bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase
Authors: Drakas Robert , Tu Xiao , Baserga Renato
Published: June 2004

The insulin-like growth factor I/insulin receptor substrate 1 axis controls, in a nonredundant way, ≈50% of cell and body size in animals from
Drosophila
to mice and in cells in culture. Although other factors may also intervene, cell size is strongly dependent on ribosome biogenesis, which is under the control of RNA polymerase I activity. We have previously shown that insulin receptor substrate 1 (IRS-1) translocates to the nuclei and nucleoli, where it binds to the upstream binding factor (UBF) 1, a regulator of RNA polymerase I activity. Activation of UBF1 requires its phosphorylation. However, IRS-1 is not a kinase, and we searched for an intermediate kinase that can phosphorylate UBF1. We demonstrate here that IRS-1 binds also to the phosphatidylinositol 3-kinase (PI3-K) subunits in nuclear extracts, and that the p110 subunit of PI3-K directly phosphorylates and activates UBF1, an exclusively nucleolar protein. The interaction of IRS-1, PI3-K, and UBF1 in the nucleoli provides one of the mechanisms for the effects of IRS-1 on cell and body size.
Collegiate or compliant? Primary teachers in post‐McCrone Scotland
Authors: Macdonald Ann
Published: June 2004

Collegiality was cited in the post‐McCrone Agreement as a vital quality for a professional teaching force in Scotland in the twenty‐first century. The Agreement directed schools to henceforth operate more collegially and it was anticipated that this recommendation, alongside the new two‐tier promotion system, would facilitate the transformation of the currently hierarchical school culture into a more collegiate one. Drawing on data concerning the relationship of a small group of Scottish primary teachers with their head teacher, and their attitudes to local and national educational innovations, including the post‐McCrone Agreement, this article suggests that such an assumption is problematical. The tendencies of teachers to adopt a subordinate persona, and to comply with the wishes of the hierarchy despite their own professional reservations, point towards the existence of a hegemonic system in which collegiality has little locus.
Inhibitory sensory preconditioning
Authors: Espinet Alfredo , González Felisa , Balleine Bernard W.
Published: June 2004

In two experiments rats were preexposed to neutral stimuli. Both experiments used a between-subjects design in which a paired group was preexposed to intermixed presentations of A→ Band AX, and an unpaired control group was preexposed to intermixed presentations of A, B, and AX. After the conditioning of B, in Experiment 1, conditioned responding to X was acquired more slowly in the paired than in the unpaired group. Furthermore, in Experiment 2, Xreduced conditioned responding to a separately trained excitor in a summation test but only in the paired group. Together, these results provide evidence of an inhibitory form of sensory preconditioning.
Perceptual learning in humans: Roles of preexposure schedule, feedback, and discrimination assay
Authors: Dwyer D. M. , Hodder K. I. , Honey R. C.
Published: June 2004

In three experiments, humans received preexposure to two compound flavours (AX and BX: saline–lemon and sucrose–lemon) that were presented either in an intermixed (e.g., AX, BX,… BX, AX,…) or a blocked (e.g., AX, AX,… BX, BX…) fashion. Subsequently, AX was paired with an unpleasant bitter taste, and the discriminability of AX and BX was assessed using the accuracy of same/different judgements and by the extent to which any learned dislike of AX generalized to BX. When participants received feedback about the accuracy of their same/different judgements during preexposure those given intermixed preexposure were more accurate in making these judgements during the test than those given blocked preexposure (Experiments 1 and 2A), however, there was no evidence of any learned dislike in these experiments. In Experiment 2B, in which participants did not receive feedback about the accuracy of their judgements, there was no effect of the preexposure regime on same/different judgements, but there was a learned dislike of AX, and this generalized less to BX in participants given intermixed than in those given blocked preexposure. The beneficial effects of intermixed preexposure are consistent with results from other species (chicks and rats), but the differences created by the presence or absence of feedback place constraints on the analysis of these effects.
Flavour aversion produced by running and attenuated by prior exposure to wheels
Authors: Baysari Melissa T. , Boakes Robert A.
Published: June 2004

In two experiments hungry rats were given access to running wheels. When given the novel flavour, almond, prior to novel access to the wheels, a conditioned aversion to almond was revealed by a subsequent two-bottle test. No such aversion was found in rats with previous experience of wheel running, whether this prior running occurred in the absence of any novel flavour, as in Experiment 1, or following access to saccharin, as in Experiment 2. These results suggest that the failure of rats with prior experience of the running wheels to develop a flavour aversion (unconditioned stimulus, US, preexposure effect) is unlikely to be due to associative blocking. Instead it seems that increasing exposure to a wheel produces habituation of its nausea-inducing properties.
The Role of Associative History in Models of Associative Learning: A Selective Review and a Hybrid Model
Authors: Le Pelley M. E.
Published: June 2004

Associative learning theories strive to capture the processes underlying and driving the change in strength of the associations between representations of stimuli that develop as a result of experience of the predictive relationships between those stimuli. Historically, formal models of associative learning have focused on two potential factors underlying associative change, namely processing of the conditioned stimulus (in terms of changes in associability) and processing of the unconditioned stimulus (in terms of changes in error). This review constitutes an analysis of the proper role of these two factors, specifically with regard to the way in which they are influenced by associative history (the prior training undergone by cues). A novel “hybrid” model of associative learning is proposed and is shown to provide a more satisfactory account of the effects of associative history on subsequent learning than any previous single-process theory.
Measuring split renal function in renal donors: can computed tomography replace renography?
Authors: Nilsson H. , Wadström J. , Andersson L.‐G. , Raland H. , Magnusson A.
Published: June 2004

Purpose: To develop and evaluate a method of calculating split renal function from computed tomography (CT) images based on the assumption that the accumulation of contrast medium is proportional to the renal function, and to compare the results with the renogram.

Material and Methods: The study comprised a retrospective analysis of CT images and renograms from previous donors. Twenty‐seven potential renal donors were studied using a technique for measuring the area and mean attenuation of the separate CT slices, and for calculating the volume and total attenuation of the whole kidney.

Results: Correlation between CT and renography was moderate ( r=0.43), but the range of results was narrow. The ratio between the two kidneys was more even with CT (50±2.1%) than with the renogram (48±2.9%) (right kidney), and the mean difference between the two methods was 3±2.3 percentage points.

Conclusion: The renogram can be replaced using calculations from the CT examination in estimating split renal function in potential renal donors.
Color Doppler ultrasonography findings of bladder tumors: correlation with stage and histopathologic grade
Authors: Karahan O. I. , Yikilmaz A. , Ekmekcioglu O. , Ozturk F. , Sevinc H.
Published: June 2004

Purpose: To describe color Doppler ultrasonography findings of bladder tumors and to investigate the correlation between these findings with stage and histopathological grade.

Material and Methods: Twenty‐four patients with bladder tumors were assessed with color Doppler ultrasonography for tumor size, presence of vascularity, vascular pattern, and spectral properties. All patients underwent surgery. Stage and histopathological grades of tumors were determined and compared with color Doppler ultrasonography findings.

Results: Presence of vascularity was related to tumor size ( P<0.05) and color Doppler signal was detected when tumors reached 24 mm in size. There was no statistically significant relationship between tumor stage and histopathological grade with tumor size, presence and pattern of vascularity, and spectral color Doppler ultrasonography findings ( P>0.05).

Conclusion: The evaluation of vascularity in bladder tumors by color Doppler ultrasonography is not helpful in predicting tumor stage and histopathological grade before surgery.
Visualization of pancreaticobiliary reflux in anomalous pancreaticobiliary junction by secretin‐stimulated dynamic magnetic resonance cholangiopancreatography
Authors: Hosoki T. , Hasuike Y. , Takeda Y. , Michita T. , Watanabe Y. , Sakamori R. , Tokuda Y. , Yutani K. , Sai C. , Mitomo M.
Published: June 2004

Purpose: To assess the utility of secretin‐stimulated dynamic MR cholangiopancreatography (MRCP) for the visualization of pancreaticobiliary reflux in patients with anomalous pancreaticobiliary junction (PBJ).

Material and Methods: Ten controls and seven patients diagnosed as having anomalous PBJ were prospectively examined by dynamic MRCP after secretin injection using a breath‐hold, single‐shot turbo spin‐echo T2‐weighted sequence. The optimal MRCP section was repeated 35 times at approx. 10‐second interval after secretin injection; the acquisition time was 4 s per image. The signal intensity (SI) changes of the extrahepatic and intrahepatic bile ducts, presence or absence of intraluminal signal void, caliber change of the bile duct, duodenal filling, and peak time of the SI ratio of the extrahepatic bile duct after secretin injection were compared between the controls and patients.

Results: In the controls, the extrahepatic and intrahepatic bile ducts showed neither enhancement nor caliber change over the observation period, providing no apparent peak time. Of the seven patients, the extrahepatic bile duct showed retrograde enhancement and sequential delay in occurrence of the peak time from its distal third to its proximal third ( n=6) with a signal void in its distal part ( n=4); its caliber increased subsequently to pancreatic secretion ( n=5); the intrahepatic bile ducts showed a slight enhancement following SI increase of the proximal extrahepatic bile duct ( n=6); duodenal filling grade tended to be lower in the patients than volunteers ( P<.005).

Conclusion: In patients with anomalous PBJ pancreaticobiliary reflux were demonstrated by dynamic secretin‐stimulated MRCP.
Volume adjustment of lung density by computed tomography scans in patients with emphysema
Authors: Shaker S. B. , Dirksen A. , Laursen L. C. , Skovgaard L. T. , Holstein‐Rathlou N.‐H.
Published: June 2004

Purpose: To determine how to adjust lung density measurements for the volume of the lung calculated from computed tomography (CT) scans in patients with emphysema.

Material and Methods: Fifty patients with emphysema underwent 3 CT scans at 2‐week intervals. The scans were analyzed with a software package that detected the lung in contiguous images and subsequently generated a histogram of the pixel attenuation values. The total lung volume (TLV), lung weight, percentile density (PD), and relative area of emphysema (RA) were calculated from this histogram. RA and PD are commonly applied measures of pulmonary emphysema derived from CT scans. These parameters are markedly influenced by changes in the level of inspiration. The variability of lung density due to within‐subject variation in TLV was explored by plotting TLV against PD and RA.

Results: The coefficients for volume adjustment for PD were relatively stable over a wide range from the 10th to the 80th percentile, whereas for RA the coefficients showed large variability especially in the lower range, which is the most relevant for quantitation of pulmonary emphysema.

Conclusion: Volume adjustment is mandatory in repeated CT densitometry and is more robust for PD than for RA. Therefore, PD seems more suitable for monitoring the progression of emphysema.
Risk factors of new compression fractures in adjacent vertebrae after percutaneous vertebroplasty
Authors: Kim S. H. , Kang H. S. , Choi J.‐A. , Ahn J. M.
Published: June 2004

Purpose: To evaluate the risk factors related to the development of new fractures in adjacent vertebrae after vertebroplasty.

Material and Methods: The study was conducted on 106 patients in whom 212 vertebroplasties were performed during a period of 3 years. Evaluations of the five vertebrae superior and inferior to the treated vertebra were performed. Consequently, 913 vertebrae were evaluated and the fracture‐free interval of the vertebral body adjacent to the treated vertebra was calculated. Survival analysis was performed using the Kaplan‐Meier method and Cox proportional hazards regression analysis.

Results: Seventy‐two (7.9%) new fractures were revealed. The Kaplan‐Meier estimate of the 1‐year fracture‐free rate was 93.1%. The mean fracture‐free interval was 32 months (95% CI, 32∼33 months). The greater degree of height restoration of the treated vertebra, the location of the adjacent vertebra in the TL junction, and the shorter distance between the treated and the adjacent vertebra increased the risk of new vertebral fractures.

Conclusion: Thoracolumbar junction, shorter distance from the treated vertebrae, and greater degree of height restoration of the cemented vertebrae may increase the fracture risk of vertebrae adjacent to cement vertebrae after vertebroplasty.
Abdominal hydatid disease: long‐term results of percutaneous treatment
Authors: Etlik O. , Arslan H. , Bay A. , Sakarya M. E. , Harman M. , Temizoz O. , Kayan M. , Bakan V. , Unal O.
Published: June 2004

Purpose: To evaluate the effectiveness of percutaneous treatment under sonographic guidance in abdominal hydatid cysts.

Material and Methods: Fifty‐two hydatid cysts in 33 patients were treated using a percutaneous approach under sonographic guidance. Forty‐five cysts were located in the liver, 6 in the spleen, and 1 in the pancreas. Forty‐nine cysts were type I, and 3 were type II. Thirty‐one cysts in 15 patients were treated with puncture and aspiration of the contents, injection of hypertonic saline solution, and respiration (PAIR); 15 cysts in 14 patients were treated with puncture, aspiration of cyst contents, injection of hypertonic saline solution, drainage, and injection of sclerosing agent (PAIDS); and 6 cysts in 4 patients were treated with puncture, aspiration of cyst contents, injection of sclerosing agent, and re‐aspiration (mPAIDS). Hypertonic saline or alcohol was used as a scolicidal agent. The follow‐up period was between 17 and 53 months.

Results: A decrease in the dimensions of the cysts, solidification of the contents, and irregularity in the walls of cysts, all of which were considered signs of cure, were found in all patients. Recurrence was observed in one case and anaphylaxis in one.

Conclusion: Percutaneous treatment of abdominal hydatid cysts is a safe, easily applicable, well‐tolerated, and effective method.
Structural, Optical and Electrochromic Properties of Nanocrystalline TiO2 Thin Films Prepared by Spin Coating
Authors: Jourdani R. , Outzourhit A. , Oueriagli A. , Aitelhabti D. , Ameziane E. L. , Barazzouk S. , Hotchandani S.
Published: June 2004

Nanocrystalline TiO2 thin filmswere prepared by spin coating on covered glass substrates with an indium tin oxide (ITO) layer. The structural, electrochromic and optical properties of the films were investigated. The films are crystallized predominantly in the anatase phase with lattice parameters a = b = 0.378 nm and c = 0.958 nm . The crystallite size was found to be of the order of 14 nm. The films showed reversible coloration/bleaching cycles as demonstrated by cyclic voltametry and current–time transients. The transmission of the blue colored films decreased and their
absorption edge was less sharp and shifted to higher wavelengths as a result of the intercalation of Li+
ions.
Anisotropic Chemical Etching of III—V Crystals Dissolution Slowness Surface and Application to GaAs
Authors: Tellier C. R. , Huve G. , Leblois T. G.
Published: June 2004

The analytical equation for the dissolution slowness surface of III–V crystals that belong to point group is derived using a tensorial analysis of the anisotropic chemical dissolution. The role played by orientation functions in the generation of the dissolution slowness extrema is discussed. Four different databases composed of dissolution constants are proposed. The final shape of cross‐sectional dissolution profiles etched in differently oriented GaAs surfaces is analyzed and compared with published experimental results. Finally etching shapes of
micromachined membranes and mesa are derived showing that the anisotropy for the GaAs crystal is probably of type 2 rather than of type 1.
Current‐Controlled Sawtooth Generator
Authors: Abuelma′atti Muhammad Taher , Alabsi Munir Kulaib
Published: June 2004

A simple current‐controlled sawtooth generator is presented. Both the amplitude and the frequency of the generated sawtooth can be current‐controlled. The circuit uses off‐the‐shelf components. Experimental results are included.
Novel Two‐Dimensional (2‐D) Defected Ground Array for Planar Circuits
Authors: Liu Haiwen , Sun Xiaowei , Li Zhengfan
Published: June 2004

This paper presents a novel two‐dimensional (2‐D) defected ground array (DGA) for planar circuits, which has horizontal and vertical periodicities of defect structure. The defected unit cell of DGA is composed of a Sierpinski carpet structure to improve the effective inductance. Measurements show that the proposed DGA provides steeper cutoff characteristics, lower cutoff frequency, and higher slow‐wave factors than the conventional
periodic defected ground structure in the same occupied surface.
Déposition par Pulvé Risation Cathodique Radio Fréquence et Caracté Risation Électronique, Structurale et Optique de Couches Minces du Dioxyde de Titane
Authors: Hafidi K. , Azizan M. , Ijdiyaou Y. , Ameziane E. L.
Published: June 2004

Deposited titanium oxide thin films are used as optical protector films for several materials and as energy converters for solar cells. In this work, titanium oxide thin films are deposited on c‐Si and glass substrates by reactive radiofrequency sputtering. All the deposits are grown at ambient temperature and the sputtering gas is a mixture of oxygen and argon with an overall pressure of 10−2
mbar. The oxygen partial pressure ratios varies from 5% to 20%.

Characterization of deposited films is made by grazing incidence X‐ray diffraction (GIXD), grazing incidence X‐ray reflection (GIXR), X‐ray photoemission spectroscopy (XPS) and optical transmission spectroscopy. The characterization results reveal that deposited films of TiO2 are polycrystalline and present both rutile and anatase phases. The chemical composition of raw films in Ti:O ratio is equal to 1:2.02, and the titanium at surface is completely oxidized. In fact, the Ti2p core level behavior shows that the oxidization state of Ti is equal to +4.

The specularily reflected intensity according to incidence angle of the X‐ray on TiO2/glass structure shows one critical angle attributed to the TiO2 film equal to 0.283º. This angle value involves film density between rutile and anatase phases. The optical characterization shows that TiO2 thin films obtained are transparent in visible range, and have a refraction index value equal to 2.45 and when extrapolated to infrared range, it is equal to 2.23. The
value of gap energy (3.35 eV) is deduced from variation of absorption coefficient versus incident radiation energy.
A Current‐mode Logarithmic Function Circuit
Authors: Abuelma′atti Muhammad Taher , Faris Osama Oglah
Published: June 2004

A new current‐mode analog circuit configuration that implements the function ln (x/y) is proposed. The circuit uses bipolar transistors and resistors and is suitable for integration. In the proposed circuit the ratio (x/y) can be larger or smaller than unity. Simulation results are included.
The Use of Streptolysin O for the Treatment of Scars, Adhesions and Fibrosis: Initial Investigations Using Murine Models of Scleroderma
Authors: Mamber Stephen W. , Long Vit , Rhodes Ryan G. , Pond-Tor Sunthorn , Wheeler Lyn R. , Fredericks Kellie , VanScoy Brian , Sauniere Jean-Frederic , Steinschneider Remy , Laurent Jean-Claude , McMichael John
Published: June 2004

Diseases and conditions involving the deposition of excessive amounts of collagen include scleroderma, fibrosis, and scar and surgical adhesion formation. Diseases such as scleroderma may result from acute and chronic inflammation, disturbances in the normal parenchymal area, and activation of fibroblasts. ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is being developed for the treatment of such collagen-related disorders. At sublytic concentrations in vitro, ML-05 was shown to activate CD44 expression. This may modulate production of collagen, hyaluronate, and their associated enzymes to allow a restoration of normal extracellular matrices within tissues. More importantly, ML-05 appeared to decrease skin collagen levels in two in vivo models of collagen disorders, the tight skin mouse (Tsk) model of scleroderma, and the bleomycin-induced mouse skin fibrosis model. In the Tsk model, levels of hydroxyproline (a measure of total collagen) decreased by 25% in the Tsk+ML-05 treatment group relative to the Tsk+saline control group over a 3-month period. In the bleomycin-induced skin fibrosis study, hydroxyproline levels decreased from 15–22% over a 6-week period in a bleomycin-induced ML-05 treatment group (relative to levels in a bleomycin-induced, untreated control group). Hydroxyproline levels in samples from this treatment group were only slightly greater than levels in an uninduced control group at 8 weeks. Thus, ML-05 treatment appeared to reduce collagen levels in two separate mouse skin fibrosis models, one genetically based and the other chemically induced.
Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca2+ influx and PKC activation
Authors: Nagano Osamu , Murakami Daizo , Hartmann Dieter , de Strooper Bart , Saftig Paul , Iwatsubo Takeshi , Nakajima Motowo , Shinohara Masanori , Saya Hideyuki
Published: June 2004

CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca2+ influx or the activation of protein kinase C. Here we show that CD44-mediated cell–matrix adhesion is terminated by two independent ADAM family metalloproteinases, ADAM10 and ADAM17, differentially regulated in response to those stimuli. Ca2+ influx activates ADAM10 by regulating the association between calmodulin and ADAM10, leading to CD44 ectodomain cleavage. Depletion of ADAM10 strongly inhibits the Ca2+ influx-induced cell detachment from matrix. On the other hand, phorbol ester stimulation activates ADAM17 through the activation of PKC and small GTPase Rac, inducing proteolysis of CD44. Furthermore, depletion of ADAM10 or ADAM17 markedly suppressed CD44-dependent cancer cell migration on HA, but not on fibronectin. The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell–matrix interaction and cell migration.
Deregulation of cyclin E in human cells interferes with prereplication complex assembly
Authors: Ekholm-Reed Susanna , Méndez Juan , Tedesco Donato , Zetterberg Anders , Stillman Bruce , Reed Steven I.
Published: June 2004

Deregulation of cyclin E expression has been associated with a broad spectrum of human malignancies. Analysis of DNA replication in cells constitutively expressing cyclin E at levels similar to those observed in a subset of tumor-derived cell lines indicates that initiation of replication and possibly fork movement are severely impaired. Such cells show a specific defect in loading of initiator proteins Mcm4, Mcm7, and to a lesser degree, Mcm2 onto chromatin during telophase and early G1 when Mcm2–7 are normally recruited to license origins of replication. Because minichromosome maintenance complex proteins are thought to function as a heterohexamer, loading of Mcm2-, Mcm4-, and Mcm7-depleted complexes is likely to underlie the S phase defects observed in cyclin E–deregulated cells, consistent with a role for minichromosome maintenance complex proteins in initiation of replication and fork movement. Cyclin E–mediated impairment of DNA replication provides a potential mechanism for chromosome instability observed as a consequence of cyclin E deregulation.
Toll-like Receptor 9–Dependent and –Independent Dendritic Cell Activation by Chromatin–Immunoglobulin G Complexes
Authors: Boulé Melissa W. , Broughton Courtney , Mackay Fabienne , Akira Shizuo , Marshak-Rothstein Ann , Rifkin Ian R.
Published: June 2004

Dendritic cell (DC) activation by nucleic acid–containing immunoglobulin (Ig)G complexes has been implicated in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms responsible for activation and subsequent disease induction are not completely understood. Here we show that murine DCs are much more effectively activated by immune complexes that contain IgG bound to chromatin than by immune complexes that contain foreign protein. Activation by these chromatin immune complexes occurs by two distinct pathways. One pathway involves dual engagement of the Fc receptor FcγRIII and Toll-like receptor (TLR)9, whereas the other is TLR9 independent. Furthermore, there is a characteristic cytokine profile elicited by the chromatin immune complexes that distinguishes this response from that of conventional TLR ligands, notably the induction of BAFF and the lack of induction of interleukin 12. The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE.
Phosphorylation of Histone H2B at DNA Double-Strand Breaks
Authors: Fernandez-Capetillo Oscar , Allis C. David , Nussenzweig André
Published: June 2004

Posttranslational modifications of histone tails regulate numerous biological processes including transcription, DNA repair, and apoptosis. Although recent studies suggest that structural alterations in chromatin are critical for triggering the DNA damage response, very little is known about the nature of DNA damage-induced chromatin perturbations. Here we show that the serine 14 residue in the NH2-terminal tail of histone H2B is rapidly phosphorylated at sites of DNA double-strand breaks. At late time points after irradiation, the phosphorylated form of H2B, H2B-Ser14P, accumulates into irradiation-induced foci. H2B-Ser14P foci formation is not associated with the apoptotic phosphorylation of H2B but is strictly dependent on the phosphorylated isoform of H2AX. Our results broaden the spectrum of histone modifications that constitute the DNA damage “histone code” and suggest a model for the underlying chromatin structure within damage-induced foci.
Representation of Objects in Space by Two Classes of Hippocampal Pyramidal Cells
Authors: Rivard Bruno , Li Yu , Lenck-Santini Pierre-Pascal , Poucet Bruno , Muller Robert U.
Published: June 2004

Humans can recognize and navigate in a room when its contents have been rearranged. Rats also adapt rapidly to movements of objects in a familiar environment. We therefore set out to investigate the neural machinery that underlies this capacity by further investigating the place cell–based map of the surroundings found in the rat hippocampus. We recorded from single CA1 pyramidal cells as rats foraged for food in a cylindrical arena (the room) containing a tall barrier (the furniture). Our main finding is a new class of cells that signal proximity to the barrier. If the barrier is fixed in position, these cells appear to be ordinary place cells. When, however, the barrier is moved, their activity moves equally and thereby conveys information about the barrier's position relative to the arena. When the barrier is removed, such cells stop firing, further suggesting they represent the barrier. Finally, if the barrier is put into a different arena where place cell activity is changed beyond recognition (“remapping”), these cells continue to discharge at the barrier. We also saw, in addition to barrier cells and place cells, a small number of cells whose activity seemed to require the barrier to be in a specific place in the environment. We conclude that barrier cells represent the location of the barrier in an environment-specific, place cell framework. The combined place + barrier cell activity thus mimics the current arrangement of the environment in an unexpectedly realistic fashion.
Phg2, a Kinase Involved in Adhesion and Focal Site Modeling inDictyostelium
Authors: Gebbie Leigh , Benghezal Mohammed , Cornillon Sophie , Froquet Romain , Cherix Nathalie , Malbouyres Marilyne , Lefkir Yaya , Grangeasse Christophe , Fache Sébastien , Dalous Jérémie , Brückert Franz , Letourneur François , Cosson Pierre
Published: June 2004

The amoeba Dictyostelium is a simple genetic system for analyzing substrate adhesion, motility and phagocytosis. A new adhesion-defective mutant named phg2 was isolated in this system, and PHG2 encodes a novel serine/threonine kinase with a ras-binding domain. We compared the phenotype of phg2 null cells to other previously isolated adhesion mutants to evaluate the specific role of each gene product. Phg1, Phg2, myosin VII, and talin all play similar roles in cellular adhesion. Like myosin VII and talin, Phg2 also is involved in the organization of the actin cytoskeleton. In addition, phg2 mutant cells have defects in the organization of the actin cytoskeleton at the cell-substrate interface, and in cell motility. Because these last two defects are not seen in phg1, myoVII, or talin mutants, this suggests a specific role for Phg2 in the control of local actin polymerization/depolymerization. This study establishes a functional hierarchy in the roles of Phg1, Phg2, myosinVII, and talin in cellular adhesion, actin cytoskeleton organization, and motility.
Identification of Integrin β Subunit Mutations that Alter Heterodimer Function In Situ
Authors: Jannuzi Alison L. , Bunch Thomas A. , West Robert F. , Brower Danny L.
Published: June 2004

We conducted a genetic screen for mutations in myospheroid, the gene encoding the Drosophila βPS integrin subunit, and identified point mutants in all of the structural domains of the protein. Surprisingly, we find that mutations in very strongly conserved residues will often allow sufficient integrin function to support the development of adult animals, including mutations in the ADMIDAS site and in a cytoplasmic NPXY motif. Many mutations in the I-like domain reduce integrin expression specifically when βPS is combined with activating αPS2 cytoplasmic mutations, indicating that integrins in the extended conformation are unstable relative to the inactive, bent heterodimers. Interestingly, the screen has identified alleles that show gain-of-function characteristics in cell culture, but have negative effects on animal development or viability. This is illustrated by the allele mysb58; available structural models suggest that the molecular lesion of mysb58, V409>D, should promote the “open” conformation of the β subunit I-like domain. This expectation is supported by the finding that αPS2βPS (V409>D) promotes adhesion and spreading of S2 cells more effectively than does wild-type αPS2βPS, even when βPS is paired with αPS2 containing activating cytoplasmic mutations. Finally, comparisons with the sequence of human β8 suggest that evolution has targeted the “mysb58” residue as a means of affecting integrin activity.
Inositol 1,4,5-Trisphosphate Signaling Regulates Rhythmic Contractile Activity of Myoepithelial Sheath Cells inCaenorhabditis elegans
Authors: Yin Xiaoyan , Gower Nicholas J.D. , Baylis Howard A. , Strange Kevin
Published: June 2004

Intercellular communication between germ cells and neighboring somatic cells is essential for reproduction. Caenorhabditis elegans oocytes are surrounded by and coupled via gap junctions to smooth muscle-like myoepithelial sheath cells. Rhythmic sheath cell contraction drives ovulation and is triggered by a factor secreted from oocytes undergoing meiotic maturation. We demonstrate for the first time that signaling through the epidermal growth factor-like ligand LIN-3 and the LET-23 tyrosine kinase receptor induces ovulatory contractions of sheath cells. Reduction-of-function mutations in the inositol 1,4,5-trisphosphate (IP3) receptor gene itr-1 and knockdown of itr-1 expression by RNA interference inhibit sheath contractile activity. itr-1 gain-of-function mutations increase the rate and force of basal contractions and induce tonic sheath contraction during ovulation. Sheath contractile activity is disrupted by RNAi of plc-3, one of six phospholipase C-encoding genes in the C. elegans genome. PLC-3 is a PLC-γ homolog and is expressed in contractile sheath cells of the proximal gonad. Maintenance of sheath contractile activity requires plasma membrane Ca2+entry. We conclude that IP3generated by LET-23 mediated activation of PLC-γ induces repetitive intracellular Ca2+release that drives rhythmic sheath cell contraction. Calcium entry may function to trigger Ca2+release via IP3receptors and/or refill intracellular Ca2+stores.
A new yeast PUF family protein, Puf6p, represses ASH1 mRNA translation and is required for its localization
Authors: Gu Wei , Deng Yingfeng , Zenklusen Daniel , Singer Robert H.
Published: June 2004

In yeast Saccharomyces cerevisiae, Ash1p, a protein determinant for mating-type switching, is segregated within the daughter cell nucleus to establish asymmetry of HO expression. The accumulation of Ash1p results from ASH1 mRNA that is sorted as a ribonucleoprotein particle (mRNP or locasome) to the distal tip of the bud where translation occurs. To study the mechanism regulating ASH1 mRNA translation, we isolated the ASH1 locasome and characterized the associated proteins by MALDI-TOF. One of these proteins was Puf6p, a new member of the PUF family of highly conserved RNA-binding proteins such as Pumilio in Drosophila, responsible for translational repression, usually to effect asymmetric expression. Puf6p-bound PUF consensus sequences in the 3′UTR of ASH1 mRNA and repressed the translation of ASH1 mRNA both in vivo and in vitro. In the puf6Δ strain, asymmetric localization of both Ash1p and ASH1 mRNA were significantly reduced. We propose that Puf6p is a protein that functions in the translational control of ASH1 mRNA, and this translational inhibition is necessary before localization can proceed.
In vivo convergence of BMP and MAPK signaling pathways: impact of differential Smad1 phosphorylation on development and homeostasis
Authors: Aubin Josée , Davy Alice , Soriano Philippe
Published: June 2004

Integration of diverse signaling pathways is essential in development and homeostasis for cells to interpret context-dependent cues. BMP and MAPK signaling converge on Smads, resulting in differential phosphorylation. To understand the physiological significance of this observation, we have generated Smad1 mutant mice carrying mutations that prevent phosphorylation of either the C-terminal motif required for BMP downstream transcriptional activation (Smad1C mutation) or of the MAPK motifs in the linker region (Smad1L mutation). Smad1C/C mutants recapitulate many Smad1-/- phenotypes, including defective allantois formation and the lack of primordial germ cells (PGC), but also show phenotypes that are both more severe (head and branchial arches) and less severe (allantois growth) than the null. Smad1L/L mutants survive embryogenesis but exhibit defects in gastric epithelial homeostasis correlated with changes in cell contacts, actin cytoskeleton remodeling, and nuclear β-catenin accumulation. In addition, formation of PGCs is impaired in Smad1L/L mutants, but restored by allelic complementation in Smad1C/L compound mutants. These results underscore the need to tightly balance BMP and MAPK signaling pathways through Smad1.
Form follows function: the genomic organization of cellular differentiation
Authors: Kosak Steven T. , Groudine Mark
Published: June 2004

The extent to which the nucleus is functionally organized has broad biological implications. Evidence supports the idea that basic nuclear functions, such as transcription, are structurally integrated within the nucleus. Moreover, recent studies indicate that the linear arrangement of genes within eukaryotic genomes is nonrandom. We suggest that determining the relationship between nuclear organization and the linear arrangement of genes will lead to a greater understanding of how transcriptomes, dedicated to a particular cellular function or fate, are coordinately regulated. Current network theories may provide a useful framework for modeling the inherent complexity the functional organization of the nucleus.
The Insertional History of an Active Family of L1 Retrotransposons in Humans
Authors: Boissinot Stéphane , Entezam Ali , Young Lynn , Munson Peter J. , Furano Anthony V.
Published: June 2004

As humans contain a currently active L1 (LINE-1) non-LTR retrotransposon family (Ta-1), the human genome database likely provides only a partial picture of Ta-1-generated diversity. We used a non-biased method to clone Ta-1 retrotransposon-containing loci from representatives of four ethnic populations. We obtained 277 distinct Ta-1 loci and identified an additional 67 loci in the human genome database. This collection represents ∼90% of the Ta-1 population in the individuals examined and is thus more representative of the insertional history of Ta-1 than the human genome database, which lacked ∼40% of our cloned Ta-1 elements. As both polymorphic and fixed Ta-1 elements are as abundant in the GC-poor genomic regions as in ancestral L1 elements, the enrichment of L1 elements in GC-poor areas is likely due to insertional bias rather than selection. Although the chromosomal distribution of Ta-1 inserts is generally a function of chromosomal length and gene density, chromosome 4 significantly deviates from this pattern and has been much more hospitable to Ta-1 insertions than any other chromosome. Also, the intra-chromosomal distribution of Ta-1 elements is not uniform. Ta-1 elements tend to cluster, and the maximal gaps between Ta-1 inserts are larger than would be expected from a model of uniform random insertion.
Extensive Expansion of the Claudin Gene Family in the Teleost Fish, Fugu rubripes
Authors: Loh Yong Hwee , Christoffels Alan , Brenner Sydney , Hunziker Walter , Venkatesh Byrappa
Published: June 2004

In humans, the claudin superfamily consists of 19 homologous proteins that commonly localize to tight junctions of epithelial and endothelial cells. Besides being structural tight-junction components, claudins participate in cell–cell adhesion and the paracellular transport of solutes. Here, we identify and annotate the claudin genes in the whole-genome of the teleost fish, Fugu rubripes (Fugu), and determine their phylogenetic relationships to those in mammals. Our analysis reveals extensive gene duplications in the teleost lineage, leading to 56 claudin genes in Fugu. A total of 35 Fugu claudin genes can be assigned orthology to 17 mammalian claudin genes, with the remaining 21 genes being specific to the fish lineage. Thus, a significant number of the additional Fugu genes are not the result of the proposed whole-genome duplication in the fish lineage. Expression profiling shows that most of the 56 Fugu claudin genes are expressed in a more-or-less tissue-specific fashion, or at particular developmental stages. We postulate that the expansion of the claudin gene family in teleosts allowed the acquisition of novel functions during evolution, and that fish-specific novel members of gene families such as claudins contribute to a large extent to the distinct physiology of fishes and mammals.
Comparative Sequence and X-Inactivation Analyses of a Domain of Escape in Human Xp11.2 and the Conserved Segment in Mouse
Authors: Tsuchiya Karen D. , Greally John M. , Yi Yajun , Noel Kevin P. , Truong Jean-Pierre , Disteche Christine M.
Published: June 2004

We have performed X-inactivation and sequence analyses on 350 kb of sequence from human Xp11.2, a region shown previously to contain a cluster of genes that escape X inactivation, and we compared this region with the region of conserved synteny in mouse. We identified several new transcripts from this region in human and in mouse, which defined the full extent of the domain escaping X inactivation in both species. In human, escape from X inactivation involves an uninterrupted 235-kb domain of multiple genes. Despite highly conserved gene content and order between the two species, Smcx is the only mouse gene from the conserved segment that escapes inactivation. As repetitive sequences are believed to facilitate spreading of X inactivation along the chromosome, we compared the repetitive sequence composition of this region between the two species. We found that long terminal repeats (LTRs) were decreased in the human domain of escape, but not in the majority of the conserved mouse region adjacent to Smcx in which genes were subject to X inactivation, suggesting that these repeats might be excluded from escape domains to prevent spreading of silencing. Our findings indicate that genomic context, as well as gene-specific regulatory elements, interact to determine expression of a gene from the inactive X-chromosome.
Online Conference Netherlands
Authors: Farace Dominic
Published: June 2004

Outlines a selection of the main points of the Online Conference Netherlands 2004, held in Amsterdam in April 2004.
American Chemical Society National Meeting
Authors: Love April M.
Published: June 2004

Reports on the 227th National Meeting of the American Chemical Society (ACS) which took place at the end of March 2004 in Anaheim, California. Notes that the national meeting of the society is held twice a year, and is a working meeting of the membership, most of whom are involved in chemical research in the industrial and academic sectors; notes also that the range of topics at this meeting varied widely. Outlines several of the papers presented, including one which the author delivered. The highlight of the whole conference for the author was a presentation in the General Papers session “New ways to integrate data and information”, which discussed the organization of information and how to improve access performance by using federated data sources, linking using data wrappers, application software and user defined libraries, and database extenders.
New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene
Authors: Zerres K , Senderek J , Rudnik‐Schöneborn S , Eggermann T , Kunze J , Mononen T , Kääriäinen H , Kirfel J , Moser M , Buettner R , Bergmann C
Published: June 2004

Due to the poor prognosis of severe autosomal recessive polycystic kidney disease (ARPKD), there is a strong demand for prenatal diagnosis (PD). Reliable PD testing is possible by molecular genetic analysis only. Although haplotype‐based analysis is feasible in most cases, it is associated with a risk of misdiagnosis in families without pathoanatomically proven diagnosis. Linkage analysis is impossible in families where DNA of the index patient is not available. Direct mutation analysis of the recently identified polycystic kidney and hepatic disease 1 gene opens new options in families to whom a reliable PD cannot be offered on the basis of linkage analysis. We for the first time report two cases with PD based on mutation detection, illustrating the new options for PD in ARPKD.
Association of parental consanguinity with congenital malformations among Arab newborns in Jerusalem
Authors: Bromiker R , Glam‐Baruch M , Gofin R , Hammerman C , Amitai Y
Published: June 2004

The aim of this work was to determine the impact of parental consanguinity on congenital malformations in a mixed urban and rural Arab community in Jerusalem, Israel. Arab mothers admitted to four hospitals in west Jerusalem were interviewed after delivery. Demographic and obstetric data were recorded. Neonatal data were extracted from the medical records of the nursery. When malformations were suspected, a 4‐ to 10‐month follow up was achieved for confirming the diagnosis. Of 561 infants, 253 (45%) were born to consanguineous couples. The incidence of major congenital malformations in the offspring was 8.7, 7.1 and 2.6% in cases of first cousins, all consanguineous, and non‐consanguineous couples, respectively. No association was found between parental consanguinity and prematurity (p = 0.357) or low birth weight (p = 0.589). Parental consanguinity was also associated with an increased incidence of death in previous siblings (p < 0.000). The increased incidence of congenital malformations and infant mortality in cases of inbreeding prompt the necessity of establishing programs to avoid these complications in the offspring.
High frequency of subtelomeric rearrangements in a cohort of 92 patients with severe mental retardation and dysmorphism
Authors: Novelli A , Ceccarini C , Bernardini L , Zuccarello D , Caputo V , Digilio MC , Mingarelli R , Dallapiccola B
Published: June 2004

About 5–10% of patients with dysmorphisms, severe mental retardation, and normal standard karyotype are affected by subtelomeric chromosome rearrangements. Sequence homology between different chromosomes and variability between homologs make these regions more susceptible to breakage and reunion. We analyzed the telomeric regions of 92 of these patients, selected with strict clinical criteria. Fifteen individuals (16.3%) had subtelomeric rearrangements. Nine had a unique anomaly, which in one case had been inherited from a balanced parent. Six subjects had double segmental imbalances, including three de novo imbalances. This study provides further evidence for the plasticity of subtelomeric regions, which often results in cryptic rearrangements, and recommends stringent criteria for selecting patient candidates to telomere analysis.
Cholesterol at the crossroads: Alzheimer's disease and lipid metabolism
Authors: Wellington CL
Published: June 2004

Alzheimer's Disease (AD) is a devastating disease that affects millions of elderly persons. Despite years of intense investigations, genetic risk factors that affect the majority of AD cases have yet to be determined. Recent studies suggest that cholesterol metabolism has integral part in AD pathogenesis, suggesting that genes that regulate lipid metabolism may also play roles in AD. This review will first describe emerging evidence that links cholesterol to the mechanisms thought to underlie AD. Based on this rationale, candidate genes located in regions implicated in AD that have roles in lipid metabolism will then be discussed.
Loose tongues
Authors: Kureishi Hanif
Published: June 2004

This article is not available online, but does appear in the printed issue.