bluuebunny/crossref_metadata_2025 huggingface dataset:
Supported Lipid Bilayers
Authors: Kiessling Volker , Domanska Marta K. , Murray David , Wan Chen , Tamm Lukas K.
Published: August 2008

Lipid bilayers supported on solid substrates were developed almost a quarter century ago as a new model membrane system to study fundamental properties of biological membranes and their constituent lipid and protein molecules, as well as for numerous practical applications. In this review, we summarize the development of supported bilayer‐based model membrane systems of increasing complexity while always keeping in mind their primary purpose, which is to reproduce the complex fluid structure of biological membranes to mimic cell membrane‐based molecular processes as close to physiological reality as possible. This process must include maintaining the structure and fluidity of the lipid bilayer, as well as the structure and function of reconstituted membrane proteins. We start the review with a general description of a contemporary picture of a generic biological membrane and proceed with an account of how supported membranes recapture different physiological aspects of biological membranes, such as membrane fusion, cell adhesion, or membrane permeability. Supported membranes are particularly good models for reproducing the fluidity of cell membranes even when different liquid lipid phases coexist. They are also superb models for measuring ligand‐receptor interactions between membrane‐bound receptors and soluble or membrane‐bound ligands. The chemical biology of these and many other lipid–lipid, lipid–protein, and protein–protein interactions that have been investigated in supported bilayers are summarized in several sections that form the main body of this review. The article closes with summaries of practical procedures to prepare and characterize supported bilayers.
Anxiety Disorders: Macromolecular Pathways and Interactions
Authors: Toth Miklos
Published: August 2008

Fear and anxiety can be a normal adaptive reaction to help cope with stress in the short term, but when the emotional, cognitive, and physical manifestations are long lasting, extreme, and disproportionate to threat, whether real or preceived, anxiety is maladaptive and has become a disabling disorder. Anxiety disorders may be deconstructed to elementary behaviors/symptoms that can be conceptualized as quantitative characters determined by the combined effects of several risk genes and nongenetic factors (e.g., early‐life adversity). Progress in neurogenetics, molecular and cellular neuroscience, and neuroimaging is beginning to yield significant insights of how genetic and nongenetic factors contribute to specific manifestations of anxiety disorders. The aim of this overview is to summarize and integrate the current knowledge on anxiety‐related macromolecular pathways and mechanisms initiated by genetic risk and envionmental factors. These pathways interact with each other, often during specific periods of development, and could lead to alterations in the formation and function of neuronal circuits that encode emotional behavior.
Protein Trafficking Diseases: Small Molecule Approaches
Authors: Sampson Heidi M. , Thomas David Y.
Published: August 2008

Many diseases are caused by defects in protein trafficking. Protein trafficking diseases occur when a mutant protein is recognized by the endoplasmic reticulum (ER) quality control system (ERQC), retained in the ER, and degraded in the cytosol by the proteasome rather than being trafficked to its correct site of action. Among these diseases are cystic fibrosis, lysosomal storage diseases (Fabry, Gaucher, and Tay‐Sachs), nephrogenic diabetes insipidus, oculocutaneous albinism, protein C deficiency, and many others. A characteristic of many of these diseases is that the mutant protein remains functional, but it cannot escape the stringent ER quality‐control machinery, and it is retained in the ER. This characteristic suggests that pharmacological interventions that promote the correct folding of the mutant protein would enable its escape from the ER and ameliorate the symptoms of the disease. In this review, we focus on specific examples of protein trafficking diseases in pharmacological or chemical chaperones have been shown to rescue trafficking of the mutant protein.
Electron Paramagnetic Resonance (EPR) in Enzymology
Authors: Liu Aimin
Published: August 2008

Electron paramagnetic resonance (EPR) is a versatile tool for chemical biology research. A remarkable wealth of information about the mechanistic enzymology has been obtained by EPR experiments. As an analytical method, EPR can obtain these two useful pieces of information in a study of enzymatic reaction mechanisms: 1) detection and complete description of free radicals and 2) characterization of the electronic structures of paramagnetic metal ions and their response to changes of the protein environment or substrate binding. The first feature has spurred the development of the new field known as radical enzymology; the second has enhanced the understanding of the mechanisms of metalloenzyme action. The potential of EPR spectroscopy to serve as an important biophysical tool for the future development of enzymology is highlighted by several selected examples.
Schizophrenia: Biological Mechanisms
Authors: Perrone‐Bizzozero Nora I. , Bullock W. Michael
Published: August 2008

Schizophrenia is a chronic and severely debilitating mental disorder that affects approximately 1% of the world's population. Although schizophrenia has been recognized for over 100 years, the causes and pathophysiological mechanisms of this illness remained rather elusive until recently. Evidence obtained during the last 3 decades suggests that schizophrenia is a neurodevelopmental disorder that affects the structure and function of distributed brain regions. Multiple neurotransmitter systems have been implicated, as have both gray and white matter abnormalities. These structural alterations result in synaptic miscommunication at local neuronal circuits and long‐distance functional disconnectivity, with both genetic and environmental factors contributing to these deficits. This article will discuss our current understanding of the biological and neurochemical bases of schizophrenia and will describe new pharmacological, genetic, and lesion models used for testing the mechanisms that underlie this devastating disease.
Chronic Obstructive Pulmonary Disease (
COPD
): Biological Mechanisms
Authors: Barnes Peter J.
Published: August 2008

Airway obstruction in chronic obstructive pulmonary disease (COPD) is caused by narrowing of small airways as a result of inflammation and fibrosis and the disruption of their alveolar attachments as a result of emphysema. COPD is characterized by a complex inflammatory disease process that increases as the disease progresses, which leads to increasing airflow limitation. Many inflammatory cells and mediators have now been implicated in the pathogenesis of COPD. Increased numbers of macrophages, neutrophils, T‐lymphocytes (particularly CD8
+
cells) and B‐lymphocytes have been observed, as well as the release of multiple inflammatory mediators (lipids, chemokines, cytokines, growth factors). Macrophages seem to play an important role in orchestrating the inflammatory process, which includes the recruitment of neutrophils and T‐cells into small airways and lung parenchyma and the secretion of proteinases that lead to emphysema. A high level of oxidative and nitrative stress may amplify this inflammation through the reduction in histone deacetylase‐2, which also results in corticosteroid resistance.
Depression: Chemical Mechanisms
Authors: Baker Glen B. , Mitchell Nicholas D.
Published: August 2008

Although the etiology of depression remains to be elucidated, our knowledge of the neurobiology and biochemistry of this mental disorder has been updated increasingly. Early research focused on the biogenic amines norepinephrine (NE; noradrenaline) and 5‐hydroxytryptamine (5‐HT; serotonin). The biogenic amine (monoamine) hypothesis of depression states that depression is the result of a functional deficiency of NE and/or 5‐HT at central synapses. However, it soon became obvious that other factors were also important in the neurobiology of depression. Dopamine is thought to be involved in various aspects, which include reward and locomotion. The amino acids gamma‐aminobutyric acid (GABA) and glutamate, their receptors, and various neuroactive steroids that act as allosteric modulators at GABA‐A and/or NMDA glutamate receptors have been proposed to have an important role. Stress and the hypothalamic‐pituitary‐adrenal (HPA) axis play a central role, and it has been proposed that increased secretion of corticotropin releasing factor (CRF) may be critical in producing the symptoms of depression. Various other neurochemicals have also been implicated in depression, and in several cases they have links to the HPA axis. Abnormal levels of Substance P have been reported in depression, which led to development of potential antidepressants that interact with neurokinin receptors. Abnormalities in the immune system, which presumably involve cytokines, have been reported in depression. Cell loss seems to occur in some brain areas (e.g., hippocampus) in depression, and such loss can be produced by stress and prevented by antidepressants (which also increase expression of various neurotrophic and transcription factors). Agonists at melatonin receptors have been proposed in recent years as effective antidepressants. The possible involvement of the various neurochemicals mentioned above in depression will be reviewed, and some other neurochemicals that are being examined will also be mentioned.
A stochastic Hammerstein model for control of oxygen uptake during robotics‐assisted gait
Authors: Hunt K. J. , Allan D. B.
Published: August 2008

Robotics‐assisted gait devices have been introduced as part of rehabilitation therapy for people with neurological impairment. The scope of application has recently been expanded to encompass cardiopulmonary training and assessment, but the response of oxygen uptake to progressively increasing work rate while walking with robotics assistance can be strongly nonlinear. This hampers efforts to estimate cardiopulmonary performance parameters.

We hypothesized that a linear increase in oxygen uptake can be achieved by employing feedback control. We aimed to develop a nonlinear stochastic model of oxygen uptake response to work rate during robotics‐assisted gait, and to employ this model to design and test feedback strategies for control of oxygen uptake during incremental exercise testing.

A new model structure was developed consisting of a Hammerstein component, i.e. a static nonlinear gain combined with a linear time‐invariant transfer function, and a stochastic approximation of regularized breath‐by‐breath fluctuations in oxygen uptake.

Simulation results using the model and a range of control design parameters confirmed the ability of feedback to achieve a linear increase in work rate in the face of strong plant nonlinearity.

This new approach could be applied during incremental exercise tests and may lead to improved understanding and estimates of the sub‐maximal gas exchange threshold and peak cardiorespiratory performance parameters. Copyright © 2008 John Wiley & Sons, Ltd.
Cover Picture: Texture Evolution During Bending of a Single Crystal Copper Nanowire Studied by EBSD and Crystal Plasticity Finite Element Simulations (Adv. Eng. Mater. 8/2008)
Authors: Weber F. , Schestakow I. , Roters F. , Raabe D.
Published: August 2008

The cover shows a bending test on a Cu single crystal nanowire. The distribution of the geometrically necessry dislocations in the bent wire was determined using high resolution electron back scatter diffraction and predicted using a crystal plasticity finite element method which uses a dislocation based constitutive law. More details can be found in the article of F. Weber, I. Schestakow, F. Roters, D. Raabe on page 737.
State of the art in developmental toxicity screening methods and a way forward: a meeting report addressing embryonic stem cells, whole embryo culture, and zebrafish
Authors: Chapin Robert , Augustine‐Rauch Karen , Beyer Bruce , Daston George , Finnell Richard , Flynn Thomas , Hunter Sidney , Mirkes Phillip , Sue O'Shea K. , Piersma Aldert , Sandler David , Vanparys Philippe , Van Maele‐Fabry Geneviève
Published: August 2008

A meeting was convened so that users of three models for in vitro developmental toxicity (embryonic stem cells, whole embryo culture, and zebrafish) could share their experiences with each model, and explore the areas for improvement. We present a summary of this meeting and the recommendations of the group. Birth Defects Res (Part B) 83:446–456, 2008. Published 2008 Wiley‐Liss, Inc.
Sensory‐dependent asymmetry for a urine‐responsive olfactory bulb glomerulus
Authors: Oliva Anthony M. , Jones Kevin R. , Restrepo Diego
Published: August 2008

An unusual property of the olfactory system is that sensory input at the level of the first synapse in the olfactory bulb takes place at two mirror‐image glomerular maps that appear identical across the axis of symmetry. It is puzzling how two identical odor maps would contribute to sensory function. The functional units in these maps are the glomeruli, ovoid neuropil structures formed by axons from olfactory sensory neurons expressing the same olfactory receptor. Here we find that the genetically identified P2 glomeruli are asymmetric across the axis of symmetry in terms of responsiveness to urine volatiles and neuroanatomical structure. Furthermore, P2 asymmetry is modified by sensory deprivation and abolished by decreased BDNF levels. Thus, while mirror odor maps show symmetry at the macroscopic level in maps encompassing the entire surface of the olfactory bulb, they display asymmetry at the level of the single glomerulus. J. Comp. Neurol. 510:475–483, 2008. © 2008 Wiley‐Liss, Inc.
Muscarinic‐2 and orexin‐2 receptors on GABAergic and other neurons in the rat mesopontine tegmentum and their potential role in sleep–wake state control
Authors: Brischoux Frédéric , Mainville Lynda , Jones Barbara E.
Published: August 2008

Acetylcholine (ACh) plays an important role in the promotion of paradoxical sleep (PS) with muscle atonia through the muscarinic‐2 receptor (M2R) in the mesopontine tegmentum. Conversely, orexin (Orx or hypocretin) appears to be critical for the maintenance of waking with muscle tone through the orexin‐2 (or hypocretin‐B) receptor (Orx2R), which is lacking in dogs having narcolepsy with cataplexy. In dual‐immunostained material viewed under fluorescence microscopy, we examined the presence and distribution of M2R or Orx2R labeling on all neuronal nuclei (NeuN)‐stained neurons or on glutamic acid decarboxylase (GAD)‐stained neurons through the mesopontine tegmentum. Applying stereological analysis, we determined that many neurons bear M2Rs on their membrane (≈6,300), including relatively large, non‐GABAergic cells, which predominate (>75%) in the oral and caudal pontine (PnO and PnC) reticular fields, and small, GABAergic cells (≈2,800), which predominate (>80%) in the mesencephalic (Mes) reticular formation. Many neurons bear Orx2Rs on their membrane (≈6,800), including relatively large, non‐GABAergic cells, which predominate (>70%) through all reticular fields, and comparatively few GABAergic cells (≈700). In triple‐immunostained material viewed by confocal microscopy, many large neurons in PnO and PnC appear to bear both M2Rs and Orx2Rs on their membrane, indicating that ACh and Orx could exert opposing influences of inhibition vs. excitation on putative reticulo‐spinal neurons and thus attenuate vs. facilitate activity and muscle tone. A few GABAergic cells bear both receptors and could as PS inhibitor neurons serve under these different influences to control PS effector neurons and accordingly gate PS and muscle atonia appropriately across sleep–wake states. J. Comp. Neurol. 510:607–630, 2008. © 2008 Wiley‐Liss, Inc.
Probing neurochemical structure and function of retinal ON bipolar cells with a transgenic mouse
Authors: Dhingra Anuradha , Sulaiman Pyroja , Xu Ying , Fina Marie E. , Veh Rüdiger W. , Vardi Noga
Published: August 2008

Retinal ON bipolar cells make up about 70% of all bipolar cells. Glutamate hyperpolarizes these cells by binding to the metabotropic glutamate receptor mGluR6, activating the G‐protein Go1, and closing an unidentified cation channel. To facilitate investigation of ON bipolar cells, we here report on the production of a transgenic mouse (Grm6‐GFP) in which enhanced green fluorescent protein (EGFP), under control of mGluR6 promoter, was expressed in all and only ON bipolar cells. We used the mouse to determine density of ON bipolar cells, which in central retina was 29,600 cells/mm2. We further sorted the fluorescent cells and created a pure ON bipolar cDNA library that was negative for photoreceptor unique genes. With this library, we determined expression of 27 genes of interest. We obtained positive transcripts for Go interactors: regulators of G‐protein signaling (RGS), Ret‐RGS1 (a variant of RGS20), RGS16, RGS7, purkinje cell protein 2 (PCP2, also called L7 or GPSM4), synembryn (RIC‐8), LGN (GPSM2), RAP1GAP, and Gβ5; cGMP modulators: guanylyl cyclase (GC) 1α1, GC1β1, phosphodiesterase (PDE) 1C, and PDE9A; and channels: inwardly rectifying potassium channel Kir2.4, transient receptor potential TRPC2, and sperm‐specific cation channels CatSper 2–4. The following transcripts were not found in our library: AGS3 (GPSM1), RGS10, RGS19 (GAIP), calbindin, GC1α2, GC1β2, PDE5, PDE2A, amiloride‐sensitive sodium channel ACCN4, and CatSper1. We then localized Kir2.4 to several cell types and showed that, in ON bipolar cells, the channel concentrates in their dendritic tips. The channels and modulators found in ON bipolar cells likely shape their light response. Additional uses of the Grm6‐GFP mouse are also discussed. J. Comp. Neurol. 510:484–496, 2008. © 2008 Wiley‐Liss, Inc.
The ventral nucleus of the lateral lemniscus of the gerbil (Meriones unguiculatus): Organization of connections with the cochlear nucleus and the inferior colliculus
Authors: Benson Christina G. , Cant Nell B.
Published: August 2008

The spatial organization of projections from the ventral cochlear nucleus (VCN) to the ventral nucleus of the lateral lemniscus (VNLL) and from the VNLL to the central nucleus of the inferior colliculus (CNIC) was investigated by using neuroanatomical tracing methods in the gerbil. In order to label cells in the VNLL that project to the CNIC, focal injections of biotinylated dextran amine (BDA) were made into different CNIC regions. Retrogradely labeled cells were distributed throughout the dorsal‐to‐ventral axis of the VNLL in all cases. In contrast, the distribution of labeled cells across the lateral‐to‐medial dimension of the VNLL was related to the location of the injection site along the dorsolateral to ventromedial (frequency) axis of the CNIC. Cells projecting to dorsolateral (low‐frequency) regions of the CNIC were located peripherally in the VNLL, mainly laterally and caudally, whereas those projecting to ventromedial (high‐frequency) regions of the CNIC tended to be clustered centrally. Projections to the VNLL were labeled anterogradely following injections of BDA in the VCN. The distribution of terminal fields in the VNLL closely paralleled the topographic arrangement of cells projecting to the CNIC; projections from ventrolateral (low‐frequency) areas of the VCN terminated mainly along the lateral and caudal borders of the VNLL, whereas projections from dorsomedial (high‐frequency) areas terminated in more central regions. The results demonstrate a topographic organization of the major afferent and efferent connections of the gerbil VNLL. J. Comp. Neurol. 510:673–690, 2008. © 2008 Wiley‐Liss, Inc.
Serine racemase is predominantly localized in neurons in mouse brain
Authors: Miya Kazushi , Inoue Ran , Takata Yoshimi , Abe Manabu , Natsume Rie , Sakimura Kenji , Hongou Kazuhisa , Miyawaki Toshio , Mori Hisashi
Published: August 2008

D‐Serine is the endogenous ligand for the glycine binding site of the N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptor (GluR) channel and is involved in the regulation of synaptic plasticity, neural network formation, and neurodegenerative disorders. D‐Serine is synthesized from L‐serine by serine racemase (SR), which was first reported to be localized in astrocytes. However, recently, SR mRNA and its protein have been detected in neurons. In this study, we examined the SR distribution in the brain during postnatal development and in cultured cells by using novel SR knockout mice as negative controls. We found that SR is predominantly localized in pyramidal neurons in the cerebral cortex and hippocampal CA1 region. Double immunofluorescence staining revealed that SR signals colocalized with those of the neuron‐specific nuclear protein, but not with the astrocytic markers glial fibrillary acid protein and 3‐phosphoglycerate dehydrogenase. In the striatum, we observed SR expression in γ‐aminobutyric acid (GABA)ergic medium‐spiny neurons. Furthermore, in the adult cerebellum, we detected weak but significant SR signals in GABAergic Purkinje cells. From these findings, we conclude that SR is expressed predominantly in many types of neuron in the brain and plays a key role in the regulation of brain functions under physiological and pathological conditions via the production of the neuromodulator D‐serine. J. Comp. Neurol. 510:641–654, 2008. © 2008 Wiley‐Liss, Inc.
Dynamic modeling of cable system using a new nodal position finite element method
Authors: Zhu Z. H.
Published: August 2008

The handling of cable systems onboard surface ships and submarines presents a significant technical challenge to design engineers in defense and ocean industries. The current approaches rely heavily on empirical methods and time‐consuming/expensive prototype testing. Computer simulation provides a cost effective way to reduce the high risks associated with the design of the cable‐towed system. This paper presents a new nodal position finite element method (FEM) to effectively simulate the dynamics of cable system experiencing large rigid body rotation coupled with small elastic deformation. The existing FEM deals with the large rigid body rotation by linearized incremental approximation that is prone to numerical inaccuracies resulting from large 3D rotations. By solving for the position directly instead of indirectly via the displacement, the new FEM does not need to decouple the elastic deformation from the rigid body rotation and thus eliminates the error source arising from the linearized incremental approximation in existing FEM. Analysis results demonstrate that the new FEM algorithm is simple and robust by comparing with numerical benchmark test and experiments including sea trial data. Copyright © 2008 John Wiley & Sons, Ltd.
A novel key management scheme for dynamic multicast communications
Authors: Chang Chin‐Chen , Cheng Yi‐Fang , Lin Iuon‐Chang
Published: August 2008

Secure multicasting allows the sender to deliver an identical secret to an arbitrary set of recipients through an insecure broadcasting channel, whereas the unintended recipients cannot obtain the secret. A practical approach for securing multicast communications is to apply a session key to encrypt the transmitted data. However, the challenges of secure multicast are to manage the session keys possessed by a dynamic group of recipients and to reduce the overhead of computation and transmission when the membership is changed. In this paper, we propose a new key management scheme for dynamic multicast communication, which is based on privacy homomorphism and Chinese remainder theorem. Our scheme can efficiently and securely deliver an identical message to multiple recipients. In particular, the complexity of the key update process in our scheme isO(1). Copyright © 2008 John Wiley & Sons, Ltd.
1D, 2D and 3D Coordination Polymers of Aromatic Carboxylate TbIII: Structure, Thermolysis Kinetics and Fluorescence
Authors: Zhou Ying‐Xia , Shen Xiao‐Qing , Du Chen‐Xia , Wu Ben‐Lai , Zhang Hong‐Yun
Published: August 2008

Reactions of TbCl3·6H2O with aromatic acids, namely, pyridine‐2,3‐dicarboxylic acid (H2pda), isophthalic acid (H2ipa) and isonicotinic acid (Hina) gave rise to three new coordination polymers {[Tb(pda)(Hpda)]·3H2O}n (1), {[KTb(ipa)2(H2O)3(μ‐H2O)]·2H2O}n (2) and [Tb(ina)3(H2O)2]n (3), respectively. Complex 1 constructed by eight‐coordinate TbIII nodes connected with completely and half‐deprotonated pda and Hpda spacers is a novel 3D metal–organic architecture with nanosized hexagonal 1D channels hosting guest water, whereas complex 2 is a 2D heterometal sheet built by completely deprotonated ipa spacers bridging eight‐coordinate KI and nine‐coordinate TbIII. As for 3, deprotonated monoacid ina anions link eight‐coordinate TbIII centres into a 1D double‐chain structure. As excited at 320 nm, complexes 1–3 all display a serial of emissions centred at about 486, 545, 582 and 620 nm, which is assigned to the characteristic 5D4 → 7Fj (j = 6; 5; 4; 3) electronic transitions of TbIII. The overall fluorescence nature of 1–3 is extremely alike, but their fluorescence intensity and lifetime are affected by the architectures. Very interestingly, the fluorescence intensity of 2, especially emitting at 545 nm, is largely enhanced owing to the coordination of alkali metal KI in the TbIII–carboxylate network. Furthermore, thermal behaviours of 1–3 under a nitrogen atmosphere as well as the thermolysis nonisothermal kinetics of 2 are researched.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
FRET in Orthogonally Arranged Chromophores
Authors: Langhals Heinz , Poxleitner Simon , Krotz Oswald , Pust Tim , Walter Andreas
Published: August 2008

Perylene and benzoperylene carboxylic imides were arranged to form a bichromophoric dye with orthogonal electronic transition moments. Thus, exciton interactions between the two chromophores could be excluded, in spite of their proximity. However, quantitative Förster‐type energy transfer proceeds between the chromophores indicated by a fluorescence quantum yield close to unity even with hypsochromic excitation. Applications are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis of Substituted Oxazoles from N‐Acyl‐β‐hydroxyamino Acid Derivatives
Authors: Ferreira Paula M. T. , Monteiro Luís S. , Pereira Goreti
Published: August 2008

Several N‐acyl‐β‐hydroxyamino acids were prepared and treated with di‐tert‐butyl dicarbonate in the presence of 4‐(dimethylamino)pyridine, followed by treatment with N,N,N′,N′‐tetramethylguanidine to give the corresponding N‐acyldehydroamino acids in good to high yields. These were then treated with I2/K2CO3 followed by 1,8‐diazabicyclo[5.4.0]undec‐7‐ene. The methyl esters of N‐acyldehydroaminobutyric acid gave the corresponding substituted oxazoles in good to high yields. The N‐acyldehydrophenylalanines gave 5‐phenyloxazole derivatives in low to moderate yields together with β‐iododehydrophenylalanines. Under the same conditions, N‐acyldehydroalanines failed to give the corresponding oxazoles. However, when the reaction was carried out in the absence of DBU, it was possible to isolate the β,β‐diiododehydroalanine derivatives. Although the reason for the different reactivities of the N‐acyldehydroamino acids is not completely clear to us, cyclic voltammetry studies showed that the less‐reactive derivatives have higher reduction potentials. This suggests that the double bonds in dehydroaminobutyric acid derivatives are more susceptible to electrophilic attack by iodine.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Pd(OAc)2/p‐Benzoquinone‐Catalyzed Anaerobic Electrooxidative Homocoupling of Arylboronic Acids, Arylboronates and Aryltrifluoroborates in DMF and/or Water
Authors: Amatore Christian , Cammoun Chama , Jutand Anny
Published: August 2008

A new anaerobic electrooxidative homocoupling of arylboronic acids, arylboronates and aryltrifluoroborates was developed in the presence of catalytic amounts of Pd(OAc)2 and p‐benzoquinone, which serves as a redox mediator for the oxidation of transient Pd0 to the active PdII species. The homocoupling was performed in DMF, DMF/water or in pure water. This electrochemical process avoids the use of a stoichiometric amount of chemical oxidants and subsequent formation of co‐ and by‐products.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Making plans for healthy diet: The role of motivation and action orientation
Authors: De Ridder Denise , de Wit John , Adriaanse Marieke A.
Published: August 2008

The main objective of the present study was to examine the role of motivation and action orientation in forming spontaneous (i.e., without specific instruction or manipulation) implementation intentions for a healthy diet goal. We hypothesized that (1) the adoption of a diet goal would be determined by (either intrinsic or extrinsic) motivation only whereas, (2) forming implementation intentions would be determined by intrinsic motivation and (either low or high) action orientation. These hypotheses were addressed in a sample of 142 normal weight subjects who were concerned about their dietary habits. Primary outcomes were goal intentions and implementation intentions. Our hypothesis regarding the prediction of goal intentions was confirmed whereas results relating to the prediction of implementation intentions demonstrated that intrinsic motivation and low (but not high) action orientation proved significant predictors of intentions to implement a healthy diet goal. These findings suggest that self‐regulatory skills as assessed by the concept of action orientation may relate to short‐term strategies of initiating behavior change only. Copyright © 2008 John Wiley & Sons, Ltd.
Anti‐Interferent Properties of Oxidized Nickel Based on Layered Double Hydroxide in Glucose Amperometric Biosensors
Authors: Scavetta Erika , Guadagnini Lorella , Mignani Adriana , Tonelli Domenica
Published: August 2008

An amperometric biosensor based on Pt electrodes modified with a thin film of a Ni, Al layered double hydroxide (LDH), submitted to a preliminary oxidative treatment in order to have the nickel centers at the oxidation state +4, and glucose oxidase (GOx) is presented. The oxidized LDH acts both as a system to support the enzyme and as a barrier to anions since it acquires an overall negative charge, as demonstrated by electrochemical impedance spectroscopy. Even if the biosensor response is due to the detection of H2O2 at anodic potentials, glucose can be accurately determined in the presence of ascorbic acid or other interferences, commonly present in real matrices in anionic form, since they can not reach the electrode surface. The effectiveness of the developed biosensor has been demonstrated by measuring glucose in samples of fruit juices containing ascorbic acid at high levels.
Hypoosmotic swelling affects zinc homeostasis in cultured rat astrocytes
Authors: Kruczek Caroline , Görg Boris , Keitel Verena , Pirev Elvis , Kröncke Klaus D. , Schliess Freimut , Häussinger Dieter
Published: August 2008

Astrocyte swelling is observed in different types of brain injury including hepatic encephalopathy (HE). This study investigates the role of astrocyte swelling on Zn2+ homeostasis in hypoosmotically treated astrocytes by using the Zn2+ indicators Newport‐Green, Zinquin, and RhodZin‐3. Hypoosmolarity (205 mosmol/L) led to a persistent increase of the intracellular “free” Zn2+ concentration [Zn2+]i within 15 min, which was reversible after reinstitution of normoosmolarity (305 mosmol/L). The hypoosmotic [Zn2+]i increase was abolished in the presence of the Zn2+ chelator TPEN, the NMDA receptor antagonists MK‐801 and AP5, the antioxidant epigallocatechin gallate, and the nitric oxide synthase inhibitors L‐NMMA and TRIM. Hypoosmolarity triggered nuclear accumulation of the metal response element‐binding transcription factor MTF‐1 and the specificity protein Sp1 and expression of the mRNAs encoding metallothionein and the Sp1‐regulated peripheral‐type benzodiazepine receptor (PBR). These effects were abolished by the Zn2+ chelator TPEN. The data suggest that astrocyte swelling affects gene expression by modulation of [Zn2+]i. Whereas Zn2+‐dependent upregulation of metallothionein may help to counteract excessive astrocyte swelling and production of reactive oxygen and nitrogen oxide species, stimulation of PBR expression may augment HE development. © 2008 Wiley‐Liss, Inc.
Stress perception and commuting
Authors: Gottholmseder Georg , Nowotny Klaus , Pruckner Gerald J. , Theurl Engelbert
Published: August 2008

This paper analyzes the determinants of the perceived stress level of workers with a special focus on the effects of commuting, while controlling for personal and work‐related characteristics. Using ordered logistic regression we find that several dimensions of the commuting situation, such as impedance, control and predictability of commuting, significantly influence the perceived stress level. Therefore, stress and stress‐related health problems should be taken into consideration when analyzing the economic costs of commuting. Copyright © 2008 John Wiley & Sons, Ltd.
Investing time in health: do socioeconomically disadvantaged patients spend more or less extra time on diabetes self‐care?
Authors: Ettner Susan L. , Cadwell Betsy L. , Russell Louise B. , Brown Arleen , Karter Andrew J. , Safford Monika , Mangione Carol , Beckles Gloria , Herman William H. , Thompson Theodore J. ,   and The TRIAD Study Group
Published: August 2008

Background: Research on self‐care for chronic disease has not examined time requirements. Translating Research into Action for Diabetes (TRIAD), a multi‐site study of managed care patients with diabetes, is among the first to assess self‐care time.

Objective: To examine associations between socioeconomic position and extra time patients spend on foot care, shopping/cooking, and exercise due to diabetes.

Data: Eleven thousand nine hundred and twenty‐seven patient surveys from 2000 to 2001.

Methods: Bayesian two‐part models were used to estimate associations of self‐reported extra time spent on self‐care with race/ethnicity, education, and income, controlling for demographic and clinical characteristics.

Results: Proportions of patients spending no extra time on foot care, shopping/cooking, and exercise were, respectively, 37, 52, and 31%. Extra time spent on foot care and shopping/cooking was greater among racial/ethnic minorities, less‐educated and lower‐income patients. For example, African‐Americans were about 10 percentage points more likely to report spending extra time on foot care than whites and extra time spent was about 3 min more per day.

Discussion: Extra time spent on self‐care was greater for socioeconomically disadvantaged patients than for advantaged patients, perhaps because their perceived opportunity cost of time is lower or they cannot afford substitutes. Our findings suggest that poorly controlled diabetes risk factors among disadvantaged populations may not be attributable to self‐care practices. Copyright © 2008 John Wiley & Sons, Ltd.
Four potential biomarkers as prognostic factors in stage III serous ovarian adenocarcinomas
Authors: Partheen Karolina , Levan Kristina , Österberg Lovisa , Claesson Ingela , Fallenius Ghita , Sundfeldt Karin , Horvath György
Published: August 2008

The mortality rate for patients with ovarian carcinomas is high and the available prognostic factors are insufficient. The use of biomarkers may contribute to better prediction and survival for these patients. We aimed to study the gene and protein expressions for 7 potential biomarkers, to determine if it is possible to use them as prognostic factors. Genes selected from our previous microarray analysis (2006), CLU, ITGB3, TACC1, MUC5B, CAPG, PRAME and TROAP, were analyzed in 19 of the tumors with quantitative real‐time polymerase chain reaction (QPCR). We found that CLU and ITGB3 were more expressed in tumors from survivors and PRAME and CAPG were more expressed in tumors from deceased patients. None of the other 3 genes were significantly differently expressed. The protein expressions of CLU, ITGB3, PRAME and CAPG were analyzed in 43 of the tumors with western blot for semiquantitative analysis. We established that the mRNA and protein expressions correlated and that all 4 proteins were significantly differently expressed. Further, immunohistochemistry (IHC) was used to localize the expression of the proteins in the tumor samples. According to our results, the 4 biomarkers CLU, ITGB3, PRAME and CAPG may be used as prognostic factors for patients with stage III serous ovarian adenocarcinomas. © 2008 Wiley‐Liss, Inc.
Loss of Drop1 expression already at early tumor stages in a wide range of human carcinomas
Authors: Marmé Alexander , Zimmermann Hans‐Peter , Moldenhauer Gerhard , Schorpp‐Kistner Marina , Müller Claudia , Keberlein Olga , Giersch Antje , Kretschmer Jürgen , Seib Brigitte , Spiess Eberhard , Hunziker Andreas , Merchán Faustino , Möller Peter , Hahn Uwe , Kurek Raffael , Marmé Frederik , Bastert Gunther , Wallwiener Diethelm , Ponstingl Herwig
Published: August 2008

In a study on gene deregulation in ovarian carcinoma we found a mRNA coding for a 350 kDa protein, Drop1, to be downregulated 20‐ to 180‐fold in the majority of ovarian and mammary carcinomas. The mRNA is encoded by a set of exons in the 5′ region of the SYNE1 gene. Immunohistochemical staining for Drop1 protein by a specific monoclonal antibody corresponds to the pattern seen for the mRNA. cDNA arrays of matched pairs of tumor and normal tissue and in situ hybridizations confirmed the drastic loss of Drop1 mRNA as a common feature in uterus, cervix, kidney, lung, thyroid and pancreas carcinomas, already at early tumor stages and in all metastases. Two‐hybrid studies suggest a role of this deficiency in the malignant progression of epithelial tumors. © 2008 Wiley‐Liss, Inc.
Modification of the inverse association between dietary vitamin D intake and colorectal cancer risk by a FokI variant supports a chemoprotective action of Vitamin D intake mediated through VDR binding
Authors: Theodoratou Evropi , Farrington Susan M. , Tenesa Albert , McNeill Geraldine , Cetnarskyj Roseanne , Barnetson Rebecca A. , Porteous Mary E. , Dunlop Malcolm G. , Campbell Harry
Published: August 2008

Vitamin D has anticarcinogenic properties and might influence colorectal cancer (CRC) risk, but the epidemiological evidence is inconsistent. Many mechanisms of action for vitamin D have been proposed, with some of them initiating via its binding to the vitamin D receptor (VDR). Using a large Scottish case–control study, we investigated (i) main associations between CRC, vitamin D and calcium dietary intake and 4 VDR single nucleotide polymorphisms (rs10735810, rs1544410, rs11568820, rs7975232) and (ii) interaction associations between the VDR variants, vitamin D and calcium intakes. Inverse and dose‐dependent associations were found between CRC risk, dietary [Odds ratio (OR) = 0.77, 95% confidence intervals (CI) 0.63, 0.92, p‐trend = 0.012] and total vitamin D (OR = 0.80, 95% CI 0.65, 0.98, p‐trend = 0.014) intake in multivariable‐adjusted logistic regression models, whereas neither calcium intake nor any of the VDR variants were associated with CRC. Additionally, we observed statistically significant interactions (case–control, case‐only designs) between vitamin D and calcium intake and rs10735810 (p‐interaction 0.02, 0.006, respectively). We conducted meta‐analyses of cohort, case–control and serum studies that also showed an inverse association between dietary vitamin D intake and CRC (serum studies: combined OR = 0.70, 95% CI 0.56, 0.87). The evidence of interaction we report here further supports the inverse association between vitamin D mediated through binding to the VDR. © 2008 Wiley‐Liss, Inc.
Highly sensitive detection of early‐stage pancreatic cancer by multimodal near‐infrared molecular imaging in living mice
Authors: von Burstin Johannes , Eser Stefan , Seidler Barbara , Meining Alexander , Bajbouj Monther , Mages Jörg , Lang Roland , Kind Alexander J. , Schnieke Angelika E. , Schmid Roland M. , Schneider Günter , Saur Dieter
Published: August 2008

Pancreatic cancer is a serious disease with poor patient outcome, often as a consequence of late diagnosis in advanced stages. This is in large part due to the lack of diagnostic tools for early detection. To address this deficiency, we have investigated novel molecular near‐infrared fluorescent (NIRF) in vivo imaging techniques in clinically relevant mouse models of pancreatic cancer. Genome wide gene expression profiling was used to identify cathepsin cystein proteases and matrix metalloproteinases (MMP) as targets for NIRF imaging. Appropriate protease activatable probes were evaluated for detection of early‐stage pancreatic cancer in mice with orthotopically implanted pancreatic cancer cell lines. Mice with pancreatitis served as controls. Whole body in vivo NIRF imaging using activatable cathepsin sensitive probes specifically detected pancreatic tumors as small as 1–2 mm diameter. Imaging of MMP activity demonstrated high specificity for MMP positive tumors. Intravital flexible confocal fluorescence lasermicroscopy of protease activity enabled specific detection of pancreatic tumors at the cellular level. Importantly, topical application of NIRF‐probes markedly reduced background without altering signal intensity. Taken together, macroscopic and confocal lasermicroscopic molecular in vivo imaging of protease activity is highly sensitive, specific and allows discrimination between normal pancreatic tissue, inflammation and pancreatic cancer. Translation of this approach to the clinic could significantly improve endoscopic and laparoscopic detection of early‐stage pancreatic cancer. © 2008 Wiley‐Liss, Inc.
Nucleotide excision repair genes and risk of lung cancer among San Francisco Bay Area Latinos and African Americans
Authors: Chang Jeffrey S. , Wrensch Margaret R. , Hansen Helen M. , Sison Jennette D. , Aldrich Melinda C. , Quesenberry Charles P. , Seldin Michael F. , Kelsey Karl T. , Kittles Rick A. , Silva Gabriel , Wiencke John K.
Published: August 2008

Few studies on the association between nucleotide excision repair (NER) variants and lung cancer risk have included Latinos and African Americans. We examine variants in 6 NER genes (ERCC2, ERCC4, ERCC5, LIG1, RAD23B and XPC) in association with primary lung cancer risk among 113 Latino and 255 African American subjects newly diagnosed with primary lung cancer from 1998 to 2003 in the San Francisco Bay Area and 579 healthy controls (299 Latinos and 280 African Americans). Individual single nucleotide polymorphism and haplotype analyses, multifactor dimensionality reduction (MDR) and principal components analysis (PCA) were performed to assess the association between 6 genes in the NER pathway and lung cancer risk. Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) was associated with reduced lung cancer risk [odds ratio (OR) of 0.65 and 95% confidence interval (CI): 0.44–0.97], especially among nonsmokers (OR = 0.29; 95% CI: 0.12–0.67). From MDR analysis, in Latinos, smoking and 3 SNPs (ERCC2 rs171140, ERCC5 rs17655 and LIG1 rs20581) together had a prediction accuracy of 67.4% (p = 0.001) for lung cancer. Among African Americans, His/His genotype of ERCC5 His1104Asp (rs17655) was associated with increased lung cancer risk (OR = 1.78; 95% CI: 1.09–2.91), and LIG1 haplotype GGGAA (rs20581, rs156641, rs3730931, rs20579 and rs439132) was associated with reduced lung cancer risk (OR = 0.61; 95% CI: 0.42–0.88). Our study suggests different elements of the NER pathway may be important in the different ethnic groups resulting either from different linkage relationship, genetic backgrounds and/or exposure histories. © 2008 Wiley‐Liss, Inc.
Validation of a novel biomarker for acute axonal injury in experimental autoimmune encephalomyelitis
Authors: Gresle Melissa M. , Shaw Gerry , Jarrott Bevyn , Alexandrou Estella N. , Friedhuber Anna , Kilpatrick Trevor J. , Butzkueven Helmut
Published: August 2008

In multiple sclerosis, inflammatory axonal injury is a key pathological mechanism responsible for the development of progressive neurological dysfunction. The injured axon represents a therapeutic target in this disease; however, therapeutic trials of neuroprotective candidates will initially require preclinical testing in an animal model of inflammatory axonal injury and subsequently the development of a reliable paraclinical measure of axonal degeneration in humans. In the present study, we demonstrate the validity of serum phosphorylated neurofilament H (pNF‐H) as a marker of axonal injury in murine experimental autoimmune encephalomyelitis (EAE). At the time of maximum disease severity (EAE day 22), the average serum pNF‐H level reached 5.7 ng/ml, correlating significantly with the EAE paraplegia score (r = 0.75, P < 0.001). On average, 40% of axons in the spinal cord were lost in EAE, and serum pNF‐H levels were highly correlated with axon loss (r = 0.8, P < 0.001). Axonal injury was a severe and acute event, insofar as serum pNF‐H levels were not significantly elevated at early (EAE day 12) or late (EAE days 35 and 50) disease time points. Our results demonstrate that acute inflammatory axonal injury is a pathological feature of murine MOG35–55 EAE, indicating that this model may mirror the acute pathological events in active multiple sclerosis lesions. Furthermore, we have validated the serum pNF‐H assay as an unbiased measurement of axonal injury in EAE, facilitating rapid screening of potential neuroprotective therapies in this model. © 2008 Wiley‐Liss, Inc.
Retinal pigment epithelial cells promote spatial reorganization and differentiation of retina photoreceptors
Authors: German Olga L. , Buzzi Edgardo , Rotstein Nora P. , Rodríguez‐Boulan Enrique , Politi Luis E.
Published: August 2008

Retina differentiation involves the acquisition of a precise layered arrangement, with RPE cells in the first layer in intimate contact with photoreceptors in the second layer. Here, we developed an in vitro coculture model, to test the hypothesis that RPE cells play a pivotal role in organizing the spatial structure of the retina. We cocultured rat retinal neurons with ARPE‐19 epithelial cells under various experimental conditions. Strikingly, when seeded over RPE cells, photoreceptors attached to their apical surfaces and proceeded with their development, including the increased synthesis of rhodopsin. Conversely, when we seeded RPE cells over neurons, the RPE cells rapidly detached photoreceptors from their substrata and positioned themselves underneath, thus restoring the normal in vivo arrangement. Treatment with the metalloproteinase inhibitor TIMP‐1 blocked this reorganization, suggesting the involvement of metalloproteinases in this process. Reorganization was highly selective for photoreceptors because 98% of photoreceptors but very few amacrine neurons were found to redistribute on top of RPE cells. Interestingly, RPE cells were much more efficient than other epithelial or nonepithelial cells in promoting this reorganization. RPE cells also promoted the growth of photoreceptor axons away from them. An additional factor that contributed to the distal arrangement of photoreceptor axons was the migration of photoreceptor cell bodies along their own neurites toward the RPE cells. Our results demonstrate that RPE and photoreceptor cells interact in vitro in very specific ways. They also show that in vitro studies may provide important insights into the process of pattern formation in the retina. © 2008 Wiley‐Liss, Inc.