bluuebunny/crossref_metadata_2025 huggingface dataset:
Compositional End Members and Thermodynamic Components of Illite and Dioctahedral Aluminous Smectite Solid Solutions
Authors: Ransom Barbara , Helgeson Harold C.
Published: August 2006

Consideration of XRD, TEM, AEM, and analytical data reported in the literature indicates that dioctahedral aluminous smectite and illite form two separate solid solutions that differ chemically from one another primarily by the extent of Al substitution for Si, the amount of interlayer K, and the presence of interlayer H2O. The data indicate that limited dioctahedral-trioctahedral and dioctahedral-vacancy compositional variations occur in both minerals. Excluding interlayer H2O and based on a half unit cell [i.e., O10(OH)2], natural dioctahedral smectite and illite solid solutions fall within the compositional limits represented by A0.3${\rm{R}}_{1.9}^{3 + }$Si4O10(OH)2-AR2+ R3+ Si4O10(OH)2-A0.25${\rm{R}}_{0.3}^{2 + }{\rm{R}}_{1.8}^{3 + }$Al0.25Si3.75O10(OH)2 for smectites and A0.8${\rm{R}}_{1.9}^{3 + }$Al0.5Si3.5O10(OH)2-A0.55${\rm{R}}_{0.45}^{2 + }{\rm{R}}_{1.55}^{3 + }$Al0.1Si3.9O10(OH)2-A0.9${\rm{R}}_{0.3}^{2 + }{\rm{R}}_{1.8}^{3 + }$Al0.9Si3.1O10(OH)2 for illites, where A represents either monovalent cations or divalent cations expressed as their monovalent equivalent (e.g., Ca2+/2); R2+ stands for the divalent cations Mg2+ and Fe2+ and R3+ refers to the trivalent cations Al3+ and Fe3+. Taking account of these compositional limits, smectite and illite solid solutions can be described in terms of nine and six thermodynamic components, respectively, all of which are consistent with both the law of definite proportions and the concept of a unit cell. Thermodynamic components that can be used to describe natural smectite solid solutions in terms of a half unit cell [i.e., O10(OH)2] can be expressed as NaAl3Si3O10(OH)2, NaAl3Si3O10(OH)2 ·4.5H2O, Al2Si4O10(OH)2, Fe2Si4O10(OH)2, Mg3Si4O10(OH)2, Fe3Si4O10(OH)2, K3AlSi4O10(OH)2, KAl3Si3O10(OH)2, and Ca0.5Al3Si3O10(OH)2. Of these, NaAl3Si3O10(OH)2 ·4.5H2O provides explicitly for the presence of interlayer H2O in the mineral. Thermodynamic components representing illite solid solutions in natural systems can be written for a half unit cell as KAl3Si3O10(OH)2, KMg3AlSi3O10(OH)2, KFe3AlSi3O10(OH)2, Al2Si4O10(OH)2, KFe2AlSi3O10(OH)2, and K3AlSi4O10(OH)2. The calculations and observations summarized below indicate that neither smectite nor illite occur in nature as stoichiometric phases and that the two minerals do not form a mutual solid solution corresponding to mixed-layered illite/smectite.
Polytype Diversity of the Hydrotalcite-Like Minerals I. Possible Polytypes and their Diffraction Features
Authors: Bookin A. S. , Drits V. A.
Published: August 2006

All possible polytypes of hydrotalcite-like minerals with a periodicity along the c axis of one-, two- and three-layers, as well as the simplest six-layer polytypes, were derived on the basis of the concept of closely packed brucite-like layers. Multilayer structures were found to be possible in several polytype modifications—three two-layer, nine three-layer, and a set of six-layer polytypes. The neighboring layers may be stacked in two different ways, building two kinds of interlayers: P-type where OH sheets lie one above another forming prisms and O-type where OH groups forms octahedra. Based on the kind of interlayer space, all polytypes may be separated into three groups: homogeneous interlayers of O-, or P-type, and alternating interlayers of both types. For the members of the first two groups, powder XRD patterns were calculated and criteria for distinguishing polytypes with the same number of layers per unit cell are suggested.
Stacking Order in a K/Mg Interstratified Vermiculite from Malawi
Authors: de la Calle C. , de Vidales J. L. Martin , Pons C. H.
Published: August 2006

The stacking order of a bi-ionic K/Mg vermiculite from Malawi (Nyasaland), has been determined from Weissenberg data. The sample corresponds to a K/Mg interstratified vermiculite containing 50% K layers (dK = 1.01 nm) and 50% Mg layers with two layers of water (dMg = 1.44 nm). The observed intensities along (0, 0), (h, 0), (0, k) and (1, k) reciprocal rods were compared to the calculated intensities given by model defect structures. It was found that: 1) The (h, 0), (0, k) and (1, k) rods reveal the interstratification phenomenon which was previously observed on the (0, 0) rod; 2) The exchange of Mg by K does not occur randomly in a single interlayer, but occurs in interlayer domains sufficiently extensive to allow the reorganisation of the layer stacking and development of the ordered K-vermiculite structure from the semi-ordered structure characteristic of magnesium vermiculites; 3) For this sample, the interlayer water of the Mg phase occurs in two coexisting configurations; one configuration has water molecules forming octahedral coordination around the Mg2+, the other has water which is not linked to the Mg2+ cation forming two planes.
Formation Mechanism of Aluminum Hydroxide Polymorphs
Authors: Violante A. , Huang P. M.
Published: August 2006

Substantial studies have been carried out to investigate the mechanism of the formation of Al(OH)3 polymorphs. The influence of the nature of Al precipitation products on the formation of Al(OH)3 polymorphs still remains obscure. In this study, X-ray diffraction, infrared and thermal analyses, and electron microscopic observations of the Al precipitates formed at the initial pH 8.2 and at a citric acid/Al molar ratio of 0.01 and aged for 3 hr to 60 days revealed that the transformation from the initially formed noncrystalline materials to pseudoboehmite occurred through the formation of intermediate materials with various degrees of ordering and sizes of particles that apparently had a wide range of solubility. By increasing the pH of the suspension of precipitation products of Al to 10.0 after 3 hr and 3, 11, 31, and 60 days or longer, the crystalline precipitation products were hayerite, nordstrandite and bayerite, nordstrandite and pseudoboehmite, pseudoboehmite and gibbsite, and pseudoboehmite, respectively. This work shows evidence that, as the nature of the starting Al precipitates changed, the rate of their dissolution apparently changed, and various Al(OH)3 polymorphs consequently formed. Therefore, the data substantiate the hypothesis that the mechanism of the formation of an Al(OH)3 polymorph is determined by the rate of its nucleation, which is, in turn, influenced by the rate of dissolution of the noncrystalline or poorly ordered Al-oxides initially formed.
The Effect of Mechanical Treatment on the Crystal Structure and Thermal Behavior of Kaolinite
Authors: Kristóf Éva , Juhász A. Zoltán , Vassányi István
Published: August 2006

The destruction of the crystal structure of kaolinite caused by mechanical forces was investigated by X-ray diffraction, thermal analysis, infrared spectroscopy, and specific surface area determination. Attention was also directed to the change of thermal reactions of milled kaolinite. Grinding experiments for 5 min, 10 min, and 1, 2, 4, 6, and 10 h were carried out in an AGO I planetary mill. After 1 h of grinding, the crystalline order of kaolin is destroyed; but the amorphization continues in the course of prolonged grinding. Grinding for 1 h produces a favorable state for forming mullite-type crystals after heating even at 1000°C.
Kaolinite Particle Sizes in the <2 µm Range Using Laser Scattering
Authors: Mackinnon Ian D. R. , Uwins Philippa J. R. , Yago Anya , Page David
Published: August 2006

The Clay Minerals Society Source Clay kaolinites, Georgia KGa-1 and KGa-2, have been subjected to particle size determinations by 1) conventional sedimentation methods, 2) electron microscopy and image analysis, and 3) laser scattering using improved algorithms for the interaction of light with small particles. Particle shape, size distribution, and crystallinity vary considerably for each kaolinite. Replicate analyses of separated size fractions showed that in the <2 µm range, the sedimentation/centrifugation method of Tanner and Jackson (1947) is reproducible for different kaolinite types and that the calculated size ranges are in reasonable agreement with the size bins estimated from laser scattering. Particle sizes determined by laser scattering must be calculated using Mie theory when the dominant particle size is less than ∼5 µm. Based on this study of two well-known and structurally different kaolinites, laser scattering, with improved data reduction algorithms that include Mie theory, should be considered an internally consistent and rapid technique for clay particle sizing.
The Chemical Form of Vanadium (IV) in Kaolinite
Authors: Gehring A. U. , Fry I. V. , Luster J. , Sposito Garrison
Published: August 2006

A combined application of electron paramagnetic resonance (EPR) and Fourier-transform infrared (FTIR) spectroscopies with thermal methods was used to determine the chemical form of V(IV) in a Georgia kaolinite (KGa-I). Precise values of the EPR spectroscopic g-values and hyperfine coupling constants were obtained for an untreated sample (g∥ = 1.940, A∦ = 18.71 mT; g⊥ = 1.966, A⊥ = 7.63 mT). Heating the sample to 1000°C in steps while monitoring phase changes with EPR and FTIR spectra led to the following structural interpretations: 1) Vanadium (IV) occurs almost entirely as an isomorphically substituted species in the octahedral sheet of KGa-1 kaolinite; 2) during the dehydroxylation of kaolinite at about 500°C and the subsequent formation of metakaolinite, V(IV)-substituted octahedral sites are readily converted into truncated octahedra exhibiting fourfold coordination; and 3) in these highly distorted four-coordinated sites, V(IV) is metastable, being completely oxidized at about 800°C.
A Chemical, XRD, and 27Al MAS NMR Investigation of Miocene Gulf Coast Shales with Application to Understanding Illite/Smectite Crystal-Chemistry
Authors: Schroeder Paul A.
Published: August 2006

This study assesses the distribution of Al and Fe in mixed-layer illite/smectites (I/S) in shales undergoing burial diagenetic changes, using evidence from 27Al NMR, XRD, and chemical analyses. Samples studied include a sequence of mixed-layer I/S (ranging from 40% to 68% illite layers) in shales from a well located in the Caillou Island Oil Field, Terrebonne Parish, Louisiana, as well as synthetic mica-montmorillonite (Syn-1), Silver Hill illite (IMt-1), K-benonite (ISMt-1), an Fe-bearing muscovite, phengitic muscovite, and a randomly interstratified mixed-layer I/S with 50% illite layers. Using a simplified model, where Fe3+ isomorphously substitutes randomly for [6]Al in the dioctahedral 2:1 structure, the 27Al NMR signal intensities are examined with regard to the paramagnetic deshielding effect of the Fe3+. The rapid decrease in paramagnetic deshielding with distance allows for a spherical “wipeout” model with a radius of 6 Å, over which there is complete effective paramagnetic line broadening (i.e., Al within the sphere is not “seen”). Using the average dimensions of a dioctahedral mica, the expected relative intensities of the octahedral and tetrahedral Al signal are determined as a function of Fe2O3 content.

Observed 27Al signals, normalized per unit weight of Al2O3 and relative to the lowest Fe-bearing phase, show a clear trend of decreasing intensity with increasing Fe2O3 content. Normative fitting of oxide data to structural formulae reveals a similar trend of decreasing 27Al intensity with increasing fraction of dioctahedral site occupied by Fe3+. Agreement between the observed 27Al intensities of low Fe-bearing 2:1 phyllosilicates and 27Al intensities predicted using the wipeout model indicate regular ordering of Fe and Al within the low Fe-bearing phases. However, observed 27Al intensities for the I/S specimens fall into a region where the amount of Al seen is in excess for the given XFe, thus indicating segregation of Al and Fe domains.

The second order quadrupole effect for the [6]Al site in the I/S fraction of shales decreases very slightly with increasing depth and percent of illite in the I/S, but not enough to effect site quantitation. Quantitative apportionment of elements into the I/S phase of the <0.2 µm fraction using NMR constraints shows directly a trend of increasing number of [4]Al sites and no change in the number of [6]Al sites with increasing degree of illitization for samples from the Gulf Coast diagenetic environment. Stoichiometry indicates an approximate 1:1 substitution of tetrahedral Al for Si over the 40–68% range of illite in I/S examined.
The Effect of Dissolved Ligands upon the Sorption of Cu(II) by Ca-Montmorillonite
Authors: Stadler Markus , Schindler Paul W.
Published: August 2006

The effect of three organic ligands on the adsorption of Cu on Ca-montmorillonite was studied. The results indicate that these effects include three different processes:

1)

Enhanced uptake of positively charged Cu-ligand complexes by ion-exchange.

2)

Formation of ternary surface complexes involving surface aluminol groups.

3)

Inhibited uptake due to competition between the surface ligands and the dissolved ligands for dissolved copper.

Ethylenediamine promotes Cu uptake by ion-exchange at low pH but tends to suppress adsorption at aluminol groups by ligand competition at high pH. The same mechanisms are operative for β-alanine; however, the uptake of Cu(β-ala)+ by ion-exchange is not promoted by the attached ligand. The influence of malonate includes both ligand competition and formation of ternary complexes. A quantitative interpretation based on the surface complexation model using the least-square programs FITEQL (Westall, 1982) and GRFIT (Ludwig, 1992) is presented. The obtained equilibrium constants are listed in Tables 2b and 3.
Hydroxy-Chromium Smectite
Authors: Volzone C. , Cesio A. M. , Sánchez R. M. Torres , Pereira E.
Published: August 2006

Hydroxy-chromium solutions were prepared from chromium nitrate solutions by adding NaOH with OH/Cr = 2.

The solutions were treated at 20°C and 60°C. The hydrolysis times were from 1 to 100 days. Polymeric species in hydrolyzed chromium solutions were followed by visible absorption spectra within the range 325–800 nm and by pH measurement. OH-Cr-smectite with high d(001) spacing (2.07 nm) was obtained when hydroxy-chromium solution was prepared at 60°C and with 1-day hydrolysis. When this sample was heated up to 350°C the basal spacing collapsed at 1.8 nm.

The samples were characterized by X-ray diffraction and N2 adsorption-desorption isotherms.
Kaolinite: NMF Intercalates
Authors: Uwins Philippa J. R. , Mackinnon Ian D. R. , Thompson John G. , Yago Anya J. E.
Published: August 2006

Bulk and size-fractionated kaolinites from seven localities in Australia as well as the Clay Minerals Society Source Clays Georgia KGa-1 and KGa-2 have been studied by X-ray diffraction (XRD), laser scattering, and electron microscopy in order to understand the variation of particle characteristics across a range of environments and to correlate specific particle characteristics with intercalation behavior. All kaolinites have been intercalated with N-methyl (NMF) after pretreatment with hydrazine hydrate, and the relative efficiency of intercalation has been determined using XRD. Intercalate yields of kaolinite: NMF are consistently low for bulk samples that have a high proportion of small-sized particles (i.e., <0.5 µm) and for biphased kaolinites with a high percentage (>60%) of low-defect phase. In general, particle size appears to be a more significant controlling factor than defect distribution in determining the relative yield of kaolinite: NMF intercalate.
Brønsted Acidification Observed during Hydrothermal Treatment of a Calcium Montmorillonite
Authors: Heimann Robert B.
Published: August 2006

An aluminous Ca-montmorillonite from southern Manitoba, Canada, has been shown to generate very low pH values in clay/groundwater slurries over a range of ionic strength of the groundwater (fresh and saline) and temperatures from 25°–90°C. Dialysis experiments as well as results of X-ray diffraction and FTIR vibration spectroscopy point to an acidification mechanism that involves hydrolysis of exchangeable Al3+ ions, thus releasing protons, and the subsequent intercalation of gibbsite-like hydroxy-Al complexes into the smectite lattice forming a non-expandable “Al”-montmorillonite.
Clay Mineralogy and Illite Crystallinity of the Atoka Formation, Arkoma Basin, and Frontal Ouachita Mountains
Authors: Spötl Christoph , Houseknecht David W. , Jaques Robert
Published: August 2006

Clay mineralogy (including illite crystallinity) was studied in Pennsylvanian synorogenic sediments (Atoka Formation) in the subsurface of the Arkoma Basin and the adjacent Ouachita thrust belt. Vitrinite reflectance values range from ≥0.8% at the surface up to as high as 4.7% Roat the base of the Atoka Formation. The mineralogy of the <2µm fraction of the mudrocks is fairly monotonous and composed of illite (<10% interstratified smectite), Fe-chlorite, kaolinite, quartz, and traces of feldspars. Kaolinite is common at shallow levels and “disappears” in most wells at a thermal maturity of 1.9–2.1% Ro, suggesting its possible use as an independent paleothermal indicator in this basin. Illite crystallinity (IC) values are fairly high (0.3–0.5° 2θ) and show little variation throughout the entire maturity range. In addition, no relation was observed between vitrinite reflectance and illite crystallinity, indicating that IC is not a useful paleothermal indicator in these rocks. Illite is almost exclusively of the 2M1polytype, suggesting a predominantly detrital origin. Incipient metamorphic and low-grade metamorphic mudrocks in the Ouachita thrust belt to the east of the Arkoma Basin are regarded as the source rocks for the clays of the Atoka Formation. Rapid transportation and deposition by turbidity currents probably played a key role in protecting these unweathered micas from pervasive alteration in the terrestrial environment.
Modeling Seasonal Variations in Carbon Dioxide and Nitrous Oxide in the Vadose Zone
Authors: Cannavo P. , Lafolie F. , Nicolardot B. , Renault P.
Published: August 2006

Soil CO2 and N2O concentrations were simulated with a model predicting C and N transport in the vadose zone during a 7‐mo field experiment, after maize (Zea mays L.) harvesting and incorporation of maize residues into the soil. The gas transport model was based on the dusty gas theory and combined with the PASTIS model. During the experiment, soil atmosphere (CO2 and N2O), soil solution (NO3− and dissolved organic carbon [DOC]), soil water content and temperature, and potential denitrifying and aerobic respiratory activities were measured in a 2.50‐m‐thick soil profile. Soil gas concentrations were correctly simulated even though the model did not simulate all the biological processes that produced N2O. Nitrous oxide concentration peaks after rain were slightly overestimated, as the WFPS (water‐filled pore space) was not estimated accurately enough to predict local anoxic conditions. To model CO2 concentrations, account had to be taken of DOC adsorption onto soil mineral particles and of zymogenous biomass death during the period when the ground was frozen. The model satisfactorily simulated NO3− concentrations in the top soil profile, notably during major rainfall events, and maize residue dry matter loss during the experiment. The modeling of biological processes needs to be improved to provide a better simulation of C and N transport in the vadose zone. In particular, the use of WFPS was not sufficient to predict anoxic periods; simulations should improve if soil aggregate structure is also taken into account.
Laboratory Characterization of a Commercial Capacitance Sensor for Estimating Permittivity and Inferring Soil Water Content
Authors: Schwank Mike , Green Timothy R. , Mätzler Christian , Benedickter Hansruedi , Flühler Hannes
Published: August 2006

Ring‐capacitor sensors are used widely for real‐time estimation of volumetric soil water content θ from measured resonant frequencyfr, which is directly affected by the bulk soil permittivity ε. However, the relationshipfr(ε) requires improved quantification. We conducted laboratory experiments to characterize the response of the Sentek EnviroSMART sensor system for a full range of ε values from air to water and a range of temperatures. Water–dioxane mixtures were placed into a solvent‐resistant container equipped with custom tools for heating and mixing the fluid, removing air bubbles from sensitive surfaces, measuring permittivity in situ, and creating an axisymmetric metal disturbance to the electric field. Total capacitanceCwas measured using a vector network analyzer (VNA) connected to one sensor, while four other sensors provided replicatedfrreadings. The measured temperature response of free water permittivity was linear with a negative slope, which is qualitatively consistent with theory. A precise nonlinear relationship between ε and normalizedfrwas derived. The instrumental error in ε was RMSEε= 0.226 (for 3 < ε < 43), which corresponds to a measurement precision in θ(ε) derived from Topp's equation of RMSEθ= 0.0034 m3m−3Axisymmetric numerical simulations of the electric field supplemented the experimental results. The characteristic length scale for the distance measured radially from the access tube is 12.5 mm, meaning that 80 and 95% of the signal are sensed within approximately 20 and 37 mm of the access tube, respectively. The results are crucial for scientific applications of the investigated sensor type to environmental media.
Multiphase, Multicomponent Parameter Estimation for Liquid and Vapor Fluxes in Deep Arid Systems Using Hydrologic Data and Natural Environmental Tracers
Authors: Kwicklis Edward M. , Wolfsberg Andrew V. , Stauffer Philip H. , Walvoord Michelle A. , Sully Michael J.
Published: August 2006

Multiphase, multicomponent numerical models of long‐term unsaturated‐zone liquid and vapor movement were created for a thick alluvial basin at the Nevada Test Site to predict present‐day liquid and vapor fluxes. The numerical models are based on recently developed conceptual models of unsaturated‐zone moisture movement in thick alluvium that explain present‐day water potential and tracer profiles in terms of major climate and vegetation transitions that have occurred during the past 10 000 yr or more. The numerical models were calibrated using borehole hydrologic and environmental tracer data available from a low‐level radioactive waste management site located in a former nuclear weapons testing area. The environmental tracer data used in the model calibration includes tracers that migrate in both the liquid and vapor phases (δD, δ18O) and tracers that migrate solely as dissolved solutes (Cl), thus enabling the estimation of some gas‐phase as well as liquid‐phase transport parameters. Parameter uncertainties and correlations identified during model calibration were used to generate parameter combinations for a set of Monte Carlo simulations to more fully characterize the uncertainty in liquid and vapor fluxes. The calculated background liquid and vapor fluxes decrease as the estimated time since the transition to the present‐day arid climate increases. However, on the whole, the estimated fluxes display relatively little variability because correlations among parameters tend to create parameter sets for which changes in some parameters offset the effects of others in the set. Independent estimates on the timing since the climate transition established from packrat midden data were essential for constraining the model calibration results. The study demonstrates the utility of environmental tracer data in developing numerical models of liquid‐ and gas‐phase moisture movement and the importance of considering parameter correlations when using Monte Carlo analysis to characterize the uncertainty in moisture fluxes.
Isolation and Characterization of Proinsulin-Producing Medullary Thymic Epithelial Cell Clones
Authors: Palumbo Michael O. , Levi Dina , Chentoufi Aziz Alami , Polychronakos Constantin
Published: August 2006

Proinsulin, like many tissue-specific antigens, is expressed by rare (1–3%) cells of the thymus medullary stroma, presumably for the purpose of self-tolerance. Levels of this expression are associated with type 1 diabetes susceptibility in humans and in the NOD mouse. To further understand the mechanism of central tolerance induction by these rare cells, we have isolated and cultured two proinsulin-producing epithelial cell clones from murine thymus. These cells have a typical epithelial morphology and, by flow cytometry, a surface phenotype representative of mature thymic medullary epithelial cells (G8.8+/UEA-1+/DEC205−/CD45−/MHC II+). By RT-PCR, they express predominantly Ins2 as opposed to Ins1, as does whole thymus. Expression of the transcription factor Aire, implicated in enhancing promiscuous thymic expression of tissue-specific antigens, fell to very low levels after a few passages but increased 20-fold upon exposure to an agonistic anti-lymphotoxin B antibody, concurrent with 2.5-fold enhanced insulin expression. RNA of Pdx-1, Glut-2, and Gck was detectable by RT-PCR in whole thymus but not in the clones, suggesting thymic proinsulin expression is Pdx-1 independent and that Pdx-1, Glut-2, and Gck are likely expressed in the thymus as antigens, not as regulatory molecules.
CD40–CD40 Ligand Interaction Activates Proinflammatory Pathways in Pancreatic Islets
Authors: Barbé-Tuana Florencia M. , Klein Dagmar , Ichii Hirohito , Berman Dora M. , Coffey Lane , Kenyon Norma S. , Ricordi Camillo , Pastori Ricardo L.
Published: August 2006

Pancreatic islet transplantation is becoming an alternative to insulin therapy in patients suffering from brittle type 1 diabetes. A major obstacle to the procedure is the early graft loss caused by nonspecific inflammation at the site of implantation. We recently discovered that CD40, a member of tumor necrosis factor (TNF) receptor family, is expressed in pancreatic β-cells. CD40 expression in nonhematopoietic cells is generally associated with inflammation. Therefore, we investigated the potential proinflammatory role of CD40 in human and nonhuman primate islets. Islet β-cells responded to CD40L interaction by secreting interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein (MIP)-1β, the latter a chemokine first reported to be produced by islets. Induction of IL-8 and MIP-1β was confirmed at the transcriptional level by quantitative RT-PCR. MIP-1β expression in β-cells was verified by double-immunofluorescence staining. CD40-CD40L interaction activates extracellular signal–regulated kinase 1/2 and nuclear factor-κB pathways in insulinoma NIT-1 cells, and inhibitors of either pathway suppress cytokine/chemokine production in islets. Moreover, ligation of CD40 receptor upregulates intercellular adhesion molecule-1, associated with inflammation, at both transcriptional and translational levels. Our results in vitro indicate that the CD40 receptor expressed by β-cells could be activated in vivo, inducing proinflammatory responses contributing to early islet graft loss after transplantation.
Enhanced Proatherogenic Responses in Macrophages and Vascular Smooth Muscle Cells Derived From Diabetic db/db Mice
Authors: Li Shu-lian , Reddy Marpadga A. , Cai Qiangjun , Meng Li , Yuan Hang , Lanting Linda , Natarajan Rama
Published: August 2006

Diabetes is associated with enhanced inflammatory responses and cardiovascular complications such as atherosclerosis. However, it is unclear whether similar responses are present in cells derived from experimental animal models of diabetes. We examined our hypothesis that macrophages and short-term cultured vascular smooth muscle cells (VSMCs) derived from obese, insulin-resistant, and diabetic db/db mice would exhibit increased proatherogenic responses relative to those from control db/+ mice. We observed that macrophages from db/db mice exhibit significantly increased expression of key inflammatory cytokines and chemokines as well as arachidonic acid–metabolizing enzymes cyclooxygenase-2 and 12/15-lipoxygenase that generate inflammatory lipids. Furthermore, VSMCs derived from db/db mice also showed similar enhanced expression of inflammatory genes. Expression of inflammatory genes was also significantly increased in aortas derived from db/db mice. Both macrophages and VSMCs from db/db mice demonstrated significantly increased oxidant stress, activation of key signaling kinases, and transcription factors cAMP response element–binding protein and nuclear factor-κB, involved in the regulation of atherogenic and inflammatory genes. Interestingly, VSMCs from db/db mice displayed enhanced migration as well as adhesion to WEHI mouse monocytes relative to db/+. Thus, the diabetic milieu and a potential hyperglycemic memory can induce aberrant behavior of vascular cells. These new results demonstrate that monocyte/macrophages and VSMCs derived from db/db mice display a “preactivated” and proinflammatory phenotype associated with the pathogenesis of diabetic vascular dysfunction and atherosclerosis.
Common Variants in Maturity-Onset Diabetes of the Young Genes Contribute to Risk of Type 2 Diabetes in Finns
Authors: Bonnycastle Lori L. , Willer Cristen J. , Conneely Karen N. , Jackson Anne U. , Burrill Cecily P. , Watanabe Richard M. , Chines Peter S. , Narisu Narisu , Scott Laura J. , Enloe Sareena T. , Swift Amy J. , Duren William L. , Stringham Heather M. , Erdos Michael R. , Riebow Nancy L. , Buchanan Thomas A. , Valle Timo T. , Tuomilehto Jaakko , Bergman Richard N. , Mohlke Karen L. , Boehnke Michael , Collins Francis S.
Published: August 2006

Prior reports have suggested that variants in the genes for maturity-onset diabetes of the young (MODY) may confer susceptibility to type 2 diabetes, but results have been conflicting and coverage of the MODY genes has been incomplete. To complement our previous studies of HNF4A, we examined the other five known MODY genes for association with type 2 diabetes in Finnish individuals. For each of the five genes, we selected 1) nonredundant single nucleotide polymorphisms (SNPs) (r2< 0.8 with other SNPs) from the HapMap database or another linkage disequilibrium map, 2) SNPs with previously reported type 2 diabetes association, and 3) nonsynonymous coding SNPs. We tested 128 SNPs for association with type 2 diabetes in 786 index cases from type 2 diabetic families and 619 normal glucose-tolerant control subjects. We followed up 35 of the most significant SNPs by genotyping them on another 384 case subjects and 366 control subjects from Finland. We also supplemented our previous HNF4A results by genotyping 12 SNPs on additional Finnish samples. After correcting for testing multiple correlated SNPs within a gene, we find evidence of type 2 diabetes association with SNPs in five of the six known MODY genes: GCK, HNF1A, HNF1B, NEUROD1, and HNF4A. Our data suggest that common variants in several MODY genes play a modest role in type 2 diabetes susceptibility.
Glucose Induces Opposite Intracellular Ca2+ Concentration Oscillatory Patterns in Identified α- and β-Cells Within Intact Human Islets of Langerhans
Authors: Quesada Ivan , Todorova Mariana G. , Alonso-Magdalena Paloma , Beltrá Marta , Carneiro Everardo M. , Martin Franz , Nadal Angel , Soria Bernat
Published: August 2006

Homeostasis of blood glucose is mainly regulated by the coordinated secretion of glucagon and insulin from α- and β-cells within the islets of Langerhans. The release of both hormones is Ca2+ dependent. In the current study, we used confocal microscopy and immunocytochemistry to unequivocally characterize the glucose-induced Ca2+ signals in α- and β-cells within intact human islets. Extracellular glucose stimulation induced an opposite response in these two cell types. Although the intracellular Ca2+ concentration ([Ca2+]i) in β-cells remained stable at low glucose concentrations, α-cells exhibited an oscillatory [Ca2+]i response. Conversely, the elevation of extracellular glucose elicited an oscillatory [Ca2+]i pattern in β-cells but inhibited low-glucose–induced [Ca2+]i signals in α-cells. These Ca2+ signals were synchronic among β-cells grouped in clusters within the islet, although they were not coordinated among the whole β-cell population. The response of α-cells was totally asynchronic. Therefore, both the α- and β-cell populations within human islets did not work as a syncitium in response to glucose. A deeper knowledge of α- and β-cell behavior within intact human islets is important to better understand the physiology of the human endocrine pancreas and may be useful to select high-quality islets for transplantation.
Altered Adipose and Plasma Sphingolipid Metabolism in Obesity
Authors: Samad Fahumiya , Hester Kelly D. , Yang Guang , Hannun Yusuf A. , Bielawski Jacek
Published: August 2006

The adipose tissue has become a central focus in the pathogenesis of obesity-mediated cardiovascular and metabolic disease. Here we demonstrate that adipose sphingolipid metabolism is altered in genetically obese (ob/ob) mice. Expression of enzymes involved in ceramide generation (neutral sphingomyelinase [NSMase], acid sphingomyelinase [ASMase], and serine-palmitoyl-transferase [SPT]) and ceramide hydrolysis (ceramidase) are elevated in obese adipose tissues. Our data also suggest that hyperinsulinemia and elevated tumor necrosis factor (TNF)-α associated with obesity may contribute to the observed increase in adipose NSMase, ASMase, and SPT mRNA in this murine model of obesity. Liquid chromatography/mass spectroscopy revealed a decrease in total adipose sphingomyelin and ceramide levels but an increase in sphingosine in ob/ob mice compared with lean mice. In contrast to the adipose tissue, plasma levels of total sphingomyelin, ceramide, sphingosine, and sphingosine 1-phosphate (S1P) were elevated in ob/ob mice. In cultured adipocytes, ceramide, sphingosine, and S1P induced gene expression of plasminogen activator inhibitor-1, TNF-α, monocyte chemoattractant protein-1, interleukin-6, and keratinocyte-derived chemokine. Collectively, our results identify a novel role for sphingolipids in contributing to the prothrombotic and proinflammatory phenotype of the obese adipose tissue currently believed to play a major role in the pathogenesis of obesity-mediated cardiovascular and metabolic disease.
Polymorphisms in the Transcription Factor 7-Like 2 (TCF7L2) Gene Are Associated With Type 2 Diabetes in the Amish
Authors: Damcott Coleen M. , Pollin Toni I. , Reinhart Laurie J. , Ott Sandra H. , Shen Haiqing , Silver Kristi D. , Mitchell Braxton D. , Shuldiner Alan R.
Published: August 2006

Transcription factor 7-like 2 (TCF7L2) regulates genes involved in cell proliferation and differentiation. The TCF7L2 gene is located on chromosome 10q25 in a region of replicated linkage to type 2 diabetes. Recently, a microsatellite marker in intron 3 (DG10S478) and five correlated single nucleotide polymorphisms (SNPs) were identified in Icelandic individuals that showed strong association with type 2 diabetes, which was replicated in Danish and European-American cohorts. We genotyped four of the SNPs (rs7901695, rs7903146, rs11196205, and rs12255372) in Amish subjects with type 2 diabetes (n = 137), impaired glucose tolerance (IGT; n = 139), and normal glucose tolerance (NGT; n = 342). We compared genotype frequencies in subjects with type 2 diabetes with those with NGT and found marginal association for rs7901695 (P = 0.05; odds ratio [OR] 1.51); comparison between NGT control subjects and the combined type 2 diabetes/IGT case group showed strong association with rs7901695 and rs7903146 (P = 0.008–0.01; OR 1.53–1.57) and marginal association with rs11196205 and rs12255372 (P = 0.07 and P = 0.04, respectively). In an expanded set of 698 Amish subjects without diabetes, we found no association with insulin and glucose levels during a 3-h oral glucose tolerance test. We also genotyped these SNPs in nondiabetic, non-Amish subjects (n = 48), in whom intravenous glucose tolerance tests were performed, and found an association between rs7901695 and rs7903146 and insulin sensitivity (P = 0.003 and P = 0.005, respectively) and disposition index (P = 0.04 and P = 0.007, respectively). These data provide replicating evidence that variants in TCF7L2 increase the risk for type 2 diabetes and novel evidence that the variants likely influence both insulin secretion and insulin sensitivity.
Association of Transcription Factor 7-Like 2 (TCF7L2) Variants With Type 2 Diabetes in a Finnish Sample
Authors: Scott Laura J. , Bonnycastle Lori L. , Willer Cristen J. , Sprau Andrew G. , Jackson Anne U. , Narisu Narisu , Duren William L. , Chines Peter S. , Stringham Heather M. , Erdos Michael R. , Valle Timo T. , Tuomilehto Jaakko , Bergman Richard N. , Mohlke Karen L. , Collins Francis S. , Boehnke Michael
Published: August 2006

Transcription factor 7-like 2 (TCF7L2) is part of the Wnt signaling pathway. Genetic variants within TCF7L2 on chromosome 10q were recently reported to be associated with type 2 diabetes in Icelandic, Danish, and American (U.S.) samples. We previously observed a modest logarithm of odds score of 0.61 on chromosome 10q, ∼1 Mb from TCF7L2, in the Finland-United States Investigation of NIDDM Genetics study. We tested the five associated TCF7L2 single nucleotide polymorphism (SNP) variants in a Finnish sample of 1,151 type 2 diabetic patients and 953 control subjects. We confirmed the association with the same risk allele (P value <0.05) for all five SNPs. Our strongest results were for rs12255372 (odds ratio [OR] 1.36 [95% CI 1.15–1.61], P = 0.00026) and rs7903146 (1.33 [1.14–1.56], P = 0.00042). Based on the CEU HapMap data, we selected and tested 12 additional SNPs to tag SNPs in linkage disequilibrium with rs12255372. None of these SNPs showed stronger evidence of association than rs12255372 or rs7903146 (OR ≤1.26, P ≥ 0.0054). Our results strengthen the evidence that one or more variants in TCF7L2 are associated with increased risk of type 2 diabetes.
Association Analysis of 6,736 U.K. Subjects Provides Replication and Confirms TCF7L2 as a Type 2 Diabetes Susceptibility Gene With a Substantial Effect on Individual Risk
Authors: Groves Christopher J. , Zeggini Eleftheria , Minton Jayne , Frayling Timothy M. , Weedon Michael N. , Rayner Nigel W. , Hitman Graham A. , Walker Mark , Wiltshire Steven , Hattersley Andrew T. , McCarthy Mark I.
Published: August 2006

Recent data suggest that common variation in the transcription factor 7-like 2 (TCF7L2) gene is associated with type 2 diabetes. Evaluation of such associations in independent samples provides necessary replication and a robust assessment of effect size. Using four TCF7L2 single nucleotide polymorphisms (SNPs; including the two most associated in the previous study), we conducted a case-control study in 2,158 type 2 diabetic subjects and 2,574 control subjects and a family-based association analysis in 388 parent-offspring trios all from the U.K. All SNPs showed powerful associations with diabetes in the case-control analysis, with strongest effects at rs7903146 (allele-wise relative risk 1.36 [95% CI 1.24–1.48], P = 1.3 × 10−11). Data were consistent with a multiplicative model. The family-based analyses provided independent evidence for association at all loci (e.g., rs4506565, 62% transmission, P = 7 × 10−5) with no parent-of-origin effects. The frequency of diabetes-associated TCF7L2 genotypes was greater in cases ascertained for positive family history and early onset (rs4606565, P = 0.02); the population-attributable risk, estimated from the least-selected cases, is ∼16%. The overall evidence for association for these variants (P = 4.4 × 10−14 combining case-control and family-based analyses for rs4506565) exceeds genome-wide significance criteria and clearly establishes TCF7L2 as a type 2 diabetes susceptibility gene of substantial importance.
ATP Sensitivity of the ATP-Sensitive K+ Channel in Intact and Permeabilized Pancreatic β-Cells
Authors: Tarasov Andrei I. , Girard Christophe A.J. , Ashcroft Frances M.
Published: August 2006

ATP-sensitive K+ channels (KATP channels) couple cell metabolism to electrical activity and thereby to physiological processes such as hormone secretion, muscle contraction, and neuronal activity. However, the mechanism by which metabolism regulates KATP channel activity, and the channel sensitivity to inhibition by ATP in its native environment, remain controversial. Here, we used α-toxin to permeabilize single pancreatic β-cells and measure KATP channel ATP sensitivity. We show that the channel ATP sensitivity is approximately sevenfold lower in the permeabilized cell than in the inside-out patch and that this is caused by interaction of Mg-nucleotides with the nucleotide-binding domains of the SUR1 subunit of the channel. The ATP sensitivity observed in permeabilized cells accounts quantitatively for KATP channel activity in intact cells. Thus, our results show that the principal metabolic regulators of KATP channel activity are MgATP and MgADP.
A Disease Haplotype for Advanced Nephropathy in Type 2 Diabetes at the ACE Locus
Authors: Ng Daniel P.K. , Placha Grzegorz , Choo Serena , Chia Kee-seng , Warram James H. , Krolewski Andrzej S.
Published: August 2006

Previous investigations of the ACE gene as a susceptibility factor for diabetic nephropathy have primarily focused on its insertion/deletion (Ins/Del) polymorphism. In a departure from these earlier studies, we used three tagging markers (A-5466C, T-3892C, and Ins/Del) at the ACE locus to test for disease haplotype associations. A case-control study design was used where case subjects were type 2 diabetic patients with advanced diabetic nephropathy, as indicated by the presence of proteinuria or chronic renal failure/end-stage renal disease, while control subjects were normoalbuminuric, despite >6 years of diabetes. None of the individual markers showed significant disease association when considered on their own. However, haplotype analyses revealed a near doubling in the prevalence of the A.T.D risk haplotype in case subjects (0.136) compared with control subjects (0.075) (P = 0.009), thus providing first evidence for a disease haplotype for advanced diabetic nephropathy at the ACE locus.
Relationships of Serum Ferritin, Transferrin Saturation, and HFE Mutations and Self-Reported Diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) Study
Authors: Acton Ronald T. , Barton James C. , Passmore Leah V. , Adams Paul C. , Speechley Mark R. , Dawkins Fitzroy W. , Sholinsky Phyliss , Reboussin David M. , McLaren Gordon D. , Harris Emily L. , Bent Thomas C. , Vogt Thomas M. , Castro Oswaldo
Published: August 2006

OBJECTIVE—We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study.

RESEARCH DESIGN AND METHODS—Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis.

RESULTS—The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center.

CONCLUSIONS—Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload.
Disparities in HbA1c Levels Between African-American and Non-Hispanic White Adults With Diabetes
Authors: Kirk Julienne K. , D’Agostino Ralph B. , Bell Ronny A. , Passmore Leah V. , Bonds Denise E. , Karter Andrew J. , Narayan K.M. Venkat
Published: August 2006

OBJECTIVE—Among individuals with diabetes, a comparison of HbA1c (A1C) levels between African Americans and non-Hispanic whites was evaluated. Data sources included PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health, the Cochrane Library, the Combined Health Information Database, and the Education Resources Information Center.

RESEARCH DESIGN AND METHODS—We executed a search for articles published between 1993 and 2005. Data on sample size, age, sex, A1C, geographical location, and study design were extracted. Cross-sectional data and baseline data from clinical trials and cohort studies for African Americans and non-Hispanic whites with diabetes were included. Diabetic subjects aged <18 years and those with pre-diabetes or gestational diabetes were excluded. We conducted a meta-analysis to estimate the difference in the mean values of A1C for African Americans and non-Hispanic whites.

RESULTS—A total of 391 studies were reviewed, of which 78 contained A1C data. Eleven had data on A1C for African Americans and non-Hispanic whites and met selection criteria. A meta-analysis revealed the standard effect to be 0.31 (95% CI 0.39–0.25). This standard effect correlates to an A1C difference between groups of ∼0.65%, indicating a higher A1C across studies for African Americans. Grouping studies by study type (cross-sectional or cohort), method of data collection for A1C (chart review or blood draw), and insurance status (managed care or nonmanaged care) showed similar results.

CONCLUSIONS—The higher A1C observed in this meta-analysis among African Americans compared with non-Hispanic whites may contribute to disparity in diabetes morbidity and mortality in this population.