bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Isotope Fractionation during Pedogenesis in Redoximorphic Soils
Authors: Wiederhold Jan G. , Teutsch Nadya , Kraemer Stephan M. , Halliday Alex N. , Kretzschmar Ruben
Published: November 2007

Stable Fe isotopes provide a potential new tool for tracing the biogeochemical cycle of Fe in soils. Iron isotope ratios in two redoximorphic soils were measured by multicollector inductively coupled plasma mass spectrometry to study the relationships between pedogenic Fe transformation and redistribution processes, and mass‐dependent fractionation of Fe isotopes. Redoximorphic Fe depletion and enrichment zones were sampled in addition to the bulk soil samples. A three‐step sequential extraction procedure was used to separate different Fe pools, which were examined in addition to total soil digests. Significant enrichments of heavy Fe isotopes of about 0.3‰ in δ57Fe were found in total soil digests of Fe‐depleted zones compared with bulk soil samples and were explained by the preferential removal of light isotopes, presumably during microbially mediated Fe oxide dissolution under anoxic conditions. Accordingly, pedogenic Fe enrichment zones were found to be slightly enriched in light Fe isotopes. Distinct Fe isotope variations of >1‰ in δ57Fe were found between different Fe pools within soil samples, specifically enrichments of light isotopes in pedogenic oxides contrasting with heavy isotope signatures of residual silicate‐bound Fe. Our data demonstrate that pedogenic Fe transformations in redoximorphic soils are linked to isotope fractionation, revealing greater mobility of lighter Fe isotopes compared with heavier isotopes during pedogenesis. No simple quantitative relationship between Fe depletion and isotope fractionation could be inferred, however. Our findings provide new insights into the behavior of Fe isotopes in soils and contribute to the development of Fe isotopes as a tracer for the biogeochemical Fe cycle.
Root Zone Leachate from High Chemical Oxygen Demand Cannery Water Irrigation
Authors: Johns Mitchell M. , Bauder James W.
Published: November 2007

Food processing frequently results in substantial land application of wastewater of impaired quality, which requires consideration of soil and groundwater degradation. Of particular concern is the potential for impact by high organic loadings from this practice. This study evaluated the consequences of irrigating soil columns with fruit cannery wastewater (CW) at high chemical oxygen demand (COD) loadings. A CW having a COD of 9216 mg L−1 and Na adsorption ratio of 11.4 (mmolc L−1)−1/2 was applied weekly to grassed soil. Loading rates equated to 467, 701, and 934 kg COD ha−1 d−1, the lowest rate equivalent to the historic loading rate for the soil. Percolate chemistry was evaluated during dosing and after a rest period followed by rainfall. Nearly all organic constituents were mineralized (88–99%); the balance of COD‐sourced C was retained in the soil. There was no evidence of COD waste in the percolate, suggesting that the CW was primarily labile. However, CW dosing resulted in modestly alkaline post‐study soil conditions and Na+ leaching below the rooting zone. Neither NO3−–N nor total salt concentration in the leachate was high enough to warrant environmental concern under the circumstances of this study. Outcomes substantiate CW COD loadings in land application at rates exceeding current practices in some locations, although high‐COD CW loading rates are not necessarily recommended best management practices. Sodium management and loading rates matching the site evapotranspiration potential can minimize the potential for soil and groundwater degradation from CW land application.
Erosion of Noncohesive Sediment by Ground Water Seepage: Lysimeter Experiments and Stability Modeling
Authors: Fox Garey A. , Chu-Agor Ma Librada (Maria) , Wilson Glenn V.
Published: November 2007

Seepage may be a significant mechanism of streambank erosion and failure in numerous geographical locations. Previous research investigated erosion by lateral subsurface flow and developed a sediment transport model similar to an excess shear stress equation. As a continuation of this earlier research, slope destabilization driven by lateral, subsurface flow was studied to further verify the recently proposed sediment transport model. Laboratory experiments were performed using a two‐dimensional soil lysimeter. The experiments were conducted on two sandy soils: a field soil (loamy sand) and sieved sand with greater sand content and less cohesion. A series of seven lysimeter experiments were performed for the two different sands by varying the bank slope (90, 60, 45, 36, and 26°). Flow and sediment concentrations were measured at the outflow flume. Pencil‐size tensiometers were used to measure soil pore‐water pressure. A slight modification of the existing seepage sediment transport model adequately simulated lysimeter experiments for both noncohesive soils without modifying the seepage parameters of the excess shear stress equation, especially for bank angles >45°. The research then determined whether integrated finite element and bank stability models were capable of capturing both small‐ and large‐scale sapping failures. The models predicted large‐scale failures for bank angles >45° in which tension cracks formed on the bank surface. The models failed to predict collapses for bank angles <45° in which tension cracks formed on the seepage face. The failure to predict collapse was hypothesized to be due to the assumption of circular arc slip surfaces. More analytically complex stability approaches are needed to capture bank slope undermining.
Aggregate Stability as Affected by Polyacrylamide Molecular Weight, Soil Texture, and Water Quality
Authors: Mamedov A. I. , Beckmann S. , Huang C. , Levy G. J.
Published: November 2007

The favorable effects of the environmentally friendly, nontoxic, anionic polyacrylamide (PAM) as a soil conditioner have long been established. Some uncertainties exist, however, regarding the effects of PAM molecular weight (MW) on its performance as a soil amendment and its ability to penetrate into aggregates and stabilize interior surfaces. We studied the effects of two anionic polymers, a high‐MW (12 × 106Da) and a medium‐MW (2 × 105Da) PAM, using deionized water (electrical conductivity of 0.004 dS m−1) or a 15 mmol L−1gypsum solution, on the stability of aggregates from four smectitic soils varying in clay content. Penetration of PAM into the aggregates was estimated from treating 0.5‐ to 1.0‐ and 1.0‐ to 2.0‐mm aggregates with PAM and thereafter comparing the stability of the small aggregates to that of the large aggregates after the latter had been crushed and sieved to 0.5‐ to 1.0‐mm size. The stability ratio (SR) ranged from 0.090 to 0.900 and tended to (i) increase with the increase in soil clay content, (ii) maintain, in the absence of PAM, a greater level with electrolyte solution than deionized water, and (iii) be greater for the PAM‐treated aggregates than the control. In the finer textured soils, the SR of the initially small aggregates was generally greater than that of the initially large aggregates, indicating that most of the PAM was adsorbed on the exterior surfaces and only a small fraction of the PAM added, if any, entered into pores. A significant interaction among the treatments tested (PAM MW, aggregate size, and solution ionic strength), with respect to their effect on the SR, was identified. Consequently, neither of the two PAM polymers tested could have been singled out as preferable.
Assessing access to safe water and monitoring progress on MDG7 target 10 (access to safe water and basic sanitation): Lessons from Kazakhstan
Authors: O'Hara Sarah , Hannan Tim , Genina Maria
Published: November 2007

The Millennium Development Goals (MDGs), designed to combat global poverty and hunger, protect the environment, improve health and sanitation and promote education and gender equality, were agreed at the UN Millennium Summit in September 2000. The importance of access to clean water in the overall MDG process has been highlighted and shown to contribute to all other goals and targets. Goal 7 target 10 aims to “halve, by 2015, the proportion of people without sustainable access to safe drinking water and improved sanitation”, compared with 1990. The aim of this MDG is clear and considered to be achievable in most countries. However, it is argued that the base data upon which the targets are set and against which progress will be measured can be problematic, partly because of reliance on poor government information and also on the apparent need of the UN to have a consistent base year and set of definitions across the world.

In this paper, we report the findings of a major water and sanitation survey conducted in Kazakhstan designed specifically to quantify the current level of access, providing the base upon which to determine implementation priorities and against which to measure progress. As well as providing country-specific information the survey highlighted several important issues that have more general relevance. We raise three major questions associated with Target 10: how to define “access”, how to define “improved source” or “improved sanitation” and whether 1990 is always an appropriate base year. Moreover, we argue that there is need to reconsider the way progress is monitored and that the focus on global comparisons is detrimental to making real progress. In conclusion we argue that improving water supply and sanitation can be done in a way that is (1) appropriate for the country, (2) feasible (and fairly easy) to monitor progress and (3) more likely to be accepted by government as there is a sense of relevance.
Integrated modelling under uncertainty in watershed-level assessment and management
Authors: Ham J.H. , Yoon C.G. , Jung K.W. , Jang J.H.
Published: November 2007

Uncertainty in water quality model predictions is inevitably high due to natural stochasticity, model uncertainty, and parameter uncertainty. An integrated modelling system (modified-BASINS) under uncertainty is described and demonstrated for use in receiving-water quality prediction and watershed management. A Monte Carlo simulation was used to investigate the effect of various uncertainty types on output prediction. Without pollution control measures in the watershed, the concentrations of total nitrogen (T-N) and total phosphorus (T-P) in the Hwaong Reservoir, considering three uncertainty types, would be less than about 4.4 and 0.23 mg L−1, respectively, in 2012, with 90% confidence. The effects of two watershed management practices, wastewater treatment plants (WWTP) and constructed wetlands (WETLAND), were evaluated. The combined scenario (WWTP + WETLAND) was the most effective at improving reservoir water quality, bringing concentrations of T-N and T-P in the Hwaong Reservoir to less than 3.4 and 0.14 mg L−1, 24 and 41% improvements, respectively, with 90% confidence. Overall, the Monte Carlo simulation in the integrated modelling system was practical for estimating uncertainty and reliable in water quality prediction. The approach described here may allow decisions to be made based on the probability and level of risk, and its application is recommended.
Using the Climate Assessment Tool (CAT) in U.S. EPA BASINS integrated modeling system to assess watershed vulnerability to climate change
Authors: Imhoff J.C. , Kittle J.L. , Gray M.R. , Johnson T.E.
Published: November 2007

During the last century, much of the United States experienced warming temperatures and changes in amount and intensity of precipitation. Changes in future climate conditions present additional risk to water and watershed managers. The most recent release of U.S. EPA's BASINS watershed modeling system includes a Climate Assessment Tool (CAT) that provides new capabilities for assessing impacts of climate change on water resources. The BASINS CAT provides users with the ability to modify historical climate and conduct systematic sensitivity analyses of specific hydrologic and water quality endpoints to changes in climate using the BASINS models (Hydrologic Simulation Program – FORTRAN (HSPF)). These capabilities are well suited for addressing questions about the potential impacts of climate change on key hydrologic and water quality goals using the watershed scale at which most important planning decisions are made.

This paper discusses the concepts that motivated the CAT development effort; the resulting capabilities incorporated into BASINS CAT; and the opportunities that result from integrating climate assessment capabilities into a comprehensive watershed water quality modeling system.
BSM2 Plant-Wide Model construction and comparative analysis with other methodologies for integrated modelling
Authors: Grau P. , Vanrolleghem P. , Ayesa E.
Published: November 2007

In this paper, a new methodology for integrated modelling of the WWTP has been used for the construction of the Benchmark Simulation Model N°2 (BSM2). The transformations-approach proposed in this methodology does not require the development of specific transformers to interface unit process models and allows the construction of tailored models for a particular WWTP guaranteeing the mass and charge continuity for the whole model. The BSM2 PWM constructed as case study, is evaluated by means of simulations under different scenarios and its validity in reproducing water and sludge lines in WWTP is demonstrated. Furthermore the advantages that this methodology presents compared to other approaches for integrated modelling are verified in terms of flexibility and coherence.
Benchmark simulation model no 2: general protocol and exploratory case studies
Authors: Jeppsson U. , Pons M.-N. , Nopens I. , Alex J. , Copp J.B. , Gernaey K.V. , Rosen C. , Steyer J.-P. , Vanrolleghem P.A.
Published: November 2007

Over a decade ago, the concept of objectively evaluating the performance of control strategies by simulating them using a standard model implementation was introduced for activated sludge wastewater treatment plants. The resulting Benchmark Simulation Model No 1 (BSM1) has been the basis for a significant new development that is reported on here: Rather than only evaluating control strategies at the level of the activated sludge unit (bioreactors and secondary clarifier) the new BSM2 now allows the evaluation of control strategies at the level of the whole plant, including primary clarifier and sludge treatment with anaerobic sludge digestion.

In this contribution, the decisions that have been made over the past three years regarding the models used within the BSM2 are presented and argued, with particular emphasis on the ADM1 description of the digester, the interfaces between activated sludge and digester models, the included temperature dependencies and the reject water storage. BSM2-implementations are now available in a wide range of simulation platforms and a ring test has verified their proper implementation, consistent with the BSM2 definition. This guarantees that users can focus on the control strategy evaluation rather than on modelling issues. Finally, for illustration, twelve simple operational strategies have been implemented in BSM2 and their performance evaluated. Results show that it is an interesting control engineering challenge to further improve the performance of the BSM2 plant (which is the whole idea behind benchmarking) and that integrated control (i.e. acting at different places in the whole plant) is certainly worthwhile to achieve overall improvement.
Runoff characteristics and application of HEC-HMS for modelling stormflow hydrograph in an oil palm catchment
Authors: Yusop Z. , Chan C.H. , Katimon A.
Published: November 2007

Rainfall-runoff processes in a small oil palm catchment (8.2 ha) in Johor, Malaysia were examined. Storm hydrographs show rapid responses to rainfall with a short time to peak. The estimated initial hydrologic loss for the oil palm catchment is 5 mm. Despite the low initial loss, the catchment exhibits a high proportion of baseflow, approximately 54% of the total runoff. On an event basis, the stormflow response factor and runoff coefficient ranges from 0.003 to 0.21, and 0.02 to 0.44, respectively. Peakflow and stormflow volume were moderately correlated with rainfall. The hydrographs were satisfactorily modelled using the Hydrologic Engineering Centre–Hydrologic Modelling System (HEC-HMS). The efficiency indexes of the calibration and validation exercises are 0.81 and 0.82, respectively. Based on these preliminary findings, it could be suggested that an oil palm plantation would be able to serve reasonably well in regulating basic hydrological functions.
Influence of wastewater composition on denitrification and biological P-removal in the S-DN-P-process: Effects of different substrates (a)
Authors: Choi Hee-Jeong , Choi Chul-Ho , Lee Seung-Mok
Published: November 2007

The influence of the wastewater composition on the denitrification and biological P-elimination in the Sorption Denitrification P-eliminations Process (S-DN-P-process) was examined. Batch type experiments were performed to examine the influence of various substrates. Among the three different substrates prepared, only 11% CODfilt was taken up from starch containing wastewater (starch preparation). Acetate is an easily degradable substrate for the biological P-elimination, and showed ca. 30% more acetate was taken up compared to the raw wastewater (wastewater preparation). Starch is a barely degradable substance, because it must be hydrolysed before digestion. Starch initially sorbs slowly (approximately 30 min), and may be hydrolysed during this time. During the investigations, the biological P-elimination and the denitrification were found to be dependent on the wastewater composition. The P-elimination rate was determined to be 38% with the acetate preparation, while a P-elimination of 6% was obtained with the starch preparation. The wastewater preparation showed a P-elimination of 56%, the value of which was almost 18% more than the acetate preparation. The biological P-elimination and denitrification depend not only on the dissolved parts in the wastewater, but also on the undissolved content.
Large GLUT4 Vesicles Are Stationary While Locally and Reversibly Depleted During Transient Insulin Stimulation of Skeletal Muscle of Living Mice
Authors: Lauritzen Hans P.M.M. , Galbo Henrik , Brandauer Josef , Goodyear Laurie J. , Ploug Thorkil
Published: November 2007

OBJECTIVE—Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady-state recycling and subsequent re-internalization of GLUT4 on an insulin bolus.

RESEARCH DESIGN AND METHODS—A confocal imaging technique was used in GLUT4-enhanced green fluorescent protein–transfected superficial muscle fibers in living mice.

RESULTS—During the first 30 min of insulin stimulation, very few superficially or deeply located GLUT4 storage vesicles (>1 μm) moved in toto. Rather, big vesicles were stationary in their original position at sarcolemma or t-tubules and were locally depleted of GLUT4 by budding off of smaller vesicles. Photobleaching experiments revealed that during initial translocation and steady-state recycling, GLUT4 microvesicles (<1 μm) move from perinuclear GLUT4 depots out along the plasma membrane. Furthermore, after photobleaching of t-tubule areas, recovery of GLUT4 was slow or absent, indicating no recycling of GLUT4 from perinuclear or adjacent (1 μm) or more distant (20 μm) t-tubule areas. During waning of insulin effect, GLUT4 was re-internalized to basal stores with a delay in t-tubules compared with sarcolemma, probably reflecting delayed disappearance of insulin from t-tubules.

CONCLUSIONS—In skeletal muscle, insulin reversibly stimulates local depletion of GLUT4 storage vesicles at sarcolemma and t-tubules rather than inducing movement of intact storage vesicles. During steady-state stimulation, recycling of GLUT4-containing microvesicles over longer distances (10–20 μm) takes place between perinuclear depots and sarcolemma but not at t-tubules.
Attenuation of Interstitial Fibrosis and Tubular Apoptosis in db/db Transgenic Mice Overexpressing Catalase in Renal Proximal Tubular Cells
Authors: Brezniceanu Marie-Luise , Liu Fang , Wei Chih-Chang , Chénier Isabelle , Godin Nicolas , Zhang Shao-Ling , Filep Janos G. , Ingelfinger Julie R. , Chan John S.D.
Published: November 2007

OBJECTIVE—The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg).

RESEARCH DESIGN AND METHODS—Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology and apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels.

RESULTS—db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type IV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice.

CONCLUSIONS—Our results indicate a crucial role for intra-renal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation.
Impaired Glucose-Stimulated Insulin Secretion Is Coupled With Exocrine Pancreatic Lesions in the Cohen Diabetic Rat
Authors: Weksler-Zangen Sarah , Raz Itamar , Lenzen Sigurd , Jörns Anne , Ehrenfeld Shira , Amir Gail , Oprescu Andrei , Yagil Yoram , Yagil Chana , Zangen David H. , Kaiser Nurit
Published: November 2007

OBJECTIVE—The Cohen diabetes–sensitive rat develops postprandial hyperglycemia when fed a high-sucrose, copper-poor diet, whereas the Cohen diabetes–resistant rat maintains normoglycemia. The pathophysiological basis of diabetes was studied in the Cohen diabetic rat centering on the interplay between the exocrine and endocrine compartments of the pancreas.

RESEARCH DESIGN AND METHODS—Studies used male Cohen diabetes–sensitive and Cohen diabetes–resistant rats fed 1-month high-sucrose, copper-poor diet. Serum insulin and glucose levels were measured during glucose and insulin tolerance tests. The pancreas was evaluated for weight, insulin content, macrophage, and fat infiltration. Glucose-stimulated insulin secretion (GSIS) was determined in isolated perfused pancreas and in islets.

RESULTS—Hyperglycemic Cohen diabetes–sensitive rats exhibited reduced pancreatic weight with lipid deposits and interleukin-1β–positive macrophage infiltration in the exocrine pancreas. Islet morphology was preserved, and total pancreatic insulin content did not differ from that of Cohen diabetes–resistant rats. Lipids did not accumulate in skeletal muscle, nor was insulin resistance observed in hyperglycemic Cohen diabetes–sensitive rats. Intravenous glucose-tolerance test revealed markedly elevated glucose levels associated with diminished insulin output. Insulin release was induced in vivo by the non-nutrient secretagogues arginine and tolbutamide, suggesting a selective unresponsiveness to glucose. Decreased GSIS was observed in the isolated perfused pancreas of the hyperglycemic Cohen diabetes–sensitive rat, whereas islets isolated from these rats exhibited glucose-dependent insulin secretion and proinsulin biosynthesis.

CONCLUSIONS—The association of the in vivo insulin secretory defect with lipid accumulation and activated macrophage infiltration in the exocrine pancreas suggests that changes in the islet microenvironment are the culprit in the insulin secretory malfunction observed in vivo.
Impact of Common Type 2 Diabetes Risk Polymorphisms in the DESIR Prospective Study
Authors: Vaxillaire Martine , Veslot Jacques , Dina Christian , Proença Christine , Cauchi Stéphane , Charpentier Guillaume , Tichet Jean , Fumeron Frédéric , Marre Michel , Meyre David , Balkau Beverley , Froguel Philippe ,   for the DESIR Study Group
Published: November 2007

OBJECTIVE— The emerging picture of type 2 diabetes genetics involves differently assembled gene variants, each modestly increasing risk with environmental exposure. However, the relevance of these genes for disease prediction has not been extensively tested.

RESEARCH DESIGN AND METHODS— We analyzed 19 common polymorphisms of 14 known candidate genes for their contribution to prevalence and incidence of glucose intolerance in the DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) prospective study of middle-aged Caucasian subjects, including 3,877 participants (16.8% with hyperglycemia and 7.9% with diabetes after the 9-year study).

RESULTS— The GCK (Glucokinase) −30A allele was associated with increased type 2 diabetes risk at the end of the follow-up study (adjusted OR 1.34 [95% CI 1.07–1.69]) under an additive model, as supported in independent French diabetic case subjects (OR 1.22, P = 0.007), with increased fasting glycemia (0.85% per A allele, P = 6 × 10−5) and decreased homeostasis model assessment of β-cell function (4%, P = 0.0009). IL6 (Interleukin- 6) −174 G/C interacts with age in disease risk and modulates fasting glycemia according to age (1.36% decrease over 56 years, P = 5 × 10−5). These polymorphisms together with KCNJ11 (Kir6.2)-E23K and TCF7L2-rs7903146 may predict diabetes incidence in the DESIR cohort. Each additional risk allele at GCK, TCF7L2, and IL6 increased risk by 1.34 (P = 2 × 10−6), with an OR of 2.48 (95% CI 1.59–3.86), in carriers of at least four at-risk alleles compared with those with none or one risk allele.

CONCLUSIONS— Our data confirm several at-risk polymorphisms for type 2 diabetes in a general population and demonstrate that prospective studies are valuable designs to complement classical genetic approaches.
Insulin Action in the Double Incretin Receptor Knockout Mouse
Authors: Ayala Julio E. , Bracy Deanna P. , Hansotia Tanya , Flock Grace , Seino Yutaka , Wasserman David H. , Drucker Daniel J.
Published: November 2007

OBJECTIVE—The incretins glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide have been postulated to play a role in regulating insulin action, although the mechanisms behind this relationship remain obscure. We used the hyperinsulinemic-euglycemic clamp to determine sites where insulin action may be modulated in double incretin receptor knockout (DIRKO) mice, which lack endogenous incretin action.

RESEARCH DESIGN AND METHODS—DIRKO and wild-type mice were fed regular chow or high-fat diet for 4 months. Clamps were performed on 5-h–fasted, conscious, unrestrained mice using an arterial catheter for sampling.

RESULTS—Compared with wild-type mice, chow and high fat–fed DIRKO mice exhibited decreased fat and muscle mass associated with increased energy expenditure and ambulatory activity. Clamp rates of glucose infusion (GIR), endogenous glucose production (endoRa), and disappearance (Rd) were not different in chow-fed wild-type and DIRKO mice, although insulin levels were lower in DIRKO mice. Liver Akt expression was decreased but Akt activation was increased in chow-fed DIRKO compared with wild-type mice. High-fat feeding resulted in fasting hyperinsulinemia and hyperglycemia in wild-type but not in DIRKO mice. GIR, suppression of endoRa, and stimulation of Rd were inhibited in high fat–fed wild-type mice but not in DIRKO mice. High-fat feeding resulted in impaired tissue glucose uptake (Rg) in skeletal muscle of wild-type mice but not of DIRKO mice. Liver and muscle Akt activation was enhanced in high fat–fed DIRKO compared with wild-type mice.

CONCLUSIONS—In summary, DIRKO mice exhibit enhanced insulin action compared with wild-type mice when fed a regular chow diet and are protected from high-fat diet–induced obesity and insulin resistance.
Key Role for AMP-Activated Protein Kinase in the Ventromedial Hypothalamus in Regulating Counterregulatory Hormone Responses to Acute Hypoglycemia
Authors: McCrimmon Rory J. , Shaw Margaret , Fan Xiaoning , Cheng Haiying , Ding Yuyan , Vella Monica C. , Zhou Ligang , McNay Ewan C. , Sherwin Robert S.
Published: November 2007

OBJECTIVE—To examine in vivo in a rodent model the potential role of AMP-activated protein kinase (AMPK) within the ventromedial hypothalamus (VMH) in glucose sensing during hypoglycemia.

RESEARCH DESIGN AND METHODS—Using gene silencing technology to selectively downregulate AMPK in the VMH, a key hypothalamic glucose-sensing region, we demonstrate a key role for AMPK in the detection of hypoglycemia. In vivo hyperinsulinemic-hypoglycemic (50 mg dl−1) clamp studies were performed in awake, chronically catheterized Sprague-Dawley rats that had been microinjected bilaterally to the VMH with an adeno-associated viral (AAV) vector expressing a short hairpin RNA for AMPKα.

RESULTS—In comparison with control studies, VMH AMPK downregulation resulted in suppressed glucagon (∼60%) and epinephrine (∼40%) responses to acute hypoglycemia. Rats with VMH AMPK downregulation also required more exogenous glucose to maintain the hypoglycemia plateau and showed significant reductions in endogenous glucose production and whole-body glucose uptake.

CONCLUSIONS—We conclude that AMPK in the VMH plays a key role in the detection of acute hypoglycemia and initiation of the glucose counterregulatory response.
Fas-Associated Death Receptor Signaling Evoked by Human Amylin in Islet β-Cells
Authors: Zhang Shaoping , Liu Hong , Yu Hua , Cooper Garth J.S.
Published: November 2007

OBJECTIVE— Aggregation of human amylin (hA) into β-sheet–containing oligomers is linked to islet β-cell dysfunction and the pathogenesis of type 2 diabetes. Here, we investigated possible contributions of Fas-associated death-receptor signaling to the mechanism of hA-evoked β-cell apoptosis.

RESEARCH DESIGN AND METHODS— We measured responses to hA in isolated mouse islets and two insulinoma cell lines, wherein we measured Fas/Fas ligand (FasL) and Fas-associated death domain (FADD) expression by quantitative RT-PCR, Western blotting, and immunofluorescence staining. We used two anti-Fas/FasL blocking antibodies and the Fas/FasL antagonist Kp7–6 to probe roles of Fas interactions in the regulation of apoptosis in hA-treated β-cells and measured Kp7–6–mediated effects on β-sheet formation and aggregation using circular dichroism and thioflavin-T binding.

RESULTS— hA treatment stimulated Fas and FADD expression in β-cells. Both blocking antibodies suppressed hA-evoked apoptosis but did not modify its aggregation. Therefore, Fas receptor interactions played a critical role in induction of this pathway. Interestingly, hA-evoked β-cell apoptosis was suppressed and rescued by Kp7–6, which also impaired hA β-sheet formation.

CONCLUSIONS— This is the first report linking hA-evoked induction and activation of Fas and FADD to β-cell apoptosis. We have identified a Fas/FasL antagonist, Kp7–6, as a potent inhibitor of hA aggregation and related β-cell death. These results also support an interaction between hA and Fas on the surface of apoptotic β-cells. Increased expression and activation of Fas in β-cells could constitute a molecular event common to the pathogenesis of both type 1 and type 2 diabetes, although the mode of pathway activation may differ between these common forms of diabetes.
High Visceral and Low Abdominal Subcutaneous Fat Stores in the Obese Adolescent
Authors: Taksali Sara E. , Caprio Sonia , Dziura James , Dufour Sylvie , Calí Anna M.G. , Goodman T. Robin , Papademetris Xenophon , Burgert Tania S. , Pierpont Bridget M. , Savoye Mary , Shaw Melissa , Seyal Aisha A. , Weiss Ram
Published: November 2007

OBJECTIVE— To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome.

RESEARCH DESIGN AND METHODS— We stratified our multi-ethnic cohort of 118 obese adolescents into tertiles based on the proportion of abdominal fat in the visceral depot. Abdominal and liver fat were measured by magnetic resonance imaging and muscle lipid (intramyocellular lipid) by proton magnetic resonance spectroscopy.

RESULTS— There were no differences in age, BMI Z score, or fat-free mass across tertiles. However, as the proportion of visceral fat increased across tertiles, BMI and percentage of fat and subcutaneous fat decreased, while hepatic fat increased. In addition, there was an increase in 2-h glucose, insulin, c-peptide, triglyceride levels, and insulin resistance. Notably, both leptin and total adiponectin were significantly lower in tertile 3 than 1, while C-reactive protein and interleukin-6 were not different across tertiles. There was a significant increase in the odds ratio for the metabolic syndrome, with subjects in tertile 3 5.2 times more likely to have the metabolic syndrome than those in tertile 1.

CONCLUSIONS— Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications and are at a high risk of having the metabolic syndrome.
Insulin Signaling Stimulates Insulin Transport by Bovine Aortic Endothelial Cells
Authors: Wang Hong , Wang Aileen X. , Liu Zhenqi , Barrett Eugene J.
Published: November 2007

OBJECTIVE—In vivo evidence suggests that insulin entry into skeletal muscle is rate limiting for its overall metabolic action. Although there has been controversy regarding whether insulin crosses the endothelium by a passive (transcellular or paracellular) or mediated process, accumulating data favor the latter. Here, we addressed whether insulin signaling within the endothelial cell is required for the first step of transendothelial insulin transport: its uptake by the endothelial cell.

RESEARCH DESIGN AND METHODS—Bovine aortic endothelial cells (bAECs) were incubated in serum-free medium for 6 h before addition of 50 nmol/l fluoroisothiocyanate (FITC)-labeled insulin for 30 min, and uptake of FITC insulin was quantified by confocal immunocytochemistry.

RESULTS—Cellular insulin uptake was temperature dependent, being greater at 37 vs. 4°C (P < 0.05). Inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) (wortmannin), mitogen-activated protein kinase kinase (MEK) (PD98059), the cSrc-family tyrosine kinase (PP1), or the insulin receptor tyrosine kinase (genistein) markedly diminished FITC insulin uptake (P < 0.05 for each). In contrast, inhibiting the phosphotyrosine phosphatase protein tyrosine phosphatase 1B further stimulated insulin uptake (P < 0.05). Addition of the inflammatory cytokine 5 ng/ml tumor necrosis factor-α (TNF-α) for 6 h before adding 50 nmol/l FITC insulin diminished insulin uptake significantly (P < 0.05). This inhibitory effect of TNF-α could be partially reversed by a specific p38 MAPK inhibitor (SB203580).

CONCLUSIONS—Insulin uptake by bAECs requires intact insulin signaling via both the PI 3-kinase and MEK signaling cascades and the cSrc-family tyrosine kinases, and endothelial cell insulin uptake is sensitive to cytokine-induced insulin resistance.
Increased Glucose Levels Are Associated With Episodic Memory in Nondiabetic Women
Authors: Rolandsson Olov , Backeström Anna , Eriksson Sture , Hallmans Göran , Nilsson Lars-Göran
Published: November 2007

OBJECTIVE—Patients with type 2 diabetes have an increased risk of a reduction in cognitive function. We investigated the hypothesis that plasma glucose is associated with a reduction in episodic and/or semantic memory already in nondiabetic subjects.

RESEARCH DESIGN AND METHODS—We linked two large population-based datasets in Sweden: the Betula study, in which a random sample from the population aged 35–85 years was investigated for cognitive function, including episodic and semantic memory; and the Västerbotten Intervention Program, a health survey with subjects aged 40, 50, and 60 years, that includes measuring of fasting and 2-h plasma glucose, along with other risk factors for diabetes and cardiovascular disease. We identified 411 (179 men and 232 women, mean age 50.6 ± 8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within 6 months.

RESULTS—Women had better episodic (score 7.37 ± 1.42) and semantic memory (score 16.05 ± 2.76) than men (score 6.59 ± 1.29 and 15.15 ± 2.92, respectively, P < 0.001 for both). In an adjusted multivariate model, fasting plasma glucose (fPG) and 2-h plasma glucose (2hPG) were significantly negatively associated with episodic memory (fPG: B −0.198, SE 0.068, β −0.209, P = 0.004; and 2hPG: B −0.061, SE 0.031, β −0.148, P = 0.048, respectively) in women but not in men. The association was not found in relation to semantic memory.

CONCLUSIONS—We conclude that an increase in plasma glucose is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels.
Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs
Authors: Yu Hong , Bao En-dong , Zhao Ru-qian , Lv Qiong-xia
Published: November 2007

Objective—To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs.

Animals—24 pigs (mean weight, 20 ± 1 kg).

Procedures—Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA.

Results—No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs.

Conclusions and Clinical Relevance—Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.
Comparison of insertion characteristics of two types of hydroxyapatite-coated and uncoated positive profile transfixation pins in the third metacarpal bone of horses
Authors: Zacharias Josh R. , Lescun Timothy B. , Moore George E. , Van Sickle David C.
Published: November 2007

Objective—To determine the effect of 2 hydroxyapatite pin coatings on heat generated at the bone-pin interface and torque required for insertion of transfixation pins into cadaveric equine third metacarpal bone.

Sample Population—Third metacarpal bone pairs from 27 cadavers of adult horses.

Procedures—Peak temperature of the bone at the cis-cortex and the hardware and pin at the trans-cortex was measured during insertion of a plasma-sprayed hydroxyapatite (PSHA)—coated, biomimetic hydroxyapatite (BMHA)—coated, or uncoated large animal transfixation pin. End-insertional torque was measured for each pin. The bone-pin interface was examined grossly and histologically for damage to the bone and coating.

Results—The BMHA-coated transfixation pins had similar insertion characteristics to uncoated pins. The PSHA-coated pins had greater mean peak bone temperature at the cis-cortex and greater peak temperature at the trans-cortex (70.9 ± 6.4°C) than the uncoated pins (38.7 ± 8.4°C). The PSHA-coated pins required more insertional torque (10,380 ± 5,387.8 Nmm) than the BMHA-coated pins (5,123.3 ± 2,296.9 Nmm). Four of the PSHA-coated pins became immovable after full insertion, and 1 gross fracture occurred during insertion of this type of pin.

Conclusions and Clinical Relevance—The PSHA coating was not feasible for use without modification of presently available pin hardware. The BMHA-coated pins performed similarly to uncoated pins. Further testing is required in an in vivo model to determine the extent of osteointegration associated with the BMHA-coated pins in equine bone.
Effects of changes in loading conditions and heart rate on the myocardial performance index in cats
Authors: Hori Yasutomo , Uechi Masami , Indou Atsuko
Published: November 2007

Objective—To evaluate the effect of changes in hemodynamics on the myocardial performance index (MPI) in cats.

Animals—6 mixed-breed cats.

Procedures—Cats were anesthetized by administration of thiopental sodium; anesthesia was maintained by administration of isoflurane. Systolic arterial pressure and central venous pressure were measured by use of catheters, and heart rate was controlled by right atrial pacing. Afterload was increased by balloon occlusion of the descending aorta, and preload was increased by IV infusion of lactated Ringer's solution at a rate of 40 mL/kg/h. Echocardiography was performed for each condition.

Results—Atrial pacing significantly increased heart rate. The MPI did not change with heart rate. Arterial pressure and MPI increased significantly during aortic occlusion. The IV infusion increased fractional shortening but did not change the MPI. Multiple regression analysis revealed that the MPI was not affected by heart rate, systolic arterial pressure, central venous pressure, fractional shortening, or velocity of the E wave.

Conclusions and Clinical Relevance—The MPI can be used to assess cardiac function in healthy cats. The MPI is independent of heart rate and systolic arterial pressure but is sensitive to changes in afterload.
Assessment of exercise-induced alterations in neutrophil function in horses
Authors: Donovan Douglas C. , Jackson Christie A. , Colahan Patrick T. , Norton Natalie N. , Clapper Joan L. , Moore James N. , Hurley David J.
Published: November 2007

Objective—To evaluate the effects of a standardized exercise test to exhaustion in horses on leukocyte function ex vivo.

Animals—6 Thoroughbred geldings.

Procedures—Blood samples were obtained from each horse before exercise; at exhaustion (termed failure); and at 2, 6, 24, 48, and 72 hours after exercise to evaluate hematologic changes, rate of leukocyte apoptosis, and leukocyte production of reactive oxygen species (ROS) ex vivo. To assess leukocyte function, leukocyte ROS production in response to stimulation with lipopolysaccharide, peptidoglycan, zymosan, and phorbol myristate acetate was evaluated. Apoptosis was evaluated via assessment of caspase activity in leukocyte lysates.

Results—In response to lipopolysaccharide, production of ROS by leukocytes was significantly increased at 2 hours and remained increased (albeit not significantly) at 6 hours after exercise, compared with the preexercise value. In the absence of any stimulus, leukocyte ROS production was significantly increased at 6 and 24 hours after exercise. In contrast, ROS production in response to phorbol myristate acetate was significantly decreased at 6, 24, and 72 hours after exercise. Leukocyte ROS production induced by zymosan or peptidoglycan was not altered by exercise. Leukocytosis was evident for 24 hours after exercise, and neutrophilia was detected during the first 6 hours. A significant increase in the rate of leukocyte apoptosis was detected at failure and 72 hours after exercise.

Conclusions and Clinical Relevance—Results indicated that strenuous exercise undertaken by horses causes alterations in innate immune system functions, some of which persist for as long as 72 hours after exercise.
Early laminar events involving endothelial activation in horses with black walnut– induced laminitis
Authors: Loftus John P. , Black Samuel J. , Pettigrew Amanda , Abrahamsen Eric J. , Belknap James K.
Published: November 2007

Objective—To determine proinflammatory gene expression, endothelial adhesion molecule gene expression, and matrix metalloproteinase (MMP) concentrations in laminar specimens at 1.5 hours after administration of black walnut extract (BWE) and to compare these values with later time points.

Animals—25 horses.

Procedures—After nasogastric administration of BWE, anesthesia was induced at 1.5 hours in early time point (ETP) horses (n = 5), between 3 and 4 hours in developmental time point horses (5), and between 9 and 10 hours in acute onset of lameness time point horses (5). Anesthesia was induced at 3 and 10 hours after nasogastric administration of water in 2 groups of control horses (3-hour control group, n = 5; 10-hour control group, 5). Real-time quantitative PCR assay was performed on laminar specimens from control and ETP horses for cyclooxygenase (COX)-1, COX-2, interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-8, IL-10, MMP-2, and MMP-9 gene expression; and on laminar specimens from all groups for endothelial adhesion molecules, intercellular adhesion molecule (ICAM)-1, and E-selectin gene expression. Leukocyte emigration was assessed via CD13 immunohistochemistry, and gelatinase accumulation was determined by gelatin zymography.

Results—Laminar concentrations of IL-1β, IL-6, IL-8, COX-2, ICAM-1, and E-selectin mRNA were significantly increased in ETP horses, compared with control horses. Concentrations of IL-1β, IL-8, ICAM-1, and E-selectin mRNA peaked at 1.5 hours. In ETP horses, leukocyte emigration was present in 3 of 5 horses and pro–MMP-9 was detected in 2 of 5 horses.

Conclusions and Clinical Relevance—Results indicated that endothelial activation and laminar inflammation are early events in laminitis; MMP accumulation likely is a downstream event.