bluuebunny/crossref_metadata_2025 huggingface dataset:
Dust radiative feedback on Saharan boundary layer dynamics and dust mobilization
Authors: Heinold B. , Tegen I. , Schepanski K. , Hellmuth O.
Published: October 2008

Mineral dust radiative effects and feedbacks upon Saharan boundary layer meteorology are estimated by means of regional dust simulations for a one‐week period in May 2006. The regional dust model system LM‐MUSCAT is used, which allows online interaction of the computed dust load with the solar and thermal radiation and consequently with the model dynamics. For the Bodélé depression, a mechanism is proposed that describes positive and negative dust radiative feedbacks on surface wind speeds and dust emission in dependence on atmospheric stratification, dust‐induced stabilization, and baroclinity. These effects are attributed to the formation and breakdown of the low‐level jet (LLJ), which is a common phenomenon in the Bodélé. However, such processes are likely also relevant for other Saharan regions.
Geomagnetic field variations during the last 400 kyr in the western equatorial Pacific: Paleointensity‐inclination correlation revisited
Authors: Yamazaki Toshitsugu , Kanamatsu Toshiya , Mizuno Sakiko , Hokanishi Natsumi , Gaffar Eddy Z.
Published: October 2008

A paleomagnetic study was conducted on four piston cores newly obtained from the West Caroline Basin in the western equatorial Pacific in order to investigate variations in paleointensity and inclination during the last 400 kyr. An inclination‐intensity correlation was previously reported in this region using giant piston cores, but the quality of the paleomagnetic data of the younger end, the last ca. 300 kyr, was needed to be checked because the upper part of the giant piston cores could suffer from perturbation by oversampling. Age control is based on the oxygen‐isotope ratios for one core and inter‐core correlation using relative paleointensity for other cores. Stacked curves of paleointensity and inclination were constructed from the four cores. It was confirmed that variations on the order of 104 to 105 years occur in inclination as well as paleointensity. A cross‐correlation analysis showed that significant in‐phase correlation occurs between intensity and inclination for periods longer than about 25 kyr, and power spectra of both paleointensity and inclination variations have peaks at ∼100 kyr periods. The regional paleointensity stack with higher resolution than the Sint‐800 stack (Guyodo and Valet, 1999) should be useful for paleointensity‐assisted chronostratigraphy.
Effects of compositional and rheological stratifications on small‐scale convection under the oceans: Implications for the thickness of oceanic lithosphere and seafloor flattening
Authors: Afonso J. C. , Zlotnik S. , Fernàndez M.
Published: October 2008

Pressure‐release melting at mid‐ocean ridges generate compositional and rheological layering in the oceanic mantle that may control the evolution of the oceanic lithosphere. We use dynamic models coupled with melting and petrological models to explore 1) the influence of this layering on the development of small‐scale convection under the oceans, 2) its role in determining the thickness of oceanic lithosphere, and 3) its feasibility as responsible for the deviations of seafloor and surface heat flow from predictions by conductive models in mature oceanic lithosphere. Here we show that the existence of small‐scale convection is entirely compatible with experimental creep parameters and flow laws, and that the viscosity stratification due to melt extraction (i.e., H2O removal) is the main factor controlling the plate's thermal evolution, its asymptotic thickness, and the flattening of seafloor and surface heat flow at ages ≳70 Ma. The effects of Al‐rich phase transitions and compositional layering are minor.
Stirring in the global surface ocean
Authors: Waugh Darryn W. , Abraham Edward R.
Published: October 2008

Global variations of stirring in the surface ocean are quantified using finite‐time Lyapunov exponents (FTLEs) calculated from currents derived from satellite altimetry. It is shown that the stirring is highly non‐uniform, and the probability distribution functions (PDFs) of the FTLEs are broad, asymmetric, and have long high‐stretch tails. The characteristics of the PDFs vary with mesoscale activity and integration time: There are larger values and broader PDFs in regions of high strain rates and eddy kinetic energy (EKE), e.g., western boundary currents and the Antarctic Circumpolar Current, and for shorter integration times. The PDFs have a near‐universal relationship with the mean strain of a region, and are reasonably well fit by Weibull distributions. The above variations in the stirring may help our understanding of the distribution and spatial heterogeneities of biogeochemical tracers, and raise the possibility of developing a parameterization of the stirring based on the, easily‐calculated, EKE.
Seasonal and longitudinal dependence of equatorial disturbance vertical plasma drifts
Authors: Fejer Bela G. , Jensen John W. , Su Shin‐Yi
Published: October 2008

We used equatorial measurements from the ROCSAT‐1 satellite to determine the seasonal and longitudinal dependent equatorial F region disturbance vertical plasma drifts. Following sudden increases in geomagnetic activity, the prompt penetration vertical drifts are upward during the day and downward at night, and have strong local time dependence at all seasons. The largest prompt penetration drifts near dusk and dawn occur during June solstice. The daytime disturbance dynamo drifts are small at all seasons. They are downward near dusk with largest (smallest) values during equinox (June solstice); the nighttime drifts are upward with the largest magnitudes in the postmidnight sector during December solstice. During equinox, the downward disturbance dynamo drifts near sunset are largest in the eastern hemisphere, while the late night upward drifts are largest in the western hemisphere. The longitudinal dependence of the disturbance dynamo drifts is in good agreement with results from simulation studies.
World water tower: An atmospheric perspective
Authors: Xu Xiangde , Lu Chungu , Shi Xiaohui , Gao Shouting
Published: October 2008

A large amount of water is stored in the world's highest and largest plateau, the Tibetan Plateau, in the forms of glaciers, snowpacks, lakes, and rivers. It is vital to understand where these waters come from and whether the supply to these water resources has been experiencing any changes during recent global warming. Here we show the maintenance of water content in the atmosphere over the Tibetan Plateau, the atmospheric circulations and transports of water vapor to this part of the world, and the trend of the water vapor supply. The Tibetan Plateau serves as a role of “the world water tower”, and its land‐ocean‐atmosphere interaction provides a profound impact on the global natural and climate environment. The analyses of a half‐century time series of atmospheric water vapor, precipitation, and surface temperature indicate that the atmospheric supply to this water tower presents an increasing trend under recent global warming condition.
Modeling the thermospheric response to solar flares
Authors: Pawlowski David J. , Ridley Aaron J.
Published: October 2008

Measurements of the incoming solar extreme ultraviolet (EUV) irradiance now allow models to be driven at higher temporal resolution and with better accuracy than with proxy‐based models. Using solar irradiance measurements from the Solar EUV Experiment (SEE) instrument to drive the Global Ionosphere‐Thermosphere Model, the global thermospheric response to the 28 October 2003 and 6 November 2004 solar flares is presented. The model indicates that the thermospheric density at 400 km can increase by as much as 14.6% in under 2 hours because of the flare and takes 12 hours to settle to close to a nominal state. Intense dayside heating launches nightward propagating gravity waves that transport energy efficiently to the nightside at velocities near the local sound speed plus the bulk wind velocity. Measurements from the Champ satellite indicate that the simulated day to night propagation time is similar to the observed one. Substantial density enhancements occur near the midnight sector as the wave converges on itself. In some locations the nightside perturbations are as large as those on the dayside. The convergence of the wave also leads to significant adiabatic heating of the nightside thermosphere. Eventually, the wave is reflected back toward the dayside but is quickly damped.
V‐shaped VLF streaks recorded on DEMETER above powerful thunderstorms
Authors: Parrot M. , Inan U. S. , Lehtinen N. G.
Published: October 2008

We report the observation of unusual V‐shaped streaks on VLF spectra observed on the low‐altitude satellite DEMETER during its overcrossing of highly active (i.e., high lightning flash rate) thunderstorms. At ∼700 km, wave activity observed on the E‐field spectrograms at mid‐to‐low latitudes during nighttime are mainly dominated by upgoing 0+ whistlers and occasional reflected (from the other hemisphere) whistler components. Over a 3 year period, 87 events with V‐shaped streaks associated with intense and numerous 0+ whistlers in VLF range have been observed. Using the National Lightning Detection Network for cases above the North American region indicates that these V‐shaped streaks exclusively occur when DEMETER passes above intense isolated thunderstorms, with relatively high (tens per second) lightning flash activity. Using a new model of VLF propagation in the Earth‐ionosphere waveguide, and transionospheric leakage to the satellite altitude, it is shown that the funnel‐like “V” shape of the streaks is a simple consequence of the mapping to high altitude of frequency‐dependent position of mode interference nulls (and crests) within the Earth‐ionosphere waveguide.
Regional variability of the composition of mineral dust from western Africa: Results from the AMMA SOP0/DABEX and DODO field campaigns
Authors: Formenti P. , Rajot J. L. , Desboeufs K. , Caquineau S. , Chevaillier S. , Nava S. , Gaudichet A. , Journet E. , Triquet S. , Alfaro S. , Chiari M. , Haywood J. , Coe H. , Highwood E.
Published: October 2008

This paper presents data on elemental and mineralogical composition of mineral dust from various source regions of Africa collected during the African Monsoon Multidisciplinary Analyses (AMMA) SOP0/DABEX and Dust Ouflow and Deposition to the Ocean (DODO) DODO1 experiments (January–February 2006), and the DODO2 campaign (August 2006). Bulk filter samples were collected at the AMMA supersite of Banizoumbou, Niger, as well as on board the Facility for Airborne Atmospheric Measurements (FAAM) BAe‐146 aircraft. Both mineral dust and biomass burning in external mixing occurred in surface and elevated layers during the winter field phase of the campaign. However, mineral dust was overwhelming, accounting for 72% of the estimated aerosol mass in aged elevated biomass burning layers and up to 93% in plumes of mineral dust, which generally occurred in the boundary layer. A number of well‐defined episodes of advection of mineral dust could be identified both at the ground and on the aircraft. The elemental and mineralogical composition varied depending on source region. This variability could be well traced by the calcium content, which is enhanced in dust from North Africa but depleted in dust from the Sahel. Iron oxides in the form of hematite and goethite are enriched in dust emitted within Sahel and in Mauritania, whereas dust from the Bodélé depression is iron‐oxide depleted. Iron oxides represented between 2.4% and 4.5% of the total estimated dust oxide mass. This regional variability will have to be taken into account in estimating the optical properties of absorption of mineral dust from western Africa.
Coordinated analysis of delayed sprites with high‐speed images and remote electromagnetic fields
Authors: Li J. , Cummer S. A. , Lyons W. A. , Nelson T. E.
Published: October 2008

Simultaneous measurements of high‐altitude optical emissions and magnetic fields produced by sprite‐associated lightning discharges enable a close examination of the link between low‐altitude lightning processes and high‐altitude sprite processes. We report results of the coordinated analysis of high‐speed sprite video and wideband magnetic field measurements recorded simultaneously at Yucca Ridge Field Station and Duke University. From June to August 2005, sprites were detected following 67 lightning strokes, all of which had positive polarity. Our data showed that 46% of the 83 discrete sprite events in these sequences initiated more than 10 ms after the lightning return stroke, and we focus on these delayed sprites in this work. All delayed sprites were preceded by continuing current moments that averaged at least 11 kA km between the return stroke and sprites. The total lightning charge moment change at sprite initiation varied from 600 to 18,600 C km, and the minimum value to initiate long‐delayed sprites ranged from 600 for 15 ms delay to 2000 C km for more than 120 ms delay. We numerically simulated electric fields at altitudes above these lightning discharges and found that the maximum normalized electric fields are essentially the same as fields that produce short‐delayed sprites. Both estimated and simulation‐predicted sprite initiation altitudes indicate that long‐delayed sprites generally initiate around 5 km lower than short‐delayed sprites. The simulation results also reveal that slow (5–20 ms) intensifications in continuing current can play a major role in initiating delayed sprites.
On the correlation structure of water vapor and carbon dioxide in the atmospheric surface layer: A basis for flux partitioning
Authors: Scanlon Todd M. , Sahu Parameswar
Published: October 2008

High‐frequency measurements of water vapor (q) and carbon dioxide (c) concentrations were collected over the course of a transition from dry to wet surface conditions in an agricultural setting on the eastern shore of Virginia. Daytime correlation coefficients between q and c were close to −1 during the dry conditions but became degraded during the wet conditions. An application of wavelet analysis to the high‐frequency time series showed that the degraded q‐c correlations on the wet day were mainly caused by the influence of large‐scale eddies, which introduced positively correlated q‐c components to the half‐hour time series. Consistent differences in q‐c correlation were also observed for smaller eddy scales, which are more indicative of the surface‐atmosphere exchange. Correlations between q and c for this range of eddy scales were likewise closer to −1 for dry conditions, when transfer efficiencies of both scalars exhibited greater similarity. These correlations are influenced by the nonidentical source‐sink distributions of the water vapor and carbon dioxide fluxes and the relative magnitude of their constituent fluxes. A new method is introduced to estimate the components of the water vapor flux (transpiration and direct evaporation) and carbon dioxide flux (photosynthesis and respiration) by applying flux variance similarity assumptions separately to the stomatal and the nonstomatal exchange and by considering q‐c correlation. Water use efficiency for the vegetation, and how it varies with respect to vapor pressure deficit, is the only input needed for this approach that uses standard eddy covariance measurements. Reasonable estimates yielded by this technique when applied to the contrasting wet and dry days demonstrate its potential for flux partitioning.
GO faster ChEBI with Reasonable Biochemistry
Authors: Hull Duncan
Published: October 2008

Chemical Entities of Biological Interest (ChEBI) [1] is a database and ontology that represents knowledge about more than 15,000 small molecules and their biochemistry. The database does not currently use description logic reasoning or OWL, but is investigating this possibility for better, cheaper and faster ontology development in the future. This poster describes four specific problems and solutions to reasoning in ChEBI: 1. Using necessary and sufficient conditions 2. identifying inconsistencies 3. Improving alignment with the the Gene Ontology (GO) 4. Reasoning with chemical structures.
Apolipoprotein A‐IV, a Putative Satiety/Antiatherogenic Factor, Rises After Gastric Bypass
Authors: Culnan Derek M. , Cooney Robert N. , Stanley Bruce , Lynch Christopher J.
Published: October 2008

Roux‐en‐Y gastric bypass surgery (RYGBP) leads to improvements in satiety and obesity‐related comorbidities. The mechanism(s) underlying these improvements are not known but may be revealed in part by discovery proteomics. Therefore, fasting plasma was collected from 12 subjects (mean BMI >45) during RYGBP and during a second procedure ∼17 months later. Body weight, obesity‐related comorbidities, and medication use were decreased after RYGBP. Mass spectrometry‐based proteomic analysis was performed on a subset of seven samples using isobaric isotope‐coded affinity tags (four plex iTRAQ). Initial proteomic analysis (n = 7) quantified and identified hundreds of plasma proteins. Manual inspection of the data revealed a 2.6 ± 0.5‐fold increase in apolipoprotein A‐IV (apo A‐IV, gene designation: APOA4), a ∼46‐kDa glycoprotein synthesized mainly in the bypassed small bowel and liver after RYGBP. The change in apo A‐IV was significantly greater than other apolipoproteins. Immunoblot analysis of the full longitudinal sample set (n = 12) indicated even higher increases (8.3 ± 0.2 fold) in apo A‐IV. Thus iTRAQ may underestimate the changes in protein concentrations compared to western blotting of apo A‐IV. Apo A‐IV inhibits gastric emptying and serves as a satiety factor whose synthesis and secretion are increased by the ingestion of dietary fat. It also possesses anti‐inflammatory and antiatherogenic properties. Based on these functions, we speculate changes in apo A‐IV may contribute to weight loss as well as the improvements in inflammation and cardiovascular disease after RYGBP. In addition, the findings provide evidence validating the use of iTRAQ proteomics in discovery‐based studies of post‐RYGBP improvements in obesity‐related medical comorbidities.
A Rapid PCR‐based Method for the Identification of ob Mutant Mice
Authors: Ellett Justin D. , Evans Zachary P. , Zhang Guojing , Chavin Kenneth D. , Spyropoulos Demetri D.
Published: October 2008

With increasing incidence of obesity, there is greater demand for suitable research and therapeutic models. The ob/ob mouse model develops obesity by 5 weeks of age. Previously, a method using DNA purification, PCR, and restriction digestion of products was devised to identify mice bearing the ob allele. Here, we describe a direct PCR method that requires no DNA purification. Wild‐type and ob‐specific primers are used under the same conditions in two separate and simultaneously run three‐primer PCRs. Standard PCR using the wild‐type primer mix produces 191 bp and 104 bp bands in +/+ and ob/+ and only the control 191 bp band in ob/ob animals. The ob‐specific primer reaction produces 191 bp and 123 bp bands in ob/+ and ob/ob and only the control 191 bp band in +/+ animals. Phenotypic weight gain in offspring of heterozygous intercrosses was used to validate genotypes. This primer‐specific PCR method allows simultaneous identification of +/+, ob/+, and ob/ob genotypes prior to breeding age to facilitate breeding and research studies in an important model of clinical obesity.
Impact of Waist Circumference on Cardiac Phenotype in Hypertensives According to Gender
Authors: Tsioufis Costas P. , Tsiachris Dimitris L. , Selima Maria N. , Dimitriadis Kyriakos S. , Thomopoulos Costas G. , Tsiliggiris Dimitris C. , Gennadi Aliki S. , Syrseloudis Dimitris C. , Stefanadi Elli S. , Toutouzas Kostas P. , Kallikazaros Ioannis E. , Stefanadis Christodoulos I.
Published: October 2008

Our aim was to assess the differential effect of waist circumference on left‐ventricular (LV) structural and functional alterations, in hypertensive males and females. One thousand seven hundred and eighty nine consecutive, nondiabetic, essential hypertensives (aged 55.8 ± 13.5 years, 966 females), included in the 3H Study, an ongoing registry of hypertension‐related‐target‐organ damage, were classified to obese and nonobese groups according to Adult Treatment Panel III criteria. All participants underwent complete echocardiographic study including LV diastolic function evaluation by means of conventional and tissue Doppler imaging (TDI) methods, averaging early and late diastolic mitral annular peak velocities (Em, Am, Em/Am) from four separate sites of measurement. Hypertensive obese women compared with nonobese exhibited significantly greater LV mass index and prevalence of LV hypertrophy (by 5.5 g/m2, P = 0.003, and 8.8%, P = 0.005, respectively), while such differences were not present among men. Obese women compared to nonobese ones were accompanied by lower transmitral E/A (by 0.08, P < 0.001), TDI‐derived Em/Am (by 0.12, P < 0.001), and higher E/Em ratio (by 0.8, P = 0.016). In contrast, hypertensive obese men compared to nonobese ones exhibited lower E and Em (by 0.04 m/s and 0.6 cm/s, both P < 0.05). A significant interaction between sex and abdominal obesity was observed only regarding TDI‐derived Am and Em/Am. Furthermore, waist circumference was a predictor of E/A (β = −0.097, P = 0.002) and Em/Am (β = −0.116, P = 0.001), independently of body size, in females but not in males. The adverse effect of abdominal obesity on LV alterations is more pronounced among female hypertensives, suggesting that routine measurement of waist circumference provides additional information on cardiac phenotype especially in women.
Association of the FTO rs9939609 Single Nucleotide Polymorphism With C‐reactive Protein Levels
Authors: Fisher Eva , Schulze Matthias B. , Stefan Norbert , Häring Hans‐Ulrich , Döring Frank , Joost Hans‐Georg , Al‐Hasani Hadi , Boeing Heiner , Pischon Tobias
Published: October 2008

Adipose tissue is a key factor determining C‐reactive protein (CRP) plasma levels. Variation at the fat‐mass and obesity‐associated (FTO) gene locus has been reported to be associated with increased body fat. We investigated whether the FTO rs9939609 T>A single nucleotide polymorphism might alter CRP levels in a population‐based sample of 2,415 participants from a large prospective cohort study. Genotype/phenotype relationships were studied by linear trend analysis stratified by sex. The rs9939609 A‐allele was significantly associated with CRP levels in both genders (men, +21%, P = 0.002; women, +14%, P = 0.01 per A‐allele). The association was attenuated, but remained statistically significant after additional adjustment for BMI, waist‐to‐hip ratio, and other potential confounding factors (men, +14%, P = 0.03; women, +12%, P = 0.02; per A‐allele). Similar results were obtained when subjects with CRP levels higher then 10 mg/l were excluded. Our data provide preliminary evidence that the FTO rs9939609 T>A polymorphism contributes to variation in plasma CRP levels independently of obesity indices.
The Regulation of Acyl‐CoA Dehydrogenases in Adipose Tissue by Rosiglitazone
Authors: Goetzman Eric S.
Published: October 2008

The acyl‐CoA dehydrogenases (ACADs), which catalyze the rate‐limiting step in the mitochondrial β‐oxidation spiral, were investigated in white adipose tissue (WAT) of C57Bl/6 mice treated with 10 mg/kg/day rosiglitazone. Rosiglitazone was also administered to PPAR‐α knockout mice. ACAD abundance and activity were determined using western blotting and an ACAD enzyme activity assay. Rosiglitazone increased ACAD activity in both epididymal and inguinal WAT but not in brown adipose tissue, liver, or muscle. Given the known function of PPAR‐α in regulating the expression of ACAD genes in liver, it was hypothesized that PPAR‐α may be involved in upregulating the ACADs during rosiglitazone‐mediated adipose tissue remodeling. However, the effect of rosiglitazone on adipose tissue ACAD activity was the same in wild‐type and PPAR‐α knockout mice. In conclusion, rosiglitazone increases expression and activity of ACAD enzymes in WAT independently of PPAR‐α.
Inverse Association Between BMI and Prefrontal Metabolic Activity in Healthy Adults
Authors: Volkow Nora D. , Wang Gene‐Jack , Telang Frank , Fowler Joanna S. , Goldstein Rita Z. , Alia‐Klein Nelly , Logan Jean , Wong Christopher , Thanos Panayotis K. , Ma Yemine , Pradhan Kith
Published: October 2008

Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2‐deoxy‐2[18F]fluoro‐d‐glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19–37 kg/m2) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity.
The Q121 Variant of ENPP1 May Protect From Childhood Overweight/obesity in the Italian Population
Authors: Morandi Anita , Pinelli Leonardo , Petrone Antonio , Vatin Vincent , Buzzetti Raffaella , Froguel Philippe , Meyre David
Published: October 2008

Ectonucleotide Pyrophosphatase Phosphodiesterase 1 (ENPP1) downregulates insulin signaling by inhibiting the insulin receptor's tyrosine‐kinase. K121Q and other ENPP1 single‐nucleotide polymorphisms (SNPs), IVS20delT‐11 and A/G+1044TGA, have been previously associated with obesity in French children, and the risk haplotype QdelTG has also been associated with this condition in both French and German children. Our aim was to perform a case‐control replication study in order to assess the possible association of childhood obesity and overweight with the above‐mentioned ENPP1 SNPs, and with the QdelTG haplotype, in the Italian population. A total of 865 healthy Italian children were studied: 453 normal‐weight, 243 overweight and 169 obese subjects. Genotyping was performed by Taq‐Man or Light‐Cycler Technology. The Q variant of K121Q showed a negative association with overweight‐obesity under both additive (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.57–0.97, P = 0.030) and recessive (OR = 0.32, 95% CI = 0.10–0.97, P = 0.035) modes of inheritance. The Z‐score of BMI showed a significant decreasing trend from children K/K homozygous to K/Q heterozygous, and to Q/Q homozygous (0.45 vs. 0.28 vs. −0.19; P = 0.009), according to the additive model. The two other SNPs and the QdelTG haplotype did not exhibit any association with overweight/obesity. This is the first child‐based study showing a protective role of the 121Q variant of ENPP1 against overweight/obesity.
Isorhamnetin Represses Adipogenesis in 3T3‐L1 Cells
Authors: Lee Jongsung , Jung Eunsun , Lee Jienny , Kim Saebom , Huh Sungran , Kim Youngsoo , Kim Yongwoo , Byun Sang Yo , Kim Yeong‐Shik , Park Deokhoon
Published: October 2008

Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol‐3‐phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator‐activated receptor‐γ (PPAR‐γ) and CCAAT/enhancer‐binding protein‐α (C/EBP‐α), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP‐β and ‐δ, the upstream regulators of PPAR‐γ and C/EBP‐α, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR‐γ target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor‐α (LXR‐α) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR‐γ expression as a possible mechanism underlying the isorhamnetin‐mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR‐γ and C/EBP‐α.
Changes in the Serum Composition of Free‐fatty Acids During an Intravenous Glucose Tolerance Test
Authors: Soriguer Federico , García‐Serrano Sara , García‐Almeida Jose M. , Garrido‐Sánchez Lourdes , García‐Arnés Juan , Tinahones Francisco J. , Cardona Isabel , Rivas‐Marín Jose , Gallego‐Perales Jose L. , García‐Fuentes Eduardo
Published: October 2008

Recent studies suggest that measuring the free‐fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal‐fasting glucose (NFG) than in the severely obese persons with impaired‐fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n‐6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.
Dietary Resistant Starch Increases Hypothalamic POMC Expression in Rats
Authors: Shen Li , Keenan Michael J. , Martin Roy J. , Tulley Richard T. , Raggio Anne M. , McCutcheon Kathleen L. , Zhou Jun
Published: October 2008

Resistant starch (RS) is fermentable dietary fiber. Inclusion of RS in the diet causes decreased body fat accumulation and altered gut hormone profile. This study investigates the effect of feeding RS on the neuropeptide messenger RNA (mRNA) expressions in the arcuate nucleus (ARC) of the hypothalamus and whether vagal afferent nerves are involved. The rats were injected intraperitoneally with capsaicin to destroy unmyelinated small vagal afferent nerve fibers. The cholecystokinin (CCK) food suppression test was performed to validate the effectiveness of the capsaicin treatment. Then, capsaicin‐treated rats and vehicle‐treated rats were subdivided into a control diet or a RS diet group, and fed the corresponding diet for 65 days. At the end of study, body fat, food intake, plasma peptide YY (PYY) and glucagon‐like peptide 1 (GLP‐1), and hypothalamic pro‐opiomelanocortin (POMC), neuropeptide Y (NPY), agouti‐related peptide (AgRP) gene expressions were measured. RS‐fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP‐1 in both the capsaicin and vehicle‐treated rats. Hypothalamic NPY and AgRP gene expressions were not changed by RS or capsaicin. Therefore, destruction of the capsaicin‐sensitive afferent nerves did not alter the response to RS in rats. These findings suggest that dietary RS might reduce body fat through increasing the hypothalamic POMC expression and vagal afferent nerves are not involved in this process. This is the first study to show that dietary RS can alter hypothalamic POMC expression.
Effects of Maintained Weight Loss on Sleep Dynamics and Neck Morphology in Severely Obese Adults
Authors: Hernandez Teri L. , Ballard Robert D. , Weil Kathleen M. , Shepard Trudy Y. , Scherzinger Ann L. , Stamm Elizabeth R. , Sharp Teresa A. , Eckel Robert H.
Published: October 2008

The goals of the study were to determine if moderate weight loss in severely obese adults resulted in (i) reduction in apnea/hypopnea index (AHI), (ii) improved pharyngeal patency, (iii) reduced total body oxygen consumption (VO2) and carbon dioxide production (VCO2) during sleep, and (iv) improved sleep quality. The main outcome was the change in AHI from before to after weight loss. Fourteen severely obese (BMI > 40 kg/m2) patients (3 males, 11 females) completed a highly controlled weight reduction program which included 3 months of weight loss and 3 months of weight maintenance. At baseline and postweight loss, patients underwent pulmonary function testing, polysomnography, and magnetic resonance imaging (MRI) to assess neck morphology. Weight decreased from 134 ±6.6 kg to 118 ± 6.1 kg (mean ± s.e.m.; F = 113.763, P < 0.0001). There was a significant reduction in the AHI between baseline and postweight loss (subject, F = 11.11, P = 0.007). Moreover, patients with worse sleep‐disordered breathing (SDB) at baseline had the greatest improvements in AHI (group, F = 9.00, P = 0.005). Reductions in VO2 (285 ± 12 to 234 ±16 ml/min; F = 24.85, P < 0.0001) and VCO2 (231 ± 9 to 186 ± 12 ml/min; F = 27.74, P < 0.0001) were also observed, and pulmonary function testing showed improvements in spirometry parameters. Sleep studies revealed improved minimum oxygen saturation (minSaO2) (83.4 ± 61.9% to 89.1 ± 1.2%; F = 7.59, P = 0.016), and mean SaO2 (90.4 ± 1.1% to 93.8 ± 1.0%; F = 6.89, P = 0.022), and a significant increase in the number of arousals (8.1 ± 1.4 at baseline, to 17.1 ± 3.0 after weight loss; F = 18.13, P = 0.001). In severely obese patients, even moderate weight loss (∼10%) boasts substantial benefit in terms of the severity of SDB and sleep dynamics.
Fat in Liver/Muscle Correlates More Strongly With Insulin Sensitivity in Rats Than Abdominal Fat
Authors: Lim Soo , Son Kyu R. , Song In C. , Park Ho S. , Jin Cheng J. , Jang Hak C. , Park Kyong S. , Kim Young‐Bum , Lee Hong K.
Published: October 2008

Intrahepatic or intramuscular lipid (IHL/IML) content has been reported to be correlated with insulin resistance. Visceral fat has also been shown to be associated with insulin resistance. Thus, we investigated whether IHL/IML or visceral fat content is more closely associated with insulin resistance. Twenty Sprague‐Dawley rats were divided into two groups based on regular chow diet (RCD) or high‐fat diet (HFD; 40% fat). The insulin‐sensitivity index (ISI) was determined by euglycemic glucose clamp study, the amount of visceral fat by computed tomography (CT), and the IHL/IML content by magnetic resonance spectroscopy (MRS). Weight, food, and water intake, physical activity, energy expenditure, lipid profile, adiponectin, and high‐sensitivity C‐reactive protein (hsCRP) levels were measured. At the study end point, visceral fat, and the IHL/IML content were higher in the HFD group than in the RCD group. The IHL/IML content was more highly correlated with ISI than was visceral fat amount. Stronger correlations were also found between adiponectin or hsCRP level and IML/IHL content than visceral fat, especially in the HFD group. Furthermore, the IHL/IML content was significantly associated with the ISI in the multiple regression models but visceral fat was not. There was clear discrimination between RCD and HFD groups in scatter plots of IML/IHL against the ISI, but substantial overlap in that of visceral fat against the ISI. This result suggests that IHL/IML contents are closely related with insulin resistance or atherosclerosis and is a better metabolic index of insulin sensitivity than the visceral fat.
Alterations in Fatty Acid Kinetics in Obese Adolescents With Increased Intrahepatic Triglyceride Content
Authors: Fabbrini Elisa , DeHaseth Dinky , Deivanayagam Sheela , Mohammed B. Selma , Vitola Bernadette E. , Klein Samuel
Published: October 2008

Objective: It has been hypothesized that excessive fatty acid availability contributes to steatosis and the metabolic abnormalities associated with nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to evaluate whether adipose tissue lipolytic activity and the rate of fatty acid release into plasma are increased in obese adolescents with NAFLD.

Methods: Palmitate kinetics were determined in obese adolescents with normal (n = 9; BMI = 37 ± 2 kg/m2; intrahepatic triglyceride (IHTG) ≤5.5% of liver volume) and increased (n = 9; BMI = 36 ± 2 kg/m2; IHTG ≥ 10% of liver volume) IHTG content during the basal state (postabsorptive condition) and during physiological hyperinsulinemia (postprandial condition). Both groups were matched on body weight, BMI, percent body fat, age, sex, and Tanner stage. The hyperinsulinemic‐euglycemic clamp procedure, in conjunction with a deuterated palmitate tracer infusion, was used to determine free‐fatty acid (FFA) kinetics, and magnetic resonance spectroscopy was used to determine IHTG content.

Results: The rate of whole‐body palmitate release into plasma was greater in subjects with NAFLD than those with normal IHTG content during basal conditions, (87 ± 7 vs. 127 ± 13 µmol/min; P < 0.01) and during physiological hyperinsulinemia, (24 ± 2 vs. 44 ± 8 µmol/min; P < 0.01).

Discussion: These results demonstrate that adipose tissue lipolytic activity is increased in obese adolescents with NAFLD and results in an increase in the rate of fatty acid release into plasma throughout the day. This continual excess in fatty acid flux supports the hypothesis that adipose insulin resistance is involved in the pathogenesis of steatosis and contributes to the metabolic complications associated with NAFLD.
Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate1
Authors: Pereira Da Silva Ana Paula , El-Bacha Tatiana , Kyaw Nattascha , Dos Santos Reinaldo Sousa , Da-Silva Wagner Seixas , Almeida Fabio C. L. , Da Poian Andrea T. , Galina Antonio
Published: October 2008

3-BrPA (3-bromopyruvate) is an alkylating agent with anti-tumoral activity on hepatocellular carcinoma. This compound inhibits cellular ATP production owing to its action on glycolysis and oxidative phosphorylation; however, the specific metabolic steps and mechanisms of 3-BrPA action in human hepatocellular carcinomas, particularly its effects on mitochondrial energetics, are poorly understood. In the present study it was found that incubation of HepG2 cells with a low concentration of 3-BrPA for a short period (150 μM for 30 min) significantly affected both glycolysis and mitochondrial respiratory functions. The activity of mitochondrial hexokinase was not inhibited by 150 μM 3-BrPA, but this concentration caused more than 70% inhibition of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and 3-phosphoglycerate kinase activities. Additionally, 3-BrPA treatment significantly impaired lactate production by HepG2 cells, even when glucose was withdrawn from the incubation medium. Oxygen consumption of HepG2 cells supported by either pyruvate/malate or succinate was inhibited when cells were pre-incubated with 3-BrPA in glucose-free medium. On the other hand, when cells were pre-incubated in glucose-supplemented medium, oxygen consumption was affected only when succinate was used as the oxidizable substrate. An increase in oligomycin-independent respiration was observed in HepG2 cells treated with 3-BrPA only when incubated in glucose-supplemented medium, indicating that 3-BrPA induces mitochondrial proton leakage as well as blocking the electron transport system. The activity of succinate dehydrogenase was inhibited by 70% by 3-BrPA treatment. These results suggest that the combined action of 3-BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death.
New insights into the role of Fur proteins: FurB (All2473) from Anabaena protects DNA and increases cell survival under oxidative stress
Authors: López-Gomollón Sara , Sevilla Emma , Bes M. Teresa , Peleato M. Luisa , Fillat María F.
Published: October 2008

Fur (ferric uptake regulator) is a prokaryotic transcriptional regulator that controls a large number of genes mainly related to iron metabolism. Several Fur homologues with different physiological roles are frequently found in the same organism. The genome of the filamentous cyanobacterium Anabaena (Nostoc) sp. PCC 7120 codes for three different fur genes. FurA is an essential protein involved in iron homoeostasis that also modulates dinitrogen fixation. FurA interacts with haem, impairing its DNA-binding ability. To explore functional differences between Fur homologues in Anabaena, factors affecting their regulation, as well as some biochemical characteristics, have been investigated. Although incubation of FurB with haem severely hinders its ability to interact with DNA, binding of haem to FurC could not be detected. Oxidative stress enhances the transcription of the three fur genes, especially that of furB and furC. In addition, overexpression of FurA and FurB in Escherichia coli increases survival when the cells are challenged with H2O2 or Methyl Viologen (paraquat), a superoxide-anion-generating reagent. When present in saturating concentrations, FurB exhibits unspecific DNA-binding activity and protects DNA from cleavage produced by hydroxyl radicals or DNaseI. On the basis of these results, we suggest that, whereas at low concentrations FurB would act as a member of the Fur family, at saturating concentrations FurB protects DNA, showing a DNA-protection-during-starvation-like behaviour.
Reactivity of nitric oxide with the [4Fe–4S] cluster of dihydroxyacid dehydratase fromEscherichia coli
Authors: Duan Xuewu , Yang Juanjuan , Ren Binbin , Tan Guoqiang , Ding Huangen
Published: October 2008

Although the NO (nitric oxide)-mediated modification of iron–sulfur proteins has been well-documented in bacteria and mammalian cells, specific reactivity of NO with iron–sulfur proteins still remains elusive. In the present study, we report the first kinetic characterization of the reaction between NO and iron–sulfur clusters in protein using the Escherichia coli IlvD (dihydroxyacid dehydratase) [4Fe–4S] cluster as an example. Combining a sensitive NO electrode with EPR (electron paramagnetic resonance) spectroscopy and an enzyme activity assay, we demonstrate that NO is rapidly consumed by the IlvD [4Fe–4S] cluster with the concomitant formation of the IlvD-bound DNIC (dinitrosyl–iron complex) and inactivation of the enzyme activity under anaerobic conditions. The rate constant for the initial reaction between NO and the IlvD [4Fe–4S] cluster is estimated to be (7.0±2.0)×106 M−2·s−1 at 25 °C, which is approx. 2–3 times faster than that of the NO autoxidation by O2 in aqueous solution. Addition of GSH failed to prevent the NO-mediated modification of the IlvD [4Fe–4S] cluster regardless of the presence of O2 in the medium, further suggesting that NO is more reactive with the IlvD [4Fe–4S] cluster than with GSH or O2. Purified aconitase B [4Fe–4S] cluster from E. coli has an almost identical NO reactivity as the IlvD [4Fe–4S] cluster. However, the reaction between NO and the endonuclease III [4Fe–4S] cluster is relatively slow, apparently because the [4Fe–4S] cluster in endonuclease III is less accessible to solvent than those in IlvD and aconitase B. When E. coli cells containing recombinant IlvD, aconitase B or endonuclease III are exposed to NO using the Silastic tubing NO delivery system under aerobic and anaerobic conditions, the [4Fe–4S] clusters in IlvD and aconitase B, but not in endonuclease III, are efficiently modified forming the protein-bound DNICs, confirming that NO has a higher reactivity with the [4Fe–4S] clusters in IlvD and aconitase B than with O2 or GSH. The results suggest that the iron–sulfur clusters in proteins such as IlvD and aconitase B may constitute the primary targets of the NO cytotoxicity under both aerobic and anaerobic conditions.
Direct interaction of a small-molecule modulator with G551D-CFTR, a cystic fibrosis-causing mutation associated with severe disease
Authors: Pasyk Stan , Li Canhui , Ramjeesingh Mohabir , Bear Christine E.
Published: October 2008

CF (cystic fibrosis) is caused by mutations in CFTR (CF transmembrane conductance regulator), which cause its mistrafficking and/or dysfunction as a regulated chloride channel on the apical surface of epithelia. CFTR is a member of the ABC (ATP-binding-cassette) superfamily of membrane proteins and a disease-causing missense mutation within the ABC signature sequence; G551D-CFTR exhibits defective phosphorylation and ATP-dependent channel gating. Studies of the purified and reconstituted G551D-CFTR protein revealed that faulty gating is associated with defective ATP binding and ATPase activity, reflecting the key role of G551 in these functions. Recently, high-throughput screens of chemical libraries led to identification of modulators that enhance channel activity of G551D-CFTR. However, the molecular target(s) for these modulators and their mechanism of action remain unclear. In the present study, we evaluated the mechanism of action of one small-molecule modulator, VRT-532, identified as a specific modulator of CF-causing mutants. First, we confirmed that VRT-532 causes a significant increase in channel activity of G551D-CFTR using a novel assay of CFTR function in inside-out membrane vesicles. Biochemical studies of purified and reconstituted G551D-CFTR revealed that potentiation of the ATPase activity of VRT-532 is mediated by enhancing the affinity of the mutant for ATP. Interestingly, VRT-532 did not affect the ATPase activity of the Wt (wild-type) CFTR, supporting the idea that this compound corrects the specific molecular defect in this mutant. To summarize, these studies provide direct evidence that this compound binds to G551D-CFTR to rescue its specific defect in ATP binding and hydrolysis.