bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Sgk1 in salt and potassium homeostasis
Authors: Vallon Volker , Wulff Peer , Huang Dan Yang , Loffing Johannes , Völkl Harald , Kuhl Dietmar , Lang Florian
Published: December 2004

Aldosterone plays a pivotal role in NaCl and K+homeostasis by stimulation of Na+reabsorption and K+secretion in the aldosterone-sensitive distal nephron (ASDN). Recent studies demonstrated that the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by aldosterone in the ASDN and that polymorphisms of the kinase associate with arterial blood pressure in normotensive subjects. This review discusses the role of Sgk1 in NaCl and K+homeostasis as evidenced by in vivo studies, including those in Sgk1-deficient mice. The studies indicate that Sgk1 is not absolutely required for Na+reabsorption and K+secretion in the ASDN. On a standard NaCl and K+diet, modestly enhanced plasma aldosterone concentrations appear sufficient to establish a compensated phenotype in the absence of Sgk1. The kinase is necessary, however, for upregulation of transcellular Na+reabsorption in the ASDN. This may involve Sgk1-mediated stimulation of basolateral Na+-K+-ATPase as well as retention of epithelial Na+channel, ENaC, in the apical membrane. Such an upregulation is a prerequisite for adequate adaptation of 1) renal NaCl reabsorption during restricted dietary NaCl intake, as well as 2) K+secretion in response to enhanced K+intake. Thus gain-of-function mutations of Sgk1 are expected to result in renal NaCl retention and enhanced K+secretion. Further studies are required to elucidate renal and nonrenal aldosterone-induced effects of Sgk1, the role of other Sgk1 activators, as well as the link of Sgk1 polymorphisms to arterial hypertension in humans.
Salt-sensitive hypertension develops after transient induction of ANG II-dependent hypertension in Cyp1a1-Ren2 transgenic rats
Authors: Howard Laura L. , Patterson Matthew E. , Mullins John J. , Mitchell Kenneth D.
Published: December 2004

Transient exposure to ANG II results in the development of salt-sensitive hypertension in rats. This study was performed to determine whether a transient hypertensive episode can induce salt-sensitive hypertension in transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name TGR(Cyp1a1-Ren2)]. Systolic blood pressures were measured in conscious male Cyp1a1-Ren2 rats ( n = 6) during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.15%, wt/wt), for 14 days. Systolic pressure increased from 135 ± 5 to 233 ± 7 mmHg by day 14. I3C administration was terminated and blood pressure returned to normal levels (137 ± 5 mmHg) within 10 days. Subsequently, the rats were placed on a high-salt diet (8% NaCl) for 10 days. Systolic pressure increased by 34 ± 2 mmHg throughout 10 days of the high-salt diet. Neither glomerular filtration rate nor renal plasma flow was altered in Cyp1a1-Ren2 rats with salt-sensitive hypertension. In a separate group of male Cyp1a1-Ren2 rats ( n = 6) transiently induced with 0.15% I3C for 14 days, administration of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, 2 mM) attenuated the increase in systolic pressure induced by high salt. Systolic pressure increased by only 11 ± 1 mmHg throughout 8 days of a high-salt diet and tempol administration. Thus transient induction of ANG II-dependent hypertension via activation of the Cyp1a1-Ren2 transgene induces salt-sensitive hypertension in these transgenic rats. The attenuation by tempol of the high salt-induced blood pressure elevation indicates that ANG II-induced production of superoxide anion contributes to the development of salt-sensitive hypertension after transient induction of ANG II-dependent hypertension.
Powder diffraction investigations of naphthalenesulfonic acids and their complexes with DMAN
Authors: Rafalska-Lasocha A. , Grzywa M. , Włodarczyk-Gajda B. , Lasocha W.
Published: December 2004

The X-ray diffraction patterns of two organic acids 1-naphthalenesulfonic acid dihydrate and 2-naphthalenesulfonic acid hydrate were measured at room temperature. Complexes of these acids with 1,8-bis(dimethylamino)naphthalene (DMAN) were synthesized, purified and investigated by means of X-ray powder diffraction. 1-Naphthalenesulfonic acid dihydrate as well as its complex with 1,8-bis(dimethylamino)naphthalene crystallize in the monoclinic system with unit cell parameters refined toa=0.91531(8) nm,b=0.7919(1) nm,c=0.8184(1) nm, β=101.618(9)° space group P21/m (11) anda=1.7781(4) nm,b=2.0122(4) nm,c=1.2337(2) nm, β=96.54(3)°, space group C2/m (12), respectively. 2-Naphthalenesulfonic acid hydrate crystallizes in the orthorhombic system witha=2.2749(3) nm,b=0.7745(1) nm,c=0.591 36(9) nm, space group Pnma, whereas its complex with 1,8-bis(dimethylamino)naphthalene crystallizes in the triclinic systema=1.3969(6) nm,b=1.4292(5) nm,c=1.1741(6) nm, α=90.93(3)°, β=98.14(3)°, γ=113.93(3)°, space group P-1 (2).
A Rietveld refinement investigation of a Mg-stabilized triclinic tricalcium silicate using synchrotron X-ray powder diffraction data
Authors: Peterson Vanessa Kate
Published: December 2004

A Mg-stabilized triclinic tricalcium silicate form of type Ca3−xMgxSiO5, T3, was synthesized. Rietveld analysis using synchrotron X-ray powder diffraction data suggested that unlike the T1 form, the T3 structure was unmodulated. This refinement illustrated that the only existing model for a triclinic form of tricalcium silicate (T1) can be used to describe the nonmodulated T3 form.
Evaluation of experimental stress–strain dependence in thermally cycled Al thin film on Si(100)
Authors: Keckes J. , Hafok M. , Eiper E. , Hofer A. , Resel R. , Eisenmenger-Sittner C.
Published: December 2004

A new method is introduced for the evaluation of experimental stress–strain dependence in thermally cycled thin films. The method is demonstrated on the analysis of an Al thin film on a Si(100) substrate characterized using in situ high-temperature X-ray diffraction 25–450 °C. Diffraction data are used to evaluate in-plane elastic strain in the film as a function of thermal strain originating from the mismatch of thermal expansion coefficients (TECs) between the film and the substrate. The magnitude of the thermal strain is calculated from experimental TECs of the film and the substrate at every measurement temperature. By relating in-plane stresses to thermal strains, an experimental stress–strain dependence for the Al thin film is obtained. The proposed method allows one to identify elastic behavior and to quantify plastic strain in the film. Finally, advantages of the method are discussed in particular its independence from using TECs reported in the literature.
Generation of a polyclonal rabbit anti-mouse tissue factor antibody by nucleic acid immunisation
Authors: Mumford Andrew , Chen Daxin , Dorling Anthony , Kemball-Cook Geoffrey , McVey John
Published: December 2004

Tissue factor (TF) the cellular receptor and cofactor for factor VII, initiates coagulation and has also been implicated in several coagulation-independent functions, including inflammation, angiogenesis and tumour metastasis. Investigations of TF expression in mouse models of these processes has been limited by the availability of antibodies that specifically recognise mouse TF.We have generated a rabbit polyclonal antibody to mTF by DNA immunisation. This has yielded an antiserum that recognises native mTF in immunohistochemical and flow cytometric analyses.Furthermore,the antiserum is inhibitory in coagulation assays.This antiserum will be a valuable investigative tool in the analysis of mTF expression.
Plasma glycocalicin as a source of GPIbα in the von Willebrand factor ristocetin cofactor ELISA
Authors: Pareyn Inge , Schlammadinger Agota , Vauteri Stephan , Hoylaerts Marc , Arnout Jef , Deckmyn Hans , Vanhoorelbeke Karen
Published: December 2004

We have previously demonstrated that the von Willebrand factor ristocetin cofactor activity (VWF:RCo),used in the diagnosis of vonWillebrand disease (VWD),can be accurately determined via ELISA by measuring the ristocetin-induced binding ofVWF to a captured recombinant fragment of GPIb α (rfGPIb α ,AA 1–289) (Vanhoorelbeke et al., Thromb Haemost 2000; 83: 107-13). This ELISA is more reliable than the currently used platelet agglutination test. Normal plasma contains relatively high concentrations of glycocalicin, a proteolytic fragment of GPIb α . We therefore studied whether non-purified plasma glycocalicin can replace rfGPIbα in our ELISA. Of 42 anti-GPIbα monoclonal antibodies (MAbs) capable of binding plasma glycocalicin, only one MAb captured glycocalicin in a spatial orientation exposing theVWF-binding site in glycocalicin,allowing a specific and dosedependent ristocetin-mediated VWF-binding. Intra- and interassay variability were comparable with those for the rfGPIbα basedVWF:RCo ELISA.TheVWF:RCo activity of plasma from 33 normal individuals, 19 type 1, 16 type 2A, 9 type 2B, 8 type 2M and 7 type 3VWD patients was determined with this ELISA and allowed a clear identification ofVWD patients.Furthermore,determination of the VWF:RCo/VWF:Ag ratio resulted in the discrimination between type 1 and type 2 VWD patients. Results for the glycocalicin based and the rfGPIb α basedVWF:RCo ELISAs were in good agreement (r = 0.943).There was also a good correlation between the glycocalicin based ELISA and the standard platelet agglutination test (r = 0.963).In conclusion,to diagnose VWD, a VWF:RCo ELISA based on antibody immobilized plasma glycocalicin can be performed reliably.
Herbal remedies and anticoagulant therapy
Authors: Samuels Noah
Published: December 2004

Herbal remedies, considered to be both safe and effective by most consumers, may interact with conventional drugs.Warfarin, a vitamin K antagonist originally derived from the sweet clover plant, has a narrow therapeutic window which can be monitored using prothrombin international normalized ratios (PT-INR). Many herbs can increase the risk for bleeding when combined with warfarin, either by augmenting the anticoagulant effects of the drug (with increased PT-INR levels) or through intrinsic anti-platelet properties (without altering PT-INR levels). The increased risk for bleeding among such patients may be difficult to predict, especially when formulas which contain many herbs are used. Further research into herb-drug interactions is warranted, as are guidelines for the use of herbal remedies by patients on chronic anticoagulation therapy.
The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke
Authors: García Encarna , Leebeek Frank , Brouwers Geert-Jan , Koudstaal Peter , Dippel Diederik , Goor Mary-Lou
Published: December 2004

High levels of plasminogen activator inhibitor type 1 (PAI-1) have been implicated as a risk factor for cardiovascular disease, but its precise role remains controversial.The 4G allele of the PAI-1 4G/5G promoter polymorphism is associated with higher levels of PAI-1. We studied the relationship between ischemic stroke and the PAI-1 4G/5G polymorphism and PAI-1 antigen levels. We performed a case-control study among patients aged 18–75 years with first ischemic stroke, confirmed by CT.All patients were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. We excluded patients with a definite non-atherosclerotic cause of the stroke and patients using oral anticoagulants. Population-controls were age -and sex-matched, without a history of stroke, and of the Caucasian race.Venous blood samples were taken for PAI-1 4G/5G polymorphism and PAI-1 level one week after stroke.We included 124 patients and 125 controls. Mean age was 56 yrs (range 18 to 75 yrs). Sixty one patients (50%) and 58 (47%) controls were heterozygous for the PAI-1 4G/5G polymorphism.The homozygous 4G/4G genotype was found in 33 patients (27%) and in 36 controls (29%). The odds ratio of ischemic stroke associated with 4G-carriers versus 5G/5G homozygotes was 1.0 (95% CI: 0.6–1.8).The relative risk of ischemic stroke associated with the level of PAI-1 in the upper quartile was 0.73 (95%CI: 0.4 to 1.4). Neither the PAI-1 4G/5G polymorphism nor the PAI-1 antigen level is a strong risk factor for ischemic stroke.
Blood and bone: two tissues whose fates are intertwined to create the hematopoietic stem-cell niche
Authors: Taichman Russell S.
Published: December 2004

The mechanisms of bone and blood formation have traditionally been viewed as distinct, unrelated processes, but compelling evidence suggests that they are intertwined. Based on observations that hematopoietic precursors reside close to endosteal surfaces, it was hypothesized that osteoblasts play a central role in hematopoiesis, and it has been shown that osteoblasts produce many factors essential for the survival, renewal, and maturation of hematopoietic stem cells (HSCs). Preceding these observations are studies demonstrating that the disruption or perturbation of normal osteoblastic function has a profound and central role in defining the operational structure of the HSC niche. These observations provide a glimpse of the dimensions and ramifications of HSC-osteoblast interactions. Although more research is required to secure a broader grasp of the molecular mechanisms that govern blood and bone biology, the central role for osteoblasts in hematopoietic stem cell regulation is reviewed herein from the perspectives of (1) historical context; (2) the role of the osteoblast in supporting stem cell survival, proliferation, and maintenance; (3) the participation, if any, of osteoblasts in the creation of a stem cell niche; (4) the molecules that mediate HSC-osteoblast interactions; (5) the role of osteoblasts in stem cell transplantation; and (6) possible future directions for investigation.
Vessel wall–derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells
Authors: Ingram David A. , Mead Laura E. , Moore Daniel B. , Woodard Wayne , Fenoglio Amy , Yoder Mervin C.
Published: December 2004

Endothelial progenitor cells (EPCs) can be isolated from adult peripheral and umbilical cord blood and expanded exponentially ex vivo. In contrast, human umbilical vein endothelial cells (HUVECs) or human aortic endothelial cells (HAECs) derived from vessel walls are widely considered to be differentiated, mature endothelial cells (ECs). However, similar to adult- and cord blood–derived EPCs, HUVECs and HAECs derived from vessel walls can be passaged for at least 40 population doublings in vitro. Based on this paradox, we tested whether EPCs reside in HUVECs or HAECs utilizing a novel single cell deposition assay that discriminates EPCs based on their proliferative and clonogenic potential. We demonstrate that a complete hierarchy of EPCs can be identified in HUVECs and HAECs derived from vessel walls and discriminated by their clonogenic and proliferative potential. This study provides evidence that a diversity of EPCs exists in human vessels and provides a conceptual framework for determining both the origin and function of EPCs in maintaining vessel integrity.
Data-driven approaches to the modelling of bioprocesses
Authors: Bernaerts Kristel , Van Impe Jan F.
Published: December 2004

Bioprocess modelling presents a challenging subject, which requires a meticulous modelling strategy. During the modelling process, experimental data form a key ingredient during structure characterization and parameter estimation. Accurate system identification can only be guaranteed if the experimental data contain sufficient information on the process dynamics. In this respect, sufficient effort should be spent on optimal experiment design in order to maximize the information that can be extracted from data, particularly because experimental data generation for bioprocesses is usually a time-consuming, labour-intensive and costly job. This paper reviews the modelling cycle of bioprocesses, emphasizing the need for careful experimental data collection. The concepts of optimal experiment design for parameter estimation are outlined in particular. Application of this methodology is illustrated for a case study involving the optimal estimation of two model parameters describing temperature dependence of microbial growth kinetics.
CAN bus applied on hydraulic computed force control
Authors: Virvalo Tapio , Lammila Mika , Lehto Erkki
Published: December 2004

The application range of fluid power is very wide, from fast and light pneumatic applications to heavy hydraulic applications. Control systems have been used in efforts to overcome the drawbacks in fluid power systems. This means more integrated electronics in components like valves, pumps and actuators. The acceptance of field buses within hydraulic systems is restricted because of the special nature of the hydraulics market. Due to limited space in the electronics housing and the extremely harsh environment to which valves are typically exposed, the integration of the required electronics is demanding. In this study, the CAN bus is used in a hydraulic motion control system in forward and feedback loops. The motion controller is realized with a so-called computed force controller. Good steady-state and dynamic performance, as well as high efficiency, are features that are required for with this kind of a control system. The positioning and stroke-time accuracy as well as dynamic behaviour are compared between the traditional method and different methods using the CAN bus. The influence of the baud rate of the CAN bus on the performance of the studied servo system is analysed. Theoretical background is presented and experimental results are shown.
Kinetics, Pharmacokinetics, and Regulation of l‐Carnitine and Acetyl‐l‐carnitine Metabolism
Authors: REBOUCHE CHARLES J.
Published: December 2004

Abstract: In mammals, the carnitine pool consists of nonesterified l‐carnitine and many acylcarnitine esters. Of these esters, acetyl‐l‐carnitine is quantitatively and functionally the most significant. Carnitine homeostasis is maintained by absorption from diet, a modest rate of synthesis, and efficient renal reabsorption. Dietary l‐carnitine is absorbed by active and passive transfer across enterocyte membranes. Bioavailability of dietary l‐carnitine is 54‐87% and is dependent on the amount of l‐carnitine in the meal. Absorption of l‐carnitine dietary supplements (0.5‐6 g) is primarily passive; bioavailability is 14‐18% of dose. Unabsorbed l‐carnitine is mostly degraded by microorganisms in the large intestine. Circulating l‐carnitine is distributed to two kinetically defined compartments: one large and slow‐turnover (presumably muscle), and another relatively small and rapid‐turnover (presumably liver, kidney, and other tissues). At normal dietary l‐carnitine intake, whole‐body turnover time in humans is 38‐119 h. In vitro experiments suggest that acetyl‐l‐carnitine is partially hydrolyzed in enterocytes during absorption. In vivo, circulating acetyl‐l‐carnitine concentration was increased 43% after oral acetyl‐l‐carnitine supplements of 2 g/day, indicating that acetyl‐l‐carnitine is absorbed at least partially without hydrolysis. After single‐dose intravenous administration (0.5 g), acetyl‐l‐carnitine is rapidly, but not completely hydrolyzed, and acetyl‐l‐carnitine and l‐carnitine concentrations return to baseline within 12 h. At normal circulating l‐carnitine concentrations, renal l‐carnitine reabsorption is highly efficient (90‐99% of filtered load; clearance, 1‐3 mL/min), but displays saturation kinetics. Thus, as circulating l‐carnitine concentration increases (as after high‐dose intravenous or oral administration of l‐carnitine), efficiency of reabsorption decreases and clearance increases, resulting in rapid decline of circulating l‐carnitine concentration to baseline. Elimination kinetics for acetyl‐l‐carnitine are similar to those for l‐carnitine. There is evidence for renal tubular secretion of both l‐carnitine and acetyl‐l‐carnitine. Future research should address the correlation of supplement dosage, changes and maintenance of tissue l‐carnitine and acetyl‐l‐carnitine concentrations, and metabolic and functional changes and outcomes.
Acetyl‐l‐carnitine for the Treatment of HIV Lipoatrophy
Authors: DAY LARRY , SHIKUMA CECILIA , GERSCHENSON MARIANA
Published: December 2004

Abstract: Lipodystrophy is an increasingly recognized complication of antiretroviral therapy for human immunodeficiency virus (HIV) infection. This syndrome encompasses both fat accumulation and wasting, which may be accompanied by metabolic derangements in glucose and lipid metabolism. While the precise mechanism of its development is not fully understood, lipodystrophy may represent chronic mitochondrial toxicity due to antiretroviral therapy and/or chronic HIV infection. Treatment of this condition has proven difficult, prompting research into agents that promote fat metabolism and mitochondrial function. l‐Carnitine is a nonessential micronutrient that regulates fatty acid transport into the mitochondrial matrix for metabolism via β‐oxidation. HIV‐infected individuals on antiretroviral therapy may become deficient in this cofactor, limiting mitochondrial fat metabolism. While studies have shown some benefit for carnitine supplementation in cardiovascular disease, mitochondrial myopathies, and possibly male infertility, the data for its use in HIV‐infected individuals are limited. Given its known physiologic function and the hypothesized mitochondrial basis for lipodystrophy, carnitine supplementation for this antiretroviral toxicity is reviewed. The available data from several small studies are inconclusive, although further research into this promising agent is warranted.
Effects of Carnitine on Thyroid Hormone Action
Authors: BENVENGA SALVATORE , AMATO ANTONINO , CALVANI MENOTTI , TRIMARCHI FRANCESCO
Published: December 2004

Abstract: By experiments on cells (neurons, hepatocytes, and fibroblasts) that are targets for thyroid hormones and a randomized clinical trial on iatrogenic hyperthyroidism, we validated the concept that l‐carnitine is a peripheral antagonist of thyroid hormone action. In particular, l‐carnitine inhibits both triiodothyronine (T3) and thyroxine (T4) entry into the cell nuclei. This is relevant because thyroid hormone action is mainly mediated by specific nuclear receptors. In the randomized trial, we showed that 2 and 4 grams per day of oral l‐carnitine are capable of reversing hyperthyroid symptoms (and biochemical changes in the hyperthyroid direction) as well as preventing (or minimizing) the appearance of hyperthyroid symptoms (or biochemical changes in the hyperthyroid direction). It is noteworthy that some biochemical parameters (thyrotropin and urine hydroxyproline) were refractory to the l‐carnitine inhibition of thyroid hormone action, while osteocalcin changed in the hyperthyroid direction, but with a beneficial end result on bone. A very recent clinical observation proved the usefulness of l‐carnitine in the most serious form of hyperthyroidism: thyroid storm. Since hyperthyroidism impoverishes the tissue deposits of carnitine, there is a rationale for using l‐carnitine at least in certain clinical settings.
Inhibition of neurogenesis at the zebrafish midbrain-hindbrain boundary by the combined and dose-dependent activity of a newhairy/E(spl)gene pair
Authors: Ninkovic Jovica , Tallafuss Alexandra , Leucht Christoph , Topczewski Jacek , Tannhäuser Birgit , Solnica-Krezel Lilianna , Bally-Cuif Laure
Published: December 2004

The intervening zone (IZ) is a pool of progenitor cells located at the midbrain-hindbrain boundary (MHB) and important for MHB maintenance,midbrain-hindbrain growth and the generation of midbrain-hindbrain neurons. Recently, we implicated the Hairy/E(spl) transcription factor Her5 in the formation of the medial (most basal) part of the IZ (MIZ) in zebrafish; the molecular bases for lateral IZ (LIZ) formation, however, remain unknown. We now demonstrate that her5 is physically linked to a new family member, him, displaying an identical MHB expression pattern. Using single and double knockdowns of him and her5, as well as a him+her5 deletion mutant background (b404), we demonstrate that Him and Her5 are equally necessary for MIZ formation, and that they act redundantly in LIZ formation in vivo. We show that these processes do not involve cross-regulation between Him and Her5 expression or activities,although Him and Her5 can heterodimerize with high affinity. Increasing the function of one factor when the other is depleted further shows that Him and Her5 are functionally interchangeable. Together, our results demonstrate that patterning and neurogenesis are integrated by the her5-himgene pair to maintain a progenitor pool at the embryonic MHB. We propose a molecular mechanism for this process where the global `Him+Her5' activity inhibits ngn1 expression in a dose-dependent manner and through different sensitivity thresholds along the medio-lateral axis of the neural plate.
Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3
Authors: Kim Anna J. , Shi Yuanyuan , Austin Richard C. , Werstuck Geoff H.
Published: December 2004

A wide range of agents and conditions are known to disrupt the ability of the endoplasmic reticulum (ER) to fold proteins properly, resulting in the onset of ER dysfunction/stress. We and others have shown that ER stress can induce intracellular lipid accumulation through the activation of the sterol responsive element binding proteins (SREBPs) and initiate programmed cell death by activation of caspases. It has been suggested that ER stress-induced lipid accumulation and cell death play a role in the pathogenesis of disorders including Alzheimer's disease, Parkinson's disease, type-1 diabetes mellitus and hepatic steatosis. Here we show that exposure of HepG2 cells to the branch chain fatty acid, valproate, increases cellular resistance to ER stress-induced dysfunction. Two distinctly different potential mechanisms for this protective effect were investigated. We show that exposure to valproate increases the expression of chaperones that assist in the folding of proteins in the ER including GRP78/BiP, GRP94, PDI and calreticulin as well as the cytosolic chaperone, HSP70. However, exposure of HepG2 cells to valproate does not decrease the apparent ER stress response in cells challenged with tunicamycin, A23187 or glucosamine, suggesting that valproate-conferred protection occurs downstream of ER dysfunction. Finally, we demonstrate that valproate directly inhibits the glycogen synthase kinases (GSK)-3α/β. The ability of lithium, another inhibitor of GSK3α/β to protect cells from ER stress-induced lipid accumulation suggests that GSK3 plays a central role in signaling downstream effects of ER stress. Strategies to protect cells from agents/conditions that induce ER stress may have potential in the treatment of the growing number of diseases and disorders linked to ER dysfunction.
Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell-sheet movement
Authors: Farooqui Rizwan , Fenteany Gabriel
Published: December 2004

The mechanism by which epithelial, endothelial and other strongly cell-cell adhesive cells migrate collectively as continuous sheets is not clear, even though this process is crucial for embryonic development and tissue repair in virtually all multicellular animals. Wound closure in Madin-Darby canine kidney (MDCK) epithelial cell monolayers involves Rac GTPase-dependent migration of cells both at and behind the wound edge. We report here for the first time that cells behind the margin of wounded MDCK cell monolayers, even hundreds of microns from the edge, extend `cryptic' lamellipodia against the substratum beneath cells in front of them, toward the wound, as determined by confocal, two-photon and transmission electron microscopy. These so-called submarginal cells nevertheless strictly maintain their more apical cell-cell contacts when they migrate as part of a coherent cell sheet, hiding their basal protrusions from conventional microscopy. The submarginal protrusions display the hallmarks of traditional lamellipodia based on morphology and dynamics. Cells behind the margin therefore actively crawl, instead of just moving passively when cells at the margin pull on them. The rate of migration is inversely proportional to the distance from the margin, and cells move co-ordinately, yet still in part autonomously, toward the wound area. We also clarify the ancillary role played by nonprotrusive contractile actin bundles that assemble in a Rho GTPase-dependent manner at the margin after wounding. In addition, some cell proliferation occurs at a delay after wounding but does not contribute to closure. Instead, it apparently serves to replace damaged cells so that intact spread cells can revert to their normal cuboidal morphology and the original cell density of the unbroken sheet can be restored.
Cortactin regulates cell migration through activation of N-WASP
Authors: Kowalski Jennifer R. , Egile Coumaran , Gil Susana , Snapper Scott B. , Li Rong , Thomas Sheila M.
Published: December 2004

Cortactin is an actin-associated scaffolding protein that regulates cell migration. Amplification of the human gene, EMS1, has been detected in breast, head and neck tumors, where it correlates with increased invasiveness. Cortactin can regulate actin dynamics directly via its N-terminal half, which can bind and activate the Arp2/3 complex. The C-terminal portion of cortactin, however, is thought to have limited function in its regulation of the actin polymerization machinery. In this report, we identify a role for the cortactin C-terminus in regulating cell migration and, more specifically, actin dynamics. Overexpression of either full-length cortactin or cortactin C-terminus is sufficient to enhance migration of mammary epithelial cells. In vitro, cortactin binds to and activates, via its SH3 domain, a regulator of the Arp2/3 complex, neural Wiskott Aldrich Syndrome protein (N-WASP). This in vitro activation of N-WASP is likely to be important in vivo, as cortactin-enhanced migration is dependent upon N-WASP. Thus, our results suggest that cortactin has multiple mechanisms by which it can recruit and modulate the actin machinery and ultimately regulate cell migration.
‘Today’s terrorist is tomorrow’s statesman’: the United States and Angolan nationalism in the early 1960s
Authors: Nuno Rodrigues Luís
Published: December 2004

In the early 1960s, the US government and some private organizations developed close contacts with Angolan nationalist movements. In Washington, this policy gained momentum with the new African policy followed by the Kennedy administration in 1961. Kennedy wanted to extend the ‘new
frontier’ to Africa and his administration adopted a policy of favouring self-determination and independence of former colonial territories in that continent. This African policy had several aspects, from the votes and public statements in the United Nations to the increased investment
in educational programmes for future African leaders and to the close contacts with those leaders and organizations that could play a decisive role in the future of African nations.
The Art and Science of Visualization: Metaphorical Maps and Cultural Models
Authors: Cox Donna J.
Published: December 2004

The author has collaborated in research teams to visualize supercomputer simulations and real-time data. She describes these collaborative projects that employ advanced-technology graphics and novel digital displays that include large-format IMAX film, high-definition television productions,
and a museum digital dome at the American Museum of Natural History. The popularity of these images and the function that they provide in popular culture are discussed. She also describes two key technologies that she was part of designing: IntelliBadge(tm), a real-time visualization and ‘smart’
tracking system; and Virtual Director(tm), a virtual camera choreography and remote collaboration system. The process of data-visualization involves the mapping of data from numerical form into an iconic representational form in the attempt to provide humans with insight and understanding
of a phenomenon. This is discussed in the context of metaphor, cognition, and postcolonial theory. Because data-visualizations carry the ‘weight of scientific accuracy and advanced technology’, most general audiences confuse these visualizations as ‘real’; however,
it is argued that data-visualizations are models and metaphors, not reality. In metaphor theory, the mapping of attributes from one domain of information into another is how humans understand, create, and engender new meaning. Data mapping is correlated with this theory. The author explores
how the use of mapping information is culturally contingent. In the spirit of scientific inquiry, she deconstructs the very professional activity for which she is most famous.
Applied Research in Accounting: A Commentary*
Authors: RICHARDSON ALAN J.
Published: December 2004

The mission of Canadian Accounting Perspectives is to provide a forum for “applied research” in accounting, but this key term is not defined. I identify three forms of applied research: (1) the use of existing knowledge to find solutions to current problems; (2) the use of positivist research methods to conduct critical tests between current alternative accounting methods and to identify empirical regularities that contribute to the development of technologies of practice; and (3) the use of disciplined inquiry and action research to develop mid‐range theory and generate empirical results that advance the interests or increase the capabilities of an identified community. This third form of applied research may provide the best approach to bridging the schism between academe and practice.
CAP Forum on E‐Business: The Management of Financial Disclosure on Corporate Websites: A Conceptual Model*
Authors: TRABELSI SAMIR , LABELLE RÉAL , LAURIN CLAUDE
Published: December 2004

This paper addresses the impact of Internet financial reporting (IFR) on financial accounting theory by incorporating it into the general Gibbins, Richardson, and Waterhouse (GRW) (1990) disclosure‐management framework. The GRW model assumes that the firm has a relatively stable process of disclosure management. This process varies between two positions: one ritualistic and the other opportunistic. These dimensions can coexist in the same firm but, on average, the policy of a firm will be either more ritualistic or more opportunistic. Our survey of the financial information disclosed in traditional financial reporting (TFR) as compared with the website disclosures of a random sample of Canadian companies documents a significant difference between TFR and IFR, as well as a wide variability among the sample firms in their use of IFR content, format, and technology. We interpret this variability in the incremental difference of IFR over TFR as an indication that a firm's ritualistic or opportunistic behaviour under IFR is not different from its behaviour under TFR. Thus, the adapted GRW (1990) conceptual model appears to have the potential to support future research in the management of financial disclosure on corporate websites.
CAP Forum on E‐Business: E‐Commerce and Tax Planning: Canadian Experiences*
Authors: CARNAGHAN CARLA , DOWNER PAULINE , KLASSEN KEN , PITTMAN JEFFREY
Published: December 2004

This paper explores the deployment of e‐commerce by Canadian firms in the global marketplace, with an emphasis on the implications of e‐commerce for tax planning. The business press and various government task forces have discussed challenges raised by e‐commerce for traditional “source‐based” tax systems; however, these discussions have presented little evidence of firms' reliance on e‐commerce for tax‐planning purposes. Similarly, academic research has seldom examined whether firms' decisions to implement e‐commerce are by tax‐planning considerations.

It is thus largely unknown whether firms actively consider taxation issues when evaluating e‐commerce, how the factors that have been identified as influencing decisions to implement e‐commerce systems are balanced against tax‐planning considerations, and what barriers might exist in practice to using e‐commerce for tax planning. We choose a qualitative interview‐based approach to explore these issues.

Our findings suggest that tax planning is not considered by most of our respondent companies in their decisions to deploy e‐commerce. The companies we interviewed tended to implement e‐commerce over several years, starting with back‐office technologies like enterprise resource planning (ERP) systems. Accordingly, the ability to perform online sales transactions, which is a key component of using e‐commerce for tax planning, often was not yet in place. One implication of these results is that if concerns over tax revenue losses are realistic, tax policymakers may have some time to refine tax legislation to address the challenges raised by e‐commerce.
CAP Forum on E‐Business: Compromise or Customize: XBRL's Paradoxical Power
Authors: COHEN ERIC E.
Published: December 2004

Business reports are changing in response to regulatory and market demands. Requests by regulators for electronic filings of financial statements and tax forms are increasing and such filings are rapidly becoming mandatory in many countries. In response, extensible business reporting language (XBRL) is a market‐driven, collaborative effort to make electronic filings more useful to, and to reduce the burden on, both publishers and consumers of business reports.

XBRL does much more than simply list data items that can be submitted in an electronic filing. XBRL is a complete set of tools for regulators or groups to fully communicate the meanings of and interrelationships among the business reporting concepts. In addition, core sets of concepts from regulators or groups can be extended, expanded, or otherwise modified for more specific communication by jurisdictions, industries, or individual corporations.

This unique customization capability lets companies better present their electronic filings as parallels to their paper filings. A “customizable standard” offers new opportunities and new challenges. This paper discusses XBRL's paradoxical power ‐ the trade‐offs between customizing to better parallel existing paper reports and compromising to more closely match the standards, and the research needed for the transition from freeform to customized reports.
Executive Dysfunction in Cocaine Addiction: Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity
Authors: Hester Robert , Garavan Hugh
Published: December 2004

Using a GO-NOGO response inhibition task in which working memory (WM) demands can be varied, we demonstrate that the compromised abilities of cocaine users to exert control over strong prepotent urges are associated with reduced activity in anterior cingulate and right prefrontal cortices, two regions thought to be critical for implementing cognitive control. Furthermore, unlike drug-naive controls, and opposite to the anterior cingulate pattern, cocaine users showed an over-reliance on the left cerebellum, a compensatory pattern previously seen in alcohol addiction. The results indicate that cocaine users find it difficult to inhibit their own actions, particularly when WM demands, which have been shown previously to increase during cue-induced craving for the drug, are increased. The results reveal a neuroanatomical basis for this dysexecutive component to addiction, supporting the suggested importance cognitive functions may play in prolonging abuse or predisposing users toward relapse.
Receptive Field Properties of the Macaque Second Somatosensory Cortex: Evidence for Multiple Functional Representations
Authors: Fitzgerald Paul J. , Lane John W. , Thakur Pramodsingh H. , Hsiao Steven S.
Published: December 2004

The detailed functional organization of the macaque second somatosensory cortex (SII) is not well understood. Here we report the results of a study of the functional organization of the SII hand region that combines microelectrode mapping using hand-held stimuli with single-unit recordings using a motorized, computer-controlled tactile oriented bar. The data indicate that the SII hand region extends ∼10 mm in the anteroposterior (AP) dimension, primarily within the upper bank of the lateral sulcus. Furthermore, we find evidence that this region consists of multiple functional fields, with a central field containing neurons that are driven well by cutaneous stimuli, flanked by an anterior field and a posterior field that each contain neurons that are driven well by proprioceptive stimuli and less well by cutaneous stimuli. The anterior field extends ∼4-5 mm AP, the central field extends ∼3-4 mm, and the posterior field extends ∼3 mm. Data from the motorized stimulator indicate that neurons in the central field are more responsive to oriented bars, more frequently exhibit orientation tuning, and have larger receptive fields than neurons in the anterior and posterior fields. We speculate that the three putative fields play different functional roles in tactile perception; the anterior and posterior fields process information that involves both proprioceptive and cutaneous input such as sensorimotor integration or stereognosis, whereas the central field processes primarily cutaneous information.
Global Forebrain Dynamics Predict Rat Behavioral States and Their Transitions
Authors: Gervasoni Damien , Lin Shih-Chieh , Ribeiro Sidarta , Soares Ernesto S. , Pantoja Janaina , Nicolelis Miguel A. L.
Published: December 2004

The wake-sleep cycle, a spontaneous succession of global brain states that correspond to major overt behaviors, occurs in all higher vertebrates. The transitions between these states, at once rapid and drastic, remain poorly understood. Here, intracranial local field potentials (LFPs) recorded in the cortex, hippocampus, striatum, and thalamus were used to characterize the neurophysiological correlates of the rat wake-sleep cycle. By way of a new method for the objective classification and quantitative investigation of all major brain states, we demonstrate that global brain state transitions occur simultaneously across multiple forebrain areas as specific spectral trajectories with characteristic path, duration, and coherence bandwidth. During state transitions, striking changes in neural synchronization are effected by the prominent narrow-band LFP oscillations that mark state boundaries. Our results demonstrate that distant forebrain areas tightly coordinate the processing of neural information during and between global brain states, indicating a very high degree of functional integration across the entire wake-sleep cycle. We propose that transient oscillatory synchronization of synaptic inputs, which underlie the rapid switching of global brain states, may facilitate the exchange of information within and across brain areas at the boundaries of very distinct neural processing regimens.
A “Synaptoplasmic Cistern” Mediates Rapid Inhibition of Cochlear Hair Cells
Authors: Lioudyno Maria , Hiel Hakim , Kong Jee-Hyun , Katz Eleonora , Waldman Erik , Parameshwaran-Iyer Suchitra , Glowatzki Elisabeth , Fuchs Paul A.
Published: December 2004

Cochlear hair cells are inhibited by cholinergic efferent neurons. The acetylcholine (ACh) receptor of the hair cell is a ligand-gated cation channel through which calcium enters to activate potassium channels and hyperpolarize the cell. It has been proposed that calcium-induced calcium release (CICR) from a near-membrane postsynaptic store supplements this process. Here, we demonstrate expression of type I ryanodine receptors in outer hair cells in the apical turn of the rat cochlea. Consistent with this finding, ryanodine and other store-active compounds alter the amplitude of transient currents produced by synaptic release of ACh, as well as the response of the hair cell to exogenous ACh. Like the sarcoplasmic reticulum of muscle, the “synaptoplasmic” cistern of the hair cell efficiently couples synaptic input to CICR.
Facile Syntheses of Aminocyclopropanes:

N

,

N

‐Dibenzyl‐

N

‐(2‐Ethenylcyclopropyl)Amine
Authors: de Meijere Armin , Winsel Harald , Stecker Björn
Published: December 2004

N,N‐
Dibenzyl‐
N‐
(2‐ethylenylcyclopropyl)amine

N,N‐
Dimethylformamide

Methyl tris(isopropoxy)titanium

Titanium tetraisopropoxide

Titanium tetrachloride

Methyllithium
dl

‐Selective Pinacol‐Type Coupling Using Zinc, Chlorosilane, and Catalytic Amounts of
Cp
2
VCl
2
;

dl

‐1,2‐dicyclohexylethanediol
Authors: Hirao Toshikazu , Ogawa Akiya , Asahara Motoki , Muguruma Yasuaki , Sakurai Hidehiro
Published: December 2004

Dichlorodicyclopentadienylvanadium

Chlorotrimethylsilane

Cyclohexanecarboxaldehyde

1,2‐Cyclohexylethanediol
Synthesis of
N
‐(

tert

‐Butoxycarbonyl)‐β‐Iodoalanine Methyl Ester: A Useful Building Block in the Synthesis of Nonnatural α‐Amino Acids via Palladium Catalyzed Cross Coupling Reactions
Authors: Jackson Richard F. W. , Perez‐Gonzalez Manuel
Published: December 2004

N‐(tert‐
Butoxycarbonyl)‐L‐serine methyl ester

N‐(tert‐
Butoxycarbonyl)‐beta‐iodoalanine methyl ester

N
‐(
tert‐
Butoxycarbonyl)‐beta‐4‐(methoxycarbonyl)phenylalanine methyl ester

4‐Diaminopyridine

Tris(dibenzylideneacetone)dipalladium
Synthesis of 3‐Pyridylboronic Acid and its Pinacol Ester. Application of 3‐Pyridylboronic Acid in
S
uzuki Coupling to Prepare 3‐Pyridin‐3‐ylquinoline
Authors: Li Wenjie , Nelson Dorian P. , Jensen Mark S. , Hoerrner R. Scott , Cai Dongwei , Larsen Robert D.
Published: December 2004

3‐Pyridylboronic acid

Tris(3‐pryidyl)boroxin

3‐(4,4,5,5‐Tetramethyl‐[1,3,2]dioxaborlan‐2‐yl)‐pyridine

3‐Pyridin‐3‐ylquinoline

Pinacol
Synthesis of 5‐Bromoisoquinoline and 5‐Bromo‐8‐nitroisoquinoline
Authors: Dalby Brown William , Haahr Gouliaev Alex
Published: December 2004

Isoquinoline

N‐
Bromosuccinimide

5‐Bromoisoquinoline

5‐Bromo‐8‐nitroisoquinoline
Practical Synthesis of Novel Chiral Allenamides: (
R
)‐4‐Phenyl‐3‐(1,2‐propadienyl)oxazolidin‐2‐one
Authors: Xiong H. , Tracey M. R. , Grebe T. , Mulder J. A. , Hsung R. P.
Published: December 2004

(R)‐4‐Phenyl‐2‐oxazolidinone

R‐
4‐Phenyl‐3‐(2‐propynyl)‐2‐oxazolidinone

R‐
Phenyl‐3‐(1, 2‐propadieny)2‐oxaloldinone

Potassium
tert‐
butoxide
Synthesis and
Ru
(
II
)‐
BINAP
Reduction of a Ketoester Derived from Hydroxyproline: 2(
S
)‐(β‐
tert
‐Butoxycarbonyl‐α‐(
S
) and α‐(
R
)‐hydroxyethyl)‐4(
R
)‐hydroxypyrrolidine‐1‐carboxylic acid,
tert
‐Butyl Ester
Authors: King Steven A. , Armstrong Joseph , Keller Jennifer
Published: December 2004

2(
S)‐(
beta‐
tert‐
Butoxycarbonyl‐alpha‐(
S)‐
hydroxyethyl)‐4‐R‐hydroxypyrrolidine‐1‐carboxylic acid,
tert‐
butyl ester

(2
S‐
4
R)‐
2‐
tert‐
Butoxycarbonylacetyl‐4‐hydroxypyrrolidine‐1‐carboxylic acid,
tert‐
butyl ester

R‐BINAP

Lithium hexamethyldisilylamide

N‐Boc hydroxyproline methyl ester
A Convenient Preparation of an Orthogonally ProtectedCα,Cα‐Disubstituted Amino Acid Analog of Lysine: 1‐tert‐butyloxycarbonyl‐4‐((9‐fluorenylmethyloxycarbonyl)amino)‐piperidine‐4‐carboxylic Acid
Authors: Hammarström Lars G. J. , Fu Yanwen , Vail Sidney , Hammer Robert P. , McLaughlin Mark L.
Published: December 2004

DMAP(4‐Dimethylamino)pyridine

1‐tert‐Butoxycarbonylpiperidine‐4‐spiro‐5′‐(1′,3′‐bis(tert‐butoxycarbonyl)hydantoin

4‐Amino1‐tert‐butoxycarbonylpiperidine‐4‐carboxylic acid

1‐tert‐Butyloxycarbonyl‐4‐(9‐fluorenylmethyloxyamino)piperidine‐4‐carboxylic acid

9‐Fluorenylmethyl chlorformate

4‐Piperidone monohydrate hydrochloride

Piperidine‐4‐spiro‐5′‐hydantoin