bluuebunny/crossref_metadata_2025 huggingface dataset:
HISTORY AND ITS ENDS IN CHARTIST EPIC
Authors: Gilbert Pamela K.
Published: February 2009

In the mid-1800s, two significant and widelyread Chartist poems appeared, both written in prison by Chartist organizers, and both using the epic form to interrogate the present, body forth a utopian future, and rewrite a history conceived both as broadly human and specifically national. These long poems, Thomas Cooper'sPurgatory of Suicides(1845) and Ernest Jones'sThe New World, first published in 1851 and then republished after 1857 as theRevolt of Hindostan, have much to tell us about how radicals envisioned the history of Britain, its relationship with empire, and the fulfillment of the ends of history. Cooper's poem proceeds in ten books, written in Spenserian stanzas, in which he dreams of visiting a purgatory of suicides: mythical and historical personages who have committed suicide debate the reasons for their condition and the condition of the world. Jones's poem was written in couplets, supposedly on the torn pages of a prayer book, in his own blood. The poem surveys the rise and fall of multiple empires, and also surveys recent political history closer to home. The two poems look to the past and the future, to universal history and its end. They thus participate in utopian political discourse, with its emphasis on the end of history, as well as the epic tradition. Both utopian and epic discourse in this period were affiliated with specifically national narratives, and the internationalist and universal elements of the poems sometimes inhabit these genres uneasily. Additionally, both poets attend to the religious tradition of eschatological discourse that underlies the secular notion of the end of history, and work to reconcile it with the political vision they are promoting. These writers use unique combinations of spatial and temporal frames to achieve the reconciliation of their diverse goals with the genres and discourses that they claim and transform.
JOHN RUSKIN: CLIMBING AND THE VULNERABLE EYE
Authors: Colley Ann C.
Published: February 2009

Most readers either overlook or dismissJohn Ruskin's climbs in the Alps as being insignificant compared to his avid interest in geology and mountain form. However, I want to suggest that Ruskin's climbing – his physical and kinetic relationship to the mountains – is essential to his understanding of them. His numerous and repeated ascents in the lower Alps were not always easy: in fact, they were often tough and sometimes dangerous. Through a few select examples, in the first part of the essay, I establish just how difficult many of these scrambles were so that I may proceed, in the body of the paper, to talk about how these strenuous experiences influenced his way of seeing the mountain landscape he admired, and how, in turn, they helped shape his concept of imperfect vision.
RACIAL STRATEGIES INJANE EYRE
Authors: McKee Patricia
Published: February 2009

In Charlotte Brontë'sJane Eyre(1847), multiple discursive strategies contend with the difficulty of determining racial identity. My aim here is not to delineate a straightforward or unambiguous racial discourse in the novel but rather to clarify the usefulness of ambiguity to the narrative's racialism. If, as Ann Laura Stoler has argued, racism in the nineteenth century depended on flexible rather than fixed criteria, Brontë's novel allows for the study of such criteria and of the discursive displacements that assign them to diverse human qualities.
ALICE'S ADVENTURES AT THE CARNIVAL
Authors: Hennelly Mark M.
Published: February 2009

Imagine a story featuring a dreamy descentunderground, grotesquely gigantic and dwarfish carnality, a prodigious pool of body fluid, cartwheels and pratfalls, cornucopian helpings of food and drink, antic playgrounds, riddling language and name games, repeated nonsense (re)verses, various negative capabilities, mathematical miracles, voyages of discovery, cycles of crowning and uncrowning, not to mention metalists like the previous catalogue in this sentence. It seems curious that this tangled tale, Lewis Carroll's in theAlices, has never been linked to the Carnival tradition typified by François Rabelais'sGargantua and Pantagruel(1532–64) even though our imagined story equally describes Rabelais's glorious epic. At least, it's never been linked much beyond Northrop Frye's suggestion that “[t]he Alice books are perfect Menippean satires, and so is [Charles Kingsley's]The Water-Babies, which has been influenced by Rabelais” (310) and Martin Gardner's note toLooking-Glassthat Medieval and “Renaissance chess games were sometimes played with human pieces on enormous fields” as in “Gargantua and Pantagruel” (135, n. 2). And yet, to spin William Empson's memorable take on Freudian readings (357), one has only to tell Alice's story to make it a carnival tale.
HORSE-SENSE: UNDERSTANDING THE WORKING HORSE IN VICTORIAN LONDON
Authors: Miele Kathryn
Published: February 2009

Several important studies of animalsin Victorian Britain have considered the ways that animals have served as surrogates for the discussion of human relationships. Historical statements about the treatment of animals are often interpreted as telling stories about issues such as class dynamics or social problems among humans. But must one always imagine animals to have been only the ostensible subject of discussion? While it is certainly important to study how historical discussions about animals have reflected and expressed opinions about sensitive, tense, or otherwise difficult relationships among humans and groups of humans, it is unreasonable to dismiss all discussion of the welfare of animals as a cover for what is really a concern about humans. Is it not just as interesting – and important – to consider the ways in which humans have identified with animals as animals? The introduction of the animal as animal into the discussion of human culture reveals a level of complexity in life and history that is all too easily overlooked.
MASCULINITY, HEROISM, AND THE EMPIRE: ROBERT BROWNING'S “CLIVE” AND OTHER VICTORIAN RE-CONSTRUCTIONS OF THE STORY OF ROBERT CLIVE
Authors: Sifaki Evgenia
Published: February 2009

The core of this paperis a reading of Robert Browning's “Clive” (1880); it attempts to account for the formalist demands of this generically complex and relentlessly ironic poetic text, while at the same time it construes the accomplishment of Browning's poetic language and form as intricate cultural critique. However, in order to better understand Browning's poem an additional discussion of its intertexts is required, the most important being Thomas Babington Macaulay's essay “On Clive” (1840).
“FEARFUL CONSEQUENCES . . . OF LIVING UP TO ONE'S TEAPOT”: MEN, WOMEN, AND “CULTCHAH” IN THE ENGLISH AESTHETIC MOVEMENT c. 1870–1900
Authors: Anderson Anne
Published: February 2009

The Aesthetic or “Patience” teapotis renowned as the ultimate parody of Aesthetic sensibilities. Composed of the head and torso of a male and female back-to-back dressed in the “greenery-yallery of the Grosvenor Gallery,” with puce hats and fashionable Pre-Raphaelite red hair, the teapot was designed by James Hadley (1838–1903) for the Royal Worcester manufactory following the success of W. S. Gilbert and Arthur Sullivan's operettaPatiencein 1881. Bearing on its base the inscription, “Fearful consequences through the laws of Natural Selection and Evolution of living up to one's teapot,” the vessel took a swipe at Darwin's theories of evolution, as well as Oscar Wilde's famous aphorism. This teapot is certainly not “fit for its purpose,” defying “form must follow function”; rather it is a whim of fashion, novel but transitory. Recognized as a “limited edition” and expensive, its function being primarily for show rather than use, it marks the appearance of the modern “collectable,” in effect a souvenir of Aestheticism and now seen to commemorate its apogee. Yet although loaded with aesthetic signifiers – sunflowers, lilies and gender-bending – no scholar has attempted to unwrap the teapot's meaning, in terms of the identification of china and tea with “life-style aestheticism” (Figure 15).
INTERSTITIAL CARTOGRAPHER: DAVID LIVINGSTONE AND THE INVENTION OF SOUTH CENTRAL AFRICA
Authors: Wisnicki Adrian S.
Published: February 2009

Upon returning to England in December 1856 after sixteen years in the interior of southern Africa, David Livingstone, the celebrated missionary and explorer, received an enthusiastic welcome. Already a household name because of his well-publicized discoveries and travels, Livingstone now found himself a hero of national stature. The Royal Geographical Society and the London Missionary Society organized large receptions in his honor; he received the freedoms of several cities, including London, Edinburgh, and Glasgow; Oxford University awarded him an honorary D.C.L. (Doctor of Civil Law); and Queen Victoria invited him to a private audience (Schapera ix-x). Likewise, the encyclopedic narrative of his adventures, Missionary Travels and Researches in South Africa (1857), garnered numerous favorable reviews, sold some 70,000 copies, and ultimately made the explorer a rich man. Livingstone's narrative, wrote one early reviewer, opened up “a mystic and inscrutable continent,” while the story of Livingstone's famous four-year transcontinental journey – the first such documented journey in history – inspired admiration for being “performed without the help of civilized associate, trusting only to the resources of his own gallant heart and to the protection of the missionary's God” (“Dr. Livingstone's African Researches” 107). In promoting the Zambesi River as a natural highway into the interior of Africa and in advocating for the three C's – Christianity, commerce, and civilization – as a means to ending the slave-trade and opening the continent's natural riches to the outside world, Missionary Travels also struck a resounding chord with the public. Reviewers welcomed Livingstone's pronouncements, while describing the missionary as “an instrument, divinely appointed by Providence for the amelioration of the human race and the furtherance of God's glory” (“Livingstone's Missionary Travels” 74).
COMRADES IN ADVERSITY: WILLIAM ROBERTSON SMITH AND RICHARD BURTON
Authors: Booth Gordon K.
Published: February 2009

At first sight these two eminent Victorians appear to be most incongruous travelling companions: the one a relatively austere young professor of Hebrew in the Free Church of Scotland, the other a mature, hard-swearing, short-tempered, thoroughly agnostic trouble-maker with an unconcealed penchant for oriental erotica. Both men, however, had provoked widespread controversy and were regarded in high places as “unsound.”
VICTORIANS LIVE
Authors: Sussman Herbert
Published: February 2009

Victorians Live examines the afterlife of the Victorians, the ways that Victorian literature and culture remain alive, continue to live in our own day.

Twenty-First Century Millais

ELIZABETH PRETTEJOHN

The Labor of Photography

GEOFFREY BATCHEN

Art & Emancipation in Jamaica: Isaac Mendes Belisario and His Worlds

HERBERT SUSSMAN

Sondheim's Sweeney Todd on Stage and Screen

SHARON ARONOFSKY WELTMAN
VICTORIAN JOURNALISM IN PLENTY
Authors: Mitchell Sally
Published: February 2009

Although theOED's first citationfor “journalism” is dated 1833 (it comes fromWestminster Review), the current dramatic expansion of digital resources suggests that scholarly use of Victorian journals may be reaching a point of transition. In addition, the number, variety, breadth, and depth of recent studies, most of them finished before the new materials went online, is truly remarkable.
Should prospective payments be differentiated for public and private healthcare providers?
Authors: MASON ANNE , STREET ANDREW , MIRALDO MARISA , SICILIANI LUIGI
Published: February 2009

The English government has encouraged private providers – known as Independent Sector Treatment Centres (ISTCs) – to treat publicly funded (NHS) patients. All providers are to be remunerated under a prospective payment system that offers a price per case treated, adjusted by the Market Forces Factor (MFF) to reflect geographical variation in specific input costs. This payment system presupposes that any remaining cost differentials between providers result from inefficiencies. However, the validity of this assumption is unclear. This article describes the constraints that could cause public and private provider costs to differ for reasons outside their control. These constraints may be regulatory in nature, such as taxes and performance management regimens, or relate to the production process, such as input costs, the provision of emergency care, and case mix issues. Most of these exogenous cost differentials can be rectified by adjustments either to the regulatory system or to the payment method. However, differences in capital costs appear less tractable and further investigation into possible solutions is warranted.
A reanalysis of phospholipid fatty acids as ecological biomarkers for methanotrophic bacteria
Authors: Bodelier Paul L E , Bär Gillisen Marie-José , Hordijk Kees , Sinninghe Damsté Jaap S , Rijpstra W Irene C , Geenevasen Jan A J , Dunfield Peter F
Published: February 2009

Aerobic methane-oxidizing bacteria (MB) are the primary terrestrial sinks for the greenhouse gas methane. A distinct characteristic of MB is the presence of specific phospholipid ester-linked fatty acids (PLFA) in their membranes that differentiate them from each other and also from all other organisms. These distinct PLFA patterns facilitate microbial ecology studies. For example, the assimilation of C from methane into PLFA can be traced in environmental samples using stable isotope (13C) probing (SIP), which links the activity of MB to their community composition in situ. However, the phylogenetic resolution of this method is low because of a lack of PLFA profiles from cultured MB species. In this study, PLFA profiles of 22 alphaproteobacterial (type II) MB were analysed after growth on methane, methanol or both substrates together. Growth on different substrates did not affect the PLFA profiles of the investigated strains. A number of Methylocystis strains contained novel C18:2 fatty acids (ω7c,12c and ω6c,12c) that can be used as diagnostic biomarkers. The detection of these novel PLFA, combined with the analyses of multiple type II strains, increased the phylogenetic resolution of PLFA analysis substantially. Multivariate analysis of the expanded MB PLFA database identified species groups that closely reflected phylogenies based on 16S rRNA and pmoA gene sequences. The PLFA database therefore provides a robust framework for linking identity to activity in MB communities with a higher resolution than was previously possible.
Obesity Attenuates the Contribution of African Admixture to the Insulin Secretory Profile in Peripubertal Children: A Longitudinal Analysis
Authors: Casazza Krista , Phadke Radhika P. , Fernandez Jose R. , Watanabe Richard M. , Goran Michael I. , Gower Barbara A.
Published: February 2009

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C‐peptide modeling; genetic ancestry by admixture analysis. Mixed‐model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first‐phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first‐phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first‐phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the β‐cell response to glucose in a manner that differs with ethnic/genetic background.
Absence of Association Between the INSIG2 Gene Polymorphism (rs7566605) and Obesity in the European Youth Heart Study (EYHS)
Authors: Vimaleswaran Karani S. , Franks Paul W. , Brage Soren , Sardinha Luis B. , Andersen Lars B. , Wareham Nicholas J. , Ekelund Ulf , Loos Ruth J.F.
Published: February 2009

The first genome‐wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin‐induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity‐ and lipid‐related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school‐based, cross‐sectional study of pre‐ and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age‐group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low‐density lipoprotein, or high‐density lipoprotein. There were no gender‐specific (P = 0.55), age‐group‐specific (P = 0.63) or country‐specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity‐related traits and lipids in the EYHS.
Adult Obesity and Office‐based Quality of Care in the United States
Authors: Ma Jun , Xiao Lan , Stafford Randall S.
Published: February 2009

Nationally representative data on the quality of care for obese patients in US‐ambulatory care settings are limited. We conducted a cross‐sectional analysis of the 2005 and 2006 National Ambulatory Medical Care Survey (NAMCS). We examined obesity screening, diagnosis, and counseling during adult visits and associations with patient and provider characteristics. We also assessed performance on 15 previously published ambulatory quality indicators for obese vs. normal/overweight patients. Nearly 50% (95% confidence interval (CI): 46–54%) of visits lacked complete height and weight data needed to screen for obesity using BMI. Of visits by patients with clinical obesity (BMI ≥30.0 kg/m2), 70% (66–74%) were not diagnosed and 63% (59–68%) received no counseling for diet, exercise, or weight reduction. The percentage of visits not being screened (48%), diagnosed (66%), or counseled (54%) for obesity was also notably higher than expected even for patients with known obesity comorbidities. Performance (defined as the percentage of applicable visits receiving appropriate care) on the quality indicators was suboptimal overall. In particular, performance was no better than 50% for eight quality indicators, which are all related to the prevention and treatment of obesity comorbidities, e.g., coronary artery disease, hypertension, hyperlipidemia, asthma, and depression. Performance did not differ by weight status for any of the 15 quality indicators; however, poorer performance was consistently associated with lack of height and weight measurements. In conclusion, many opportunities are missed for obesity screening and diagnosis, as well as for the prevention and treatment of obesity comorbidities, in office‐based practices across the United States, regardless of patient and provider characteristics.
Interactions Between Lipoproteins and Platelet Membranes in Obesity
Authors: Raffaelli Francesca , Nanetti Laura , D'Angelo Monica , Montecchiani Giorgio , Alidori Alessandro , Montesi Luca , Faloia Emanuela , Vignini Arianna , Mazzanti Laura
Published: February 2009

The aim was to investigate low‐density lipoprotein (LDL) composition and Na+/K+ adenosine triphosphatase (ATPase) and Ca2+ ATPase activities and membrane fluidity measured by 1‐(4‐trimethylaminophenyl)‐6‐phenyl‐1,3,5‐hexatriene (TMA‐DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical–physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na+/K+ ATPase and Ca2+ ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA‐DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.
Impact of Race/Ethnicity on the Relationship Between Visceral Fat and Inflammatory Biomarkers
Authors: Carroll Joan F. , Fulda Kimberly G. , Chiapa Ana L. , Rodriquez Mayra , Phelps David R. , Cardarelli Kathryn M. , Vishwanatha Jamboor K. , Cardarelli Roberto
Published: February 2009

The purpose of this study was to determine whether racial/ethnic differences exist in the relationship between visceral adipose tissue (VAT) and selected inflammatory biomarkers. Subjects included 136 African‐American, 133 Hispanic, and 100 white men and women, aged ≥45. Waist circumference and BMI were measured using standard methods. Total VAT, and VAT and subcutaneous adipose tissue (SAT) at the L4L5 spinal level were measured using computed tomography. Interleukin‐6 (IL‐6), C‐reactive protein (CRP), and fibrinogen were measured from fasting blood samples. Results revealed that waist circumference and BMI were similar among groups but African Americans had significantly lower L4L5 VAT compared with Hispanics and whites. Despite lower VAT, African‐American men had similar concentrations of inflammatory biomarkers. On the other hand, African‐American women had higher CRP and IL‐6 than white women, and higher fibrinogen than both Hispanic and white women. After controlling for L4L5 VAT, L4L5 SAT, and age, African‐American women had higher concentrations of IL‐6 and fibrinogen. Stratified analyses for CRP indicated that L4L5 SAT was associated with CRP in African‐American and white women after controlling for L4L5 VAT and age, but that the reverse was not true. These data indicate that African Americans had lower VAT but similar or higher concentrations of inflammatory biomarkers. African‐American women consistently displayed greater inflammation compared with whites, even after controlling for VAT or SAT.
Visceral and Subcutaneous Adipose Tissue Diacylglycerol Acyltransferase Activity in Humans
Authors: Hou Xin Guo , Moser Sonja , Sarr Michael G. , Thompson Geoffrey B. , Que Florencia G. , Jensen Michael D.
Published: February 2009

Diacylglycerol acyltransferase (DGAT) could be a rate limiting step in triglyceride (TG) synthesis as it is the final step in this pathway. As such, between depot differences in DGAT activity could influence regional fat storage. DGAT activity and in vitro rates of direct free fatty acid (FFA) storage were measured in abdominal subcutaneous and omental adipose tissue samples from 12 nonobese (BMI <30 kg/m2) and 23 obese men and women (BMI >30 kg/m2) undergoing elective surgery. DGAT activity was greater in omental than in abdominal subcutaneous adipose tissue from nonobese patients (2.0 ± 0.9 vs. 0.9 ± 0.3 pmol/min/mg lipid, respectively, P = 0.003), but not from obese patients (1.4 ± 0.6 vs. 1.7 ± 0.7 pmol/min/mg lipid, respectively, P = 0.10). DGAT activity per unit adipose weight was negatively correlated with adipocyte size (P < 0.01) and positively correlated with direct FFA storage in omental (P < 0.001) but not in abdominal subcutaneous fat. Tissue DGAT activity varies as a function of adipocyte size, but this relationship differs between visceral and abdominal subcutaneous fat in obese and nonobese humans. Our results are consistent with the hypothesis that interindividual variations in DGAT activity may be an important regulatory step in visceral adipose tissue FFA uptake/storage.
BMI and Severity of Clinical and Radiographic Signs of Hip Osteoarthritis
Authors: Lübbeke Anne , Duc Sylvain , Garavaglia Guido , Finckh Axel , Hoffmeyer Pierre
Published: February 2009

Obesity might be involved in the pathogenesis of osteoarthritis (OA) not only via increased mechanical loading, but also via an inflammatory component possibly causing increased pain and functional disability. The study aim was to examine the relationship between BMI and clinical symptoms as well as radiographic severity of OA in patients scheduled for primary total hip arthroplasty (THA). We conducted a cross‐sectional study of 855 patients scheduled for a first THA for primary OA at a single centre between November 2001 and December 2006. The primary outcome was clinical and radiographic severity of OA, which was evaluated in four BMI categories (18.5–24.9, 25–29.9, 30–34.9 and ≥35 kg/m2). We used the Harris Hip Score (HHS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) to assess pain and function. The severity of radiographic hip joint damage was evaluated using the Kellgren–Lawrence classification. Multivariate analyses were performed to adjust for potential confounders. In patients scheduled for THA, increasing BMI was associated with significantly higher levels of pain and functional disability on both HHS (P for trend <0.001) and WOMAC (P for trend <0.001). However, the degree of radiographic joint damage remained similar across BMI categories. These findings emphasize the need to further investigate the potential pathogenic role of obesity and low‐grade inflammation in OA and underscore the importance of obesity prevention to avoid early prosthetic replacement of the hip.
Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality
Authors: Reis Jared P. , Macera Caroline A. , Araneta Maria R. , Lindsay Suzanne P. , Marshall Simon J. , Wingard Deborah L.
Published: February 2009

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (Ptrend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (Ptrend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m2) and obese (BMI ≥30.0 kg/m2) adults. In older adults (65–102 years), a higher BMI in both sexes (Ptrend <0.05) and WC in men (Ptrend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.
Adipocyte Fatty Acid‐binding Protein as a Determinant of Insulin Sensitivity in Morbid‐obese Women
Authors: Simón Inmaculada , Escoté Xavier , Vilarrasa Núria , Gómez José , Fernández‐Real José M. , Megía Ana , Gutiérrez Cristina , Gallart Lluis , Masdevall Carles , Vendrell Joan
Published: February 2009

The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid‐binding protein (A‐FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A‐FABP were measured in 77 morbid‐obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL‐18), adiponectin, and high‐sensitive C‐reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. After massive weight loss, A‐FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P < 0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow‐up, was observed. A decrease in sTNFR2, IL‐18, hsCRP, and an increase in adiponectin levels (P < 0.001 in all cases) were observed after the gastric bypass. HOMA‐IR index improved 1 year after surgery and after multiple regression analysis remained associated with A‐FABP after controlling for confounding variables (β = 0.322, P = 0.014; R2 for the model 0.281). In morbid‐obese women, plasma A‐FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA‐IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A‐FABP in the pathogenesis of insulin resistance in morbid obesity.
Prospective Investigation of Metabolic Characteristics in Relation to Weight Gain in Older Adults: The Hoorn Study
Authors: Wedick Nicole M. , Snijder Marieke B. , Dekker Jacqueline M. , Heine Robert J. , Stehouwer Coen D.A. , Nijpels Giel , van Dam Rob M.
Published: February 2009

The objective of this investigation was to determine the relation between baseline glucose, insulin, adiponectin, and leptin levels and subsequent 6‐year weight and waist change in older men and women without diabetes in a prospective cohort study. Participants were 1,198 Dutch men and women without diabetes who were aged 50–77 years when baseline metabolic and anthropometric measurements were evaluated (1989–1991). Approximately 6 years later, body weight and waist circumference were re‐measured at a follow‐up examination (1996–1998). Metabolic variables (fasting plasma glucose, 2‐h postchallenge plasma glucose, homeostasis model assessment of insulin resistance (HOMA‐IR), adiponectin, and leptin) were evaluated as predictors of changes in weight and waist circumference. Postchallenge plasma glucose (mmol/l) significantly predicted less gain in both weight and waist circumference (β = −0.28 kg, s.e. = 0.11; β = −0.31 cm, s.e. = 0.14, respectively) during follow‐up. Leptin (µg/l) significantly predicted greater increases in weight (β = 0.29 kg, s.e. = 0.07) and waist (β = 0.16 cm, s.e. = 0.08) among men and in waist among women (β = 0.06 cm, s.e. = 0.02). Fasting plasma glucose (mmol/l) predicted an increase in waist among women (β = 1.59 cm, s.e. = 0.63), but not in men (β = −0.74 cm, s.e. = 0.55). Adiponectin and insulin did not predict weight or waist change. The authors conclude that lower postchallenge plasma glucose and higher fasting leptin levels significantly predicted long‐term increases in weight and waist circumference. In contrast, measures of insulin resistance and adiponectin were not associated with weight change in this cohort of older persons without diabetes.
In Utero Gender Dimorphism of Adiponectin Reflects Insulin Sensitivity and Adiposity of the Fetus
Authors: Basu Subhabrata , Laffineuse Laura , Presley Larraine , Minium Judi , Catalano Patrick M. , Mouzon Sylvie Hauguel‐de
Published: February 2009

Circulating adiponectin reflects the degree of energy homeostasis and insulin sensitivity of adult individuals. Low abundance of the high molecular weight (HMW) multimers, the most active forms mediating the insulin‐sensitizing effects of adiponectin, is indicative of impaired metabolic status. The increase in fetal adiponectin HMW compared with adults is a distinctive features of human neonates. To further understand the functional properties of adiponectin during fetal life, we have evaluated the associations of adiponectin with insulin sensitivity, body composition, and gender. Umbilical cord adiponectin, adiponectin complexes, and metabolic parameters were measured at term by elective cesarean delivery. The associations between adiponectin, measures of body composition, and insulin sensitivity were evaluated in relation to fetal gender in 121 singleton neonates. Higher total adiponectin concentrations in female compared with male fetuses (34.3 ± 9.5 vs. 24.9 ± 8.6, P < 0.001) were associated with a 3.2‐fold greater abundance in circulating HMW complexes (0.20 ± 0.03 vs. 0.08 ± 0.03, P < 0.001, n = 9). Adiponectin was positively correlated with neonatal fat mass (r = 0.27, P < 0.04) and percent body fat in female fetuses (r = 0.28, P < 0.03) and with lean mass in males (r = 0.28, P < 0.03). There was no significant correlation between cord adiponectin and fasting insulin concentrations or fetal insulin sensitivity as estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). The gender dimorphism for plasma adiponectin concentration and complex distribution first appears in utero. In sharp contrast to the inverse correlation found in adults, the positive relationship between adiponectin and body fat is a specific feature of the fetus.
Weight Status, Quality of Life, and Self‐concept in African American, Hispanic, and White Fifth‐grade Children
Authors: Wallander Jan L. , Taylor Wendell C. , Grunbaum Jo Anne , Franklin Frank A. , Harrison Gail G. , Kelder Steven H. , Schuster Mark A.
Published: February 2009

This study examined the association between weight status and quality of life (QOL) in fifth‐grade African American, Hispanic, and white children and the potential mediation of this relationship by self‐concept. A sample was recruited from fifth‐grade public school students in three sites, of whom 599 were African American (40%), Hispanic (34%), or white (26%). During a home interview, physical and psychosocial QOL and global and body‐specific self‐concept were measured. Measured height and weight were used to calculate BMI. In this sample, 57% were classified by BMI as not overweight, 17%, overweight, and 26%, obese. Although there was no significant interaction between weight classification and race/ethnicity for QOL, obese children reported significantly lower psychosocial but not physical QOL than those classified as not overweight. There was a significant association between BMI (measured continuously) and psychosocial QOL, but only 2% of the variance was accounted for. Both global self‐concept and body dissatisfaction independently mediated significant portions of the association between BMI and psychosocial QOL. Being obese in childhood may have negative psychosocial effects.
Lack of Association Between a Common Polymorphism Near the INSIG2 Gene and BMI, Myocardial Infarction, and Cardiovascular Risk Factors
Authors: Wiedmann Silke , Neureuther Katharina , Stark Klaus , Reinhard Wibke , Kallmünzer Bernd , Baessler Andrea , Fischer Marcus , Linsel‐Nitschke Patrick , Erdmann Jeanette , Schunkert Heribert , Hengstenberg Christian
Published: February 2009

Epidemiological studies revealed an increasing prevalence of and a steep increase in obesity, a risk factor for cardiovascular disease. Because significant influence of a polymorphism, rs7566605, near the INSIG2 gene on BMI has been shown in the general population and in obesity cohorts, we hypothesized that this polymorphism might also act through an elevated BMI on the development of coronary artery disease (CAD) or myocardial infarction (MI). We pursued two strategies: First, the polymorphism rs7566605 was investigated for association with BMI, CAD/MI, and cardiovascular risk factors in a large German cohort at high risk for CAD and MI (n = 1,460 MI patients) as compared to unrelated healthy controls (n = 1,215); second, we extended our analyses on the families of MI patients and performed family‐based association testing (n = 5,390 individuals). The polymorphism rs7566605 was analyzed using TaqMan technology. No deviation from Hardy–Weinberg equilibrium could be observed, and the call rate was 98.2%. No significant associations of rs7566605 with CAD/MI, BMI, and classical cardiovascular risk factors could be detected in the full sample size or in the subgroups. A total of 6,878 individuals were investigated in a population of German MI patients and their family members. Although the number of individuals was large enough, no influence of the rs7566605 INSIG2 polymorphism was detected on BMI and CAD/MI. We therefore conclude that in our sample the SNP rs7566605 near the INSIG2 gene does not influence BMI and is not associated directly with CAD/MI or indirectly through cardiovascular risk factors.
Physical state of κ-carrageenan modulates the mode of action of κ-carrageenase from Pseudoalteromonas carrageenovora
Authors: Lemoine Maud , Nyvall Collén Pi , Helbert William
Published: February 2009

Pseudoalteromonas carrageenovora κ-carrageenase is a glycoside hydrolase involved in the bioconversion of carrageenans. Carrageenans are sulfated galactans that are densely packed in red algal cell walls. Previous crystallographic investigations revealed that the active site of κ-carrageenase has a tunnel-shaped topology, suggesting a processive mode of action for this enzyme. To biochemically characterize the enzymatic depolymerization of κ-carrageenan, soluble and solid substrates (in both gel and powder forms) were incubated with P. carrageenovora κ-carrageenase. The average molecular mass of soluble carrageenan decreased rapidly, and all possible degradation products were observed, suggesting random degradation of κ-carrageenan. In contrast, as expected for a processive-type carrageenase, the average molecular mass of solid carrageenan decreased very slowly, and tetrasaccharide production was high. Interestingly, experimentally determined processivity was similar for gel and powder, suggesting that, in addition to an adapted catalytic site, the substrate must be in the solid state for κ-carrageenase processivity to operate, whatever the level of carrageenan ordering.
The C-terminus of the P22 tailspike protein acts as an independent oligomerization domain for monomeric proteins
Authors: Webber Tawnya , Gurung Sarsati , Saul Justin , Baker Trenton , Spatara Michelle , Freyer Matthew , Robinson Anne Skaja , Gage Matthew J.
Published: February 2009

TSP (P22 tailspike protein) is a well-established model system for studying the folding and assembly of oligomeric proteins, and previous studies have documented both in vivo and in vitro folding intermediates using this protein. Especially important is the C-terminus of TSP, which plays a critical role in the assembly and maturation of the protrimer intermediate to its final trimeric form. In the present study, we show that by grafting the C-terminus of TSP on to the monomeric MBP (maltose-binding protein), the resulting chimaera (MBP-537) is a trimeric protein. Moreover, Western blot studies (using an anti-TSP antibody) indicate that the TSP C-terminus in the MBP-537 chimaera has the same conformation as the native TSP. The oligomerization of the MBP-537 chimaera appears to involve hydrophobic interactions and a refolding sequence, both of which are analogous to the native TSP. These results underscore the importance of the TSP C-terminus in the assembly of the mature trimer and demonstrate its potential utility as a model to study the folding and assembly of the TSP C-terminus in isolation.
Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities
Authors: Patham Bhargavi , Duffy Josh , Lane Ariel , Davis Richard C. , Wipf Peter , Fewell Sheara W. , Brodsky Jeffrey L. , Mensa-Wilmot Kojo
Published: February 2009

HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 μM (MAL3-101), 3.3 μM (equisetin) and 7 μM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify ‘new chemical entities’ (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.
Antibody-mediated disruption of the interaction between PCSK9 and the low-density lipoprotein receptor
Authors: Duff Christopher J. , Scott Martin J. , Kirby Ian T. , Hutchinson Sue E. , Martin Steve L. , Hooper Nigel M.
Published: February 2009

PCSK9 (proprotein convertase subtilisin/kexin type 9) promotes degradation of the LDLR [LDL (low-density lipoprotein) receptor] through an as-yet-undefined mechanism, leading to a reduction in cellular LDLc (LDL-cholesterol) and a concomitant increase in serum LDLc. Central to the function of PCSK9 is a direct protein–protein interaction formed with the LDLR. In the present study, we investigated a strategy to modulate LDL uptake by blocking this interaction using specific antibodies directed against PCSK9. Studies using surface plasmon resonance demonstrated that direct binding of PCSK9 to the LDLR could be abolished with three different anti-PCSK9 antibodies. Two of these antibodies were raised against peptide epitopes in a region of the catalytic domain of PCSK9 that is involved in the interaction with the LDLR. Such antibodies restored LDL uptake in HepG2 cells treated with exogenous PCSK9 and in HepG2 cells engineered to overexpress recombinant PCSK9. This latter observation indicates that antibodies blocking the PCSK9–LDLR interaction can inhibit the action of PCSK9 produced endogenously in a cell-based system. These antibodies also disrupted the higher-affinity interaction between the natural gain-of-function mutant of PCSK9, D374Y, and the LDLR in both the cell-free and cell-based assays. These data indicate that antibodies targeting PCSK9 can reverse the PCSK9-mediated modulation of cell-surface LDLRs.
Role of matrix metalloproteinases and their tissue inhibitors as potential biomarkers of left ventricular remodelling in the athlete's heart
Authors: Vianello Annamaria , Caponi Laura , Franzoni Ferdinando , Galetta Fabio , Rossi Marco , Taddei Marco , Malvaldi Gino , Pietrini Pietro , Santoro Gino
Published: February 2009

The aim of the present study was to verify whether plasma MMPs (matrix metalloproteinases) and TIMPs (tissue inhibitors of MMPs) could be used as potential markers of paraphysiological remodelling in the athlete's heart, and to correlate these matrix parameters with echocardiographic signs of LV (left ventricular) remodelling. Plasma MMP-2 and MMP-9 were measured by zymography, and TIMP-1 and TIMP-2 were measured by ELISA in 42 veteran marathoners with AH (athlete's heart), and in 25 sedentary healthy subjects (CTL). All subjects were submitted to a clinical examination and two-dimensional colour Doppler echocardiography together with the measurement of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide); GGT (γ-glutamyl transpeptidase) was evaluated as a marker of cardiovascular disease. Veteran athletes had a significant elevation in LV dimensions and calculated LV mass index. Diastolic and systolic functions were normal for both groups. MMP-9 levels were significantly lower in AH than in CTL subjects (56.9±4.3 compared with 119.4±21.5 m-units/l, P<0.01). There were significant differences in MMP-2 between the two groups, with a down-regulation in the AH subjects (182.5±16.8 units/ml in CTL compared with 117.1±9.1 units/ml in AH, P<0.01). MMP-2 and MMP-2/TIMP-2 were inversely correlated with myocardial indices of hypertrophy in AH and CTL subjects. AH and CTL subjects showed similar TIMP values. The results of the present study indicate that MMPs and TIMPs could represent potential biomarkers of adaptive heart remodelling in the athletes. In addition, the inverse correlation of the MMP-2/TIMP-2 system with echocardiographic signs of myocardial hypertrophy could represent a new diagnostic and prognostic indicator useful in the evaluation of cardiovascular risk in athletes.