bluuebunny/crossref_metadata_2025 huggingface dataset:
La crise de la médecine générale
Authors: Winckler Martin
Published: May 2009

Résumé Quatre aspects de la crise de la médecine générale sont soulignés : crise symbolique (la médecine générale est méprisée), crise politique et sociale (les politiques de santé ne s’appuient pas sur elle), crise de la formation (les généralistes sont formés par une université élitiste, dirigée par les spécialistes), crise de l’investissement individuel (ses conditions d’exercice sont si difficiles – en particulier pour les femmes – que des mesures prioritaires devraient faciliter leur installation et leurs conditions de travail, mais ces mesures ne sont pas prises).
L'hôpital en crise ?
Authors: Évin Claude
Published: May 2009

Résumé L’hôpital public représente des atouts importants aussi bien pour notre système de santé qu’à travers le rôle social qu’il assume. Il est toutefois confronté à des enjeux considérables : défi démographique, évolution des missions et notamment hyperspécialisation de certaines techniques, modification des règles de financement avec la mise en place de la tarification à l’activité dans un contexte budgétaire très contraint… Soit l’hôpital subit ces contraintes et nous assisterons à un affaiblissement des missions de service public qu’il remplit, soit il assure sa mutation en développant de véritables stratégies de groupe mettant en œuvre des rapprochements entre établissements publics, voire entre établissements publics et privés lorsque le maintien d’une offre de soins de qualité l’impose. Plusieurs outils contenus dans le projet de loi « Hôpital, patients, santé, territoires » permettront ces évolutions. L’hôpital doit aussi améliorer son efficience interne. S’il a, sur ce point, beaucoup d’efforts à faire, il ne faudrait pas que des lourdeurs et des contraintes administratives viennent freiner sa bonne volonté.
Determination of Size, Morphology, and Nitrogen Impurity Location in Treated Detonation Nanodiamond by Transmission Electron Microscopy
Authors: Turner Stuart , Lebedev Oleg I. , Shenderova Olga , Vlasov Igor I. , Verbeeck Jo , Van Tendeloo Gustaaf
Published: May 2009

Size, morphology, and nitrogen impurity location, all of which are all thought to be related to the luminescent properties of detonation nanodiamonds, are determined in several detonation nanodiamond samples using a combination of transmission electron microscopy techniques. Results obtained from annealed and cleaned detonation nanodiamond samples are compared to results from conventionally purified detonation nanodiamond. Detailed electron energy loss spectroscopy combined with model‐based quantification provides direct evidence for the sp3 like embedding of nitrogen impurities into the diamond cores of all the studied nanodiamond samples. Simultaneously, the structure and morphology of the cleaned detonation nanodiamond particles are studied using high resolution transmission electron microscopy. The results show that the size and morphology of detonation nanodiamonds can be modified by temperature treatment and that by applying a special cleaning procedure after temperature treatment, nanodiamond particles with clean facets almost free from sp2 carbon can be prepared. These clean facets are clear evidence that nanodiamond cores are not necessarily in coexistence with a graphitic shell of non‐diamond carbon.
Water versus Solvent‐Free Conditions for the Enantioselective Inter‐ and Intramolecular Aldol Reaction Employing L‐Prolinamides and L‐Prolinethioamides as Organocatalysts
Authors: Almaşi Diana , Alonso Diego A. , Balaguer Andrea‐Nekane , Nájera Carmen
Published: May 2009

magnified image

Organocatalysts 1, derived from L‐proline and (1S,2R)‐cis‐1‐aminoindan‐2‐ol or (R)‐1‐aminoindane, are evaluated as promoters in the direct asymmetric aldol reaction between ketones and aromatic aldehydes in the presence of water and under solvent‐free reaction conditions. L‐Prolinethioamides 1c and 1d exhibited higher enantioselectivity than the corresponding prolinamides 1a and 1b in the model aldol reaction between cyclohexanone and 4‐nitrobenzaldehyde in the presence of 4‐nitrobenzoic acid as cocatalyst. In particular, L‐prolinethioamide 1d (5 mol%), derived from L‐proline and (R)‐1‐aminoindane, is shown as the most efficient organocatalyst studied promoting the direct aldol reaction of cycloalkyl, alkyl, and α‐functionalized ketones with aromatic aldehydes in the presence of water and under solvent‐free reaction conditions employing only 2 equivalents of nucleophile. Generally, anti‐aldol products are obtained in high yields and excellent diastereo‐ and enantioselectivities (up to >98/2 anti/syn, up to 98% ee). Solvent‐free conditions give slightly higher dr and ee than using water as solvent. In addition, organocatalyst 1d can be easily recovered by extractive work‐up and reused. Prolinethioamide 1d (5 mol%) in combination with 4‐NO2C6H4CO2H (5 mol%) is also a very effective organocatalytic system for the asymmetric solvent‐free intramolecular Hajos–Parrish–Eder–Sauer–Wiechert reaction with comparable or higher levels of enantioselectivity (up to 88% ee) to other reported catalysts in organic solvents.
Brief communication: Blue eyes in lemurs and humans: Same phenotype, different genetic mechanism
Authors: Bradley Brenda J. , Pedersen Anja , Mundy Nicholas I.
Published: May 2009

Almost all mammals have brown or darkly‐pigmented eyes (irises), but among primates, there are some prominent blue‐eyed exceptions. The blue eyes of some humans and lemurs are a striking example of convergent evolution of a rare phenotype on distant branches of the primate tree. Recent work on humans indicates that blue eye color is associated with, and likely caused by, a single nucleotide polymorphism (rs12913832) in an intron of the gene HERC2, which likely regulates expression of the neighboring pigmentation gene OCA2. This raises the immediate question of whether blue eyes in lemurs might have a similar genetic basis. We addressed this by sequencing the homologous genetic region in the blue‐eyed black lemur (Eulemur macaco flavifrons; N = 4) and the closely‐related black lemur (Eulemur macaco macaco; N = 4), which has brown eyes. We then compared a 166‐bp segment corresponding to and flanking the human eye‐color‐associated region in these lemurs, as well as other primates (human, chimpanzee, orangutan, macaque, ring‐tailed lemur, mouse lemur). Aligned sequences indicated that this region is strongly conserved in both Eulemur macaco subspecies as well as the other primates (except blue‐eyed humans). Therefore, it is unlikely that this regulatory segment plays a major role in eye color differences among lemurs as it does in humans. Although convergent phenotypes can sometimes come about via the same or similar genetic changes occurring independently, this does not seem to be the case here, as we have shown that the genetic basis of blue eyes in lemurs differs from that of humans. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.
Possible relationship of cranial traumatic injuries with violence in the south‐east Iberian Peninsula from the Neolithic to the Bronze Age
Authors: Jiménez‐Brobeil S.A. , du Souich Ph. , Al Oumaoui I.
Published: May 2009

The main aim of this study was to analyze the presence and distribution of cranial trauma, as possible evidence of violence, in remains from the Neolithic to Bronze Age from the SE Iberian Peninsula. The sample contains skulls, crania, and cranial vaults belonging to 410 prehistoric individuals. We also studied 267 crania from medieval and modern times for comparative purposes. All lesions in the prehistoric crania are healed and none of them can be attributed to a specific weapon. In all studied populations, injuries were more frequent in adults than in subadults and also in males than in females, denoting a sexual division in the risk of suffering accidents or intentional violence. According to the archeological record, the development of societies in the SE Iberian Peninsula during these periods must have entailed an increase in conflict. However, a high frequency of cranial traumatic injuries was observed in the Neolithic series, theoretically a less conflictive time, and the lowest frequency was in crania from the 3rd millennium B.C. (Copper Age), which is characterized by the archeologists as a period of increasing violence. The relatively large size and the high rate of injuries in Neolithic crania and the practice of cannibalism are strongly suggestive of episodes of interpersonal or intergroup conflict. The number and distribution of injuries in Bronze Age is consistent with the increase in violence at that time described by most archeologists. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.
End‐on‐Stickstoffinsertion einer Diazoverbindung in eine GeII‐H‐Bindung und eine vergleichbare Reaktion mit Azodicarbonsäurediethylester
Authors: Jana Anukul , Sen Sakya S. , Roesky Herbert W. , Schulzke Carola , Dutta Sudipta , Pati Swapan K.
Published: May 2009

End‐on gebundenes Stickstoffatom: Das Germanium(II)‐hydrid [LGeH] mit L=[HC{(CMe)(2,6‐iPr2C6H3N)}2] reagiert mit einem Diazoalkan zum Hydrazonderivat (siehe Molekülstruktur). Die Reaktion resultiert aus einer zuvor unbekannten End‐on‐Insertion der Diazoverbindung.

magnified image
Nomenklatur der Rotaxane und Pseudorotaxane
Authors: Schomburg Ida
Published: May 2009

Wo genau sich welche Ringe auf der/den Achsenkomponenten eines Rotaxans befinden, kann mit der hier vorgestellten Nomenklatur eindeutig angegeben werden. Der generische Name von Rotaxanen wie den hier gezeigten (E=Endgruppe) lautet (Präfix)‐[v]{[w][Name(n) der Achsenkomponente(n)]‐rotaxa‐[x][Name(n) der makrocyclischen Komponente(n)]}.

magnified image

Dieser Text bietet ausführliche Definitionen von Rotaxanen, Pseudorotaxanen, ihren Komponenten und anderen sie betreffenden Begriffen. Einheitliche Prinzipien zur Klassifizierung und Benennung der Rotaxan‐ und Pseudorotaxantypen werden beschrieben und mit Beispielen illustriert. Des Weiteren werden Empfehlungen für eine eindeutige Benennung von Rotaxanisomeren mit speziellen Deskriptoren gegeben, die Informationen zu den Positionen der Rotaxankomponenten enthalten.
Titelbild: Photoprogrammable Organic Light‐Emitting Diodes (Angew. Chem. 22/2009)
Authors: Zacharias Philipp , Gather Malte C. , Köhnen Anne , Rehmann Nina , Meerholz Klaus
Published: May 2009

Programmierbare organische Leuchtdioden: Ein Oxetan‐funktionalisiertes Dithienylethen wird durch UV‐Bestrahlung von der farblosen offenen Form in eine dunkelblaue geschlossene Form umgewandelt, während sichtbares Licht die Reaktion wieder umkehrt. Basierend auf diesem Prinzip entwickelten K. Meerholz et al. eine reversibel schaltbare organische Leuchtdiode, die in der Zuschrift auf S. 4098 ff. vorgestellt wird.

magnified image
Inside Cover: Switching the Chirality of Single Adsorbate Complexes (Angew. Chem. Int. Ed. 22/2009)
Authors: Parschau Manfred , Passerone Daniele , Rieder Karl‐Heinz , Hug Hans J. , Ernst Karl‐Heinz
Published: May 2009

Wrong handedness? No problem! K.‐H. Ernst et al. describe in their Communication on page 4065 ff. how the chirality of single adsorbates can be switched into the opposite enantiomeric state. By using inelastically tunneling electrons from the tip of a scanning tunneling microscope in an ultra‐high vacuum, certain molecular vibrations are excited that, in turn, cause different actions such as hopping, rotation, and chirality conversion at the surface.

magnified image
Pervaporation membranes from natural rubber latex grafted with poly(2‐hydroxyethyl methacrylate) (NR‐g‐PHEMA) for the separation of water–acetone mixtures
Authors: Amnuaypanich Sittipong , Ratpolsan Pikul
Published: May 2009

NR‐graft‐PHEMA latexes were synthesized by the use of graft emulsion polymerization. By increasing the HEMA monomer concentration, we found that the grafting percentage (GP) also increased. In addition, GP increased significantly at low initiator concentrations before it leveled off at moderate concentrations, and a slight decrease was observed at high initiator concentrations. NR‐g‐PHEMA latexes were prepared as pervaporation membranes for the separation of water–acetone mixtures. From the equilibrium swelling, the nonideal behavior of membrane swelling in water–acetone mixtures was found such that there appeared the maximum swelling degree at a certain concentration of liquid mixtures. Moreover, the water concentration at maximum swelling shifted to high water concentration with increasing amount of graft‐PHEMA. The sorption study suggested the preferential sorption of water on the membranes. Also, the sorption isotherms implied that there was a coupling between water and acetone molecules. Pervaporation separation of water–acetone mixtures was studied with NR‐g‐PHEMA membranes. As the feed water concentration increased, the partial water fluxes increased in contrast to the partial fluxes of acetone. From the permeation ratio, θw, the strong coupling of acetone on the water transport was observed, particularly for the membrane with high graft‐PHEMA under acetone‐rich conditions. As the feed temperature increased, the total permeation across the membranes was enhanced. The partial fluxes of water and acetone as a function of temperature followed the Arrhenius relationship by which the activation energies for permeation were estimated as 3.53 kJ/mol for water and 21.95 kJ/mol for acetone. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
A Lorentz model for weak magnetic field bioeffects: Part II—Secondary transduction mechanisms and measures of reactivity
Authors: Muehsam David J. , Pilla Arthur A.
Published: May 2009

In Part I it was shown that the thermal component of the motion of a charged particle in an oscillator potential, that is, within a molecular binding site, rotates at the Larmor frequency in an applied magnetic field. It was also shown that the Larmor angular frequency is independent of the thermal noise strength and thus offers a mechanism for the biological detection of weak (µT‐range) magnetic fields. Part II addresses the question of how the Larmor trajectory could affect biological reactivity. The projection of the motion onto a Cartesian axis measures the nonuniformity of the Larmor trajectory in AC and combined AC/DC magnetic fields, suggesting a means of assessing resonances. A physically meaningful measure of reactivity based upon the classical oscillator trajectory is suggested, and the problem of initial conditions is addressed through averaging over AC phases. AC resonance frequencies occur at the Larmor frequency and at other frequencies, and are dependent upon the ratio of AC/DC amplitudes and target kinetics via binding lifetime. The model is compared with experimental data reported for a test of the ion parametric resonance (IPR) model on data from Ca2+ flux in membrane vesicles, neurite outgrowth from PC‐12 cells and a cell‐free calmodulin‐dependent myosin phosphorylation system, and suggests Mg2+ is the target for these systems. The results do not require multiple‐ion targets, selection of isotopes, or additional curve fitting. The sole fitting parameter is the binding lifetime of the target system and the results shown are consistent with the literature on binding kinetics. Bioelectromagnetics 30:476–488, 2009. © 2009 Wiley‐Liss, Inc.
Photoluminescence properties of a novel phosphor CaB2O4:Eu3+ under NUV excitation
Authors: Huang Junli , Zhou Liya , Pang Qi , Gong Fuzhong , Sun Jianhua , Wang Wei
Published: May 2009

The new borate phosphor CaB2O4:Eu3+ was synthesized by solid‐state method and their photoluminescence properties were investigated. The results show that the pure phase of CaB2O4 could be available at 900°C, CaB2O4:Eu3+ phosphor could be effectively excited by the near ultraviolet light (NUV) (392 nm), and the luminescent intensity of CaB2O4:Eu3+ phosphor reached to the highest when the doped‐Eu3+ content was 4 mol%. The emission spectra of CaB2O4:Eu3+ phosphor could exhibit red emission at 612 nm and orange emission at 588 nm, which are ascribed to the 5D0–7F2 and 5D0–7F1 transitions of Eu3+ ions. Copyright © 2009 John Wiley & Sons, Ltd.
A New Approach for Reversible RNA Photocrosslinking Reaction: Application to Sequence‐Specific RNA Selection
Authors: Yoshimura Yoshinaga , Ohtake Tomoko , Okada Hajime , Fujimoto Kenzo
Published: May 2009

On and off in a flash: We describe a novel, ultrafast, reversible, interstrand RNA photocrosslinking reaction via 3‐cyanovinylcarbazole nucleoside. The interstrand RNA‐photocrosslinking reaction showed a high degree of sequence specificity and can be used in the selection of a target RNA sequence.

magnified image
Electronic Structure and Bonding in Neutral and Dianionic Boradiphospholes: R′BC2P2R2 (R=H, tBu, R′=H, Ph)
Authors: Usharani Dandamudi , Poduska Anne , Nixon John F. , Jemmis Eluvathingal D.
Published: May 2009

Classical and non‐classical isomers of both neutral and dianionic BC2P2H3 species, which are isolobal to Cp+ and Cp−, are studied at both B3LYP/6‐311++G(d,p) and G3B3 levels of theory. The global minimum structure given by B3LYP/6‐311++G(d,p) for BC2P2H3 is based on a vinylcyclopropenyl‐type structure, whereas BC2P2H32− has a planar aromatic cyclopentadienyl‐ion‐like structure. However, at the G3B3 level, there are three low‐energy isomers for BC2P2H3: 1) tricyclopentane, 2) nido and 3) vinylcyclopropenyl‐type structures, all within 1.7 kcal mol−1 of each other. On the contrary, for the dianionic species the cyclic planar structure is still the minimum. In comparison to the isolobal Cp+ and HnCnP5−n+ isomers, BC2P2H3 shows a competition between π‐delocalised vinylcyclopropenyl‐ and cluster‐type structures (nido and tricyclopentane). Substitution of H on C by tBu, and H on B by Ph, in BC2P2H3 increases the energy difference between the low‐lying isomers, giving the lowest energy structure as a tricyclopentane type. Similar substitution in BC2P2H32− merely favours different positional isomers of the cyclic planar geometry, as observed in 1) isoelectronic neutral heterodiphospholes EtBu2C2P2 (E=S, Se, Te), 2) monoanionic heterophospholyl rings EtBu2C2P2 (E=P−, As−, Sb−) and 3) polyphospholyl rings anions tBu5−nCnP5−n (n=0–5). The principal factors that affect the stability of three‐, four‐, and five‐membered ring and acyclic geometrical and positional isomers of neutral and dianionic BC2P2H3 isomers appear to be: 1) relative bond strengths, 2) availability of electrons for the empty 2p boron orbital and 3) steric effects of the tBu groups in the HBC2P2tBu2 systems.
Intermediate filaments in Caenorhabditis elegans
Authors: Carberry Katrin , Wiesenfahrt Tobias , Windoffer Reinhard , Bossinger Olaf , Leube Rudolf E.
Published: May 2009

Intermediate filaments (IFs) make up one of the three major fibrous cytoskeletal systems in metazoans. Numerous IF polypeptides are synthesized in cell type‐specific combinations suggesting specialized functions. The review concentrates on IFs in the model organism Caenorhabditis elegans which carries great promise to elucidate the still unresolved mechanisms of IF assembly into complex networks and to determine IF function in a living organism. In contrast to Drosophila melanogaster, which lacks cytoplasmic IFs altogether, the nematode genome contains 11 genes coding for cytoplasmic IFs and only a single gene for a nuclear lamin. Its cytoplasmic IFs are expressed in developmentally and spatially defined patterns. As an example we present the case of the intestinal IFs which are abundant in the mechanically resilient endotube, a prominent feature of the C. elegans intestinal terminal web region. This IF‐rich structure brings together all three cytoskeletal filaments that are integrated into a coherent entity by the C. elegans apical junction (CeAJ) thereby completely surrounding and stabilizing the intestinal lumen with its characteristic brush border. Concepts on the developmental establishment of the endotube in relation to polarization and its function for maintenance of epithelial integrity are discussed. Furthermore, possible connections of the cytoplasmic cytoskeleton to the nuclear lamin IFs and the importance of these links for nuclear positioning are summarized. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.
Helicobacter pylori activates protein kinase C delta to control Raf in MAP kinase signalling: Role in AGS epithelial cell scattering and elongation
Authors: Brandt Sabine , Wessler Silja , Hartig Roland , Backert Steffen
Published: May 2009

Helicobacter pylori is a major etiological agent in the development of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. Virulent H. pylori strains harbor a type IV secretion system (T4SS) encoded by the cag pathogenicity island. This T4SS injects the CagA protein into gastric epithelial cells leading to actin‐cytoskeletal rearrangements followed by cell elongation and scattering. Here we report that PMA (4β‐phorbol‐12‐myristate‐13‐acetate), a well‐known cell‐permeable activator of protein kinase C (PKC), induces a remarkably similar cellular phenotype as compared to infection with H. pylori. PKCs comprise a large family of serine/threonine kinases which are important for multiple physiological processes of host cells. We therefore investigated the role of individual PKC members and the signalling pathways involved in phenotypical outcome. Using isoform‐specific silencing RNAs and pharmacological inhibitors we found that two isoforms, PKC‐α and PKC‐δ, were essential for both PMA‐ and H. pylori‐induced elongation phenotype. Furthermore, we provide evidence that PKC‐δ activity is profoundly stimulated during the course of infection using activation‐specific antibodies against PKC phosphorylated at threonine residue 505 or serine residue 660. Infection with H. pylori wild‐type and mutants showed that at least two bacterial factors activate PKC‐δ in a time‐dependent manner, one of which is CagA. Immunofluorescence microscopy studies further demonstrated that phosphorylated PKC‐δ is accumulated and recruited to dynamic actin‐structures at the cell membrane. Finally, we show that PKC‐δ specifically targets Raf kinase to stimulate the Erk1/2 kinase pathway, which is also crucial for phenotypical outcome. Thus, PKC‐δ is another important mediator of H. pylori‐induced pathogenesis. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.
Sustainable Chemical Manufacturing: A Matter of Resources, Wastes, Hazards, and Costs.
Authors: Lange Jean‐Paul
Published: May 2009

Chemical processes can be made more sustainable by minimizing their consumption of natural resources, the impact of wastes, their hazards, and their costs. These four basic dimensions are discussed and applied to three chemical processes that Shell applies commercially and has improved over several decades.

magnified image

Sustainable development is gaining importance in the chemical industry. It encompasses social, environmental, and economical aspects. Herein, sustainable development is translated into four basic dimensions, called “sustainability stresses”: resources, wastes, hazards, and costs. These sustainability stresses are discussed in some detail and their usefulness is illustrated by applying them to three manufacturing processes applied commercially by Shell, namely Shell’s OMEGA, SMPO, and “low monol” technologies for producing ethene diol, styrene/propene oxide, and polyether polyols, respectively. These examples show that large reductions in sustainable stresses have been achieved in a few decades. They also show that the economical, environmental, and social issues are not in conflict when tackled at their roots: they can be all addressed simultaneously.
Flow cytometric analysis of reticulocyte maturation after erythropoietin administration in rats
Authors: Wiczling Pawel , Ait‐Oudhia Sihem , Krzyzanski Wojciech
Published: May 2009

We have proposed a technique for transforming reticulocyte (RET) flow cytometry count into the age distribution allowing for a quantitative characterization of RETs dynamics. This technique was evaluated in homeostatic and erythropoietically stimulated rats. We administered a single intravenous dose (4,050 IU/kg) of recombinant human erythropoietin to Wistar rats, then stained their RETs with thiazole orange, and measured the distribution of the fluorescent signal using flow cytometry. The RET age distribution was determined assuming an exponential decline of RET RNA. The RET distribution over time was characterized by median age, production rate of mature red blood cell in the blood, bone marrow and blood maturation times, and RET loss from the blood. Erythropoietin was found to cause complex changes not only in RET count but also in age distribution. Generally, an increase in RET count was accompanied by the presence of young RETs and a decrease with the presence of old RETs. The rate at which RETs were removed from the blood was affected considerably by erythropoietin administration, and their death was attributed to it. Flow cytometric analysis of RET age distribution expands our understanding of erythropoiesis and augments the information we can obtain from RET measurements. © 2009 International Society for Advancement of Cytometry
Bayesian methods in cost–effectiveness studies: objectivity, computation and other relevant aspects
Authors: Armero C. , García‐Donato G. , López‐Quílez A.
Published: May 2009

In a probabilistic sensitivity analysis (PSA) of a cost–effectiveness (CE) study, the unknown parameters are considered as random variables. A crucial question is what probabilistic distribution is suitable for synthesizing the available information (mainly data from clinical trials) about these parameters. In this context, the important role of Bayesian methodology has been recognized, where the parameters are of a random nature. We explore, in the context of CE analyses, how formal objective Bayesian methods can be implemented. We fully illustrate the methodology using two CE problems that frequently appear in the CE literature. The results are compared with those obtained with other popular approaches to PSA. We find that the discrepancies can be quite marked, specially when the number of patients enrolled in the simulated cohort under study is large. Finally, we describe in detail the numerical methods that need to be used to obtain the results. Copyright © 2009 John Wiley & Sons, Ltd.
Spatially localized hippocampal shape analysis in late‐life cognitive decline
Authors: Xie Jing , Alcantara Dan , Amenta Nina , Fletcher Evan , Martinez Oliver , Persianinova Maria , DeCarli Charles , Carmichael Owen
Published: May 2009

We present a method for generating data‐driven, concise, and spatially localized parameterizations of hippocampal (HP) shape, and use the method to analyze HP atrophy in late‐life cognitive decline. The method optimizes a set of shape basis vectors (shape components) that strike a balance between spatial locality and compact representation of population shape characteristics. The method can be used for exploratory analysis of localized shape deformations in any population of HP on which point‐to‐point correspondence mappings have been established via anatomical landmarking or high‐dimensional warping. Experiments combine the method with an automated HP to HP mapping method to analyze tracings of 101 elderly subjects with normal cognition, mild cognitive impairment, and Alzheimer's Disease (AD) from an AD Center population. Results suggest that shape components corresponding to atrophy to the CA1 and subiculum HP fields—where early AD pathology is located—correlate strongly with robust measures of the cognitive dysfunction that is typical of early AD. Furthermore, the energy function minimized by the shape component optimization technique is shown to be smooth with few local minima, suggesting that the method may be relatively easy to apply in practice. © 2009 Wiley‐Liss, Inc.
Effects of exercise training on hippocampus concentrations of insulin and IGF‐1 in diabetic rats
Authors: Gomes Ricardo José , de Oliveira Camila Aparecida Machado , Ribeiro Carla , Mota Clécia Soares de Alencar , Moura Leandro Pereira , Tognoli Lilian Mari Marcondes Cesar , Leme José Alexandre Curiacos de Almeida , Luciano Eliete , de Mello Maria Alice Rostom
Published: May 2009

The present study investigated the role of swimming training on cerebral metabolism and hippocampus concentrations of insulin and IGF‐1 in diabetic rats. Wistar rats were divided in sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Diabetes was induced by Alloxan (35 mg kg−1b.w.). Training program consisted in swimming 5 days/week, 1 h/day, 8 weeks, supporting a load corresponding to 90% of maximal lactate steady state (MLSS). For MLSS determination, rats were submitted to three sessions of 25‐min supporting loads of 4, 5, or 6% of body wt, with intervals of 1 week. Blood samples were collected every 5 min for lactate determination. An acute exercise test (25 min to 90% of MLSS) was done in 7th week to confirm the efficacy of training. All dependent variables were analyzed by one‐way analysis of variance (ANOVA) and a significance level ofP< 0.05 was used for all comparisons. The Bonferroni test was used for post hoc comparisons. At the end of the training period, rats were sacrificed and sample blood was collected for determinations of serum glucose, insulin, GH, and IGF‐1. Samples of gastrocnemius muscle and liver were removed to evaluate glycogen content. Hippocampus was extracted to determinate glycogen, insulin, and IGF‐1 contents. Diabetes decreased serum GH, IGF‐1, and liver glycogen stores in SD. Diabetes also increased hippocampus glycogen and reduced hippocampus IGF‐1 content. Physical training recovered liver and hippocampus glycogen stores and promoted increases in serum IGF‐1 in TD group. Physical training restored hippocampus IGF‐1 content in diabetic group. It was concluded that in diabetic rats, physical training induces important metabolic and hormonal alterations that areassociated with an improvement in glucose homeostasis and with an increased activity in the systemic and hippocampus IGF‐1 peptide. © 2009 Wiley‐Liss, Inc.
Changes in Nearshore Zooplankton Associated with Species Invasions and Potential Effects on Larval Lake Whitefish (Coregonus clupeaformis)
Authors: Fernandez Randolph J. , Rennie Michael D. , Sprules W. Gary
Published: May 2009

We examined changes in the nearshore zooplankton community of South Bay, Lake Huron before (1982) and after (2002–2005) the invasions of dreissenid mussels and Bythotrephes longimanus and found substantial changes including lower cladoceran abundance, particularly Bosminidae, and higher copepod abundance after invasion. We also estimated changes in the energy content of zooplankton potentially available to larval lake whitefish before and after invasion using published values of energy content per unit mass. There were no differences in available zooplankton energy in May, the period when larvae feed inshore based on thermal preferences and surface temperature data. We conclude that changes in nearshore zooplankton communities following these species invasions probably do not affect larval lake whitefish. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Degradable metallic biomaterials: Design and development of Fe–Mn alloys for stents
Authors: Hermawan Hendra , Dubé Dominique , Mantovani Diego
Published: May 2009

Designing materials having suitable mechanical properties and targeted degradation behavior is the key for the development of biodegradable materials for medical applications, including stents. A series of Fe–Mn alloys was developed with the objective to obtain mechanical properties similar to those of stainless steel 316L and degradation behavior more suited than pure iron. Four alloys with Mn content ranging between 20 and 35 wt % were compared in this study. Their microstructure, mechanical properties, magnetic properties as well as degradation behavior were carefully investigated. Results show that their microstructure is mainly composed of γ phase with the appearance of ϵ phase in alloys having a lower Mn content. The yield strength and elongation of alloys was comprised between 234 MPa and 32% for Fe‐35%Mn alloy to 421 MPa and 7.5% for the Fe‐20%Mn alloy. All alloys show similar magnetic susceptibility (∼1.8 × 10−7 m3/kg) in the quenched condition. This magnetic susceptibility remains constant after plastic deformation for all the tested alloys except for the Fe‐20%Mn alloy. The corrosion rate was higher than pure iron. Among the alloys studied in this work, the Fe‐35%Mn alloy shows mechanical properties and degradation behavior closely approaching those required for biodegradable stents application. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Patterned macroarray plates in comparison of bacterial adhesion inhibition of tantalum, titanium, and chromium compared with diamond‐like carbon
Authors: Levon Jaakko , Myllymaa Katja , Kouri Vesa‐Petteri , Rautemaa Riina , Kinnari Teemu , Myllymaa Sami , Konttinen Yrjö T. , Lappalainen Reijo
Published: May 2009

Staphylococcus aureus device‐related infection is a common complication in implantology. Bacterial adhesion on implant surfaces is the initial step in the infective process. The aim was to develop a method suitable for quantitative bacterial adherence studies and to test a new diamond‐like carbon (DLC) coating against commonly used metallic biomaterials with regards to Staphylococcus aureus adhesion. Patterned silicon chips with spots of tantalum, titanium, chromium, and DLC were produced using ultraviolet lithography and physical vapor deposition. These patterned chips were used as such or glued to array plates, pretreated with serum and exposed to S. aureus (S‐15981) for 90 min, followed by acridine orange staining and fluorescence microscopy. An adhesion index showed that the ranking order of the biomaterials was titanium, tantalum, chromium, and DLC, with the DLC being clearly most resistant against colonization with S. aureus. Micropatterned surfaces are useful for quantitative comparison of bacterial adherence on different biomaterials. In the presence of serum, DLC is superior in its ability to resist adhesion and colonization by S. aureus compared with the commonly used biomaterial metals tantalum, titanium, and chromium. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Emotional intelligence and mental disorder
Authors: Hertel Janine , Schütz Astrid , Lammers Claas‐Hinrich
Published: May 2009

Emotional abilities were measured with a performance test of emotional intelligence (The Mayer‐Salovey‐Caruso Emotional Intelligence Test; Mayer, Salovey, & Caruso, 2002) in patients diagnosed with major depressive disorder, substance abuse disorder, or borderline personality disorder (BPD), and a nonclinical control group. Findings showed that all clinical groups differed from controls with respect to their overall emotional intelligence score, which dovetails with previous findings from self‐report measures. Specifically, we found that the ability to understand emotional information and the ability to regulate emotions best distinguished the groups. Findings showed that patients with substance abuse disorder and BPD patients were most impaired. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1–13, 2009.
Does attachment avoidance help people cope with loss? the moderating effects of relationship quality
Authors: Mancini Anthony D. , Robinaugh Don , Shear Katherine , Bonanno George A.
Published: May 2009

Previous research has been inconsistent about the role of attachment avoidance in coping with loss. The present study sought to resolve this issue by examining the potential moderating role of relationship quality with the deceased. The authors used longitudinal data on bereaved spouses (N=50) collected at 4 and 18 months postloss. Three‐way effects emerged among attachment avoidance, attachment anxiety, and marital quality in the prediction of complicated grief (CG) symptoms at 18 months, controlling for 4‐month symptoms. Findings indicated that, in the context of high but not low marital quality, persons with a dismissingly avoidant attachment style (high avoidance, low anxiety) experienced marked reductions in CG symptoms from 4 to 18 months. Findings clarify the role of attachment avoidance in coping with loss and underscore that relationship quality is a critical factor in the attachment‐grief relationship. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1–10, 2009.
Syntheses and fluorescent properties of 2‐amino substituted 6,7‐dimethoxy‐4‐(trifluoromethyl)quinolines
Authors: Stadlbauer Wolfgang , Avhale Appasaheb B. , Badgujar Naresh S. , Uray Georg
Published: May 2009

magnified image

2‐Amino‐substituted 6,7‐dimethoxy‐4‐trifluoromethyl‐quinolines were synthesized from the 2‐oxo compound 1 via 2‐chloroquinoline 2 and aminated with anilines or benzylamine to give highly fluorescent molecules 4, 5. 2‐Aminoquinoline 8 was obtained via azidation of 2, 3, 3a, 3b, 3c, 4, 4a, 4b, 4c, 5, 6A, 6T, reaction to the phosphazene 7, and hydrolysis. 4‐Ethoxycarbonyl derivative 4b is suitable for linking appropriate biomolecules. The construction of a linking group was achieved by conversion of 4b via carboxylic acid 9 to the reactive O‐succinimide ester 10, which reacts easily with amino acids or peptides to amides 11 and 12. The fluorescent properties were investigated and are comparable with derivatives of 1. J. Heterocyclic Chem., (2009).
Developing bifunctional β‐lactamase molecules with built‐in target‐recognizing module for prodrug therapy: identification of Enterobacter Cloacae P99 cephalosporinase loops suitable for randomization and phage‐display selection
Authors: Shukla Girja S. , Krag David N.
Published: May 2009

This study was focused on developing catalytically active β‐lactamase enzyme molecules that have target‐recognizing sites built within their scaffold. Using phage‐display approach, nine libraries were constructed by inserting the randomized linear or cysteine‐constrained heptapeptides in the five different loops on the outer surface of P99 β‐lactamase molecule. The pIII signal peptide of Sec‐pathway was employed for a periplasmic translocation of the β‐lactamase fusion protein, which we found more efficient than the DsbA signal peptide of SRP‐pathway. The randomized heptapeptide loops replaced native amino acids between positions 34Y‐37K, 238M‐246A, 275N‐280A, 305A‐311S, or 329I‐334I of the P99 β‐lactamase molecules for generating the loop‐1 to ‐5 libraries, respectively. The diversity of each loop library was judged by counting the primary and β‐lactamase‐active clones. The linear peptide inserts in the loop‐2 library showed the maximum number of the β‐lactamase‐active clones, followed by the loop‐5, loop‐3, and loop‐4. The insertion of the cysteine‐constrained loops exhibited a dramatic loss of the enzyme‐active β‐lactamase clones. The complexity of the loop‐2 linear library, as determined by the frequency and diversity of amino acid distributions in the randomized region, appears consistent with the standards of other types of phage display library systems. The selection of the loop‐2 linear library on streptavidin protein as a test target identified several β‐lactamase clones that specifically bound to streptavidin. In conclusion, this study identified the suitability of the loop‐2 of P99 β‐lactamase for constructing a phage‐display library of the β‐lactamase enzyme‐active molecules that can be selected against a target. This is an enabling step in our long‐term goal of developing bifunctional β‐lactamase molecules against cancer‐specific targets for enzyme prodrug therapy of cancer. Copyright © 2009 John Wiley & Sons, Ltd.
Noninvasive in vivo electron paramagnetic resonance study to estimate pulmonary reducing ability in mice exposed to NiO or C60 nanoparticles
Authors: Yokoyama Hidekatsu , Ono Taizo , Morimoto Yasuo , Myojo Toshihiko , Tanaka Isamu , Shimada Manabu , Wang Wei‐Ning , Endoh Shigehisa , Uchida Kunio
Published: May 2009

Purpose

To develop new methods that can estimate the influences of manufactured nanomaterials on biological systems, the in vivo pulmonary reducing ability of mice that had received inhalation exposures to NiO or C60 nanoparticles was investigated using a 700 MHz electron paramagnetic resonance (EPR) spectrometer.

Materials and Methods

NiO or C60 suspensions were atomized and mice in exposure chambers inhaled the resulting aerosol particles for 3 hours. The exposure conditions, number‐based geometric average diameters, and the average number concentration were precisely controlled at almost the same levels for both NiO and C60 nanoparticles. Two days or 2 weeks after exposure, an EPR study was conducted noninvasively. Temporal changes in EPR signal intensity at the target area (ie, lung field) were obtained by the region‐selected intensity determination (RSID) method.

Results

NiO nanoparticles significantly suppressed pulmonary reducing ability 2 days and 2 weeks after exposure, but C60 nanoparticles had no such effect.

Conclusion

This is the first in vivo estimation of the reducing ability in experimental animals exposed to manufactured nanoparticles. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.
Simultaneous efflux of endogenous D‐ser and L‐glu from single acute hippocampus slices during oxygen glucose deprivation
Authors: Kirschner Daniel L. , Wilson Ann L. , Drew Kelly L. , Green Thomas K.
Published: May 2009

D‐serine and L‐glutamate play crucial roles in excitotoxicity through N‐methyl‐D‐aspartate receptor coactivation, but little is known about the temporal profile of efflux during cerebral ischemia. We utilized a newly designed brain slice microperfusion device coupled offline to capillary electrophoresis laser‐induced fluorescence to monitor dynamic efflux of endogenous D‐ser and L‐glu in response to oxygen glucose deprivation (OGD) in single acute hippocampus slices. Efflux profiles with 2‐min temporal resolution in response to 24‐min OGD show that efflux of D‐ser slightly precedes efflux of L‐glu by one 2‐min sampling interval. Thus both coagonists are available to activate NMDA receptors by the time when glu is released. The magnitude of D‐ser efflux relative to baseline values is, however, less than that for L‐glu. Peak efflux during OGD, expressed as pre‐OGD baseline values, was as follows: D‐ser 254% ± 24%, L‐glu 1,675% ± 259%, L‐asp 519% ± 128%, and L‐thr 313% ± 33%. L‐glutamine efflux was shown to decrease significantly in response to OGD. The microperfusion/CE‐LIF approach shows several promising attributes for studying endogenous chemical efflux from single, acute brain slices. © 2009 Wiley‐Liss, Inc.
Mitochondrial dysfunction in a neural cell model of spinal muscular atrophy
Authors: Acsadi Gyula , Lee Icksoo , Li Xingli , Khaidakov Magomed , Pecinova Alena , Parker Graham C. , Hüttemann Maik
Published: May 2009

Mutations of the survival motor neuron (SMN) gene in spinal muscular atrophy (SMA) lead to anterior horn cell death. The cause is unknown, but motor neurons depend substantially on mitochondrial oxidative phosphorylation (OxPhos) for normal function. Therefore, mitochondrial parameters were analyzed in an SMA cell culture model using small interfering RNA (siRNA) transfection that decreased Smn expression in NSC‐34 cells to disease levels. Smn siRNA knock‐down resulted in 35% and 66% reduced Smn protein levels 48 and 72 hr posttransfection, respectively. ATP levels were reduced by 14% and 26% at 48 and 72 hr posttransfection, respectively, suggesting decreased ATP production or increased energy demand in neural cells. Smn knock‐down resulted in increased mitochondrial membrane potential and increased free radical production. Changes in activity of cytochrome c oxidase (CcO), a key OxPhos component, were observed at 72 hr with a 26% increase in oxygen consumption. This suggests a compensatory activation of the aerobic pathway, resulting in increased mitochondrial membrane potentials, a condition known to lead to the observed increase in free radical production. Further testing suggested that changes in ATP at 24 hr precede observable indices of cell injury at 48 hr. We propose that energy paucity and increased mitochondrial free radical production lead to accumulated cell damage and eventual cell death in Smn‐depleted neural cells. Mitochondrial dysfunction may therefore be important in SMA pathology and may represent a new therapeutic target. © 2009 Wiley‐Liss, Inc.
Mitochondrial cytochrome c oxidase expression in the central nervous system is elevated at sites of pressure gradient elevation but not absolute pressure increase
Authors: Balaratnasingam Chandrakumar , Pham Duy , Morgan William H. , Bass Louise , Cringle Stephen J. , Yu Dao‐Yi
Published: May 2009

The paucity of suitable experimental models has made it difficult to isolate the pathogenic role of mitochondria in central nervous system diseases associated with absolute pressure elevation and increased pressure gradients. Experimental models of traumatic brain injury (TBI) and hydrocephalus have been useful for examining the mitochondrial response following pressure increase in the central nervous system; however, the presence of multiple pathogenic factors acting on the brain in these previous studies has made it difficult to determine whether the induced changes were a result of mechanical damage, intracranial pressure elevation, or other pathogenic factors. By direct monitoring and control of pressures in the intraocular, intracranial, and vascular compartments, we use the pig optic nerve, a typical central white matter tract, to compare the temporal sequence of cytochrome c oxidase (CcO) levels between regions of absolute pressure elevation and pressure gradient increase. We demonstrate that a rise in pressure gradient without traumatic injury up‐regulates CcO levels across the site of the gradient, in a manner similar to what has been previously reported for hydrocephalus. We also demonstrate that CcO changes do not occur following an absolute pressure rise. These findings taken together with our recent reports suggest that mitochondria initiate an early compensatory response to axonal damage following pressure gradient increase. Extrapolation of our results also suggests that decreased CcO levels in TBI may be secondary to mechanical damage. This study emphasises the importance of pressure gradients in regulating mitochondrial function in the central nervous system. © 2009 Wiley‐Liss, Inc.
Disruption of the midkine gene (Mdk) delays degeneration and regeneration in injured peripheral nerve
Authors: Sakakima Harutoshi , Yoshida Yoshihiro , Yamazaki Yoshiki , Matsuda Fumiyo , Ikutomo Masako , Ijiri Kosei , Muramatsu Hisako , Muramatsu Takashi , Kadomatsu Kenji
Published: May 2009

Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild‐type (Mdk+/+) mice with MK‐deficient (Mdk−/−) mice after freezing injury. In the Mdk−/− mice, a regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). The relative wet weight of the soleus muscle slowly declined, and recovery was delayed compared with that in the Mdk+/+ mice. In the regenerating nerve, unmyelinated axons were unevenly distributed, and some axons contained myelin‐like, concentrically lamellated bodies. In the endplates of soleus muscles, nerve terminals containing synaptic vesicles disappeared in both mice. In Mdk−/− mice, the appearance of nerve terminals was delayed in synaptic vesicles of terminal buttons after injury. The recovery of evoked electromyogram was delayed in Mdk−/− mice compared with Mdk+/+ mice. Our results suggested a delay in axonal degeneration and regeneration in Mdk−/− mice compared with Mdk+/+ mice, and the delayed regeneration was associated with a delayed recovery of motor function. These findings show that a lack of MK following peripheral nerve injury is a critical factor in degeneration and regeneration, and manipulation of the supply of MK may offer interesting therapeutic options for the treatment of peripheral nerve damage. © 2009 Wiley‐Liss, Inc.