bluuebunny/crossref_metadata_2025 huggingface dataset:
An exploration of the main sources of shame in an eating‐disordered population
Authors: Keith Laura , Gillanders David , Simpson Susan
Published: July 2009

Objectives: Shame has received increased attention over recent years and has been shown to be a feature of many forms of psychopathology, including eating disorders. The current study contributes to this field by exploring relationships between shame and a variety of factors hypothesized to contribute to shame in a sample of 52 females with eating disorders.

Design: A cross‐sectional questionnaire design was used.

Methods: Participants were 52 women with eating disorders. They completed six questionnaires: The Experience of Shame Scale, the Parental Bonding Inventory, the Social Isolation Subscale of the Young Schema Questionnaire, the Eating Disorder Diagnostic Scale and the Hospital Anxiety & Depression Scale.

Results: High levels of shame were observed, and not only shame around eating. A multiple regression analysis, with shame as the dependent variable and other variables as predictor variables revealed that the Social Isolation schema explained a substantial amount of total shame scores. Negative experiences of maternal care and eating disorder pathology also contributed a small but significant amount to the variance in shame scores.

Conclusions: People with eating disorders experience generalized shame in relation to many aspects of their self and behaviour, not just shame around eating. Implications for future research, including the importance of prospective longitudinal designs, are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Cyanoimide‐Bridged, Bi‐ and Trinuclear, Heterometallic Complexes with an NCN–Mo–NCN Phosphinic Core
Authors: Cunha Sónia M. P. R. M. , Guedes da Silva M. Fátima C. , Fraústo da Silva João J. R. , Pombeiro Armando J. L.
Published: July 2009

The heterometallic dinuclear complexes of the types trans‐[Mo(NCN)(dppe)2(μ‐NCN)M] [M = WCl4(PPh3), ReOCl3(PPh3) or mer‐ReCl(N2)(PMePh2)3; dppe = Ph2PCH2CH2PPh2] and [Mo(NCN)(dppe)2(μ‐NCN)M][BF4]Br [M = trans‐Fe(NCC6H4NO2‐4)(depe)2; depe = Et2PCH2CH2PEt2] and the trinuclear ones [Mo(dppe)2{(μ‐NCN)M}2] [M = VCl3(thf) or PtCl2(PEt3)] were prepared by reaction of the bis(cyanoimido)molybdenum complex trans‐[Mo(NCN)2(dppe)2] with the corresponding transition‐metal Lewis acid (M) precursors, particularly [VCl3(thf)3], [WCl4(PPh3)2], [ReOCl3(PPh3)2], trans‐[ReCl(N2)(PMePh2)4], trans‐[FeBr(NCC6H4NO2‐4)(depe)2][BF4] and [Pt2Cl4(PEt3)2]. These adducts were characterized by FTIR, 1H, 13C and 31P{1H} NMR spectroscopy, mass spectrometry and cyclic voltammetry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enamine–Metal Lewis Acid Bifunctional Catalysis: Application to Direct Asymmetric Aldol Reaction of Ketones
Authors: Xu Zhenghu , Daka Philias , Budik Ilya , Wang Hong , Bai Fu‐Quan , Zhang Hong‐Xing
Published: July 2009

Unprecedented bifunctional enamine–metal Lewis acid catalysts have been developed. In this bifunctional catalytic system, a tridentate ligand tethered with a chiral secondary amine was designed to solve the acid–base self‐quenching problem leading to catalyst inactivation. This new bifunctional enamine–metal Lewis acid catalyst was found to catalyze aldol reactions of ketones efficiently in high yields and good to excellent diastereoselectivities and enantioselectivities.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Differential mutagenicity of aflatoxin B1 in the liver of neonatal and adult mice
Authors: Chen Tao , Heflich Robert H. , Moore Martha M. , Mei Nan
Published: July 2009

Children are generally more sensitive to toxicants than adults, including an increased sensitivity to genotoxic carcinogens. We previously demonstrated that neonatal mice are also more sensitive to the mutagenic effects of the direct alkylating agents N‐ethyl‐N‐nitrosoamine and the arylamine 4‐aminobiphenyl than adult mice. In this study, we have evaluated the effect of age on the mutagenicity of the fungal toxin and liver carcinogen aflatoxin B1 (AFB1). Neonatal Big Blue transgenic mice were treated with 6 mg/kg AFB1, a treatment that produces liver tumors, while adult mice were treated with 6 and 60 mg/kg AFB1, treatments that do not result in tumors. The cII liver mutant frequency (MF) in mice treated with AFB1 as neonates was 22‐fold higher than in control neonatal mice, whereas the treatment of adult mice with either dose of AFB1 did not significantly increase the liver MF over the controls. In AFB1‐treated neonatal mice, the frequency of G:C → T:A transversion, a major type of mutation induced by AFB1, was about 82‐fold higher than for the control and 31‐fold higher than for adult mice treated with 60 mg/kg AFB1. Our mutagenicity findings parallel the relative carcinogenicity of AFB1 in neonatal and adult mice, and are consistent with previous observations of the lower level of hepatic glutathione S‐transferase and higher level of hepatic AFB1‐DNA adduction in neonatal mice compared to adult mice. Environ. Mol. Mutagen. 2010. Published 2009 by Wiley‐Liss, Inc.
Enhanced removal of organic matter and ammonia nitrogen in a one‐stage vertical flow constructed wetland system
Authors: Du Xiaoli , Xu Zuxin , Wang Sheng
Published: July 2009

A modified cyclic batch constructed wetland was innovated to examine the removal of organic matter and ammonia nitrogen from rural wastewater in the eastern area of China. The results demonstrated that mean percentage removal of BOD5 and NH‐N in the modified cyclic batch constructed wetland treating rural wastewater were 80 and 97%, respectively. Compared with conventional constructed wetland systems, the quality of effluent from the modified cyclic batch constructed wetland was higher when treating rural wastewater. The predominant process for BOD5 removal was aerobic biodegradation and biomass assimilation in the system, which accounted for more than 99% of total removal. Mass balance calculation of NH‐N showed that the average rate of nitrification was 6.247 g m−2 day−1, which was 7.5 times more than the amount removed by biomass assimilation. The supply of oxygen by the modified methods in the modified cyclic batch constructed wetland was significantly high for available oxygen, which was 76.984 g m−2 day−1, much higher than the demand for rural wastewater treatment. © 2009 American Institute of Chemical Engineers Environ Prog, 2010
Adsorption and desorption of Cu(II), Zn(II), Pb(II), and Cd(II) on the soils amended with nanoscale hydroxyapatite
Authors: Chen Jie‐hua , Wang Yu‐jun , Zhou Dong‐mei , Cui Yu‐xia , Wang Shen‐qiang , Chen Yu‐cheng
Published: July 2009

Adsorption and desorption of Cu(II), Zn(II), Pb(II) and Cd(II) on a Red soil (RS, Udic Ferrosols) and a Wushan soil (WS, Anthrosol) amended with nanoscale hydroxyapatite (nano‐HAP) were studied by batch experiments. The adsorption isotherms show that different kinds of heavy metals had different affinity to the soils in the order of Cu(II) > Pb(II) > Cd(II) > Zn(II). The amount of each heavy metal adsorbed on the RS was lower than that on the WS, because the former had lower CEC and pH than the latter. The amendment of nano‐HAP in the soils significantly enhanced the adsorption of heavy metals, in comparison with the treatment receiving no nano‐HAP. The Kf, simulated from the adsorption isotherms, increased from 78 to 2180 for Cu(II), 16.6 to 59.5 for Zn(II), and 17.9 to174 for Cd(II) on the RS, and from 995 to 6410 for Cu(II), 52.5 to 92.4 for Zn(II), and 59.2 to 199 for Cd(II) on the WS, when 0.20 g nano‐HAP was added into 1.00 g soil. The nano‐HAP remarkably inhibited desorption of heavy metals from the soils, suggesting that the addition of nano‐HAP can significantly reduce the mobilization of heavy metals and increase their geochemical stability in metal contaminated soils. © 2009 American Institute of Chemical Engineers Environ Prog, 2010
Geomorphological, stratigraphic and geochronological evidence of fast Pleistocene coastal uplift in the westernmost part of the Corinth Gulf Rift (Greece)
Authors: Palyvos N. , Mancini M. , Sorel D. , Lemeille F. , Pantosti D. , Julia R. , Triantaphyllou M. , De Martini P.‐M.
Published: July 2009

Rapid extension and active normal faulting in the western extremity of the Corinth Gulf are accompanied by fast coastal uplift. We investigate Pleistocene uplift west of Aigion, by attempting to date remains of marine terraces and sedimentary sequences by calcareous nannoplankton and U‐series analyses. Net uplift initiated recently, due to abandonment of an older rift‐bounding fault zone and increase in activity on the presently active, coastal fault zone. This change apparently coincides with an abrupt slow down (or, termination) of secondary fault block tilting within the broader hangingwall block of the older zone, indicated by an angular unconformity that dates in the early part of MIS10 (∼390–350 ka BP, preferably, in the earlier part of this period). Net uplift driven by the coastal zone resulted in the formation of MIS9c (330 ka) and younger terraces. The formation of the unconformity and the initiation of net uplift coincide temporally with a ∼300–400 ka unconformity recognized by recent studies in a wide area offshore Aigion i.e. they could be part of an evolutionary event that affected the entire western part of the Corinth Rift or, a large area therein. Uplift rate estimates at four locations are discussed with reference to the morphotectonic context of differential uplift of secondary fault blocks, and the context of possible increase in uplift rate with time. The most reliable and most useful estimate for uplift rate at the longitude of the studied transect is 1.74–1.85 mm/year (time‐averaged estimate for the last ∼240 ka, based on calcareous nannoplankton and sequence‐stratigraphic interpretation). Copyright © 2009 John Wiley & Sons, Ltd.
Genetic variation in CYP17A1 and pancreatic cancer in a population‐based case‐control study in the San Francisco Bay Area, California
Authors: Duell Eric J. , Holly Elizabeth A. , Kelsey Karl T. , Bracci Paige M.
Published: July 2009

Pancreatic cancer is the fourth leading cause of cancer‐related death in men and women in the United States. Reproductive factors and steroid hormones have been suspected risk factors for many years, but the results from epidemiologic studies to date have been inconclusive. CYP17A1 encodes cytochrome P450c17α, an enzyme with 17α‐hydroxylase and 17,20‐lyase activities in estradiol biosynthesis. A polymorphism in the 5′UTR promoter region of CYP17A1‐34T/C(A1/A2) has been associated with circulating estrogens in premenopausal women and with susceptibility to breast, prostate, and endometrial cancer. Questionnaire data and germline DNA collected in a San Francisco Bay Area population‐based case‐control study of pancreatic cancer (cases = 532, controls = 1701) were used to conduct analyses of pancreatic cancer susceptibility related to the CYP17A1 polymorphism and whether effects associated with smoking and reproductive risk factors were modified by this polymorphism. Mass spectrometry– and TaqMan‐based methods were used to determine CYP17A1 genotypes in DNA samples from 308 cases and 964 controls. Results showed that carriers of the A2 allele (vs. A1/A1) were significantly less likely to have been diagnosed with pancreatic cancer (A1/A2, adjusted odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.58‐1.0; A2/A2, OR = 0.63, 95%CI = 0.42‐0.93; p‐trend = 0.01). ORs for CYP17A1 genotypes did not differ by sex, but the observed inverse association was stronger in postmenopausal women. ORs for smoking and pancreatic cancer were not modified by CYP17A1 genotype. Our results suggest that the CYP17A1 A2 allele may be associated with a lower risk of pancreatic cancer in both men and women.
EFNA1 ligand and its receptor EphA2: potential biomarkers for hepatocellular carcinoma
Authors: Cui Xiang‐Dan , Lee Mi‐Jin , Yu Goung‐Ran , Kim In‐Hee , Yu Hee‐Chul , Song Eun‐Young , Kim Dae‐Ghon
Published: July 2009

Novel biomarkers are needed for early detection and progression evaluation of hepatocellular carcinoma (HCC). The purpose of this study was to identify useful biomolecular markers for HCC. The 26 genes that encode membrane or secretory proteins were identified from cDNA microarray data. We further examined the expression of EFNA1 and its receptor EphA2 and determined their biological implications during the development and progression of HCC. The EFNA1 mRNA was overexpressed in most HCCs as compared with its expression in corresponding nontumor tissues (36 out of 40 cases, 90%), but EphA2 expression was noted in only half of the HCC tissues (20 of 40 cases, 50%). In most of the hepatoma cell lines, the EFNA1 protein expression was positively associated with alpha‐fetoprotien (AFP) expression but inversely associated with EphA2 expression. Furthermore, EFNA1 levels were detectable in the supernatant of the cultured hepatoma cells and in the serum of patients with HCC. In contrast, EphA2 expression was prominent in highly invasive hepatoma cells, and its overexpression was significantly correlated with decreased differentiation (r = 0.0248, p < 0.010) and poor survival (p = 0.0453) for HCC patients. EFNA1 and EphA2 may be useful serum markers for the detection of HCC development and progression, respectively.
Cancer incidence among children and adolescents in Brazil: First report of 14 population‐based cancer registries
Authors: de Camargo Beatriz , de Oliveira Santos Marceli , Rebelo Marise Souto , de Souza Reis Rejane , Ferman Sima , Noronha Claudio Pompeaino , Pombo‐de‐Oliveira Maria S.
Published: July 2009

The Brazilian Population‐Based Cancer Registry (PBCR) was started in 1967; today there are 20 PBCRs in Brazil. We report the first descriptive analysis of the incidence of childhood cancer based on data from 14 PBCRs, corresponding to 15% of the child and adolescent population in Brazil. Data were obtained from registry databases, including information on population coverage and data quality indicators. The International Classification of Childhood Cancer was used. Age‐adjusted rates were calculated by world population. Incidence by cancer registry, age, sex, and cancer type were calculated per 1,000,000 children. Age‐adjusted rates per 1,000,000 children/adolescents ranged from 92 to 220 among the 14 PBCRs. The principal groups of cancers were leukemia, lymphoma and central nervous tumors. The median incidence rate of childhood cancer in the 14 PBCRs was 154.3 per million; children 1–4 years of age had the highest incidence rates. The Brazilian PBCRs provide important information about pediatric cancer incidence in an emerging country. The observed incidence rates of childhood leukemia were similar to previous reported rates, and the age‐specific incidence rates of retinoblastoma (0–4 years of age) were higher than those for developed countries. These data can be used as baseline incidence rates of childhood and adolescent cancer in Brazil in future epidemiological studies.
Monocyte chemoattractant protein‐1 (MCP‐1)/CCL2 secreted by hepatic myofibroblasts promotes migration and invasion of human hepatoma cells
Authors: Dagouassat Maylis , Suffee Nadine , Hlawaty Hanna , Haddad Oualid , Charni Faten , Laguillier Christelle , Vassy Roger , Martin Loïc , Schischmanoff Pierre‐Olivier , Gattegno Liliane , Oudar Olivier , Sutton Angela , Charnaux Nathalie
Published: July 2009

The aim of our study was to investigate whether myofibroblasts and the chemokine monocyte chemoattractant protein‐1 (MCP‐1)/CCL2 may play a role in hepatocellular carcinoma progression. We observed that hepatic myofibroblast LI90 cells express MCP‐1/CCL2 mRNA and secrete this chemokine. Moreover, myofibroblast LI90 cell‐conditioned medium (LI90‐CM) induces human hepatoma Huh7 cell migration and invasion. These effects are strongly reduced when a MCP‐1/CCL2‐depleted LI90‐CM was used. We showed that MCP‐1/CCL2 induces Huh7 cell migration and invasion through its G‐protein–coupled receptor CCR2 and, to a lesser extent, through CCR1 only at high MCP‐1/CCL2 concentrations. MCP‐1/CCL2's chemotactic activities rely on tyrosine phosphorylation of focal adhesion components and depend on matrix metalloproteinase (MMP)‐2 and MMP‐9. Furthermore, we observed that Huh7 cell migration and invasion induced by the chemokine are strongly inhibited by heparin, by β‐D‐xyloside treatment of cells and by anti‐syndecan‐1 and ‐4 antibodies. Finally, we developed a 3‐dimensional coculture model of myofibroblast LI90 and Huh7 cells and demonstrated that MCP‐1/CCL2 and its membrane partners, CCR1 and CCR2, may be involved in the formation of mixed hepatoma‐myofibroblast spheroids. In conclusion, our data show that human liver myofibroblasts act on hepatoma cells in a paracrine manner to increase their invasiveness and suggest that myofibroblast‐derived MCP‐1/CCL2 could be involved in the pathogenesis of hepatocellular carcinoma.
A short history of the development studies association
Authors: Tribe Michael
Published: July 2009

This paper outlines the origins of the Development Studies Association (DSA) in the 1960s together with the main features of the association since its formation in 1978. Some of the leading individuals in this evolution are identified, but it is made clear that institutional pressures have also been important over the years. Issues which threaten the Association include ‘free‐riding’ (the obverse of which is ‘externalities’) as well as the linked question of those involved in ‘development’ who are neither members nor involved in the activities of the association. The paper also considers whether the DSA has ‘made a difference’, links the DSA to its European sister association, the European Association of Development Research and Training Institutes (EADI), and describes recent and prospective future developments. Copyright © 2009 John Wiley & Sons, Ltd.
Liberalisation and poverty in Africa since 1990–Why is the operation of the ‘invisible hand’ uneven?
Authors: Mosley Paul , Chiripanhura Blessing
Published: July 2009

The dramatic reduction in poverty in Uganda and Ghana in the 1990s was derived largely from the liberalisation of the export price received by a labour‐intensive peasant export sector. Other African economies ought to be able to derive inspiration from this manifestation of the invisible hand, but can they? Several other African peasant export economies experienced price liberalisation during the structural adjustment period, but without experiencing anything like the same positive poverty reduction dynamic. Two reasons are fairly clear—liberalising countries varied in the extent to which they passed on higher export prices, and they also varied in the extent to which they impacted on dimensions of governance, especially the politics of market access, in the rest of the economy. The latter continues to be an important research frontier for future investigators. Copyright © 2009 John Wiley & Sons, Ltd.
Development with dearer food: Can the invisible hand guide us?
Authors: Toye John
Published: July 2009

This paper argues that, notwithstanding the current global recession, the tripling of food prices in the period 2005–2008 presages a permanent increase in the average real price of food over the next 30 years. The underlying causes are likely to be rising energy prices, adverse effects of climate change on agriculture and rising food consumption in Asia. The consequences will be increased social and political turbulence of the urban poor and misguided government policies to try to mitigate this instability. Adam Smith's invisible hand indicates the shape of more constructive policies, consistent with economic development objectives. Copyright © 2009 John Wiley & Sons, Ltd.
Three invisible hands: Comments on the plenary presentations at the DSA conference 2008 by past presidents Paul Mosley, Frances Stewart, John Toye—and the essay by past president John Harriss
Authors: Harriss‐White Barbara
Published: July 2009

Responding to three plenary addresses at the DSA conference 2008, and another written contribution, this paper comments on the invisible hand; the dynamics of institutional change; the role of the (commodified) state; ‘markets’ versus actually existing capitalism and the implications of global warming for development studies. Copyright © 2009 John Wiley & Sons, Ltd.
Should God play a role in development?
Authors: de Kadt Emanuel
Published: July 2009

Faith‐based organisations (FBOs) have made important contributions to the furthering of development, particularly in health care and education. They have also stood up to dictatorial regimes, as with the Roman Catholic Church in Latin America during the 1970s and 1980s. Protestant organisations, especially its Evangelical variants, have played a more ambivalent role, also because these were at times ‘promoted’ by military regimes subject to RC criticism. They also reveal why FBOs, for whom religion is the only relevant aspect of identity, can have a negative effect on development, especially if they promote rigid and inflexible beliefs, limiting individual freedom. Taking religion seriously is important in development studies, but there are good reasons to resist the ‘faith‐based bandwagon’, not least because this increasingly obscures the borderline between analysis and endorsement. Copyright © 2009 John Wiley & Sons, Ltd.
Where next for development studies? Coverage, capacity, communications
Authors: Maxwell Simon
Published: July 2009

Three challenges face development studies and development studies institutions—the three ‘C's’. The first ‘C’ is coverage: making sure that the sector has sufficient coverage of new topics. The second ‘C’ is capacities: recognising that growth in the number and strength of developing country institutions requires developed country institutions to re‐think their role. The third ‘C’ is communications: using new technology to deliver policy messages faster and more effectively. With the geographical scope of the development studies ‘industry’ also changing, as more countries reach middle income status, change management becomes a high priority. Copyright © 2009 John Wiley & Sons, Ltd.
After 2015: What are the ingredients of an ‘MDG‐PLUS’ agenda for poverty reduction?
Authors: Sumner Andy , Tiwari Meera
Published: July 2009

The United Nations Millennium Development Goals (MDGs), for better or worse, have played a major role in focusing development policy since their original incarnation in the 1990s. Some development agencies have gone as far as to judge the value of all their activities on the contribution to achieving the MDGs. This paper asks how is the context for poverty reduction changing, what has been the impact of the MDG paradigm to date, and what, if anything should replace the MDGs in 2015 as a policy focus (or foci) or paradigm. The paper is based on the authors' own ideas and draws upon the presentations and background papers from the ‘After 2015’ panel held at the DSA 2008 conference. Copyright © 2009 John Wiley & Sons, Ltd.
Microscale synthesis and kinetic isotope effect analysis of (4R)‐[Ad‐14C,4‐2H] NADPH and (4R)‐[Ad‐3H,4‐2H] NADPH
Authors: Yahashiri Atsushi , Sen Arundhuti , Kohen Amnon
Published: July 2009

We present a one‐pot chemo‐enzymatic microscale synthesis of NADPH with two different patterns of isotopic labels: (4R)‐[Ad‐14C,4‐2H] NADPH and (4R)‐[Ad‐3H,4‐2H] NADPH. These co‐factors are required by an enormous range of enzymes, and isotopically labeled nicotinamides are consequently of significant interest to researchers. In the current procedure, [Ad‐14C] NAD+ and [Ad‐3H] NAD+ were phosphorylated by NAD+ kinase to produce [Ad‐14C] NADP+ and [Ad‐3H] NADP+, respectively. Thermoanaerobium brockii alcohol dehydrogenase was then used to stereospecifically transfer deuterium from C2 of isopropanol to the re face of C4 of NADP+. After purification by HPLC, NMR analysis indicated that the deuterium content at the 4R position is more than 99.7%. The labeled cofactors were then used to successfully and sensitively measure kinetic isotope effects for R67 dihydrofolate reductase, providing strong evidence for the utility of this synthetic methodology. Copyright © 2009 John Wiley & Sons, Ltd.
Implementation of the symmetric doped double‐gate MOSFET model in Verilog‐A for circuit simulation
Authors: Alvarado Joaquín , Iñiguez Benjamin , Estrada Magali , Flandre Denis , Cerdeira Antonio
Published: July 2009

Recently we developed a model for symmetric double‐gate MOSFETs (SDDGM) that, for the first time, considers the doping concentration in the Si film in the complete range from 1×1014 to 3×1018 cm−3. The model covers a wide range of technological parameters and includes short channel effects. It was validated for different devices using data from simulations, as well as measured in real devices. In this paper, we present the implementation in Verilog‐A code of this model, which allows its introduction in commercial simulators. The Verilog‐A implementation was optimized to achieve reduction in computational time, as well as good accuracy. Results are compared with data from 2D simulations, showing a very good agreement in all transistor operation regions. Copyright © 2009 John Wiley & Sons, Ltd.
Memantine lowers amyloid‐β peptide levels in neuronal cultures and in APP/PS1 transgenic mice
Authors: Alley George M. , Bailey Jason A. , Chen DeMao , Ray Balmiki , Puli Lakshman K. , Tanila Heikki , Banerjee Pradeep K. , Lahiri Debomoy K.
Published: July 2009

Memantine is a moderate‐affinity, uncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist that stabilizes cognitive, functional, and behavioral decline in patients with moderate to severe Alzheimer's disease (AD). In AD, the extracellular deposition of fibrillogenic amyloid‐β peptides (Aβ) occurs as a result of aberrant processing of the full‐length Aβ precursor protein (APP). Memantine protects neurons from the neurotoxic effects of Aβ and improves cognition in transgenic mice with high brain levels of Aβ. However, it is unknown how memantine protects cells against neurodegeneration and affects APP processing and Aβ production. We report the effects of memantine in three different systems. In human neuroblastoma cells, memantine, at therapeutically relevant concentrations (1–4 μM), decreased levels of secreted APP and Aβ1–40. Levels of the potentially amylodogenic Aβ1–42 were undetectable in these cells. In primary rat cortical neuronal cultures, memantine treatment lowered Aβ1–42 secretion. At the concentrations used, memantine treatment was not toxic to neuroblastoma or primary cultures and increased cell viability and/or metabolic activity under certain conditions. In APP/presenilin‐1 (PS1) transgenic mice exhibiting high brain levels of Aβ1–42, oral dosing of memantine (20 mg/kg/day for 8 days) produced a plasma drug concentration of 0.96 μM and significantly reduced the cortical levels of soluble Aβ1–42. The ratio of Aβ1–40/Aβ1–42 increased in treated mice, suggesting effects on the γ‐secretase complex. Thus, memantine reduces the levels of Aβ peptides at therapeutic concentrations and may inhibit the accumulation of fibrillogenic Aβ in mammalian brains. Memantine's ability to preserve neuronal cells against neurodegeneration, to increase metabolic activity, and to lower Aβ level has therapeutic implications for neurodegenerative disorders. © 2009 Wiley‐Liss, Inc.
Down‐modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis
Authors: Wang Chunhe , Li Yuexin , Proctor Thomas M. , Vandenbark Arthur A. , Offner Halina
Published: July 2009

The regulatory role of programmed death 1 (PD‐1) was investigated in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Typical EAE could be induced by immunization without pertussis toxin (PTX) in PD‐1‐null but not in wild‐type (WT) mice. However, both strains developed a similar EAE phenotype when immunized with PTX or by adoptive transfer of pathogenic T cells. In WT mice that did not develop EAE after immunization without PTX, the frequency of CD4+FoxP3+ Treg cells was boosted in the periphery but not in the thymus. This increase in Treg frequency was abrogated by PD‐1 deficiency or inclusion of PTX. In addition, PD‐1 expression was critical to in vitro conversion of naïve myelin‐specific CD4 T cells into Treg cells and was directly related to Treg suppressive activity. Finally, PD‐1 was markedly down‐modulated in the periphery of WT mice after administration of PTX. Therefore, down‐modulation of PD‐1 in Treg cells may abrogate Treg‐mediated immune suppression, permitting the activation of myelin‐reactive T cells and induction of EAE. © 2009 Wiley‐Liss, Inc.
Deletion of tau attenuates heat shock‐induced injury in cultured cortical neurons
Authors: Miao Yanying , Chen Jie , Zhang Qipeng , Sun Anyang
Published: July 2009

The microtubule‐associated protein tau has been implicated in β‐amyloid‐ and glutamate‐induced neurotoxicity. However, the potential role of tau in response to other insults to neurons remains unclear. In this study, we examined whether deletion of tau would change cell injury induced by heat shock in primary cultures of cortical neurons. After 30 min of a 45°C heat shock, lactate dehydrogenase (LDH) release increased, reaching a peak at 6 hr in wild‐type (WT) neurons. A significantly lower LDH release, with a peak delayed by 24 hr, was detected in tau knockout (TKO) neurons. After heat shock treatment, MAP‐2 and tubulin staining of the processes of WT neurons revealed more dramatic abnormalities than in TKO neurons. Both WT and TKO neurons exhibited a similar elevation of HSP70 level but different time courses of Akt phosphorylation. In contrast to an early, brief response in WT neurons, TKO neurons displayed a late, but long‐lasting increase in phosphorylation of Akt and its downstream target, glycogen synthase kinase 3β. Additionally, inhibition of Akt activity aggravated the cell morbidity caused by heat shock exposure in both WT and TKO neurons, indicating a protective role of Akt against cell injury. In conclusion, our results demonstrate that deletion of tau attenuated heat shock‐induced neuronal injury. Enhanced Akt response in the absence of endogenous tau is suggested to represent a compensatory mechanism for regulating cell reactions to stress stimuli. © 2009 Wiley‐Liss, Inc.
Neurodevelopmental consequences of Smn depletion in a mouse model of spinal muscular atrophy
Authors: Liu Hong , Shafey Dina , Moores Justin N. , Kothary Rashmi
Published: July 2009

Deletions or mutations in survival of motor neuron 1 (SMN1) cause motor neuron loss and spinal muscular atrophy (SMA), a neuromuscular disorder, with the most severe type manifesting in utero. Whether SMA is a disease of defects in neurodevelopment and/or neuromaintenance remains unclear. We performed an analysis of Smn gene and protein expression during murine embryogenesis. Furthermore, we examined Smn−/−;SMN2 mice, a model of very severe SMA, for developmental, morphological, and molecular abnormalities. We demonstrate that Smn transcript levels are regulated in a tissue‐ and developmental stage‐specific manner and that the Smn protein expression pattern generally followed that of the Smn mRNA. Cell death and pathological foci were observed in E10.5 Smn‐depleted embryos, and this increased in the telencephalon at E14.5. Furthermore, we show an altered morphology of cranial nerves as well as truncated lumbar spinal nerves in a subset of E10.5 Smn−/−;SMN2 embryos. Finally, we compared the splicing of a subset of genes shown recently to be aberrantly spliced in phenotypic‐stage SMA mice. Changes in alternative splicing of the Slc38a5 and Uspl1 genes were detectable in prephenotypic‐stage embryos and neonates but became more pronounced with the severity of the phenotype. By comparison, Hif3a alternative splicing was affected only at the end stage of disease. This result suggests that alterations in mRNA splicing in SMA occur, in part, as a result of disease progression. Overall, we conclude that Smn depletion affects developmental processes, which ultimately may also contribute to SMA pathogenesis. © 2009 Wiley‐Liss, Inc.
Pivot‐shift test: Analysis and quantification of knee laxity parameters using a navigation system
Authors: Lopomo Nicola , Zaffagnini Stefano , Bignozzi Simone , Visani Andrea , Marcacci Maurilio
Published: July 2009

Lachman, drawer, and pivot‐shift (PS) tests are important in the assessment of ACL reconstruction. The goal of this work was to analyze the reliability of the PS test using a navigation system, identifying a set of new quantitative parameters and evaluating their clinical relevance. Eighteen patients that underwent anatomic double‐bundle ACL reconstruction were included. The new dynamic parameters were: anteroposterior translation of the medial and lateral compartments and the joint center and internal/external and varus/valgus rotations of the joint. For each parameter we measured the peaks and the areas obtained during the test. Intratester repeatability, comparisons of pre‐ and postoperative laxities, and correlations between the PS peaks and the corresponding peaks obtained with standard static tests were evaluated. Areas, peaks, and static laxity outcomes were compared, grouping patients according to the preoperative International Knee Documentation Committee (IKDC) score. The PS test was reliable in identifying the surgical reconstruction. Correlation analysis showed good coefficients both for pre‐ and postoperative values. Patients with IKDC grade “D” had larger areas during the PS compared to patients with grade “C”. Our analysis is helpful for characterizing patient‐specific laxity and surgical performance, thus highlighting the clinical relevance of the PS test. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:164–169, 2010
Rapid seed oil analysis using UPLC for quality control and authentication
Authors: Lee Peter J. , Di Gioia Alice J.
Published: July 2009

Without derivatization and halogenated solvent, various seed oil samples were rapidly characterized using a UPLC (Ultra Performance LC) equipped with UV photodiode array and mass spectrometer detectors. The method acquires multiple types of data in a single injection to authenticate seed oil, analyze triacylglycerol composition, and evaluate seed oil oxidation. It can, for example, identify olive oil samples adulterated with <1% of other seed oils. Compared with conventional high‐performance liquid chromatography methods, the UPLC solution shortens analysis time, reduces solvent usage, and provides more information, resulting in cost benefit. The reduction in analysis time and solvent usage align with the principles of green chemistry.
Getting to grips with “inconsistent processes”
Authors: Dijkstra Albert J.
Published: July 2009

Effective product quality control is only possible when it is known what effect changing a process parameter setting has on one or more product properties in quantitative terms. “Adding so much more bleaching earth reduces the colour by so much.” Accordingly, such quantitative relationships have to be determined experimentally in the plant. However, the raw materials used in the plant and the plant performance may be inconsistent, vary gradually over time. Diacylglycerols for instance, affect the rate of crystallisation and their concentration varies from one lot of raw material to another. Consequently, an investigation method is required that is not affected by these inconsistencies or eliminates their influence on the correlations being sought. Such an investigation method is described in the present paper. It makes use of changes that either occur inadvertently or that have been introduced deliberately and measures the effect these changes have on dependent parameters. “What effect has a change in hydrogenation catalyst level on hydrogenation time or trans content?” Since these changes are sudden, they are superimposed on the gradual changes and can thus be separated. By introducing changes on a systematic basis, the effect of these changes can be quantified to the degree of accuracy required for product quality control. Moreover, the effect can be used to optimise the process by a kind evolutionary operation.
The regulation of energy balance
Authors: Stanley John C.
Published: July 2009

Storage of excess energy as body fat happens when the human body loses its ability to match rates of energy intake to rates of energy expenditure. Studies of genetically obese mice and their human counterparts have revealed the importance of leptin: a hormone secreted by body fat which acts on the hypothalamus to inhibit energy intake and stimulate energy expenditure. Defects in the ability of leptin to inhibit energy intake are responsible for all the human congenital obesity syndromes so far identified. Leptin also shifts energy production away from carbohydrate oxidation and towards fat oxidation. A wide range of hormones secreted by the gastrointestinal system also regulate energy intake including ghrelin which stimulates it and cholecystokinin which inhibits it. The fact that energy intake can be genetically determined means that the drive to eat is not necessarily a voluntary act and this has implications for the success of strategies aimed at managing obesity.
Rethinking dietary saturated fats
Authors: Westman Eric C.
Published: July 2009

A re‐evaluation of the diet/heart disease hypothesis is occurring, and the link between dietary fat and heart disease is not as conclusive as once was thought. A re‐evaluation of assessment of cardiometabolic risk is also occurring – from serum low density lipoprotein to serum triacylglycerol and high density lipoprotein. As the focus of cardiometabolic risk changes, the emphasis will change from dietary fat restriction (which lowers low density lipoprotein) to dietary carbohydrate restriction (which lowers triacylglycerol and raises high density lipoprotein). If these re‐evaluations continue to de‐emphasize dietary fat restriction, then products to support low‐carbohydrate, high‐fat lifestyles could rise in importance.
Tuberculosis in liver transplant recipients: A systematic review and meta-analysis of individual patient data
Authors: Holty Jon-Erik C. , Gould Michael K. , Meinke Laura , Keeffe Emmet B. , Ruoss Stephen J.
Published: July 2009

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894–906, 2009. © 2009 AASLD.
Is Roux-en-Y choledochojejunostomy an independent risk factor for nonanastomotic biliary strictures after liver transplantation?
Authors: Hoekstra Harm , Buis Carlijn I. , Verdonk Robert C. , van der Hilst Christian S. , van der Jagt Eric J. , Haagsma Elizabeth B. , Porte Robert J.
Published: July 2009

Biliary reconstruction using Roux-en-Y choledochojejunostomy has been suggested as a risk factor for the development of nonanastomotic biliary strictures (NAS) after liver transplantation. Roux-en-Y reconstruction, however, is preferentially used in patients transplanted for primary sclerosing cholangitis (PSC), and the disease itself is also associated with a higher incidence of NAS. The aim of this study was to determine whether Roux-en-Y reconstruction is really an independent risk factor for NAS. A series of 486 consecutive adult liver transplants were studied. Biliary reconstruction in patients transplanted for PSC was either by Roux-en-Y choledochojejunostomy or by duct-to-duct anastomosis, depending on the quality of the recipient's extrahepatic bile duct. Univariate and multivariate statistical analyses were used to identify risk factors for the development of NAS. The overall incidence of NAS was 16.5% (80/486). In univariate analyses, the following variables were significantly associated with NAS: PSC as the indication for transplantation, type of biliary reconstruction (Roux-en-Y versus duct-to-duct), and postoperative cytomegalovirus infection. After multivariate logistic regression analysis, PSC as the indication for transplantation (odds ratio, 2.813; 95% confidence interval, 1.624-4.875; P < 0.001) and postoperative cytomegalovirus infection (odds ratio, 2.098; 95% confidence interval, 1.266-3.477; P = 0.004) remained as independent risk factors for NAS. Biliary reconstruction using Roux-en-Y choledochojejunostomy was not identified as an independent risk factor for NAS. In conclusion, the association between Roux-en-Y choledochojejunostomy and NAS observed in previous studies can be explained by the more frequent use of Roux-en-Y reconstruction in patients with PSC. Roux-en-Y reconstruction itself is not an independent risk factor for NAS. Liver Transpl 15:924–930, 2009. © 2009 AASLD.
CpG oligodeoxynucleotide triggers the liver inflammatory reaction and abrogates spontaneous tolerance
Authors: Ma Lian-Li , Gao Xiudan , Liu Liping , Xiang Zhidan , Blackwell Timothy S. , Williams Philip , Chari Ravi S. , Yin Deng-Ping
Published: July 2009

Liver allografts are spontaneously accepted in the liver transplantation mouse model; however, the basis for this tolerance and the conditions that abrogate spontaneous tolerance to liver allografts are incompletely understood. We examined the role of CpG oligodeoxynucleotide (ODN) in triggering the liver inflammatory reaction and allograft rejection. Bioluminescence imaging quantified the activation of nuclear transcriptional factor κB (NF-κB) at different time points post-transplantation. Intrahepatic lymphocyte subsets were analyzed by immunofluorescence assay and flow cytometry. The results showed that liver allografts survived for more than 100 days without a requirement for any immunosuppressive therapy. Donor-matched cardiac allografts were permanently accepted, whereas third-party cardiac grafts were rejected with delayed kinetics; this confirmed donor-specific tolerance. NF-κB activation in the liver allografts was transiently increased on day 1 and diminished by day 4; in comparison, it was elevated up to 10 days post-transplantation in the cardiac allografts. When CpG ODN was administered at a high dose (50 μg per mouse × 1) to the recipients on day 7 post-transplantation, it induced an acute liver inflammatory reaction with elevated NF-κB activation in both allogeneic and syngeneic liver grafts. Multiple doses of CpG ODN (10 μg per mouse × 3) elicited acute rejection of the liver allografts with significant T cell infiltration in the liver allografts, reduced T regulatory cells, and enhanced interferon gamma–producing cells in the intrahepatic infiltrating lymphocytes. These data demonstrate that CpG ODN initiates an inflammatory reaction and abrogates spontaneous tolerance in the liver transplantation mouse model. Liver Transpl 15:915–923, 2009. © 2009 AASLD.
Late protocol liver biopsies in the liver allograft: A neglected investigation?
Authors: Mells George , Mann Caroline , Hubscher Stefan , Neuberger James
Published: July 2009

As outcomes from liver transplantation have improved, attention has focused on long-term outcomes: patient and graft survival is affected by many factors, including the consequences of both overimmunosuppression (eg, renal failure and cancer) and underimmunosuppression (eg, rejection). The use of protocol (rather than event-driven) biopsies of the liver allograft, except for those grafted for HCV infection, has been largely abandoned. The aim of this study was to determine if protocol biopsies can improve the management of liver allograft recipients. A retrospective analysis of liver allograft recipients who had undergone protocol liver biopsies between 2000 and 2006 was performed. One hundred seventy-eight patients with normal liver tests (alcoholic liver disease, 49; autoimmune hepatitis, 20; and primary biliary cirrhosis, 107) who had undergone 235 protocol biopsies were identified. No significant complication from the biopsy was recorded. Liver histology was reported as normal or nearly normal in only 57 (24%). Chronic hepatitis (not obviously related to disease recurrence) was present in 78 (33%). Interpreted in the light of the calculated creatinine clearance, the biopsy findings indicated that overall immunosuppression (IMS) should be maintained or increased with standard calcineurin inhibitor (CNI)–based IMS in 25% of cases, that overall IMS should be reduced in 15% of cases, and that overall IMS should be maintained or increased by the substitution of non-nephrotoxic agents for CNIs in 9% of cases. The histological findings led to a documented change in IMS in 76 (32%) (increased IMS, 11; decreased IMS, 58; and switch from CNI, 7). In conclusion, protocol liver biopsy provides important histological information about graft function that is not available from standard liver tests and safely allows modification of IMS to ensure that long-term side effects of drug therapy (eg, renal failure) are minimized while graft function is sustained. Liver Transpl 15:931–938, 2009. © 2009 AASLD.
Syntheses and Electrochemical Properties of TEMPO Radical Substituted Silicones: Active Material for Organic Radical Batteries
Authors: Suguro Masahiro , Mori Atsunori , Iwasa Shigeyuki , Nakahara Kentaro , Nakano Kaichiro
Published: July 2009

A silicone‐based radical polymer 2 was synthesized by hydrosilylation of PMHS with 4‐allyl‐2,2,6,6‐tetramethylpiperidine‐N‐oxyl ether 1 in the presence of a platinum‐ or rhodium‐catalyst. A reversible redox peak of 2 at 3.56 V (vs. Li/Li+) was observed by CV measurements. A coin‐shaped cell of 2 shows a discharge capacity of 46 mAh · g−1, which is 47% of the theoretical capacity of 2 (98 mAh · g−1). A directly TEMPO‐substituted silicone, poly[methyl(2,2,6,6‐tetramethylpiperidine‐N‐oxyl‐4‐oxyl)siloxane] 3 was also obtained by rhodium‐catalyzed dehydrogenative alcoholysis of PMHS with TEMPO‐OH. The coin‐shaped cell of 3 shows a discharge capacity of 80 mAh · g−1, which is 69% of the theoretical capacity of 3 (116 mAh · g−1).

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