bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and comparative characterization of Gq‐coupled invertebrate visual pigments and melanopsin
Authors: Terakita Akihisa , Tsukamoto Hisao , Koyanagi Mitsumasa , Sugahara Michio , Yamashita Takahiro , Shichida Yoshinori
Published: January 2008

A non‐visual pigment melanopsin, which is localized in photosensitive retinal ganglion cells and is involved in the circadian photoentrainment and pupillary responses in mammals, is phylogenetically close to the visual pigments of invertebrates, such as insects and cephalopods. Recent studies suggested that melanopsin is a bistable pigment and drives a Gq‐mediated signal transduction cascade, like the invertebrate visual pigments. Because detailed electrophysiological properties are somewhat different between the visual cells and the photosensitive ganglion cells, we here expressed and purified the invertebrate visual pigment and melanopsin to comparatively investigate their Gq‐activation abilities. We successfully expressed and purified UV and blue light‐sensitive visual pigments of the honeybee as well as the amphioxus melanopsin. Although the purified UV‐sensitive pigment and the melanopsin lost their bistable nature during purification, reconstitution of the pigments in lipid vesicles resulted in return of the bistable nature. The light‐dependent Gq‐activation abilities among these reconstituted pigments are similar, suggesting that the electrophysiological differences do not depend on the Gq‐activation step but rather on the other signal transduction steps and/or on cell properties. Our findings are also important in that this is the first report describes a heterologous large‐scale expression of the Gq‐coupled invertebrate visual pigments in cultured cells.
Differential regulation of c‐Jun N‐terminal kinase and NF‐κB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells
Authors: Choi Kyungsun , Choi Chulhee
Published: January 2008

Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor κB (NF‐κB) and subsequent anti‐inflammatory activity. In this study, we report that (i) CAPE exerts its anti‐inflammatory action (inhibition of tumor necrosis factor‐induced expression of intercellular adhesion molecule‐1 and CC chemokine ligand‐2) via NF‐κB inhibition by two distinct molecular mechanisms in a cell‐specific manner: CAPE inhibited downstream pathways of inhibitor κB (IκB) degradation in monocytic cells, while activation of upstream IκB kinase was suppressed by CAPE pre‐treatment in astroglial cells; and (ii) CAPE paradoxically activates the c‐Jun N‐terminal kinase (JNK) pathway, which might be responsible for its pro‐apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand‐8.
The GSK3 hypothesis of Alzheimer’s disease
Authors: Hooper Claudie , Killick Richard , Lovestone Simon
Published: January 2008

J. Neurochem. (2008) 104, 1433–1439.

Glycogen synthase kinase 3 (GSK3) is a constitutively active, proline‐directed serine/threonine kinase that plays a part in a number of physiological processes ranging from glycogen metabolism to gene transcription. GSK3 also plays a pivotal and central role in the pathogenesis of both sporadic and familial forms of Alzheimer’s disease (AD), an observation that has led us to coin the ‘GSK3 hypothesis of AD’. According to this hypothesis, over‐activity of GSK3 accounts for memory impairment, tau hyper‐phosphorylation, increased β‐amyloid production and local plaque‐associated microglial‐mediated inflammatory responses; all of which are hallmark characteristics of AD. If our ‘GSK3 hypothesis of AD’ is substantiated and GSK3 is indeed a causal mediator of AD then inhibitors of GSK3 would provide a novel avenue for therapeutic intervention in this devastating disorder.
HIV‐infected macrophages mediate neuronal apoptosis through mitochondrial glutaminase
Authors: Tian Changhai , Erdmann Nathan , Zhao Jianxing , Cao Zhijun , Peng Hui , Zheng Jialin
Published: January 2008

A significant number of patients infected with human immunodeficiency virus‐1 (HIV‐1) suffer cognitive impairment ranging from mild to severe HIV‐associated dementia (HAD), a result of neuronal degeneration in the basal ganglia, cerebral cortex and hippocampus. Mononuclear phagocyte dysfunction is thought to play an important role in the pathogenesis of HAD. Glutamate neurotoxicity is triggered primarily by massive Ca2+ influx arising from over‐stimulation of the NMDA subtype of glutamate receptors. The underlying mechanisms, however, remain elusive. We have tested the hypothesis that mitochondrial glutaminase in HIV‐infected macrophages is involved in converting glutamine to glutamate. Our results demonstrate that the concentration of glutamate in HIV‐1 infected conditioned media was dependent on glutamine dose, and HIV‐1 infected conditioned medium mediated glutamine‐dependent neurotoxicity. These results indicate HIV‐infection mediates neurotoxicity through glutamate production. In addition, glutamate‐mediated neurotoxicity correlated with caspase activation and neuronal cell cycle re‐activation. Inhibition of mitochondrial glutaminase diminished the HIV‐induced glutamate production, and attenuated NMDA over‐stimulation and subsequent neuronal apoptosis. These data implicate mitochondrial glutaminase in the induction of glutamate‐mediated neuronal apoptosis during HIV‐associated dementia, and provides a possible therapeutic strategy for HAD treatment.
Serotonin‐1A receptor function in the dorsal raphe nucleus following chronic administration of the selective serotonin reuptake inhibitor sertraline
Authors: Rossi Dania V. , Burke Teresa F. , McCasland Melissa , Hensler Julie G.
Published: January 2008

Serotonin‐1A (5‐HT1A) receptors in the dorsal raphe nucleus (DRN) function as somatodendritic autoreceptors, and therefore play a critical role in controlling serotonergic cell firing and serotonergic neurotransmission. We hypothesized that a decrease in the capacity of 5‐HT1A receptors to activate G proteins was a general mechanism by which 5‐HT1A receptors in the DRN are desensitized following chronic administration of selective serotonin reuptake inhibitors (SSRIs). Using in vivo microdialysis, we found that the ability of the 5‐HT1A receptor agonist 8‐hydroxydipropylaminotetralin hydrobromide (8‐OH‐DPAT) (0.025 mg/kg, s.c.) to decrease extracellular 5‐HT levels in striatum was attenuated following chronic treatment of rats with the SSRIs sertraline or fluoxetine. This apparent desensitization of somatodendritic 5‐HT1A autoreceptor function was not accompanied by a decrease in 5‐HT1A receptor sites in the coupled, high‐affinity agonist state as measured by the binding of [3H]8‐OH‐DPAT. In marked contrast to what was observed following chronic administration of fluoxetine, 5‐HT1A receptor‐stimulated [35S]GTPγS binding in the DRN was not altered following chronic sertraline treatment. Thus, desensitization of 5‐HT1A somatodendritic autoreceptor function following chronic sertraline administration appears not to be due to a decrease in the capacity 5‐HT1A receptors to activate G proteins in the DRN. Our findings suggest that the SSRIs may not be a homogeneous class of antidepressant drug with regard to the mechanism by which the function of somatodendritic 5‐HT1A autoreceptors is regulated.
Statins reduce neuronal α‐synuclein aggregation in in vitro models of Parkinson’s disease
Authors: Bar‐On Pazit , Crews Leslie , Koob Andrew O. , Mizuno Hideya , Adame Anthony , Spencer Brian , Masliah Eliezer
Published: January 2008

Aggregation of α‐synuclein (α‐syn) is believed to play a critical role in the pathogenesis of disorders such as dementia with Lewy bodies and Parkinson’s disease. The function of α‐syn remains unclear, although several lines of evidence suggest that α‐syn is involved in synaptic vesicle trafficking probably via lipid binding. Moreover, interactions with cholesterol and lipids have been shown to be involved in α‐syn aggregation. In this context, the main objective of this study was to determine if statins – cholesterol synthesis inhibitors – might interfere with α‐syn accumulation in cellular models. For this purpose, we studied the effects of lovastatin, simvastatin, and pravastatin on the accumulation of α‐syn in a stably transfected neuronal cell line and in primary human neurons. Statins reduced the levels of α‐syn accumulation in the detergent insoluble fraction of the transfected cells. This was accompanied by a redistribution of α‐syn in caveolar fractions, a reduction in oxidized α‐syn, and enhanced neurite outgrowth. In contrast, supplementation of the media with cholesterol increased α‐syn aggregation in detergent insoluble fractions of transfected cells and was accompanied by reduced neurite outgrowth. Taken together, these results suggest that regulation of cholesterol levels with cholesterol inhibitors might be a novel approach for the treatment of Parkinson’s disease.
Brain‐specific carnitine palmitoyl‐transferase‐1c: role in CNS fatty acid metabolism, food intake, and body weight
Authors: Wolfgang Michael J. , Cha Seung Hun , Millington David S. , Cline Gary , Shulman Gerald I. , Suwa Akira , Asaumi Makoto , Kurama Takeshi , Shimokawa Teruhiko , Lane M. Daniel
Published: January 2008

While the brain does not utilize fatty acids as a primary energy source, recent evidence shows that intermediates of fatty acid metabolism serve as hypothalamic sensors of energy status. Increased hypothalamic malonyl‐CoA, an intermediate in fatty acid synthesis, is indicative of energy surplus and leads to the suppression of food intake and increased energy expenditure. Malonyl‐CoA functions as an inhibitor of carnitine palmitoyl‐transferase 1 (CPT1), a mitochondrial outer membrane enzyme that initiates translocation of fatty acids into mitochondria for oxidation. The mammalian brain expresses a unique homologous CPT1, CPT1c, that binds malonyl‐CoA tightly but does not support fatty acid oxidation in vivo, in hypothalamic explants or in heterologous cell culture systems. CPT1c knockout (KO) mice under fasted or refed conditions do not exhibit an altered CNS transcriptome of genes known to be involved in fatty acid metabolism. CPT1c KO mice exhibit normal levels of metabolites and of hypothalamic malonyl‐CoA and fatty acyl‐CoA levels either in the fasted or refed states. However, CPT1c KO mice exhibit decreased food intake and lower body weight than wild‐type littermates. In contrast, CPT1c KO mice gain excessive body weight and body fat when fed a high‐fat diet while maintaining lower or equivalent food intake. Heterozygous mice display an intermediate phenotype. These findings provide further evidence that CPT1c plays a role in maintaining energy homeostasis, but not through altered fatty acid oxidation.
Relaxation induced by red wine polyphenolic compounds in rat pulmonary arteries: lack of inhibition by NO‐synthase inhibitor
Authors: Leblais Véronique , Krisa Stéphanie , Valls Josep , Courtois Arnaud , Abdelouhab Sabrina , Vila Alicia Martin , Mérillon Jean‐Michel , Muller Bernard
Published: January 2008

Some red wine polyphenols exert nitric oxide (NO)‐dependent relaxation in systemic arteries, following activation of endothelial NO synthase (eNOS). In this study, the effect of red wine polyphenols was determined in rat intrapulmonary arteries, and the effect of some of these compounds was compared with the responses obtained in rat aorta. In pulmonary arteries, red wine polyphenolic extract (> 300 μg/mL) exerted relaxation that was not inhibited by the NOS inhibitor Nω‐nitro‐l‐arginine methylester (l‐NAME) or endothelium removal. Among the several fractions obtained from the extract, the one enriched with anthocyanins was less active than fractions containing non‐anthocyanins. Among the latter, the most active for relaxing pulmonary arteries was the one enriched in the stilbene derivative trans‐resveratrol (relaxation for concentration >10 μg/mL). Trans‐piceid, the glucoside derivative of trans‐resveratrol, was almost inactive. Trans‐resveratrol‐induced relaxation, as well as relaxation to the anthocyanin delphinidin, was l‐NAME‐insensitive in pulmonary arteries. In aorta, trans‐resveratrol and trans‐piceid exerted similar effects to those in pulmonary arteries that were also not inhibited by l‐NAME. However, red wine polyphenolic extract and delphinidin induced relaxation of aorta at much lower concentrations (about 10 μg/mL) than in pulmonary arteries, and their effects were inhibited by l‐NAME. These data show differences between small intrapulmonary arteries and systemic conductance arteries in their responses to red wine polyphenols, the major difference being that the relaxant effect of these compounds is not blunted by NOS inhibitor in pulmonary arteries. They suggest that red wine polyphenols act directly on smooth muscle to promote pulmonary artery relaxation.
Drugs and their molecular targets: an updated overview
Authors: Landry Yves , Gies Jean‐Pierre
Published: January 2008

About 330 targets bind approved drugs, 270 encoded by the human genome and 60 belonging to pathogenic organisms. A large number of druggable targets have been recently proposed from preclinical and first clinical data, but a huge reservoir of putative drug targets, possibly several thousands, remains to be explored. This overview considers the different types of ligands and their selectivity in the main superfamilies of drug targets, enzymes, membrane transporters and ion channels, and the various classes of membrane and nuclear receptors with their signalling pathway. Recently approved drugs such as monoclonal antibodies, tyrosine kinase and proteasome inhibitors, and major drugs under clinical studies are reviewed with their molecular target and therapeutic interest. The druggability of emerging targets is discussed, such as multidrug resistance transporters and cystic fibrosis transmembrane conductance regulator (CFTR), hyperpolarization‐activated cyclic nucleotides‐gated (HCN), cyclic nucleotide‐gated (CNG) and transient receptor potential (TRP) ion channels, tumour necrosis factor (TNF) and receptor activator of NFκB (RANK) receptors, integrins, and orphan or recently deorphanized G‐protein‐coupled and nuclear receptors. Large advances have been made in the therapeutical use of recombinant cytokines and growth factors (i.e. tasonermin, TNFα‐1a; becaplermin, platelet‐derived growth factor (PDGF); dibotermin‐alpha, bone morphogenetic proteins (BMP)2; anakinra, interleukin‐1 receptor antagonist protein (IRAP), and in enzyme replacement therapy, i.e. algasidase (alpha‐galactosidase) and laronidase (alpha‐l‐iduronidase). New receptor classes are emerging, e.g. membrane aminopeptidases, and novel concepts are stimulating drug research, e.g. epigenetic therapy, but the molecular target of some approved drugs, such as paracetamol and imidazolines, still need to be identified.
Impact of nevirapine or efavirenz co‐administration on ritonavir‐boosted amprenavir pharmacokinetics in HIV‐infected patients
Authors: Dailly Eric , Raffi François , Biron Charlotte , Allavena C. , Jolliet P.
Published: January 2008

The influence of nevirapine or efavirenz co‐administration on ritonavir‐boosted amprenavir pharmacokinetics was investigated in HIV‐infected patients with a population pharmacokinetic approach. The analysis was performed with a population of 61 patients treated with fosamprenavir/ritonavir (700 mg/100 mg twice daily) combined with nucleoside/nucleotide reverse transcriptase inhibitors ± enfuvirtide and no other antiretroviral drugs (group A, n = 46) or nevirapine (group B, n = 10) or efavirenz (group C, n = 5). No significant increase in amprenavir clearance [mean ± standard deviation: 22.49 ± 10.32 (group A) vs. 21.57 ± 9.62 (group B) vs. 20.15 ± 5.18 (group C) L/h] and no significant decrease in trough amprenavir plasma concentrations [1.75 ± 0.95 (group A) vs. 1.82 ± 0.72 (group B) vs. 1.55 ± 0.66 (group C) mg/L] were found in groups B and C in comparison with group A, although nevirapine and efavirenz are inductors of protease inhibitors metabolism. These results suggest that fosamprenavir/ritonavir should be used at standard doses of 700 mg/100 mg twice daily when combined with efavirenz or nevirapine.
The effects of NG‐nitro‐l‐arginine methyl ester on systolic pressure, diastolic pressure and pulse pressure according to the initial level of blood pressure
Authors: Ruiz Antonio , López Ruth M. , Pérez Teresa , Castillo Carlos , Castillo Enrique F.
Published: January 2008

The objective of this study was to re‐examine whether the effect of the nitric oxide synthesis inhibitor, NG‐nitro‐l‐arginine methyl ester (l‐NAME), on blood pressure depends on peripheral vascular tone. The effects of l‐NAME (10 mg/kg, i.v.) on diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP) and heart rate (HR) were studied in pithed rats. Sal‐pithed rats received 0.9% NaCl, 10 μl/kg/min. Vascular tone was step‐wise increased with 3, 10 and 30 μg/kg/min intravenous phenylephrine infusion (LPhe‐pithed, MPhe‐pithed and HPhe‐pithed rats respectively). l‐NAME elicited vasopressor responses in all the animals studied. l‐NAME increases in SBP and DBP in Sal‐pithed rats were significantly smaller than the ones obtained in phenylephrine infused rats. The increases in DBP elicited by l‐NAME were greater in LPhe‐pithed rats compared with those of MPhe‐pithed and HPhe‐pithed rats (i.e. the step‐wise rises in DBP obtained with phenylephrine were inversely related to the increases in DBP produced by l‐NAME); however, the increases in SBP were similar between these experimental groups. The PP increased during l‐NAME‐induced pressor responses in phenylephrine‐infused rats. l‐NAME increases in PP showed the following order: Sal‐pithed < LPhe‐pithed < MPhe‐pithed ≤ HPhe‐pithed rats. HR was not modified by l‐NAME. In conclusion, the vasopressor responses produced by l‐NAME in pithed rats are influenced by the pre‐existing vasomotor tone in complex form. We did not find a simple positive correlation between the vascular tone or level of arterial pressure, and the magnitude of the diastolic and systolic pressor responses elicited by l‐NAME. Interestingly, the increase in PP induced by l‐NAME was greater in accordance with the increasing value of baseline arterial pressure. NO synthesis inhibition in the arterial endothelium may possibly explain the increase in PP caused by l‐NAME, as resulting from the reduction in proximal conduit artery compliance.
Effects of cooling and warming on 5‐hydroxytryptamine‐ and acetylcholine‐induced contractions of human umbilical vessels: role of nitric oxide
Authors: Atalık K.E. , Kılıç M. , Nurullahoğlu Z.Ü. , Doğan N.
Published: January 2008

The effects of cooling (to 28 °C) and warming (to 41 °C) on the vasoconstrictions induced by 5‐hydroxytryptamine (5‐HT) and acetylcholine (ACh) and the role of nitric oxide in these effects were analyzed in human umbilical artery and vein. 5‐HT (10−9–10−4 m) and ACh (10−9–10−4 m) induced concentration‐dependent contractions at 37, 28 and 41 °C. During cooling, the sensitivity, but not the maximal response, of 5‐HT and ACh was significantly higher than at 37 °C; and during warming, again the sensitivity, but not the maximal response, of both contractile agents was significantly lower than at 37 °C. Neither cooling to 28 °C nor warming to 41 °C, after treatment with NG‐nitro‐l‐arginine methyl esther (l‐NAME, 10−4 m), modify the effect of temperature in both vessels. These results suggest that cooling‐ and warming‐induced responses in human umbilical artery and vein are independent of nitric oxide.
Preen waxes do not protect carotenoid plumage from bleaching by sunlight
Authors: SURMACKI ADRIAN
Published: January 2008

The plumage coloration of wild birds often changes during the breeding season. One of the possible reasons for this is that sunlight, and particularly ultraviolet (UV) wavelengths, degrades the pigments responsible for plumage coloration. It has been suggested that birds may apply preen wax to feathers to protect feathers from bleaching. This hypothesis is tested by exposing carotenoid‐based breast feathers of Great Tits to ambient light, light filtered to exclude UV and darkness. Preen waxes were experimentally removed from feather samples and the effect of light on coloration of treatment and control feathers compared. Ambient light had an effect on feather colour but preen wax did not. Feathers exposed to sun gradually became less saturated and hues shifted towards shorter wavelengths. This was not apparent in control feathers kept in darkness. Feathers exposed to full‐spectra sunlight faded more than those that were kept in light with UV wavelengths removed. There was a decrease in brightness of feathers in both experimental and control groups, which was assumed to be an effect of dirt accumulation. This experiment confirmed earlier suspicions regarding the detrimental effects of UV irradiation on carotenoid‐based coloration of avian feathers but failed to show any protective function of preen waxes. The possible consequences of these mechanisms of colour change for birds with regard to mating strategies are discussed.
Evidence that age‐related changes in p38 MAP kinase contribute to the decreased steroid production by the adrenocortical cells from old rats
Authors: Abidi Parveen , Leers‐Sucheta Susan , Cortez Yuan , Han Jiahuai , Azhar Salman
Published: January 2008

The current studies were initiated to investigate whether excessive oxidative stress exerts its antisteroidogenic action through modulation of oxidant‐sensitive mitogen‐activated protein kinase (MAPK) signaling pathways. Western blot analysis indicated that aging caused increased phosphorylation and activation of rat adrenal p38 MAPK, but not the ERK1/2 or JNK1/2. Lipid peroxidation measurements (an index of cellular oxidative stress) indicated that adrenal membranes from young animals contained only minimal levels of endogenous thiobarbituric acid‐reactive substances (TBARS), and exposure of membranes to enzymatic and non‐enzymatic pro‐oxidants enhanced TBARS formation approximately 12‐ and 20‐fold, respectively. The adrenal membranes from old animals showed much more susceptibility to lipid peroxidation and exhibited roughly 4‐ to 6‐fold higher TBARS formation than young controls both under basal conditions and in response to pro‐oxidants. Qualitatively similar results were obtained when lipid peroxide formation was measured using a sensitive FOXRS (ferrous oxidation‐xylenol orange‐reactive substances) technique. We next tested whether aging‐induced excessive oxidative insult alters steroidogenesis through modulation of MAPK signaling pathway. Treatment of adrenocortical cells from old rats with specific p38 MAPK inhibitors restored Bt2cAMP‐stimulated steroidogenesis ~60–70% of the value seen in cells of young animals. Likewise, pretreatment of cells with reactive oxygen species (ROS) scavengers MnTMPyP and N‐acetyl cysteine also partially rescued age‐induced loss of steroid production. In contrast, simultaneous treatment of cells with ROS scavengers and p38 MAPK inhibitor did not produce any additional effect suggesting that both types of inhibitors exert their stimulatory action through inhibition of p38 MAPK activation. Collectively, these results indicate that p38 MAPK functions as a signaling effector in oxidative stress‐induced inhibition of steroidogenesis during aging.
Architectural changes in the thymus of aging mice
Authors: Aw Danielle , Silva Alberto B. , Maddick Mandy , Von Zglinicki Thomas , Palmer Donald B.
Published: January 2008

Age‐associated thymic involution is one of the most dramatic and ubiquitous changes in the immune system, although the precise mechanisms involved still remain obscured. Several hypotheses have been proposed incorporating extrinsic and intrinsic factors, however, changes in the thymic microenvironment itself is one of the least investigated. We therefore decided to undertake a detailed histological examination of the aging thymus in order to elucidate possible mechanisms of thymic atrophy. This investigation provides insight into the changes within the murine thymus with age, demonstrating a new approach to quantify protein expressional differences while preserving the thymic architecture. There is a decline in expression of thymic epithelial cell‐specific makers and an increase in fibroblast content in the aging mouse thymus. This is concurrent with a disorganization of the thymic compartments, a morphological transformation within the epithelial cells and alterations of their archetypal staining patterns. Furthermore, this is linked to a rise in apoptotic cells and the novel finding of increased senescence in the thymus of older mice that appears to be colocalized in the epithelial compartment. These changes within the thymic epithelial cells may be in part accountable for thymic atrophy and responsible for the decline in T‐cell output.
Valproic acid extendsCaenorhabditis eleganslifespan
Authors: Evason Kimberley , Collins James J. , Huang Cheng , Hughes Stacie , Kornfeld Kerry
Published: January 2008

Aging is an important biological phenomenon and a major contributor to human disease and disability, but no drugs have been demonstrated to delay human aging.Caenorhabditis elegansis a valuable model for studies of animal aging, and the analysis of drugs that extend the lifespan of this animal can elucidate mechanisms of aging and might lead to treatments for age‐related disease. By testing drugs that are Food and Drug Administration approved for human use, we discovered that the mood stabilizer and anticonvulsant valproic acid (VA) extendedC. eleganslifespan. VA also delayed age‐related declines of body movement, indicating that VA delays aging. Valproic acid is a small carboxylic acid that is the most frequently prescribed anticonvulsant drug in humans. A structure–activity analysis demonstrated that the related compound valpromide also extends lifespan. Valproic acid treatment may modulate the insulin/IGF‐1 growth factor signaling pathway, because VA promoted dauer larvae formation and DAF‐16 nuclear localization. To investigate the mechanism of action of VA in delaying aging, we analyzed the effects of combining VA with other compounds that extend the lifespan ofC. elegans. Combined treatment of animals with VA and the heterocyclic anticonvulsant trimethadione caused a lifespan extension that was significantly greater than treatment with either of these drugs alone. These data suggest that the mechanism of action of VA is distinct from that of trimethadione, and demonstrate that lifespan‐extending drugs can be combined to produce additive effects.
The Liquidity Effect in the Federal Funds Market: Evidence at the Monthly Frequency
Authors: CARPENTER SETH , DEMIRALP SELVA
Published: January 2008

In this paper, we argue that much of the research into the link between money and interest rates suffers from misspecification. The measure of money and the measure of interest rates are not always well matched. In examining the transmission of monetary policy, we show that using an appropriate measure of money, Federal Reserve balances, and the appropriate interest rate, the federal funds rate, a clear liquidity effect exists. Furthermore, we explain how a lack of a clear institutional understanding may have contributed to the finding of a “liquidity puzzle” in the past.
Consumers' Use of Debit Cards: Patterns, Preferences, and Price Response
Authors: BORZEKOWSKI RON , ELIZABETH K. KISER , SHAISTA AHMED
Published: January 2008

Debit card use at the point of sale has grown dramatically in recent years in the United States and now exceeds the number of credit card transactions. However, many questions remain regarding patterns of debit card use, consumer preferences when using debit, and how consumers might respond to explicit pricing of card transactions. Using a new nationally representative consumer survey, this paper describes the current use of debit cards by U.S. consumers, including how demographics affect use. In addition, consumers' stated reasons for using debit cards are used to analyze how consumers substitute between debit and other payment instruments. We also examine the relationship between household financial conditions and payment choice. Finally, we use a key variable on bank‐imposed transaction fees to analyze price sensitivity of card use, and find a 12% decline in overall use in reaction to a mean 1.8% fee charged on certain debit card transactions; we believe this represents the first microeconomic evidence in the United States on price sensitivity for a card payment at the point of sale.
Information Contagion and Bank Herding
Authors: ACHARYA VIRAL V. , YORULMAZER TANJU
Published: January 2008

We show that the likelihood of information contagion induces profit‐maximizing bank owners to herd with other banks. When bank loan returns have a common systematic factor, the cost of borrowing for a bank increases when there is adverse news on other banks since such news conveys adverse information about the common factor. The increase in a bank's cost of borrowing relative to the situation of good news about other banks is greater when bank loan returns have less commonality (in addition to the systematic risk factor). Hence, banks herd and undertake correlated investments so as to minimize the impact of such information contagion on the expected cost of borrowing. Competitive effects such as superior margins from lending in different industries mitigate herding incentives.
Percutaneous Treatment for Mitral Regurgitation: The QuantumCor System
Authors: HEUSER RICHARD R. , WITZEL THOMAS , DICKENS DUANE , TAKEDA PATRICIA A.
Published: January 2008

Aims:

Percutaneous edge‐to‐edge techniques and annuloplasty have been used to treat mitral regurgitation (MR). However, neither intervention can be performed reliably a second time and, with annuloplasty, a foreign body is left behind. The mitral and tricuspid annuli are areas of dense collagen (

Fig. 1

); treatment with radiofrequency (RF) energy in sheep reduces their size, and can be repeated without affecting the coronary sinus. RF energy may also be used in leaflet procedures. Our aim was to improve mitral valve competence using techniques that can be incorporated into a minimally invasive approach.

This trichrome stain slide shows the amount of collagen present in the mitral annulus (in green).

image

Methods:

In open‐heart procedures in 16 healthy sheep (6 with naturally occurring MR), we used a malleable probe (QuantumCor, Inc., Lake Forest, CA) that conforms to the annular shape to deliver RF energy via a standard generator to replicate a surgical mitral annular ring. Four segments of the posterior mitral valve annulus were treated while on cardiopulmonary support via a left thoracotomy with access via the atrial appendage. Seven sheep were followed chronically.

Results:

All sheep underwent intracardiac echocardiography (ICE) or direct circumferential measurement of the mitral annulus before and after RF therapy. RF therapy was administered in less than 4 minutes in each case, and the mean anteroposterior (AP) annular distance was reduced by a mean of 5.75 ± 0.86 mm (23.8% reduction, P< 0.001). In the 6 sheep with nonischemic MR, regurgitation was eliminated. Acute histopathology (HP) demonstrated no damage to the leaflets, coronary sinuses, or coronary arteries. At 30 days, the AP distance continued to be reduced in the 7 surviving sheep (mean 5.0 ± .6 mm, 21.4% reduction, P< 0.001).

Conclusions:

In a sheep model, RF energy applied for less than 4 minutes per case at subablative temperatures in four quadrants of the posterior mitral valve annulus reduced the AP and circumferential annular distances significantly, and eliminated nonischemic MR. Results will need to be confirmed in follow‐up studies to determine safety and efficacy. RF energy administered as a novel, percutaneous method of mitral valve annuloplasty may have the potential to reduce morbidity and mortality associated with current surgical techniques.
Left Ventricular Function by Pressure‐Volume Loop Analysis before and after Percutaneous Repair of Large Atrial Septal Defects
Authors: LIM D. S. , GUTGESELL HOWARD P. , ROCCHINI ALBERT P.
Published: January 2008

Aim

The intent of the present study was to evaluate changes in ventricular function with percutaneous closure of atrial septal defect (ASD), as it is associated with alterations in ventricular loading and function. Transcatheter occlusion of ASD imparts acute changes in volume loading of the left ventricle (LV) that obscures measurement of ventricular function by load‐dependent indices. To differentiate between changes in ventricular loading and function, load‐independent indices of ventricular function must be utilized.

Methods

During transcatheter occlusion of ASD, subjects underwent measurement of LV pressure and volume by the conductance catheter method. Load‐dependent indices of ventricular function included: systolic and diastolic pressures, +dP/dtmax, and −dP/dtmax. Load‐independent indices included: elastance and tau, the preload‐independent time constant ofisovolumic relaxation. To obtain elastance, afterload was augmented by phenylephrine bolus pre‐ and post‐device occlusion.

Results

In total, 29 patients (age 2–79 years) underwent ASD device occlusion (device size 12–38 mm, median 28 mm). Load‐dependent indices were obtained in all, and satisfactory pressure‐volume loops in 11. At baseline, LV end‐diastolic pressure was 5–23 mmHg (13 ± 5 mmHg) and tau was 31 ± 6 ms. Postclosure of the ASD, LV systolic and diastolic pressures rose by 10 ± 11 mmHg and 5 ± 3 mmHg, respectively (P < 0.05), and +dP/dtmax rose from 1,288 ± 313 mmHg/sec to 1,415 ± 465 mmHg/sec (P < 0.05), but −dP/dtmax was unchanged. Elastance significantly improved (9.4 ± 8.3 mmHg/mL vs. 13.0 ± 7.3 mmHg/mL, P < 0.05) and tau was unchanged.

Conclusions

Transcatheter occlusion of ASD is associated with acute improvement in load‐independent indices of systolic function in this cohort, without significant worsening of the preload‐independent index of diastolic function. (J Interven Cardiol 2014;27:204–211)
Infrared Heating in Food Processing: An Overview
Authors: Krishnamurthy Kathiravan , Khurana Harpreet Kaur , Soojin Jun , Irudayaraj Joseph , Demirci Ali
Published: January 2008

ABSTRACT: Infrared (IR) heating provides significant advantages over conventional heating, including reduced heating time, uniform heating, reduced quality losses, absence of solute migration in food material, versatile, simple, and compact equipment, and significant energy saving. Infrared heating can be applied to various food processing operations, namely, drying, baking, roasting, blanching, pasteurization, and sterilization. Combinations of IR heating with microwave heating and other common conductive and convective modes of heating have been gaining momentum because of increased energy throughput. This article reviews aspects of IR heating and presents a theoretical basis for IR heat processing of food materials and the interaction of IR radiation with food components. The effect of IR on food quality attributes is discussed in the context of samples and process parameters. Applications of IR heating in food processing operations and future research potential are also reviewed.
Functional and Edible Uses of Soy Protein Products
Authors: Singh Preeti , Kumar R. , Sabapathy S. N. , Bawa A. S.
Published: January 2008

ABSTRACT:  Consumers are becoming increasingly interested in healthful foods and are open to soy protein ingredients. Soybeans as food are very versatile and a rich source of essential nutrients. They are also an excellent source of good‐quality protein, comparable to other protein foods, and suitable for all ages. Adverse nutritional and other undesirable effects followed by the consumption of raw soybean meal have been attributed to the presence of endogenous inhibitors of digestive enzymes and lectins, as well as poor digestibility. To improve the nutritional quality of soy foods, inhibitors and lectins are generally inactivated by heat or eliminated by fractionation during food processing. Soybeans provide an alternative source of protein for people who are allergic to milk protein. Soy protein is highly digestible (92% to 100%) and contains all essential amino acids. Although relatively low in methionine, it is a good source of lysine. Soy‐protein products contain a high concentration of isoflavones, up to 1 g/kg. Increased acceptance of soy proteins is due to unmatched qualities like good functional properties in food applications, high nutritional quality, abundance, availability, and low cost. At present the various forms of soy proteins are primarily utilized for their functional effects rather than their nutritional properties. This article summarizes the integrated overview of the widely available, scattered information about the nutritional and functional uses of the soy proteins when applied in food systems and intends to present the most current knowledge with an interest to stimulate further research to optimize their beneficial effects.
The Carotenoid Pigment Zeaxanthin—A Review
Authors: Sajilata M.G. , Singhal R.S. , Kamat M.Y.
Published: January 2008

ABSTRACT:  Scientific evidence linking several diseases with diet has brought to light the beneficial effects of a number of natural food ingredients. Zeaxanthin is one such natural pigment emphasized for its critical role in the prevention of age‐related macular degeneration (AMD), the leading cause of blindness. The review highlights zeaxanthin as a carotenoid pigment with promising nutraceutical implications, and enumerates the important plant and microbial sources for its production, the absorptive pathway of zeaxanthin in human system, and methods to assess its bioavailability besides other relevant aspects.
Kinetic Modeling of Food Quality: A Critical Review
Authors: Van Boekel Martinus A.J.S.
Published: January 2008

ABSTRACT: This article discusses the possibilities to study relevant quality aspects of food, such as color, nutrient content, and safety, in a quantitative way via mathematical models. These quality parameters are governed by chemical, biochemical, microbial, and physical changes. It is argued that the modeling of such quality aspects is in fact kinetic modeling. Therefore, attention is paid to chemical kinetics, and its possibilities and limitations are discussed when applied to changes occurring in foods. The discussion is illustrated with examples from the literature. A major difficulty is that principles from chemical kinetics are strictly speaking only valid for simple elementary reactions, and foods are all but simple. Interactions in the food matrix and variability are 2 complicating factors. It is discussed how this difficulty can be tackled, and research priorities are suggested to come to better models in food science, and thereby to a better control of food quality.
Invasion biology and host specificity of the grapevine yellows disease vector Hyalesthes obsoletus in Europe
Authors: Johannesen Jes , Lux Benjamin , Michel Kristina , Seitz Alfred , Maixner Michael
Published: January 2008

Within the past 10 years, the yellows disease ‘bois noir’ (BN) has become one of the commercially most important diseases of grapevine [Vitis vinifera L. (Vitaceae)] in Europe. Infection pressure is caused by phytoplasmas of the stolbur 16SrXII‐A group that are transmitted by a planthopper vector, Hyalesthes obsoletus Signoret (Homoptera: Auchenorrhyncha). Infestation happens as an accidental side‐effect of the feeding behaviour of the vector, as vector and pathogen proliferation is dependent on other plants. In Germany, the increase of BN is correlated with the use of a new host plant by the vector, increase in abundance of the vector on the new host plant, and dissemination of host plant‐specific pathogen strains. In this article, we investigate geographic and host‐associated range expansion of the vector. We test whether host‐plant utilization in Germany, hence the increase in BN, is related to genetic host races of the vector and, if so, whether these have evolved locally or have immigrated from southern populations that traditionally use the new host plant. The genetic population analysis demonstrates a recent expansion and circum‐alpine invasion of H. obsoletus into German and northern French wine‐growing regions, which coincides with the emergence of BN. No H. obsoletus mitochondrial DNA haplotype host‐plant affiliation was found, implying that the ability to use alternative host plants is genetically intrinsic to H. obsoletus. However, subtle yet significant random amplified polymorphic DNA (RAPD) genetic differentiation was found among host plant populations. When combined, these results suggest that a geographic range expansion of H. obsoletus only partly explains the increase of BN, and that interactions with host plants also occur. Further possible beneficial factors to H. obsoletus, such as temperature increase and phytoplasma interactions, are discussed.
Negotiation and Nonviolent Action: Interacting in the World of Conflict
Authors: Finnegan Amy C. , Hackley Susan G.
Published: January 2008

Negotiation and nonviolent action are arguably the two best methods humanity has developed for engaging constructively with conflict. Both have played central roles in helping manage or resolve seemingly intractable conflicts, sometimes sequentially and sometimes in tandem. But experts and practitioners in both fields often underestimate the relevance and effectiveness of the other. This article explores the interface between the fields of negotiation and nonviolent action, their mutual commitment to engage constructively with conflict, and the concern both methods share for leverage, power, and strategic preparation and action. After examining the shared linkages, this article highlights how the two fields have synergistic qualities when utilized together in the same conflict. Using examples from a diverse set of conflicts, the overlap explored in this article lays an important foundation for the future convergence of the two fields.
A Conceptual Framework for Modeling Automated Negotiations in Multiagent Systems
Authors: Ayatollahzadeh Shirazi Mohammad Reza , Barfouroush Ahmad Abdollahzadeh
Published: January 2008

In fully automated e‐negotiation all involved parties are software agents, so negotiation takes place in a multiagent system between software agents that have been developed as a computer system for automating tasks in a specific application domain. A multiagent system is a group of agents that interact and cooperate with each other to fulfill their objectives or to improve their performance. How do these agents negotiate with each other to manage their task interdependencies? What negotiation mechanisms are needed? These are important questions.

In this article, we present a conceptual framework for modeling and developing automated negotiation systems. This framework represents and specifies all the necessary concepts and entities for developing a negotiation system as well as the relationships among these concepts. This framework can also be used to model human negotiations scenarios for analyzing these types of negotiations and simulating them with multiagent systems. The work reported in this article is the first unified framework that represents all the needed elements for modeling and developing automated negotiation systems and existing relationships between them.
New Technology Meets an Old Teaching Challenge: Using Digital Video Recordings, Annotation Software, and Deliberate Practice Techniques to Improve Student Negotiation Skills
Authors: Williams Gerald R. , Farmer Larry C. , Manwaring Melissa
Published: January 2008

There is a world of difference between teaching negotiation theory, which pertains to conceptual understanding, and teaching negotiation skills, which pertain to actual behavior in real‐world situations. The principle of reflective practice is widely used for theoretical instruction. Deliberate practice, however, is a more powerful model for skills training. Cognitive scientists have discovered that subjects will learn skills best when they perform well‐defined tasks at appropriate levels of difficulty, and when they are given immediate feedback, an opportunity to correct their errors, and an opportunity to practice until the tasks become routine.

To satisfy the deliberate practice conditions for large graduate‐level negotiation courses (some as large as seventy students), students were assigned to use webcams with their laptop computers to video record their negotiation exercises. Before each exercise, students were assigned to prepare for and to concentrate on performing two or three well‐defined tasks. Students reviewed these recordings and commented on their performances in a journal before uploading the videos and journals to an assigned network folder. The instructor and teaching assistants then reviewed the journals and specified portions of the videos and provided individual written feedback to the students.

The instructors found that student negotiating skills have improved significantly using this new system. In comparison with earlier semesters, students also felt they were involved in a more intense and personal learning experience. A majority of students reported they intend to apply the principles of deliberate practice in their professional lives after graduation. The authors have found this method continues to challenge their ability to identify and describe the skills used by expert negotiators.

As an addition to this new methodology, two of the authors have spearheaded the development of video annotation software, known as “MediaNotes,” to help students and instructors review, comment upon, and learn from video recordings of negotiations. Based on their experiences using the software to support deliberate practice, the authors expect this tool to initiate a significant advance in our ability to recognize and describe expert negotiation behavior and in students’ ability to improve their negotiating skills.
Reduced subjective quality of life in persons at risk for psychosis
Authors: Ruhrmann S. , Paruch J. , Bechdolf A. , Pukrop R. , Wagner M. , Berning J. , Schultze‐Lutter F. , Janssen B. , Gaebel W. , Möller H.‐J. , Maier W. , Klosterkötter J.
Published: January 2008

Objective:  Subjective quality of life (sQoL) and potentially contributing factors were investigated in individuals putatively in an early (EIPS) or late initial prodromal state (LIPS) and healthy controls (HC).

Method:  Participants comprised 58 EIPS individuals, 157 LIPS individuals and 87 HC individuals. sQoL was assessed together with locus of control (LoC), coping, demography and psychopathology.

Results:  Putatively prodromal groups exhibited markedly lower sQoL than HC (all domains P < 0.00001). EIPS and LIPS individuals did not differ significantly. Depression was the most consistent explaining variable of sQoL in EIPS and LIPS individuals. In EIPS individuals, LoC emerged as an additional predictor.

Conclusion:  Individuals at risk for psychosis experienced a marked impairment of sQoL across all domains. This was evident even in the early state, showed no significant further deterioration during the late state and was predominantly explained by non‐specific symptoms.