bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Ground‐Water Flow Theory to a Subsurface Oil Spilla
Authors: Holzer Thomas L.
Published: July 2006

Fuel oil, underlying approximately four acres, was discovered floating on the water table beneath oil products' storage tanks. The oil, of unknown origin, originally was observed discharging to a river adjacent to the storage tank area from an abandoned clay tile. Approximately 35,000 gallons (132,500 liters) of oil were intercepted and contained prior to the field investigation by borings.

Hantush's (1968) theory for the formation of a fresh‐water lens in an unconfined saline aquifer was used to examine the decay of an oil lens resulting from a catastrophic oil spill at the site. The theory indicated that too much time had elapsed from the first detection of oil at the surface to the collection of subsurface information to make it feasible to speculate on the precise nature of the spill event–catastrophic or a slow leak. Application of the theory and consideration of the ground‐water hydrology of the site did make it possible to identify the probable source area of the spill. Analysis of the flow system also assisted in the selection of the appropriate collection system to clean‐up the spill.

Subsequent to the boring program, an electrical resistivity survey was conducted to test the feasibility of delineating the extent of the subsurface oil by this method. Only modest success was achieved, apparently because of the thinness of the oil‐bearing zone.
Increasing the End‐Point Resolution of the EDTA Titrimetric Method for Determining Water Hardnessa
Authors: Hall David M. , Smith Robert F.
Published: July 2006

The sharpness of the end point during the titration for magnesium or calcium using the EDTA titrimetric method is improved by using the free acid form of CI Mordant Black 11 buffered to pH 10 with ammonium hydroxide rather than its sodium salt. Apparently, the ammonium salt of the dye sorbs more strongly in the blue region than does the corresponding sodium salt increasing the end point resolution; hence use of the free acid rather than the commercially available sodium salt is suggested as the end point indicator. Methods for converting the commercial dye to the free acid are given.
Water Quality Variations for Pumping Wells
Authors: Schmidt Kenneth D.
Published: July 2006

Past ground‐water quality monitoring programs have often involved sampling of low‐capacity wells near point or line sources of recharge or pollution. However, large‐capacity wells produce much of the ground water pumped for municipal, industrial, and agricultural uses. Short‐term, seasonal, and long‐term fluctuations in quality are common for water pumped from many large‐capacity wells. In many cases, there is a considerable difference between in‐situ “ground‐water quality” and the quality of water sampled at the well discharge.

Short‐term pump tests for several municipal wells in the San Joaquin Valley, California have indicated that nitrate concentrations decreased exponentially with pumping time. Variability in pump operation creates substantial short‐term changes in well‐water quality. Short‐term changes are most evident for infrequently pumped, shallow wells near point or line sources of recharge or pollution. Seasonal changes in quality have been documented for water from wells in areas of diffuse sources of pollution, such as agricultural return flow and septic tanks. These changes are primarily due to significant changes in depth to water and vertical hydraulic head gradient. Once the short‐term and seasonal trends are established, the optimal sampling approach can be determined in order to establish long‐term trends.
Fault Control of Subsidence, Houston, Texasa
Authors: Kreitler Charles W.
Published: July 2006

Land subsidence increases the area in the Texas Coastal Zone which will be inundated by marine waters from hurricane flooding. Storm surge from a Carla‐sized hurricane in 1976 would flood at least 25 square miles (65 km2) more land than Hurricane Carla did in 1961.

Land subsidence in Harris and Galveston Counties results primarily from ground‐water production. The two‐county area is interlaced with active surface faults with topographic escarpments and surface faults with no topographic escarpments that control drainage patterns and create subtle photographic linear patterns. Ground‐water production activates these faults by differential compaction of the aquifer. The faults appear to be partial hydrologic barriers that compartmentalize land subsidence into several individual basins.
Modeling of Unconfined Ground‐Water Systems
Authors: Murray Willard A. , Johnson Robert L.
Published: July 2006

Mathematical modeling of regional unconfined ground‐water flow is most often accomplished by using a linearized Dupuit‐Forchheimer (DF) equation. The depth of flow, h, in the general DF equation appears as a squared (h3) term and also as a linear term (h). Linearization of the DF equation is generally accomplished with the first method of linearization presented by Polubarinova‐Kochina (PK), in which h2 is replaced with h times some average depth of flow. The resulting equation is then linear in h. The second method of linearization described by PK is accomplished by replacing h with h2 divided by an average flow depth, and hence the resulting equation becomes linear in h2. If the second method of linearization is used, the same “heat conduction type” equation is obtained as that from the first method of linearization, but it tends to yield more accurate predictions of water‐table locations. Furthermore, by simply altering the numerical values of boundary condition constants, most existing mathematical models, based on the first method of linearization, can be easily converted to yield solutions to the more accurate equation linearized by the second method.
Impact of a Power Plant on the Ground‐Water System of a Wetland
Authors: Andrews Charles B. , Anderson Mary P.
Published: July 2006

The impacts of a coal‐fired power plant on the ground‐water system of a river floodplain wetland in central Wisconsin were quantified. The most important impacts were those related to the construction of a 200‐ha cooling lake and a 28‐ha ash pit.

Several two‐dimensional vertically‐oriented steady‐state models of the ground‐water flow system were used to simulate ground‐water flows before and after the filling of the cooling lake. The results of the simulation and supporting field evidence indicate that the creation of the cooling lake greatly altered the configuration of the flow system and increased the discharge of ground water to the wetland west of the lake by a factor of six. Moreover, ground‐water temperatures have increased because of heat input from the cooling lake. Although the wetland biota are responding to the altered physical environment, the high rate of leakage from the cooling lake is not undesirable from a lake management standpoint. Seepage to the ground‐water system prevents a buildup of dissolved solids which would necessitate periodic flushing of the lake and release of saline water to the Wisconsin River.

Since 1975, concentrations of Ca+2 and SO4‐2 have increased in ground water around the ash pit, suggesting that seepage is occurring. However, the plume of contaminated ground water is presently confined to a relatively small area around the ash pit.
Monitoring of Subsurface Injection of Wastes, Florida
Authors: Vecchioli John
Published: July 2006

Injection of waste liquids into Florida's subsurface is physically feasible in many places but should be accompanied by monitoring of the waste‐receiving aquifer system in addition to the injection facility. Monitoring of the interaction of factors including hydrogeologic conditions, well construction, waste volumes and characteristics, and potable‐water sources is desirable to assure that fresh‐water resources are not being adversely affected. An effective aquifer‐system monitoring program includes on‐site wells located close to an injection well and open to the next‐higher permeable stratum, satellite wells located hundreds to several thousands of feet from an injection well and open to the receiving aquifer, and regional wells located miles from individual injection wells and open to the receiving aquifer. An extensive aquifer‐system monitoring program associated with two waste‐injection facilities near Pensacola, Florida, has provided data which have aided hydrologists to understand the aquifer system's response to the injection and, accordingly, to evaluate the potential for affecting the area's fresh‐water resources.
Prediction and Field Verification of Subsurface‐Water Quality Changes During Artificial Recharge, Lubbock, Texas
Authors: Grovea David B. , Wood Warren W.
Published: July 2006

A structure‐imitating numerical model is described that simulates one‐dimensional ion movement with chemical reactions. The reactions include nonlinear ion exchange, dissolution, precipitation and ion complex formation and dissociation. The reactions assume equilibrium conditions and the model accounts for hydrodynamic dispersion. A two‐step computational approach separates the convective and dispersive transport from the chemical reactions. This procedure allows ease in changing grid size, time step size and permits the simple insertion of alternative chemical reactions as subroutines. Chemical parameters for the model were developed in the laboratory using batch experimental techniques. The model, with these experimental parameters, was used to predict solute concentrations exiting from a laboratory column. A field study was also modeled using these same chemical parameters. Verification of the model's predictive capabilities was extablished by comparison between the numerical results of the model and the values from the field experiment.
Distributive Justice, Welfare Economics and Liberalism
Authors: COOPER J. H.
Published: July 2006

“…whereas the normal way of testing a theory in positive economics is to test its conclusions, the normal way of testing a welfare proposition is to test its assumptions… The welfare cake…is so hard to taste that we must sample its ingredients before baking”

‐ J. de V. Graaff, Theoretical Welfare Economics.

“An economist or policy maker who wants an ultimate answer to questions involving distribution, or questions involving choices among alternatives that are not comparable under the Pareto criterion, could use an Arrow Social Welfare Function for guidance. Unfortunately, Arrow showed that…Arrow functions do not exist”

‐ A. Feldman, “Welfare Econimics”, in The New Palgrave: A Dictionary of Economics.
ARE AFRICAN CENTRAL BANKS SUFFICIENTLY INDEPENDENT FOR MONETARY CONVERGENCE?
Authors: Wessels Buks
Published: July 2006

Central bank independence (CBI) is currently a widely debated and topical issue commanding the centre point of many economical and political debates, filling the pages of many scholarly journals. Both central bank independence and accountability are currently regarded as necessary best practices for achieving price stability. The importance of CBI rests on the premise that inflation is primarily a monetary phenomenon, and that the cost of reducing inflation can be lowered by an independent central bank with credibility. Support for CBI also stems from the argument that the power to create money should generally be separated from the power to spend it. This is even more relevant for countries with weak political institutions. However, various studies (cited below) detected lower inflation in those countries where independence of their central banks is the strongest. Countries all over – including some on the African continent – have increased the independence of their central banks accordingly.
ASYMMETRIC PRICE TRANSMISSION AND MARKET CONCENTRATION: AN INVESTIGATION INTO FOUR SOUTH AFRICAN AGRO‐FOOD INDUSTRIES
Authors: Cutts Michela , Kirsten Johann
Published: July 2006

“Market power is like the wind. You can feel it but you cannot see it”

(Kohls and Uhl 2002, p 270)

During 2002 and 2003 retail food prices in South Africa increased dramatically. These increases put the spotlight on the concentration and market power of food manufacturing firms and retailers in the food supply chain. The proprietary nature of information on processes within the supply chain makes it difficult to identify uncompetitive behaviour. This paper reports on the application of a series of econometric analyses to test for asymmetric price transmission in the South African agro‐food sector. The paper specifically seeks to show how market concentration increases the degree of asymmetry by comparing different levels of asymmetry between commodity and retail prices in the South African Economy. The results show that in South Africa industries that are considered to be concentrated at some level show a high degree of asymmetric price transmission, which, however, decreases when the retail product is perishable.
Finite Element Modeling of Structural Relaxation During Annealing of a Precision-Molded Glass Lens
Authors: Jain Anurag , Yi Allen Y.
Published: July 2006

The precision lens molding process is numerically modeled by incorporating the characteristic structural relaxation phenomenon of glass during the annealing stage. A review of the structural relaxation theory as explained by the Narayanaswamy model (Narayanaswamy, 1971, J. Am. Ceram. Soc., 54(10), pp. 491–498) is provided and is then implemented into the simulation model. The commercial finite element method (FEM) program MSC MARC is utilized for the analysis. Glass material is modeled as a linear Newtonian fluid during the molding stage and as a viscoelastic material exhibiting stress and structural relaxation during the annealing stage. A comparison between the final lens shape and volume results obtained by implementing structural relaxation and thermal expansion coefficient is shown. The results demonstrate the need for including structural relaxation in the simulation model for reliable predictions. The results also show that the FEM can be used to predict the process, improve performance, and also provide a deeper process understanding.
Toughness and Oblique Metalcutting
Authors: Atkins A. G.
Published: July 2006

The implications of whether new surfaces in cutting are formed just by plastic flow past the tool or by some fracturelike separation process involving significant surface work, are discussed. Oblique metalcutting is investigated using the ideas contained in a new algebraic model for the orthogonal machining of metals (Atkins, A. G., 2003, “Modeling Metalcutting Using Modern Ductile Fracture Mechanics: Quantitative Explanations for Some Longstanding Problems,” Int. J. Mech. Sci., 45, pp. 373–396) in which significant surface work (ductile fracture toughnesses) is incorporated. The model is able to predict explicit material-dependent primary shear plane angles ϕ and provides explanations for a variety of well-known effects in cutting, such as the reduction of ϕ at small uncut chip thicknesses; the quasilinear plots of cutting force versus depth of cut; the existence of a positive force intercept in such plots; why, in the size-effect regime of machining, anomalously high values of yield stress are determined; and why finite element method simulations of cutting have to employ a “separation criterion” at the tool tip. Predictions from the new analysis for oblique cutting (including an investigation of Stabler’s rule for the relation between the chip flow velocity angle ηC and the angle of blade inclination i) compare consistently and favorably with experimental results.
Angled Line Method for Measuring Continuously Distributed Strain in Sheet Bending
Authors: Swillo Slawomir J. , Iyer Kaushik , Hu S. Jack
Published: July 2006

A new method and optical system have been developed to measure the strain distribution in sheet metal bending. The method relies on a simple pattern, i.e., a single line of certain width, or an area having a boundary line, marked on the sheet before deformation. The line traverses a width of the sheet metal at an angle. The sheet metal is deformed and an equivalent two-dimensional image of the line after deformation is obtained. By comparing the two-dimensional equivalent of the line after deformation with that before deformation, the strain on the surface of the deformed region is determined. Experiments using sheet metal flanging and hemming were conducted to verify the effectiveness and determine the limitation of the proposed method.
A Single Amino Acid Mutation Contributes to Adaptive Beach Mouse Color Pattern
Authors: Hoekstra Hopi E. , Hirschmann Rachel J. , Bundey Richard A. , Insel Paul A. , Crossland Janet P.
Published: July 2006

Natural populations of beach mice exhibit a characteristic color pattern, relative to their mainland conspecifics, driven by natural selection for crypsis. We identified a derived, charge-changing amino acid mutation in the melanocortin-1 receptor (
Mc1r
) in beach mice, which decreases receptor function. In genetic crosses, allelic variation at
Mc1r
explains 9.8% to 36.4% of the variation in seven pigmentation traits determining color pattern. The derived
Mc1r
allele is present in Florida's Gulf Coast beach mice but not in Atlantic coast mice with similar light coloration, suggesting that different molecular mechanisms are responsible for convergent phenotypic evolution. Here, we link a single mutation in the coding region of a pigmentation gene to adaptive quantitative variation in the wild.
Photoproduction of Proton Gradients with π-Stacked Fluorophore Scaffolds in Lipid Bilayers
Authors: Bhosale Sheshanath , Sisson Adam L. , Talukdar Pinaki , Fürstenberg Alexandre , Banerji Natalie , Vauthey Eric , Bollot Guillaume , Mareda Jiri , Röger Cornelia , Würthner Frank , Sakai Naomi , Matile Stefan
Published: July 2006

Rigid
p
-octiphenyl rods were used to create helical tetrameric π-stacks of blue, red-fluorescent naphthalene diimides that can span lipid bilayer membranes. In lipid vesicles containing quinone as electron acceptors and surrounded by ethylenediaminetetraacetic acid as hole acceptors, transmembrane proton gradients arose through quinone reduction upon excitation with visible light. Quantitative ultrafast and relatively long-lived charge separation was confirmed as the origin of photosynthetic activity by femtosecond fluorescence and transient absorption spectroscopy. Supramolecular self-organization was essential in that photoactivity was lost upon rod shortening (from
p
-octiphenyl to biphenyl) and chromophore expansion (from naphthalene diimide to perylene diimide). Ligand intercalation transformed the photoactive scaffolds into ion channels.
Presymptomatic Detection of Prions in Blood
Authors: Saá Paula , Castilla Joaquín , Soto Claudio
Published: July 2006

Prions are thought to be the proteinaceous infectious agents responsible for transmissible spongiform encephalopathies (TSEs). PrP
Sc
, the main component of the infectious agent, is also the only validated surrogate marker for the disease, and its sensitive detection is critical for minimizing the spread of the disease. We detected PrP
Sc
biochemically in the blood of hamsters infected with scrapie during most of the presymptomatic phase of the disease. At early stages of the incubation period, PrP
Sc
detected in blood was likely to be from the peripheral replication of prions, whereas at the symptomatic phase, PrP
Sc
in blood was more likely to have leaked from the brain. The ability to detect prions biochemically in the blood of infected but not clinically sick animals offers a great promise for the noninvasive early diagnosis of TSEs.
Histological processing variability in the determination of lateral resection margins in rectal cancer
Authors: Eid I , El-Muhtaseb M S , Mukherjee R , Renwick R , Gardiner D S , Macdonald A
Published: July 2006

Background:Involvement of the lateral resection margin (LRM) has been shown to be a reliable predictor of local recurrence of rectal cancer. Accurate determination of the LRM status is crucial in selecting patients for postoperative radiotherapy. However, variability in processing factors may affect the measurement of the LRM.

Aim:To investigate how formalin fixation and laboratory processing affects the measurement of the LRM.

Methods:For this study, rectal cancer specimens (n = 9) were fixed in formalin for 4 days and then sectioned transversally, and one half of the specimen was sent for processing. The effacing tumours were placed back in formalin for another 3 days. At day 7, the effacing tumour block (mirror image) was sent for processing. The longest and the shortest perpendicular resection margins for each of the day 4 and day 7 specimens were measured. In a second experiment, control tissue (colon; n = 40), length 10 (0.05) mm, was also processed from a normal sigmoid colon.

Specimens were retained in formalin for 24 h (n = 12), 48 h (n = 12), 72 h (n = 9) and 96 h (n = 7). The degree of tissue shrinkage was then recorded. Variations in the recorded LRM and length of colonic tissue are presented as a median (interquartile range) and data were compared using analysis of variance.

Results:In the cases of rectal cancer, the variation in measured LRM between day 4 and day 7 specimens was 3.2 (1.5–5) mm. In 30 of the 37 comparisons, the day 7 LRM increased in length, whereas in the remaining 7 it decreased. In the second experiment, control tissue of the original length 10 (0.05) mm increased in length to 10.9 (8.9–13.0) mm, p<0.01.

Conclusion:These results suggest that the fixation period/laboratory processes result in measurable differences in the reported LRM. This degree of variation has implications for the reliable reporting of the LRM, predicting local recurrence rates and planning subsequent adjuvant radiotherapy.
Digital radiography. A comparison with modern conventional imaging
Authors: Bansal G J
Published: July 2006

The development of computed radiography over the past two decades has transformed radiological imaging. The radiology departments in the 21st century will look very different from those in the preceding period. In this review, the development of digital radiography is presented with a description of its various forms and a comparison with screen film radiography.
Spontaneous renal haemorrhage in the peritoneal cavity
Authors: Abdellaoui A , Al-Daraji W , Natarajan V , Sandilands D
Published: July 2006

A 49 year old woman was admitted to hospital after a sudden onset of severe back pain. Twelve hours later, the haemoglobin had decreased to 5.9 and became unstable. She underwent emergency laparotomy that showed intraperitoneal bleeding, secondary to spontaneous kidney rupture. The patient was given a nephrectomy. Histological examination showed an angiomyolipoma as the cause of the bleeding. To the knowledge of the authors, only five previous cases of spontaneous renal bleeding into the peritoneal cavity have been reported in English literature.
Myeloma associated amyloidosis presenting as subacute liver failure
Authors: Cross T J S , Wendon J A , Quaglia A , Salisbury J R , Heneghan M A , Harrison P M
Published: July 2006

Multiple myeloma related amyloidosis is rare and its presentation with subacute liver failure (SALF) has not been reported. A case is described of a 46 year old woman presenting with a six week history of nausea, abdominal pain, and jaundice. Routine tests failed to establish a cause. Computed tomography showed a small volume liver consistent with SALF. Emergency liver transplantation was not undertaken because of the suspicion of underlying malignancy. At necropsy, liver biopsy showed amyloid deposition and bone marrow biopsy showed multiple myeloma. Thus, amyloidosis should be added to the list of potential causes of SALF.
Cellulose Synthesis in Higher Plants
Authors: Somerville Chris
Published: July 2006

Cellulose microfibrils play essential roles in the organization of plant cell walls, thereby allowing a growth habit based on turgor. The fibrils are made by 30 nm diameter plasma membrane complexes composed of approximately 36 subunits representing at least three types of related CESA proteins. The complexes assemble in the Golgi, where they are inactive, and move to the plasma membrane, where they become activated. The complexes move through the plasma membrane during cellulose synthesis in directions that coincide with the orientation of microtubules. Recent, simultaneous, live-cell imaging of cellulose synthase and microtubules indicates that the microtubules exert a direct influence on the orientation of cellulose deposition. Genetic studies in Arabidopsis have identified a number of genes that contribute to the overall process of cellulose synthesis, but the role of these proteins is not yet known.
Abnormal regulatory interactions of I148T-CFTR and the epithelial Na+channel inXenopusoocytes
Authors: Suaud Laurence , Yan Wusheng , Rubenstein Ronald C.
Published: July 2006

The mechanisms underlying regulatory interactions of the cystic fibrosis transmembrane conductance regulator (CFTR) and the epithelial Na+channel (ENaC) in Xenopus oocytes are controversial. CFTR's first nucleotide binding domain (NBD-1) may be important in these interactions, because mutations within NBD-1 impair these functional interactions. We hypothesized that an abnormal CFTR containing a non-NBD-1 mutation and able to transport chloride would retain regulatory interactions with murine ENaC (mENaC). We tested this hypothesis for I148T-CFTR, where the mutation is located in CFTR's first intracellular loop. I148T-CFTR has been associated with a severe CF phenotype, perhaps because of defects in its regulation of bicarbonate transport, but it transports chloride similarly to wild-type CFTR in model systems (Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S. Nature 410: 94–97, 2001). cRNAs encoding αβγ-mENaC and I148T-CFTR were injected separately or together into Xenopus oocytes. mENaC and CFTR functional expression were assessed by two-electrode voltage clamp. mENaC whole oocyte expression was determined by immunoblotting, and surface expression was quantitated by surface biotinylation. Injection of I148T-CFTR cRNA alone yielded high levels of CFTR functional expression. In coinjected oocytes, mENaC functional and surface expression was not altered by activation of I148T-CFTR with forskolin/ IBMX. Furthermore, the CFTR potentiator genistein both enhanced functional expression of I148T-CFTR and restored regulation of mENaC surface expression by activated I148T-CFTR. These data suggest that the ability to transport chloride is not a critical determinant of regulation of mENaC by activated CFTR in Xenopus oocytes and provide further evidence that I148T-CFTR is dysfunctional despite maintaining the ability to transport chloride.
Three-dimensional mitochondrial arrangement in ventricular myocytes: from chaos to order
Authors: Birkedal Rikke , Shiels Holly A. , Vendelin Marko
Published: July 2006

We have developed a novel method to quantitatively analyze mitochondrial positioning in three dimensions. Using this method, we compared the relative positioning of mitochondria in adult rat and rainbow trout ( Oncorhynchus mykiss) ventricular myocytes. Energetic data suggest that trout, in contrast to the rat, have two subpopulations of mitochondria in their cardiomyocytes. Therefore, we speculated whether trout cardiomyocytes exhibit two types of mitochondrial patterns. Stacks of confocal images of mitochondria were acquired in live cardiomyocytes. The images were processed and mitochondrial centers were detected automatically. The mitochondrial arrangement was analyzed by calculating the three-dimensional probability density and distribution functions describing the distances between neighboring mitochondrial centers. In the rat (8 cells with a total of 7,546 mitochondrial centers), intermyofibrillar mitochondria are highly ordered and arranged in parallel strands. These strands are separated by ∼1.8 μm and can be found in any transversal direction relative to each other. Neighboring strands exhibit the same mitochondrial periodicity. In contrast to the rat, trout ventricular myocytes (22 cells; 5,528 mitochondrial centers) exhibit a relatively chaotic mitochondrial pattern. Neighboring mitochondria can be found in any direction relative to each other. Thus, two potential subpopulations of mitochondria in trout are not distinguishable by their pattern. The developed method required minor interaction in the filtering of the mitochondrial centers. It is therefore a practical approach to describe intracellular organization and may also be used for analysis of time-dependent organizational changes. The obtained quantitative description of mitochondrial organization is a requisite for accurate mathematical analysis of mitochondrial systems biology.
Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor
Authors: Verghese George M. , Gutknecht Michael F. , Caughey George H.
Published: July 2006

Prostasin, a trypsinlike serine peptidase, is highly expressed in prostate, kidney, and lung epithelia, where it is bound to the cell surface, secreted, or both. Prostasin activates the epithelial sodium channel (ENaC) and suppresses invasion of prostate and breast cancer cells. The studies reported here establish mechanisms of membrane anchoring and secretion in kidney and lung epithelial cells and demonstrate a critical role for prostasin in regulating epithelial monolayer function. We report that endogenous mouse prostasin is glycosylphosphatidylinositol (GPI) anchored to the cell surface and is constitutively secreted from the apical surface of kidney cortical collecting duct cells. Using site-directed mutagenesis, detergent phase separation, and RNA interference approaches, we show that prostasin secretion depends on GPI anchor cleavage by endogenous GPI-specific phospholipase D1 (Gpld1). Secretion of prostasin by kidney and lung epithelial cells, in contrast to prostate epithelium, does not depend on COOH-terminal processing at conserved Arg322. Using stably transfected M-1 cells expressing wild-type, catalytically inactive, or chimeric transmembrane (not GPI)-anchored prostasins we establish that prostasin regulates transepithelial resistance, current, and paracellular permeability by GPI anchor- and protease activity-dependent mechanisms. These studies demonstrate a novel role for prostasin in regulating epithelial monolayer resistance and permeability in kidney epithelial cells and, furthermore, show specifically that prostasin is a critical regulator of transepithelial ion transport in M-1 cells. These functions depend on the GPI anchor as well as the peptidase activity of prostasin. These studies suggest that cell-specific Gpld1- or peptidase-dependent pathways for prostasin secretion may control prostasin functions in a tissue-specific manner.
Evidence that endogenous SST inhibits ACTH and ghrelin expression by independent pathways
Authors: Luque Raul M. , Gahete Manuel D. , Hochgeschwender Ute , Kineman Rhonda D.
Published: July 2006

Corticosterone and total ghrelin levels are increased in somatostatin (SST) knockout mice ( Sst−/−) compared with SST-intact controls ( Sst+/+). Because exogenous ghrelin can increase glucocorticoids, the question arises whether elevated levels of ghrelin contribute to elevated corticosterone levels in Sst−/−mice. We report that Sst−/−mice had elevated mRNA levels for pituitary proopiomelanocortin (POMC), the precursor of adrenocorticotropic hormone (ACTH), whereas mRNA levels for hypothalamic corticotropin-releasing hormone (CRH) did not differ from Sst+/+mice. Furthermore, SST suppressed pituitary POMC mRNA levels and ACTH release in vitro independently of CRH actions. In contrast, it has been reported that ghrelin increases glucocorticoids via a central effect on CRH secretion and that n-octanoyl ghrelin is the form of ghrelin that activates the GHS-R1a and modulates CRH neuronal activity. Consistent with elevations in total ghrelin levels, Sst−/−mice displayed an increase in stomach ghrelin mRNA levels, whereas hypothalamic and pituitary expression of ghrelin was not altered. Despite the increase in total ghrelin levels, circulating levels of n-octanoyl ghrelin were not altered in Sst−/−mice. Because glucocorticoids and ghrelin increase in response to fasting, we examined the impact of fasting on the adrenal axis and ghrelin in Sst+/+and Sst−/−mice and found that endogenous SST does not significantly contribute to this adaptive response. We conclude that endogenous SST inhibits basal ghrelin gene expression in a tissue specific manner and independently and directly inhibits pituitary ACTH synthesis and release. Thus endogenous SST exerts an inhibitory effect on ghrelin synthesis and on the adrenal axis through independent pathways.
Transforming growth factor-β in the brain regulates fat metabolism during endurance exercise
Authors: Ishikawa Toma , Mizunoya Wataru , Shibakusa Tetsuro , Inoue Kazuo , Fushiki Tohru
Published: July 2006

We have previously reported that the concentration of transforming growth factor-β (TGF-β) increases in the cerebrospinal fluid of rats during exercise and that there is an increase in whole body fat oxidation following the intracisternal administration of TGF-β. These results led us to postulate that TGF-β in the brain regulates the enhancement of fatty acid oxidation during exercise. To test this hypothesis, we carried out respiratory gas analysis during treadmill running following the inhibition of TGF-β activity in rat brain by intracisternal administration of anti-TGF-β antibody or SB-431542, an inhibitor of the type 1 TGF-β receptor. We found that each reagent partially blocked the increase in the fatty acid oxidation. We also compared the plasma concentrations of energy substrates in the group administered anti-TGF-β antibody and the control group during running. We found that the plasma concentrations of nonesterified fatty acids and ketone bodies in the group administered anti-TGF-β antibody were lower than in the control group at the end of running. In the same way, we carried out respiratory gas analysis during treadmill running after depressing corticotropin-releasing factor activity in the brain using intracisternal administration of astressin, an inhibitor of the corticotropin-releasing factor receptor. However, there were no significant differences in respiratory exchange ratio or oxygen consumption in moderate running (60% maximum oxygen consumption). These results suggest that brain TGF-β has a role in enhancing fatty acid oxidation during endurance exercise and that this regulation is executed at least partly via the type 1 TGF-β receptor signal transduction system.
Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise
Authors: Roepstorff Carsten , Donsmark Morten , Thiele Maja , Vistisen Bodil , Stewart Greg , Vissing Kristian , Schjerling Peter , Hardie D. Grahame , Galbo Henrik , Kiens Bente
Published: July 2006

Women have been shown to use more intramuscular triacylglycerol (IMTG) during exercise than men. To investigate whether this could be due to sex-specific regulation of hormone-sensitive lipase (HSL) and to use sex comparison as a model to gain further insight into HSL regulation, nine women and eight men performed bicycle exercise (90 min, 60% V̇o2peak), and skeletal muscle HSL expression, phosphorylation, and activity were determined. Supporting previous findings, basal IMTG content ( P < 0.001) and net IMTG decrease during exercise ( P < 0.01) were higher in women than in men and correlated significantly ( r = 0.72, P = 0.001). Muscle HSL mRNA (80%, P = 0.11) and protein content (50%, P < 0.05) were higher in women than in men. HSL total activity increased during exercise (47%, P < 0.05) but did not differ between sexes. Accordingly, HSL specific activity (HSL activity per HSL protein content) increased during exercise (62%, P < 0.05) and was generally higher in men than in women (82%, P < 0.05). A similar pattern was observed for HSL Ser659phosphorylation, suggesting a role in regulation of HSL activity. Likewise, plasma epinephrine increased during exercise ( P < 0.05) and was higher in men than in women during the end of the exercise bout ( P < 0.05). We conclude that, although HSL expression and Ser659phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes. The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women.
Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice
Authors: Chueh Fu-Yu , Malabanan Carlo , McGuinness Owen P.
Published: July 2006

Previous studies in mice suggest that portal venous infusion of glucose at a low rate paradoxically causes hypoglycemia; this does not occur in dogs, rats, and humans. A possible explanation is that fasting status in the mouse studies may have altered the response. We sought to determine whether the response to portal glucose delivery in the mouse was similar to that seen in other species and whether it was dependent on fasting status. Studies were performed on chronically catheterized conscious mice. Catheters were placed into the portal and jugular veins and carotid artery 5 days before study. After a 5- or 16-h fast, glucose was infused into either the portal (PO) or the jugular vein (JU) for 6 h at 25 μg·g−1·min−1. [3-3H]glucose was infused into the JU to measure glucose turnover. In 5-h-fasted mice, PO and JU exhibited similar increases in arterial blood glucose from 155 ± 11 to 173 ± 19 and 147 ± 8 to 173 ± 10 mg/dl, respectively. Endogenous glucose production decreased and arterial insulin increased to the same extent in both PO and JU. A similar response was observed in 16-h-fasted mice; however, the proportion of hepatic glycogen synthesis occurring by the indirect pathway was increased by fasting. In summary, portal glucose delivery in the mouse did not cause hypoglycemia even when the duration of the fast was extended. The explanation of the differing response from previous reports in the mouse is unclear.
S-adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in the rat liver
Authors: Bailey Shannon M. , Robinson Gloria , Pinner Anita , Chamlee Laura , Ulasova Elena , Pompilius Melissa , Page Grier P. , Chhieng David , Jhala Nirag , Landar Aimee , Kharbanda Kusum K. , Ballinger Scott , Darley-Usmar Victor
Published: July 2006

An early event that occurs in response to alcohol consumption is mitochondrial dysfunction, which is evident in changes to the mitochondrial proteome, respiration defects, and mitochondrial DNA (mtDNA) damage. S-adenosylmethionine (SAM) has emerged as a potential therapeutic for treating alcoholic liver disease through mechanisms that appear to involve decreases in oxidative stress and proinflammatory cytokine production as well as the alleviation of steatosis. Because mitochondria are a source of reactive oxygen/nitrogen species and a target for oxidative damage, we tested the hypothesis that SAM treatment during alcohol exposure preserves organelle function. Mitochondria were isolated from livers of rats fed control and ethanol diets with and without SAM for 5 wk. Alcohol feeding caused a significant decrease in state 3 respiration and the respiratory control ratio, whereas SAM administration prevented these alcohol-mediated defects and preserved hepatic SAM levels. SAM treatment prevented alcohol-associated increases in mitochondrial superoxide production, mtDNA damage, and inducible nitric oxide synthase induction, without a significant lessening of steatosis. Accompanying these indexes of oxidant damage, SAM prevented alcohol-mediated losses in cytochrome c oxidase subunits as shown using blue native PAGE proteomics and immunoblot analysis, which resulted in partial preservation of complex IV activity. SAM treatment attenuated the upregulation of the mitochondrial stress chaperone prohibitin. Although SAM supplementation did not alleviate steatosis by itself, SAM prevented several key alcohol-mediated defects to the mitochondria genome and proteome that contribute to the bioenergetic defect in the liver after alcohol consumption. These findings reveal new molecular targets through which SAM may work to alleviate one critical component of alcohol-induced liver injury: mitochondria dysfunction.
Induction of CD8+regulatory T cells in the intestine byHeligmosomoides polygyrusinfection
Authors: Metwali Ahmed , Setiawan Tommy , Blum Arthur M. , Urban Joseph , Elliott David E. , Hang Long , Weinstock Joel V.
Published: July 2006

This study determined whether Heligmosomoides polygyrus induces intestinal regulatory T cells. Splenic T cells proliferate strongly when cultured with anti-CD3 and antigen-presenting cells (APC). Lamina propria T cells from mice with H. polygyrus mixed with normal splenic T cells from uninfected mice inhibited proliferation over 90%. Lamina propria T cells from mice without H. polygyrus only modestly affected T cell proliferation. The worm-induced regulatory T cell was CD8+and required splenic T cell contact to inhibit proliferation. The regulation also was IL-10 independent, but TAP-dependent, suggesting that it requires major histocompatibility complex (MHC) class I interaction. Additional studies employed mice with transgenic T cells that did not express functional TGF-β receptors. The lamina propria T regulator inhibited proliferation of these transgenic T cells nearly 100%, suggesting that TGF-β signaling via the T cell was not required. CD8+T cells were needed for worms to reverse piroxicam-induced colitis in Rag mice (T and B cell deficient) reconstituted with IL-10−/−T cells. Thus H. polygyrus induces a regulatory CD8+lamina propria T cell that inhibits T cell proliferation and that appears to have a role in control of colitis.
Absence of CFTR is associated with pleiotropic effects on mucins in mouse gallbladder epithelial cells
Authors: Kuver Rahul , Wong Thomas , Klinkspoor Johanne Henriette , Lee Sum P.
Published: July 2006

Mucus of cystic fibrosis patients exhibits altered biochemical composition and biophysical behavior, but the causal relationships between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the abnormal mucus seen in various organ systems remain unclear. We used cultured gallbladder epithelial cells (GBEC) from wild-type and Cftr(−/−) mice to investigate mucin gene and protein expression, kinetics of postexocytotic mucous granule content expansion, and biochemical and ionic compositions of secreted mucins. Muc1, Muc3, Muc4, Muc5ac, and Muc5b mRNA levels were significantly lower in Cftr(−/−) GBEC compared with wild-type cells, whereas Muc2 mRNA levels were higher in Cftr(−/−) cells. Quantitative immunoblotting demonstrated a trend toward lower MUC1, MUC2, MUC3, MUC5AC, and MUC5B mucin levels in Cftr(−/−) cells compared with cells from wild-type mice. In contrast, the levels of secreted MUC1, MUC3, MUC5B, and MUC6 mucins were significantly higher from Cftr(−/−) cells; a trend toward higher levels of secreted MUC2 and MUC5AC was also noted from Cftr(−/−) cells. Cftr(−/−) cells demonstrated slower postexocytotic mucous granule content expansion. Calcium concentration was significantly elevated in the mucous gel secreted by Cftr(−/−) cells compared with wild-type cells. Secreted mucins from Cftr(−/−) cells contained higher sulfate concentrations. Thus absence of CFTR is associated with pleiotropic effects on mucins in murine GBEC.
Endothelial cell barrier enhancement by ATP is mediated by the small GTPase Rac and cortactin
Authors: Jacobson Jeffrey R. , Dudek Steven M. , Singleton Patrick A. , Kolosova Irina A. , Verin Alexander D. , Garcia Joe G. N.
Published: July 2006

ATP is a physiologically relevant agonist released by various sources, including activated platelets, with complex effects mediated via activation of P2purinergic receptors. ATP-induced endothelial cell (EC) production of prostacyclin and nitric oxide is recognized, and EC barrier enhancement evoked by ATP has been described. ATP effects on EC barrier function and vascular permeability, however, remain poorly characterized. Although the mechanisms involved are unclear, we previously identified activation of the small GTPase Rac and translocation of cortactin, an actin-binding protein, as key to EC barrier augmentation induced by simvastatin and sphingosine 1-phosphate and therefore examined the role of these molecules in ATP-induced EC barrier enhancement. ATP induced rapid, dose-dependent barrier enhancement in human pulmonary artery EC as measured by transendothelial electrical resistance, with a peak effect appreciable at 25 min (39% increase, 10 μM) and persisting at 2 h. These effects were associated with rearrangement of the EC actin cytoskeleton, early myosin light chain phosphorylation, and spatially defined (cell periphery) translocation of both Rac and cortactin. ATP (10 μM)-treated EC demonstrated a significant increase in Rac activation relative to controls, with a maximal effect (∼4-fold increase) at 10 min. Finally, ATP-induced barrier enhancement was markedly attenuated by reductions of either Rac or cortactin (small interfering RNA) relative to controls. Our results suggest for the first time that ATP-mediated barrier protection is associated with cytoskeletal activation and is dependent on both Rac activation and cortactin.
Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain
Authors: Evrard Henry C.
Published: July 2006

The data summarized here suggest the existence of a new central pathway for the hormonal regulation of pain. These data mainly collected in quail, a useful model in neuroendocrinology, demonstrate that numerous neurons in the superficial laminae of the spinal cord express aromatase (estrogen-synthase). Chronic and systemic blockade of this enzyme in quail alters nociception within days, indicating that the slow genomic effects of sex steroids on nociception classically observed in mammals also occur in birds and require aromatization of androgens into estrogens. However, by contrast with these slow effects, acute intrathecal inhibition of aromatase in restricted spinal cord segments reveals that estrogens can also control nociception much faster, within 1 min, presumably through the activation of a nongenomic pathway and in a manner that depends on an immediate response to fast activation/deactivation of local aromatase activity. This emergent central and rapid paracrine mechanism might permit instantaneous and segment-specific changes in pain sensitivity; it draws new interesting perspectives for the study of the estrogenic control of pain, thus far limited to the classical view of slow genomic changes in pain, depending on peripheral estrogens. The expression of aromatase in the spinal cord in other species and in other central nociception-related areas is also briefly discussed.