bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of alcohol consumption on endothelial adhesion molecule expression
Authors: Sacanella E , Estruch R
Published: January 2004

Endothelial adhesion molecules (AM) play an important role in the pathogenesis of several diseases namely infections, neoplasms and chronic inflammatory diseases. Because alcoholic hepatitis and even atherosclerosis are considered as inflammatory diseases and ethanol may modulate inflammatory response, several researchers have investigated the link between ethanol consumption, endothelial AM and the development of both processes. In vitro, animal and human studies have analysed the effects of ethanol and non‐alcoholic components of alcoholic beverages on inflammatory biomarkers of atherosclerosis such as monocyte and endothelial AM. These studies have shown that both ethanol and non‐alcoholic components of alcoholic beverages, mainly polyphenols, reduce intercellular adhesion molecule‐1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin expression of vascular endothelium, as well as monocyte adhesion to this endothelium. These data suggest that moderate alcohol intake has an anti‐inflammatory effect on the cardiovascular system and reduces early serum markers of atherosclerosis. However, at higher doses ethanol may exert an inflammatory effect. In fact, chronic alcoholics exhibit significantly higher serum levels of endothelial AM than abstainers and moderate drinkers. In addition, an upregulation of E‐selectin, ICAM‐1 and VCAM‐1 is also detected in liver biopsies obtained from patients with alcoholic hepatitis and cirrhosis. The clinical usefulness of the measurement of serum endothelial AM is discussed.
Malignant Glomus Tumour: A Case Report and Review of the Literature
Authors: De Chiara Annarosaria , Apice Gaetano , Mori Stefano , Silvestro Giustino , Losito Simona N. , Botti Gerardo , Ninfo Vito
Published: January 2004

Purpose: Glomus tumours are characteristically benign solitary tumours. At our knowledge, about 23 reports are present in
literature regarding the malignant counterpart, but only a minority developed metastases. We describe a locally aggressive
glomus tumour with lymphnode metastasis.

Patient: The patient was a 40 year‐old man presenting a 1.5‐cm lesion on the right wrist incompletely excised and a recurrent
tumour, 4 × 2 cm in size, removed after 9 months, for which he received radiotherapy. After 2 years he developed an axillary
lymphnode metastasis.

Results: Histologically, both tumours (primary and metastasis) were similar. There were sheets and nests of uniform small
cells with scant eosinophilic cytoplasm and round to polygonal nuclei; there was some degree of pleomorphism and the
mitotic index was high (up to 18 m/10 HPF). The tumour cells were positive for vimentin and smooth muscle actin, but
negative for desmin, NSE, Factor VIII, chromogranin, cytokeratin. Remarkably, in the primary, the cells strongly expressed
p53 (70%) and MIB‐1 (35%).

Discussions: In many reported malignant cases, the histology of the tumour cells suggested that they were malignant, yet the
clinical course has been benign. Carefully reviewing the literature, it seems that actually we have enough histological criteria
to identify the cases with biological adverse outcome. Those unfortunate cases behave as high grade sarcomas and therefore
may deserve an aggressive therapeutic treatment.
Immunohistochemistry Evaluation of the Effect in Vivo of Tumor Necrosis Factor(TNF)‐α on Blood VesselDensity in Murine Fibrosarcoma
Authors: Eisenthal Avi , Schwartz Ignat , Issakov Josephine , Klausner Yossef , Misonzhnik Faina , Lifschitz-Mercer Beatriz
Published: January 2004

Purpose: Angiogenesis is essential for tumor growth and metastases, thus bestowing obvious importance upon methodologies
which could enable its inhibition.

Materials: C57BL/6 female mice bearing a subcutaneous (s.c.) MCA205 fibrosarcoma were used.

Methods: Ten mice were divided equally into two groups. One group was injected intraperitoneally (i.p.) with 10 μg tumor
necrosis factor‐α (TNF‐α and the other (controls) with Hanks balanced salt solution (HBSS). Tumor growth was monitored
at least twice weekly. The number of endothelial cells in the blood microvessels was assessed by immunohistostaining on
paraffin‐embedded tumor tissue sections using vascular endothelial growth factor (VEGF) and Factor 8 antibodies.
Expression of the p53 gene was similarly assessed by immunohistostaining.

Results: Injection of 10 μg TNF‐α into the tumor‐bearing mice reduced the number of endothelial cells in the blood
microvessels by 46% on day 3 post‐injection which was accompanied by an increase (by 37%) in the expression of p53 in
these cells. It also inhibited tumor growth compared to the HBSS‐injected group starting at 17 days post‐cytokine injection.

Discussion: The antitumor in vivo effect exerted by TNF‐α on established murine sarcoma s.c. tumors may be due to an
earlier effect of the cytokine on the tumor′s blood microvessels, probably through an apoptotic mechanism involving the
p53 gene.
Analysis of Lung Metastases in Patients with Primary Extremity Sarcoma
Authors: Songür N. , Dinç M. , Özdilekcan C. , Eke S. , Ok U. , Oz M.
Published: January 2004

Purpose: To investigate the incidence, radiographic findings, and the time course for the appearence of lung metastases from
primary extremity sarcoma.

Patients and methods: Four‐hundred patients with extremity sarcoma were evaluated retrospectively for lung metastases.
Multiple clinical factors were analyzed for possible influence on the metastases‐free interval and subsequent metastases
development. Radiographic findings of metastases were also reviewed.

Results: Ninety of 400 patients (23%) developed lung metastases. Median time from presentation to detection of metastasis
was 8.0 ± 1.1 months (95% CI: 6.02–9.98). More than 75% of patients developed metastases within 1 year after presentation
of the primary sarcoma. As disease grade increased, the metastases‐free intervals shortened significantly. Histologically,
synoviosarcoma and osteogenic sarcoma were more often associated with the development of lung metastases. In this
subgroup, 54 patients (60%), the presence of solitary (11) or multiple (43) nodular metastases was the only radiological
finding. In 36 of 90 patients (40%), parenchymal mass, pleural effusion, hilar lymphadenopathy and pneumothorax were
found.

Conclusions: Twenty‐three percent of patients in our study developed lung metastases. As the grade of the disease increased,
metastases‐free intervals are shortened. Although it has been reported that lung metastases in patients with extremity
sarcomas may present as solitary or multiple nodules in earlier trials with radiographic screening methods, the current review
of 400 patients found that a substantial number of patients may present radiological appearances other than nodular
formations.
Synovial Chondromatosis and Chondrosarcoma: A Diagnostic Dilemma
Authors: Sperling Brita L. , Angel Steven , Stoneham Grant , Chow Vance , McFadden Andrew , Chibbar Rajni
Published: January 2004

Purpose: The progression of synovial chondromatosis to chondrosarcoma is very rare. Distinction between these two entities
may be difficult on histology alone, and should be based on clinical, radiographic and microscopic evidence.
Immunohistochemical markers that would facilitate differentiation between synovial chondromatosis and chondrosarcoma
are currently being investigated.

Patients: We describe the cases of two patients who presented with synovial chondromatosis and progression to synovial
chondrosarcoma during periods of 7 and 11 years. Several biopsies and resected specimens demonstrated synovial
chondromatosis before a diagnosis of chondrosarcoma was made.

Method: We have examined five markers (Bcl2, Ki67, p27, p16, and p53) in all specimens from these cases, as well as known
cases of chondromatosis and chondrosarcoma for control purposes.

Results: We found increased expression of Bcl2 in benign chondromatosis compared to synovial or central chondrosarcomas.

Discussion: Distinction between chondromatosis and its progression to low grade chondrosarcoma is difficult at histological
level, and must involve incorporation of clinical and radiographical data. Although preliminary, our study suggests that
reduced or absent expression of Bcl2 is associated withmalignant transformation of chondromatosis.
Distal Recurrence of Periosteal Osteosarcoma After Complete Excision of Proximal Primary Tumour With Good Excision Margins
Authors: Barakat M. J. , Collins C. , Dixon J. H.
Published: January 2004

We present this case of an unusual recurrence of a periosteal osteosarcoma in the distal right tibia
2 years after a successful proximal right tibia primary periosteal osteosarcoma excision with a successful
fibular graft. This recurrence lead to a right below‐knee amputation.
Metastatic Secondary Fibrosarcoma of Bone Responsive to RepeatedCourses of Ifosfamide and Associated With Hypoglycemia
Authors: Bouttell Elaine S. , Rodger N. Wilson , Bramwell Vivien H. C.
Published: January 2004

We present a case of a 40‐year‐old man with secondary fibrosarcoma of bone, arising from a non‐ossifying fibroma. He
subsequently developed metastatic disease that responded to four successive chemotherapy courses, the last three using the
same dose/schedule of single agent ifosfamide. Eventual rapid progression of a huge intra‐abdominal mass was associated
with the syndrome of extrapancreatic tumour hypoglycemia (EPTH). The clinicopathological behaviour of fibrosarcoma of
bone, and the mechanism of EPTH are discussed.
The Risks of Social Reproduction: the middle class and education markets
Authors: Ball Stephen J.
Published: January 2004

We live, as some theorists put it, in a 'risk society'. Risks are diverse and new forms are constantly arising. There is an 'over-production' of risk. We face the brittle uncertainties of individual self-management, as Beck sees it, alone and 'fragmented across (life) phases, space
and time' (1997, p. 26). This is a bleak and elemental social world. This paper takes a rather different view of risk, as having both collective and divisive dynamics and effects. It offers not so much an alternative view as one that is re-socialised. Focusing on middle class families and
the 'risks' of school choice some key features of the 'prudentialist' risk management regime extant in the UK are examined. That is, those 'definite social exertions' that middle class families must make on their own part or face the very real prospect of generational decline are considered.
Risks are perceived to arise from the engagements between the family and the education marketplace, and are embedded in the paradox wherein society becomes structurally more meritocratic but processually less so, as the middle class work harder to maintain their advantages in the new conditions
of choice and competition in education. The paper is peppered with extracts from interviews with middle-class parents. These serve for illustration and discussion.
Learning to be Human: teaching, culture and human cognitive evolution
Authors: Bailey Richard
Published: January 2004

Psychology has taken an evolutionary turn of late. This paper acknowledges the importance of adopting an evolutionary perspective in attempting to understand human cognition and development, but it suggests that the model adopted by many evolutionary psychologists is incomplete. Learning,
teaching and cultural transmission play vital roles in the distinctive human life pattern, but have received inadequate attention in the literature. Drawing upon primatological, anthropological and psychological data, this paper offers an articulation of 'cultural learning', which, it is claimed,
is a peculiarly accurate and resilient form of social form, made possible by the uniquely human capacity for an intersubjective engagement with the mental and intentional lives of other people. The paper discusses the character and appearance of imitative, collaborative and instructed forms
of learning within early childhood, and tentatively identifies implications for child development and contemporary schooling.
Debating the Digital Curriculum: intersections of the public and the private in educational and cultural policy
Authors: Scanlon Margaret , Buckingham David
Published: January 2004

In January 2003, the British government approved the BBC's Digital Curriculum, a new £150 million initiative to provide educational software to schools and homes. The decision was widely criticised by representatives of the UK software publishing industry, and by defenders of
public service broadcasting. This article traces the debates that led to the decision, and the broader issues that it raises. It suggests that the initiative can be seen as symptomatic of the interpenetration of public and private imperatives that is characteristic of New Labour policy-making;
but it also suggests that, when educational and cultural policy come together, there may be unresolved tensions between them.
Trail Records and Navigational Learning
Authors: Peterson Don , Levene Mark
Published: January 2004

An emerging wave of 'ambient' technologies has the potential to support learning in new and particular ways. In this paper we propose a 'trail model' of 'navigational learning' which links some particular learning needs to the potentialities of these technologies. In this context, we
outline the design and use of an 'experience recorder', a technology to support learning in museums. In terms of policy for the e-society, these proposals are relevant to the need for personalised and individualised learning support.
Educational Research and Policymaking: findings from some transitional countries
Authors: Temple Paul
Published: January 2004

This paper explores the debate about the relationship between educational research and educational policymaking and practice. It considers why the translation of research into practice appears to be limited, and the policy implications that arise from these limitations. In this epistemic
setting, aspects of the organisation of educational research in some western countries, and the contrasting position in some transitional countries, are considered. Demands on educational research in both settings, it is argued, are based partly on misunderstandings of what it can achieve.
It is important to reach a clearer understanding of the possibilities if the benefits that are available from research are to be realised.
Raising the Achievement of Caribbean Pupils in British Schools: unacknowledged problems and challenges for policy makers
Authors: Demie Feyisa
Published: January 2004

Over the last decade the underperforming groups issues that have shaped thinking practice in schools have changed significantly. Today, a high level of education is no longer a luxury for some groups or social classes, but a necessity for every one in British society. Yet Black Caribbean
heritage pupils' achievements lag far behind the average achievement of the majority of their peers and the gap is growing at the end of primary and secondary education. Despite much academic debate and policy makers' concern about underachievement in schools, the needs of Black Caribbean
pupils have not been addressed in the education system and have been largely neglected. This research paper examines critically the national policy agenda, the extent of and reasons for underachievement of pupils of Black Caribbean heritage throughout each key stage in an inner city LEA. Statistical
trends and patterns of performance are analysed by ethnic factors to illustrate differences in attainment. The paper questions the current national policy agenda for improving achievement for all pupils, and argues critically that the issues surrounding Black Caribbean pupils' underachievement
are real and should not be underestimated in national policy formulation. Policy implications for government and for all concerned with school improvement are highlighted, as well as many practical suggestions.
CD1d-dependent Activation of NKT Cells Aggravates Atherosclerosis
Authors: Tupin Emmanuel , Nicoletti Antonino , Elhage Rima , Rudling Mats , Ljunggren Hans-Gustaf , Hansson Göran K. , Berne Gabrielle Paulsson
Published: January 2004

Adaptive and innate immunity have been implicated in the pathogenesis of atherosclerosis. Given their abundance in the lesion, lipids might be targets of the atherosclerosis-associated immune response. Natural killer T (NKT) cells can recognize lipid antigens presented by CD1 molecules. We have explored the role of CD1d-restricted NKT cells in atherosclerosis by using apolipoprotein E–deficient (apoE−/−) mice, a hypercholesterolemic mouse model that develops atherosclerosis. ApoE−/− mice crossed with CD1d−/− (CD1d−/−apoE−/−) mice exhibited a 25% decrease in lesion size compared with apoE−/− mice. Administration of α-galactosylceramide, a synthetic glycolipid that activates NKT cells via CD1d, induced a 50% increase in lesion size in apoE−/− mice, whereas it did not affect lesion size in apoE−/−CD1d−/− mice. Treatment was accompanied by an early burst of cytokines (IFNγ, MCP-1, TNFα, IL-2, IL-4, IL-5, and IL-6) followed by sustained increases in IFNγ and IL-4 transcripts in the spleen and aorta. Early activation of both T and B cells was followed by recruitment of T and NKT cells to the aorta and activation of inflammatory genes. These results show that activation of CD1d-restricted NKT cells exacerbates atherosclerosis.
The Na+ Channel Inactivation Gate Is a Molecular Complex
Authors: Motoike Howard K. , Liu Huajun , Glaaser Ian W. , Yang An-Suei , Tateyama Michihiro , Kass Robert S.
Published: January 2004

Electrical activity in nerve, skeletal muscle, and heart requires finely tuned activity of voltage-gated Na+ channels that open and then enter a nonconducting inactivated state upon depolarization. Inactivation occurs when the gate, the cytoplasmic loop linking domains III and IV of the α subunit, occludes the open pore. Subtle destabilization of inactivation by mutation is causally associated with diverse human disease. Here we show for the first time that the inactivation gate is a molecular complex consisting of the III-IV loop and the COOH terminus (C-T), which is necessary to stabilize the closed gate and minimize channel reopening. When this interaction is disrupted by mutation, inactivation is destabilized allowing a small, but important, fraction of channels to reopen, conduct inward current, and delay cellular repolarization. Thus, our results demonstrate for the first time that physiologically crucial stabilization of inactivation of the Na+ channel requires complex interactions of intracellular structures and indicate a novel structural role of the C-T domain in this process.
Membrane Tension Accelerates Rate-limiting Voltage-dependent Activation and Slow Inactivation Steps in a Shaker Channel
Authors: Laitko Ulrike , Morris Catherine E.
Published: January 2004

A classical voltage-sensitive channel is tension sensitive—the kinetics of Shaker and S3–S4 linker deletion mutants change with membrane stretch (Tabarean, I.V., and C.E. Morris. 2002. Biophys. J. 82:2982–2994.). Does stretch distort the channel protein, producing novel channel states, or, more interestingly, are existing transitions inherently tension sensitive? We examined stretch and voltage dependence of mutant 5aa, whose ultra-simple activation (Gonzalez, C., E. Rosenman, F. Bezanilla, O. Alvarez, and R. Latorre. 2000. J. Gen. Physiol. 115:193–208.) and temporally matched activation and slow inactivation were ideal for these studies. We focused on macroscopic patch current parameters related to elementary channel transitions: maximum slope and delay of current rise, and time constant of current decline. Stretch altered the magnitude of these parameters, but not, or minimally, their voltage dependence. Maximum slope and delay versus voltage with and without stretch as well as current rising phases were well described by expressions derived for an irreversible four-step activation model, indicating there is no separate stretch-activated opening pathway. This model, with slow inactivation added, explains most of our data. From this we infer that the voltage-dependent activation path is inherently stretch sensitive. Simulated currents for schemes with additional activation steps were compared against datasets; this showed that generally, additional complexity was not called for. Because the voltage sensitivities of activation and inactivation differ, it was not possible to substitute depolarization for stretch so as to produce the same overall PO time course. What we found, however, was that at a given voltage, stretch-accelerated current rise and decline almost identically—normalized current traces with and without stretch could be matched by a rescaling of time. Rate-limitation of the current falling phase by activation was ruled out. We hypothesize, therefore, that stretch-induced bilayer decompression facilitates an in-plane expansion of the protein in both activation and inactivation. Dynamic structural models of this class of channels will need to take into account the inherent mechanosensitivity of voltage-dependent gating.
Classes and Narrowing Selectivity of Olfactory Receptor Neurons of Xenopus laevis Tadpoles
Authors: Manzini Ivan , Schild Detlev
Published: January 2004

In olfactory receptor neurons (ORNs) of aquatic animals amino acids have been shown to be potent stimuli. Here we report on calcium imaging experiments in slices of the olfactory mucosa of Xenopus laevis tadpoles. We were able to determine the response profiles of 283 ORNs to 19 amino acids, where one profile comprises the responses of one ORN to 19 amino acids. 204 out of the 283 response profiles differed from each other. 36 response spectra occurred more than once, i.e., there were 36 classes of ORNs identically responding to the 19 amino acids. The number of ORNs that formed a class ranged from 2 to 13. Shape and duration of amino acid-elicited [Ca2+]i transients showed a high degree of similarity upon repeated stimulation with the same amino acid. Different amino acids, however, in some cases led to clearly distinguishable calcium responses in individual ORNs. Furthermore, ORNs clearly appeared to gain selectivity over time, i.e., ORNs of later developmental stages responded to less amino acids than ORNs of earlier stages. We discuss the narrowing of ORN selectivity over stages in the context of expression of olfactory receptors.
A Store-operated Calcium Channel in Drosophila S2 Cells
Authors: Yeromin Andriy V. , Roos Jack , Stauderman Kenneth A. , Cahalan Michael D.
Published: January 2004

Using whole-cell recording in Drosophila S2 cells, we characterized a Ca2+-selective current that is activated by depletion of intracellular Ca2+ stores. Passive store depletion with a Ca2+-free pipette solution containing 12 mM BAPTA activated an inwardly rectifying Ca2+ current with a reversal potential >60 mV. Inward currents developed with a delay and reached a maximum of 20–50 pA at −110 mV. This current doubled in amplitude upon increasing external Ca2+ from 2 to 20 mM and was not affected by substitution of choline for Na+. A pipette solution containing ∼300 nM free Ca2+ and 10 mM EGTA prevented spontaneous activation, but Ca2+ current activated promptly upon application of ionomycin or thapsigargin, or during dialysis with IP3. Isotonic substitution of 20 mM Ca2+ by test divalent cations revealed a selectivity sequence of Ba2+ > Sr2+ > Ca2+ >> Mg2+. Ba2+ and Sr2+ currents inactivated within seconds of exposure to zero-Ca2+ solution at a holding potential of 10 mV. Inactivation of Ba2+ and Sr2+ currents showed recovery during strong hyperpolarizing pulses. Noise analysis provided an estimate of unitary conductance values in 20 mM Ca2+ and Ba2+ of 36 and 420 fS, respectively. Upon removal of all external divalent ions, a transient monovalent current exhibited strong selectivity for Na+ over Cs+. The Ca2+ current was completely and reversibly blocked by Gd3+, with an IC50 value of ∼50 nM, and was also blocked by 20 μM SKF 96365 and by 20 μM 2-APB. At concentrations between 5 and 14 μM, application of 2-APB increased the magnitude of Ca2+ currents. We conclude that S2 cells express store-operated Ca2+ channels with many of the same biophysical characteristics as CRAC channels in mammalian cells.
Identification of a Novel Sequence in PDZ-RhoGEF That Mediates Interaction with the Actin Cytoskeleton
Authors: Banerjee Jayashree , Wedegaertner Philip B.
Published: January 2004

Small GTPases of the Rho family are crucial regulators of actin cytoskeleton rearrangements. Rho is activated by members of the Rho guanine-nucleotide exchange factor (GEF) family; however, mechanisms that regulate RhoGEFs are not well understood. This report demonstrates that PDZ-RhoGEF, a member of a subfamily of RhoGEFs that contain regulator of G protein signaling domains, is partially localized at or near the plasma membranes in 293T, COS-7, and Neuro2a cells, and this localization is coincident with cortical actin. Disruption of the cortical actin cytoskeleton in cells by using latrunculin B prevents the peri-plasma membrane localization of PDZ-RhoGEF. Coimmunoprecipitation and F-actin cosedimentation assays demonstrate that PDZ-RhoGEF binds to actin. Extensive deletion mutagenesis revealed the presence of a novel 25-amino acid sequence in PDZ-RhoGEF, located at amino acids 561–585, that is necessary and sufficient for localization to the actin cytoskeleton and interaction with actin. Last, PDZ-RhoGEF mutants that fail to interact with the actin cytoskeleton display enhanced Rho-dependent signaling compared with wild-type PDZ-RhoGEF. These results identify interaction with the actin cytoskeleton as a novel function for PDZ-RhoGEF, thus implicating actin interaction in organizing PDZ-RhoGEF signaling.
Association with Membrane Protrusions Makes ErbB2 an Internalization-resistant Receptor
Authors: Hommelgaard Anette M. , Lerdrup Mads , van Deurs Bo
Published: January 2004

In contrast to the epidermal growth factor (EGF) receptor, ErbB2 is known to remain at the plasma membrane after ligand binding and dimerization. However, why ErbB2 is not efficiently down-regulated has remained elusive. Basically, two possibilities exist: ErbB2 is internalization resistant or it is efficiently recycled after internalization. By a combination of confocal microscopy, immunogold labeling electron microscopy, and biochemical techniques we show that ErbB2 is preferentially associated with membrane protrusions. Moreover, it is efficiently excluded from clathrin-coated pits and is not seen in transferrin receptor-containing endosomes. This pattern is not changed after binding of EGF, heregulin, or herceptin. The exclusion from coated pits is so pronounced that it cannot just be explained by lack of an internalization signal. Although ErbB2 is a raft-associated protein, the localization of ErbB2 to protrusions is not a result of raft binding. Also, an intact actin cytoskeleton is not required for keeping ErbB2 away from coated pits. However, after efficient cross-linking, ErbB2 is removed from protrusions to occur on the bulk membrane, in coated pits, and in endosomes. These data show that ErbB2 is a remarkably internalization-resistant receptor and suggest that the mechanism underlying the firm association of ErbB2 with protrusions also is the reason for this resistance.
NO66, a Highly Conserved Dual Location Protein in the Nucleolus and in a Special Type of Synchronously Replicating Chromatin
Authors: Eilbracht Jens , Reichenzeller Michaela , Hergt Michaela , Schnölzer Martina , Heid Hans , Stöhr Michael , Franke Werner W. , Schmidt-Zachmann Marion S.
Published: January 2004

It has recently become clear that the nucleolus, the most prominent nuclear subcompartment, harbors diverse functions beyond its classic role in ribosome biogenesis. To gain insight into nucleolar functions, we have purified amplified nucleoli from Xenopus laevis oocytes using a novel approach involving fluorescence-activated cell sorting techniques. The resulting protein fraction was analyzed by mass spectrometry and used for the generation of monoclonal antibodies directed against nucleolar components. Here, we report the identification and molecular characterization of a novel, ubiquitous protein, which in most cell types appears to be a constitutive nucleolar component. Immunolocalization studies have revealed that this protein, termed NO66, is highly conserved during evolution and shows in most cells analyzed a dual localization pattern, i.e., a strong enrichment in the granular part of nucleoli and in distinct nucleoplasmic entities. Colocalizations with proteins Ki-67, HP1α, and PCNA, respectively, have further shown that the staining pattern of NO66 overlaps with certain clusters of late replicating chromatin. Biochemical experiments have revealed that protein NO66 cofractionates with large preribosomal particles but is absent from cytoplasmic ribosomes. We propose that in addition to its role in ribosome biogenesis protein NO66 has functions in the replication or remodeling of certain heterochromatic regions.
Countercurrent Distribution of Two Distinct SNARE Complexes Mediating Transport within the Golgi Stack
Authors: Volchuk Allen , Ravazzola Mariella , Perrelet Alain , Eng William S. , Di Liberto Maurizio , Varlamov Oleg , Fukasawa Masayoshi , Engel Thomas , Söllner Thomas H. , Rothman James E. , Orci Lelio
Published: January 2004

Genetic and biochemical evidence has established that a SNARE complex consisting of syntaxin 5 (Sed5)-mYkt6 (Ykt6)-GOS28 (Gos1)-GS15 (Sft1) is required for transport of proteins across the Golgi stack in animals (yeast). We have utilized quantitative immunogold labeling to establish the cis-trans distribution of the v-SNARE GS15 and the t-SNARE subunits GOS28 and syntaxin 5. Whereas the distribution of the t-SNARE is nearly even across the Golgi stack from the cis to the trans side, the v-SNARE GS15 is present in a gradient of increasing concentration toward the trans face of the stack. This contrasts with a second distinct SNARE complex, also required for intra-Golgi transport, consisting of syntaxin 5 (Sed5)-membrin (Bos1)-ERS24 (Sec22)-rBet1 (Bet1), whose v-(rBet1) and t-SNARE subunits (membrin and ERS24), progressively decrease in concentration toward the trans face. Transport within the stack therefore appears to utilize countercurrent gradients of two Golgi SNAREpins and may involve a mechanism akin to homotypic fusion.
S-Phase Checkpoint Genes Safeguard High-Fidelity Sister Chromatid Cohesion
Authors: Warren Cheryl D. , Eckley D. Mark , Lee Marina S. , Hanna Joseph S. , Hughes Adam , Peyser Brian , Jie Chunfa , Irizarry Rafael , Spencer Forrest A.
Published: January 2004

Cohesion establishment and maintenance are carried out by proteins that modify the activity of Cohesin, an essential complex that holds sister chromatids together. Constituents of the replication fork, such as the DNA polymerase α-binding protein Ctf4, contribute to cohesion in ways that are poorly understood. To identify additional cohesion components, we analyzed a ctf4Δ synthetic lethal screen performed on microarrays. We focused on a subset of ctf4Δ-interacting genes with genetic instability of their own. Our analyses revealed that 17 previously studied genes are also necessary for the maintenance of robust association of sisters in metaphase. Among these were subunits of the MRX complex, which forms a molecular structure similar to Cohesin. Further investigation indicated that the MRX complex did not contribute to metaphase cohesion independent of Cohesin, although an additional role may be contributed by XRS2. In general, results from the screen indicated a sister chromatid cohesion role for a specific subset of genes that function in DNA replication and repair. This subset is particularly enriched for genes that support the S-phase checkpoint. We suggest that these genes promote and protect a chromatin environment conducive to robust cohesion.
RNAi-mediated Hip1R Silencing Results in Stable Association between the Endocytic Machinery and the Actin Assembly Machinery
Authors: Engqvist-Goldstein Åsa E. Y. , Zhang Claire X. , Carreno Sebastien , Barroso Consuelo , Heuser John E. , Drubin David G.
Published: January 2004

Actin filaments transiently associate with the endocytic machinery during clathrin-coated vesicle formation. Although several proteins that might mediate or regulate this association have been identified, in vivo demonstration of such an activity has not been achieved. Huntingtin interacting protein 1R (Hip1R) is a candidate cytoskeletal-endocytic linker or regulator because it binds to clathrin and actin. Here, Hip1R levels were lowered by RNA interference (RNAi). Surprisingly, rather than disrupting the transient association between endocytic and cytoskeletal proteins, clathrin-coated structures (CCSs) and their endocytic cargo became stably associated with dynamin, actin, the Arp2/3 complex, and its activator, cortactin. RNAi double-depletion experiments demonstrated that accumulation of the cortical actin-endocytic complexes depended on cortactin. Fluorescence recovery after photobleaching showed that dynamic actin filament assembly can occur at CCSs. Our results provide evidence that Hip1R helps to make the interaction between actin and the endocytic machinery functional and transient.
Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory
Authors: Vuckovich Joseph A. , Semel Mara E. , Baxter Mark G.
Published: January 2004

A recent studysuggests that lesions to all major areas of the cholinergic
basal forebrain in the rat (medial septum, horizontal limb of the diagonal
band of Broca, and nucleus basalis magnocellularis) impair a spatial working
memory task. However, this experiment used a surgical technique that mayhave
damaged cerebellar Purkinje cells. The present studytested rats with
highlyselective lesions of cholinergic neurons in all major areas of the basal
forebrain on a spatial working memorytask in the radial arm maze. In
postoperative testing, there were no significant differences between lesion
and control groups in working memory, even with a delayperiod of 8 h, with the
exception of a transient impairment during the first 2 d of postoperative
testing at shorter delays (0 or 2 h). This finding corroborates other results
that indicate that the cholinergic basal forebrain does not playa significant
role in spatial working memory. Furthermore, it underscores the presence of
intact memoryfunctions after cholinergic basal forebrain damage, despite
attentional impairments that follow these lesions, demonstrated in other task
paradigms.
Galantamine Facilitates Acquisition of a Trace-Conditioned Eyeblink Response in Healthy, Young Rabbits
Authors: Simon Barbara B. , Knuckley Bryan , Powell Donald A.
Published: January 2004

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of an eyeblink (EB) classical conditioningtask in healthy, younganimals. We trained 24 rabbits (n= 8/group) in a 1000-msec trace Pavlovian EB conditioningparadigm in which a tone conditioned stimulus (CS) was presented for 500 msec, followed by a 500-msec trace period in which no stimuli were presented. A 100-msec corneal airpuff was the unconditioned stimulus (US). Acquisition sessions, consistingof 100 trials each, occurred daily for 10 consecutive days, followed by 3 d of extinction training. Animals were treated with one of three doses of GAL (0.0–3.0 mg/kg) prior to each session. Animals that received 3.0 mg/kg GAL showed significantly more EB conditioned responses (CRs) in fewer trainingtrials than animals receivingeither 1.5 mg/kg GAL or vehicle injections. GAL had no effect on CR performance duringextinction. Pseudoconditioningcontrol experiments, consistingof 200 explicitly unpaired tone–puff presentations indicated that GAL did not increase reactivity to the CS or US. These findings indicate that GAL may improve acquisition of moderately difficult associative learningtasks in healthy young organisms.
Acetylcholine and Olfactory Perceptual Learning: Figure 1
Authors: Wilson Donald A. , Fletcher Max L. , Sullivan Regina M.
Published: January 2004

Olfactory perceptual learning is a relatively long-term, learned increase
in perceptual acuity, and has been described in both humans and animals. Data
from recent electrophysiological studies have indicated that olfactory
perceptual learning may be correlated with changes in odorant receptive fields
of neurons in the olfactory bulb and piriform cortex. These changes include
enhanced representation of the molecular features of familiar odors by mitral
cells in the olfactory bulb, and synthetic coding of multiple coincident
odorant features into odor objects by cortical neurons. In this paper, data
are reviewed that show the critical role of acetylcholine (Ach) in olfactory
system function and plasticity, and cholinergic modulation of olfactory
perceptual learning at both the behavioral and cortical level.
The Cholinergic Lesion of Alzheimer's Disease: Pivotal Factor or Side Show?
Authors: Mesulam Marsel
Published: January 2004

A profound loss of cortical cholinergic innervation is a nearlyinvariant feature of advanced Alzheimer's disease (AD). The temporal course of this lesion and its relationship to other aspects of the disease have not yet been fully clarified. Despite assertions to the contrary, a review of the evidence suggests that a perturbation of cholinergic innervation is likelyto be present even in the veryearlystages of AD. This cholinergic lesion is unlikelyto be a major determinant of the clinical symptoms or of the neuropathological lesions. Nonetheless, it almost certainly contributes to the severityof the cognitive and behavioral deficits, especiallyin the areas of memoryand attention. The cholinergic lesion mayalso influence the progression of the neuropathological process through complex interactions with amyloidogenesis, τ phosphorylation and neuroplasticity.
Pluralistic ignorance: historical development and organizational applications
Authors: Halbesleben Jonathon R.B. , Buckley M. Ronald
Published: January 2004

This paper examines the historical development of pluralistic ignorance as a construct and its application to organizational studies. Pluralistic ignorance is a social comparison error where an individual holds an opinion, but mistakenly believes that others hold the opposite opinion. Pluralistic ignorance was first developed as an important social construct in the 1920s by social psychologist Floyd Allport, and has been applied to myriad settings in psychology and sociology, including racial segregation, student perceptions of alcohol use, and classroom behavior. Despite work in pluralistic ignorance for over 75 years, it has only recently been applied to management settings. Management scholars have suggested applications of pluralistic ignorance to decision‐making, business ethics, group dynamics, performance appraisal, and burnout. Other management applications are proposed as a means to guide research in pluralistic ignorance in the future.
Family business training: a Canadian perspective
Authors: Ibrahim A.B. , Soufani K. , Lam Jose
Published: January 2004

Family firms play an important role in the working of the Canadian economy; despite their importance to the economic activities and job creation it is observed that family businesses have lower survival rates than non‐family firms, some argue that this can possibly be attributed (amongst other factors) to the lack of training. Most of the training activities in Canadian family businesses tend to be limited, and it is argued that family firms tend to perceive training more as an expense than an asset that enhances future growth and development of the business. This paper introduces a training framework and a coherent strategy that provides key elements of a national training agenda for Canadian small family firms, including the role of various relevant organizations.
E‐learning in small organisations
Authors: Sambrook Sally
Published: January 2004

This paper focuses on the existing and potential role of electronic learning in small and medium‐sized organisations (SMEs). Innovations in information and communication technologies (ICTs) could create new forms of learning, particularly appealing to small organisations, to overcome traditional barriers such as lack of financial resources, time, expertise and facilities. The paper draws upon research, conducted in North Wales, exploring employee perceptions of and employer attitudes towards e‐learning. Small organisations in rural, peripheral regions such as North Wales can benefit from ICTs, not only to support e‐commerce, but also to access new opportunities for learning and development, beyond the often‐restricted local market. However, key findings from this research suggest that there are significant barriers to electronic learning, including the lack of hardware and software, and employer attitudes. A model is presented that identifies dimensions of, and factors influencing, e‐learning from employer and employee perspectives.
The role of e‐mentoring in entrepreneurial education and support: a meta‐review of academic literature
Authors: Perren Lew
Published: January 2004

This paper draws upon policy‐based research that was conducted for the SBS South East to provide a meta‐review of academic literature that examines the role of e‐mentoring in entrepreneurial education and support. Four education and training relevant themes are explored: What is e‐mentoring in SMEs? How effective is e‐mentoring in SMEs? What examples are there of e‐mentoring in SMEs? What advice is there on introducing e‐mentoring for SMEs? The article concludes that current research falls short of a robust evaluation; nevertheless, by drawing upon a range of associated e‐mentoring research it has been possible to provide some helpful examples of practice and tentative advice on the introduction of such schemes.
Stress caused by on‐line collaboration in e‐learning: a developing model
Authors: Allan John , Lawless Naomi
Published: January 2004

On‐line collaboration is becoming increasingly common in education and in organisations. It was believed that this could in itself cause stress for collaborators. An analysis of on‐line learning diaries, phone interviews and questionnaires indicated that on‐line collaboration could cause stress, and this stress was linked to the dependency of the collaborators on each other, and the level of their mutual trust. Stress could be designed out of on‐line collaborative exercises through management of the on‐line working processes. The trend in both education and management towards increased on‐line working and collaboration indicates that further research needs to be carried out into finding how to reduce stress from this cause.
The relationship between trust and team performance
Authors: Erdem Ferda , Ozen Janset , Atsan Nuray
Published: January 2004

Suggests that teamworking is a critical success factor for most organizations. The study reported in this paper sought to investigate the relationship between the level of trust between members of a workteam and the performance of that team. The study involved 148 members of 28 teams across four organisations. Suggests that though there is a relationship between trust and performance (which was found to be particularly strong within two of the organizations), there are other factors at play. Suggests a number of factors which require further investigation.
Training for design of experiments
Authors: Antony Jiju , Chou Tzu‐Yao , Ghosh Sid
Published: January 2004

Many industrial engineers perform one‐factor‐at‐a‐time (OFAT) experiments to examine situations of process improvement and for problem‐solving activities. However, OFAT experiments can prove to be inefficient and unreliable, leading to false optimal conditions. Moreover, they often consist largely of “trial and error”, relying on luck, intuition, guesswork and experience for their success. Design of experiments (DOE) takes an alternative, more structured approach. DOE is a powerful technique for discovering a set of process or design variables which are most important to the process/product/system and then assisting experimenters to determine at what levels these variables should be set/kept to optimise performance. In order to demonstrate the power of designed experiments over the traditional OFAT approach, the authors use a simple catapult experiment. They suggest that such an experiment could act as a powerful weapon in the training of engineers and managers who might be intimidated by a more “up front” statistical approach.
An overview of frequently used performance measures
Authors: Tangen Stefan
Published: January 2004

Performance measures are often used to increase the competitiveness and profitability of manufacturing companies through the support and encouragement of productivity improvements. This paper reviews the most frequently used performance measures to identify their strengths and weaknesses and the situations in which they are most appropriately deployed. The performance measures under review are compared in terms of how easily they are derived from strategic objectives, how easy they are to understand and whether they help form a long‐term view of performance. Suggests that it is important to select performance measures to match the situation in which they are to be used; more importantly, it is necessary to combine various types of performance measure to provide a fair complete and balanced view of a company or the operations under evaluation.
Computerized workplace design using CADWORK heuristics
Authors: Udosen U.J.
Published: January 2004

Presents a computerized approach to workplace design using computer aided design of workplace assembly layout (CADWORK) to design a workplace for the assembly of a product comprising 11 components. The software accepts product data (assembly sequence), workplace data (working area) and anthropometric data (relating to the operator) and heuristically designs a detailed workplace layout. The software also calculates the standard time to complete the assembly. The resulting layout can then be modified interactively to improve on the basic design. In this case such subsequent improvement was marginal.
Perceived leader integrity and ethical intentions of subordinates
Authors: Peterson Dane
Published: January 2004

This study examined the relationship between perceived leader integrity, belief in universal moral rules, and employees’ ethical intentions while controlling for socially desirable response tendencies. The results demonstrated that both higher perceived leader integrity and stronger beliefs in universal moral rules were associated with lower intentions to commit unethical acts. More importantly, the results revealed an interaction between perceived leader integrity and belief in universal moral rules. Individuals with a strong belief in universal moral rules exhibited low intentions of committing unethical acts, regardless of the perceived integrity of their leaders. For individuals who do not adhere to a belief in universal moral rules, intention to commit unethical acts decreased as the perceived integrity of the leaders increased.