bluuebunny/crossref_metadata_2025 huggingface dataset:
3D geometric modelling of an external orogenic domain: a case history from the western Alps (massif de Morges, Pelvoux)
Authors: Calcagno Philippe , Lazarre Joëlle , Courrioux Gabriel , Ledru Patrick
Published: August 2007

Describing the 3D geometry of geological surfaces is a fundamental step to infer their structural history, especially when they have recorded successive deformation phases. This study aims at testing the contribution of 3D modelling to the understanding of orogenic domains. It focuses on the cover/basement contact of an External Crystalline Massif of the French Alps considered as a marker of the finite deformation at orogen scale. This contact is observable in outliers of Mesozoic cover in the test area located in the Massif de Morges (Pelvoux Massif).

A 3D geometric model has been built from map and cross-section data derived from field structural and kinematic observations using STRIM software (Matra Datavision). 3D modelling ensures geometric consistency of geological interpretation. Moreover, the model has been unfolded to restore surfaces and to quantify shortening. Together with field analyses, those results show that two sub-perpendicular phases of deformation related to the Alpine cycle have occurred. The first and main one consisted of the NNE-SSW inversion of previous extensional paleo-faults that controlled the geometry of the Tethyan margin. The second one was an E-W compression of post-Early Oligocene age.
Ostracods and lithofacies of the Middle/Upper Devonian boundary stratotype (Puech de la Suque, Montagne Noire, France)
Authors: Casier Jean-Georges , Préat Alain
Published: August 2007

This paper discusses ostracods and their environmental setting close to the Givetian/Frasnian boundary in the Puech de la Suque Global Stratotype Section and Point. The ostracod fauna belongs exclusively to the Eifelian mega-assemblage and is largely dominated by Podocopina instars. Consequently, the majority of the 33 species recognised and illustrated is described in open nomenclature. The abundance of instars also indicates that most of beds are related to storm deposition. The composition of the fauna suggests a regression in the late Givetian followed by a transgression at the beginning of the Frasnian. Only one ostracod assemblage collected in the upper part of the section indicates a deeper setting below the storm wave base. Eight taxa disappeared in two steps near the Givetian / Frasnian boundary, probably in relation to the Frasnes Event.

The sedimentological analysis confirms that the section is constituted principally of storm deposits and reveals in addition the presence of numerous reddish hardgrounds highlighting an important condensation of the sequence.
First occurrence of the ‘hunting hyena’ Chasmaporthetes in the Late Miocene fossil bearing localities of Toros Menalla, Chad (Africa)
Authors: de Bonis Louis , Peigne Stephane , Likius Andossa , Makaye Hassane T. , Brunet Michel , Vignaud Patrick
Published: August 2007

Late Miocene localities of Toros Menalla (Chad) have yielded many bones of fossil vertebrates with a lot of mammalian remains. Among the mammals, there are several Carnivora taxa, especially hyenids. The family Hyaenidae is very well developed during this period with classical bone crusher species but also with flesh eater taxa which are called hunting hyenas. The genus Chasmaporthetes is one of these taxa. It was described from North America, Asia, Euro-pa and South Africa but it is recorded for the first time in central Africa. The Chadian specimens are close to the South African species C. australis (Hendey, 1974) but differs through some morphological and metrical details. C. australis is a huge hunting hyena, a little bigger than the extant species Crocuta crocuta, the spotted hyena. An isolated premolar recorded in the locality Sahabi (Libya) belongs probably to the same group. The spreading of this large hunting species is probably correlated with the abundance of large ungulates in the local faunas.
Possible Mechanisms Leading to a Delay in Carbon Stock Recovery after Land Use Change
Authors: Arai Hirotsugu , Tokuchi Naoko , Koba Keisuke
Published: August 2007

Changes in land use sometimes lead to soil C loss, and a long time may be required for the C stock to recover to initial levels. Thus, it is important to evaluate the mechanisms related to accumulation of newly input C following land use changes. In this study, we sought to determine the signature of newly input C in the soil profile after land use change. We used stable and radioactive C isotopes with soil fractionation methods in a C3 coniferous plantation converted from C4 grassland in Japan. The difference in δ13C values between the surface litter and the soil organic carbon (SOC) below the litter was 5‰ or greater; this large isotopic difference was attributed to rapid decomposition in the litter layer and preservation of C derived from the previous C4 vegetation. Most SOC Δ14C values were negative throughout the soil profile, suggesting that most of the SOC in the soil profile was recalcitrant and had been preserved for a long time. Only the surface sand values were slightly positive. These results suggest that most newly input C is consumed at the soil surface. The low ability of these soils to preserve newly input C is one factor in the slow recovery of soil C.
Tillage Management Alters Surface Soil Organic Matter Composition: A Pyrolysis Mass Spectroscopy Study
Authors: Sleutel Steven , Kader Mohammed Abdul , Leinweber Peter , D'Haene Karoline , De Neve Stefaan
Published: August 2007

We examined the effects of 10 yr of reduced tillage (RT) management, compared with conventional tillage (CT), on the chemical composition of soil organic matter (SOM) using a combination of physical fractionation and pyrolysis–field ionization mass spectroscopy (Py–FIMS). Surface soil samples (0–10 cm), which were collected from two adjacent CT and RT managed fields, were separated into particulate organic matter (POM) fractions and sand, silt, and clay size separates. Higher amounts of C (77%) and N (64%) were observed in all size separates of the RT soil and, in particular, the proportion of intramicroaggregate POM was two times as large as in the CT soil. The Py–FIMS spectra showed that larger proportions of free fatty acids, sterols, and N‐containing compounds were present in the RT soil's sand fraction than in the CT soil. Similar observations were also made for both free and intramicroaggregate POM fractions. In the silt and clay size fractions, no substantial differences in SOM composition were measured between tillage treatments, except that the RT soil's clay fraction had a higher proportion of N‐containing compounds and a lower proportion of alkylaromatics. Ratios of carbohydrate hexose to pentose subunits and of lignin monomers + phenols to lignin dimers confirmed a less decomposed character of the SOM in the silt and clay size fractions of the RT soil. These observations can be logically linked to the reduced mixing of crop residues and manure in the soil profile and higher surface soil microbial biomass under RT.
Climate Variability Controls on Unsaturated Water and Chemical Movement, High Plains Aquifer, USA
Authors: Gurdak Jason J. , Hanson Randall T. , McMahon Peter B. , Bruce Breton W. , McCray John E. , Thyne Geoffrey D. , Reedy Robert C.
Published: August 2007

Responses in the vadose zone and groundwater to interannual, interdecadal, and multidecadal climate variability have important implications for groundwater resource sustainability, yet they are poorly documented and not well understood in most aquifers of the USA. This investigation systematically examines the role of interannual to multidecadal climate variability on groundwater levels, deep infiltration (3–23 m) events, and downward displacement (>1 m) of chloride and nitrate reservoirs in thick (15–50 m) vadose zones across the regionally extensive High Plains aquifer. Such vadose zone responses are unexpected across much of the aquifer given a priori that unsaturated total‐potential profiles indicate upward water movement from the water table toward the root zone, mean annual potential evapotranspiration exceeds mean annual precipitation, and millennia‐scale evapoconcentration results in substantial vadose zone chloride and nitrate reservoirs. Using singular spectrum analysis (SSA) to reconstruct precipitation and groundwater level time‐series components, variability was identified in all time series as partially coincident with known climate cycles, such as the Pacific Decadal Oscillation (PDO) (10–25 yr) and the El Niño/Southern Oscillation (ENSO) (2–6 yr). Using these lag‐correlated hydrologic time series, a new method is demonstrated to estimate climate‐varying unsaturated water flux. The results suggest the importance of interannual to interdecadal climate variability on water‐flux estimation in thick vadose zones and provide better understanding of the climate‐induced transients responsible for the observed deep infiltration and chemical‐mobilization events. Based on these results, we discuss implications for climate‐related sustainability of the High Plains aquifer.
Regional Differences in Climate Change Impacts on Groundwater and Stream Discharge in Denmark
Authors: van Roosmalen Lieke , Christensen Britt S. B. , Sonnenborg Torben O.
Published: August 2007

Regional impact studies of the effects of future climate change are necessary because projected changes in meteorological variables vary regionally, and different hydrological systems can react in various ways to the same changes. In this study the effects of climate change on groundwater recharge, storage, and discharge to streams are compared in two geologically and climatologically different regions in Denmark. Outputs are used for the periods 1961 to 1990 and 2071 to 2100 from a regional climate model representing the Intergovernmental Panel on Climate Change (IPCC) scenarios A2 and B2. A physically based, distributed hydrological model simulates changes in groundwater head, recharge, and discharge. Precipitation, temperature, and reference evapotranspiration increased for both the A2 and B2 scenarios. This results in a significant increase in mean annual net precipitation, but with decreased values in the summer months. The magnitude of the hydrological response to the simulated climate change is highly dependent on the geological setting of the model area. In the Jylland area, characterized by sandy top soils and large interconnected aquifers, groundwater recharge increased significantly, resulting in higher groundwater levels and increasing groundwater–river interaction. On Sjaelland, where the topsoil is dominated by low‐permeability soils and the aquifers are protected by thick clay layers of regional extent, only minor changes in groundwater levels are predicted. The primary effect in this area is the change in stream discharge, caused by changes in drain flow and overland flow, with up to 50% increase in winter and 50% decrease in summer. This study shows the added value of studying different climate scenarios and hydrological systems, so that the simulated effects can be compared both qualitatively and quantitatively.
Scale Dependence of the Effective Matrix Diffusion Coefficient: Some Analytical Results
Authors: Liu H. H. , Zhang Y. Q. , Molz F. J.
Published: August 2007

Matrix diffusion is an important process affecting solute transport in fractured rock, and the matrix diffusion coefficient is a key parameter for describing this process. Previous studies have indicated that effective matrix diffusion coefficient values obtained from a number of field tracer tests are enhanced in comparison with local values and may increase with test scale. In this communication, we develop analytical expressions for the effective matrix diffusion coefficient for two simple fracture–matrix systems and demonstrate that heterogeneities in the rock matrix at different scales may contribute to the scale dependence of the effective matrix diffusion coefficient.
A Review of Multidimensional, Multifluid, Intermediate‐Scale Experiments: Flow Behavior, Saturation Imaging, and Tracer Detection and Quantification
Authors: Oostrom M. , Dane J. H. , Wietsma T. W.
Published: August 2007

A review is presented of original multidimensional, intermediate‐scale experiments involving nonaqueous phase liquid (NAPL) flow behavior, imaging, and detection and quantification with solute tracers. In a companion paper (Oostrom et al., 2006a), experiments related to aqueous dissolution and enhanced remediation were discussed. The experiments investigating flow behavior include infiltration and redistribution experiments with both light and dense NAPLs in homogeneous and heterogeneous porous medium systems. The techniques used for NAPL saturation mapping for intermediate‐scale experiments include photon‐attenuation methods such as gamma and X‐ray techniques, and photographic methods such as the light reflection, light transmission, and multispectral image analysis techniques. Solute tracer methods used for detection and quantification of NAPL in the subsurface are primarily limited to variations of techniques comparing the behavior of conservative and partitioning tracers. Besides a discussion of the experimental efforts, recommendations for future research at this laboratory scale are provided.
Direct Effect of Cholesterol on Insulin Secretion
Authors: Hao Mingming , Head W. Steven , Gunawardana Subhadra C. , Hasty Alyssa H. , Piston David W.
Published: August 2007

OBJECTIVE—Type 2 diabetes is often accompanied by abnormal blood lipid and lipoprotein levels, but most studies on the link between hyperlipidemia and diabetes have focused on free fatty acids (FFAs). In this study, we examined the relationship between cholesterol and insulin secretion from pancreatic β-cells that is independent of the effects of FFAs.

RESEARCH DESIGN AND METHODS—Several methods were used to modulate cholesterol levels in intact islets and cultured β-cells, including a recently developed mouse model that exhibits elevated cholesterol but normal FFA levels. Acute and metabolic alteration of cholesterol was done using pharmacological reagents.

RESULTS—We found a direct link between elevated serum cholesterol and reduced insulin secretion, with normal secretion restored by cholesterol depletion. We further demonstrate that excess cholesterol inhibits secretion by downregulation of metabolism through increased neuronal nitric oxide synthase dimerization.

CONCLUSIONS—This direct effect of cholesterol on β-cell metabolism opens a novel set of mechanisms that may contribute to β-cell dysfunction and the onset of diabetes in obese patients.
Free Fatty Acid–Induced Reduction in Glucose-Stimulated Insulin Secretion
Authors: Oprescu Andrei I. , Bikopoulos George , Naassan Anthony , Allister Emma M. , Tang Christine , Park Edward , Uchino Hiroshi , Lewis Gary F. , Fantus I. George , Rozakis-Adcock Maria , Wheeler Michael B. , Giacca Adria
Published: August 2007

OBJECTIVE—An important mechanism in the pathogenesis of type 2 diabetes in obese individuals is elevation of plasma free fatty acids (FFAs), which induce insulin resistance and chronically decrease β-cell function and mass. Our objective was to investigate the role of oxidative stress in FFA-induced decrease in β-cell function.

RESEARCH DESIGN AND METHODS—We used an in vivo model of 48-h intravenous oleate infusion in Wistar rats followed by hyperglycemic clamps or islet secretion studies ex vivo and in vitro models of 48-h exposure to oleate in islets and MIN6 cells.

RESULTS—Forty-eight–hour infusion of oleate decreased the insulin and C-peptide responses to a hyperglycemic clamp (P < 0.01), an effect prevented by coinfusion of the antioxidants N-acetylcysteine (NAC) and taurine. Similar to the findings in vivo, 48-h infusion of oleate decreased glucose-stimulated insulin secretion ex vivo (P < 0.01) and induced oxidative stress (P < 0.001) in isolated islets, effects prevented by coinfusion of the antioxidants NAC, taurine, or tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl). Forty-eight–hour infusion of olive oil induced oxidative stress (P < 0.001) and decreased the insulin response of isolated islets similar to oleate (P < 0.01). Islets exposed to oleate or palmitate and MIN6 cells exposed to oleate showed a decreased insulin response to high glucose and increased levels of oxidative stress (both P < 0.001), effects prevented by taurine. Real-time RT-PCR showed increased mRNA levels of antioxidant genes in MIN6 cells after oleate exposure, an effect partially prevented by taurine.

CONCLUSIONS—Our data are the first demonstration that oxidative stress plays a role in the decrease in β-cell secretory function induced by prolonged exposure to FFAs in vitro and in vivo.
Normal Relationship of β- and Non–β-Cells Not Needed for Successful Islet Transplantation
Authors: King Aileen J.F. , Fernandes Justin R. , Hollister-Lock Jennifer , Nienaber Cameron E. , Bonner-Weir Susan , Weir Gordon C.
Published: August 2007

Islets are composed mostly of β-cells, and therefore stem cell research has concentrated on generating purified β-cells, neglecting the other endocrine cell types in the islet. We investigated the presence of endocrine non–β-cells after islet transplantation. In addition, we studied whether the transplantation of pure β-cells, in volumes similar to that used in islet transplantation, would suffice to reverse hyperglycemia in diabetic mice. Rat islets were dispersed and β-cells were purified by fluorescence-activated cell sorting according to their endogenous fluorescence. After reaggregation, 600 islet equivalents of the purified β-cell aggregates were implanted into diabetic SCID mice. In mice implanted with β-cell–enriched aggregates, the hyperglycemia was reversed and good graft function over a 12-week period was observed with regard to glucose and insulin levels, glucose tolerance tests, and graft insulin content. The endocrine cell composition of the β-cell–enriched aggregates remained constant; before and 12 weeks after transplantation, the β-cell–enriched aggregates comprised 95% β-cells and 5% endocrine non–β-cells. However, islet grafts, despite originally having comprised 75% β-cells and 25% endocrine non–β-cells, comprised just 5% endocrine non–β-cells after transplantation, indicating a loss of these cells. β-Cell–enriched aggregates can effectively reverse hyperglycemia in mice, and transplanted intact islets are depleted in non–β-cells. It is therefore likely that islet non–β-cells are not essential for successful islet transplantation.
Reduced Expression of Nuclear-Encoded Genes Involved in Mitochondrial Oxidative Metabolism in Skeletal Muscle of Insulin-Resistant Women With Polycystic Ovary Syndrome
Authors: Skov Vibe , Glintborg Dorte , Knudsen Steen , Jensen Thomas , Kruse Torben A. , Tan Qihua , Brusgaard Klaus , Beck-Nielsen Henning , Højlund Kurt
Published: August 2007

Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative and nonoxidative glucose disposal in PCOS patients are associated with a consistent downregulation of OXPHOS gene expression using GSEA and GenMAPP analysis. Quantitative real-time PCR analysis validated these findings and showed that reduced levels of peroxisome proliferator–activated receptor γ coactivator α (PGC-1α) could play a role in the downregulation of OXPHOS genes in PCOS. In these women with PCOS, the decrease in OXPHOS gene expression in skeletal muscle cannot be ascribed to obesity and diabetes. This supports the hypothesis of an early association between insulin resistance and impaired mitochondrial oxidative metabolism, which is, in part, mediated by reduced PGC-1α levels. These abnormalities may contribute to the increased risk of type 2 diabetes observed in women with PCOS.
Screening for Insulitis in Adult Autoantibody-Positive Organ Donors
Authors: In't Veld Peter , Lievens Dirk , De Grijse Joeri , Ling Zhidong , Van der Auwera Bart , Pipeleers-Marichal Miriam , Gorus Frans , Pipeleers Daniel
Published: August 2007

Antibodies against islet cell antigens are used as predictive markers of type 1 diabetes, but it is unknown whether they reflect an ongoing autoimmune process in islet tissue. We investigated whether organs from adult donors that are positive for autoantibodies (aAbs) against islet cell antigens exhibit insulitis and/or a reduced β-cell mass. Serum from 1,507 organ donors (age 25–60 years) was analyzed for islet cell antibodies (ICAs), glutamate decarboxylase aAbs (GADAs), insulinoma-associated protein 2 aAbs (IA-2As), and insulin aAbs. Tissue from the 62 aAb+ donors (4.1%) and from matched controls was examined for the presence of insulitis and for the relative area of insulin+ cells. Insulitis was detected in two cases; it was found in 3 and 9% of the islets and consisted of CD3+/CD8+ T-cells and CD68+ macrophages; in one case, it was associated with insulin+ cells that expressed the proliferation marker Ki67. Both subjects belonged to the subgroup of three donors with positivity for ICA, GADA, and IA-2-Ab and for the susceptible HLA-DQ genotype. Comparison of relative β-cell area in aAb+ and aAb− donors did not show a significant difference. Insulitis was found in two of the three cases that presented at least three aAbs but in none of the other 59 antibody+ subjects or 62 matched controls. It was only detected in <10% of the islets, some of which presented signs of β-cell proliferation. No decrease in β-cell mass was detected in cases with insulitis or in the group of antibody+ subjects.
Metabolic Mechanisms of Failure of Intraportally Transplanted Pancreatic β-Cells in Rats
Authors: Lee Young , Ravazzola Mariella , Park Byung-Hyun , Bashmakov Yuriy K. , Orci Lelio , Unger Roger H.
Published: August 2007

The objective of this study was to determine whether the late failure of β-cells in islets transplanted via the portal vein is caused by excess insulin-stimulated lipogenesis and lipotoxicity and, if so, whether the damage can be prevented by reducing lipogenesis surrounding the islets. Based on the premise that high portal vein levels of nutrients and incretins would stimulate hyperinsulinemia, thereby inducing intense lipogenesis in nearby hepatocytes, normal islets were transplanted into livers of syngeneic streptozotocin-induced diabetic recipients. Hydrolysis of the surrounding fat would flood the islet grafts with fatty acids that could damage and destroy the β-cells. Reducing lipogenesis by leptin or caloric restriction should prevent or reduce the destruction. After a rise after transplantation, insulin levels gradually declined and hyperglycemia increased. Four weeks after transplantation mRNA of the lipogenic transcription factor, sterol regulatory element–binding protein-1c (SREBP-1c) and its lipogenic target enzymes were elevated in livers of these recipients, as was triacylglycerol content. Positive oil red O staining for lipids and immunostaining for SREBP-1 were observed in hepatocytes surrounding islets with damaged β-cells. Leptin-induced lipopenia prevented and caloric restriction reduced steatosis, hyperglycemia, and apoptotic β-cell destruction. Excessive SREBP-1c–mediated lipogenesis, induced in hepatocytes by insulin hypersecretion, is followed by β-cell destruction in the grafts and reappearance of diabetes. Graft failure is prevented by blocking lipogenesis. The results suggest that strict antilipogenic intervention might improve outcomes after human islet transplantation.
Abnormal Connexin Expression Underlies Delayed Wound Healing in Diabetic Skin
Authors: Wang Chiuhui Mary , Lincoln Jill , Cook Jeremy E. , Becker David L.
Published: August 2007

OBJECTIVE—Dynamically regulated expression of the gap junction protein connexin (Cx)43 plays pivotal roles in wound healing. Cx43 is normally downregulated and Cx26 upregulated in keratinocytes at the edge of the wound as they adopt a migratory phenotype. We have examined the dynamics of Cx expression during wound healing in diabetic rats, which is known to be slow.

RESEARCH DESIGN AND METHODS—We induced diabetes with streptozotocin and examined Cx expression and communication in intact and healing skin.

RESULTS—We found that diabetes decreased Cx43 and Cx26 protein and communication in the intact epidermis and increased Cx43 protein and communication in the intact dermis. Diabetes also altered the dynamic changes of Cxs associated with wound healing. Within 24 h, Cx43 was upregulated in a thickened bulb of keratinocytes at the wound edge (rather than downregulated as in controls, which formed a thin process of migratory cells). Cx43 decline was delayed until 48 h, when reepithelialization began. Although Cx26 was upregulated as normal after wounding in diabetic skin, its distribution at the wound edge was abnormal, being more widespread. Application of Cx43-specific antisense gel to diabetic wounds prevented the abnormal upregulation of Cx43 and doubled the rate of reepithelialization, which exceeded control levels.

CONCLUSIONS—Cx expression in diabetic skin is abnormal, as is the dynamic response of Cx43 to injury, which may underlie the delayed healing of diabetic wounds. Preventing the upregulation of Cx43 in diabetic wounds significantly improves the rate of healing and clearly has potential therapeutic value.
Calmodulin-Binding Domain of AS160 Regulates Contraction- but Not Insulin-Stimulated Glucose Uptake in Skeletal Muscle
Authors: Kramer Henning F. , Taylor Eric B. , Witczak Carol A. , Fujii Nobuharu , Hirshman Michael F. , Goodyear Laurie J.
Published: August 2007

OBJECTIVE—Insulin and contraction increase skeletal muscle glucose uptake through distinct and additive mechanisms. However, recent reports have demonstrated that both signals converge on the Akt substrate of 160 kDa (AS160), a protein that regulates GLUT4 translocation. Although AS160 phosphorylation is believed to be the primary factor affecting its activity, AS160 also possesses a calmodulin-binding domain (CBD). This raises the possibility that contraction-stimulated increases in Ca2+/calmodulin could also modulate AS160 function.

RESEARCH DESIGN AND METHODS—To evaluate the AS160 CBD in skeletal muscle, empty-vector, wild-type, or CBD-mutant AS160 cDNAs were injected into mouse muscles followed by in vivo electroporation. One week later, AS160 was overexpressed by ∼14-fold over endogenous protein.

RESULTS—Immunoprecipitates of wild-type and CBD-mutant AS160 were incubated with biotinylated calmodulin in the presence of Ca2+. Wild-type AS160, but not the CBD-mutant AS160, associated with calmodulin. Next, we measured insulin- and contraction-stimulated glucose uptake in vivo. Compared with empty-vector and wild-type AS160, insulin-stimulated glucose uptake was not altered in muscles expressing CBD-mutant AS160. In contrast, contraction-stimulated glucose uptake was significantly decreased in CBD-mutant–expressing muscles. This inhibitory effect on glucose uptake was not associated with aberrant contraction-stimulated AS160 phosphorylation. Interestingly, AS160 expressing both calmodulin-binding and Rab-GAP (GTPase-activating protein) domain point mutations (CBD + R/K) fully restored contraction-stimulated glucose uptake.

CONCLUSIONS—Our results suggest that the AS160 CBD directly regulates contraction-induced glucose uptake in mouse muscle and that calmodulin provides an additional means of modulating AS160 Rab-GAP function independent of phosphorylation. These findings define a novel AS160 signaling component, unique to contraction and not insulin, leading to glucose uptake in skeletal muscle.
Short-Term Caloric Restriction Induces Accumulation of Myocardial Triglycerides and Decreases Left Ventricular Diastolic Function in Healthy Subjects
Authors: van der Meer Rutger W. , Hammer Sebastiaan , Smit Johannes W.A. , Frölich Marijke , Bax Jeroen J. , Diamant Michaela , Rijzewijk Luuk J. , de Roos Albert , Romijn Johannes A. , Lamb Hildo J.
Published: August 2007

OBJECTIVE—Diabetes and obesity are associated with increased plasma nonesterified fatty acid (NEFA) levels, myocardial triglyceride accumulation, and myocardial dysfunction. Because a very low–calorie diet (VLCD) also increases plasma NEFA levels, we studied the effect of a VLCD on myocardial triglyceride content and cardiac function in healthy subjects.

RESEARCH DESIGN AND METHODS—Fourteen healthy nonobese men underwent 1H-magnetic resonance spectroscopy (MRS) to determine myocardial and hepatic triglyceride content, 31P-MRS to assess myocardial high-energy phosphate (HEP) metabolism (phosphocreatine/ATP), and magnetic resonance imaging of myocardial function at baseline and after a 3-day VLCD.

RESULTS—After the dietary intervention, plasma NEFA levels increased compared with those at baseline (from 0.5 ± 0.1 to 1.1 ± 0.1 mmol/l, P < 0.05). Concomitantly, myocardial triglyceride content increased by ∼55% compared with that at baseline (from 0.38 ± 0.05 to 0.59 ± 0.06%, P < 0.05), whereas liver triglyceride content decreased by ∼32% (from 2.2 ± 0.5 to 1.5 ± 0.4%, P < 0.05). The VLCD did not change myocardial phosphocreatine-to-ATP ratio (2.33 ± 0.15 vs. 2.33 ± 0.08, P > 0.05) or systolic function. Interestingly, deceleration of the early diastolic flow across the mitral valve decreased after the VLCD (from 3.37 ± 0.20 to 2.91 ± 0.16 ml/s2 × 10−3, P < 0.05). This decrease in diastolic function was significantly correlated with the increase in myocardial triglyceride content.

CONCLUSIONS—Short-term VLCD induces accumulation of myocardial triglycerides. In addition, VLCD decreases left ventricular diastolic function, without alterations in myocardial HEP metabolism. This study documents diet-dependent physiological variations in myocardial triglyceride content and diastolic function in healthy subjects.
All-Cause Mortality Associated With Specific Combinations of the Metabolic Syndrome According to Recent Definitions
Authors: Guize Louis , Thomas Frédérique , Pannier Bruno , Bean Kathy , Jego Bertrand , Benetos Athanase
Published: August 2007

OBJECTIVE—The aim was to evaluate the impact of specific component combinations of the metabolic syndrome on all-cause mortality risk in a large French cohort.

RESEARCH DESIGN AND METHODS—The population was composed of 39,998 men (aged 52.6 ± 8.3 years) and 20,756 women (aged 54.7 ± 9.2 years) who were examined at the Investigations Préventives et Cliniques Center from 1999 to 2002. Mean follow-up was 3.57 ± 1.12 years. Metabolic syndrome was defined according to three definitions: the National Cholesterol Educational Program (NCEP 2001), the revised NCEP (NCEP-R; American Heart Association/National Heart, Lung, and Blood Institute 2005), and the International Diabetes Federation (IDF 2005). Subjects with metabolic syndrome were compared with subjects without metabolic syndrome and with subjects with no metabolic syndrome components using Cox regression models.

RESULTS—The prevalence of metabolic syndrome increased from 10.3% (NCEP) to 17.7% (NCEP-R) and 23.4% (IDF). After adjustment for age, sex, classical risk factors, and socioprofessional categories, and compared with subjects without metabolic syndrome, the risk of all-cause mortality was 1.79 (95% CI 1.35–2.38), 1.46 (1.14–1.88), and 1.32 (1.04–1.67) with the NCEP, NCEP-R, and IDF definitions, respectively. Among the combinations significantly associated with all-cause mortality, the following three-component combinations and the four-component combination were more highly significant than other combinations (P < 0.05): elevated waist circumference plus elevated glucose, plus either elevated blood pressure or elevated triglycerides, and the combination of all four of these.

CONCLUSIONS—In a large middle-aged French population, four specific components of metabolic syndrome are associated with a much higher mortality risk. These results may have a significant impact on detecting high-risk subjects suffering from metabolic disorders and underline the fact that metabolic syndrome is a nonhomogeneous syndrome.
Hyperglycemia and Externalizing Behavior in Children With Type 1 Diabetes
Authors: McDonnell Ciara M. , Northam Elisabeth A. , Donath Susan M. , Werther George A. , Cameron Fergus J.
Published: August 2007

OBJECTIVE—Ancedotally, parents report behavioral changes in their diabetic children who have fluctuating blood glucose levels. This study aimed to test associations between intercurrent glycemia and child behavior in an ambulant setting.

RESEARCH DESIGN AND METHODS—Prepubertal children attending the Royal Children's Hospital, Melbourne, Australia, with type 1 diabetes received glycemic assessment and simultaneous behavioral assessment on two occasions 6 months apart. Subjects wore a continuous glucose monitor over a 72-h period, and parents completed the Behavior Assessment System for Children at the two study time points.

RESULTS—There was a high correlation between intra-individual externalizing and internalizing behavior scores (r = 0.88, P < 0.001 and r = 0.81, P < 0.001, respectively) at the two time points. Mean blood glucose (MBG) was significantly associated with the mean externalizing behavior score (β = 1.7 [95% CI 0.6–2.8], adjusted r2 = 0.088). Percentage of time in the normal (r = −0.2 [−0.3 to −0.5], adjusted r2 = 0.068) and high (r = 0.2 [0.07–0.3], adjusted r2 = 0.089) glycemic ranges were significantly associated with the mean externalizing behavior score. For every 5% increase in time in the normal glycemic range, there was a decrease in the externalizing behavior score of 1.0, and for every 5% increase in time in the high glycemic range there was an increase in the externalizing behavior score of 1.0. There was no significant association between MBG and the mean internalizing behavior score.

CONCLUSIONS—Externalizing behaviors were associated with intercurrent glycemic status. These findings underscore the importance of understanding the mechanisms of this association and how it might impact ultimate diabetes outcomes.
Depression Screening Disparities Among Veterans With Diabetes Compared With the General Veteran Population
Authors: Jones Laura E. , Doebbeling Caroline Carney
Published: August 2007

OBJECTIVE—We sought to describe the proportion of veterans with diabetes screened for depression compared with the general population of veterans.

RESEARCH DESIGN AND METHODS—Electronic medical records (fiscal years 2001–2004) from a Midwestern Veterans Health Administration (VHA) facility and VHA External Peer Review Program (EPRP) data were used for the study. Facility-level data included inpatient and outpatient encounters, which included depression screen results. EPRP data were facility-level summary data, which detailed the proportion of general population veterans nationwide and patients at the Midwestern facility who were screened for depression. Logistic regression tested for associations between depression screen receipt and screening positive and demographic/clinical characteristics among patients with diabetes.

RESULTS—Depression screening among those with diabetes improved from 62% in fiscal year 2001 to 83% in 2004. Screening was 9–23% lower and 11–22% lower in patients with diabetes compared with the general population of veterans nationwide and patients at the Midwestern facility, respectively. Seventeen percent of subjects with diabetes screened positive, which is two times higher than in the general population. Women (odds ratio 0.45 [95% CI 0.35–0.60]) and subjects with unknown A1C (0.40 [0.34–0.46]) were less likely to be screened for depression. A ≥50% service-connected disability rating was inversely associated with screening (0.84 [0.72–0.99]) but positively associated with screening positive for depression (1.56 [1.33–1.82]).

CONCLUSIONS—Screening for depression among veterans with diabetes improved 21% but is considerably lower than the proportion of general population veterans screened nationally and at the facility of interest. Targeted interventions to improve screening in patients with diabetes are required based on evidence that screening translates into increased provider recognition and treatment of depression.
Regional Brain Volume Differences Associated With Hyperglycemia and Severe Hypoglycemia in Youth With Type 1 Diabetes
Authors: Perantie Dana C. , Wu Jenny , Koller Jonathan M. , Lim Audrey , Warren Stacie L. , Black Kevin J. , Sadler Michelle , White Neil H. , Hershey Tamara
Published: August 2007

OBJECTIVE—Despite interest in the effects of type 1 diabetes on the developing brain, structural brain volumes in youth with this disease have not previously been examined. This study is the first to quantify regional brain volume differences in a large sample of youth with diabetes.

RESEARCH DESIGN AND METHODS—Magnetic resonance images (MRIs) were acquired from youth with diabetes (n = 108) and healthy sibling control subjects (n = 51) aged 7–17 years. History of severe hypoglycemia was assessed by parent interview and included seizure, loss of consciousness, or requiring assistance to treat. A1C values since diagnosis were obtained from medical records; median A1C was weighted by duration of disease. Voxel-based morphometry was used to determine the relationships of prior hypo- and hyperglycemia to regional grey and white matter volumes across the whole brain.

RESULTS—No significant differences were found between diabetic and healthy control groups in grey or white matter. However, within the diabetic group, a history of severe hypoglycemia was associated with smaller grey matter volume in the left superior temporal region. Greater exposure to hyperglycemia was associated with smaller grey matter volume in the right cuneus and precuneus, smaller white matter volume in a right posterior parietal region, and larger grey matter volume in a right prefrontal region.

CONCLUSIONS—Qualitatively different relationships were found between hypo- and hyperglycemia and regional brain volumes in youth with type 1 diabetes. Future studies should investigate whether these differences relate to cognitive function and how these regions are affected by further exposure.
Muscle-Strengthening Activity and Its Association With Insulin Sensitivity
Authors: Cheng Yiling J. , Gregg Edward W. , De Rekeneire Nathalie , Williams Desmond E. , Imperatore Giuseppina , Caspersen Carl J. , Kahn Henry S.
Published: August 2007

OBJECTIVE—Muscle-strengthening activities (MSAs) may increase insulin sensitivity, thereby reducing the risk of diabetes. The purpose of this study was to assess the relationship between MSAs and insulin sensitivity among American adults.

RESEARCH DESIGN AND METHODS—We analyzed data on 4,504 adults without diabetes, aged 20–79 years, who participated in the National Health and Nutrition Examination Survey 1999–2004 and had information on MSAs. Self-reported frequency (times/week) of MSAs was grouped as low (<1), moderate (1–2.9), or high (≥3). Insulin sensitivity was measured by the fasting quantitative insulin sensitivity check index × 100 (QUICKI).

RESULTS—After adjustment for age, race/ethnicity, physical activity other than MSAs, BMI, smoking, alcohol consumption, and daily total caloric intake, the mean values for QUICKI by low, moderate, and high MSA were 33.6, 33.9, and 34.2, respectively (P for linear trend = 0.008) for men and 34.2, 34.6, 34.6, respectively (P for linear trend = 0.009) for women. Mean fasting insulin (picomols per liter) concentrations were 75.0, 68.9, and 65.9, respectively (P for linear trend = 0.017) for men and 66.9, 63.3, 61.2, respectively (P for linear trend = 0.007) for women. There were no significant differences across MSA groups for fasting glucose among men or women.

CONCLUSIONS—MSA is independently associated with higher insulin sensitivity among U.S. adults. Efforts to increase MSA may be a realistic, feasible, and effective method of reducing insulin resistance among the U.S. population.
Microvascular Diabetes Complications in Wolfram Syndrome (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness [DIDMOAD])
Authors: Cano Aline , Molines Laurent , Valéro René , Simonin Gilbert , Paquis-Flucklinger Véronique , Vialettes Bernard ,   the French Group of Wolfram Syndrome
Published: August 2007

OBJECTIVE—Some previous studies suggested that patients suffering from Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) might be relatively preserved from diabetic retinopathy and nephropathy. However, these data were not conclusive because either observations were only anecdotic or did not match with control type 1 diabetic populations.

RESEARCH DESIGN AND METHODS—A group of 26 French diabetic patients with DIDMOAD was compared with a population of 52 patients with common type 1 diabetes matched for age at diabetes diagnosis (8.62 ± 1.84 vs. 8.27 ± 1.30 years; P = NS) and diabetes duration (12.88 ± 1.58 vs. 12.87 ± 1.13 years; P = NS) to study the quality of glycemic control and the incidence of microvascular complications.

RESULTS—Glycemic control was significantly better in the DIDMOAD group than in the type 1 diabetic group (A1C: 7.72 ± 0.21 vs. 8.99 ± 0.25%, respectively; P = 0.002), with significant lower daily insulin requirements (0.71 ± 0.07 vs. 0.88 ± 0.04 UI · kg−1 · day−1, respectively; P = 0.0325). The prevalence of microvascular complications in the DIDMOAD group was half that observed in the type 1 diabetic group, but the difference was not significant.

CONCLUSIONS—Diabetes in DIDMOAD patients is more easily controlled despite the presence of other handicaps. This better glycemic control could explain the trend to decreased microvascular diabetes complications observed in previous studies.
Increased Body Iron Stores of Obese Women With Polycystic Ovary Syndrome Are a Consequence of Insulin Resistance and Hyperinsulinism and Are Not a Result of Reduced Menstrual Losses
Authors: Luque-Ramírez Manuel , Álvarez-Blasco Francisco , Botella-Carretero José I. , Sanchón Raul , San Millán José L. , Escobar-Morreale Héctor F.
Published: August 2007

OBJECTIVE—Increased serum ferritin levels, indicating increased body iron stores, have been found in overweight and obese women with polycystic ovary syndrome (PCOS). This finding might result from reduced menstrual losses secondary to oligo- or amenorrhea or from hyperinsulinism secondary to insulin resistance, because insulin favors the intestinal absorption and the tissue deposition of iron. To explore which of these mechanisms is responsible for the increase in body iron stores in women with PCOS, we have monitored the changes in serum ferritin levels during treatment with an antiandrogenic oral contraceptive or an insulin sensitizer.

RESEARCH DESIGN AND METHODS—Thirty-four consecutive PCOS patients were randomized to an oral contraceptive containing 35 μg ethinyl-estradiol plus 2 mg cyproterone acetate (Diane35 Diario) or metformin (850 mg twice daily), and their serum ferritin levels were evaluated at baseline and after 12 and 24 weeks of treatment.

RESULTS—Despite the fact that treatment with Diane35 Diario restored regular menstrual cycles in all the patients, whereas metformin only did so in 50% of them, serum ferritin levels decreased at 12 and 24 weeks of treatment only with metformin, in association with a marked increase in insulin sensitivity. On the contrary, no changes in ferritin and insulin sensitivity were observed with Diane35 Diario.

CONCLUSIONS—Our present results suggest that insulin resistance and hyperinsulinism, and not the reduced menstrual losses secondary to from oligo- or amenorrhea, are responsible of the increased ferritin levels and body iron stores found in overweight and obese women with PCOS.
Disordered Eating: Identifying, Treating, Preventing, and Differentiating It From Eating Disorders
Authors: Pereira Raquel Franzini , Alvarenga Marle
Published: August 2007

In Brief

Disordered eating is prevalent among people with diabetes and can significantly increase diabetes mortality and morbidity. When disordered eating behaviors are culturally accepted and performed with significant frequency by a variety of groups, it can lead to the perception that these behaviors are “normal,” which can be detrimental to the prevention and treatment of diabetes. Diabetes educators are capable of improving their diagnostic skills and treatment methods to meet the special needs of people with diabetes who also suffer from disordered eating. It is important to integrate key questions into assessment interviews and to ensure that the diabetes care team has the skill, knowledge, and tools to diagnose and treat disordered eating to improve outcomes for individuals with diabetes.
Chondromyxoid Fibroma of the Nasal Septum: A Case Report Emphasizing Clinical Correlation
Authors: Wang Chen , Morrow Todd , Friedman Paul , Lara Jonathan F.
Published: August 2007

Chondromyxoid fibromas are uncommon tumors most often seen in long bones of adolescent and young males. Involvement of craniofacial bones is extremely unusual, with sporadic case reports described in the literature. We describe the first case of chondromyxoid fibroma arising in the nasal septum with local destruction and expansile growth into the ethmoid bone and inferior turbinate in a 60-year-old female. The fortuitous discovery of this otherwise asymptomatic lesion and its follow-up are detailed. The literature is reviewed and salient clinical, radiographic, and pathologic correlative findings are emphasized.
Histopathology of Tissue Samples Removed Using the Microdebrider Technique: Implications for Endoscopic Sinus Surgery
Authors: Zweig Julie L , Schaitkin Barry M. , Fan Chun-Yang , Barnes E. Leon
Published: August 2007

Microdebriders are being used with increasing frequency in endoscopic sinus surgery to provide precise removal of soft tissue and bone with simultaneous suction and irrigation. To date, no one has analyzed whether histopathology of tissue processed through a microdebrider is maintained. Fifteen tissue samples (squamous cell cancer, esthesioneuroblastoma, lymphoma, sarcoma, inverted papilloma, benign thyroid, and nasal mucosa) were processed though a microdebrider in various modes and speeds. Pathology slides were developed, coded, and presented as unknowns to the pathologist for diagnosis. Specimens taken from routine biopsy techniques were then compared to those passed through the microdebrider. The study found no significant loss of morphologic features in the tissue passed through the microdebrider. The microdebrider may be used for both routine and oncologic procedures without altering the histopathology necessary for diagnosis.