bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil gelatinase–associated lipocalin is a predictor of the course of global and renal childhood‐onset systemic lupus erythematosus disease activity
Authors: Hinze Claas H. , Suzuki Michiko , Klein‐Gitelman Marisa , Passo Murray H. , Olson Judyann , Singer Nora G. , Haines Kathleen A. , Onel Karen , O'Neil Kathleen , Silverman Earl D. , Tucker Lori , Ying Jun , Devarajan Prasad , Brunner Hermine I.
Published: August 2009

Objective

To determine whether neutrophil gelatinase–associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood‐onset systemic lupus erythematosus (SLE).

Methods

One hundred eleven patients with childhood‐onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme‐linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed‐effect models.

Results

Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.

Conclusion

Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood‐onset SLE disease activity.
Decreased physical function and increased pain sensitivity in mice deficient for type IX collagen
Authors: Allen Kyle D. , Griffin Timothy M. , Rodriguiz Ramona M. , Wetsel William C. , Kraus Virginia B. , Huebner Janet L. , Boyd Lawrence M. , Setton Lori A.
Published: August 2009

Objective

In mice with Col9a1 gene inactivation (Col9a1−/−), osteoarthritis (OA) and intervertebral disc degeneration develop prematurely. The aim of this study was to investigate Col9a1−/−mice for functional and symptomatic changes that may be associated with these pathologies.

Methods

Col9a1−/−and wild‐type mice were investigated for reflexes, functional impairment (beam walking, pole climbing, wire hang, grip strength), sensorimotor skills (rotarod), mechanical sensitivity (von Frey hair), and thermal sensitivity (hot plate/tail flick). Gait was also analyzed to determine velocity, stride frequency, symmetry, percentage stance time, stride length, and step width. Postmortem, sera obtained from the mice were analyzed for hyaluronan, and their knees and spines were graded histologically for degeneration.

Results

Col9a1−/−mice had compensatory gait changes, increased mechanical sensitivity, and impaired physical ability. Col9a1−/−mice ambulated with gaits characterized by increased percentage stance times and shorter stride lengths. These mice also had heightened mechanical sensitivity and were deficient in contact righting, wire hang, rotarod, and pole climbing tasks. Male Col9a1−/−mice had the highest mean serum hyaluronan levels and strong histologic evidence of cartilage erosion. Intervertebral disc degeneration was also detected, with Col9a1−/−mice having an increased incidence of disc tears.

Conclusion

These data describe a Col9a1−/−behavioral phenotype characterized by altered gait, increased mechanical sensitivity, and impaired function. These gait and functional differences suggest that Col9a1−/−mice select locomotive behaviors that limit joint loads. The nature and magnitude of behavioral changes were largest in male mice, which also had the greatest evidence of knee degeneration. These findings suggest that Col9a1−/−mice present behavioral changes consistent with anatomic signs of OA and intervertebral disc degeneration.
Polymyalgia rheumatica prevalence in a population‐based sample
Authors: Bernatsky S. , Joseph L. , Pineau C. A. , Belisle P. , Lix L. , Banerjee D. , Clarke A. E.
Published: August 2009

Objective

To determine polymyalgia rheumatica (PMR) prevalence using population‐based administrative data, and to estimate the error associated with case ascertainment approaches when using these databases.

Methods

Cases were ascertained using physician billing and hospitalization data from the province of Manitoba (population 1.1 million). Focusing on the population age ≥45 years, we compared 3 different case definition algorithms and also used statistical methods that accounted for imperfect case ascertainment to estimate the prevalence and the properties of the ascertainment algorithms. A hierarchical Bayesian latent class regression model was developed that also allowed us to assess differences across patient demographics (sex and region of residence).

Results

Using methods that account for the imperfect nature of both billing and hospitalization databases, we estimated the prevalence of PMR in women age ≥45 years to be lower in urban areas (754.5 cases/100,000; 95% credible interval [95% CrI] 674.1–850.3) compared with rural areas (1,004 cases/100,000; 95% CrI 886.3–1,143). This regional trend was also seen in men age ≥45 years, where the prevalence was estimated at 273.6 cases/100,000 (95% CrI 219.8–347.6) in urban areas and 380.7 cases/100,000 (95% CrI 311.3–468.1) in rural areas. Billing data appeared more sensitive in ascertaining cases than hospitalization data, and a large proportion of diagnoses was made by physicians other than rheumatologists.

Conclusion

These data suggest a higher prevalence of PMR in rural versus urban regions. Our approach demonstrates the usefulness of methods that adjust for the imperfect nature of multiple information sources, which also allow for estimation of the sensitivity of different case ascertainment approaches.
Shared and idiosyncratic cortical activation patterns in autism revealed under continuous real‐life viewing conditions
Authors: Hasson Uri , Avidan Galia , Gelbard Hagar , Vallines Ignacio , Harel Michal , Minshew Nancy , Behrmann Marlene
Published: August 2009

Although widespread alterations in cortical structure have been documented in individuals with autism, the functional implications of these alterations remain to be determined. Here, we adopted a novel inter‐subject correlation (inter‐SC) and intra‐subject correlation (intra‐SC) technique to quantify the reliability of the spatio‐temporal responses of functional MR activity in adults with autism during free‐viewing of a popular audio–visual movie. Whereas these complex stimuli evoke highly reliable shared response time courses in typical individuals, cortical activity was more variable across individuals with autism (low inter‐SC). Interestingly, when we measured the responses within an autistic individual across repeated presentations of the movie, we observed a unique, idiosyncratic response time course that was reliably replicated within each individual (high intra‐SC). Encouragingly, after filtering out the idiosyncratic responses from each individual time course, we were able to uncover a more typical response profile, which resembles the shared responses seen in the typical subjects. These findings indicate that, under conditions approximating real‐life situations, the neural activity of individuals with autism is characterized by individualistic responses that, although reliable within an autistic individual, are both highly variable across autistic individuals and different from the responses observed within the typical subjects. These idiosyncratic responses may underlie the atypical behaviors observed in autism. At the same time, we are encouraged by the presence of the more typical activation pattern lurking beneath these idiosyncratic fluctuations. Taken together, these findings may pave the way to future research aimed at characterizing the idiosyncratic response profiles, which, in turn, might contribute to a better understanding of the heterogeneity of the autism spectrum and its diagnosis.
Terminology of developmental abnormalities in common laboratory mammals (Version 2)
Authors: Makris Susan L. , Solomon Howard M. , Clark Ruth , Shiota Kohei , Barbellion Stephane , Buschmann Jochen , Ema Makoto , Fujiwara Michio , Grote Konstanze , Hazelden Keith P. , Hew Kok Wah , Horimoto Masao , Ooshima Yojiro , Parkinson Meg , Wise L. David
Published: August 2009

This update (Version 2) of the Terminology of Developmental Abnormalities in Common Laboratory Mammals (Version 1) by Wise et al. (1997) incorporates improvements and enhancements to both content and organization of the terminology, to enable greater flexibility in its application, while maintaining a consistent approach to the description of findings. The revisions are the result of an international collaboration among interested organizations, advised by individual experts and the outcomes of several workshops. The terminology remains organized into tables under the broad categories of external, visceral, and skeletal observations, following the manner in which data are typically collected and recorded in developmental toxicity studies. This arrangement of the tables, as well as other information provided in appendices, is intended to facilitate the process of specimen evaluation at the laboratory bench level. Only the commonly used laboratory mammals (i.e., rats, mice, rabbits) are addressed in the current terminology tables. The inclusion of other species that are used in developmental toxicity testing, such as primates, is considered outside the scope of the present update. Similarly, categorization of findings as, for example, “malformation” or “variation” remains unaddressed, in accordance with the overall principle that the focus of this document is descriptive terminology and not diagnosis/interpretation. The skeletal terms have been augmented to accommodate cartilage findings. Birth Defects Res (Part B) 86:227–327, 2009. © 2009 Wiley‐Liss, Inc.
Origin and evolution of chromosomal sperm proteins
Authors: Eirín‐López José M. , Ausió Juan
Published: August 2009

In the eukaryotic cell, DNA compaction is achieved through its interaction with histones, constituting a nucleoprotein complex called chromatin. During metazoan evolution, the different structural and functional constraints imposed on the somatic and germinal cell lines led to a unique process of specialization of the sperm nuclear basic proteins (SNBPs) associated with chromatin in male germ cells. SNBPs encompass a heterogeneous group of proteins which, since their discovery in the nineteenth century, have been studied extensively in different organisms. However, the origin and controversial mechanisms driving the evolution of this group of proteins has only recently started to be understood. Here, we analyze in detail the histone hypothesis for the vertical parallel evolution of SNBPs, involving a “vertical” transition from a histone to a protamine‐like and finally protamine types (H → PL → P), the last one of which is present in the sperm of organisms at the uppermost tips of the phylogenetic tree. In particular, the common ancestry shared by the protamine‐like (PL)‐ and protamine (P)‐types with histone H1 is discussed within the context of the diverse structural and functional constraints acting upon these proteins during bilaterian evolution.
Left‐right asymmetry in gut development: what happens next?
Authors: Burn Sally F , Hill Robert E
Published: August 2009

The gastrointestinal tract is an asymmetrically patterned organ system. The signals which initiate left‐right asymmetry in the developing embryo have been extensively studied, but the downstream steps required to confer asymmetric morphogenesis on the gut organ primordia are less well understood. In this paper we outline key findings on the tissue mechanics underlying gut asymmetry, across a range of species, and use these to synthesise a conserved model for asymmetric gut morphogenesis. We also discuss the importance of correct establishment of left‐right asymmetry for gut development and the consequences of perturbations in this process.
Metabolic systems maintain stable non‐equilibrium via thermodynamic buffering
Authors: Igamberdiev Abir U. , Kleczkowski Leszek A.
Published: August 2009

Here, we analyze how the set of nucleotides in the cell is equilibrated and how this generates simple rules that help the cell to organize itself via maintenance of a stable non‐equilibrium state. A major mechanism operating to achieve this state is thermodynamic buffering via high activities of equilibrating enzymes such as adenylate kinase. Under stable non‐equilibrium, the ratios of free and Mg‐bound adenylates, Mg2+ and membrane potentials are interdependent and can be computed. The adenylate status is balanced with the levels of reduced and oxidized pyridine nucleotides through regulated uncoupling of the pyridine nucleotide pool from ATP production in mitochondria, and through oxidation of substrates non‐coupled to NAD+ reduction in peroxisomes. The set of adenylates and pyridine nucleotides constitutes a generalized cell energy status and determines rates of major metabolic fluxes. As the result, fluxes of energy and information become organized spatially and temporally, providing conditions for self‐maintenance of metabolism.
Identification and targeting of cancer stem cells
Authors: Schatton Tobias , Frank Natasha Y. , Frank Markus H.
Published: August 2009

Cancer stem cells (CSC) represent malignant cell subsets in hierarchically organized tumors, which are selectively capable of tumor initiation and self‐renewal and give rise to bulk populations of non‐tumorigenic cancer cell progeny through differentiation. Robust evidence for the existence of prospectively identifiable CSC among cancer bulk populations has been generated using marker‐specific genetic lineage tracking of molecularly defined cancer subpopulations in competitive tumor development models. Moreover, novel mechanisms and relationships have been discovered that link CSC to cancer therapeutic resistance and clinical tumor progression. Importantly, proof‐of‐principle for the potential therapeutic utility of the CSC concept has recently been provided by demonstrating that selective killing of CSC through a prospective molecular marker can inhibit tumor growth. Herein, we review these novel and translationally relevant research developments and discuss potential strategies for CSC‐targeted therapy in the context of resistance mechanisms and molecular pathways preferentially operative in CSC.
Changing phosphoinositides “on the fly”: how trafficking vesicles avoid an identity crisis
Authors: Botelho Roberto J.
Published: August 2009

Joining an antagonistic phosphoinositide (PtdInsP) kinase and phosphatase into a single protein complex may regulate rapid and local PtdInsP changes. This may be important for processes such as membrane fission that require a specific PtdInsP and that are innately local and rapid. Such a complex could couple vesicle formation, with erasing of the identity of the donor organelle from the vesicle prior to its fusion with target organelles, thus preventing organelle identity intermixing. Coordinating signals are postulated to switch the relative activities of the kinase and phosphatase in a spatio‐temporal manner that matches membrane fission events. The discovery of two such complexes supports this hypothesis. One regulates the interconversion of phosphatidylinositol and PtdIns(3)P by joining the Vps34 PtdIns 3‐kinase and the myotubularin 3‐phosphatases. The other regulates the interconversion between PtdIns(3)P and PtdIns(3,5)P2 through the Fab1/PIKfyve kinase and the Fig4/mFig4 phosphatase. These lipids are essential components of the endosomal identity code.
Comparison of an Ion Exchanger and an In‐House Electrodialysis Unit for Recovery of L‐Lactic Acid from Fungal Fermentation Broth
Authors: Boonkong W. , Sangvanich P. , Petsom A. , Thongchul N.
Published: August 2009

Lactic acid has long been widely used in many applications. Currently, the worldwide market is increasing due to the discovery of biodegradable polylactic acid. In this work, L‐lactic acid separations from filamentous fungal fermentation broth using ion‐exchange chromatography and in‐house electrodialysis, were studied and compared. Dowex Marathon WBA was used for the lactic acid separation. The adsorption equilibrium followed a Langmuir isotherm. The optimal conditions for lactic acid adsorption in a fixed‐bed column were at pH 6.0, and 0.8 mL/min and elution by a mixture of 1.0 M sulfuric acid and 1.0 M phosphoric acid in a ratio of 30:70 at 0.3 mL/min. The final lactic acid recovery was 76 % with 90 % purity. A laboratory scale in‐house electrodialysis apparatus was constructed with an effective membrane area of 2.925 · 10–3 m2. The effects of feeding solution concentration, flow rate, pH of the fermentation broth, and applicable voltage were studied. Under the optimal conditions, lactic acid recovery was 92 % with 100 % purity and a specific energy consumption of 0.6122 kWh/kg.
Prognosis and patterns of care in elderly patients with glioma
Authors: Iwamoto Fabio M. , Reiner Anne S. , Nayak Lakshmi , Panageas Katherine S. , Elkin Elena B. , Abrey Lauren E.
Published: August 2009

BACKGROUND:

The current study was conducted to evaluate the patterns of care and survival of older adults with oligodendroglioma (OLI) and astrocytoma (AST) from a large population‐based registry.

METHODS:

The authors identified a cohort of OLI and AST patients aged ≥65 years from Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims between 1994 and 2002. Patients with a diagnosis of glioblastoma were excluded. The impact of demographic characteristics and comorbidities on the probability of undergoing surgical resection, radiotherapy (RT), and chemotherapy within 6 months of diagnosis was assessed using multivariate logistic regression.

RESULTS:

A total of 1067 patients (891 with AST and 176 with OLI) were included; the median survival was 9 months for patients with low‐grade AST, 4 months for patients with anaplastic AST, 57 months for patients with low‐grade OLI, and 9 months for patients with anaplastic OLI. Approximately 54% of patients underwent resection at the time of diagnosis; 66% received RT, and 13% received chemotherapy within 6 months of diagnosis. In a multivariate regression analysis, age and tumor grade were found to be the most significant predictors of resection, RT, or chemotherapy. Patients with anaplastic tumors were treated with resection, RT, and chemotherapy more often than patients with low‐grade tumors, and OLI patients received chemotherapy more frequently than AST.

CONCLUSIONS:

Data from the current study suggested that histologic diagnosis and tumor grade retained significant prognostic value in this elderly AST and OLI population. Furthermore, age and tumor grade were found to influence the probability of undergoing surgery, RT, and chemotherapy in this cohort. Cancer 2009. © 2009 American Cancer Society.
Radiotherapy or surgery for head and neck squamous cell cancer
Authors: Hall Stephen F. , Groome Patti A. , Irish Jonathan , O'Sullivan Brian
Published: August 2009

BACKGROUND:

The authors compared the survival outcomes of radiotherapy +/− salvage surgery to surgery +/− postoperative radiotherapy for patients with squamous cell cancer of the hypopharynx. There was no evidence beyond observational studies and no consensus on the which treatment is most effective for this patient group.

METHODS:

The authors conducted a retrospective population‐based study of 595 patients from Ontario Canada diagnosed between January 1, 1990 and December 31, 1999. Three different methodological approaches were used for the survival analysis including a restricted cohort study, a matched case‐control study, and a natural experiment study across defined geographic regions.

RESULTS:

The authors found no survival advantage for either radiotherapy +/− salvage surgery or surgery +/− postoperative radiotherapy.

CONCLUSIONS:

This study set the baseline for clinical decisions that was not previously established there is no difference in survival for patients with hypopharynx comparing primary surgery to primary radiotherapy. This information is essential for the interpretation of current treatment results, the planning of future clinical studies and the treatment of patients who are not having chemoradiotherapy. Cancer 2009. © 2009 American Cancer Society.
Thyroid fine‐needle aspiration with atypia of undetermined significance
Authors: Shi Yan , Ding Xin , Klein Melissa , Sugrue Chiara , Matano Sandra , Edelman Morris , Wasserman Patricia
Published: August 2009

BACKGROUND:

Atypia of undetermined significance is a controversial category in thyroid fine‐needle aspiration (FNA), not only for its questioned clinical utility, but also for its very existence as an expression of uncertainty. The current study was performed to investigate the potential impact of eliminating this category on the sensitivity and specificity for detecting thyroid neoplasms by FNA.

METHODS:

Forty cases originally diagnosed as atypia of undetermined significance with histologic follow‐up were selected for the present study. These cases were reinterpreted blindly by 2 experienced reviewers, who eliminated atypia of undetermined significance as a diagnostic possibility and reclassified these cases as either benign, follicular neoplasm, suspicious for malignancy, or malignant. Twenty‐six cases of atypia of undetermined significance were randomly selected and reevaluated 6 months later to study intraobserver variation.

RESULTS:

After eliminating the atypia of undetermined significance category, the sensitivity for detecting papillary thyroid carcinoma (PTC) was reduced from 100% to 27% (P = .04). In those atypia of undetermined significance cases that were reclassified as benign, 37% had PTC. In those reclassified as follicular neoplasm or suspicious for malignancy, 38% were histologically proven to be benign lesions. Unanimous interobserver and intraobserver agreement was observed in only 60% of cases.

CONCLUSIONS:

Eliminating the diagnosis of atypia of undetermined significance substantially decreases the sensitivity of thyroid FNAs and increases both false‐positive and false‐negative rates. In addition, it increases interobserver and intraobserver variability. Therefore, the atypia of undetermined significance category should not be eliminated; but we advocate minimizing its use. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Amplification of Chirality and Enantioselectivity in the Asymmetric Autocatalytic Soai Reaction
Authors: Schiaffino Luca , Ercolani Gianfranco
Published: August 2009

From a kinetic analysis of the “dimer model”, which is the most prominent mechanism of the Soai reaction, an equation is derived predicting the amplification of enantiomeric excess as a function of initial conditions. The role played by the enantioselectivity of the catalyst‐product is also taken into account. Comparison with experimental data obtained at 0 °C by Soai et al. shows that the predicted enantiomeric excesses are lower than the experimental values by up to four orders of magnitude, and thus revision of the dimer model in the low‐temperature regime is warranted. A kinetic analysis including the formation of tetramers is presented that fits the data at 0 °C and indicates that 2:2 heterochiral tetramers are more stable than homochiral and 3:1 heterochiral tetramers. A DFT study on diastereomers of barrel‐like tetramers indeed shows higher stability of 2:2 heterochiral tetramers and thus lends support to the above kinetic analysis.
Single‐Molecule Spectroscopy on a Ladder‐Type Conjugated Polymer: Electron–Phonon Coupling and Spectral Diffusion
Authors: Hildner Richard , Winterling Laura , Lemmer Ulrich , Scherf Ullrich , Köhler Jürgen
Published: August 2009

We employ low‐temperature single‐molecule spectroscopy combined with pattern recognition techniques for data analysis on a methyl‐substituted ladder‐type poly(para‐phenylene) (MeLPPP) to investigate the electron–phonon coupling to low‐energy vibrational modes as well as the origin of the strong spectral diffusion processes observed for this conjugated polymer. The results indicate weak electron–phonon coupling to low‐frequency vibrations of the surrounding matrix of the chromophores, and that low‐energy intrachain vibrations of the conjugated backbone do not couple to the electronic transitions of MeLPPP at low temperatures. Furthermore, these findings suggest that the main line‐broadening mechanism of the zero‐phonon lines of MeLPPP is fast, unresolved spectral diffusion, which arises from conformational fluctuations of the side groups attached to the MeLPPP backbone as well as of the surrounding host material.
Deposition of Mo Oxide and Metallic Mo Films by Chemical Vapor Transport of MoO3(OH)2
Authors: Lee Young Jung , Seo Young Ik , Kim Se Hoon , Kim Dae‐Gun , Kim Young Do
Published: August 2009

Molybdenum oxides have attracted interest as gas sensing, catalytic, photochromic, and electrochromic materials. Molybdenum coatings are currently applied to materials for friction and wear control over a wide temperature range; they are also resistant to corrosion and chemicals. In this study, a new technique for deposition of MoO2 and metallic Mo, through the chemical vapor transport (CVT) of MoO3(OH)2 during hydrogen reduction of a MoO3 powder, is presented. MoO2 and metallic Mo are deposited in two temperature ranges during hydrogen reduction, namely, MoO3 → MoO2 and MoO2 → Mo, respectively. The MoO2 film is directly deposited by using volatile MoO3(OH)2 gas formed during the hydrogen reduction of MoO3 to MoO2 at the lower temperature, while metallic Mo film is obtained by simultaneous hydrogen reduction of deposited MoO2 at the higher temperature.
Four‐ and five‐color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: A reference document based on a systematic approach by the GTLLF and GEIL
Authors: Arnoulet Christine , Béné Marie C. , Durrieu Françoise , Feuillard Jean , Fossat Chantal , Husson Bernard , Jouault Hélène , Maynadié Marc , Lacombe Francis
Published: August 2009

Background:

The development of multiparameter flow cytometry (FCM) and increasingly sophisticated analysis software has considerably improved the exploration of hematological disorders. These tools have been widely applied in leukaemias, lymphomas, and myelodysplasias, yet with very heterogeneous approaches. Consequently, there is no extensive reference document reporting on the characteristics of normal human bone marrow (BM) in multiparameter FCM. Here, we report a reference analysis procedure using relevant antibody combinations in normal human BM.

Methods:

A first panel of 23 antibodies, constructed after literature review, was tested in four‐color combinations (including CD45 in each) on 30 samples of BM. After evaluation of the data, a second set of 22 antibodies was further applied to another 35 BM samples. All list‐modes from the 65 bone marrow samples were reviewed collectively. A systematised protocol for data analysis was established including biparametric representations and color codes for the three major lineages and undifferentiated cells.

Results:

This strategy has allowed to obtain a reference atlas of relevant patterns of differentiation antigens expression in normal human BM that is available within the European LeukemiaNet. This manuscript describes how this atlas was constructed.

Conclusions:

Both the strategy and atlas could prove very useful as a reference of normality, for the determination of leukemia‐associated immunophenotypic patterns, analysis of myelodysplasia and, ultimately, investigation of minimal residual disease in the BM. © 2009 Clinical Cytometry Society
Association between serotonin transporter gene polymorphism and eating disorders: A meta‐analytic study
Authors: Lee Yu , Lin Pao‐Yen
Published: August 2009

Objective

Compelling evidence has suggested a role for serotonin system dysfunction in the pathogenesis of eating disorders (EDs), including anorexia nervosa (AN) and bulimia nervosa (BN). Studies have examined the association between EDs and a functional polymorphism of the serotonin transporter gene promoter (5‐HTTLPR). These studies have yielded inconsistent results. The present study aimed to determine conclusively whether there is an association by using a meta‐analytic method.

Method

Data of over 2,000 participants from eight independent case–controlassociation studies were pooled by using a random effects model.

Results

AN was found to be significantly associated with the S allele (p < .001) and S carrier (SS + LS) genotype (p = .007). However, BN was associated neither with the S allele (p = .49) nor with the S carrier genotype (p = .33).

Discussion

These results suggested that the genetic variance of the serotonin transporter gene promoter contributed to the susceptibility of AN. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:498–504
Nocturnal eating: Association with binge eating, obesity, and psychological distress
Authors: Striegel‐Moore Ruth H. , Rosselli Francine , Wilson G. Terence , Perrin Nancy , Harvey Kate , DeBar Lynn
Published: August 2009

Objective

To examine clinical correlates of nocturnal eating, a core behavioral symptom of night eating syndrome.

Method

Data from 285 women who had participated in a two‐stage screening for binge eating were utilized. Women (n = 41) who reported one or more nocturnal eating episodes in the past 28 days on the eating disorder examination and women who did not report nocturnal eating (n = 244) were compared on eating disorder symptomatology, body mass index (BMI), and on measures of psychosocial adjustment.

Results

Nocturnal eaters were significantly more likely to report binge eating and differed significantly from non‐nocturnal eaters (with responses indicating greater disturbance) on weight and shape concern, eating concern, self‐esteem, depression, and functional impairment, but not on BMI or dietary restraint. Group differences remained significant in analyses adjusting for binge eating.

Discussion

This study confirms the association between nocturnal eating and binge eating previously found in treatment seeking samples yet also suggests that the elevated eating disorder symptoms and decreased psychosocial adjustment observed in nocturnal eaters is not simply a function of binge eating. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:520–526
Syntheses, Structures and Theoretical Investigations of [Li(thf)4]2[Ti2Cu8S4(SPh)10] and [Ti2Ag6S6Cl2(PPhiPr2)6]
Authors: Sommer Heino , Drebov Nedko , Eichhöfer Andreas , Ahlrichs Reinhart , Fenske Dieter
Published: August 2009

The reaction of CuOAc (OAc = acetate) with TiCl4·2thf and LiSPh in thf leads to the formation of tiny deep‐red crystals of [Li(thf)4]2[Ti2Cu8S4(SPh)10]. The silver/titanium cluster complex [Ti2Ag6S6Cl2(PPhiPr2)6] was synthesized by the reaction of TiCl4·2thf with AgPhCO2 and S(SiMe3)2 in the presence of PPhiPr2. The crystal structures of the compounds were determined by X‐ray analysis of single crystals. Additionally, theoretical investigations were performed to assign the proper chlorine/sulfur atomic positions and to rationalize the bonding situation in 1 and 2. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthesis, Structure and Electrochemical Properties of a Ferrocene‐Bridged Bis[tris(arylselenolato)stannyl] Compound
Authors: Nayek Hari Pada , Hilt Gerhard , Dehnen Stefanie
Published: August 2009

Two ferrocene‐bridged bis[tris(arylselenolate)stannyl] compounds with the general formula (RSe)3Sn–Fc–Sn(SeR)3 [Fc = ferrocene; R = Ph (1), 1‐Np (2)] were synthesized and characterized by means of NMR spectroscopy (1, 2) as well as X‐ray diffraction (1). It was shown by DFT calculations that the observed mixed cis/trans conformation of the SePh groups in 1 represents the global minimum on the energy hyperface in the presence of an Fc bridge between the two tin atoms. Investigation of the electrochemical behavior of 1 indicated the electrochemically driven conversion under cleavage of the tin–selenium bond.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Stepwise geographical traceability of virgin olive oils by chemical profiles using artificial neural network models
Authors: García‐González Diego L. , Luna Guadalupe , Morales Maria T. , Aparicio Ramón
Published: August 2009

The geographical traceability of virgin olive oils implies the use of analytical methods that allow the identification of the origin of the oil and the authentication of the information boasted on the labels. In this work, the geographical identification of the virgin olive oils has been addressed by complete chemical characterisation of samples (64 compounds analysed by GC and HPLC) and the design of artificial neural network (ANN) models for each one of the levels of a proposed classification scheme. A high number of samples (687) from Spain, Italy and Portugal served as training and test sets for the ANN models. The highest classification level, focused on the grouping of samples by country, was achieved through analysis of fatty acids, with 99.9% of samples classified. Other levels (region, province, Protected Designations of Origin or PDO) were focused on Spanish oils and required additional series of compounds (sterols, alcohols, hydrocarbons) as well as the fatty acids to obtain classification rates higher than 90%. The classification of oils into different PDOs – the last and most difficult level of classification – showed the highest root mean square errors. The classification percentages, however, were still higher than 90% in the test set, which proves the application of the traceability methodology for a chemical verification of PDO claims.
In‐vitro study on the efficacy of tannin fractions of edible nuts as antioxidants
Authors: Karamać Magdalena
Published: August 2009

Tannin fractions were isolated from crude acetonic extracts of defatted walnut, hazelnut and almond kernels using Sephadex LH‐20 column chromatography. The obtained material was characterized by content of total phenolics and electrophoretic separations using capillary zone electrophoresis (CZE). The antioxidant activities of the tannin fractions were analyzed by several methods: DPPH and ABTS assays, photochemiluminescence (PCL) method, as well as in two lipid model systems: emulsion with β‐carotene‐linoleic acid and L‐α‐lecithin liposomes. The contents of total phenolics in the tannin fractions of walnuts, hazelnuts and almonds were 550, 329 and 83 mg catechin eq/g, respectively. The electrophoretic profiles of hazelnut and almond tannin fractions were similar, in contrast to the walnut profile. All analyzed fractions exhibited strong antioxidant properties. The antioxidant capacity of lipid‐soluble (ACL) compounds determined by PCL method was the highest for the fraction isolated from walnuts – 7.35 mmol Trolox eq/g. The DPPH radical and the ABTS radical cation were scavenged by the walnut tannin fraction with a higher efficacy than by the two other fractions. EC50 values of the DPPH method were 1.8 times higher for the hazelnut fraction and 2.3 times higher for the almond fraction when compared to the walnut tannins. In turn, the total antioxidant activity values were 8.17, 2.82 and 1.98 mmol Trolox eq/g for the walnut, hazelnut and almond fractions, respectively. On the other hand, in both lipid models applied, lower antioxidant activity of walnut tannins than of hazelnut tannins was noted. The antioxidant effect of almond tannins was weaker or similar than that of walnut tannins in the β‐carotene‐linoleic acid emulsion and the L‐α‐lecithin liposomal system, respectively.
Distribution of monomeric, dimeric and polymeric products of stigmasterol during thermo‐oxidation
Authors: Lampi Anna‐Maija , Kemmo Suvi , Mäkelä Anu , Heikkinen Susanna , Piironen Vieno
Published: August 2009

When plant sterols are oxidized at moderate temperatures (≤100 °C), products mainly derive from hydroperoxides, but at temperatures close to 200 °C, thermal reactions such as dehydration and condensation become important. Although sterols are often subjected to frying conditions, very little is known of their thermal reactions. In this study, stigmasterol was thermo‐oxidized at 180 °C, and the formation of dimers and polymers and the amounts of monomers were measured by high‐performance size‐exclusion chromatography. The products were further characterized by polarity using solid‐phase extraction fractionation. During heating, the amounts of monomers decreased at a steady rate, and those of dimers and polymers increased. After 3 h of heating, 21% of the material existed in higher‐molecular‐weight products. The amount of polar monomers increased especially during the first hour, demonstrating the formation of oxides and their further reactions, while that of mid‐polar monomers decreased constantly, indicating losses of stigmasterol. Polar dimers contributed to approximately 60% of the dimers, and polar polymers to approximately 78% of the polymers, which suggests that in most higher‐molecular‐weight products at least one of the sterol moieties was oxidized. This study showed that a significant proportion of thermo‐oxidation products are not polar monomeric oxides which are commonly analyzed as oxidation products.
Mutagenicity of blue rayon extracts of fish bile as a biomarker in a field study
Authors: dos Santos Patrícia Estevam , Kummrow Fábio , de Albergaria‐Barbosa Ana Cecília Rizzatti , Bícego Márcia Caruso , Umbuzeiro Gisela de Aragão
Published: August 2009

Blue rayon (BR) in combination with the Salmonella/microsome assay was used to evaluate the mutagenicity of fish bile samples. Specimens of Mugil curema from two sites were collected over a 1‐year period. Piaçaguera channel contains high concentrations of total polycyclic aromatic hydrocarbons (PAHs) and other contaminants, while Bertioga channel was considered the reference sites in this study. Bile was extracted with BR and tested with TA98, TA100, and YG1041 strains with and without S9 in dose response experiments. PAH metabolite equivalents were analyzed using reverse‐phase high performance liquid chromatography /fluorescence. Higher mutagenic responses were observed for the contaminated site; YG1041 with S9 was the most sensitive strain/condition. Mutagenicity ranged from 3,900 to 14,000 rev./mg at the contaminated site and from 1,200 to 2,500 rev./mg of BR at the reference site. The responses of YG1041 were much higher in comparison with the TA98 indicating the presence of polycyclic compounds from the aromatic amine class that cause frameshift mutation. TA100 showed a positive mutagenic response that was enhanced following S9 treatment at both sites suggesting the presence of polycyclic compounds that require metabolic activation. benzo(a)pyrene, naphthalene, and phenanthrene metabolite equivalents were also higher in the bile of fish collected at the contaminated site. It was not possible to correlate the PAH metabolite quantities with the mutagenic potency. Thus, a combination of the Salmonella/microsome assay with YG1041 with S9 from BR bile extract seems to be an acceptable biomarker for monitoring the exposure of fish to mutagenic polycyclic compounds. Environ. Mol. Mutagen., 2010. © 2009 Wiley‐Liss, Inc.
An evaluation of the mode of action framework for mutagenic carcinogens case study II: Chromium (VI)
Authors: McCarroll Nancy , Keshava Nagalakshmi , Chen Jonathan , Akerman Gregory , Kligerman Andrew , Rinde Esther
Published: August 2009

In response to the 2005 revised U.S Environmental Protection Agency's (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with additional information to determine whether the initiating step in carcinogenesis is through a mutagenic mode of action (MOA). This information is necessary to decide if age‐dependent adjustment factors (ADAFs) should be applied to the risk assessment. Chromium (VI) [Cr (VI)], a carcinogen in animals and humans via inhalation, was reassessed by the National Toxicology Program (NTP) in 2‐year drinking water studies in rodents. From these data, NTP concluded that the results with Cr (VI) showed clear evidence of carcinogenicity in male and female mice and rats. Cr (VI) is also mutagenic, in numerous in vitro assays, in animals (mice and rats) and in humans. Accordingly, Cr (VI) was processed through the MOA framework; postulated key steps in tumor formation were interaction of DNA with Cr (VI) and reduction to Cr (III), mutagenesis, cell proliferation, and tumor formation. Within the timeframe and tumorigenic dose range for early events, genetic changes in mice (single/double‐stranded DNA breaks) commence within 24 hr. Mechanistic evidence was also found for oxidative damage and DNA adduct formation contributing to the tumor response. The weight of evidence supports the plausibility that Cr (VI) may act through a mutagenic MOA. Therefore, the Cancer Guidelines recommend a linear extrapolation for the oral risk assessment. Cr (VI) also induces germ cell mutagenicity and causes DNA deletions in developing embryos; thus, it is recommended that the ADAFs be applied. Environ. Mol. Mutagen., 2010. Published 2009 Wiley‐Liss, Inc.
The paleoanthropology of Greece
Authors: Harvati Katerina , Panagopoulou Eleni , Runnels Curtis
Published: August 2009

European paleoanthropology and paleolithic archeology were already well‐established by the early twentieth century. The human fossil record from this continent is the longest known and perhaps most intensively studied. Nonetheless, important gaps remain to this day in the map of Pleistocene Europe; perhaps the most glaring of these is located in the southeastern corner of the continent. This region's record is critical for addressing questions about the course of human evolution in Europe because its geographic position lends it a dual role: on one hand, it encompasses a frequently hypothesized dispersal corridor from Africa into Europe for both archaic and early modern humans; on the other, as one of the three Mediterranean peninsulas, it acted as a refugium for plant, animal, and, most likely, human populations during glacial conditions. This article is a review of the paleoanthopological record of Greece, one of the least known in Europe.
Epigenetic Silence of Ankyrin-Repeat–Containing, Sh3-Domain–Containing, and Proline-Rich-Region– Containing Protein 1 ( Aspp1 ) and Aspp2 Genes Promotes Tumor Growth in Hepatitis B Virus–Positive Hepatocellular Carcinoma
Authors: Zhao Jian , Wu Guobin , Bu Fangfang , Lu Bin , Liang Anmin , Cao Lei , Tong Xin , Lu Xin , Wu Mengchao , Guo Yajun
Published: August 2009

The ankyrin-repeat–containing, SH3-domain–containing, and proline-rich-region–containing protein (ASPP) family of proteins regulates apoptosis through interaction with p53 and its family members. This study evaluated the epigenetic regulation of

ASPP1

and

ASPP2

in hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) and explores the effects of down-regulation of

ASPP1

and

ASPP2

on the development of HCC. HCC cell lines and tissues from HCC patients were used to examine the expression and methylation of

ASPP1

and

ASPP2

. The expression of

ASPP1

and

ASPP2

was diminished in HCC cells by epigenetic silence owing to hypermethylation of

ASPP1

and

ASPP2

promoters. Analyses of 51 paired HCC and surrounding nontumor tissues revealed that methylation of

ASPP1

and

ASPP2

was associated with the decreased expression of

ASPP1

and

ASPP2

in tumor tissues and the early development of HCC. Moreover,

ASPP2

became methylated upon HBV x protein (HBx) expression. The suppressive effects on tumor growth by

ASPP1

and

ASPP2

were examined with RNA interference-mediated gene silence. Down-regulation of

ASPP1

and

ASPP2

promoted the growth of HCC cells in soft agar and in nude mice and decreased the sensitivity of HCC cells to apoptotic stimuli.

Conclusion: ASPP1

and

ASPP2

genes are frequently down-regulated by DNA methylation in HBV-positive HCC, which may play important roles in the development of HCC. These findings provide new insight into the molecular mechanisms leading to hepatocarcinogenesis and may have potent therapeutic applications. (Hepatology 2010;51:142–153.)
Increased Tumor Necrosis Factor α–Converting Enzyme Activity Induces Insulin Resistance and Hepatosteatosis in Mice
Authors: Fiorentino Loredana , Vivanti Alessia , Cavalera Michele , Marzano Valeria , Ronci Maurizio , Fabrizi Marta , Menini Stefano , Pugliese Giuseppe , Menghini Rossella , Khokha Rama , Lauro Renato , Urbani Andrea , Federici Massimo
Published: August 2009

Tumor necrosis factor α–converting enzyme (TACE, also known as ADAM17) was recently involved in the pathogenesis of insulin resistance. We observed that TACE activity was significantly higher in livers of mice fed a high-fat diet (HFD) for 1 month, and this activity was increased in liver > white adipose tissue > muscle after 5 months compared with chow control. In mouse hepatocytes, C2C12 myocytes, and 3T3F442A adipocytes, TACE activity was triggered by palmitic acid, lipolysaccharide, high glucose, and high insulin. TACE overexpression significantly impaired insulin-dependent phosphorylation of AKT, GSK3, and FoxO1 in mouse hepatocytes. To test the role of TACE activation

in vivo

, we used tissue inhibitor of metalloproteinase 3 (Timp3) null mice, because Timp3 is the specific inhibitor of TACE and

Timp3

−/− mice have higher TACE activity compared with wild-type (WT) mice.

Timp3

−/− mice fed a HFD for 5 months are glucose-intolerant and insulin-resistant; they showed macrovesicular steatosis and ballooning degeneration compared with WT mice, which presented only microvesicular steatosis. Shotgun proteomics analysis revealed that

Timp3

−/− liver showed a significant differential expression of 38 proteins, including lower levels of adenosine kinase, methionine adenosysltransferase I/III, and glycine

N

-methyltransferase and higher levels of liver fatty acid-binding protein 1. These changes in protein levels were also observed in hepatocytes infected with adenovirus encoding TACE. All these proteins play a role in fatty acid uptake, triglyceride synthesis, and methionine metabolism, providing a molecular explanation for the increased hepatosteatosis observed in

Timp3

−/− compared with WT mice.

Conclusion:

We have identified novel mechanisms, governed by the TACE–Timp3 interaction, involved in the determination of insulin resistance and liver steatosis during overfeeding in mice. (Hepatology 2009.)