , Barry Kerrie , Malfatti Stephanie , Goessmann Alexander , Robinson-Rechavi Marc , van der Meer Jan R
Published: February 2013

Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host’s chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.
Quality or quantity: is nutrient transfer driven more by symbiont identity and productivity than by symbiont abundance?
Authors: Freeman Christopher J , Thacker Robert W , Baker David M , Fogel Marilyn L
Published: February 2013

By forming symbiotic interactions with microbes, many animals and plants gain access to the products of novel metabolic pathways. We investigated the transfer of symbiont-derived carbon and nitrogen to the sponges Aplysina cauliformis, Aplysina fulva, Chondrilla caribensis, Neopetrosia subtriangularis and Xestospongia bocatorensis, all of which host abundant microbial populations, and Niphates erecta, which hosts a sparse symbiont community. We incubated sponges in light and dark bottles containing seawater spiked with 13C- and 15N-enriched inorganic compounds and then measured 13C and 15N enrichment in the microbial (nutrient assimilation) and sponge (nutrient transfer) fractions. Surprisingly, although most sponges hosting abundant microbial communities were more enriched in 13C than N. erecta, only N. subtriangularis was more enriched in 15N than N. erecta. Although photosymbiont abundance varied substantially across species, 13C and 15N enrichment was not significantly correlated with photosymbiont abundance. Enrichment was significantly correlated with the ratio of gross productivity to respiration (P:R), which varied across host species and symbiont phylotype. Because irradiance impacts P:R ratios, we also incubated A. cauliformis in 13C-enriched seawater under different irradiances to determine whether symbiont carbon fixation and transfer are dependent on irradiance. Carbon fixation and transfer to the sponge host occurred in all treatments, but was greatest at higher irradiances and was significantly correlated with P:R ratios. Taken together, these results demonstrate that nutrient transfer from microbial symbionts to host sponges is influenced more by host–symbiont identities and P:R ratios than by symbiont abundance.
“The Caterpillar”: A Novel Reading Passage for Assessment of Motor Speech Disorders
Authors: Patel Rupal , Connaghan Kathryn , Franco Diana , Edsall Erika , Forgit Dory , Olsen Laura , Ramage Lianna , Tyler Emily , Russell Scott
Published: February 2013

Purpose

A review of the salient characteristics of motor speech disorders and common assessment protocols revealed the need for a novel reading passage tailored specifically to differentiate between and among the dysarthrias (DYSs) and apraxia of speech (AOS).

Method

“The Caterpillar” passage was designed to provide a contemporary, easily read, contextual speech sample with specific tasks (e.g., prosodic contrasts, words of increasing length and complexity) targeted to inform the assessment of motor speech disorders. Twenty-two adults, 15 with DYS or AOS and 7 healthy controls (HC), were recorded reading “The Caterpillar” passage to demonstrate its utility in examining motor speech performance.

Conclusion

Analysis of performance across a subset of segmental and prosodic variables illustrated that “The Caterpillar” passage showed promise for extracting individual profiles of impairment that could augment current assessment protocols and inform treatment planning in motor speech disorders.
Communicative Gesture Use in Infants With and Without Autism: A Retrospective Home Video Study
Authors: Watson Linda R. , Crais Elizabeth R. , Baranek Grace T. , Dykstra Jessica R. , Wilson Kaitlyn P.
Published: February 2013

Purpose

The authors aimed to compare gesture use in infants with autism with gesture use in infants with other developmental disabilities (DD) or typical development (TD).

Method

Children with autism (
n
= 43), DD (
n
= 30), and TD (
n
= 36) were recruited at ages 2 to 7 years. Parents provided home videotapes of children in infancy. Staff compiled video samples for 2 age intervals (9–12 and 15–18 months) and coded samples for frequency of social interaction (SI), behavior regulation (BR), and joint attention (JA) gestures.

Results

At 9–12 months, infants with autism were less likely to use JA gestures than infants with DD or TD, and less likely to use BR gestures than infants with TD. At 15–18 months, infants with autism were less likely than infants with DD to use SI or JA gestures, and less likely than infants with TD to use BR, SI, or JA gestures. Among infants able to use gestures, infants with autism used fewer BR gestures than those with TD at 9–12 months, and fewer JA gestures than infants with DD or TD at 15–18 months.

Conclusion

Differences in gesture use in infancy have implications for early autism screening, assessment, and intervention.
An Evidence-Based Systematic Review on Communication Treatments for Individuals With Right Hemisphere Brain Damage
Authors: Lehman Blake Margaret , Frymark Tobi , Venedictov Rebecca
Published: February 2013

Purpose

The purpose of this review is to evaluate and summarize the research evidence related to the treatment of individuals with right hemisphere communication disorders.

Method

A comprehensive search of the literature using key words related to right hemisphere brain damage and communication treatment was conducted in 27 databases (e.g., PubMed, CINAHL). On the basis of a set of pre-established clinical questions, inclusion/exclusion criteria, and search parameters, studies investigating sentence- or discourse-level treatments were identified and evaluated for methodological quality. Data regarding participant, intervention, and outcome variables were reported.

Results

Only 5 studies were identified, each representing a different sentence- or discourse-level treatment approach and reporting a wide range of prosodic, expressive, receptive, and pragmatic outcomes.

Conclusion

Although the state of the evidence pertaining to right hemisphere communication treatments is at a very preliminary stage, some positive findings were identified to assist speech-language pathologists who are working with individuals with right hemisphere brain damage. Clinical implications and recommendations for future research are explored.