bluuebunny/crossref_metadata_2025 huggingface dataset:
The management of potato cyst nematodes using resistant Solanaceae potato clones as trap crops
Authors: Turner S.J. , Martin T.J.G. , McAleavey P.B.W. , Fleming C.C.
Published: November 2006

The concept of using a range of Solanaceae potato clones as trap crops for potato cyst nematode (PCN) management was investigated. A series of field trials were undertaken from 1999 to 2002 that evaluated 10 clones of either wild Solanum potato species, breeder’s hybrid lines or commercial cultivars. All had high resistance to all known PCN pathotypes (both Globodera rostochiensis and Globodera pallida) and the ability to stimulate high levels of PCN hatch. Investigations showed potential for the development of some clones as a means of reducing high PCN field population levels and for use by organic potato producers.
Tuber induction and initiation during production and early field growth of transplants from in vitro‐derived potato plants
Authors: Lommen W.J.M. , Struik P.C.
Published: November 2006

In transplants from in vitro‐derived plantlets from very early potato (Solanum tuberosum) cultivars, a lower degree of tuber induction at the time of field planting is thought to increase tuber production. Leaf‐bud cuttings were used to assess the progress to tuber induction in in vitro‐derived potato plantlets during the transplant production phase and after subsequent transplanting into the field. Induction and initiation of tubers on the same plants were assessed to study the effects of the duration of transplant production and conditions during transplant production for cv. Gloria (very early) and cv. Bintje (mid‐early). In vitro‐produced plantlets were not induced by the time of planting but rapidly progressed to the induced state thereafter. The progress in induction with time and the change in percentage of plants showing tubers fitted typical sigmoid curves. Plantlets achieved 50% induction ca 15 days after planting into in vivo conditions, and 50% tuber initiation usually occurred 10 days later. Shorter transplant production periods reduced the degree of induction of the transplants at field planting. Transplant production for more than 2 weeks was required to allow conditions during that period to affect induction or initiation. Long‐term non‐inducing conditions delayed the progress to tuber induction in cv. Gloria and delayed tuber initiation in both cultivars. Cv. Gloria showed no faster progress to induction than cv. Bintje but initiated tubers earlier. The results suggest that the relation between progress to induction and tuber initiation is cultivar dependent and that leaf‐bud cuttings can be used successfully in very young in vitro‐derived plants for assessing the progress to tuber induction.
Consumers' Food Choices with Voluntary Access to Genetic Modification Information
Authors: Hu Wuyang , Veeman Michele , Adamowicz Wiktor , Gao Ge
Published: November 2006

The effects on product choices of voluntarily accessed information are examined in the context of an experimental survey relating to genetically modified food. The data and analysis in this study avoid the assumption that information made available or given to consumers is equivalent to information processed by consumers. Instead we focus on information access behavior. Three different approaches to model this behavior are applied in a Bayesian estimation framework, including conditional logit (CL) models based on the full sample, ex post analysis of individual parameters from mixed logit models, and CL models within the different information scenarios. All three approaches give consistent results. However, the assumption of voluntary information access generates different results than assuming that all information is processed. The results of the analysis show that different types of information do have impacts on consumers' product choices. The nature of these effects appears to be influenced by voluntary access to information.

Les répercussions de l'accès volontaire à l'information sur les choix de produits ont été examinées dans le cadre d'un sondage expérimental sur les aliments génétiquement modifiés. Dans la présente étude, l'hypothèse voulant que l'information offerte ou transmise aux consommateurs soit équivalente à l'information que les consommateurs trouvent d'eux‐mêmes a étéécartée. Nous avons plutôt mis l'accent sur le comportement face à l'accès à l'information. Pour modéliser ce comportement, trois méthodes différentes ont été appliquées dans une structure d'estimation bayésienne, à savoir des modèles logit conditionnels fondés sur l'échantillon complet, une analyse ex post des paramètres individuels tirés de modèles logit mixtes et des modèles logit conditionnels parmi les divers scénarios d'information. Les trois méthodes ont donné des résultats concordants. Toutefois, l'hypothèse de l'accès volontaire à l'information a généré des résultats qui différaient de ceux de l'hypothèse voulant que toute l'information soit traitée. Les résultats de l'analyse ont montré que différents types d'information ont des répercussions sur les choix de produits des consommateurs. La nature de ces répercussions semble être influencée par l'accès volontaire à l'information.
A Censored Quantile Regression Analysis of Vegetable Demand: The Effects of Changes in Prices and Total Expenditure
Authors: Gustavsen Geir Wæhler , Rickertsen Kyrre
Published: November 2006

Many diseases are linked to dietary behavior. One major diet‐related risk factor is a low consumption of vegetables. The consumption may be increased through public policies. The effects on vegetable purchases of either removing the value added tax on vegetables or a general income support are investigated. Adverse health effects are most serious in households consuming low quantities of vegetables. Therefore, the effects on high‐ and low‐consuming households are estimated by using quantile regressions (QRs). Since many households did not purchase any vegetable during each survey period, censored as well as ordinary QRs are used. Our results suggest that the effects of the policy variables differ in different parts of the conditional distribution of vegetable purchases. None of the proposed policy options is likely to substantially increase vegetable purchases among low‐consuming households.

Bon nombre de maladies découlent des habitudes alimentaires. La faible consommation de légumes constitue un important facteur de risque liéà l'alimentation. Cette consommation pourrait être accrue par l'instauration de politiques gouvernementales. Nous avons examiné les effets de l'abolition de la taxe sur la valeur ajoutée ou d'un soutien du revenu sur les achats de légumes. Les effets néfastes sur la santé sont plus graves chez les ménages qui consomment de faibles quantités de légumes. Nous avons donc estimé les effets chez les ménages à forte et à faible consommation de légumes à l'aide de régressions par quantile. Comme de nombreux ménages n'ont pas acheté de légumes au cours des périodes sondées, nous avons utilisé des régressions par quantile censurées et des régressions par quantile ordinaires. Nos résultats ont indiqué que les effets des variables concernant les politiques diffèrent dans différentes parties de la distribution conditionnelle des achats de légumes. Aucune des options politiques proposées ne semble susceptible d'accroître substantiellement les achats de légumes chez les ménages qui en consomment peu.
Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles
Authors: Donato Anthony J. , Lesniewski Lisa A. , Delp Michael D.
Published: November 2006

Ageing is associated with increased leg vascular resistance and reductions in leg blood flow during rest and exercise, potentially predisposing older adults to a host of functional and cardiovascular complications. The purpose of these studies was to examine the effects and possible mechanisms of ageing and exercise training on arteriolar adrenergic vasoreactivity. Young and old male Fischer 344 rats were divided into young sedentary (YS), old sedentary (OS), young exercise‐trained (YT) or old exercise‐trained (OT) groups, where training consisted of chronic treadmill exercise. Isolated soleus (SOL) and gastrocnemius (GAS) muscle arterioles were studied in vitro. Responses to noradrenaline in endothelium‐intact and endothelium‐denuded arterioles, as well as during nitric oxide synthase (NOS) inhibition were determined. Vasodilator responses to isoproterenol and forskolin were also determined. Results: Noradrenaline‐mediated vasoconstriction was increased in SOL arterioles with ageing, and exercise training in old rats attenuated α‐adrenergic vasoconstriction in arterioles from both muscle types. Removal of the endothelium and NOS inhibition eliminated these ageing and training effects. Isoproterenol‐mediated vasodilatation was impaired with ageing in SOL and GAS arterioles, and exercise training had little effect on this response. Forskolin‐induced vasodilatation was not affected by age. The data demonstrate that ageing augments α‐adrenergic vasoconstriction while exercise training attenuates this response, and both of these alterations are mediated through an endothelial α‐receptor‐NOS‐signalling pathway. In contrast, ageing diminishes β‐receptor‐mediated vasodilatation, but this impairment is specific to the smooth muscle. These studies indicate that α‐ and β‐adrenergic mechanisms may serve to increase systemic vascular resistance with ageing, and that the effects of exercise training on adrenergic vasomotor properties could contribute to the beneficial effects of exercise on cardiovascular disease.
Cellular mechanisms of burst firing‐mediated long‐term depression in rat neocortical pyramidal cells
Authors: Czarnecki Antonny , Birtoli Barbara , Ulrich Daniel
Published: November 2006

During wakefulness and sleep, neurons in the neocortex emit action potentials tonically or in rhythmic bursts, respectively. However, the role of synchronized discharge patterns is largely unknown. We have recently shown that pairings of excitatory postsynaptic potentials (EPSPs) and action potential bursts or single spikes lead to long‐term depression (burst‐LTD) or long‐term potentiation, respectively. In this study, we elucidate the cellular mechanisms of burst‐LTD and characterize its functional properties. Whole‐cell patch‐clamp recordings were obtained from layer V pyramidal cells in somatosensory cortex of juvenile rats in vitro and composite EPSPs and EPSCs were evoked extracellularly in layers II/III. Repetitive burst‐pairings led to a long‐lasting depression of EPSPs and EPSCs that was blocked by inhibitors of metabotropic glutamate group 1 receptors, phospholipase C, protein kinase C (PKC) and calcium release from the endoplasmic reticulum, and that required an intact machinery for endocytosis. Thus, burst‐LTD is induced via a Ca2+‐ and phosphatidylinositol‐dependent activation of PKC and expressed through phosphorylation‐triggered endocytosis of AMPA receptors. Functionally, burst‐LTD is inversely related to EPSP size and bursts dominate single spikes in determining the sign of synaptic plasticity. Thus burst‐firing constitutes a signal by which coincident synaptic inputs are proportionally downsized. Overall, our data thus suggest a mechanism by which synaptic weights can be reconfigured during non‐rapid eye movement sleep.
Accelerated Evolution of Conserved Noncoding Sequences in Humans
Authors: Prabhakar Shyam , Noonan James P. , Pääbo Svante , Rubin Edward M.
Published: November 2006

Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. We identified 992 conserved noncoding sequences (CNSs) with a significant excess of human-specific substitutions. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar enrichment near neuronal adhesion genes in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with those in human, suggesting independent evolution toward different neuronal phenotypes in each species. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to uniquely human features of brain development and function.
Pattern Formation and Shape Changes in Self-Oscillating Polymer Gels
Authors: Yashin Victor V. , Balazs Anna C.
Published: November 2006

We developed an efficient model for responsive gels that captures large-scale, two-dimensional (2D) deformations and chemical reactions within a swollen polymer network. The 2D calculations allowed us to probe not only volume changes but also changes in sample shape. By focusing on gels undergoing the oscillatory Belousov-Zhabotinsky reaction, we observed traveling waves of local swelling that form a rich variety of dynamic patterns and give rise to distinctive oscillations in the gel's shape. The observed patterns depend critically on the gel's dimensions. The approach provides a useful computational tool for probing the dynamics of chemomechanical processes and uncovering morphological transformations in responsive gels.
Localization of Iron in
Arabidopsis
Seed Requires the Vacuolar Membrane Transporter VIT1
Authors: Kim Sun A. , Punshon Tracy , Lanzirotti Antonio , Li Liangtao , Alonso José M. , Ecker Joseph R. , Kaplan Jerry , Guerinot Mary Lou
Published: November 2006

Iron deficiency is a major human nutritional problem wherever plant-based diets are common. Using synchrotron x-ray fluorescence microtomography to directly visualize iron in
Arabidopsis
seeds, we show that iron is localized primarily to the provascular strands of the embryo. This localization is completely abolished when the vacuolar iron uptake transporter VIT1 is disrupted. Vacuolar iron storage is also critical for seedling development because
vit1-1
seedlings grow poorly when iron is limiting. We have uncovered a fundamental aspect of seed biology that will ultimately aid the development of nutrient-rich seed, benefiting both human health and agricultural productivity.
100 Years and Counting: Prospects for Defeating Alzheimer's Disease
Authors: Roberson Erik D. , Mucke Lennart
Published: November 2006

This week marks a century since the first description of Alzheimer's disease (AD). Despite approval of several drugs for AD, the disease continues to rob millions of their memories and their lives. Fortunately, many new therapies directly targeting the mechanisms underlying AD are now in the pipeline. Among the investigative AD therapies in clinical trials are several strategies to block pathogenic amyloid-β peptides and to rescue vulnerable neurons from degeneration. Complementary but less mature strategies aim to prevent the copathogenic effects of apolipoprotein E and the microtubule-associated protein tau. New insights into selective neuronal vulnerability and the link between aging and AD may provide additional entry points for therapeutic interventions. The predicted increase in AD cases over the next few decades makes the development of better treatments a matter of utmost importance and urgency.
Comment on "Rapid Uplift of the Altiplano Revealed Through
13
C-
18
O Bonds in Paleosol Carbonates"
Authors: Sempere T. , Hartley A. , Roperch P.
Published: November 2006

Based on stable isotope measurements, Ghosh
et al
. (Reports, 27 January 2006, p. 511) concluded that the Bolivian Altiplano uplifted 3 to 4 kilometers between ∼10.3 and ∼6.7 million years ago as a result of gravitational loss of dense lithosphere. This result stands at odds with current geological knowledge of the Central Andes, and we propose a test for the reliability of the paleoaltimetry method.
Puzzle for the existence of 3α + N structure in A=13 system
Authors: Fujiwara Mamoru , Fujimura Hisako
Published: November 2006

Spin-isospin excitations in 13 N have been studied by means of the (3 He ,t) and (3 He ,tp) reactions at the bombarding energy of E(3 He ) = 450 MeV . The zero-degree (3 He ,t) spectrum is found to be similar to those from the (p,n) reactions at intermediate energies, suggesting a simple direct reaction mechanism at E(3 He ) = 450 MeV . Three pairs of Gamow-Teller (GT) states with Jπ = 1/2- and 3/2- have been strongly excited at θlab. = 0°. Microscopic structures of the states in 13 N have been studied by observing decay protons in coincidence with high energy tritons measured at θlab. = 0°. The branching ratios for proton decay from the GT states in 13 N to the final low-lying T =0 states in 12 C were obtained. The wave functions of the excited states in 13 N are discussed in the view point of α cluster model.
COMBINING CLUSTER STRUCTURE WITH REACTIONS
Authors: FREER MARTIN
Published: November 2006

An examination of the role of the cluster in nuclear reactions is made in the longstanding case of 12 C +12 C cluster resonances in 24 Mg . A description of both resonant scattering and breakup measurements can be found in terms of shape isomeric cluster structures.
Application of JLM folding model to alpha-nucleus scattering
Authors: Furumoto T. , Sakuragi Y.
Published: November 2006

A systematic analysis of alpha(4 He )-nucleus elastic scattering is made by using a microscopic optical model potential obtained by the double folding of a complex nucleon-nucleon (NN) effective interaction based on the G-matrix theory. We adopt the so-called JLM interaction as the complex NN interaction and test its applicability to the 4 He elastic scattering by 12 C , 16 O , 28 Si and 40 Ca . The experimental cross sections for incident energies ranging from E Lab = 40 to 240 MeV are well reproduced by the double folding potential up to backward angles. Although modification of the real and imaginary potential strength by about 25% and 35%, respectively, in average is necessary to reproduce the data, the renormalization factors are found to be almost constant with respect to the incident energy and target mass number.
Many particle and many hole states in 31Mg
Authors: Kimura Masaaki
Published: November 2006

The low-lying level structure of 31 Mg has been investigated by the theoretical framework of deformed-basis antisymmetrized molecular dynamics (DAMD) plus generator coordinate method (GCM) with the Gogny D1S force. It is shown that the N =20 magic number is broken and the intruder configuration (neutron 2p3h configuration) dominates the ground state. The observed data such as the magnetic moment and β decay strength are well reproduced.
BÉZIER SUBDIVISION FOR INVERSE MOLECULAR KINEMATICS
Authors: ZHANG MING , WANG LIQUN , GOLDMAN RONALD
Published: November 2006

Conformational searching is a core task in inverse molecular kinematics. Algorithmic improvements affecting either the speed or quality of conformational searching will have a profound impact on applications including ligand-receptor docking, ab initio prediction of protein structure, and protein folding. In this paper, we investigate a specific geometry-constrained conformational searching problem, where some feature atoms have pre-specified target positions. Using Bézier subdivision, we present a method to locate and approximate the solutions of the equations derived from constraints on the feature atoms. The conformations corresponding to these solutions are all the conformations satisfying the target constraints. Three implementations of the subdivision method taking advantage of the sparsity of the coefficients of the polynomial equations are presented and the results are compared and contrasted.
SHORTEST PATH AMIDST DISC OBSTACLES IS COMPUTABLE
Authors: CHANG EE-CHIEN , CHOI SUNG WOO , KWON DO YONG , PARK HYUNGJU , YAP CHEE K.
Published: November 2006

An open question in Exact Geometric Computation is whether there are transcendental computations that can be made "geometrically exact". Perhaps the simplest such problem in computational geometry is that of computing the shortest obstacle-avoiding path between two points p,q in the plane, where the obstacles are a collection of n discs.

This problem can be solved in O(n2 log n) time in the Real RAM model, but nothing was known about its computability in the standard (Turing) model of computation. We first give a direct proof of the Turing-computability of this problem, provided the radii of the discs are rationally related. We make the usual assumption that the numerical input data are real algebraic numbers. By appealing to effective bounds from transcendental number theory, we further show a single-exponential time upper bound when the input numbers are rational.

Our result appears to be the first example of a non-algebraic combinatorial problem which is shown computable. It is also a rare example of transcendental number theory yielding positive computational results.
IL-1β stimulates rat cardiac fibroblast migration via MAP kinase pathways
Authors: Mitchell M. Darren , Laird Rebecca E. , Brown R. Dale , Long Carlin S.
Published: November 2006

The pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) are elevated following acute myocardial infarction (MI) and have been implicated in the pathophysiology of cardiac disease progression. The cardiac fibroblast represents an important effector cell target for cytokine actions. In particular, cytokine-directed cardiac fibroblast migration is likely to impact both myocardial repair following acute MI and pathological myocardial remodeling in the progression to heart failure. In the present study, we examined the migratory response of neonatal rat cardiac fibroblasts to pro-inflammatory cytokines using modified Boyden chamber assays. On the basis of the knowledge of migration in other cell types, we hypothesized that members of the mitogen-activated protein kinase (MAPK) family may regulate this process. This possibility was addressed with the use of immunoblot detection of active phosphorylated MAPK species and pharmacological inhibitors for individual members of the MAPK cascades. IL-1β stimulated robust and concentration-dependent increases in migration (maximum, 20-fold over control cells). TNF-α had lesser effect (fourfold increase over control). IL-6 did not induce migration. Activation of all three MAPK subfamilies (extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38) was shown to occur in response to cytokine stimulation. Fibroblast migration was attenuated by pharmacological inhibition of each MAPK subfamily. Understanding the regulation of cardiac fibroblast migration may provide insights in the search for therapies aimed at enhancing the functional nature of the remodeling process.
Role of lipid rafts in membrane delivery of renal epithelial Na+-K+-ATPase, thick ascending limb
Authors: Welker Pia , Geist Beate , Frühauf Jan-Henning , Salanova Michele , Groneberg David A. , Krause Eberhard , Bachmann Sebastian
Published: November 2006

Lipid rafts are cholesterol- and shingolipid-enriched membrane microdomains implicated in membrane signaling and trafficking. To assess renal epithelial raft functions through the characterization of their associated membrane proteins, we have isolated lipid rafts from rat kidney by sucrose gradient fractionation after detergent treatment. The low-density fraction was enriched in cholesterol, sphingolipid, and flotillin-1 known as lipid raft markers. Based on proteomic analysis of the low-density fraction, the protein with the highest significance score was the α-subunit of Na+-K+-ATPase (NKA), whose raft association was validated by simultaneous immunoblotting. The β-subunit of NKA was copurified from the low-density fraction. To test the role of lipid rafts in sorting and membrane delivery of renal-transporting epithelia, we have chosen to study thick ascending limb (TAL) epithelium for its high NKA activity and the property to be stimulated by antidiuretic hormone (ADH). Cultured rabbit TAL cells were studied. Cholesterol depletion and detergent extraction at warmth caused a shift of NKA to the higher-density fractions. Comparative preparations from blood monocytes revealed the absence of NKA from rafts in these nonpolarized cells. Short-term exposure of rabbit TAL cells to ADH (1 h) caused translocation and enhanced raft association of NKA via cAMP activation. Preceding cholesterol depletion prevented this effect. TAL-specific, glycosylphosphatidylinositol-anchored Tamm Horsfall protein was copurified with NKA in the same raft fraction, suggesting functional interference between these products. These results may have functional implications regarding the turnover, trafficking, and regulated surface expression of NKA as the major basolateral ion transporter of TAL.
The contribution of carotid rete variability to brain temperature variability in sheep in a thermoneutral environment
Authors: Maloney Shane K. , Mitchell Duncan , Blache Dominique
Published: November 2006

The degree of variability in the temperature difference between the brain and carotid arterial blood is greater than expected from the presumed tight coupling between brain heat production and brain blood flow. In animals with a carotid rete, some of that variability arises in the rete. Using thermometric data loggers in five sheep, we have measured the temperature of arterial blood before it enters the carotid rete and after it has perfused the carotid rete, as well as hypothalamic temperature, every 2 min for between 6 and 12 days. The sheep were conscious, unrestrained, and maintained at an ambient temperature of 20–22°C. On average, carotid arterial blood and brain temperatures were the same, with a decrease in blood temperature of 0.35°C across the rete and then an increase in temperature of the same magnitude between blood leaving the rete and the brain. Rete cooling of arterial blood took place at temperatures below the threshold for selective brain cooling. All of the variability in the temperature difference between carotid artery and brain was attributable statistically to variability in the temperature difference across the rete. The temperature difference between arterial blood leaving the rete and the brain varied from −0.1 to 0.9°C. Some of this variability was related to a thermal inertia of the brain, but the majority we attribute to instability in the relationship between brain blood flow and brain heat production.
Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus
Authors: Douglas Robert M. , Miyasaka Naoyuki , Takahashi Kan , Latuszek-Barrantes Adrianna , Haddad Gabriel G. , Hetherington Hoby P.
Published: November 2006

Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the FiO2was maintained at 11% continuously or to CIH, where the FiO2was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients.
Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension
Authors: Maduwegedera D. , Kett M. M. , Flower R. L. , Lambert G. W. , Bertram J. F. , Wintour E. M. , Denton K. M.
Published: November 2006

Previously, we demonstrated that adult blood pressure was increased in offspring of rabbit mothers with chronic secondary renal hypertension. Our study identified sex-specific differences in the programming of hypertension, with female, not male, offspring, having increased blood pressure at 30 wk of age. The aim of this study was to characterize the maternal hypertension during pregnancy to determine potential programming stimuli. Further, we examined the impact of chronic maternal hypertension on offspring birth weight, nephron number, and renal noradrenaline content (as an index of renal innervation density). Three groups of mothers and their offspring were studied: two-kidney, one-wrap (2K-1W, n = 9 mothers) hypertensive, two-kidney, two-wrap (2K-2W, n = 8) hypertensive, and a sham-operated group ( n = 9). Mean arterial blood pressure was increased by ∼20 mmHg throughout pregnancy in both hypertensive groups compared with sham mothers (PG< 0.001). Plasma renin activity (PRA; PG< 0.05) and aldosterone (PG< 0.05) levels were increased during gestation in the 2K-1W, but not the 2K-2W mothers. Birth weight was increased by ∼20% in offspring of both groups of hypertensive mothers (PT< 0.001), though this was associated with a reduction in litter size. Renal noradrenaline content was increased (∼40%, P < 0.05) at 5 wk of age in female 2K-1W offspring compared with sham offspring. Glomerular number was not reduced in female offspring of either group of hypertensive mothers; however, glomerular tuft volume was reduced in female 2K-2W offspring ( P < 0.05), indicative of a reduction in glomerular filtration surface area. In conclusion, the two models of renal hypertension produced differential effects on the offspring. The impact of a stimulated maternal renin-angiotensin system in the 2K-1W model of hypertension may influence development of the renal sympathetic nerves and contribute to programming of adult hypertension.
Progressive postnatal increases in Fos immunoreactivity in the forebrain and brain stem of rats after viscerosensory stimulation with lithium chloride
Authors: Koehnle Thomas J. , Rinaman Linda
Published: November 2006

Interoceptive signals have a powerful impact on the motivation and emotional learning of animals during stressful experiences. However, current insights into the organization of interoceptive pathways stem mainly from observation and manipulation of adults, and little is known regarding the functional development of viscerosensory signaling pathways. To address this, we have examined central neural activation patterns in rat pups after treatment with lithium chloride (LiCl), a malaise-inducing agent. Rat pups were injected intraperitoneally with 0.15 M LiCl or 0.15 M NaCl (2% body wt) on postnatal day (P)0, 7, 14, 21, or 28, perfused 60 to 90 min postinjection, and their brains assayed for Fos protein immunolabeling. Compared with saline treatment, LiCl increased Fos only slightly in the area postrema, nucleus of the solitary tract, and lateral parabrachial nucleus on P0. LiCl did not increase Fos above control levels in the central nucleus of the amygdala, bed nucleus of the stria terminalis (BNST), or paraventricular nucleus of the hypothalamus on P0 but did on P7 and later. Maximal Fos responses to LiCl were observed on P14 in all areas except the BNST, in which LiCl-induced Fos activation continued to increase through P28. These results indicate that central LiCl-sensitive interoceptive circuits in rats are not fully functional at birth, and show age-dependent increases in neural Fos responses to viscerosensory stimulation with LiCl.
The effect of exercise on nasal uptake of ozone in healthy human adults
Authors: Sawyer Keegan , Brown James S. , Hazucha Milan J. , Bennett William D.
Published: November 2006

The nose may help protect the lower respiratory tract from the effects of ambient ozone by scrubbing ozone from inspired air. Reductions in both nasal resistance and nitric oxide production with exercise may influence the efficiency of ozone uptake in the nose. Nasal ozone uptake was measured in 10 healthy volunteers before and after 15 min of moderate bicycle exercise. Ozone (0.2 parts/million) was pulled through both nostrils and out of the mouth at a constant flow while the subjects closed their epiglottises. Nasal uptake of ozone was determined by comparing the ozone concentration entering the nostrils to that exiting the mouth. Average preexercise uptake of ozone was 56 ± 7.8 and 37 ± 4.9% at 10 and 20 l/min, respectively. These averages did not significantly differ from those immediately postexercise (55 and 37%). Nasal ozone uptake increased significantly ( P < 0.001) with decreasing flow rate, but intersubject variability in uptake could not be predicted by nasal volume or cross-sectional areas (as measured by acoustic rhinometry) or endogenous nitric oxide production. However, the percent change in ozone uptake after exercise, within an individual, was correlated with both 1) percent change in nasal volume ( r = 0.70 at 10 l/min) and 2) percent change in the rate of volumetric expansion between the nasal valve and turbinates ( r = 0.82 at 10 l/min). These results may be useful for assessing human risk associated with ozone exposure during exercise.
Electromyographic activity during the reflex pharyngeal swallow in the pig: Doty and Bosma (1956) revisited
Authors: Thexton A. J. , Crompton A. W. , German R. Z.
Published: November 2006

The currently accepted description of the pattern of electromyographic (EMG) activity in the pharyngeal swallow is that reported by Doty and Bosma in 1956; however, those authors describe high levels of intramuscle and of interindividual EMG variation. We reinvestigated this pattern, testing two hypotheses concerning EMG variation: 1) that it could be reduced with modern methodology and 2) that it could be explained by selective detection of different types of motor units. In eight decerebrate infant pigs, we elicited radiographically verified pharyngeal swallows and recorded EMG activity from a total of 16 muscles. Synchronization signals from the video-radiographic system allowed the EMG activity associated with each swallow to be aligned directly with epiglottal movement. The movements were highly stereotyped, but the recorded EMG signals were variable at both the intramuscle and interanimal level. During swallowing, some muscles subserved multiple functions and contained different task units; there were also intramuscle differences in EMG latencies. In this situation, statistical methods were essential to characterize the overall patterns of EMG activity. The statistically derived multimuscle pattern approximated to the classical description by Doty and Bosma (Doty RW, Bosma JF. J Neurophysiol 19: 44–60, 1956) with a leading complex of muscle activities. However, the mylohyoid was not active earlier than other muscles, and the geniohyoid muscle was not part of the leading complex. Some muscles, classically considered inactive, were active during the pharyngeal swallow.
Hyperlipidemia and lipid peroxidation are dependent on the severity of chronic intermittent hypoxia
Authors: Li Jianguo , Savransky Vladimir , Nanayakkara Ashika , Smith Philip L. , O'Donnell Christopher P. , Polotsky Vsevolod Y.
Published: November 2006

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH) and associated with dysregulation of lipid metabolisms and atherosclerosis. Causal relationships between OSA and metabolic abnormalities have not been established because of confounding effects of underlying obesity. The goal of the study was to determine if CIH causes lipid peroxidation and dyslipidemia in the absence of obesity and whether the degrees of dyslipidemia and lipid peroxidation depend on the severity of hypoxia. Lean C57BL/6J mice were exposed to CIH for 4 wk with a fractional inspired O2(FiO2) nadir of either 10% (moderate CIH) or 5% (severe CIH). Mice exposed to severe CIH exhibited significant increases in fasting serum levels of total cholesterol (129 ± 2.9 vs. 113 ± 2.8 mg/dl in control mice, P < 0.05) and low-density lipoprotein cholesterol (85.7 ± 8.9 vs. 56.4 ± 9.7 mg/dl, P < 0.05) in conjunction with a 1.5- to 2-fold increase in lipoprotein secretion, and upregulation of hepatic stearoyl coenzyme A desaturase 1 (SCD-1). Severe CIH also markedly increased lipid peroxidation in the liver (malondialdehyde levels of 94.4 ± 5.4 vs. 57.4 ± 5.2 nmol/mg in control mice, P < 0.001). In contrast, moderate CIH did not induce hyperlipidemia or change in hepatic SCD-1 levels but did cause lipid peroxidation in the liver at a reduced level relative to severe CIH. In conclusion, CIH leads to hypercholesterolemia and lipid peroxidation in the absence of obesity, and the degree of metabolic dysregulation is dependent on the severity of the hypoxic stimulus.
Circulating Tumor Cells versus Imaging—Predicting Overall Survival in Metastatic Breast Cancer
Authors: Budd G. Thomas , Cristofanilli Massimo , Ellis Mathew J. , Stopeck Allison , Borden Ernest , Miller M. Craig , Matera Jeri , Repollet Madeline , Doyle Gerald V. , Terstappen Leon W.M.M. , Hayes Daniel F.
Published: November 2006

Purpose: The presence of ≥5 circulating tumor cells (CTC) in 7.5 mL blood from patients with measurable metastatic breast cancer before and/or after initiation of therapy is associated with shorter progression-free and overall survival. In this report, we compared the use of CTCs to radiology for prediction of overall survival.

Experimental Design: One hundred thirty-eight metastatic breast cancer patients had imaging studies done before and a median of 10 weeks after the initiation of therapy. All scans were centrally reviewed by two independent radiologists using WHO criteria to determine radiologic response. CTC counts were determined ∼4 weeks after initiation of therapy. Specimens were analyzed at one of seven laboratories and reviewed by a central laboratory.

Results: Interreader variability for radiologic responses and CTC counts were 15.2% and 0.7%, respectively. The median overall survival of 13 (9%) patients with radiologic nonprogression and ≥5 CTCs was significantly shorter than that of the 83 (60%) patients with radiologic nonprogression and <5 CTCs (15.3 versus 26.9 months; P = 0.0389). The median overall survival of the 20 (14%) patients with radiologic progression and <5 CTCs was significantly longer than the 22 (16%) patients with ≥5 CTCs that showed progression by radiology (19.9 versus 6.4 months; P = 0.0039).

Conclusions: Assessment of CTCs is an earlier, more reproducible indication of disease status than current imaging methods. CTCs may be a superior surrogate end point, as they are highly reproducible and correlate better with overall survival than do changes determined by traditional radiology.
2-Methoxyestradiol, an Endogenous Mammalian Metabolite, Radiosensitizes Colon Carcinoma Cells through c-Jun NH2-Terminal Kinase Activation
Authors: Zou HuiChao , Adachi Masaaki , Imai Kohzoh , Hareyama Masato , Yoshioka Katsuji , Zhao Shiguang , Shinomura Yasuhisa
Published: November 2006

Purpose: 2-Methoxyestradiol (2ME), an estrogen metabolite, induces apoptosis in various cell types. We investigated whether 2ME pretreatment can radiosensitize colon adenocarcinoma cells.

Experimental Design: Radiosensitizing effects of 2ME were evaluated by cell death, clonogenic assay, nuclear fragmentation, and tumor progression of xenografts. Ionizing radiation–induced DNA damage was evaluated by histone H2AX phosphorylation and its foci. The c-Jun NH2-terminal kinase (JNK) activation was evaluated by anti-phosphorylated JNK antibody and inhibited by the JNK-specific inhibitor SP600125 or dominant-negative SEK1 expression.

Results: Clonogenic assays revealed that 2ME, but not estradiol, radiosensitized three colon carcinoma cells, DLD-1, HCT-8, and HCT-15, and strongly suppressed tumor progression of DLD-1 xenografts. Gene transfer–mediated Bcl-xL overexpression largely abolished both augmented apoptosis and reduced survival fractions. Pretreatment with 2ME enhanced H2AX phosphorylation, its foci, and phosphorylation of ATM kinase and delayed re-entry of cell cycle progression after ionizing radiation. Augmentation of both radiosensitivity and H2AX phosphorylation was substantially reduced by SP600125 or overexpression of a dominant-negative mutant SEK1.

Conclusion: 2ME radiosensitized colon carcinoma cells through enhanced DNA damage via JNK activation, thereby representing a novel radiosensitizing therapy against colon cancer.
Metastasis-Suppressing Potential of Ribonucleotide Reductase Small Subunit p53R2 in Human Cancer Cells
Authors: Liu Xiyong , Zhou Bingsen , Xue Lijun , Shih Jennifer , Tye Karen , Lin Wesley , Qi Christina , Chu Peiguo , Un Frank , Wen Wei , Yen Yun
Published: November 2006

Purpose: Previous gene transfection studies have shown that the accumulation of human ribonucleotide reductase small subunit M2 (hRRM2) enhances cellular transformation, tumorigenesis, and malignancy potential. The latest identified small subunit p53R2 has 80% homology to hRRM2. Here, we investigate the role of p53R2 in cancer invasion and metastasis.

Experimental Design: The immunohistochemistry was conducted on a tissue array including 49 primary and 59 metastatic colon adenocarcinoma samples to determine the relationship between p53R2 expression and metastasis. A Matrigel invasive chamber was used to sort the highly invasive cells and to evaluate the invasion potential of p53R2.

Results: Univariate and multivariate analyses revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P < 0.05). The decrease of p53R2 is associated with cell invasion potential, which was observed in both p53 wild-type (KB) and mutant (PC-3 and Mia PaCa-2) cell lines. An increase in p53R2 expression by gene transfection significantly reduced the cellular invasion potential to 54% and 30% in KB and PC-3 cells, respectively, whereas inhibition of p53R2 by short interfering RNA resulted in a 3-fold increase in cell migration.

Conclusions: Opposite regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. The expression level of ribonucleotide reductase small subunits may serve as a biomarker to predict the malignancy potential of human cancers in the future.
Chromosomal Instability in Microsatellite-Unstable and Stable Colon Cancer
Authors: Trautmann Karolin , Terdiman Jonathan P. , French Amy J. , Roydasgupta Ritu , Sein Nancy , Kakar Sanjay , Fridlyand Jane , Snijders Antoine M. , Albertson Donna G. , Thibodeau Stephen N. , Waldman Frederic M.
Published: November 2006

Purpose: The genomic instability in colon cancer can be divided into at least two major types, microsatellite instability (MSI) or chromosomal instability (CIN). Although initially felt to be mutually exclusive, recent evidence suggests that there may be overlap between the two. The aim of this study was to identify chromosomal alterations at high resolution in sporadic colon cancers with high-level microsatellite instability (MSI-H) and to compare them to those present in a set of matched microsatellite stable (MSS) tumors.

Experimental Design: Array-based comparative genomic hybridization was used to analyze a set of 23 sporadic MSI-H and 23 MSS colon cancers matched for location, gender, stage, and age. The arrays consisted of 2,464 bacterial artificial chromosome clones.

Results: MSI and MSS colon cancers differed significantly with respect to frequency and type of chromosomal alterations. The median fraction of genome altered was lower among MSI-H tumors than MSS tumors (2.8% versus 30.7%, P = 0.00006). However, the MSI-H tumors displayed a range of genomic alterations, from the absence of detectable alterations to extensive alterations. Frequent alterations in MSI-H tumors included gains of chromosomes 8, 12, and 13, and loss of 15q14. In contrast, the most frequent alterations in MSS tumors were gains of 7, 13, 8q, and 20, and losses of 8p, 17p, and 18. A small, previously uncharacterized, genomic deletion on 16p13.2, found in 35% of MSI-H and 21% of MSS tumors, was confirmed by fluorescence in situ hybridization.

Conclusion: MSI and CIN are not mutually exclusive forms of genomic instability in sporadic colon cancer, with MSI tumors also showing varying degrees of CIN.
Reduced Expression of theBreast Cancer Metastasis Suppressor 1mRNA Is Correlated with Poor Progress in Breast Cancer
Authors: Zhang Zhenhuan , Yamashita Hiroko , Toyama Tatsuya , Yamamoto Yutaka , Kawasoe Teru , Iwase Hirotaka
Published: November 2006

Purpose: It is well established that breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis of breast cancer in animal models without affecting the growth of the primary tumor. It has also been shown to suppress the metastasis of tumors derived from breast and melanoma cell lines. However, its clinical importance for breast cancer patients remains undetermined. This prompted us to investigate its expression level in breast cancer patients to clarify its clinical significance.

Experimental Design: The level of expression of BRMS1 mRNA was assessed by LightCycler quantitative real-time reverse transcription-PCR in 161 cases of invasive carcinoma of the breast. Associations between BRMS1 mRNA expression and various clinicopathologic factors were sought.

Results: It was found that BRMS1 mRNA was expressed at significantly higher levels in patients >50 years of age, with tumor size <2 cm, or with progesterone receptor–positive and HER2-negative tumors. No differences were found between BRMS1 mRNA expression and axillary lymph node metastasis and histologic grade groups. Patients with high levels of expression of BRMS1 mRNA have a better prognosis than those with low expression. Univariate and multivariate prognostic analysis showed that BRMS1 mRNA is an independent prognostic factor for disease-free survival in breast cancer.

Conclusions: These results provide clinical evidence to support the notion that BRMS1 is a breast carcinoma metastasis suppressor gene. Our results also suggest that measuring BRMS1 expression will help to identify those breast cancer patients with worse disease-free survival.
Contralateral Normal Ear after Mastoid Surgery: Evaluation by Otoacoustic Emissions (Mastoid Drilling and Hearing Loss)
Authors: Karatas Erkan , Miman Murat Cem , Ozturan Orhan , Erdem Tamer , Kalcioglu Mahmut Tayyar
Published: November 2006

Mastoid drilling can cause transient hearing loss in the contralateral normal hearing ear. A study was designed to evaluate hearing in the contralateral normal ear before and after the mastoid surgery in a longitudinal manner and find out the duration of this temporary hearing loss. Twenty-two patients requiring mastoid surgery in their diseased ears, having contralateral normal ear were included. Pure tone audiometry and otoacoustic emissions (OAEs) were utilized for baseline evaluation. OAEs were repeated during the immediate postoperative period and daily up to the 6th postoperative day. The amplitudes of the OAEs of contralateral normal ears were found affected immediately after surgery and progressive improvement was detected with full recovery at 72–96 h. None of the patients had permanent deterioration in OAE amplitudes. The burs used during mastoid surgery can cause temporary hearing threshold changes in the contralateral ears. This adverse effect recovers spontaneously within 72–96 h postoperatively.