bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of radical nephrectomy techniques in one center: Minimal incision portless endoscopic surgery versus laparoscopic surgery
Authors: Soga Norihito , Kato Manabu , Masui Satoru , Nishikawa Kouhei , Hasegawa Yoshihiro , Yamada Yasushi , Kise Hideaki , Arima Kiminobu , Sugimura Yoshiki
Published: August 2010

This study was designed to assess the intraoperative and postoperative benefits of two techniques for treating renal cell carcinoma (portless endoscopic surgery with radical nephrectomy [PLES‐RN] and laparoscopic radical nephrectomy [LRN]) carried out at a single center. Radical nephrectomy with either PLES‐RN (14 cases) or LRN (15 cases) was carried out on 29 patients with cT1 renal cell carcinoma. There were no statistically significant between‐group differences in patient characteristics (except tumor side), operation time, and amount of blood loss (χ2 and Fisher's test). No blood transfusions were required in either group. The mean incision length of PLES‐RN was not significantly longer than that of LRN. No minor or major complications resulted. From postoperative data, the first intake of fluid (P = 0.07) and food (P = 0.02) tended to be sooner in the PLES group than the LRN group. Postsurgically, white blood cell count and C‐reactive protein were not significantly different between the two groups. The added cost of disposable instruments needed in LRN was 111 570 Japanese yen (1115.7 United States dollars). Both techniques are optimal options for surgically treating early renal cell carcinoma. The comparison related to invasiveness between the two methods should be evaluated using a large number of cases focusing on the various aspects for the future.
Tasmanian lentic wetland lawns are maintained by grazing rather than inundation
Authors: ROBERTS CYNTHIA , KIRKPATRICK J. B. , MCQUILLAN P. B.
Published: August 2010

Vertebrate grazers have been shown to be a critical element in maintaining lawns, although lawns can also form in places without such herbivores. In Tasmania lawns are widespread in lentic wetlands. We used environmental observations and exclosure experiments at two altitudinally contrasting lentic wetland lawns, and waterlogging experiments, to test the hypotheses that their structure is maintained (i) periodic inundation; and (ii) grazing. Waterlogging experiments and field observations demonstrated that the two main invading shrubs were indifferent to immersion for several months and that the distribution of the lawns was independent of inundation period, results inconsistent with the first hypothesis. The exclosure experiments showed that both woody and non‐woody plants became taller in the lawns when marsupial grazers and rabbits were excluded. It therefore seems that the lawn structure is maintained by grazing and that alternative structural states result from exclusion of grazing pressure in less than 2 years.
Ecology and bioprospecting
Authors: BEATTIE ANDREW J. , HAY MARK , MAGNUSSON BILL , de NYS ROCKY , SMEATHERS JAMES , VINCENT JULIAN F. V.
Published: August 2010

Bioprospecting is the exploration of biodiversity for new resources of social and commercial value. It is carried out by a wide range of established industries such as pharmaceuticals, manufacturing and agriculture as well as a wide range of comparatively new ones such as aquaculture, bioremediation, biomining, biomimetic engineering and nanotechnology. The benefits of bioprospecting have emerged from such a wide range of organisms and environments worldwide that it is not possible to predict what species or habitats will be critical to society, or industry, in the future. The benefits include an unexpected variety of products that include chemicals, genes, metabolic pathways, structures, materials and behaviours. These may provide physical blueprints or inspiration for new designs. Criticism aimed at bioprospecting has been addressed, in part, by international treaties and legal agreements aimed at stopping biopiracy and many activities are now funded by agencies that require capacity‐building and economic benefits in host countries. Thus, much contemporary bioprospecting has multiple goals, including the conservation of biodiversity, the sustainable management of natural resources and economic development. Ecologists are involved in three vital ways: first, applying ecological principles to the discovery of new resources. In this context, natural history becomes a vast economic database. Second, carrying out field studies, most of them demographic, to help regulate the harvest of wild species. Third, emphasizing the profound importance of millions of mostly microscopic species to the global economy.
THE EYE AND VISUAL CAPACITY
Authors: Cole Barry L.
Published: August 2010

The visual system is considered as the input side of a communication channel for the transfer of visually displayed information. The performance of the channel is limited to 5 to 10 bits/second but this limitation occurs at the processing and output levels: it is not due to limitations of the visual system which has a remarkable capacity to receive visually displayed information. However for the communication channel to work effectively the visual display of information must have dimensions which exceed the threshold characteristics of the visual system. Poor task design can limit performance and the production engineer must have a knowledge of human visual performance if he is to design visual displays that will permit maximum operator performance and minimise errors. The principal capabilities of the visual system are briefly reviewed under the headings of (1) detection (2) spatial resolution (3) colour discrimination (4) depth perception.
THE CRITICAL EYE: AN OVERVIEW OF CONTACT LENS MATERIALS
Authors: Hill Richard M.
Published: August 2010

An overview of several classes of new materials proposed and being used for the fabrication of contact lenses is made, with special references to microbiological problems, lens “aging” and the physiological tolerances of the cornea to each.
Simple Transfers, Complex Outcomes: The Impacts of Pensions on Poor Households in Brazil
Authors: Lloyd‐Sherlock Peter
Published: August 2010

Drawing on quantitative survey data and in‐depth interviews, this article seeks to map out the potential direct and indirect effects of simple cash transfers on households in impoverished rural and urban settings. Brazil is shown to have an extensive system of old age pensions, which affords almost universal coverage to households containing older people. These benefits have a significant impact on levels of poverty and vulnerability in recipient households. They also facilitate access to essential healthcare items, such as drugs, which are seldom freely available through the state health system. The in‐depth interviews reveal that pensions can have important effects on intra‐household relations, but these effects were not generalizable nor easily captured by quantitative survey tools. There was clear evidence that pensions reduced the propensity of older people to remain economically active, but this must be understood in a context of limited employment opportunities for all age groups and a high prevalence of disability. Overall, the article demonstrates the complex effects of a relatively simple cash transfer, which policy makers need to take into account.
Brazil's Bolsa Família: A Double‐Edged Sword?
Authors: Hall Anthony
Published: August 2010

In common with most Latin American countries, as governments embrace safety nets to attack poverty, conditional cash transfer (CCT) programmes have become part of mainstream social policy in Brazil. Under president Fernando Henrique Cardoso (1995–2002), and especially since Luiz Inácio Lula da Silva took office in 2003, targeted assistance in education, health and nutrition, now united under Bolsa Família, have expanded rapidly to benefit forty‐four million (24 per cent of the total population), absorbing almost two‐fifths of the social assistance budget earmarked for the poorest sectors. Despite its operational problems, Bolsa Família appears to have been effective in providing short‐term relief to some of the most deprived groups in Brazil. Yet it could prove to be a double‐edged sword. There is a risk that, due to its popularity among both the poor and Brazil's politicians, Bolsa Família could greatly increase patronage in the distribution of economic and social benefits and induce a strong dependence on government handouts. There are also early signs that it may be contributing to a reduction in social spending in key sectors such as education, housing and basic sanitation, possibly undermining the country's future social and economic development.
RELIGION AND MODERNITY  Living in the Hypercontext
Authors: Lovibond Sabina
Published: August 2010

This paper discusses Jeffrey Stout's thesis that modern societies are “secular,” not in the sense that religion has disappeared from them, but in a procedural sense having to do with what can properly be assumed by participants in moral or political discussion. I endorse this thesis, but argue that Stout employs a notion of justification (with regard to moral belief), which leans too far toward descriptivism or relativism. As an alternative account of the status of religion within “the hypercontext, modernity,” I commend Kant's view of the religious attitude as a fundamentally ethical one, destined eventually to dispense with any “historical vehicle” in the form of revealed doctrine or supernaturalism. Stout's discussion is weakened by its retreat from commitment to the unity of practical reason, though it does pay illuminating tribute to the democratic values of civility and attentiveness.
COMPARATIVE ETHICS, A COMMON MORALITY, AND HUMAN RIGHTS
Authors: Twiss Sumner B.
Published: August 2010

This essay is a brief attempt to summarize and evaluate the contributions that Democracy and Tradition makes to the field of comparative ethics. It is argued that the potential impact of these contributions would be strengthened by engagement with the common morality already imbedded in international human rights norms.
THE PRAGMATIC TURN IN THE  STUDY OF RELIGION
Authors: Davis G. Scott
Published: August 2010

Jeffrey Stout's Democracy and Tradition puts forward a complex argument in favor of American democracy as a healthy and legitimate moral and political tradition in itself. Stout does not dwell on the place of his own work in the “pragmatic” approach to the study of religion in the last thirty years. This paper attempts to situate Stout's work in the approach to religion identified with Mary Douglas and Wayne Proudfoot and to suggest some of the consequences for comparative religious ethics of his making that “pragmatic turn.”
BETWEEN EXAMPLE AND DOCTRINE  Contract Law and Common Morality
Authors: Kaveny M. Cathleen
Published: August 2010

In Democracy and Tradition, Jeffrey Stout contends that American constitutional democracy constitutes a well‐functioning moral and political tradition that is not hostile to religion, although it does not depend on any specifically religious claims. I argue that Stout's contention is supported by a consideration of the great common law subject of contracts, as taught to first‐year law students across the United States. First, I demonstrate how contract law can fruitfully be understood as a MacIntyrean tradition. Second, I illustrate the moral richness of this tradition, and the mutually interpreting nature of rules and facts, by close attention to one particularly colorful case, Syester v. Banta. I conclude by suggesting that both religious and secular ethicists might find common law cases in general and contract law cases in particular to be a source of moral reflection that is substantively rich without being religiously divisive.
GLOBAL JUSTICE AFTER THE FALL  Christian Realism and the “Law of Peoples”
Authors: Santurri Edmund N.
Published: August 2010

In The Law of Peoples John Rawls casts his proposals as an argument against what he calls “political realism.” Here, I contend that a certain version of “Christian political realism” survives Rawls's polemic against political realism sans phrase and that Rawls overstates his case against political realism writ large. Specifically, I argue that Rawls's dismissal of “empirical political realism” is underdetermined by the evidence he marshals in support of the dismissal and that his rejection of “normative political realism” is in tension with his own normative concessions to political reality as expressed in The Law of Peoples. That is, I contend that Rawls, himself, needs some form of political realism to render persuasive the full range of normative claims constituting the argument of that work.
EMBODIMENT AND VIRTUE IN A COMPARATIVE PERSPECTIVE
Authors: Schofer Jonathan Wyn
Published: August 2010

The turn to descriptive studies of ethics is inspired by the sense that our ethical theorizing needs to engage ethnography, history, and literature in order to address the full complexity of ethical life. This article examines four books that describe the cultivation of virtue in diverse cultural contexts, two concerning early China and two concerning Islam in recent years. All four emphasize the significance of embodiment, and they attend to the complex ways in which choice and agency interact with the authority of tradition. In considering these books, this article examines the relations between our academic claims concerning the self and ethics, conceptual or theoretical claims made in the elite writings of traditions, and the lived experiences of the people we study. The conclusion turns to our methodological foundations for studying these topics both comparatively and constructively.
Human Rights and the Defense of Liberal Democracy
Authors: Langlois Anthony J.
Published: August 2010

In recent issues of theJournal of Religious Ethics(2006, 2007), David Little has defended the contemporary regime of international human rights against what he thinks of as the relativizing influences of the genealogical “just‐so” story told by Jeffrey Stout in hisDemocracy and Tradition(2004). I argue that Stout is correct about just‐so stories, and that Little does not go far enough in his reclamation of liberalism against Stout's “new traditionalists.” The main weaknesses of Little's approach are his insistence on the idea that human rights are to be thought of as natural rights, and that these in turn are to be thought of as self‐evident and self‐justifying. I argue that they are neither: they come to us via a Stoutian just‐so story, and that as part of a broader reclamation of liberalism, they can continue to serve as the basis for the kind of international liberal constitutionalism that Little advocates.
USING BAYESIAN BETAS TO ESTIMATE RISK RETURN PARAMETERS: AN EMPIRICAL INVESTIGATION
Authors: Murphy J. Austin
Published: August 2010

Since its original development by Sharpe (1964), the Capital Asset Pricing Model (CAPM) has been the focus of great interest, practical usage, modifications, testing, and controversy. The basic hypothesis of the CAPM is that the minimum expected return required by investors on any asset will equal the risk‐free rate plus a premium for the asset's contribution to the variance risk of a diversified portfolio as measured by the asset's beta. The model is often utilized by investors to calculate the relevant risk and required return on an asset, while corporate officers widely employ the theory to compute the appropriate discount rate to use in estimating the net present value of capital budgeting projects when evaluating spending decisions (Gitman and Mercurio, 1982).
The UK Equity Premium: 1901–2004
Authors: Vivian Andrew
Published: August 2010

Abstract:  This paper examines the UK equity premium over more than a century using dividend growth to estimate expectations of capital gains employing the approach of Fama and French (2002). Over recent decades estimated equity premia implied by dividend growth have been much lower than that produced by average stock returns for the UK market as a whole; a finding corroborated by all economic sub‐sectors. The empirical analysis suggests this is primarily due to a declining discount rate, during the latter part of the 20th century, which would rationally stimulate unanticipated equity price rises during this period. Thus, I conclude that historical stock returns over recent decades have been above investors' expectations.
Robustness of Judicial Decisions to Valuation‐Method Innovation: An Exploratory Empirical Study
Authors: Chen Feng , Yee Kenton K. , Yoo Yong Keun
Published: August 2010

Abstract:  In shareholder litigation, judges and litigants choose from a menu of valuation methods that is evolving over time. What drives demand for new valuation methods? Does valuation method choice affect a judge's final appraisal? Is a judge more likely to favor the litigant whose valuation method coincides with the judge's if the other litigant uses a different method? Using a comprehensive hand‐collected sample of Delaware appraisal remedy shareholder litigation cases, we show that the distribution of judicial appraisal outcomes is insensitive to valuation methodology. Moreover, valuation method agreement between judge and plaintiff (or between judge and defendant) does not influence the judge's appraisal. In this sense, judicial valuation is robust to innovations in valuation technology. However, we find that judicial valuation method choice is contextual. The method a judge chooses depends on the fundamental attributes of the firm as well as the quality of litigants' proposed valuation estimates. We conclude that judges demand new valuation methods when the new methods are contextually more appropriate.
Long‐acting genipin derivative protects retinal ganglion cells from oxidative stress models in vitro and in vivo through the Nrf2/antioxidant response element signaling pathway
Authors: Koriyama Yoshiki , Chiba Kenzo , Yamazaki Matsumi , Suzuki Hirokazu , Ichiro Muramoto Ken , Kato Satoru
Published: August 2010

J. Neurochem. (2010) 115, 79–91.

Previously, we reported that genipin, a herbal iridoid, had neuritogenic and neuroprotective actions on PC12 cells. Although nitric oxide (NO)‐activated signalings were proposed to be neuritogenic, the neuroprotective action of genipin remains to be elucidated. From the standpoint of NO activation, we tested a possible protective mechanism through the nitrosative Kelch‐like ECH‐associated protein (Keap1)/NF‐E2‐related factor 2 (Nrf2)‐antioxidant response element pathway in rat retinal ganglion cells (RGC‐5 cells) in culture, and in vivo, against hydrogen peroxide and optic nerve injury (ONI), respectively, using a long‐acting (1R)‐isoPropyloxygenipin (IPRG001). IPRG001 induced NO generation and the expressions of antioxidative enzymes, such as heme oxygenase‐1 (HO‐1), in RGC‐5 cells. The protective action of IPRG001 depended on HO‐1 and NO induction. We found that S‐nitrosylation of Keap1 by IPRG001 may contribute to translocation of Nrf2 to the nucleus and triggered transcriptional activation of antioxidative enzymes. Furthermore, apoptotic cells were increased and 4‐hydroxy‐2‐nonenal was accumulated in rat retina following ONI. Pre‐treatment with IPRG001 almost completely suppressed apoptosis and accumulation of 4‐hydroxy‐2‐nonenal in RGCs following ONI accompanied by HO‐1 induction. These data demonstrate for the first time that IPRG001 exerts neuroprotective action in RGCs in vitro and in vivo, through the Nrf2/antioxidant response element pathway by S‐nitrosylation against oxidative stress.
Glypican‐1 facilitates prion conversion in lipid rafts
Authors: Hooper Nigel M.
Published: August 2010

J. Neurochem. (2011) 116, 721–725.

The conformational conversion of the cellular prion protein (PrPC) to the infectious form (PrPSc) is the critical step in the pathogenesis of prion diseases such as Creutzfeldt‐Jakob disease in humans and scrapie in sheep. Cholesterol‐rich lipid rafts play a key role in the conversion of PrPC to PrPSc and other cellular components have been identified as important cofactors to trigger, enhance, or accelerate prion formation. Amongst these heparan sulphate proteoglycans (HSPGs) and their glycosaminoglycan side‐chains have been implicated in prion metabolism. Recently, the cell‐surface HSPG glypican‐1 was demonstrated to co‐localise with PrPC on the cell surface and to promote its association with lipid rafts. Both PrPC and PrPSc co‐immunoprecipitated with glypican‐1 and the interaction was dependent on the glycosaminoglycan side chains of glypican‐1. Critically, depletion of glypican‐1 in scrapie‐infected N2a cells reduced the formation of PrPSc, indicating that this HSPG is involved in prion formation. Further work is required to understand the molecular and cellular mechanisms underpinning the role of glypican‐1 and possibly other members of the glypican family in prion metabolism, and to determine whether glypican‐1 facilitates PrPSc formation in vivo.
Pre‐synaptic BK channels selectively control glutamate versus GABA release from cortical and hippocampal nerve terminals
Authors: Martire Maria , Barrese Vincenzo , D’Amico Monia , Iannotti Fabio Arturo , Pizzarelli Rocco , Samengo Irene , Viggiano Davide , Ruth Peter , Cherubini Enrico , Taglialatela Maurizio
Published: August 2010

J. Neurochem. (2010) 115, 411–422.

In the present study, by means of genetic, biochemical, morphological, and electrophysiological approaches, the role of large‐conductance voltage‐ and Ca2+‐dependent K+ channels (BK channels) in the release of excitatory and non‐excitatory neurotransmitters at hippocampal and non‐hippocampal sites has been investigated. The results obtained show that the pharmacological modulation of pre‐synaptic BK channels selectively regulates [3H]d‐aspartate release from cortical and hippocampal rat synaptosomes, but it fails to influence the release of excitatory neurotransmitters from cerebellar nerve endings or that of [3H]GABA, [3H]Noradrenaline, or [3H]Dopamine from any of the brain regions investigated. Confocal immunofluorescence experiments in hippocampal or cerebrocortical nerve terminals revealed that the main pore‐forming BK α subunit was more abundantly expressed in glutamatergic (vGLUT1+) versus GABAergic (GAD65‐67+) nerve terminals. Double patch recordings in monosynaptically connected hippocampal neurons in culture confirmed a preferential control exerted by BK channels on glutamate over GABA release. Altogether, the present results highlight a high degree of specificity in the regulation of the release of various neurotransmitters from distinct brain regions by BK channels, supporting the concept that BK channel modulators can be used to selectively limit excessive excitatory amino acid release, a major pathogenetic mechanism in several neuropsychiatric disorders.
Lentivirus‐mediated expression of insulin‐like growth factor‐I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons
Authors: Kouroupi Georgia , Lavdas Alexandros A. , Gaitanou Maria , Thomaidou Dimitra , Stylianopoulou Fotini , Matsas Rebecca
Published: August 2010

J. Neurochem. (2010) 115, 460–474.

Strategies to enhance neural stem/precursor cell (NPC) capacity to yield multipotential, proliferative, and migrating pools of cells that can efficiently differentiate into neurons could be crucial for structural repair after neurodegenerative damage. Here, we have generated a lentiviral vector for expression of insulin‐like growth factor‐I (IGF‐1) and investigated the impact of IGF‐1 transduction on the properties of cultured NPCs (IGF‐1‐NPCs). Under proliferative conditions, IGF‐1 transduction promoted cell cycle progression via cyclin D1 up‐regulation and Akt phosphorylation. Remarkably upon differentiation‐inducing conditions, IGF‐1‐NPCs cease to proliferate and differentiate to a greater extent into neurons with significantly longer neurites, at the expense of astrocytes. Moreover, using live imaging we provide evidence that IGF‐1 transduction enhances the motility and tissue penetration of grafted NPCs in cultured cortical slices. These results illustrate the important consequence of IGF‐1 transduction in regulating NPC functions and offer a potential strategy to enhance the prospective repair potential of NPCs.
Effective heuristics for the Set Covering with Pairs Problem
Authors: Gonçalves Luciana Brugiolo , De Lima Martins Simone , Ochi Luiz Satoru
Published: August 2010

This paper deals with the Set Covering with Pairs Problem (SCPP). This problem is a generalization of the Set Covering Problem (SCP), which is known to be NP‐hard. The difference between the problems is that, in the SCPP, one element of the universe is admitted to be covered if there are at least two specific objects chosen to cover it. In this context, three constructive heuristics, one local search algorithm and a Greedy Randomized Adaptive Search Procedure are proposed. The algorithms developed were tested in 560 instances available in the literature and they were capable of achieving optimal solutions for several instances.
Systemic Sclerosis: New Insights in Autoimmunity
Authors: Kaal Suzanne E. J. , Van den hoogen Frank H. J. , De jong Elke M. G. J. , Viëtor Henk E.
Published: August 2010

The strong female predilection of systemic sclerosis, especially in women after their childbearing years, and the clinical and histopathological similarities with chronic graft‐versus‐host disease make systemic sclerosis an interesting subject of debate. Recent studies concerning the pathogenesis of this disease demonstrated the persistence of fetal cells in the maternal circulation in a majority of female patients. How or whether microchimerism is involved in the pathogenesis of systemic sclerosis remains to be elucidated. The present paper reviews the recent findings on the subject.
Age‐Related Changes in the Thyroid Hormone Effects on Malondialdehyde‐Modified Proteins in the Rat Heart
Authors: Chehade Joe , Kim Joohee , Pinnas Jacob L. , Mooradian Arshag D.
Published: August 2010

To determine the age‐related changes in thyroid hormone (TH) effects on malondialdehyde (MDA)‐modified proteins in cardiac tissue, rats at 4, 12, and 25 months of age were studied. Hyperthyroidism was induced with daily injection of L‐triiodothyronine (15 μg/100 g) intraperitoneally for 10 days. Hypothyroidism was induced with 0.025% methimazole in the drinking water for 4 weeks. MDA proteins were measured with immunoblots using a specific anti‐MDA antiserum. MDA was measured as thiobarbituric acid reactive substance.

Hypothyroidism in 4‐month‐old rats was associated with significant reduction in MDA proteins compared to euthyroid rats (13.4 ± 5.9% vs. 99.8 ± 10.4% of controls P < 0.001). Hyperthyroidism did not result in a significant change of MDA proteins. In aged rats, neither hypothyroidism nor hyperthyroidism was associated with significant changes in cardiac MDA proteins. The changes in MDA proteins did not correlate with cardiac MDA concentrations. In young rats, the MDA concentrations (nmol/mg) were significantly reduced in hypothyroidism (2.71 ± 0.21) and were increased in hyperthyroidism (8.19 ± 0.78) compared to euthyroid values (5.06 ± 0.71) P < 0.01. In aged rats, cardiac MDA content was significantly increased during both hyperthyroidism and hypothyroidism. We conclude that alterations in MDA protein content is yet another potential biochemical effect of TH in cardiac tissue. This particular effect is significantly blunted with age.
A Gravimetric Method for the Measurement of Total Spontaneous Activity in Rats
Authors: Biesiadecki Brandon J. , Brand Paul H. , Koch Lauren G. , Britton Steven L.
Published: August 2010

Currently available methods for the measurement of spontaneous activity of laboratory animals require expensive, specialized equipment and may not be suitable for use in low light conditions with nocturnal species. We developed a gravimetric method that uses common laboratory equipment to quantify the total spontaneous activity of rats and is suitable for use in the dark. The rat in its home cage is placed on a top‐loading electronic balance interfaced to a computer. Movements are recorded by the balance as changes in weight and transmitted to the computer at 10 Hz. Data are analyzed on‐line to derive the absolute value of the difference in weight between consecutive samples, and the one‐second average of the absolute values is calculated. The averages are written to file for off‐line analysis and summed over the desired observation period to provide a measure of total spontaneous activity. The results of in vitro experiments demonstrated that: 1) recorded weight changes were not influenced by position of the weight on the bottom of the cage, 2) values recorded from a series of weight changes were not significantly different from the calculated values, 3) the constantly decreasing force exerted by a swinging pendulum placed on the balance was accurately recorded, 4) the measurement of activity was not influenced by the evaporation of a fluid such as urine, and 5) the method can detect differences in the activity of sleeping and waking rats over a 10‐min period, as well as during 4‐hr intervals recorded during active (night‐time) and inactive (daytime) periods. These results demonstrate that this method provides an inexpensive, accurate, and noninvasive method to quantitate the spontaneous activity of small animals.
The Effects of Spaceflight on Mammary Metabolism in Pregnant Rats
Authors: Plaut K. , Maple R. , Vyas C. , Munaim S. , Darling A. , Casey T. , Alberts J. R.
Published: August 2010

The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of β‐casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.
Marginal Biotin Deficiency Is Teratogenic
Authors: Zempleni Janos , Mock Donald M.
Published: August 2010

Abstract.Recent studies of biotin status during pregnancy provide evidence that a marginal degree of biotin develops in a substantial proportion of women during normal pregnancy. Several lines of evidence suggest that, although the degree of biotin deficiency is not severe enough to produce the classic cutaneous and behavioral manifestations of biotin deficiency, the deficiency is severe enough to produce metabolic derangements in women and that characteristic fetal malformations occur at a high rate in some mammals. Moreover, our analysis of data from a published multivitamin supplementation study provide significant albeit indirect evidence that the marginal degree of biotin deficiency that occurs spontaneously in normal human gestation is teratogenic. Investigation of potential mechanisms provides evidence that biotin transport by the human placenta is weak. Further, proliferating cells accumulate biotin at a rate five times faster than quiescent cells; this observation suggests that there is an increased biotin requirement associated with cell proliferation. Perhaps this requirement arises from the need to synthesize additional biotin‐dependent holocarboxylases or provide additional biotin as a substrate for biotinylation of cellular histones. Reduced activity of the biotin‐dependent enzymes acetyl‐CoA carboxylase and propionyl‐CoA carboxylase can cause alterations of lipid metabolism and might theoretically lead to alterations of polyunsaturated fatty acid and prostaglandin metabolism that derange normal skeletal development.
Protective Effect of Estrogens Against Oxidative Damage to Heart and Skeletal Muscle In Vivo and In Vitro
Authors: Persky Adam M. , Green Pattie S. , Stubley Leighann , Howell Cynthia O. , Zaulyanov Larissa , Brazeau Gayle A. , Simpkins James W.
Published: August 2010

Abstract. Estrogen has been shown to protect skeletal muscle from damage and to exert antioxidant properties. The purpose of the present study was to investigate the antioxidant and protective properties of estrogens in rodent cardiac and skeletal muscle and H9c2 cells. Female Sprague‐Dawley rats were separated into three groups, ovariectomized (OVX), ovariectomized with estrogen replacement (OVX + E2), and intact control (SHAM), and were assessed at two time periods, 4 and 8 weeks. Rodents hearts were analyzed for basal and iron‐stimulated lipid peroxidation in the absence and presence of β‐estradiol (βE2) by measuring thiobarbituric acid reactive species (TBARS). Isolated soleus (SOL) and extensor digitorum longus (EDL) were analyzed for creatine kinase (CK) efflux. Using H9c2 cells, the in vitro effects of βE2 and its isomer α‐estradiol were investigated under glucose‐free/hypoxic conditions. TBARS assay was also performed on the H9c2 in the presence or absence of βE2. The results indicate that OVX rodent hearts are more susceptible to lipid peroxidation than OVX + E2 hearts. OVX soleus showed higher cumulative efflux of CK than OVX + E2. Furthermore, H9c2 survival during oxidative stress was enhanced when estrogen was present, and both OVX hearts at 4 weeks and H9c2 cells particularly were protected from oxidative damage by estrogens. We conclude that estrogen protects both skeletal and cardiac muscle from damage, and its antioxidant activity can contribute to this protection.
Dexamethasone Blocks Sepsis‐Induced Protection of the Heart from Ischemia Reperfusion Injury
Authors: Spanier Adam J. , McDonough Kathleen H.
Published: August 2010

Abstract. Previous investigations have shown that sepsis, while causing cardiac dysfunction, can protect the heart from ischemia‐reperfusion injury. Sepsis‐induced protection may be due to nitric oxide produced by an inducible form of nitric oxide synthase generated in response to cytokines released during sepsis. The glucocorticoid dexamethasone has been shown to inhibit the synthesis of the inducible form of nitric oxide synthase (iNOS). The goals of this study were to determine if dexamethasone would prevent sepsis‐induced cardiac dysfunction and sepsis‐induced protection of the heart from ischemia‐reperfusion injury. In this experiment, rats were made septic by injecting Escherichia coli into the dorsal subcutaneous space. Control rats were injected with sterile saline. At the time of surgery, some of the control and septic animals were injected intraperitoneally with dexamethasone (3 mg/kg). The next day, 24–26 hr after injection of the first dose of E. coli, animals were anesthetized, and hearts were removed and studied in the isovolumic beating‐heart preparation. Left ventricular end diastolic pressure was set to 5 mmHg, and left ventricular pressure was measured continuously throughout the protocol. Left ventricular developed pressure (LVDP) was used as an index of LV function. After stabilization, hearts were made globally ischemic for 35 min and then reperfused for 25 min. As has been shown previously, sepsis depressed LVDP but also protected the heart from further depression of LVDP by ischemia and reperfusion. Dexamethasone prevented both sepsis‐induced cardiac dysfunction and sepsis‐induced protection of the heart from ischemia‐reperfusion injury. In addition plasma nitrite/nitrate levels were not different from control levels in the dexamethasone‐treated septic rats whereas levels were elevated in the septic animals. The dexamethasone mediated abrogation of sepsis‐induced cardiac dysfunction and protection during ischemia‐reperfusion injury may be due to suppression of nitric oxide production.
Cholesteryl Ester Enrichment of Plasma Low‐Density Lipoproteins in Hamsters Fed Cereal‐Based Diets Containing Cholesterol
Authors: Carr Timothy P. , Cai Guowen , Lee Ji‐Young , Schneider Craig L.
Published: August 2010

Abstract. Male Syrian hamsters were fed 0.02, 0.03, or 0.05% cholesterol to test the hypothesis that moderate cholesterol intake increases the cholesteryl ester content of the plasma low‐density lipoproteins (LDL). Dietary cholesterol levels of 0.02%–0.05% were chosen to reflect typical human intakes of cholesterol. Hamsters were fed ad libitum a cereal‐based diet (modified NIH‐07 open formula) for 15 weeks. Increasing dietary cholesterol from 0.02% to 0.05% resulted in significantly increased plasma LDL and high‐density lipoprotein cholesterol concentration, increased liver cholesterol concentration, and increased total aorta cholesterol content. The cholesteryl ester content of plasma LDL was determined as the molar ratio of cholesteryl ester to apolipoprotein B and to surface lipid (i.e., phospholipid + free cholesterol). Increasing dietary cholesterol from 0.02% to 0.05% resulted in significantly increased cholesteryl ester content of LDL particles. Furthermore, cholesteryl ester content of LDL was directly associated with increased total aorta cholesterol, whereas a linear relationship between plasma LDL cholesterol concentration and aorta cholesterol was not observed. Thus, the data suggest that LDL cholesteryl ester content may be an important atherogenic feature of plasma LDL.
Recent Developments in the Virus Therapy of Cancer
Authors: Steele Timothy A.
Published: August 2010

Abstract. Cancer is one of the leading causes of death in the United States. Although there has been significant progress in the areas of cancer etiology, diagnostic techniques, and cancer prevention, adequate therapeutic approaches for many cancers have lagged behind. One promising line of investigation is the virus therapy of cancer. This approach entails the use of viruses, such as retroviruses, adenovirus, and vaccinia virus, to modify tumor cells so that they become more susceptible to being killed by the host immune response, chemotherapeutic agents, or programmed cell death. This review discusses recent advances in the virus therapy of cancer from both basic science and clinical perspectives. Given the potential of viruses to kill tumor cells directly or transduce desired gene products to allow a vigorous host antitumor immune response, the virus therapy of cancer holds great promise in the treatment of cancer.
Mediators and Mechanisms of Radiation Nephropathy
Authors: Cohen Eric P. , Bonsib Stephen A. , Whitehouse Elizabeth , Hopewell John W. , Robbins Mike E. C.
Published: August 2010

Abstract. Normal tissue radiation injury occurs after sufficient irradiation, thus limiting the curative potential of x‐ray therapy. In the kidney, radiation injury results in fibrosis and, ultimately, renal failure. The mediators of fibrosis in radiation nephropathy have received scant attention. Therefore, we evaluated the sequential presence of alpha smooth muscle actin (αsma), fibrin, collagen, and TGFβ1 in a porcine model of radiation nephropathy using 9.8 Gy single‐dose local kidney irradiation. During the 24‐week study, there was progressive and significant collagen accumulation in glomeruli and in interstitium. In glomeruli, this was associated with significant mesangial αsma expression by 2 weeks after irradiation, a further rise at 4 weeks, and then a gradual fall to baseline. Glomerular fibrin deposition was significant by 4 weeks after irradiation, and remained elevated thereafter. There was little or no glomerular TGFβ1 expression at any time point. Tubular fibrin deposition was significant at 4 weeks after irradiation but declined thereafter. There was little or no tubulo‐interstitial αsma expression at any time after irradiation. At 6 weeks after irradiation, there was a significant peak of tubular epithelial TGFβ1 expression that declined thereafter. The early glomerular injury is evident as mesangial αsma expression but is not proceeded by TGFβ1 expression. There is sustained glomerular fibrin deposition with deposition of fibrin in tubular lumens, suggesting that tubular fibrin derives and flows out from injured glomerular tufts. We conclude that i) αsma expression is an early marker of glomerular radiation injury, presaging scarring; ii) fibrin deposition is involved in glomerular and tubular radiation injury; and iii) TGFβ1 is not an early event in radiation nephropathy, and not apparent in glomeruli in this model, but may correlate with later tubulo‐interstitial fibrosis. Thus, the mediators of scarring in this model differ according to time after injury and also according to the affected tissue compartment.
Transport of Toxic Heavy Metals Across Cell Membranes
Authors: Foulkes E. C.
Published: August 2010

Abstract. Membrane transport of nonessential toxic heavy metals (type D heavy metals) not only controls their access to intracellular target sites but also helps determine their uptake, distribution, and excretion from the body. The critical role of membranes in the toxicology of class D metals has attracted the attention of many investigators, and extensive information has been collected on the mechanism(s) of metal transfer across membranes. Characteristics of metal transport in different cells, or even on opposite sides of the same cell, or under different physiological conditions, are not identical, and no unitary hypothesis has been formulated to explain this process in all cells. However, it seems possible that the mechanisms proposed for different cells represent variations on a few common themes.
Peptide YY Stimulates the Expression of Apolipoprotein A‐IV Gene in Caco‐2 Intestinal Cells
Authors: Sonoyama Kei , Suzuki Keiko , Kasai Takanori
Published: August 2010

Abstract. The effect of peptide YY, a gastrointestinal hormone, on the expression of the apolipoprotein A‐IV gene in the intestinal epithelial cell line Caco‐2 was examined by semiquantitative RT‐PCR followed by Southern hybridization with an inner oligonucleotide probe. Apolipoprotein A‐IV mRNA levels were increased in response to peptide YY in a dose‐ and time‐dependent fashion. Western blotting revealed that the exogenous peptide YY increased the intracellular concentration of apolipoprotein A‐IV. In contrast, apolipoprotein A‐I, B, and C‐III mRNA did not respond to peptide YY. Differentiated Caco‐2 cells expressed Y1‐ but not Y2‐ and Y5‐receptor subtype mRNA. The present results suggest that peptide YY modulates apolipoprotein A‐IV gene expression, likely via the Y1‐receptor subtype in intestinal epithelial cells.
Effects of Oral Administration of Tamoxifen, Toremifene, Dehydroepiandrosterone, and Vorozole on Uterine Histomorphology in the Rat
Authors: Nephew Kenneth P. , Osborne Elizabeth , Lubet Ronald A. , Grubbs Clinton J. , Khan Sohaib A.
Published: August 2010

Abstract. Tamoxifen, toremifene, DHEA, and vorozole inhibit tumor growth in rodent mammary carcinoma models and are promising chemotherapeutic agents for use against breast cancer development. In the present study, the effect of these agents on uterine histomorphology following oral administration to mature ovary‐intact rats (n = 380) was examined. Animals received diet only (control), tamoxifen (0.4 and 1 mg/kg of diet; 10 mg/kg BW by daily gavage), toremifene (3–30 mg/kg of diet), DHEA (24–2000 mg/kg of diet), or vorozole (0.08–1.25 mg/kg BW by daily gavage) for 28 days and were either sacrificed or returned to a basal diet and then sacrificed 21 days later. Treatment with toremifene (all doses) or tamoxifen (1 and 10 mg/kg) for 28 days produced a decrease (P < 0.05) in overall uterine size and myometrial thickness; however, uterine luminal and glandular epithelia cell height increased (P < 0.05) compared with control. These compartmentalized uterotrophic and antiestrogenic effects of toremifene and tamoxifen were still apparent after 21 days post‐treatment. Administration of DHEA (2000 mg/kg of diet) for 28 days had dramatic uterotrophic effects, increasing (P < 0.05) overall uterine size and stimulating all three uterine compartments (epithelia, stroma, and myometrium). The other doses of DHEA, however, were not uterotrophic. Interestingly, after removal of DHEA from the diet, uterine weight and myometrial thickness decreased (P < 0.05). Vorozole (1.25 mg/kg) administration for 28 days had differential, compartmentalized uterine effects, producing an increase (P < 0.05) in epithelial cell height, a decrease (P < 0.05) in stromal size, but no change in myometrial thickness. After 21 days postadministration of vorozole, luminal epithelial cell height was increased (P < 0.05) compared with control. The data suggest that oral administration of tamoxifen, toremifene, DHEA, and vorozole results in differential, compartmentalized effects in the uterus that are highly dependent on treatment dose. The data may have implications for risk assessment of these agents prior to administration to healthy, cancer‐free women.
Genomic Changes and HPV Type in Cervical Carcinoma
Authors: Matthews Connie P. , Shera Katherine A. , McDougall James K.
Published: August 2010

Abstract. To identify chromosomal regions that may include the loci of abnormally expressed cellular genes and may be specifically altered depending on the histological subtype of the tumor, we studied primary cervical carcinoma using CGH and HPV genotyping. Eighty‐seven percent of the primary tumors were positive for DNA of a “high‐risk” HPV type (e.g., 16 or 18). In the cervical carcinomas, without reference to histologic subtype, overrepresentation of chromosome 3q was the most consistent chromosomal aberration with underrepresentation of chromosome 3p also a frequent finding. Chromosome arms 1q, 5p, 20q, and Xq were overrepresented in many tumors and 3p loss and 5p, 8q, and 16q gain were only associated with squamous cell carcinoma in this series.
The Role of Integrins in Reproduction
Authors: Bowen Jeffery A. , Hunt Joan S.
Published: August 2010

Abstract. Fertilization, implantation, and placentation are dynamic cellular events that require not only synchrony between the maternal environment and the embryo, but also complex cell‐to‐cell communication. This communication involves integrins, a large family of proteins involved in the attachment, migration, invasion, and control of cellular function. Over the past decade, investigators have learned that integrins participate in multiple reproductive events including fertilization, implantation, and placentation in many species. This review will describe: (i) the expression of integrins on gametes and during the establishment and development of the placenta; (ii) regulatory pathways for controlling expression of integrins in the uterus and developing placenta; (iii) the function of integrins as determined by null‐mutations; and (iv) reproductive dysfunction in women related to inappropriate integrin expression in the uterus and/or placenta.