bluuebunny/crossref_metadata_2025 huggingface dataset:
The C-terminal domain of myosin-like protein 1 (Mlp1p) is a docking site for heterogeneous nuclear ribonucleoproteins that are required for mRNA export
Authors: Green Deanna M. , Johnson Christie P. , Hagan Henry , Corbett Anita H.
Published: February 2003

For mRNA to be transported from the nucleus to the cytoplasm, it must travel from the site of transcription through the nuclear interior to the nuclear pore. Studies in
Saccharomyces cerevisiae
have suggested a relationship between poly(A) RNA trafficking and myosin-like protein 1 (Mlp1p), a nuclear-pore associated protein that is homologous to the mammalian Tpr (translocated promoter region) protein [Kosova, B., Panté, N., Rollenhagen, C., Podtelejnikov, A., Mann, M., Aebi, U., and Hurt, E. (2000)

J. Biol. Chem
.

275, 343–350]. We identified a yeast two-hybrid interaction between the C-terminal globular domain of Mlp1p and Nab2p, a shuttling heterogeneous nuclear ribonucleoprotein that is required for mRNA export. Coimmunoprecipitation confirms that Nab2p also interacts with full-length Mlp1p and
in vitro
binding experiments show that Nab2p binds directly to the C-terminal domain of Mlp1p. In addition, our experiments reveal that the C-terminal domain of Mlp1p is both necessary and sufficient to cause accumulation of poly(A) RNA and Nab2p in the nucleus. We propose a model where Mlp1p acts as a checkpoint at the nuclear pore by interacting with export-competent ribonucleoprotein complexes through its C-terminal globular domain. This study identifies Nab2p as a heterogeneous nuclear ribonucleoprotein found in complex with Mlp1p and begins to delineate the path that mRNA travels from the chromatin to the nuclear pore.
PPARδ is a very low-density lipoprotein sensor in macrophages
Authors: Chawla Ajay , Lee Chih-Hao , Barak Yaacov , He Weimin , Rosenfeld John , Liao Debbie , Han Jungyeob , Kang Heonjoong , Evans Ronald M.
Published: February 2003

Although triglyceride-rich particles, such as very low-density lipoprotein (VLDL), contribute significantly to human atherogenesis, the molecular basis for lipoprotein-driven pathogenicity is poorly understood. We demonstrate that in macrophages, VLDL functions as a transcriptional regulator via the activation of the nuclear receptor peroxisome proliferator-activated receptor δ. The signaling components of native VLDL are its triglycerides, whose activity is enhanced by lipoprotein lipase. Generation of peroxisome proliferator-activated receptor δ null macrophages verifies the absolute requirement of this transcription factor in mediating the VLDL response. Thus, our data reveal a pathway through which dietary triglycerides and VLDL can directly regulate gene expression in atherosclerotic lesions.
No hypothermic response to serotonin in 5-HT
7
receptor knockout mice
Authors: Hedlund P. B. , Danielson P. E. , Thomas E. A. , Slanina K. , Carson M. J. , Sutcliffe J. G.
Published: February 2003

With data from recently available selective antagonists for the 5-HT
7
receptor, it has been hypothesized that 5-hydroxytryptamine (5-HT)-induced hypothermia is mediated by the 5-HT
7
receptor, an effect previously attributed to other receptor subtypes. It has been established that the biologically active lipid oleamide allosterically interacts with the 5-HT
7
receptor to regulate its transmission. The most well characterized effects of oleamide administration are induction of sleep and hypothermia. Here, we demonstrate, by using mice lacking the 5-HT
7
receptor, that 5-HT-induced hypothermia is mediated by the 5-HT
7
receptor. Both 5-HT and 5-carboxamidotryptamine, a 5-HT
1
and 5-HT
7
receptor agonist, in physiological doses fail to induce hypothermia in 5-HT
7
knockout mice. In contrast, oleamide was equally effective in inducing hypothermia in mice lacking the 5-HT
7
receptors as in wild-type mice. When administered together, 5-HT and oleamide showed additive or greater than additive effects in reducing body temperature. Taken together, the results show that 5-HT-induced hypothermia is mediated by the 5-HT
7
receptor, and that oleamide may act through an independent mechanism as well as at an allosteric 5-HT
7
receptor site to regulate body temperature.
Quantitative imaging of the T cell antitumor response by positron-emission tomography
Authors: Dubey Purnima , Su Helen , Adonai Nona , Du Shouying , Rosato Antonio , Braun Jonathan , Gambhir Sanjiv S. , Witte Owen N.
Published: February 2003

We describe a noninvasive, quantitative, and tomographic method to visualize lymphocytes within the whole animal. We used positron-emission tomography (PET) to follow the localization of adoptively transferred immune T lymphocytes. Splenic T cells from animals that had rejected a Moloney murine sarcoma virus/Moloney murine leukemia virus (M-MSV/M-MuLV)-induced tumor were marked with a PET reporter gene, injected into tumor-bearing mice, and imaged in a microPET by using a substrate specific for the reporter. Specific localization of immune T cells to the antigen-positive tumor was detected over time, by sequential imaging of the same animals. Naive T cells did not localize to the tumor site, indicating that preimmunization was required. Autoradiography and immunohistochemistry analysis corroborated the microPET data. The method we have developed can be used to assess the effects of immunomodulatory agents intended to potentiate the immune response to cancer, and can also be useful for the study of other cell-mediated immune responses, including autoimmunity.
Discovery of the breast cancer gene
BASE
using a molecular approach to enrich for genes encoding membrane and secreted proteins
Authors: Egland Kristi A. , Vincent James J. , Strausberg Robert , Lee Byungkook , Pastan Ira
Published: February 2003

To identify unknown membrane proteins that could be used as targets for breast and prostate cancer immunotherapies and secreted proteins to be used as diagnostic markers, a cDNA library was generated from membrane-associated polyribosomal RNA derived from four breast cancer cell lines, one normal breast cell line, and a prostate cancer cell line. The membrane-associated polyribosomal cDNA library was subtracted with RNA from normal brain, liver, lung, kidney, and muscle. Of the 15,581 clones sequenced from the subtracted cDNA library, sequences from 10,506 clones map to known genes, but 5,075 sequences, representing 3,181 unique transcripts, are not associated with known genes. As one example, we experimentally investigated expression of a previously uncharacterized breast cancer gene that encodes a secreted protein designated
BASE (b
reast cancer
a
nd
s
alivary gland
e
xpression).
BASE
is expressed in many breast cancers but not in essential normal tissues including the five organs used for subtraction. Further analysis of this library should yield additional gene products of use in the diagnosis or treatment of breast or prostate cancer.
Course of illness, hippocampal function, and hippocampal volume in major depression
Authors: MacQueen Glenda M. , Campbell Stephanie , McEwen Bruce S. , Macdonald Kathryn , Amano Shigeko , Joffe Russell T. , Nahmias Claude , Young L. Trevor
Published: February 2003

Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.
Growth hormone-releasing hormone (GHRH) antagonists inhibit the proliferation of androgen-dependent and -independent prostate cancers
Authors: Letsch Markus , Schally Andrew V. , Busto Rebeca , Bajo Ana M. , Varga Jozsef L.
Published: February 2003

The antiproliferative effects of an antagonist of growth hormone-releasing hormone (GHRH) JV-1-38 were evaluated in nude mice bearing s.c. xenografts of LNCaP and MDA-PCa-2b human androgen-sensitive and DU-145 androgen-independent prostate cancers. In the androgen-sensitive models, JV-1-38 greatly potentiated the antitumor effect of androgen deprivation induced by surgical castration, but was ineffective when given alone. Thus, in castrated animals bearing MDA-PCa-2b cancers, the administration of JV-1-38 for 35 days virtually arrested tumor growth (94% inhibition vs. intact control,
P
< 0.01; and 75% vs. castrated control,
P
< 0.05). The growth of LNCaP tumors was also powerfully suppressed by JV-1-38 combined with castration (83% inhibition vs. intact control,
P
< 0.01; and 68% vs. castrated control,
P
< 0.05). However, in androgen-independent DU-145 cancers, JV-1-38 alone could inhibit tumor growth by 57% (
P
< 0.05) after 45 days. In animals bearing MDA-PCa-2b and LNCaP tumors, the reduction in serum prostate-specific antigen levels, after therapy with JV-1-38, paralleled the decrease in tumor volume. Inhibition of MDA-PCa-2b and DU-145 cancers was associated with the reduction in the expression of mRNA and protein levels of vascular endothelial growth factor. The mRNA expression for GHRH receptor splice variants was found in all these models of prostate cancer. Our results demonstrate that GHRH antagonists inhibit androgen-independent prostate cancers and, after combination with androgen deprivation, also androgen-sensitive tumors. Thus, the therapy with GHRH antagonist could be considered for the management of both androgen-dependent or -independent prostate cancers.
Suppression of cortical representation through backward conditioning
Authors: Bao Shaowen , Chan Vincent T. , Zhang Li I. , Merzenich Michael M.
Published: February 2003

Temporal stimulus reinforcement sequences have been shown to determine the directions of synaptic plasticity and behavioral learning. Here, we examined whether they also control the direction of cortical reorganization. Pairing ventral tegmental area stimulation with a sound in a backward conditioning paradigm specifically reduced representations of the paired sound in the primary auditory cortex (AI). This temporal sequence-dependent bidirectional cortical plasticity modulated by dopamine release hypothetically serves to prevent the over-representation of frequently occurring stimuli resulting from their random pairing with unrelated rewards.
Definitive separation of graft-versus-leukemia- and graft-versus-host-specific CD4
+
T cells by virtue of their receptor β loci sequences
Authors: Michálek J. , Collins R. H. , Durrani H. P. , Václavková P. , Ruff L. E. , Douek D. C. , Vitetta E. S.
Published: February 2003

Although graft-versus-host (GVH) disease (GVHD) is usually associated with graft versus leukemia (GVL), GVL can occur in the absence of clinical GVHD. There is evidence to suggest that GVL and GVH are mediated by different clones of T cells. The objective of this study was to identify the two types of T cells based on their receptor sequences. To this end we used irradiated nonleukemic cells from recipients as stimulator cells in a primary mixed leukocyte reaction (MLR). The activated CD4
+
donor T cells that expressed CD25 were purified by cell sorting. To prepare GVL-specific T cells, alloreactive T cells in the primary MLR were first depleted with an anti-CD25 immunotoxin. The remaining T cells had negligible alloreactivity in a secondary MLR. The allodepleted cells were then stimulated by using purified leukemia cells from the same individual as stimulator cells, and the CD25
+
-activated cells were purified by cell sorting. The GVL- and GVH-specific T cells were analyzed for their T cell receptor (TCR) clonality by using anchored RT-PCR of all the TCRβ locus complementarity-determining region 3 (CDR3) sequences. By comparing TCRβ CDR3 sequences from transformed bacterial colonies, we were able to demonstrate that T cells mediating GVH were different from those mediating GVL in each of the eight HLA-mismatched and one HLA-matched donor/recipient pairs. By using the appropriate TCRβ CDR3-specific primers and probes, the GVH- and GVL-specific clones were monitored in a recipient undergoing an allogeneic stem cell transplant from her HLA-matched related donor.
Direct detection of antibody–antigen binding using an on-chip artificial pore
Authors: Saleh Omar A. , Sohn Lydia L.
Published: February 2003

We demonstrate a rapid and highly sensitive all-electronic technique based on the resistive pulse method of particle sizing with a pore to detect the binding of unlabeled antibodies to the surface of latex colloids. Here, we use an on-chip pore to sense colloids derivatized with streptavidin and measure accurately their diameter increase on specific binding to several different types of antibodies. We show the sensitivity of this technique to the concentration of free antibody and that it can be used to perform immunoassays in both inhibition and sandwich configurations. Overall, our technique does not require labeling of the reactants and is performed rapidly by using very little solution, and the pore itself is fabricated quickly and inexpensively by using soft lithography. Finally, because this method relies only on the volume of bound ligand, it can be generally applied to detecting a wide range of ligand–receptor binding reactions.
Interactions among three distinct CesA proteins essential for cellulose synthesis
Authors: Taylor Neil G. , Howells Rhian M. , Huttly Alison K. , Vickers Kate , Turner Simon R.
Published: February 2003

In a screen to identify novel cellulose deficient mutants, three lines were shown to be allelic and define a novel complementation group,
irregular xylem5
(
irx5
).
IRX5
was cloned and encodes a member of the CesA family of cellulose synthase catalytic subunits (AtCesA4).
irx5
plants have an identical phenotype to previously described mutations in two other members of this gene family (
IRX1
and
IRX3
). IRX5, IRX3, and IRX1 are coexpressed in exactly the same cells, and all three proteins interact in detergent solubilized extracts, suggesting that three members of this gene family are required for cellulose synthesis in secondary cell walls. The association of IRX1 and IRX3 was reduced to undetectable levels in the absence of IRX5. Consequently, these data suggest that IRX5, IRX3, and IRX1 are all essential components of the cellulose synthesizing complex and the presence of all three subunits is required for the correct assembly of this complex.
Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma
Authors: Nguyen Cu , Teo Jia-Ling , Matsuda Akihisa , Eguchi Masakatsu , Chi Emil Y. , Henderson William R. , Kahn Michael
Published: February 2003

Asthma is characterized by an oxidant/antioxidant imbalance in the lungs leading to activation of redox-sensitive transcription factors, nuclear factor κB (NF-κB), and activator protein-1 (AP-1). To develop therapeutic strategies for asthma, we used a chemogenomics approach to screen for small molecule inhibitor(s) of AP-1 transcription. We developed a β-strand mimetic template that acts as a reversible inhibitor (pseudosubstrate) of redox proteins. This template incorporates an enedione moiety to trap reactive cysteine nucleophiles in the active sites of redox proteins. Specificity for individual redox factors was achieved through variations in
X
and
Y
functionality by using a combinatorial library approach. A limited array (2 × 6) was constructed where
X
was either NHCH
3
or NHCH
2
Ph and
Y
was methyl, phenyl,
m
-cyanophenyl,
m
-nitrophenyl,
m
-acetylaniline, or
m
-methylbenzoate. These analogs were evaluated for their ability to inhibit transcription in transiently transfected human lung epithelial A549 cells from either an AP-1 or NF-κB reporter. A small-molecule inhibitor, PNRI-299, was identified that selectively inhibited AP-1 transcription (IC
50
of 20 μM) without affecting NF-κB transcription (up to 200 μM) or thioredoxin (up to 200 μM). The molecular target of PNRI-299 was determined to be the oxidoreductase, redox effector factor-1 by an affinity chromatography approach. The selective redox effector factor-1 inhibitor, PNRI-299, significantly reduced airway eosinophil infiltration, mucus hypersecretion, edema, and IL-4 levels in a mouse asthma model. These data validate AP-1 as an important therapeutic target in allergic airway inflammation.
One scorpion, two venoms: Prevenom ofParabuthus transvaalicusacts as an alternative type of venom with distinct mechanism of action
Authors: Inceoglu Bora , Lango Jozsef , Jing Jie , Chen Lili , Doymaz Fuat , Pessah Isaac N. , Hammock Bruce D.
Published: February 2003

Scorpion venom is a complex mixture of salts, small molecules, peptides, and proteins. Scorpions employ this valuable tool in several sophisticated ways for subduing prey, deterring predators, and possibly during mating. Here, a subtle but clever strategy of venom utilization by scorpions is reported. Scorpions secrete a small quantity of transparent venom when initially stimulated that we propose to name prevenom. If secretion continues, a cloudy and dense venom that is white in color is subsequently released. The prevenom contains a combination of high K+salt and several peptides including some that block rectifying K+channels and elicit significant pain and toxicity because of a massive local depolarization. The presence of high extracellular K+in the prevenom can depolarize cells and also decrease the local electrochemical gradient making it more difficult to reestablish the resting potential. When this positive change to the K+equilibrium potential is combined with the blockage of rectifying K+channels, this further delays the recovery of the resting potential, causing a prolonged effect. We propose that the prevenom of scorpions is used as a highly efficacious predator deterrent and for immobilizing small prey while conserving metabolically expensive venom until a certain level of stimuli is reached, after which the venom is secreted.
Distinct gene expression profiles characterize the histopathological stages of disease in
Helicobacter-
induced mucosa-associated lymphoid tissue lymphoma
Authors: Mueller Anne , O'Rourke Jani , Grimm Jan , Guillemin Karen , Dixon Michael F. , Lee Adrian , Falkow Stanley
Published: February 2003

Long-term colonization of humans with
Helicobacter pylori
can cause the development of gastric B cell mucosa-associated lymphoid tissue lymphoma, yet little is known about the sequence of molecular steps that accompany disease progression. We used microarray analysis and laser microdissection to identify gene expression profiles characteristic and predictive of the various histopathological stages in a mouse model of the disease. The initial step in lymphoma development is marked by infiltration of reactive lymphocytes into the stomach and the launching of a mucosal immune response. Our analysis uncovered molecular markers of both of these processes, including genes coding for the immunoglobulins and the small proline-rich protein Sprr 2A. The subsequent step is characterized histologically by the antigen-driven proliferation and aggregation of B cells and the gradual appearance of lymphoepithelial lesions. In tissues of this stage, we observed increased expression of genes previously associated with malignancy, including the laminin receptor-1 and the multidrug-resistance channel MDR-1. Finally, we found that the transition to destructive lymphoepithelial lesions and malignant lymphoma is marked by an increase in transcription of a single gene encoding calgranulin A/Mrp-8.
Depletion of a single nucleoporin, Nup107, prevents the assembly of a subset of nucleoporins into the nuclear pore complex
Authors: Boehmer Thomas , Enninga Jost , Dales Samuel , Blobel Günter , Zhong Hualin
Published: February 2003

The nuclear pore complex (NPC) is a protein assembly that contains several distinct subcomplexes. The mammalian nucleoporin (Nup)-107 is part of a hetero-oligomeric complex, that also contains Nup160, Nup133, Nup96, and the mammalian homolog of yeast Sec13p. We used transfection of HeLa cells with small interfering RNAs to specifically deplete mRNA for Nup107. In a domino effect, Nup107 depletion caused codepletion of a subset of other Nups on their protein but not on their mRNA level. Among the affected Nups was a member of the Nup107 subcomplex, Nup133, whereas two other tested members of this complex, Nup96 and Sec13, were unaffected and assembled into Nup107/Nup133-deficient NPCs. We also tested several phenylalanine-glycine repeat-containing Nups that serve as docking sites for karyopherins. Some of these, such as Nup358, Nup214 on the cytoplasmic, and Nup153 on the nucleoplasmic side of the NPC, failed to assemble into Nup107/Nup133-depleted NPCs, whereas p62, a Nup at the center of the NPC, was unaffected. Interestingly, the filamentous, NPC-associated protein Tpr also failed to assemble into the NPCs of Nup107-depleted cells. These data indicate that Nup107 functions as a keystone Nup that is required for the assembly of a subset of Nups into the NPC. Despite the depletion of Nup107 and the accompanying effects on other Nups, there was no significant effect on the growth rate of these cells and only a partial inhibition of mRNA export. These data indicate redundancy of Nups in the function of the mammalian NPC.
Children's Computer Use at Home and at School: Context and continuity
Authors: Kerawalla Lucinda , Crook Charles
Published: January 2003

ABSTRACT The home computer use of 33 children aged between 7 and 11 years is described. These children and their parents were interviewed on four occasions. In addition, domestic computer use was monitored for 30 days in respect of the identity of user(s) and the nature and duration of their software use. Although parents had strong aspirations that household computers should support their child's learning and although parents' main software purchases were educationally oriented, children spent most of their time on games of a sort not typically found in their classrooms. This observation was explored through a comparative analysis of the home and school ecology. Description of the school setting was achieved by engaging with pupils and teachers attending the five schools from which the home‐based sample was drawn. Patterns of school computer use conformed to practices commonly reported for early education. However, this classroom context of computer use was shown to be very different to that sustained in homes. Parents took few steps to orchestrate the content or motive of children's computer activity and they rarely become directly involved in that activity themselves. These observations are discussed in relation to contemporary ambitions to influence the interface of home and school through the mediation of information and communications technology (ICT).
Stability and Change in Results of Schooling
Authors: Doolaard Simone
Published: January 2003

ABSTRACT This study focuses on the stability and changes in primary school results over an eight‐year period, and stems from the tradition of school effectiveness research. To estimate the (in)stability of results, a longitudinal, multilevel design with repeated measurements at school level was used. It shows that the effects of the student background characteristics gender and ethnicity on schooling results changed over the eight‐year period. The results of estimating the stability of effectiveness are in line with earlier research and can be judged ‘middling’. About two‐thirds of schools and classes approximately retained their position in the rank order of schools. This implies that there is also a certain amount of change which might be related to changes in school characteristics and indicate real improvement or decline in results.
Auditing Failure: Moral competence and school effectiveness[1]
Authors: Weiner Gaby
Published: January 2003

ABSTRACT This article addresses school effectiveness and school improvement, as they have been interpreted through UK central and local government policy. It focuses, in particular, on recent forms of inspection and the impact they have had on schools and other educational bodies. It draws on Power's conceptualisation of the Audit Society, to understand the appeal of this form of research to politicians and administrators. Reflecting on a number of perspectives on failure, including official views and those from schools and local authorities that have been designated as ‘failing’, the argument is made that the creation of the two polar opposites—good/effective and failing/ineffective—has exacerbated rather than diminished differences between the two. If concepts of audit are to continue, such as those employed to rate whether schools are successful or not, an ethical framework is needed which is better able to encourage and support the teachers, parents, governors and students involved.
A Research‐based Model for the Development of Policy on Baseline Assessment
Authors: Kyriakides Leonidas
Published: January 2003

ABSTRACT The purpose of this article is to examine whether it is possible to combine two previously separate objectives of baseline assessment in mathematics: the use of baseline assessment for formative reasons and for value‐added functions. A review of research on early mathematics development helps to identify the importance of formative purposes of early assessment in mathematics. The development of policy on baseline assessment in mathematics is put within the broader debate about value‐added assessment. Findings of an empirical investigation into Cypriot pupils' skills and knowledge in mathematics upon entry to primary school and at the end of year 2 are presented. Significant differences among the skills and knowledge of pupils entering primary school were identified. Cluster analysis revealed five relatively homogeneous groups of pupils entering primary school according to their different knowledge and skills in mathematics. The predictive validity of baseline assessment for pupils' attainment at the end of year 2 was satisfactory. Pupil background factors were significantly related to pupils' attainment on the baseline assessment and to their attainment at the end of year 2. However, the baseline score was the most important factor in relation to pupils' progress. Pupils with special needs (either for further support or for extended activities) made less progress than pupils who were typical for their age. Differences between schools' final results were reduced substantially when account was taken of their pupil intakes, but significant differences between schools remained. It is argued that the research findings reveal the importance of developing a model of baseline assessment in mathematics attempting to achieve two purposes: identifying what pupils entering the primary school know and what they do not know in order to trigger differentiated intervention; and establishing a basis for measuring future progress in mathematics through a value‐added analysis. Implications for using such a model to raise achievement in mathematics are discussed.
The Effects of Schooling on Gender Differences
Authors: Wong Kam‐Cheung , Lam Y. Raymond , Ho Lai‐Ming
Published: January 2003

ABSTRACT The study on which this article is based examined the gender differences in educational achievements based on a longitudinal sample of more than 45,000 secondary school students in Hong Kong who took a public examination in 1997. The results coincided with the findings from recent British studies that boys did less well than girls in all areas of the school curriculum. The multilevel analyses of the effects of schooling, after controlling for initial ability, indicated that schooling did have an effect on gender differences. Girls achieved better results studying in single‐sex schools whereas boys achieved better in co‐educational schools. Compared with other students, it was those boys studying in the arts stream that did the least well in the public examination. The results are discussed in the context of the methodology of investigating gender differences and of the substantive questions of school effectiveness.
Job Motivation Profiles of Physical Educators: Theoretical background and instrument development
Authors: Moreira Herivelto , Fox Kenneth R. , Sparkes Andrew C.
Published: January 2003

ABSTRACT Motivation of physical educators at work was investigated within the perspective of Rusbult and Farrell's (1983) Investment Model. This involved the development of theory‐driven instrumentation to assess elements of motivation hypothesised to underpin job commitment—the degree of psychological attachment to the job. Two separate data collections were undertaken involving 60 and 183 British physical education teachers. Through item analyses, factor analyses, and estimates of internal reliability, the Motivation Profile for Physical Educators (MPPE) was developed. This profile includes scales to assess levels of (a) job satisfaction, (b) job dissatisfaction, (c) personal investments in the job, and (d) perceived career alternatives. The first three scales incorporate intrinsic and extrinsic subscales established through factor analysis. Internal reliability was acceptable for all scales although marginal for perceived career alternatives and the intrinsic job satisfaction subscale. Preliminary validity for the MPPE was indicated by its capacity to differentiate late career from early and mid‐career male but not female teachers, to explain significant variance in job commitment, and in logical relationships with job seeking behaviour, job seeking intentions, and also life satisfaction. The MPPE provides the first attempt at theoretically driven and systematic documentation of the complex nature of the attachment of physical educators to their work. Further research is required to replicate current findings, assess the generalisability of the MPPE to other cultures, and to more closely investigate the role that motivation plays in teacher performance. Furthermore, the theory and instrumentation may be useful for the investigation of work motivation of teachers in general.
Rites of Passage in Initial Teacher Training: Ritual, performance, ordeal and Numeracy Skills Test
Authors: McNamara Olwen , Roberts Lorna , Basit Tehmina N. , Brown Tony
Published: January 2003

ABSTRACT ‘Transition’ was identified by cultural anthropologists in the early twentieth century as the liminal stage of a ‘rite of passage’. Contemporary anthropology challenges the structural nature of these classic interpretations of ritual and analyses them as ‘performance theory’: ‘social drama’ (Turner), ‘dramatism’ (Burke), ‘interaction rituals' (Goffman), and ‘ritualisation’ (Bell). In applying a contemporary anthropological lens to initial teacher training, we identify the transition not as a linear progression but as a complex process of extended and ambiguous ‘in‐betweenness' that involves play, performance and ordeal. We depict pre‐service teachers enmeshed in the performance of symbolic acts and the undertaking of ‘ritual ordeals'; and report how they narrate their passage as a complex ‘game’ of ‘being’ and ‘becoming’, and portray the holistic experience metaphorically in terms of ‘play’. We explore, in particular, students' perceptions of the Numeracy Skills Test, the most recently imposed ‘ritual ordeal’: a ‘rite of intensification’ characterised by government as a device to police the boundaries of the teaching profession.
‘Maintains a Good Pace to Lessons': Inconsistencies and contextual factors affecting OFSTED inspections of nursery schools
Authors: Penn Helen
Published: January 2003

ABSTRACT This study explores the scope and reliability of Office for Standards in Education (OFSTED) inspections of nursery schools. All 513 inspections of nursery schools posted on the Web were coded for content. Thirty‐three nursery schools in three local authorities were visited, and basic data were collected from the schools and matched with that in the OFSTED report, and the headteachers' views on the inspections were sought. The study concludes that inspections were inconsistent, and at times misrepresented the work of the nursery schools. It argues that these inconsistencies and misrepresentations were largely due to the limited framework for inspection, which did not take account of the complexities and diversities of early years provision, and the rapid pace of change in the sector.
A Sociocultural Approach to Exclusion
Authors: Sellman Edward , Bedward Julie , Cole Ted , Daniels Harry
Published: January 2003

ABSTRACTThis essay review presents an overview of the issues surrounding young people and exclusion, with a focus on the formal procedure of permanent exclusion from school. In so doing, recent literature on the issues is critiqued amongst wider reading. It is suggested that theorisation of the processes of exclusion cannot be done at any one level of analysis. A sociocultural approach requires attention to analysis at individual, cultural, historical and institutional levels.

Book reviewed in this article:

Inclusive Education: policy, contexts and comparative perspectivesFelicityArmstrong, DerrickArmstrong& LenBarton(Eds)

Why Pick On Me? School Exclusion and Black YouthMaudBlair

Challenges to School ExclusionNevilleHarris, KarenEden& AnnBlair

Tackling Disaffection and Social Exclusion: education perspectives and policiesAnnetteHayton(Ed.)

Defying Disaffection: how schools are winning the hearts and minds of reluctant studentsRevaKlein

Alternatives to Exclusion from SchoolPamelaMunn, GwyneddLloyd& MairiAnnCullen

Education, Exclusion and CitizenshipCarlParsons

Experiencing ExclusionEvaPomeroy
Binding site for p120/δ-catenin is not required for Drosophila E-cadherin function in vivo
Authors: Pacquelet Anne , Lin Li , Rørth Pernille
Published: February 2003

Homophilic cell adhesion mediated by classical cadherins is important for many developmental processes. Proteins that interact with the cytoplasmic domain of cadherin, in particular the catenins, are thought to regulate the strength and possibly the dynamics of adhesion. β-catenin links cadherin to the actin cytoskeleton via α-catenin. The role of p120/δ-catenin proteins in regulating cadherin function is less clear. Both β-catenin and p120/δ-catenin are conserved in Drosophila. Here, we address the importance of cadherin–catenin interactions in vivo, using mutant variants of Drosophila epithelial cadherin (DE-cadherin) that are selectively defective in p120ctn (DE-cadherin-AAA) or β-catenin–armadillo (DE-cadherin-Δβ) interactions. We have analyzed the ability of these proteins to substitute for endogenous DE-cadherin activity in multiple cadherin-dependent processes during Drosophila development and oogenesis; epithelial integrity, follicle cell sorting, oocyte positioning, as well as the dynamic adhesion required for border cell migration. As expected, DE-cadherin-Δβ did not substitute for DE-cadherin in these processes, although it retained some residual activity. Surprisingly, DE-cadherin-AAA was able to substitute for the wild-type protein in all contexts with no detectable perturbations. Thus, interaction with p120/δ-catenin does not appear to be required for DE-cadherin function in vivo.
Hierarchy of protein assembly at the vertex ring domain for yeast vacuole docking and fusion
Authors: Wang Li , Merz Alexey J. , Collins Kevin M. , Wickner William
Published: February 2003

Vacuole tethering, docking, and fusion proteins assemble into a “vertex ring” around the apposed membranes of tethered vacuoles before catalyzing fusion. Inhibitors of the fusion reaction selectively interrupt protein assembly into the vertex ring, establishing a causal assembly hierarchy: (a) The Rab GTPase Ypt7p mediates vacuole tethering and forms the initial vertex ring, independent of t-SNAREs or actin; (b) F-actin disassembly and GTP-bound Ypt7p direct the localization of other fusion factors; (c) The t-SNAREs Vam3p and Vam7p regulate each other's vertex enrichment, but do not affect Ypt7p localization. The v-SNARE Vti1p is enriched at vertices by a distinct pathway that is independent of the t-SNAREs, whereas both t-SNAREs will localize to vertices when trans-pairing of SNAREs is blocked. Thus, trans-SNARE pairing is not required for SNARE vertex enrichment; and (d) The t-SNAREs regulate the vertex enrichment of both G-actin and the Ypt7p effector complex for homotypic fusion and vacuole protein sorting (HOPS). In accord with this hierarchy concept, the HOPS complex, at the end of the vertex assembly hierarchy, is most enriched at those vertices with abundant Ypt7p, which is at the start of the hierarchy. Our findings provide a unique view of the functional relationships between GTPases, SNAREs, and actin in membrane fusion.
Dynactin is required for bidirectional organelle transport
Authors: Deacon Sean W. , Serpinskaya Anna S. , Vaughan Patricia S. , Fanarraga Monica Lopez , Vernos Isabelle , Vaughan Kevin T. , Gelfand Vladimir I.
Published: February 2003

Kinesin II is a heterotrimeric plus end–directed microtubule motor responsible for the anterograde movement of organelles in various cell types. Despite substantial literature concerning the types of organelles that kinesin II transports, the question of how this motor associates with cargo organelles remains unanswered. To address this question, we have used Xenopus laevis melanophores as a model system. Through analysis of kinesin II–mediated melanosome motility, we have determined that the dynactin complex, known as an anchor for cytoplasmic dynein, also links kinesin II to organelles. Biochemical data demonstrates that the putative cargo-binding subunit of Xenopus kinesin II, Xenopus kinesin II–associated protein (XKAP), binds directly to the p150Glued subunit of dynactin. This interaction occurs through aa 530–793 of XKAP and aa 600–811 of p150Glued. These results reveal that dynactin is required for transport activity of microtubule motors of opposite polarity, cytoplasmic dynein and kinesin II, and may provide a new mechanism to coordinate their activities.
Anthrax toxin triggers endocytosis of its receptor via a lipid raft–mediated clathrin-dependent process
Authors: Abrami Laurence , Liu Shihui , Cosson Pierre , Leppla Stephen H. , van der Goot F. Gisou
Published: February 2003

The protective antigen (PA) of the anthrax toxin binds to a cell surface receptor and thereby allows lethal factor (LF) to be taken up and exert its toxic effect in the cytoplasm. Here, we report that clustering of the anthrax toxin receptor (ATR) with heptameric PA or with an antibody sandwich causes its association to specialized cholesterol and glycosphingolipid-rich microdomains of the plasma membrane (lipid rafts). We find that although endocytosis of ATR is slow, clustering it into rafts either via PA heptamerization or using an antibody sandwich is necessary and sufficient to trigger efficient internalization and allow delivery of LF to the cytoplasm. Importantly, altering raft integrity using drugs prevented LF delivery and cleavage of cytosolic MAPK kinases, suggesting that lipid rafts could be therapeutic targets for drugs against anthrax. Moreover, we show that internalization of PA is dynamin and Eps15 dependent, indicating that the clathrin-dependent pathway is the major route of anthrax toxin entry into the cell. The present work illustrates that although the physiological role of the ATR is unknown, its trafficking properties, i.e., slow endocytosis as a monomer and rapid clathrin-mediated uptake on clustering, make it an ideal anthrax toxin receptor.
Drosophila p120catenin plays a supporting role in cell adhesion but is not an essential adherens junction component
Authors: Myster Steven H. , Cavallo Robert , Anderson Charles T. , Fox Donald T. , Peifer Mark
Published: February 2003

Cadherin–catenin complexes, localized to adherens junctions, are essential for cell–cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to the hypothesis that p120 is a key regulator of cell adhesion. p120 has also been suggested to regulate the GTPase Rho and to regulate transcription via its binding partner Kaiso. To test these hypothesized functions, we turned to Drosophila, which has only a single p120 family member. It localizes to adherens junctions and binds the juxtamembrane region of DE-cadherin (DE-cad). We generated null alleles of p120 and found that mutants are viable and fertile and have no substantial changes in junction structure or function. However, p120 mutations strongly enhance mutations in the genes encoding DE-cadherin or Armadillo, the β-catenin homologue. Finally, we examined the localization of p120 during embryogenesis. p120 localizes to adherens junctions, but its localization there is less universal than that of core adherens junction proteins. Together, these data suggest that p120 is an important positive modulator of adhesion but that it is not an essential core component of adherens junctions.
LIS1 at the microtubule plus end and its role in dynein-mediated nuclear migration
Authors: Xiang Xin
Published: February 2003

The cytoplasmic dynein complex and its accessory dynactin complex are involved in many cellular activities including nuclear migration in fungi (for review see Karki and Holzbaur, 1999). LIS1, the product of a causal gene for human lissencephaly (smooth brain), has also been implicated in dynein function based on studies in fungi and more recent studies in higher eukaryotic systems (for review see Gupta et al., 2002). Exactly how LIS1 may regulate the behavior of cytoplasmic dynein in various organisms is a fascinating question. In this issue, Lee et al. (2003) describe important new findings in Saccharomyces cerevisiae regarding the role of LIS1 (Pac1) in dynein-mediated nuclear migration.
Susceptibility patterns of bacteria causing community-acquired respiratory infections in Spain: the SAUCE project
Authors:   the Spanish Surveillance Group for Respiratory Pathogens, García-de-Lomas J. , García-Rey C. , López L. , Gimeno C.
Published: January 2003

Multicentre surveillance is essential in order to monitor the prevalence of certain resistance phenotypes and to identify rapidly the emergence of new ones. However, many surveillance studies are based either on a relatively small number of isolates from a single country, or on a large number of isolates from many different countries and so are not equally meaningful. Extensive national multicentre surveillance would provide a more reliable strategy for assessing the extent of antimicrobial resistance in individual countries. This article describes Spanish experience with the surveillance network SAUCE, and summarizes the main results on antimicrobial resistance in the three key bacterial pathogens involved in community-acquired respiratory tract infections in Spain: Streptococcus pneumoniae , Haemophilus influenzae and Streptococcus pyogenes .
Nasopharyngeal carriage of Streptococcus pneumoniae: a review of the potential role of pharmacokinetics and pharmacodynamics
Authors: Wise R.
Published: January 2003

Much antibiotic prescribing is based upon irrational practice rather than scientific principles. The advent and the better understanding of the pharmacokinetics and pharmacodynamics of antimicrobials are slowly leading to a change whereby antibiotics are prescribed with a better rationale. The fundamental understanding of the pharmacokinetics of the antimicrobial, for example how well it is absorbed, metabolized, distributed and eliminated from the body, should lead to an appreciation of the correct dosing interval. Pharmacodynamic factors, in particular, appreciation of the MIC of an antimicrobial for an infecting pathogen and whether time-independent or -dependent killing occurs, will also have a profound influence upon how an antimicrobial is used. This review attempts to consider these features as they apply to nasopharyngeal carriage of Streptococcus pneumoniae . The reason for the dosing and dosing frequency of a number of agents is discussed and an attempt is made to point the way to more judicious antibiotic prescribing so as to maximize clinical efficacy yet minimize the possibility of resistance emerging during therapy.
Phosphonoacetic acid as a building block in supramolecular chemistry: salts with organic polyamines
Authors: Bowes Katharine F. , Ferguson George , Lough Alan J. , Zakaria Choudhury M. , Glidewell Christopher
Published: January 2003

Phosphonoacetic acid, (HO)2P(O)CH2COOH, forms adducts with a range of amines. The acid component in these adducts may be the neutral molecule C2H5O5P, the mono-anion (C2H4O5P)− or the di-anion (C2H3O5P)2−. The substructure formed by the acid component takes the form of simple chains in compounds (1)–(3), which are the 1:1 adducts formed with 1,4-diazabicyclo[2.2.2]octane, 4,4′-bipyridyl and 1,3-trimethylenedipiperidine, respectively. These adducts contain C2H5O5P, (C2H4O5P)− and (C2H3O5P)2−, respectively, although (3) is solvated by a mixture of methanol and water. The (C2H4O5P)− anion substructure in (4), which is the adduct formed with meso-5,5,7,12,12,14-hexa-C-methyl-1,4,8,11-tetraazacyclotetradecane, is a chain of spiro-fused rings, while the substructure in (5), which is the adduct formed with 2,2′-dipyridylamine, is a chain of edge-fused rings. In (6), the adduct formed with 1,2-bis(4′-pyridyl)ethane, the anion substructure is two-dimensional. The chain substructures are linked by the amine units into two-dimensional structures in (1) and (4) and into three-dimensional frameworks in (2), (3) and (5), while the anion sheets in (6) are likewise linked by the amine units into a three-dimensional framework.
Crystal chemistry and binding of NO2, SCN and SeCN to Co in cobalamins
Authors: Garau Gianpiero , Geremia Silvano , Marzilli Luigi G. , Nardin Giorgio , Randaccio Lucio , Tauzher Giovanni
Published: January 2003

Results of the accurate crystal structure determination of NO2Cbl·2LiCl (1), NO2Cbl·NaCl (2), NCSCbl (3) and NCSeCbl (4), based on synchrotron diffraction data collected at 100 K, are described. The nitro group in (1) was found to be disordered with two orientations that differ by a rotation of ∼60° about the Co—NO2 bond, whereas in (2) the nitro group has only one orientation. The first X-ray structural determination of a cobalamin with a Co—Se bond is reported. Comparison of the axial distances indicates that SeCN has a bond length of 2.384 (3) Å and that the trans influence on the Co—N bond is only slightly greater than that of SCN. The crystals of the thiocyanate cobalamin contain both the S- and N-bonded coordination isomers in a 3:2 ratio. The structural features of the Co—S bond in cobalamins are discussed. The crystal chemistry of cobalamins is discussed in terms of packing of roughly spherical molecules. The unit-cell parameters can be used to group the cobalamins' crystal structures in different arrays intermediate between distorted hexagonal close packing and primitive hexagonal arrangements. The structural features of cobalamins, and of cobaloximes that have the same axial fragment as the cobalamins, are reviewed and discussed in terms of the cis influence of the equatorial ligand.