bluuebunny/crossref_metadata_2025 huggingface dataset:
Error Analysis in Neuropsychological Assessment of Verbal Memory and Learning
Authors: Heubrock Dietmar
Published: April 2008

Performance on a German version of the Rey Auditory-Verbal Learning Test (AVLT) was investigated for 64 juvenile patients who were subdivided in 6 clinical groups. In addition to standard evaluation of AVLT protocols which is usually confined to items recalled correctly, an error analysis was performed. Differentiating between total errors (TE), repetition errors (RE), and misnamings (ME), substantial differences between clinical groups could be demonstrated. It is argued that error analysis of verbal memory and learning enriches the understanding of neuropsychological syndromes, and provides additional information for diagnostic and clinical use. Thus, it is possible to gain a more accurate picture so that patients can be appropriately retrained, and research into the functional causes of memory and learning disorders can be intensified.
Psychological Evidence in Court
Authors: Gudjonsson Gisli H.
Published: April 2008

Psychologists began to give evidence in European courts about a century ago. Their original role, heavily influenced by the development of experimental psychology, which has been retained and is successfully being applied to cases. Psychologists have subsequently developed an important clinical role in judicial proceedings, which complements the role fulfilled by forensic psychiatrists. The author argues that psychologists now function more independently than ever before, the demand for their services is growing rapidly both in civil and criminal proceedings, and their status is greatly enhanced.
Prehistory of the International Test Commission 1English translation by Jacques Grégoire.
Authors: Cardinet Jean
Published: April 2008

The author reports on the early stages of the International Test Commission (ITC) of which he was one of the founders. The roots of the ITC can be found in the second half of the sixties when some Swiss psychologists decided to attempt to gain a more thorough control of the distribution and the use of tests. They became quickly aware that an exclusively national action would fail because the commercial trade in tests had no such frontiers. It was necessary to create an international organization devoted to this mission. In 1974, during the Congress of the International Association of Applied Psychology in Montreal, the International Test Commission was created. And, at the beginning of 1975, the first issue of the Bulletin was published, at which time it was included in the International Review of Applied Psychology.
Cultural Bias in Assessment: Historical and Thematic Issues
Authors: Poortinga Ype H.
Published: April 2008

In this introductory article the development of ideas on cultural bias in tests since the sixties is briefly reviewed and three approaches are mentioned. A distinction is made between the tradition of culture fair use of tests that is directed more towards selection in a multicultural society and the tradition of cross-cultural comparison that is concerned more with theoretical questions about cultural differences in behavior. The concerns of the former tradition have formed the main impetus for the development of psychometric analysis techniques. It is argued that some key problems of bias cannot be solved by further sophistication of statistical procedures, suggesting that a broadening of perspective in the field of bias analysis is desirable. Directions in which this can be achieved are indicated.
A Modification of the Payne-Jones Method of Identifying Abnormal Differences in WISC-R Performance and Verbal IQ's
Authors: Hsu Louis M.
Published: April 2008

The difference (D) between a person's Verbal IQ (VIQ) and Performance IQ (PIQ) has for some time been considered clinically meaningful ( Kaufman, 1976 , 1979 ; Matarazzo, 1990 , 1991 ; Matarazzo & Herman, 1985 ; Sattler, 1982 ; Wechsler, 1984 ). Particularly useful is information about the degree to which a difference (D) between scores is “abnormal” (i.e., deviant in a standardization group) as opposed to simply “reliable” (i.e., indicative of a true score difference) ( Mittenberg, Thompson, & Schwartz, 1991 ; Silverstein, 1981 ; Payne & Jones, 1957 ). Payne and Jones (1957) proposed a formula to identify “abnormal” differences, which has been used extensively in the literature, and which has generally yielded good approximations to empirically determined “abnormal” differences ( Silverstein, 1985 ; Matarazzo & Herman, 1985 ). However applications of this formula have not taken into account the dependence (demonstrated by Kaufman, 1976 , 1979 , and Matarazzo & Herman, 1985 ) of Ds on Full Scale IQs (FSIQs). This has led to overestimation of “abnormality” of Ds of high FSIQ children, and underestimation of “abnormality” of Ds of low FSIQ children. This article presents a formula for identification of abnormal WISC-R Ds, which overcomes these problems, by explicitly taking into account the dependence of Ds on FSIQs.
Recommendations by the Canadian Psychological Association for Improving the North American Safeguards that Help Protect the Public Against Test Misuse
Authors: Simner Marvin L.
Published: April 2008

An investigation by the Canadian Psychological Association was undertaken to examine the effectiveness of the two major safeguards that the North American test industry normally employs to help protect the public against test misuse. The outcome of this investigation, which revealed serious shortcomings in the effectiveness of both safeguards, led to a series of recommendations which were approved by the Association's Board of Directors. The purpose of this article is to bring the recommendations, together with the supporting evidence that gave rise to the need for these recommendations, to the attention of the international test community.
Regulations Concerning Test Qualifications and Test Use in The Netherlands
Authors: Evers Arne
Published: April 2008

In this article the policy and regulations of the Dutch Association of Psychologists to improve the use of tests in the Netherlands are discussed. Two approaches are distinguished: the information approach and the registration approach. The Dutch Committee on Testing Affairs works primarily from the information approach point of view, such as in their regular publication of a Documentation of Tests, their rating of tests and the translation of the APA Standards for Educational and Psychological Testing. Both the history of the registration approach in the Netherlands and its present situation are discussed. The development and the official introduction in 1994 of a system of registration for psychologists who administer tests are considered a great improvement. Three categories of tests and test users were defined in the regulation with regard to buying permits. In the final section some suggestions are made for further improvement, such as a better underpinning of the registration system, taking care of a greater acceptance of the regulation in the field of work and organization, and standardizing courses in test training.
Promoting High Standards for Test Use: Developments in the United States
Authors: Fremer John
Published: April 2008

Recent developments in the United States regarding the promotion of high standards for test use are described. Four areas are covered: the development of testing standards, qualifications to purchase and use tests, educating test users, and developments to watch (computer-based testing and performance testing). It is argued that at the same time as we are opening the way to improved testing through innovative applications of computer technology and performance assessments, there are economic forces that have the potential to undermine our basic standards. Each of the professionals in the field of testing must contribute their talent to upholding high standards to that test takers derive the benefits that come from the productive use of tests.
The Role of Observational Methods in the Assessment and Analysis of Behavior Interaction in Small Groups
Authors: Nell Verena , Westmeyer Hans
Published: April 2008

This article describes an observational methodology for the assessment and analysis of behavior interactions in small groups and its links to a theory of behavior interaction between two or more persons. The observational method requires the development of a category system and the selection of an interactional setting to which it is applied, recording and coding procedures, and the identification of sequential dependencies of behavior categories. The method is illustrated by describing its application to the investigation of family triads. The substantive assumptions of the theory of behavior interaction in triads are outlined, and some results of their empirical test are reported. Finally, the issue of dependence of the degree of corroboration of the theory on the observational methods used to test the theory is discussed.
Evidence of Data and Confidence in Clinical Judgments
Authors: Gambara Hilda , Leon Orfelio G.
Published: April 2008

The literature about research on people's confidence in their general knowledge has usually reported an overconfidence effect (mean subjective probability is higher than percentage of correct answers) with tasks of moderate and extreme difficulty. With easy tasks it has found the opposite effect: underconfidence. However, there are few studies which analyze the relationship between the subjects' confidence and the way they perceive the task, and even fewer which examine this question in higher real-life fields, such as those of clinical diagnosis. For the above reasons, we analyzed people's confidence in a specific context: clinical judgments. And we carried out an experiment in order to study the relationship between perceived information in a set of clinical cases and people's confidence in their diagnostic judgment. We found a linear relationship between them.
An efficient method of selecting ocean observing locations for capturing the leading modes and reconstructing the full field
Authors: Zhang Yanwu , Bellingham James G.
Published: April 2008

We present a method of selecting a small number of observing locations for capturing the leading spatial modes of an ocean field and reconstructing the field, assuming sufficient historical data for extraction of the field's empirical orthogonal functions (EOFs). The selection metric contains two main requirements: (1) The EOFs should have large magnitudes at the selected locations. (2) The cross products between the EOFs should be small at the selected locations. We select observing points sequentially: adding points one by one, without modifying the already picked ones. Selection of each location is by a simple sorting based on the presented metric. We apply the method to the Pacific sea surface temperature (SST) field, using the Smith‐Reynolds SST data set and the Tropical Atmosphere Ocean Project (TAO) buoys' SST measurements. We demonstrate that using observations at a small number of selected locations, one can quite accurately estimate the leading modes' amplitudes. Consequently, the full field can be reconstructed by observations at the selected locations. To evaluate the performance gain realized by employing the presented algorithm, we also provide two comparisons. In the first, we confine selections to regions considered logistically accessible. In the second, we use locations of existing buoys. The reconstruction error using observing locations selected by our algorithm is significantly lower than that using the buoys' locations. The presented algorithm takes into account mismatch between the base data set and the observations.
Mean vertical motions and their time‐height variations in the lower troposphere obtained from a UHF wind profiler at Pune, a tropical Indian station
Authors: Deshpande Sachin M. , Raj P. Ernest
Published: April 2008

A 404 MHz wind profiler (UHF radar) system has been in continuous operation since June 2003 at Pune (18°32′N, 73°51′E), a tropical Indian station. The system enables measurement of all three components (zonal, meridional and vertical) of the wind field with height coverage from 1.05 km to about 10 km and a height resolution of 300 m. Daily mean profile data of vertical velocity in the lower troposphere obtained during the 3‐year period, June 2003 to May 2006, has been used in this study to investigate the long‐term mean clear‐air vertical velocity, its variability, and seasonal/intraseasonal variations. Mean vertical velocities varied between −5.30 cm s−1 and +1.30 cm s−1, and mean vertical motions are predominantly downward at altitudes above 3 km. Significant seasonal variation in vertical velocity has been observed. During southwest monsoon months (June–September) a vertical two‐cell structure in vertical velocity has been noticed with upward motions below 4 km and downward motion above. In the premonsoon months (March–May) vertical motions are predominantly downward throughout the lower troposphere. Variability is larger during the monsoon and premonsoon seasons and is smaller during postmonsoon (October–November) and winter (December–February) seasons. Vertical velocities at altitudes below 3 km reveal significant semiannual and annual oscillations. Mean diurnal variations during SW monsoon period show interesting features. The observed variability in vertical velocities, especially in layers close to the surface, is explained to be due to the highly variable weather conditions on local as well as synoptic scale at this tropical station.
Substrate‐induced DNA strand misalignment during catalytic cycling by DNA polymerase λ
Authors: Bebenek Katarzyna , Garcia‐Diaz Miguel , Foley Meredith C , Pedersen Lars C , Schlick Tamar , Kunkel Thomas A
Published: March 2008

The simple deletion of nucleotides is common in many organisms. It can be advantageous when it activates genes beneficial to microbial survival in adverse environments, and deleterious when it mutates genes relevant to survival, cancer or degenerative diseases. The classical idea is that simple deletions arise by strand slippage. A prime opportunity for slippage occurs during DNA synthesis, but it remains unclear how slippage is controlled during a polymerization cycle. Here, we report crystal structures and molecular dynamics simulations of mutant derivatives of DNA polymerase λ bound to a primer–template during strand slippage. Relative to the primer strand, the template strand is in multiple conformations, indicating intermediates on the pathway to deletion mutagenesis. Consistent with these intermediates, the mutant polymerases generate single‐base deletions at high rates. The results indicate that dNTP‐induced template strand repositioning during conformational rearrangements in the catalytic cycle is crucial to controlling the rate of strand slippage.
Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen‐induced arthritis
Authors: Gao Beixue , Lee Sang‐Myeong , Chen An , Zhang Jinping , Zhang Donna D , Kannan Krishnaswamy , Ortmann Robert A , Fang Deyu
Published: March 2008

The E3 ubiquitin ligase synoviolin (SYVN1) functions as an anti‐apoptotic factor that is responsible for the outgrowth of synovial cells during the development of rheumatoid arthritis. The molecular mechanisms underlying SYVN1 regulation of cell death are largely unknown. Here, we report that elevated SYVN1 expression correlates with decreased levels of the protein inositol‐requiring enzyme 1 (IRE1)—a pro‐apoptotic factor in the endoplasmic reticulum (ER)‐stress‐induced apoptosis pathway—in synovial fibroblasts from mice with collagen‐induced arthritis (CIA). SYVN1 interacts with and catalyses IRE1 ubiquitination and consequently promotes IRE1 degradation. Suppression of SYVN1 expression in synovial fibroblasts from CIA mice restores IRE1 protein expression and reverses the resistance of ER‐stress‐induced apoptosis of CIA synovial fibroblasts. These results show that SYVN1 causes the overgrowth of synovial cells by degrading IRE1, and therefore antagonizes ER‐stress‐induced cell death.
INS VNTR Is Not Associated With Childhood Obesity in 1,023 Families: A Family‐based Study
Authors: Bouatia‐Naji Nabila , De Graeve Franck , Brönner Günter , Lecoeur Cécile , Vatin Vincent , Durand Emmanuelle , Lichtner Peter , Nguyen Thuy T. , Heude Barbara , Weill Jacques , Lévy‐Marchal Claire , Hebebrand Johannes , Froguel Philippe , Meyre David
Published: April 2008

Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family‐based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.
Lactoferrin receptor mediates apo- but not holo-lactoferrin internalization via clathrin-mediated endocytosis in trophoblasts
Authors: Lopez Veronica , Kelleher Shannon L. , Lönnerdal Bo
Published: March 2008

LfR [Lf (lactoferrin) receptor] is expressed in most mammalian tissues, including placental trophoblasts, and is presumed to mediate the internalization of Lf. However, the physiological significance of trophoblast LfR is not understood. Using the CT (cytotrophoblast) cell model BeWo, we demonstrated that transfection with LfR siRNA (small interfering RNA) significantly decreased apo- but not holo-Lf uptake compared with mock-transfected controls and that apo- but not holo-Lf significantly increased MMP (matrix metalloproteinase)-2 activity. As Lf functionality is related to the presence (holo-Lf) or absence (apo-Lf) of iron within the Lf molecule, our results suggest that apo-Lf may play a role in cellular invasion. Moreover, we detected LfR (∼105 kDa) in association with the plasma membrane, and ligand blotting confirmed that Lf binds to a LfR of ∼105 kDa. Apo-Lf treatment significantly increased LfR abundance at the plasma membrane and internalization probably occurs via clathrin-mediated endocytosis through early and recycling endosomes, as LfR was co-localized with EEA1 (early endosome antigen 1) and TfR (transferrin receptor) using confocal microscopy, and hypertonic medium (0.4 M sucrose) significantly inhibited apo-Lf internalization. In summary, our data demonstrate that apo- but not holo-Lf is internalized by LfR and suggest that, following internalization via LfR, apo-Lf plays a role in CT invasiveness by inducing MMP-2 activity. Moreover, LfR facilitates apo-Lf uptake specifically through clathrin-mediated endocytosis into early endosomes and potentially into a recycling pathway. Taken together, our data provide a new dimension in understanding ligand-dependant function that may be directly related to the ability of LfR to selectively internalize apo- but not holo-Lf.
Quantification of PtdIns(3,4,5)P3 dynamics in EGF-stimulated carcinoma cells: a comparison of PH-domain-mediated methods with immunological methods
Authors: Yip Shu-Chin , Eddy Robert J. , Branch Angie M. , Pang Huan , Wu Haiyan , Yan Ying , Drees Beth E. , Neilsen Paul O. , Condeelis John , Backer Jonathan M.
Published: March 2008

Class IA PI3Ks (phosphoinositide 3-kinases) generate the secondary messenger PtdIns(3,4,5)P3, which plays an important role in many cellular responses. The accumulation of PtdIns(3,4,5)P3 in cell membranes is routinely measured using GFP (green fluorescent protein)-labelled PH (pleckstrin homology) domains. However, the kinetics of membrane PtdIns(3,4,5)P3 synthesis and turnover as detected by PH domains have not been validated using an independent method. In the present study, we measured EGF (epidermal growth factor)-stimulated membrane PtdIns(3,4,5)P3 production using a specific monoclonal anti-PtdIns(3,4,5)P3 antibody, and compared the results with those obtained using PH-domain-dependent methods. Anti-PtdIns(3,4,5)P3 staining rapidly accumulated at the leading edge of EGF-stimulated carcinoma cells. PtdIns(3,4,5)P3 levels were maximal at 1 min, and returned to basal levels by 5 min. In contrast, membrane PtdIns(3,4,5)P3 production, measured by the membrane translocation of an epitope-tagged BTKPH (PH domain of Bruton's tyrosine kinase), remained approx. 2-fold above basal level throughout 4–5 min of EGF stimulation. To determine the reason for this disparity, we measured the rate of PtdIns(3,4,5)P3 hydrolysis by measuring the decay of the PtdIns(3,4,5)P3 signal after LY294002 treatment of EGF-stimulated cells. LY294002 abolished anti-PtdIns(3,4,5)P3 membrane staining within 10 s of treatment, suggesting that PtdIns(3,4,5)P3 turnover occurs within seconds of synthesis. In contrast, BTKPH membrane recruitment, once initiated by EGF, was relatively insensitive to LY294002. These data suggest that sequestration of PtdIns(3,4,5)P3 by PH domains may affect the apparent kinetics of PtdIns(3,4,5)P3 accumulation and turnover; consistent with this hypothesis, we found that GRP-1 (general receptor for phosphoinositides 1) PH domains [which, like BTK, are specific for PtdIns(3,4,5)P3] inhibit PTEN (phosphatase and tensin homologue deleted on chromosome 10) dephosphorylation of PtdIns(3,4,5)P3in vitro. These data suggest that anti-PtdIns(3,4,5)P3 antibodies are a useful tool to detect localized PtdIns(3,4,5)P3, and illustrate the importance of using multiple approaches for the estimation of membrane phosphoinositides.
Structural basis for mannose recognition by a lectin from opportunistic bacteria Burkholderia cenocepacia
Authors: Lameignere Emilie , Malinovská Lenka , Sláviková Margita , Duchaud Eric , Mitchell Edward P. , Varrot Annabelle , Šedo Ondrej , Imberty Anne , Wimmerová Michaela
Published: March 2008

Chronic colonization of the lungs by opportunist bacteria such as Pseudomonas aeruginosa and members of the Bcc (Burkholderia cepacia complex) is the major cause of morbidity and mortality among CF (cystic fibrosis) patients. PA-IIL (lecB gene), a soluble lectin from Ps. aeruginosa, has been the subject of much interest because of its very strong affinity for fucose. Orthologues have been identified in the opportunist bacteria Ralstonia solanacearum, Chromobacterium violaceum and Burkholderia of Bcc. The genome of the J2315 strain of B. cenocepacia, responsible for epidemia in CF centres, contains three genes that code for proteins with PA-IIL domains. The shortest gene was cloned in Escherichia coli and pure recombinant protein, BclA (B. cenocepacia lectin A), was obtained. The presence of native BclA in B. cenocepacia extracts was checked using a proteomic approach. The specificity of recombinant BclA was characterized using surface plasmon resonance showing a preference for mannosides and supported with glycan array experiments demonstrating a strict specificity for oligomannose-type N-glycan structures. The interaction thermodynamics of BclA with methyl α-D-mannoside demonstrates a dissociation constant (Kd) of 2.75×10−6 M. The X-ray crystal structure of the complex with methyl α-D-mannoside was determined at 1.7 Å (1 Å=0.1 nm) resolution. The lectin forms homodimers with one binding site per monomer, acting co-operatively with the second dimer site. Each monomer contains two Ca2+ ions and one sugar ligand. Despite strong sequence similarity, the differences between BclA and PA-IIL in their specificity, binding site and oligomerization mode indicate that the proteins should have different roles in the bacteria.
Crystal structure and kinetic study of dihydrodipicolinate synthase from Mycobacterium tuberculosis
Authors: Kefala Georgia , Evans Genevieve L. , Griffin Michael D. W. , Devenish Sean R. A. , Pearce F. Grant , Perugini Matthew A. , Gerrard Juliet A. , Weiss Manfred S. , Dobson Renwick C. J.
Published: March 2008

The three-dimensional structure of the enzyme dihydrodipicolinate synthase (KEGG entry Rv2753c, EC 4.2.1.52) from Mycobacterium tuberculosis (Mtb-DHDPS) was determined and refined at 2.28 Å (1 Å=0.1 nm) resolution. The asymmetric unit of the crystal contains two tetramers, each of which we propose to be the functional enzyme unit. This is supported by analytical ultracentrifugation studies, which show the enzyme to be tetrameric in solution. The structure of each subunit consists of an N-terminal (β/α)8-barrel followed by a C-terminal α-helical domain. The active site comprises residues from two adjacent subunits, across an interface, and is located at the C-terminal side of the (β/α)8-barrel domain. A comparison with the other known DHDPS structures shows that the overall architecture of the active site is largely conserved, albeit the proton relay motif comprising Tyr143, Thr54 and Tyr117 appears to be disrupted. The kinetic parameters of the enzyme are reported: KMASA=0.43±0.02 mM, KMpyruvate=0.17±0.01 mM and Vmax=4.42±0.08 μmol·s−1·mg−1. Interestingly, the Vmax of Mtb-DHDPS is 6-fold higher than the corresponding value for Escherichia coli DHDPS, and the enzyme is insensitive to feedback inhibition by (S)-lysine. This can be explained by the three-dimensional structure, which shows that the (S)-lysine-binding site is not conserved in Mtb-DHDPS, when compared with DHDPS enzymes that are known to be inhibited by (S)-lysine. A selection of metabolites from the aspartate family of amino acids do not inhibit this enzyme. A comprehensive understanding of the structure and function of this important enzyme from the (S)-lysine biosynthesis pathway may provide the key for the design of new antibiotics to combat tuberculosis.
The isolated N-terminal domains of TIMP-1 and TIMP-3 are insufficient for ADAM10 inhibition
Authors: Rapti Magdalini , Atkinson Susan J. , Lee Meng-Huee , Trim Andrew , Moss Marcia , Murphy Gillian
Published: March 2008

ADAM (a disintegrin and metalloproteinase) 10 is a key member of the ADAM family of disintegrin and metalloproteinases which process membrane-associated proteins to soluble forms in a process known as ‘shedding’. Among the major targets of ADAM10 are Notch, EphrinA2 and CD44. In many cell-based studies of shedding, the activity of ADAM10 appears to overlap with that of ADAM17, which has a similar active-site topology relative to the other proteolytically active ADAMs. The tissue inhibitors of metalloproteinases, TIMPs, have proved useful in the study of ADAM function, since TIMP-1 inhibits ADAM10, but not ADAM17; however, both enzymes are inhibited by TIMP-3. In the present study, we show that, in comparison with ADAM17 and the MMPs (matrix metalloproteinases), the N-terminal domains of TIMPs alone are insufficient for the inhibition of ADAM10. This knowledge could form the basis for the design of directed inhibitors against different metalloproteinases.
The two PAN ATPases from Halobacterium display N-terminal heterogeneity and form labile complexes with the 20S proteasome
Authors: Chamieh Hala , Guetta Dorian , Franzetti Bruno
Published: March 2008

The PAN (proteasome-activating nucleotidase) proteins from archaea represent homologues of the eukaryotic 26S proteasome regulatory ATPases. In vitro the PAN complex has been previously shown to have a stimulatory effect on the peptidase activities of the 20S core. By using gradient ultracentrifugation we found that, in cellular extracts, the two PAN proteins from Halobacterium do not form stable high-molecular-mass complexes. Only PAN B was found to associate transiently with the 20S proteasome, thus suggesting that the two PAN proteins are not functionally redundant. The PAN B–20S proteasome complexes associate in an ATP-dependent manner and are stabilized upon nucleotide binding. The two PAN proteins were immunodetected in cellular extracts as N-terminal-truncated polypeptides. RNA-mapping experiments and sequence analysis indicated that this process involved transcript heterogeneities and dual translational initiation mechanisms. Taken together, our results suggest that PAN N-terminal modifications and their intracellular dynamics of assembly/association may constitute important determinants of proteolysis regulation.
Lipid phosphate phosphatases form homo- and hetero-oligomers: catalytic competency, subcellular distribution and function
Authors: Long Jaclyn S. , Pyne Nigel J. , Pyne Susan
Published: March 2008

Lipid phosphate phosphatases (LPP1–LPP3) have been topographically modelled as monomers (molecular mass of 31–36 kDa) composed of six transmembrane domains and with the catalytic site facing the extracellular side of the plasma membrane or the luminal side of intracellular membranes. The catalytic motif has three conserved domains, termed C1, C2 and C3. The C1 domain may be involved in substrate recognition, whereas C2 and C3 domains appear to participate in the catalytic dephosphorylation of the substrate. We have obtained three lines of evidence to demonstrate that LPPs exist as functional oligomers. First, we have used recombinant expression and immunoprecipitation analysis to demonstrate that LPP1, LPP2 and LPP3 form both homo- and hetero-oligomers. Secondly, large LPP oligomeric complexes that are catalytically active were isolated using gel-exclusion chromatography. Thirdly, we demonstrate that catalytically deficient guinea-pig FLAG-tagged H223L LPP1 mutant can form an oligomer with wild-type LPP1 and that wild-type LPP1 activity is preserved in the oligomer. These findings suggest that, in an oligomeric arrangement, the catalytic site of the wild-type LPP can function independently of the catalytic site of the mutant LPP. Finally, we demonstrate that endogenous LPP2 and LPP3 form homo- and hetero-oligomers, which differ in their subcellular localization and which may confer differing spatial regulation of phosphatidic acid and sphingosine 1-phosphate signalling.
The human SIRT3 protein deacetylase is exclusively mitochondrial
Authors: Cooper Helen M. , Spelbrink Johannes N.
Published: March 2008

It has recently been suggested that perhaps as many as 20% of all mitochondrial proteins are regulated through lysine acetylation while SIRT3 has been implicated as an important mitochondrial protein deacetylase. It is therefore of crucial importance that the mitochondrial localization of potential protein deacetylases is unambiguously established. Although mouse SIRT3 was recently shown to be mitochondrial, HsSIRT3 (human SIRT3) was reported to be both nuclear and mitochondrial and to relocate from the nucleus to the mitochondrion upon cellular stress. In the present study we show, using various HsSIRT3 expression constructs and a combination of immunofluorescence and careful subcellular fractionation, that in contrast with earlier reports HsSIRT3 is exclusively mitochondrial. We discuss possible experimental explanations for these discrepancies. In addition we suggest, on the basis of the analysis of public genome databases, that the full-length mouse SIRT3 protein is a 37 kDa mitochondrial precursor protein contrary to the previously suggested 29 kDa protein.
Control of AMPK-related kinases by USP9X and atypical Lys29/Lys33-linked polyubiquitin chains
Authors: Al-Hakim Abdallah K. , Zagorska Anna , Chapman Louise , Deak Maria , Peggie Mark , Alessi Dario R.
Published: March 2008

AMPK (AMP-activated protein kinase)-related kinases regulate cell polarity as well as proliferation and are activated by the LKB1-tumour suppressor kinase. In the present study we demonstrate that the AMPK-related kinases, NUAK1 (AMPK-related kinase 5) and MARK4 (microtubule-affinity-regulating kinase 4), are polyubiquitinated in vivo and interact with the deubiquitinating enzyme USP9X (ubiquitin specific protease-9). Knockdown of USP9X increased polyubiquitination of NUAK1 and MARK4, whereas overexpression of USP9X inhibited ubiquitination. USP9X, catalysed the removal of polyubiquitin chains from wild-type NUAK1, but not from a non-USP9X-binding mutant. Topological analysis revealed that ubiquitin monomers attached to NUAK1 and MARK4 are linked by Lys29 and/or Lys33 rather than the more common Lys48/Lys63. We find that AMPK and other AMPK-related kinases are also polyubiquitinated in cells. We identified non-USP9X-binding mutants of NUAK1 and MARK4 and find that these are hyper-ubiquitinated and not phosphorylated at their T-loop residue targeted by LKB1 when expressed in cells, suggesting that polyubiquitination may inhibit these enzymes. The results of the present study demonstrate that NUAK1 and MARK4 are substrates of USP9X and provide the first evidence that AMPK family kinases are regulated by unusual Lys29/Lys33-linked polyubiquitin chains.
The pluripotency rheostat Nanog functions as a dimer
Authors: Mullin Nicholas P. , Yates Adam , Rowe Arthur J. , Nijmeijer Bianca , Colby Douglas , Barlow Paul N. , Walkinshaw Malcolm D. , Chambers Ian
Published: March 2008

The defining activity of the homeodomain protein Nanog is the ability to confer cytokine-independent self-renewal upon ES (embryonic stem) cells in which it is overexpressed. However, the biochemical basis by which Nanog achieves this function remains unknown. In the present study, we show that Nanog dimerizes through a functionally critical domain. Co-immunoprecipitation of Nanog molecules tagged with distinct epitopes demonstrates that Nanog self-associates through a region in which every fifth residue is tryptophan. In vitro binding experiments establish that this region participates directly in self-association. Moreover, analytical ultracentrifugation indicates that, in solution, Nanog is in equilibrium between monomeric and dimeric forms with a Kd of 3 μM. The functional importance of Nanog dimerization is established by ES cell colony-forming assays in which deletion of the tryptophan-repeat region eliminates the capacity of Nanog to direct LIF (leukaemia inhibitory factor)-independent self-renewal.
Where in the cell is SIRT3? – functional localization of an NAD+-dependent protein deacetylase
Authors: Hallows William C. , Albaugh Brittany N. , Denu John M.
Published: March 2008

Sirtuins are NAD+-dependent enzymes that have been implicated in a wide range of cellular processes, including pathways that affect diabetes, cancer, lifespan and Parkinson's disease. To understand their cellular function in these age-related diseases, identification of sirtuin targets and their subcellular localization is paramount. SIRT3 (sirtuin 3), a human homologue of Sir2 (silent information regulator 2), has been genetically linked to lifespan in the elderly. However, the function and localization of this enzyme has been keenly debated. A number of reports have indicated that SIRT3, upon proteolytic cleavage in the mitochondria, is an active protein deacetylase against a number of mitochondrial targets. In stark contrast, some reports have suggested that full-length SIRT3 exhibits nuclear localization and histone deacetylase activity. Recently, a report comparing SIRT3−/− and SIRT+/+ mice have provided compelling evidence that endogenous SIRT3 is mitochondrial and appears to be responsible for the majority of protein deacetylation in this organelle. In this issue of the Biochemical Journal, Cooper et al. present additional results that address the mitochondrial and nuclear localization of SIRT3. Utilizing fluorescence microscopy and cellular fractionation studies, Cooper et al. have shown that SIRT3 localizes to the mitochondria and is absent in the nucleus. Thus this study provides additional evidence to establish SIRT3 as a proteolytically modified, mitochondrial deacetylase.
Regulation of the AMPK-related protein kinases by ubiquitination
Authors: Thomson David M. , Hansen Marc D. H. , Winder William W.
Published: March 2008

How can a constitutively active ‘master’ kinase with numerous downstream targets preferentially phosphorylate one or more of these without influencing all simultaneously? How might such a system be switched off? The characterization of the role of deubiquitination in regulating the phosphorylation and activation of AMPK (AMP-activated protein kinase)-related kinases by LKB1 suggests a novel and interesting mechanism for conferring signal transduction specificity and control at the kinase substrate level. In this issue of the Biochemical Journal, Al-Hakim et al. show that the AMPK-related kinases NUAK1 (AMPK-related kinase 5) and MARK4 (microtubule-affinity-regulating kinase 4) are polyubiquitinated in vivo and that they serve as substrates of the deubiquitinating enzyme USP9X; furthermore, the first evidence is provided for regulation of AMPK-related kinase family members mediated via unusual Lys29/Lys33 polyubiquitin chains, rather than the more common Lys48/Lys63 linkages.
Cruise Operations Management
Authors: Szarycz Gregory S.
Published: March 2008

Philip Gibson's monograph provides a comprehensive overview of the hotel, restaurant and corporate office sides of managing a cruise line and cruise ship and its associated systems. Taken as a whole, this book provides a much welcome addition to the area of management of hospitality and tourism enterprises, and in particular in the cruise sector. With its focus on the service economy, this book meets a long overdue need for a text on hospitality management processes and issues facing the cruise services sector. It is designed for newcomers and veterans alike, interested in developing or shaping their perspectives on cruise tourism and managerial work in tourism studies. It is relevant both as a textbook for degree-level programmes on tourism and as an important reference for human resource practitioners who are keen to be informed of the discussion of impacts and issues in modern cruise tourism management.
Particulate structure of L10 ordered ultrathin FePt films for perpendicular recording
Authors: Perumal A. , Takahashi Y. K. , Seki T. O. , Hono K.
Published: April 2008

We report the investigation of microstructure and magnetic properties of ultrathin FePt (1–10nm) films grown on oxidized Si substrates with a 10nm MgO(100) intermediate layer. The isolated FePt particles with high degree of L10 ordering and large magnetocrystalline anisotropy could be fabricated with a thickness of less than 5nm. Perpendicular coercivity of isolated FePt particles is controllable between 15 and 25kOe. These results are promising and highly desirable for magnetic recording applications.
Interplay between Er and Co magnetism in ErCo2
Authors: Herrero-Albillos J. , Paudyal D. , Bartolomé F. , García L. M. , Pecharsky V. K. , Gschneidner K. A. , Young A. T. , Jaouen N. , Rogalev A.
Published: April 2008

First principles calculations within the tight binding linear muffin tin orbital method confirm the ferrimagnetic coupling between the Er 4f and Co 3d moments in the magnetically ordered phase and the change of sign of the Co 3d magnetization across the magnetostructural transition. Both the experimental x-ray magnetic circular dichroism measurements and theoretical results show that the influence of the rare-earth moment on the Co sp band is so strong that the polarization of the sp band does not follow that of the 3d band, but is determined by the Er sublattice magnetization, both in the magnetically ordered and paramagnetic states.
Metal oxide semiconductor structure and transistor behaviour using a single and simple graph (Qψ) which takes into account all the physical and electrical parameters
Authors: Vincent Gilbert
Published: April 2008

Physical properties and electrical characteristics of the metal oxide semiconductor (MOS) structure and the MOS transistor depend on numerous parameters: doping and permittivity of the semiconductor, thickness, permittivity and charge of the oxide, temperature, and, obviously, gate, drain, and substrate voltages. In this paper, we propose a single and simple graph to visualize and highlight the impact of all these physical and electrical parameters. All main classical relationships can be easily deduced from this graph, which is an additional efficient tool to understand MOS device behaviors.
Bistable resistive states of amorphous SrRuO3 thin films
Authors: Son J. Y. , Shin Y.-H. , Park C. S.
Published: April 2008

We fabricated amorphous SrRuO3 thin films which exhibited the electronic transport behavior of an insulator that showed a three-dimensional hopping transport. Depending on the polarity of a sweep bias, bistable resistive states were observed in the capacitor consisted of an amorphous SrRuO3 thin film and Pt electrodes, which gives the opportunity for nonvolatile memory applications. From electric transport and optical conductivity data, we indirectly confirmed a probability of the mixed phase of SrO and RuO2 in the amorphous SrRuO3 thin film. This supports the applicability of a filament model as a mechanism for the bistable resistive states.
Far infrared reflection spectrum and IR-active modes of MgTiO3
Authors: Wang Chun-Hai , Kuang Xiao-Jun , Jing Xi-Ping , Lu Jing , Lü Xiang , Shao Jun
Published: April 2008

A MgTiO3 ceramic sample was synthesized by solid-state reactions and its far infrared (IR) reflection spectrum recorded. The IR-active vibrational modes of MgTiO3 were calculated using first-principle calculations and the modes were represented by linear combinations of the symmetry coordinates. Using the eigenfrequencies obtained by the density functional theory calculations as initial values, we fitted the infrared reflection spectrum using the four-parameter semiquantum (FPSQ) model and the Lorentz three-parameter classical model. The parameters (ΩjTO, ΩjLO, γjTO, γjLO in FPSQ fitting and Ωj, Sj, γj in the three-parameter model fitting) of seven of the eight modes predicted by group theory analysis were obtained. The transverse optical modes (in FPSQ) are assigned as 279cm−1 (Au), 383cm−1 (Au), 472cm−1 (Au), 673cm−1 (Au) and ∼262cm−1 (Eu), 317cm−1 (Eu), 416cm−1 (Eu), 531cm−1 (Eu). The modes Au (279cm−1), Eu (317cm−1), Au (472cm−1), and Eu (531cm−1), which contain larger components of cation vibrations, contribute most to the microwave dielectric constant and dielectric loss.
Dynamic bias temperature instability-like behaviors under Fowler–Nordheim program/erase stress in nanoscale silicon-oxide-nitride-oxide-silicon memories
Authors: Seo Seung Hwan , Kang Gu-Cheol , Roh Kang Seob , Kim Kwan Young , Lee Sunyeong , Song Kwan-Jae , Choi Chang Min , Park So Ra , Jeon Kichan , Park Jun-Hyun , Park Byung-Gook , Lee Jong Duk , Kim Dong Myong , Kim Dae Hwan
Published: April 2008

Bias temperature-dependent characteristics of nanoscale silicon-oxide-nitride-oxide-silicon memories are investigated under program/erase (P/E) Fowler–Nordheim (FN) stresses. In the erased cell, FN stress time evolution is found to be a similar physical process to the recovery of interface traps (NIT) that takes place under the dynamic negative bias temperature instability stress. In addition, anode hole injection induced holes are trapped in the bottom oxide, both in the erase and in the read conditions of the erased cell, and make significant roles in the reverse hysteresis and higher power-law exponent n at higher temperature in P/E cycled erased cells. While the temperature-independent n=0.3 is observed in the programed cell, the temperature-sensitive n=0.36–0.66 is observed in the erased cell.
The effect of annealing processes on electronic properties of sol-gel derived Al-doped ZnO films
Authors: Lin Jen-Po , Wu Jenn-Ming
Published: April 2008

Al-doped ZnO films with high transmittance and low resistivity were prepared by sol-gel method with a three-step annealing. By investigating the relative effect of the Al∕Zn ratio to the annealing on electrical and optical properties, the origin of electrical conduction is verified as the combining effect of the high temperature annealing which enhances crystal quality that provides higher mobility of electrons and the reduction annealing which releases the localized electrons caused by oxygen absorption. Varying the Al∕Zn ratio causes a small Burstein–Moss shift and a slight change in carrier concentration. In contrast, the annealing procedure produces significant changes in the carrier concentration and mobility.
Piping the Politics of Space: The Engagement of Scale in Regional Strategies of Economic Development
Authors: Underthun Anders
Published: April 2008

I examine the political campaign to bring a state-financed gas pipeline to the Norwegian region of Grenland and its existing manufacturing industry. It is argued that the politics of space for capturing and holding onto investments takes a specifically scalar form within a rescaled state that no longer provides uniform welfare distribution, but still possesses important intervention powers and fiscal capabilities. The campaign asserted that an enhanced regional competitiveness resulting from the pipeline will be in the national economic interest of Norway. I argue that the case study is a good example of broad regional mobilization around a particular policy discourse, as well as an example of how the employment of hegemonic discourses of economic restructuring at the national level may strengthen the thrust of regional strategies of development at the local level.
Touch perception reveals the dominance of spatial over digital representation of numbers
Authors: Brozzoli Claudio , Ishihara Masami , Göbel Silke M. , Salemme Roméo , Rossetti Yves , Farnè Alessandro
Published: April 2008

We learn counting on our fingers, and the digital representation of numbers we develop is still present in adulthood [Andres M,
et al.
(2007)
J Cognit Neurosci
19:563–576]. Such an anatomy–magnitude association establishes tight functional correspondences between fingers and numbers [Di Luca S,
et al.
(2006)
Q J Exp Psychol
59:1648–1663]. However, it has long been known that small-to-large magnitude information is arranged left-to-right along a mental number line [Dehaene S,
et al.
(1993)
J Exp Psychol Genet
122:371–396]. Here, we investigated touch perception to disambiguate whether number representation is embodied on the hand (“1” = thumb; “5” = little finger) or disembodied in the extrapersonal space (“1” = left; “5” = right). We directly contrasted these number representations in two experiments using a single centrally located effector (the foot) and a simple postural manipulation of the hand (palm-up vs. palm-down). We show that visual presentation of a number (“1” or “5”) shifts attention cross-modally, modulating the detection of tactile stimuli delivered on the little finger or thumb. With the hand resting palm-down, subjects perform better when reporting tactile stimuli delivered to the little finger after presentation of number “5” than number “1.” Crucially, this pattern reverses (better performance after number “1” than “5”) when the hand is in a palm-up posture, in which the position of the fingers in external space, but not their relative anatomical position, is reversed. The human brain can thus use either space- or body-based representation of numbers, but in case of competition, the former dominates the latter, showing the stronger role played by the mental number line organization.