bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐Fat High‐Energy Feeding Impairs Fasting Glucose and Increases Fasting Insulin Levels in the Göttingen Minipig
Authors: LARSEN MARIANNE OLHOLM , ROLIN BIDDA , WILKEN MICHAEL , CARR RICHARD DAVID , SVENDSEN OVE
Published: July 2010

Abstract: High‐fat diet and obesity are known to be of major importance for development of type 2 diabetes in humans. High‐fat feeding can induce syndromes of glucose intolerance and/or insulin resistance in several species, and the Göttingen minipig might be a useful model for studying the effect of dietary high‐fat intake and obesity on glucose homeostasis and the susceptibility to diabetes. The present study was designed as a pilot study to investigate the effects of obesity caused by high‐fat high‐energy feeding on oral and intravenous glucose tolerance. Male Göttingen minipigs were fed a control diet (CD) or a high‐fat high‐energy diet (HFD) for 3 months. Body weight (32.6 ± 2.4 kg vs. 24.9 ± 0.5 kg, p < 0.001) and total (13.2 ± 3.2% vs. 6.1 ± 0.5%, p= 0.002) and truncal (11.0 ± 3.9% vs. 1.8 ± 1.1%, p= 0.001) fat percent were increased significantly, whereas relative lean body mass was decreased (84.8 ± 3.3% vs. 91.9 ± 0.5%, p= 0.002) in the HFD group compared to CD. Fasting plasma glucose (4.3 ± 0.4 mM vs. 3.6 ± 0.3 mM, p= 0.023) and insulin (80 ± 23 pM vs. 23 ± 21 pM, p= 0.012) were increased in the HFD group compared to CD, but oral glucose tolerance was not significantly changed. Insulin responses to intravenous glucose were increased (6741 ± 2538 vs. 3938 ± 771 pM 3 min, p= 0.050), while glucose clearance was not changed by HFD vs. CD, thus indicating insulin resistance. In conclusion, changes in body weight and composition, resulting in minor abnormalities in glucose tolerance and insulin sensitivity, characterized by slight hyperglycemia and compensatory hyperinsulinemia, can be induced in the male Göttingen minipig by high‐fat high‐energy feeding for 3 months. This approach seems to be an interesting and promising method for establishment of a nonrodent model of insulin resistance or type 2 diabetes.
Opposing Effects of Fatty Acids and Acyl‐CoA Esters on Conformation and Cofactor Recruitment of Peroxisome Proliferator‐Activated Receptors
Authors: JØRGENSEN CLAUS , KROGSDAM ANNE‐M. , KRATCHMAROVA IRINA , WILLSON TIMOTHY M. , KNUDSEN JENS , MANDRUP SUSANNE , KRISTIANSEN KARSTEN
Published: July 2010

Abstract: The peroxisome proliferator‐activated receptors (PPARs) bind and are activated by a variety of fatty acids and derivatives thereof. Agonist binding enhances PPAR‐mediated transactivation via release of corepressors and recruitment of coactivator complexes. Recently, we and others have reported that acyl‐CoA esters act as PPAR antagonists in vitro. Here, we show that the binding of the nonhydrolyzable acyl‐CoA analogue, S‐hexadecyl‐CoA, differentially affected conformation and coactivator recruitment of the individual PPAR subtypes. In protease protection assays, S‐hexadecyl CoA increased the sensitivity of PPARα and PPARδ towards chymotrypsin, whereas the action of chymotrypsin on PPARγ was only marginally affected, suggesting distinct subtype‐dependent differences in the effects of S‐hexadecyl‐CoA on conformation of the PPARs. In keeping with these findings, S‐hexadecyl‐CoA abrogated ligand‐induced recruitment of coactivators to PPARα and PPARδ, whereas coactivator recruitment to PPARγ was unaffected by S‐hexadecyl‐CoA.
Electrical Stimulation Improves Insulin Responses in a Human Skeletal Muscle Cell Model of Hyperglycemia
Authors: AAS VIGDIS , TORBLÅ SIRI , ANDERSEN MERETHE H. , JENSEN JØRGEN , RUSTAN ARILD CHR.
Published: July 2010

Abstract: Myoblasts from human skeletal muscle were isolated from needle biopsy samples of the vastus lateralis of young and healthy volunteers. Contaminating fibroblasts were removed, and myoblasts were fused into differentiated multinucleated myotubes. These myotubes manifested both basal and insulin‐stimulated (1‐100 nM) glucose transport and glycogen synthesis. Insulin increased 2‐deoxyglucose uptake by 1.4‐fold and glycogen synthesis by 2.1‐fold. Measurements of impedance of cell‐covered gold electrodes (ECIS system) showed increased micromotion of caffeine‐stimulated cells, showing their ability to contract. Acute electrical stimulation of the myotubes increased 2‐deoxyglucose uptake by about 30%. Treatment with high glucose concentrations (10‐20 mM) for 2‐8 days reduced both basal and insulin‐stimulated glucose uptake. Maximal effect was seen after 2 days of treatment with 20 mM glucose. Baseline glucose uptake and glycogen synthesis were reduced by 35%, insulin‐stimulated glucose uptake by 25%, and insulin‐stimulated glycogen synthesis by 39%. Total cell content of glycogen was not changed by hyperglycemia. The insulin‐stimulated glucose uptake in hyperglycemia‐treated cells was improved by electrical stimulation of the cells. In conclusion, a model of hyperglycemia has been established, and electrical stimulation improved insulin responses.
Acute Elevation of NEFA Causes Hyperinsulinemia without Effect on Insulin Secretion Rate in Healthy Human Subjects
Authors: BALENT BEATE , GOSWAMI GAYOTRI , GOODLOE GEORGE , ROGATSKY EDUARD , RAUTA OLIMPIA , NEZAMI ROBERT , MINTS LISA , ANGELETTI RUTH HOGUE , STEIN DANIEL T.
Published: July 2010

Abstract: Increased circulating levels of nonesterified free fatty acids (NEFA) have been observed in such hyperinsulinemic states as obesity, impaired glucose tolerance, diabetes, and dyslipidemia where they have been causally linked to the development of insulin resistance and hyperinsulinemia. The concentration of NEFA in plasma is believed to have direct modifying effects on insulin secretion and clearance. It remains controversial whether acute increases in NEFA potentiate insulin secretion in human subjects. We studied the effect of an acute elevation of NEFA during lipid‐heparin infusion compared to a glycerol‐only control on glucose‐stimulated insulin secretion and clearance during a 120‐min hyperglycemic (10 mM) clamp in 7 healthy normoglucose‐tolerant volunteers. The metabolic clearance rate of C‐peptide (MCRCP) was measured in each subject during the study by simultaneous infusion of C‐peptide. Insulin secretion rate (ISR) was calculated from deconvolution of C‐peptide data after correction for the rate of C‐peptide infusion. Clearance rate of insulin (MCRINS) was calculated based upon endogenous ISR. Plasma glucose (mg/dL): basal (90‐115 min) 90.2 ± 2.8 vs. 90.2 ± 2.3; clamp (150‐240 min) 180.5 ± 2.8 vs. 180.9 ± 1.3. Plasma insulin (pmol/L): prebasal (fasting) 29.6 ± 10.0 vs. 29.8 ± 10.6; basal (90‐115 min) 30.1 ± 9.2 vs. 34.5 ± 12.1; second phase clamp (210‐240 min) 127.6 ± 18.2 vs. 182.5 ± 17.3*. Plasma NEFA (mM): prebasal 0.47 ± 0.08 vs. 0.52 ± 0.09; basal 0.35 ± 0.05 vs. 0.98 ± 0.02*; clamp (122‐240 min) 0.06 ± 0.02 vs. 0.77 ± 0.06*. ISR (pmol/min): prebasal 72.7 ± 7.5 vs. 72.0 ± 7.9; second phase clamp (210‐240 min) 268.5 ± 27.2 vs. 200.2 ± 23.7. MCRINS (mL/min): prebasal 3393 ± 488 vs. 3370 ± 511; clamp 2284 ± 505 vs. 1214 ± 153* (*p < 0.05 glycerol vs. intralipid/heparin). This study demonstrates that acute NEFA elevation causes hyperinsulinemia due to a significant decrease in systemic insulin clearance without increasing rates of insulin secretion.
Detection of a Promoter Polymorphism in the Gene of Intestinal Fatty Acid Binding Protein (I‐FABP)
Authors: GESCHONKE K. , KLEMPT M. , LYNCH N. , SCHREIBER S. , FENSELAU S. , SCHREZENMEIR J.
Published: July 2010

Abstract: Postprandial fat absorption is supposed to be a major factor in the development of the metabolic syndrome. In recent years, the assimilation of plasma triglycerides has been the focus of several groups, revealing a number of specific fat or fatty acid transporters. The intestinal fatty acid binding protein, I‐FABP‐2, participates in the absorption of nutritional fats. The influence of a coding polymorphism has been investigated intensively. However, it remains still unclear whether this polymorphism has a major impact on postprandial TG levels in humans. We found a polymorphism in the promoter of FABP‐2, which might involve the retinoid receptor in the transcriptional activity. In functional analysis, we have been able to demonstrate that the various promoter alleles develop different activities in the human intestinal epithelial cells and that the postprandial appearance of plasma TGs in healthy subjects also depends on their genotype. Since the distribution of the identified promoter polymorphism does not differ in subjects suffering from type 2 diabetes, the overall influence on the development of the metabolic syndrome seems to be minor.
Association of Insulin Gene VNTR Polymorphism with Polycystic Ovary Syndrome
Authors: VANKOVÁ MARKÉTA , VRBÍKOVÁ JANA , HILL MARTIN , CINEK ONDREJ , BENDLOVÁ BELA
Published: July 2010

Abstract: Variability in the number of tandem repeats of the insulin gene (INS VNTR) is known to influence several phenotypes, including polycystic ovary syndrome (PCOS), diabetes mellitus type 1, diabetes mellitus type 2, and birth weight. The presence of the class III allele of INS VNTR has been reported to be protective in diabetes mellitus type 1, but in contrary it increases the disease risk of PCOS and diabetes mellitus type 2. PCOS is a very common endocrinopathy in women of reproductive age. The etiology of PCOS is uncertain, but family history of this syndrome suggests a major genetic cause. The aim of this pilot study was to investigate the possible association of INS VNTR polymorphism with PCOS in Czech women. In PCOS, significantly higher WHR, BMI, G0, G180, I30, Cp0, Cp30, Cp60, AUC‐I, AUC‐Cp, and insulinogenic index and significantly lower AUC‐G/AUC‐I were found. No significant differences in INS VNTR genotype, phenotype, or allele frequencies were found between PCOS and controls. In spite of several differences in anthropometric and biochemical parameters (abdominal fat localization, increased β‐cell function, and lower insulin sensitivity in PCOS women), no effect of INS VNTR polymorphism was found on insulin secretion, insulin action, or any other screened parameter.
Influence of Na/Ca Exchange Stoichiometry on Model Cardiac Action Potentials
Authors: NOBLE DENIS
Published: July 2010

Abstract: Cardiac action potential simulations were done with the stoichiometry of the Na/Ca exchanger set a 4: 1. Using the Hilgemann‐Noble (1987) model, this stoichiometry reduces the resting potential unless regulation by intracellular calcium is incorporated. The Kd required for such regulation is consistent with current experimental estimates of this parameter.
The Cardiac Sodium‐Calcium Exchanger Associates with Caveolin‐3
Authors: BOSSUYT JULIE , TAYLOR BONNIE E. , JAMES‐KRACKE MARILYN , HALE CALVIN C.
Published: July 2010

Abstract: The cardiac Na/Ca exchanger's (NCX1) role in calcium homeostasis during myocardial contractility makes it a possible target of signaling factors regulating inotropy. Caveolae, structured invaginations of the plasmalemma, are known to concentrate a wide variety of signaling factors. The predominant coat proteins of caveolae, caveolins, dock to and regulate the activity of these signaling factors and other proteins through interaction with their scaffolding domain. In this study we investigated the interaction of NCX1 with caveolin proteins. Western blots of bovine cardiac sarcolemmal vesicles revealed the presence of caveolin‐1, ‐2, and ‐3. Immunoprecipitation of detergent‐solubilized vesicle proteins with either NCX1 or caveolin‐3 antibodies indicated that NCX1 coprecipitates with caveolin‐3, but not with caveolin‐1 and ‐2. Functional disruption of caveolae, by β‐cyclodextrin treatment of vesicles, diminished coprecipitation of caveolin‐3 and NCX1 activity. NCX1 has five potential caveolin‐binding motifs, two of which are in the transporter's exchange inhibitory peptide (XIP) domain. The presence of 50 mM XIP peptide enhanced coprecipitation of caveolin‐3 with NCX1 independent of calcium concentration. We conclude that NCX1 associates specifically with caveolin‐3. Partitioning of NCX1 in caveolae has implications for temporal and spatial regulation of excitation‐contraction and ‐relaxation coupling in cardiac myocytes.
Intracellular Ionic and Metabolic Regulation of Squid Nerve Na+/Ca2+ Exchanger
Authors: DIPOLO REINALDO , BEAUGÉ LUIS
Published: July 2010

Abstract: Intracellular Na+ and H+ synergistically inhibit the squid Na+/Ca2+ exchanger by reducing the affinity for Ca2+ of its regulatory site. MgATP antagonizes H+i and Na+i inhibition; this effect must occur through a phosphorylation‐dephosphorylation process, because exogenous protein phosphatases prevent MgATP activation of the exchanger. Protection by ATP against H+i and Na+i inhibition happens by decreasing the apparent affinity for the synergistic binding of these cations to the carrier. In this way ATP modifies the apparent affinity for Ca2+ of its regulatory site. Mg2+ ions play an important role in the process because they are essential for ATP activation of Na+/Ca2+ exchange but can also promote deactivation of the ATP upregulated exchanger. At constant [ATP], activation at low [Mg2+]i is followed by deactivation as [Mg2+]i is increased. The most likely explanation for deactivation is stimulation of endogenous phosphatases. We developed a kinetic model that predicts all H+i, Na+i, and MgATP described above. This scheme includes the following conditions: (i) The binding of Ca2+ to the regulatory site is essential for the binding of Na+i or Ca2+i to the transporting sites. (ii) The binding of a first H+i to the carrier displaces Ca2+i from its regulatory site and allows binding of one Na+ forming a H.E1.Na complex. The H.E1.Na complex can bind a second H+i forming a dead‐end inhibitory H2.E1.Na complex. (iii) MgATP, through an unspecified phosphorylation process, decreases the apparent affinity for the synergistic H+i and Na+i binding to the carrier.
K+‐Dependent Na+/Ca2+ Exchangers in the Brain
Authors: LYTTON JONATHAN , LI XIAO‐FANG , DONG HUI , KRAEV ALEXANDER
Published: July 2010

Abstract: Sodium‐calcium exchange was first characterized in heart myocytes and squid axon more than 3 decades ago. Since then, it has been appreciated that functioning of the Na/Ca exchanger molecule plays a critical role in calcium homeostasis in neurons. Genome analysis indicates that Na/Ca exchangers are a superfamily encoded by 7 different genes divided into 2 groups: the Na/Ca exchangers (NCX; SLC8) and the Na/Ca+K exchangers (NCKX; SLC24). Two different NCX genes, NCX1 and NCX2, are highly expressed in brain. We recently described the widespread expression of 2 NCKX‐type exchangers in brain, NCKX2 and NCKX3, and uncovered evidence for expression of another, NCKX4. The unique role that each different exchanger plays in neuronal calcium homeostasis, however, awaits further investigation. To begin exploring this central question, we examined both the expression pattern and the functional properties of the K‐dependent Na/Ca exchanger isoforms expressed in brain and compared and contrasted these with NCX‐type exchangers. Distinct patterns of transcript abundance, regional distribution, and developmental expression were noted for each isoform. Functional properties, including stoichiometry and the kinetic characteristics of ion binding, were determined for NCKX2 and are discussed in the context of cellular Ca2+ signaling.
Epigenetics: A Challenge for Genetics, Evolution, and Development?
Authors: Van de VIJVER GERTRUDIS , Van SPEYBROECK LINDA , de WAELE DANI
Published: July 2010

Abstract: In this paper, it is argued that differences in how one relates the genome to its surrounding contexts leads to diverse interpretations of the term epigenetics. Three different approaches are considered, ranging from gene‐centrism, over gene‐regulation, to dynamic systems approaches. Although epigenetics receives its widest interpretation in a systems approach, a paradigmatic shift has taken place in biology from the abandonment of a gene‐centric position on to the present. The epistemological and ontological consequences of this shift are made explicit.
The Relations between Genetics and Epigenetics
Authors: MORANGE MICHEL
Published: July 2010

Abstract: I have tried to unpack the polysemy of the word epigenetics by adopting a historical point of view and by focusing on the models that were proposed at the beginning of the 1960s to explain variations in gene activity during cell differentiation and development. Most of the questions that were or are at the core of epigenetics were posed in this period. This was due to the fact that the regulatory models and their extension to the notion of the genetic program were proposed as genetic answers to the questions raised by Waddington when he defined epigenetics in the 1940s. Studies of DNA methylation and chromatin structure, which became increasingly important in the 1960s and 1970s, were seen as alternative explanations to the regulatory mechanisms that had been previously proposed. This historical detour shows that epigenetics cannot be defined per se, but only as an evolving opposition to the piecemeal, reductionist approach of genetics.
The Changing Concept of Epigenetics
Authors: JABLONKA EVA , LAMB MARION J.
Published: July 2010

Abstract:We discuss the changing use ofepigenetics, a term coined by Conrad Waddington in the 1940s, and how the epigenetic approach to development differs from the genetic approach. Originally, epigenetics referred to the study of the way genes and their products bring the phenotype into being. Today, it is primarily concerned with the mechanisms through which cells become committed to a particular form or function and through which that functional or structural state is then transmitted in cell lineages. We argue that modern epigenetics is important not only because it has practical significance for medicine, agriculture, and species conservation, but also because it has implications for the way in which we should view heredity and evolution. In particular, recognizing that there are epigenetic inheritance systems through which non‐DNA variations can be transmitted in cell and organismal lineages broadens the concept of heredity and challenges the widely accepted gene‐centered neo‐Darwinian version of Darwinism.
Genome Organization and Reorganization in Evolution
Authors: SHAPIRO JAMES A.
Published: July 2010

Abstract:This volume deals with the role of epigenetics in life and evolution. The most dynamic forms of functional genome formatting involve DNA interacting with cellular complexes that do not alter sequence information. Such important epigenetic phenomena are the main subjects of other articles in this volume. This article focuses on the long‐lived form of genome formatting that lies within the DNA sequence itself. I argue for a computational view of genome function as the long‐term information storage organelle of each cell. Structural formatting consists of organizing various signals and coding sequences into computationally ready systems facilitating genome expression and genome transmission. The basic features of genome organization can be understood by examining theE. coli lacoperon as a paradigmatic genomic system. Multiple systems are connected through distributed signals and repetitive DNA to form higherorder genome system architectures. Molecular discoveries about mechanisms of DNA restructuring show that cells possess the natural genetic engineering functions necessary for evolutionary change by rearranging genomic components and reorganizing system architectures. The concepts of cellular computation and decision‐making, genome system architecture, and natural genetic engineering combine to provide a new way of framing evolutionary theories and understanding genome sequence information.
Amygdaloid Regional Cerebral Blood Flow and Subjective Fear during Symptom Provocation in Anxiety Disorders
Authors: FREDRIKSON MATS , FURMARK TOMAS
Published: July 2010

Abstract: Whether the amygdala is involved predominantly in emotional perception or in the generation of emotional states has been debated. We reviewed and reanalyzed data from our laboratory, indicating that subjective feelings of fear and distress are correlated with regional cerebral blood flow (rCBF) in the right but not the left amygdala during anxiety provocation in individuals with social anxiety disorder, specific phobias. and posttraumatic stress disorder. Positron emission tomography is a correlative technique, and casual inferences cannot be drawn. However, because studies demonstrate that treatment of social anxiety disorder with cognitive behavior therapy and selective serotonin reuptake inhibitors results in reduced rCBF in the amygdaloid complex and prospective studies reveal that treatment‐induced alterations in amygdala rCBF can predict 1 year follow‐up status in social anxiety disorder data support the notion that the amygdala, at least in part, seem casually involved in generating the subjective experience of fear.
Neuroimaging Studies of Amygdala Function in Anxiety Disorders
Authors: RAUCH SCOTT L. , SHIN LISA M. , WRIGHT CHRISTOPHER I.
Published: July 2010

Abstract:Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive‐behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains.
The Amygdala and Psychopathology Studies in Epilepsy
Authors: TRIMBLE MICHAEL R. , VAN ELST LUDGER TEBARTZ
Published: July 2010

Abstract: The results of volumetric studies of the amygdala and hippocampus in patients with epilepsy who also have psychopathology are described. The main data relate to the increased size of the amygdala in patients with epilepsy and psychosis. The associations between the amygdala and affective disorders, notably dysthymia and euphoria, are also discussed.
The Monoamine Hypothesis for the Pathophysiology of Paraphilic Disorders: An Update
Authors: KAFKA MARTIN P.
Published: July 2010

Abstract: A monoamine hypothesis for the pathophysiology of paraphilic disorders was first articulated in 1997 by Kafka. This hypothesis was based on four converging lines of empirical evidence. First, the monoamine neurotransmitters, dopamine, norepinephrine, and serotonin serve a modulatory role in human and mammalian sexual motivation, appetitive, and consummatory behavior. Second, the sexual effects of pharmacological agents that affect monoamine neurotransmitters can have both significant facilitative and inhibitory effects on sexual behavior. Third, paraphilic disorders appear to have Axis I comorbid associations with nonsexual psychopathologies that are associated with monoaminergic dysregulation. Last, pharmacological agents that enhance central serotonergic function in particular, have been reported to ameliorate paraphilic sexual arousal and behavior. Contemporary data supporting or refuting a monoaminergic hypothesis as a biological component associated with paraphilic sex offending behaviors will be reviewed. Particular attention will be given to pharmacological‐metabolic probe studies, reports of Axis I comorbidity, the proposed role of disinhibited sexual motivation or sexual appetitive behavior, and cumulative pharmacological treatment data sets.
Are Rapists Differentially Aroused by Coercive Sex in Phallometric Assessments?
Authors: LALUMIÈRE MARTIN L. , QUINSEY VERNON L. , HARRIS GRANT T. , RICE MARNIE E. , TRAUTRIMAS CAROLINE
Published: July 2010

Abstract: In this chapter we examine whether rapists are sexually aroused by coercive, nonconsensual sex. This question is theoretically important because it speaks to a potential sexual motivation underlying rape. It is also clinically important in that it may reveal an important assessment and treatment target. We first revisit and update quantitative reviews of studies that examined the phallometric responses of rapists and other men. We then present new data on the discriminative and diagnostic validity of a phallometric test for rapists. Finally, we discuss methodological and conceptual issues in phallometric assessment and the nature of rapists' sexual interests.
Molecular Mechanisms of Neuronal Cell Death
Authors: HEIDENREICH KIM A.
Published: July 2010

Abstract: Chronic neurodegenerative diseases, including Parkinson's disease, are characterized by a selective loss of specific subsets of neuronal populations over a period of years or even decades. While the underlying causes of the various neurodegenerative diseases are not clear, the death of neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control neuronal cell death is critical for the development of new strategies to prevent and treat neurodegenerative disorders.
Protective Effect of Neuromonitoring during Cardiac Surgery
Authors: EDMONDS HARVEY L.
Published: July 2010

This study was a retrospective examination of the influence of multimodality neuromonitoring on the incidence of serious brain injury associated with a common type of adult cardiac surgery, coronary artery bypass grafting (CABG). Multichannel EEG, cerebral oximetry, and transcranial Doppler ultrasound were used to detect and correct imbalances in cerebral perfusion and oxygenation. Imbalances were detected in 59% of the cases and successfully corrected in all but 2%. In the absence of neuromonitoring, the expected incidence of serious brain injury is 6.1%. With neuromonitoring, the actual observed incidence was 3.0% (P= 0.03). The apparent improvement can be attributed primarily to a reduction in the number of nonembolic diffuse injuries.
Neuropsychiatric Alterations in MDMA Users
Authors: HERNING RONALD I. , BETTER WARREN , TATE KIMBERLY , CADET JEAN L.
Published: July 2010

Abstract: The use of marijuana is rampant among 3,4‐methylenedioxymethamphetamine (MDMA) users. The co‐occurrence of abuse of these two drugs has made it difficult to assess the specific residual effects of MDMA alone. As a first step toward identifying the effects of long‐term MDMA use, we studied 8 MDMA abusers, 8 marijuana/MDMA abusers, 15 marijuana abusers (matched in marijuana use without MDMA use), and 17 control subjects. EEG, cerebral blood velocity by pulsed transcranial Doppler (TCD), and psychological measures were collected. Three‐minute resting eyes‐closed EEG recordings were obtained from 16 electrodes. The EEG was converted to 6 frequency bands (delta, theta, alpha‐1, alpha‐2, beta‐1, and beta‐2) using a fast Fourier transformation. Blood flow velocity was determined using a temporal window for the right and left middle cerebral arteries using TCD. Absolute log delta power in the EEG of MDMA abusers at central electrode sites was significantly higher than that of the MDMA/marijuana, marijuana abusers, and control subjects. There were also increases in alpha‐2 EEG power observed only in marijuana abusers. The blood flow measure, diastolic velocity, was increased in MDMA abusers whether they used marijuana or not. Because increases in delta power and perfusion deficits are associated with some chronic disorders, our findings in these ecstasy abusers suggest that MDMA use may be associated with a drug‐induced neuropathological state. More research is necessary to test these ideas.
Delineating and Understanding Cerebellar Neuroprotective Pathways
Authors: WU XUAN , JIANG XUEYING , MARINI ANN M. , LIPSKY ROBERT H.
Published: July 2010

The cerebellum is a brain region that is resistant to many of the neurodegenerative disorders such as stroke and Alzheimer's disease. In contrast, the neocortex (cerebrum, cerebral cortex) is vulnerable to these disorders. While there may be many reasons for the differences in vulnerability to acute and chronic neurodegenerative disorders, the cerebellum appears to be equipped with the tools necessary to protect itself against these types of insults. Over the last century, evidence has accumulated to suggest that the cerebellum is also involved in memory and higher cognitive function. We have discovered that intrinsic survival pathways exist in cerebellar granule cells that are regulated by low level stimulation of N‐methyl‐d‐aspartate (NMDA) receptors. Activation of NMDA receptors protects vulnerable neurons against glutamate‐mediated excitotoxicity acting on NMDA receptors. This report focuses on how modulation of neuronal survival by NMDA receptors through a brain‐derived neurotrophic factor (BDNF)‐mediated pathway may be incorporated into a network of cerebellar function, particularly in light of recent findings suggesting that the cerebellum plays a vital role in learning, memory, fear conditioning, and cognitive processing.
A Role for Calpain in Optic Neuritis
Authors: GUYTON M KELLY , SRIBNICK ERIC A. , RAY SWAPAN K. , BANIK NAREN L.
Published: July 2010

Abstract: Optic neuritis (ON) is one of the most commonly presenting symptoms of multiple sclerosis (MS), which is a neurodegenerative disease of the central nervous system (CNS) thought to be caused by an attack on myelin by autoreactive T cells and other immune cells. Experimental autoimmune encephalomyelitis (EAE) is a widely used model for MS and ON, which are characterized by demyelination, axonal damage, and neuronal death. The mechanisms of neurodegeneration are unclear; however, the calcium (Ca2+)‐dependent neutral protease calpain is thought to be involved. The focus of this article is to summarize the evidence suggesting that calpain plays a role in the development of EAE‐ON in Lewis rats.
Dynamic host–bacteria interactions during an acidotic state induction
Authors: Rudi Knut
Published: July 2010

Mainly due to the lack of time‐series data, we know very little about the underlying interactions leading to adverse states in the gut. I therefore investigate the host–bacteria dynamic interactions in a recently published acidotic state induction time‐series experiment. Too high levels of fermentation in the hindgut may lead to elevated serum lactate levels, which is a characteristic of the acidotic state. The acidotic state was induced through injection of oligofructose directly into the caecum of five horses, with subsequent temporal measurements of host serum lactate, and a range of caecum bacteria and metabolites. Principal component analysis (PCA) showed that equine hindgut streptococcal species (EHSS) showed the main positive correlation to caecum lactate, and negative correlation to acetate. By dynamic modelling I found that serum lactate interacted with several caecum components, with the main interactions being with caecum lactate and Enterobacteriaceae. Enterobacteriaceae showed a positive interaction with serum lactate, while the interaction between serum and caecum lactate was more complex. The main individual differences in horse serum lactate could be explained by the levels of Enterobacteriaceae and caecum lactate. In conclusion, the dynamic models revealed simple host–bacteria interactions that can explain changes and individual differences in serum lactate.
Flagella mediate attachment of enterotoxigenic Escherichia coli to fresh salad leaves
Authors: Shaw Robert K. , Berger Cedric N. , Pallen Mark J. , Sjöling Åsa , Frankel Gad
Published: July 2010

Enterotoxigenic Escherichia coli (ETEC) causes child and travelers' diarrhea and is presumed to be water‐ and food‐borne. Sporadic outbreaks were traced to consumption of contaminated fresh produce, particularly salad leaves as lettuce and parsley. Importantly, the mechanism by which ETEC binds salad leaves is not known. In this study we investigated the ability of clinical ETEC isolates to adhere to Eruca vesicaria (commonly known as rocket). Towards this end we inoculated pieces of cut E. vesicaria leaves with clinical ETEC isolates grown in Luria broth at 20°C, conditions that are not permissive for expression of the plasmid‐encoded colonization factors and hence mimic the actual transmission pathways of ETEC through intake of contaminated food. We found that ETEC strains bind E. vesicaria at various efficiencies. Examination of representative strains by scanning electron microscopy revealed that they adhere to the E. vesicaria surface in a diffuse pattern by extended filaments resembling flagella. Using the prototype ETEC strain H10407 we found that it also binds to lettuce, basil and spinach leaves. Binding of H10407 was dependent on flagella as a fliC mutant attached to leaves at a much lower efficiency. Interestingly, under the employed environmental conditions EtpA, which forms a flagellar tip structure, and colonization factor I are dispensable for leaf attachment. The results show that ETEC can bind specifically to salad leaves, which might represent an important, yet less recognized, source of infection.
WaderMORPH – a user‐friendly individual‐based model to advise shorebird policy and management
Authors: West Andrew D. , Stillman Richard A. , Drewitt Allan , Frost Natalie J. , Mander Matt , Miles Chris , Langston Rowena , Sanderson William G. , Willis Jay
Published: July 2010

1. Conservation objectives for non‐breeding shorebirds (waders) are determined from their population size. Individual‐based models (IBMs) have accurately predicted mortality rate (a determinant of population size) of these species, and are a tool for advising coastal management and policy. However, due to their complexity, the use of these IBMs has been restricted to specialist modellers in the scientific community, whereas, ideally, they should be accessible to non‐specialists with a direct interest in coastal issues.

2. We describe how this limitation has been addressed by the development of WaderMORPH, a user‐friendly interface to a shorebird IBM, MORPH, that runs within Microsoft Windows. WaderMORPH hides technical and mathematical details of parameterisation from the user and allows models to be parameterised in a series of simple steps. We provide an overview of WaderMORPH and its range of applications. WaderMORPH, its user guide and an example data set can be downloaded from http://individualecology.bournemouth.ac.uk.
Evaluation of a novel post operative treatment for sinonasal disease in the horse (1996–2007)
Authors: HART S. K. , SULLINS K. E.
Published: July 2010

Reasons for performing study:Results of surgical treatment of sinonasal disease in horses have been reported previously; however, this paper describes the outcome of horses in which a specific post operative treatment protocol was used.

Objectives:The objectives of the study were to determine: 1) short‐ and long‐term outcome; 2) complications; and 3) recurrence rates of different disease processes, when horses were treated with a specific treatment protocol.

Methods:Medical records of horses presented for surgical treatment of sinonasal disease from 1996–2007 were reviewed. Results and duration of surgical exploration were recorded. Post operatively, the sinus flaps were re‐opened with the horses standing and sedated. Number of horses requiring further treatment (debridement and/or lavage), median number of post operative days when the flap was re‐opened, median number of times the flap was opened and median duration of hospitalisation were recorded. Short‐ and long‐term survival and complication rates were determined.

Results:Ninety‐one horses were included in the study. The sinus flaps were re‐opened with the horses standing a median of 3 days post operatively. Thirty‐nine horses (43%) required further treatment at this time and 89 horses (97%) survived to discharge. Incision infection was the most common complication encountered (29%). No horse required a blood transfusion. Recurrence rates were 5% for paranasal sinus cysts, 12% for progressive ethmoid haematoma and 50% for neoplasia.

Conclusions:Rapid removal of the primary lesion followed by packing the sinuses and re‐evaluating in the standing horse in a more controlled environment offers a safe and effective means to thoroughly assess and treat sinonasal disease.

Potential relevance:Surgical time, intraoperative haemorrhage, long‐term complications and recurrence rates of paranasal sinus diseases treated via frontonasal or maxillary sinus flap may be reduced using this technique.
Microlith Supported Sulfur Tolerant Catalyst for Autothermal Reforming of E85 Fuel
Authors: Zhu Tianli , Walsh Dennis , DesJardins Joel , Roychoudhury Subir , Holcomb Franklin H. , Feickert Carl A.
Published: July 2010

Under a U.S. Army program, PCI has developed autothermal reforming catalysts for E85 to provide stable performance in the presence of fuel sulfur as well as corrosion inhibitors. The catalysts build on PCI’s Microlith™ catalyst technology and used PCI’s proprietary formulations. A stable performance was demonstrated through short-term testing (70–80h) using high sulfur doped (100ppm) fuel. At 1.11 O:C and 1.25 S:C, nearly complete conversion and 70%+ reforming efficiency (LHV based) were achieved on stabilized catalysts in the presence of 20ppm feed sulfur. The effect of ceria addition into an alumina based support was also examined.
High Power Internal-Reforming Direct Carbonate Fuel Cell Stack Development Through Mathematical Modeling and Engineering Optimization
Authors: Ma Zhiwen , Venkataraman Ramakrishnan , Farooque Mohammad
Published: July 2010

Fuel cell power generation has evolved from the laboratory and aerospace applications, and moved onto practical applications of stationary power generation and automotive propulsion, driven by its high-energy efficiency and low emissions. The success of the fuel cell technology depends on its performance, cost, and reliability in commercial applications. Fuel Cell Energy Inc. (Danbury, CT) has been developing its direct fuel cell (DFC™) technology for power generation based on internal-reforming carbonate fuel cells. The DFC technology integrates the reforming reaction within the carbonate fuel cell stack. The integration of the reforming process inside the high temperature fuel cell stack simplifies the fuel cell power plant system and makes the fuel cell technology more accessible to the practical usage with low cost and high efficiency. The internal-reforming direct carbonate fuel cell technology has progressed steadily with improvement in performance and success in precommercialization applications. Modeling and simulation of the fuel cell performance played an important role in the fuel cell development. This paper will illustrate improved mathematical model for the direct carbonate fuel cell with the internal-reforming process and complete fuel cell physical and chemical descriptions for the simulation. The model has been validated with data from real-scale fuel cell stacks and applied to fuel cell stack design. More powerful and reliable DFC stack with improved performance has been developed with the assistance of this model. This paper will present progress in developing high performance stack designs aided by modeling efforts, its impact on power increase, and cost reduction in the DFC product.
Numerical Analysis of the Heat and Mass Transfer Characteristics in an Autothermal Methane Reformer
Authors: Park Joonguen , Lee Shinku , Kim Sunyoung , Bae Joongmyeon
Published: July 2010

This paper discusses a numerical analysis of the heat and mass transfer characteristics in an autothermal methane reformer. Assuming local thermal equilibrium between the bulk gas and the surface of the catalyst, a one-medium approach for the porous medium analysis was incorporated. Also, the mass transfer between the bulk gas and the catalyst’s surface was neglected due to the relatively low gas velocity. For the catalytic surface reaction, the Langmuir–Hinshelwood model was incorporated in which methane (CH4) is reformed to hydrogen-rich gases by the autothermal reforming (ATR) reaction. Full combustion, steam reforming, water-gas shift, and direct steam reforming reactions were included in the chemical reaction model. Mass, momentum, energy, and species balance equations were simultaneously calculated with the chemical reactions for the multiphysics analysis. By varying the four operating conditions (inlet temperature, oxygen to carbon ratio (OCR), steam to carbon ratio, and gas hourly space velocity (GHSV)), the performance of the ATR reactor was estimated by the numerical calculations. The SR reaction rate was improved by an increased inlet temperature. The reforming efficiency and the fuel conversion reached their maximum values at an OCR of 0.7. When the GHSV was increased, the reforming efficiency increased but the large pressure drop may decrease the system efficiency. From these results, we can estimate the optimal operating conditions for the production of large amounts of hydrogen from methane.
A Controllable Membrane-Type Humidifier for Fuel Cell Applications—Part I: Operation, Modeling and Experimental Validation
Authors: McKay Denise A. , Stefanopoulou Anna G. , Cook Jeffrey
Published: July 2010

For temperature and humidity control of proton exchange membrane fuel cell (PEMFC) reactants, a membrane based external humidification system was designed and constructed. Here we develop and validate a physics based, low-order, control-oriented model of the external humidification system dynamics based on first principles. This model structure enables the application of feedback control for thermal and humidity management of the fuel cell reactants. The humidification strategy posed here deviates from standard internal humidifiers that are relatively compact and cheap but prohibit active humidity regulation and couple reactant humidity requirements to the PEMFC cooling demands. Additionally, in developing our model, we reduced the number of sensors required for feedback control by employing a dynamic physics based estimation of the air-vapor mixture relative humidity leaving the humidification system (supplied to the PEMFC) using temperature and pressure measurements. A simple and reproducible methodology is then employed for parameterizing the humidification system model using experimental data.
Distribution Study of Species and Current Density During Oxygen Starvation
Authors: Gerard Mathias , Poirot-Crouvezier Jean-Philippe , Hissel Daniel , Pera Marie-Cecile
Published: July 2010

In a fuel cell system the stack is strongly coupled with the main system components, among which the compressor is one of the most important. Malfunction of this auxiliary device (delay during peak power, low stoichiometry operation, emergency stop, etc.) is directly responsible for bad oxygen distribution in the cathode (substoichiometry reactants feeding). This phenomenon is usually called oxygen starvation. In this study we want to identify the consequences of oxygen starvation on the performance and durability of polymer electrolyte membrane fuel cell stacks, and more particularly, on the current distribution along the cell. The oxygen concentration decreases along the channel and induces a change in the local electrochemical response; it means that the local current density on the cell is redistributed on the surface. This bad distribution of reactive gas (in a transient time or long time) decreases the performance but may also have an effect on cathode degradation such as carbon corrosion and platinum dissolution/oxidation. The current distribution along the cell is studied by two approaches (modeling and experiments). The 3D model using serpentine bipolar plate meshing is adapted to dynamically compute for the catalyst layer local conditions (local current, temperature, gases partial pressure, and water activity). It is able to reproduce the conditions of low or high oxygen concentration in the cathode side. The experiments are performed with a bi-cell stack developed by CEA with specific design for the magnetic sensors (the local current is computed by measuring the local induced magnetic field and using the Maxwell equations).
A Feasibility Study of Ribbon Architecture for PEM Fuel Cells
Authors: Walczyk Daniel F. , Sangra Jaskaran S.
Published: July 2010

The feasibility of an alternative fuel cell architecture, called a ribbon membrane electrode assembly (MEA), is demonstrated for low-temperature polymer electrolyte membrane (PEM) fuel cells used in portable power applications by comparing it to a traditional bipolar “stack” architecture. A ribbon MEA consists of adjacent PEM cells sharing a common gas diffusion layer to allow for lateral electrical current flow and an integral gas-tight, conductive interconnect/seal, where adjacent cells meet to prevent reactant gas leakage. The resulting lateral arrangement of MEAs can be used to supply all MEAs simultaneously instead of individual bipolar plates with flow fields for a stack. A pair of two-cell ribbon MEAs, with and without an interconnect/seal, were designed, prototyped, and sealed by thermal pressing. The MEAs were clamped in a two-piece box fixture to provide reactant gases on the anode and cathode sides, hooked to a fuel cell (FC) test stand and yielded an open circuit voltage (OCV) of 1.43 V with an interconnect/seal and 0.6 V without. A two-cell bipolar stack PEMFC with identical MEA specifications had an OCV of 1.86 V. Polarization curves for the ribbon MEA with interconnect/seal showed the sensitivity of performance to clamping pressure and positioning of the copper current collectors. The ribbon MEA polarization curve was also shifted downward by 0.42 V as compared with that of the traditional stack, and suspected causes (e.g., gas leaking) are attributable to the nonoptimal test fixture design. Hence, the ribbon MEA architecture is shown to be feasible. Future work suggested includes improvements to the test fixture design, development of automated manufacturing capabilities for high volume production, and demonstration of a multicell (>2) ribbon MEA PEMFC design.
Stimulate the Mind, Fight Cancer
Authors: Wong Wei
Published: July 2010

Enriched housing environments activate a brain-adipocyte signaling axis in mice that decreases tumor burden and incidence.
Good ROS Versus Bad ROS
Authors: Ray L. Bryan
Published: July 2010

Opposite effects of chronic and acute oxidative stress are explained by distinct localization of a protein kinase and its regulatory phosphatase.
Sending a Package Through the Blood
Authors: Adler Elizabeth M.
Published: July 2010

Secreted miRNAs may act as intercellular signaling molecules.
Axon Goes Here
Authors: Wong Wei
Published: July 2010

TGF-β–mediated phosphorylation of Par-6 is required for axon specification.
Sulfur Signal Dinner
Authors: Ash Caroline
Published: July 2010

A microfluidics device reveals a common response of bacterial plankton to sulfur compounds emitted by marine algae.
Response to Comment on “Increased MKK4 Abundance with Replicative Senescence Is Linked to the Joint Reduction of Multiple MicroRNAs”
Authors: Gorospe Myriam , Srikantan Subramanya , Abdelmohsen Kotb , Marasa Bernard S.
Published: July 2010

The antibody used to detect phosphorylated PRAK is suspect.