bluuebunny/crossref_metadata_2025 huggingface dataset:
Value of information for water quality management
Authors: Borisova Tatiana , Shortle James , Horan Richard D. , Abler David
Published: June 2005

There is now much interest in comprehensive watershed‐based approaches to water quality protection. While there is much to be said in favor of such an approach, it is also clear that implementation requires information that is often lacking. Given that information acquisition is costly, decisions are required about the types and amounts of information that should be sought. We examine the expected value of different types of information for price and quantity instruments for agricultural nitrogen pollution control in the Susquehanna River Basin. We also compare the ex ante economic efficiency of price and quantity instruments. The analysis explicitly accounts for public sector uncertainty about the benefits and costs of pollution reductions, with economic efficiency measured as the expected benefits less the expected costs of pollution reductions. We find optimized price controls to outperform optimized quantity controls under a range of possible information structures. For both instruments, information collection improves policy performance, with information about the benefits of pollution reductions having the greatest impact. The performance of the quantity instrument is more sensitive to information than is the price instrument. In consequence, the value of information to reduce benefit and cost uncertainty is greater for the quantity control.
Microgravity studies of aggregation in particulate clouds
Authors: Marshall J. R. , Sauke T. B. , Cuzzi J. N.
Published: June 2005

Aggregation in clouds of submillimeter quartz and volcanic ash particles was studied in microgravity. Particle clouds generated by pulses of air immediately formed electrostatic filamentary aggregates upon cessation of air turbulence. Manual agitation of experiment chambers produced cm‐size loose grain clusters which voraciously scavenged free‐floating material in their vicinity. A dipole model accounts for these observations. Experimental results have ramifications for the behavior of natural cloud systems and primary accretion of solids in the early solar nebula.
Toward a global earthshine network: First results from two stations
Authors: Pallé E. , Goode P. R. , Montañés‐Rodriguez P. , Koonin S. E. , Rumyantsev V.
Published: June 2005

Big Bear Solar Observatory is building the world's first global earthshine network to measure Earth's large‐scale reflectance. Our first remote station was deployed in late 2003 at the Crimean Astronomical Observatory. Here we compare the data obtained from the two earthshine stations, Crimea and Big Bear. We find that the retrieved quantities from both stations are consistent and that the data may be easily combined into a single data set expanding the temporal and geographical coverage of our Earth reflectance measurements from California. We also detail our plans and the expected coverage with a larger network of stations.
Discovery of nitrogen in Saturn's inner magnetosphere
Authors: Smith H. T. , Shappirio M. , Sittler E. C. , Reisenfeld D. , Johnson R. E. , Baragiola R. A. , Crary F. J. , McComas D. J. , Young D. T.
Published: June 2005

We detected N+ in Saturn's magnetosphere in the range L ∼ 3.5 to ∼9.5 Saturn Radii (Rs) using data collected by the Cassini Plasma Spectrometer during Saturn Orbit Insertion and the following orbit (Rev A). The presence of N+ in Saturn's magnetosphere has been a source of much debate since Voyager's detection of unresolved mass/charge 14–16 amu ions in this region. Two principal nitrogen sources have been suggested: Titan's atmosphere and nitrogen compounds trapped in Saturn's icy satellite surfaces (Sittler et al., 2004; E. C. Sittler et al., Energetic nitrogen ions within the inner magnetosphere of Saturn, submitted to Journal of Geophysical Research, 2004). The latter may contain primordial nitrogen, likely as NH3 in ice (Stevenson, 1982; Squyers et al., 1983) or N+ that has been implanted in the surface (Delitsky and Lane, 2002). In addition to our nitrogen detection results, we also present an initial examination of possible sources of these ions.
Reasons for a fresher northern North Atlantic in the late 20th century
Authors: Hu Aixue , Meehl Gerald A.
Published: June 2005

Observational analyses suggest that the northern North Atlantic is fresher in the late 20th century in comparison to the 1950–60s. Here we examine possible contributors to these observed changes by analyzing a four‐member ensemble of 20th century simulations from a coupled climate model. Results show that a weaker meridional freshwater divergence related to a weaker thermohaline circulation in the North Atlantic is the primary cause for the freshening in the northern North Atlantic in the model. The increased P‐E tends to enforce it, but the reduced sea ice flux into this region tends to weaken it.
Everolimus treatment downregulates renocortical cyclooxygenase‐2 expression in the rat kidney
Authors: Höcherl Klaus , Hensel Corina , Ulbricht Bettina , Krämer Bernhard K
Published: June 2005

Based on recent evidence that renal cyclooxygenase‐2 (COX‐2) gene expression is suppressed by immunosuppressive agents such as cyclosporin A (CsA), tacrolimus and dexamethasone, this study aimed to characterize the effect of the new immunosuppressant everolimus on COX‐2 expression in the rat kidney.

Oral application of everolimus (3 mg kg−1 day−1) to male Sprague–Dawley rats (175–200 g; n=8) for 7 days lowered COX‐2 expression in the rat renal cortex and outer medulla, while COX‐2 expression in the inner medulla as well as COX‐1 expression remained unaltered. Furthermore, everolimus decreased renocortical prostaglandin (PG) E2 concentration.

Everolimus also attenuated the stimulation of renocortical COX‐2 expression by furosemide (12 mg day−1 for 7 days; s.c. via osmotic minipumps), by low salt intake (0.02% NaCl, wt wt−1) or by a combination of low salt intake with the AT1‐receptor antagonist valsartan (30 mg kg−1 day−1; oral). In line with these findings, everolimus decreased renocortical PGE2 concentration during these treatment maneuvers.

Everolimus moderately increased natriuresis and diuresis, while the urinary excretion of PGE2, 6‐keto PGF1α and thromboxane B2 was decreased.

These findings suggest that everolimus inhibits basal and also stimulated expression of renocortical COX‐2 and of tissue prostanoid formation. Since inhibition of renal prostanoid formation by everolimus was associated by an increased rather than decreased natriuresis and diuresis, it appears as if everolimus also inhibits tubular salt and water resorption.

British Journal of Pharmacology (2005) 145, 1112–1122. doi:10.1038/sj.bjp.0706259
Mast cell‐derived tumour necrosis factor‐α mediates macrophage inflammatory protein‐2‐induced recruitment of neutrophils in mice
Authors: Wang Yusheng , Thorlacius Henrik
Published: June 2005

Recent studies have indicated that mast cells play an intermediate role in chemokine‐induced neutrophil recruitment in vivo.

The aim of the present investigation was to determine the role of tumour necrosis factor‐α (TNF‐α) in neutrophil recruitment provoked by the CXC chemokine macrophage inflammatory protein‐2 (MIP‐2). For this purpose, we used mast cell‐ and TNF‐α‐deficient mice and studied neutrophil adhesion to endothelial cells in vitro and neutrophil recruitment in the mouse cremaster muscle in vivo.

In contrast to the classical chemoattractant formyl‐methionine‐leucine‐phenylalanin (fMLP), MIP‐2 dose dependently increased neutrophil accumulation in vivo. This MIP‐2‐regulated neutrophil recruitment was abolished in mast cell‐deficient mice.

TNF‐α increased E‐selectin mRNA expression in both wild‐type (WT) and mast cell‐deficient mice. In contrast, MIP‐2 challenge increased gene expression of E‐selectin in WT but not in mast cell‐deficient animals. Moreover, MIP‐2‐provoked extravascular accumulation of neutrophils was reduced by 78% in mice lacking TNF‐α.

In order to better define the role of mast cell‐derived TNF‐α in neutrophil responses to MIP‐2, we used an in vitro endothelial cell adhesion assay with and without mast cells. Interestingly, MIP‐2‐induced neutrophil adhesion to endothelial cells was decreased by 58% using TNF‐α‐deficient compared to WT mast cells. Moreover, mast cell secretion of TNF‐α increased by more than 71% in response to challenge with MIP‐2.

Taken together, our results suggest that MIP‐2‐induced neutrophil recruitment is mediated by TNF‐α released from local mast cells. These findings help to explain the complex molecular interactions between chemokines, mast cell activation and neutrophil infiltration in vivo.

British Journal of Pharmacology (2005) 145, 1062–1068. doi:10.1038/sj.bjp.0706274
Cellular responses to nicotinic receptor activation are decreased after prolonged exposure to galantamine in human neuroblastoma cells
Authors: Barik Jacques , Dajas‐Bailador Federico , Wonnacott Susan
Published: June 2005

In this study, we have examined cellular responses of neuroblastoma SH‐SY5Y cells after chronic treatment with galantamine, a drug used to treat Alzheimer's disease that has a dual mechanism of action: inhibition of acetylcholinesterase and allosteric potentiation of nicotinic acetylcholine receptors (nAChR). Acute experiments confirmed that maximum potentiation of nicotinic responses occurs at 1 μM galantamine; hence this concentration was chosen for chronic treatment.

Exposure to 1 μM galantamine for 4 days decreased Ca2+ responses (by 19.8±3.6%) or [3H]noradrenaline ([3H]NA) release (by 23.9±3.3%) elicited by acute application of nicotine. KCl‐evoked increases in intracellular Ca2+ were also inhibited by 10.0±1.9% after 4 days' treatment with galantamine. These diminished responses are consistent with the downregulation of downstream cellular processes.

Ca2+ responses evoked by activation of muscarinic acetylcholine receptors were unaffected by chronic galantamine treatment. Exposure to the more potent acetylcholinesterase inhibitor rivastigmine (1 μM) for 4 days failed to alter nicotine‐, KCl‐, or muscarinic receptor‐evoked increases in intracellular Ca2+. These observations support the hypothesis that chronic galantamine exerts its effects through interaction with nAChR in this cell line.

Exposure to 10 μM nicotine for 4 days produced decreases in acute nicotine‐ (18.0±3.5%) and KCl‐evoked Ca2+ responses (10.6±2.5%) and nicotine‐evoked [3H]NA release (26.0±3.3%) that are comparable to the effects of a corresponding exposure to galantamine.

Treatment with 1 μM galantamine did not alter numbers of [3H]epibatidine‐binding sites in SH‐SY5Y cells, in contrast to 62% upregulation of these sites in response to 10 μM nicotine.

Thus, chronic galantamine acts at nAChR to decrease subsequent functional responses to acute stimulation with nicotine or KCl. This effect appears to be independent of the upregulation of nAChR‐binding sites.

British Journal of Pharmacology (2005) 145, 1084–1092. doi:10.1038/sj.bjp.0706278; published online 6 June 2005
Characterisation of cell‐penetrating peptide‐mediated peptide delivery
Authors: Jones Simon W , Christison Richard , Bundell Ken , Voyce Catherine J , Brockbank Sarah M V , Newham Peter , Lindsay Mark A
Published: June 2005

Cell‐penetrating peptides such as antennapedia, TAT, transportan and polyarginine have been extensively employed for in vitro and in vivo delivery of biologically active peptides. However, little is known of the relative efficacy, toxicity and uptake mechanism of individual protein transduction domain–peptide conjugates, factors that will be critical in determining the most effective sequence.

In the present study, we show by FACS analysis that unconjugated antennapedia, TAT, transportan and polyarginine demonstrate similar kinetic uptake profiles, being maximal at 1–3 h and independent of cell type (HeLa, A549 and CHO cell lines). A comparison of the magnitude of uptake of cell‐penetrating peptide conjugates demonstrated that polyarginine=transportan>antennapedia>TAT.

However, examination of cellular toxicity showed that antennapedia<TAT<transportan<∩polyarginine, with antennapedia–peptide conjugates having no significant toxicity even at 100 μM.

Confocal studies of the mechanism of antennapedia‐ and TAT‐peptide uptake showed that the time course of uptake and their cellular distribution did not correlate with transferrin, a marker of clathrin‐mediated endocytosis. In contrast, the peptides co‐localised with a marker of lipid rafts domains, cholera toxin, which was attenuated following the disruption of these domains using methyl‐β‐cyclodextrin.

Overall, comparison of the uptake and toxicity suggests that antennapedia provides the optimal cell‐penetrating peptide for peptide delivery in vitro and that both antennapedia‐ and TAT‐mediated peptide delivery occurs predominantly via lipid raft‐dependent but clathrin‐independent endocytosis.

British Journal of Pharmacology (2005) 145, 1093–1102. doi:10.1038/sj.bjp.0706279; published online 6 June 2005
An analysis of primary production in the Daly River, a relatively unimpacted tropical river in northern Australia
Authors: Webster I. T. , Rea N. , Padovan A. V. , Dostine P. , Townsend S. A. , Cook S.
Published: June 2005

In this paper, the dynamics of primary production in the Daly River in tropical Australia are investigated. We used the diurnal-curve method for both oxygen and pH to calculate photosynthesis and respiration rates as indicators of whole-river productivity. The Daly River has maximum discharges during the summer, monsoonal season. Flow during the dry season is maintained by groundwater discharge via springs. The study investigated how primary production and respiration evolve during the period of low flow in the river (April–November). The relationship between primary production and the availability of light and nutrients enabled the role of these factors to be assessed in a clear, oligotrophic tropical river. The measured rate of photosynthesis was broadly consistent with the estimated mass of chlorophyll associated with the main primary producers in the river (phytoplankton, epibenthic algae, macroalgae, macrophytes). A significant result of the analysis is that during the time that plant biomass re-established after recession of the flows, net primary production proved to be ~4% of the rate of photosynthesis. This result and the observed low-nutrient concentrations in the river suggest a tight coupling between photosynthetic fixation of carbon and the microbial degradation of photosynthetic products comprising plant material and exudates.
Australia's tropical river systems: current scientific understanding and critical knowledge gaps for sustainable management
Authors: Hamilton Stephen K. , Gehrke Peter C.
Published: June 2005

Australia’s tropical river systems are poorly understood in comparison with Australia’s temperate freshwater and tropical marine systems. Tropical rivers convey ~70% of the continent’s freshwater runoff, and are increasingly being targeted for development. However, existing knowledge is inadequate to support policy for tropical regions that avoids repeating the environmental problems of water use in southern Australia. This paper summarises existing knowledge on the hydrogeomorphic drivers of tropical catchments, fluxes of sediments and nutrients, flow requirements and wetlands. Key research issues include improved quantification of available water resources, hydrological, biogeochemical and ecological linkages at systems scales, understanding and valuing ecosystem processes and services, and projecting the effects of long-term climate change. Two special considerations for tropical Australia are the location of major centres of government and research capacity outside the tropical region, and the legal title of much of tropical Australia vesting in Aboriginal communities with different cultural values for rivers. Both issues will need to be addressed if tropical research is to be effective in supporting resource management needs into the future. Systems-scale thinking is needed to identify links between system components and coastal enterprises, and to protect the environmental, social, and economic values of Australia’s tropical river systems.
Insights into Lafora disease: Malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin
Authors: Gentry Matthew S. , Worby Carolyn A. , Dixon Jack E.
Published: June 2005

Lafora disease (LD) is a fatal form of progressive myoclonus epilepsy caused by recessive mutations in either a gene encoding a dual-specificity phosphatase, known as laforin, or a recently identified gene encoding the protein known as malin. Here, we demonstrate that malin is a single subunit E3 ubiquitin (Ub) ligase and that its RING domain is necessary and sufficient to mediate ubiquitination. Additionally, malin interacts with and polyubiquitinates laforin, leading to its degradation. Missense mutations in malin that are present in LD patients abolish its ability to polyubiquitinate and signal the degradation of laforin. Our results demonstrate that laforin is a physiologic substrate of malin, and we propose possible models to explain how recessive mutations in either malin or laforin result in LD. Furthermore, these data distinguish malin as an E3 Ub ligase whose activity is necessary to prevent a neurodegenerative disease that involves formation of nonproteinacious inclusion bodies.
Methyl CpG–binding proteins induce large-scale chromatin reorganization during terminal differentiation
Authors: Brero Alessandro , Easwaran Hariharan P. , Nowak Danny , Grunewald Ingrid , Cremer Thomas , Leonhardt Heinrich , Cardoso M. Cristina
Published: June 2005

Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG–binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG–binding domain (MBD) only. Similar to MeCP2, another methyl CpG–binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation.
Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow
Authors: Ueda Yoshihiro , Kondo Motonari , Kelsoe Garnett
Published: June 2005

The coordinated production of leukocytes in bone marrow is crucial for innate and adaptive immunity. Inflammation alters normal leukocyte production by promoting granulopoiesis over lymphopoiesis, a response that supports the reactive neutrophilia that follows infection. Here we demonstrate that this specialization for granulopoiesis is determined by inflammation-induced reductions of growth and retention factors, most significantly stem cell factor and CXCL12, which act preferentially to inhibit lymphoid development. These hierarchical effects suggest that the normal equilibrium of leukocyte production in bone marrow is determined by lymphopoiesis' higher demand for specific growth factors and/or retention signals. Inflammation regulates this balance by reducing growth factors that have less impact on developing neutrophils than lymphocytes. We demonstrate that granulopoiesis and lymphopoiesis are coupled specifically in the bone marrow by development in a common niche and propose that the leukopoietic equilibrium is specified by limiting amounts of developmental resources.
Immune evasion versus recovery after acute hepatitis C virus infection from a shared source
Authors: Tester Ian , Smyk-Pearson Susan , Wang Ping , Wertheimer Anne , Yao Ermei , Lewinsohn David M. , Tavis John E. , Rosen Hugo R.
Published: June 2005

Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because of the retrospective nature and unknown source of infection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I–restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T cells that targeted a single epitope in one patient was associated with mutational escape and viral persistence. Statistical evidence for positive Darwinian selective pressure against an immunodominant epitope is presented. Wild-type cytotoxic T lymphocytes persisted even after the cognate antigen was no longer present.
Mutational escape from CD8+ T cell immunity
Authors: Bowen David G. , Walker Christopher M.
Published: June 2005

The mechanisms by which the hepatitis C virus (HCV) establishes persistence are not yet fully understood. Previous chimpanzee and now human studies suggest that mutations within MHC class I–restricted HCV epitopes might contribute to viral escape from cytotoxic T lymphocyte (CTL) responses. However, there are several outstanding questions regarding the role of escape mutations in viral persistence and their fate in the absence of immune selection pressure.
The career of Maclyn McCarty
Authors: Gotschlich Emil C. , Fischetti Vincent A.
Published: June 2005

On January 2, 2005, the scientific community lost a valued colleague and friend. Maclyn McCarty, or “Mac,” as he was better known, was perhaps most recognized for his part in the discovery of DNA as the carrier of genetic information. But McCarty's scientific career was long and fruitful, and his contributions to science were vast. This retrospective offers a look at some of Mac's other notable scientific achievements.
Harish-Chandra modules for Yangians
Authors: Futorny Vyacheslav , Molev Alexander , Ovsienko Serge
Published: June 2005

We study Harish-Chandra representations of the Yangian

Y

(

g
l

2

)

\mathrm {Y}(\mathfrak {gl}_2)

with respect to a natural maximal commutative subalgebra. We prove an analogue of the Kostant theorem showing that the restricted Yangian

Y

p

(

g
l

2

)

\mathrm {Y}_p(\mathfrak {gl}_2)

is a free module over the corresponding subalgebra

Γ
\Gamma

and show that every character of

Γ
\Gamma

defines a finite number of irreducible Harish-Chandra modules over

Y

p

(

g
l

2

)

\mathrm {Y}_p(\mathfrak {gl}_2)

. We study the categories of generic Harish-Chandra modules, describe their simple modules and indecomposable modules in tame blocks.
Cytoplasmic Dynein's Mitotic Spindle Pole Localization Requires a Functional Anaphase-promoting Complex, γ-Tubulin, and NUDF/LIS1 inAspergillus nidulans
Authors: Li Shihe , Oakley C. Elizabeth , Chen Guifang , Han Xiaoyan , Oakley Berl R. , Xiang Xin
Published: June 2005

In Aspergillus nidulans, cytoplasmic dynein and NUDF/LIS1 are found at the spindle poles during mitosis, but they seem to be targeted to this location via different mechanisms. The spindle pole localization of cytoplasmic dynein requires the function of the anaphase-promoting complex (APC), whereas that of NUDF does not. Moreover, although NUDF's localization to the spindle poles does not require a fully functional dynein motor, the function of NUDF is important for cytoplasmic dynein's targeting to the spindle poles. Interestingly, a γ-tubulin mutation, mipAR63, nearly eliminates the localization of cytoplasmic dynein to the spindle poles, but it has no apparent effect on NUDF's spindle pole localization. Live cell analysis of the mipAR63 mutant revealed a defect in chromosome separation accompanied by unscheduled spindle elongation before the completion of anaphase A, suggesting that γ-tubulin may recruit regulatory proteins to the spindle poles for mitotic progression. In A. nidulans, dynein is not apparently required for mitotic progression. In the presence of a low amount of benomyl, a microtubule-depolymerizing agent, however, a dynein mutant diploid strain exhibits a more pronounced chromosome loss phenotype than the control, indicating that cytoplasmic dynein plays a role in chromosome segregation.
Spindle Checkpoint Signaling Requires the Mis6 Kinetochore Subcomplex, Which Interacts with Mad2 and Mitotic Spindles
Authors: Saitoh Shigeaki , Ishii Kojiro , Kobayashi Yasuyo , Takahashi Kohta
Published: June 2005

The spindle checkpoint coordinates cell cycle progression and chromosome segregation by inhibiting anaphase promoting complex/cyclosome until all kinetochores interact with the spindle properly. During early mitosis, the spindle checkpoint proteins, such as Mad2 and Bub1, accumulate at kinetochores that do not associate with the spindle. Here, we assess the requirement of various kinetochore components for the accumulation of Mad2 and Bub1 on the kinetochore in fission yeast and show that the necessity of the Mis6-complex and the Nuf2-complex is an evolutionarily conserved feature in the loading of Mad2 onto the kinetochore. Furthermore, we demonstrated that Nuf2 is required for maintaining the Mis6-complex on the kinetochore during mitosis. The Mis6-complex physically interacts with Mad2 under the condition that the Mad2-dependent checkpoint is activated. Ectopically expressed N-terminal fragments of Mis6 localize along the mitotic spindle, highlighting the potential binding ability of Mis6 not only to the centromeric chromatin but also to the spindle microtubules. We propose that the Mis6-complex, in collaboration with the Nuf2-complex, monitors the spindle–kinetochore attachment state and acts as a platform for Mad2 to accumulate at unattached kinetochores.
Hsp70 Protects Mitotic Cells against Heat-induced Centrosome Damage and Division Abnormalities
Authors: Hut Henderika M.J. , Kampinga Harm H. , Sibon Ody C.M.
Published: June 2005

The effect of heat shock on centrosomes has been mainly studied in interphase cells. Centrosomes play a key role in proper segregation of DNA during mitosis. However, the direct effect and consequences of heat shock on mitotic cells and a possible cellular defense system against proteotoxic stress during mitosis have not been described in detail. Here, we show that mild heat shock, applied during mitosis, causes loss of dynamitin/p50 antibody staining from centrosomes and kinetochores. In addition, it induces division errors in most cells and in the remaining cells progression through mitosis is delayed. Expression of heat shock protein (Hsp)70 protects against most heat-induced division abnormalities. On heat shock, Hsp70 is rapidly recruited to mitotic centrosomes and normal progression through mitosis is observed immediately after release of Hsp70 from centrosomes. In addition, Hsp70 expression coincides with restoration of dynamitin/p50 antibody staining at centrosomes but not at kinetochores. Our data show that during mitosis, centrosomes are particularly affected resulting in abnormal mitosis. Hsp70 is sufficient to protect against most division abnormalities, demonstrating the involvement of Hsp70 in a repair mechanism of heat-damaged mitotic centrosomes.
EHD Proteins Associate with Syndapin I and II and Such Interactions Play a Crucial Role in Endosomal Recycling
Authors: Braun Anne , Pinyol Roser , Dahlhaus Regina , Koch Dennis , Fonarev Paul , Grant Barth D. , Kessels Michael M. , Qualmann Britta
Published: June 2005

EHD proteins were shown to function in the exit of receptors and other membrane proteins from the endosomal recycling compartment. Here, we identify syndapins, accessory proteins in vesicle formation at the plasma membrane, as differential binding partners for EHD proteins. These complexes are formed by direct eps15-homology (EH) domain/asparagine proline phenylalanine (NPF) motif interactions. Heterologous and endogenous coimmunoprecipitations as well as reconstitutions of syndapin/EHD protein complexes at intracellular membranes of living cells demonstrate the in vivo relevance of the interaction. The combination of mutational analysis and coimmunoprecipitations performed under different nucleotide conditions strongly suggest that nucleotide binding by EHD proteins modulates the association with syndapins. Colocalization studies and subcellular fractionation experiments support a role for syndapin/EHD protein complexes in membrane trafficking. Specific interferences with syndapin–EHD protein interactions by either overexpression of the isolated EHD-binding interface of syndapin II or of the EHD1 EH domain inhibited the recycling of transferrin to the plasma membrane, suggesting that EH domain/NPF interactions are critical for EHD protein function in recycling. Consistently, both inhibitions were rescued by co-overexpression of the attacked protein component. Our data thus reveal that, in addition to a crucial role in endocytic internalization, syndapin protein complexes play an important role in endocytic receptor recycling.
Inhibition of Translation Initiation by Volatile Anesthetics Involves Nutrient-sensitive GCN-independent and -dependent Processes in Yeast
Authors: Palmer Laura K. , Shoemaker Jessica L. , Baptiste Beverly A. , Wolfe Darren , Keil Ralph L.
Published: June 2005

Volatile anesthetics including isoflurane affect all cells examined, but their mechanisms of action remain unknown. To investigate the cellular basis of anesthetic action, we are studying Saccharomyces cerevisiae mutants altered in their response to anesthetics. The zzz3-1 mutation renders yeast isoflurane resistant and is an allele of GCN3. Gcn3p functions in the evolutionarily conserved general amino acid control (GCN) pathway that regulates protein synthesis and gene expression in response to nutrient availability through phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Hyperphosphorylation of eIF2α inhibits translation initiation during amino acid starvation. Isoflurane rapidly (in <15 min) inhibits yeast cell division and amino acid uptake. Unexpectedly, phosphorylation of eIF2α decreased dramatically upon initial exposure although hyperphosphorylation occurred later. Translation initiation was inhibited by isoflurane even when eIF2α phosphorylation decreased and this inhibition was GCN-independent. Maintenance of inhibition required GCN-dependent hyperphosphorylation of eIF2α. Thus, two nutrient-sensitive stages displaying unique features promote isoflurane-induced inhibition of translation initiation. The rapid phase is GCN-independent and apparently has not been recognized previously. The maintenance phase is GCN-dependent and requires inhibition of general translation imparted by enhanced eIF2α phosphorylation. Surprisingly, as shown here, the transcription activator Gcn4p does not affect anesthetic response.
Association of an A-Kinase-anchoring Protein Signaling Scaffold with Cadherin Adhesion Molecules in Neurons and Epithelial Cells
Authors: Gorski Jessica A. , Gomez Lisa L. , Scott John D. , Dell'Acqua Mark L.
Published: June 2005

A-kinase-anchoring protein (AKAP) 79/150 organizes a scaffold of cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and protein phosphatase 2B/calcineurin that regulates phosphorylation pathways underlying neuronal long-term potentiation and long-term depression (LTD) synaptic plasticity. AKAP79/150 postsynaptic targeting requires three N-terminal basic domains that bind F-actin and acidic phospholipids. Here, we report a novel interaction of these domains with cadherin adhesion molecules that are linked to actin through β-catenin (β-cat) at neuronal synapses and epithelial adherens junctions. Mapping the AKAP binding site in cadherins identified overlap with β-cat binding; however, no competition between AKAP and β-cat binding to cadherins was detected in vitro. Accordingly, AKAP79/150 exhibited polarized localization with β-cat and cadherins in epithelial cell lateral membranes, and β-cat was present in AKAP–cadherin complexes isolated from epithelial cells, cultured neurons, and rat brain synaptic membranes. Inhibition of epithelial cell cadherin adhesion and actin polymerization redistributed intact AKAP–cadherin complexes from lateral membranes to intracellular compartments. In contrast, stimulation of neuronal pathways implicated in LTD that depolymerize postsynaptic F-actin disrupted AKAP–cadherin interactions and resulted in loss of the AKAP, but not cadherins, from synapses. This neuronal regulation of AKAP79/150 targeting to cadherins may be important in functional and structural synaptic modifications underlying plasticity.
Cytosolic Phospholipase A2-α Mediates Endothelial Cell Proliferation and Is Inactivated by Association with the Golgi Apparatus
Authors: Herbert S. P. , Ponnambalam S. , Walker J. H.
Published: June 2005

Arachidonic acid and its metabolites are implicated in regulating endothelial cell proliferation. Cytosolic phospholipase A2-α (cPLA2α) is responsible for receptor-mediated arachidonic acid evolution. We tested the hypothesis that cPLA2α activity is linked to endothelial cell proliferation. The specific cPLA2α inhibitor, pyrrolidine-1, inhibited umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner. Exogenous arachidonic acid addition reversed this inhibitory effect. Inhibition of sPLA2did not affect HUVEC proliferation. The levels of cPLA2α did not differ between subconfluent and confluent cultures of cells. However, using fluorescence microscopy we observed a novel, confluence-dependent redistribution of cPLA2α to the distal Golgi apparatus in HUVECs. Association of cPLA2α with the Golgi was linked to the proliferative status of HUVECs. When associated with the Golgi apparatus, cPLA2α activity was seen to be 87% inhibited. Relocation of cPLA2α to the cytoplasm and nucleus, and cPLA2α enzyme activity were required for cell cycle entry upon mechanical wounding of confluent monolayers. Thus, cPLA2α activity and function in controlling endothelial cell proliferation is regulated by reversible association with the Golgi apparatus.
Mutations in a Highly Conserved Region of the Arf1p ActivatorGEA2Block Anterograde Golgi Transport but Not COPI Recruitment to Membranes
Authors: Park Sei-Kyoung , Hartnell Lisa M. , Jackson Catherine L.
Published: June 2005

We have identified an important functional region of the yeast Arf1 activator Gea2p upstream of the catalytic Sec7 domain and characterized a set of temperature-sensitive (ts) mutants with amino acid substitutions in this region. These gea2-ts mutants block or slow transport of proteins traversing the secretory pathway at exit from the endoplasmic reticulum (ER) and the early Golgi, and accumulate both ER and early Golgi membranes. No defects in two types of retrograde trafficking/sorting assays were observed. We find that a substantial amount of COPI is associated with Golgi membranes in the gea2-ts mutants, even after prolonged incubation at the nonpermissive temperature. COPI in these mutants is released from Golgi membranes by brefeldin A, a drug that binds directly to Gea2p and blocks Arf1 activation. Our results demonstrate that COPI function in sorting of at least three retrograde cargo proteins within the Golgi is not perturbed in these mutants, but that forward transport is severely inhibited. Hence this region of Gea2p upstream of the Sec7 domain plays a role in anterograde transport that is independent of its role in recruiting COPI for retrograde transport, at least of a subset of Golgi-ER cargo.
ERK Phosphorylates p66shcA on Ser36 and Subsequently Regulates p27kip1Expression via the Akt-FOXO3a Pathway: Implication of p27kip1in Cell Response to Oxidative Stress
Authors: Hu Yuanyu , Wang Xueying , Zeng Li , Cai De-Yu , Sabapathy Kanaga , Goff Stephen P. , Firpo Eduardo J. , Li Baojie
Published: June 2005

Mice deficient for p66shcA represent an animal model to link oxidative stress and aging. p66shcA is implicated in oxidative stress response and mitogenic signaling. Phosphorylation of p66shcA on Ser36 is critical for its function in oxidative stress response. Here we report the identification of ERK as the kinase phosphorylating p66shcA on Ser36. Activation of ERKs was necessary and sufficient for Ser36 phosphorylation. p66shcA interacted with ERK and was demonstrated to be a substrate for ERK, with Ser36 being the major phosphorylation site. Furthermore, in response to H2O2, inhibition of ERK activation repressed p66shcA-dependent phosphorylation of FOXO3a and the down-regulation of its target gene p27kip1. Down-regulation of p27 might promote cell survival, as p27 played a proapoptotic role in oxidative stress response. As a feedback regulation, Ser36 phosphorylated p66shcA attenuated H2O2-induced ERK activation, whereas p52/46shcA facilitated ERK activation, which required tyrosine phosphorylation of CH1 domain. p66shcA formed a complex with p52/46ShcA, which may provide a platform for efficient signal propagation. Taken together, the data suggest there exists an interplay between ERK and ShcA proteins, which modulates the expression of p27 and cell response to oxidative stress.
Clinical Microbiological Aspects of Epileptic Seizures in the Tropical Countries with Specific Focus on Nigeria
Authors: Kanu Ijeoma , Anyanwu Ebere C. , Nwachukwu Nkechi C. , Ehiri John E. , Merrick Joav
Published: June 2005

Epilepsy is a common neurological disorder; however, in Nigeria and other tropical regions, the causes of epileptic seizures differ greatly in etiology. This paper is an attempt to highlight some possible microbiological aspects of epileptic seizures. A literature review was carried out to identify the extent to which microbial infections were involved in the elicitation of epileptic seizures. Data were collected from several clinics in the community and hospitals in Nigeria and correlated with the evidence from the literature review. It was found that different microbial agents including viral, bacterial, protozoa, and fungal agents were involved in several aspects of epileptic seizures. Malaria was found to cause more than 88% of childhood epileptic seizures and 12% of adult seizures. Generalized tonic-clonic seizures occurred in more than 40% of adult patients. Partial seizures were uncommon. Cases of epileptic seizures associated with bacteria (e.g., brucellosis), viral, fungal, and protozoa infections were frequently reported. Malaria, tapeworm, and cysticercosis were some of the common infectious causes of epilepsy; however, in some cases, the cause remained unknown. From these findings, it was evident that microbiological aspects of epilepsies are possible research areas that might be developed. It is believed that the unraveling of the various microbiological factors in epileptic seizures would have important implications for understanding the underlying neurobiology, evaluating treatment strategies, and perhaps planning health-care resources for the affected. It will also help to improve the prognostic factors in initial seizure symptomatic etiology and presence of any structural cerebral abnormalities.
Training Pediatric Residents to Provide Smoking Cessation Counseling to Parents
Authors: Collins Rebecca L. , D'Angelo Sandy , Stearns Sarah D. , Campbell Lynn R.
Published: June 2005

The objective was to assess the effectiveness of a smoking cessation educational program on pediatric residents' counseling. Residents were randomly selected to receive the intervention. Residents who were trained were compared to untrained residents. Self-reported surveys and patient chart reviews were used. Measures included changes in self-reported knowledge, attitudes and behaviors of residents, and differences in chart documentation and caretaker-reported physician counseling behaviors. The intervention was multidimensional including a didactic presentation, a problem-solving session, clinic reminders, and provision of patient education materials. Results showed that residents who were trained were more likely to ask about tobacco use in their patients' households. They were also more likely to advise caretakers to cut down on or to quit smoking, to help set a quit date, and to follow up on the advice given at a subsequent visit. Trained residents were more likely to record a history of passive tobacco exposure in the medical record. These residents also reported improved confidence in their counseling skills and documented that they had done such counseling more often than did untrained residents. Caretakers of pediatric patients who smoke seen by intervention residents were more likely to report that they had received tobacco counseling. Following this intervention, pediatric residents significantly improved their behaviors, attitudes, and confidence in providing smoking cessation counseling to parents of their pediatric patients.
Work hard, play hard: selling Kelowna, BC, as year‐round playground
Authors: Aguiar Luis L.M. , Tomic Patricia , Trumper Ricardo
Published: June 2005

A keen interest in place making and place selling is widespread in contemporary society. While the bulk of academic research has focused on studying the restructuring of large urban conglomerates, places beyond the exploding metropolis, by comparison, have received little attention, especially when it concerns Canadian landscapes. In an attempt to study the particularities of place making in contemporary smaller, more isolated communities—hinterlands—this work analyses the city of Kelowna, in British Columbia, Canada. We argue that historically Kelowna, a small rural community specialising in ranching, forestry and fruit production, since the early 1980s, has been re‐imagined and re‐designed, on the one hand as an all‐year playground and as an innovative frontier for high‐tech industries; on the other hand, this post‐Fordist reinvention contains a discourse of ‘whiteness’, one that entices by packaging ‘place’ in terms of ‘sameness’ and ‘familiarity’. In contrast to large cosmopolitan post‐industrial cities, hinterland‐type cities are invented, sought and lived as geographies cleared from the ‘elements’ that make cities ‘unsafe’.
Les horizons géographiques, entre continu et discontinu1
Authors: Lazzarotti Olivier
Published: June 2005

Cet article analyse la métaphore de l'éducation et du politique, couramment désignée comme allégorie de la caverne de Platon. Il développe la notion géographique d'horizon de nouveauté et d'altérité comme ≪ dialectique ≫ du continu et du discontinu autant que comme articulation entre mobilité et immobilité humaines. En retour, il pose la question de l'horizontalité, toujours montrée mais jamais dite, comme critique d'une métaphore écrasée par la verticalité qui institue le lien politique non dans le rapport à l'autre mais comme transcendance et fonde l'éducation humaine sur l'écrasement de l'émotion. Au‐delà de ces lectures, le texte de Platon permet d'articuler philosophie et géographie dans un ≪ logos ≫ commun et constitue, ainsi, non seulement l'un des fondements d'une approche anthropologique de la géographie mais, avec elle, l'un de ceux du monde occidental et de sa pensée.
Assessing efforts to mitigate the impacts of drainage on wetlands in Ontario, Canada
Authors: Walters Dan , Shrubsole Dan
Published: June 2005

The protection of wetlands through the Ontario Drainage Act has been the subject of much debate. While seen as essential for increasing production and/or productivity of agricultural areas, drainage schemes have been usually approved at the expense of wetlands. Despite the presence of a referral process in Ontario's Drainage Act that is supposed to prevent the significant loss of wetland area, incremental losses continue to occur. The referral process allows landowners, drainage engineers, Drainage Superintendents, local conservation authorities and Ontario Ministry of Natural Resource officials to participate in the decision‐making process. This research examines the recommended mitigation measures and wetland gains/losses in Zorra Township between 1978 and 1997. Data sources included drainage files, wetland evaluation files, aerial photography and interviews with government officials. The results indicate that while recommended mitigation measures of drainage schemes in the vicinity of wetlands have increased, incremental losses continue to occur. The negotiated settlements among drainage engineers and the referral agencies appear to be inadequate to maintain the spatial extent of wetlands. The regulatory approach fails to motivate changes in land‐use management practices. This supports the need to include nonregulatory incentives in the effort to protect wetlands.
A framework for statistical inferential decisions in spatial pattern analysis
Authors: Csillag Ferenc , Boots Barry
Published: June 2005

The desire of many geographical information science (GIS) practitioners to undertake sophisticated spatial pattern analysis has been facilitated by the increasing availability of specialised software and the appearance of pedagogic papers illustrating the application of various techniques. However, the appropriate use of these techniques also requires an understanding of the nature of hypothesis testing and statistical inference for spatial data. Since there is little information currently available to aid the GIS practitioner in this regard, we offer such guidance here. We do so by revisiting the steps involved in spatial pattern analysis. Our perspective is based on the notion of spatial stochastic models and is presented as a decision tree. The four levels of the tree (i.e., sequential decisions) are associated with the assumptions, the type of data representation and the types of questions asked by the analyst. We emphasise the scientific and educational challenges involved.
Le classement des villes dans l'économie du savoir : une analyse intégrée des régions urbaines canadiennes et américaines
Authors: Polèse Mario , Tremblay Rémy
Published: June 2005

Des comparaisons entre villes canadiennes et américaines doivent se faire avec prudence. L'obstacle principal reste la comparabilité des séries statistiques. Nous proposons une analyse intégrée
de l'ensemble des 90 régions métropolitaines nord‐américaines de 500 000 habitants et plus, dont neuf canadiennes. Suite à une revue de divers classements, nous situons les 90 régions urbaines sur sept indicateurs, dont des variables portant sur le capital humain et le secteur tertiaire intensif en savoir, suivi d'une analyse de corrélation mettant en relation les indicateurs pour trois univers de villes (sans et avec des villes canadiennes). Nos résultats confirment le bon positionnement sur plusieurs indicateurs de métropoles américaines comme San Francisco‐Silicon Valley et Boston, mais aussi de villes comme Raleigh (research triangle) et Austin, connues pour leurs activités de recherche. Les villes canadiennes se classent plutôt bien, notamment les cinq plus grandes. Cependant, c'est moins vrai pour des villes comme Winnipeg ou Hamilton. L'analyse de corrélation fait ressortir la relation positive entre dotation en capital humain et poids du tertiaire intensif en savoir, mais ne révèle aucune relation significative avec l'indicateur de qualité de vie.