bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of the Rim Cutter™ on cement pressurization and penetration on cemented acetabular fixation in total hip arthroplasty: An in vitro study
Authors: Smith B N , Lee A J C , Timperley A J , Whitehouse S L , Crawford R W
Published: February 2010

The Rim Cutter™ (Stryker Orthopedics, Mahwah, New Jersey) is a tool designed to cut a ledge inside the rim of the acetabulum, onto which a precisely trimmed, cemented, flanged cup can be fitted. The aim was to investigate the effect of the Rim Cutter on the intra-acetabular cement mantle pressure and the depth of cement penetration during cup insertion. The study had two parts. In the first part, hemi-pelvis models were fitted with pressure sensors. Pressure in the acetabulum was measured on insertion of a conventional cemented flanged cup with and without the use of a Rim Cutter to prepare the rim of the acetabulum. The second part assessed cement penetration when the same cups were inserted into a foam shell model. The shell was mounted in a jig and had holes drilled in it; the distance that cement penetrated into the holes was measured. A significant increase in cement pressure at the apex ( p = 0.04) and the rim ( p = 0.004) is seen when the Rim Cutter is used. Cement penetration in the Rim Cutter group was significantly increased at the rim of the acetabulum ( p = 0.003). Insertion of a flanged cup after the acetabulum is prepared with the Rim Cutter leads to a significant increase in cement pressure and penetration during cup insertion in vitro when compared with conventional flanged cups.
Temperature-driven processing techniques for manufacturing fully interconnected porous scaffolds in bone tissue engineering
Authors: Guarino V , Ambrosio L
Published: February 2010

The development of structures with a predefined multiscale pore network is a major challenge in designing tissue engineering (TE) scaffolds. To address this, several strategies have been investigated to provide biocompatible, biodegradable porous materials that would be suitable for use as scaffolds, and able to guide and facilitate the cell activity involved in the generation of new tissue regeneration. This study seeks to provide an overview of different temperature-driven process technologies for developing scaffolds with tailored porosity, in which pore size distribution is strictly defined and pores are fully interconnected. Here, three-dimensional (3D) porous composite scaffolds based on poly(∊-caprolactone) (PCL) were fabricated by thermally induced phase separation (TIPS) and by melt co-continuous polymer blending (MCPB). The combination of these processes with a salt leaching technique enables the establishment of bimodal porosity within the polymer network. This feature may be exploited in the development of substrates with fully interconnected pores, which can be used effectively for tissue regeneration. Various combinations of the proposed techniques provide a range of procedures for the preparation of porous scaffolds with an appropriate combination of morphological and mechanical properties to reproduce the requisite features of the extracellular matrix (ECM) of hard tissues such as bone.
A comparative study of tribological behaviour of dental composites and tooth enamel: An energy approach
Authors: Sajewicz E
Published: February 2010

In this article, an energy approach based on the correlation between dissipated friction energy and wear volume was used to compare wear resistances of human tooth enamel and four composite dental materials: Arkon, Ecusit, Ful-Fil, and Filtek. The results of the study showed that the wear resistance of enamel is approximately one order or more higher than the one obtained for the dental materials. The effectiveness of the approach used has also been shown. Scanning electron microscopy (SEM) examinations and chemical analysis surfaces subjected to tribological experiments made it possible to uncover substantial differences in the wear mechanisms occurring on enamel and the dental material surfaces. The wear mechanism of the dental materials used in the study is characterized mainly by chemical changes, while enamel is mainly subjected to physical transformations.
Hydrophosphination of Propargylic Ethers with Diphenylphosphine in the Presence of LiHMDS, N-Heterocyclic Carbene, and Ti(NMe2)4
Authors: Sakae Ryosuke , Yamamoto Yuta , Komeyama Kimihiro , Takaki Ken
Published: February 2010

Regio- and stereoselective hydrophosphination of propargylic ethers with diphenylphosphine has been achieved using three-component catalyst, LiN(SiMe3)2/1,3-dimethylimidazol-2-ylidene/Ti(NMe2)4 (10 mol % of each).
Preparation of CpG ODN-encapsulated Anionic Poly(amino acid) Nanoparticles for Gene Delivery
Authors: Kim Hyungjin , Akagi Takami , Akashi Mitsuru
Published: February 2010

A novel method for preparation of CpG ODN-encapsulated anionic poly(amino acid) nanoparticles (NPs) was developed for gene delivery purposes. CpG ODN was successfully encapsulated into the NPs using self-assembly of amphiphilic poly(amino acid), and the amount of encapsulated CpG ODN was dependent on the complex ratio of CpG ODN and polycation. The DNA-encapsulated anionic NPs may be useful as a gene delivery and DNA vaccine system with low toxicity.
How Longer Work Lives Ease the Crunch of Population Aging
Authors: Maestas Nicole , Zissimopoulos Julie
Published: February 2010

Population aging is not a looming crisis of the future—it is already here. Economic challenges arise when the increase in people surviving to old age and the decline in the number of young people alive to support them cause the growth in society's consumption needs to outpace growth in its productive capacity. The ultimate impact of population aging on our standard of living in the future depends a great deal on how long people choose to work before they retire from the labor force. Here, there is reason for optimism. A constellation of forces, some just now gaining momentum, has raised labor force participation at older ages at just the time it is needed. We examine the most important factors behind the increase in labor force participation realized to date: the shift in the skill composition of the workforce, and technological change. We argue that forces such as changes in the structure of employer-provided pensions and Social Security are likely to propel future increases in labor force participation at older ages. The labor market is accommodating older workers to some degree, and older men and women are themselves adapting on a number of fronts, which could substantially lessen the economic impact of population aging. Age-related health declines and the reluctance of employers to hire and retain older workers present challenges, but the outlook for future gains in labor force participation at older ages is promising.
Economic Theory and the World of Practice: A Celebration of the (S,s) Model
Authors: Caplin Andrew , Leahy John
Published: February 2010

It was the question of how best to balance the costs of ordering and of running out of stock against the costs of holding excess inventory that inspired Kenneth Arrow, Theodore Harris, and Jacob Marschak to introduce the (S, s) model in 1951. In this celebratory article, we show how this model not only answered important practical questions, but also opened the door to a quite startling range of important and challenging follow-up questions, many of great practical importance and analytic depth. The (S, s) model has become one of the touchstone models of economics, opening new vistas of applied economic theory to all who internalize its structure. Today it is universally applied to solve questions faced in inventory control. The core model elements, uncertainty and fixed costs of adjustment, are ubiquitous, which has resulted in its becoming the general purpose economic model of discrete adjustment. The (S, s) model has also become a profound source of inspiration for macroeconomists seeking to understand the role that discrete microeconomic adjustments play in macroeconomic fluctuations. Looking forward, we foresee rapid growth in the use of (S, s) modeling to aid households making complex and costly financial decisions, such as when and how to terminate a mortgage. In the projected era of “household operations research,” new modeling challenges will arise due to enriched feedback from the world of practice.
The Failure Mechanics of Dealer Banks
Authors: Duffie Darrell
Published: February 2010

During the recent financial crisis, major dealer banks—that is, banks that intermediate markets for securities and derivatives—suffered from new forms of bank runs. The most vivid examples are the 2008 failures of Bear Stearns and Lehman Brothers. Dealer banks are often parts of large complex financial organizations whose failures can damage the economy significantly. As a result, they are sometimes considered “too big to fail.” The mechanics by which dealer banks can fail and the policies available to treat the systemic risk of their failures differ markedly from the case of conventional commercial bank runs. These failure mechanics are the focus of this article. This is not a review of the financial crisis of 2007–2009. Systemic risk is considered only in passing. Both the financial crisis and the systemic importance of large dealer banks are nevertheless obvious and important motivations.
Credit Default Swaps and the Credit Crisis
Authors: Stulz René M
Published: February 2010

Many observers have argued that credit default swaps contributed significantly to the credit crisis. Of particular concern to these observers are that credit default swaps trade in the largely unregulated over-the-counter market as bilateral contracts involving counterparty risk and that they facilitate speculation involving negative views of a firm's financial strength. Some observers have suggested that credit default swaps would not have made the crisis worse had they traded on exchanges. I conclude that credit default swaps did not cause the dramatic events of the credit crisis, that the over-the-counter credit default swaps market worked well during much of the crisis, and that exchange trading has both advantages and costs compared to over-the-counter trading. Though I argue that eliminating over-the-counter trading of credit default swaps could reduce social welfare, I also recognize that much research is needed to understand better and to quantify the social gains and costs of derivatives in general and credit default swaps in particular.
Pilot quality assurance programme for plasma metanephrines
Authors: Pillai Dilo , Callen Shaw
Published: February 2010

Background

Up to 2007 there was no formal external quality assurance programme for plasma free metanephrines. A pilot programme was conceived by the AACB (Australian Association of Clinical Biochemists) Working Party on biogenic amines. With support from the AACB and Royal College of Pathologists of Australasia Quality Assurance programmes, a pilot study was developed. Data from this study are presented for the first time.

Methods

Twelve lyophilized plasma samples were distributed to 15 centres. Samples were spiked with metanephrine (metadrenaline), normetanephrine (normetadrenaline) and 3-methoxytyramine, all derived from human urine. Concentrations were arranged in a linear relationship. The analytes were present at six levels and samples were duplicated.

Results

High-pressure liquid chromatography and tandem mass spectrometry methods showed acceptable precision but in general enzyme immunoassay displayed a higher degree of imprecision as well as a negative bias.

Conclusions

Differences in calibration and matrix effects are likely to have been responsible for the discrepancy between chromatographic and immunoassay methods. These differences need to be further examined although efforts at standardization between different methods have been hampered by the lack of a universal calibrator for plasma metanephrines. Meanwhile, a laboratory's performance characteristics can be monitored and enhanced by participation in suitable external quality assurance programmes.
Spurious hypokalaemia and hypophosphataemia due to extreme hyperleukocytosis in a patient with a haematological malignancy
Authors: Polak R , Huisman A , Sikma M A , Kersting S
Published: February 2010

Serious hyperleukocytosis can strongly affect laboratory results of potassium, phosphate and arterial oxygen tension. A 40-year-old woman is presented with an acute myeloid leukaemia and a strongly elevated leukocyte count (310 × 109/L). Apart from this hyperleukocytosis, initial blood tests showed hypokalaemia, hypophosphataemia and serious hypoxaemia without any corresponding complaints. Blood sampled and transported on ice or directly analysed showed no electrolyte abnormalities and hypoxaemia. The observed discrepancy in laboratory results is probably due to the metabolic activity of the leukocytes in vitro. Spurious laboratory results can be a reason for incorrect decisions concerning additional diagnostics and treatment. In conclusion, hyperleukocytosis can cause pseudohypokalaemia, pseudohypophosphataemia and pseudohypoxaemia, which can be prevented by correct sampling and immediate analysis.
Twins Switched at Birth: A Case from the Canary Islands / Research Reviews: Twin Study of Materialism; Twins and Clones; / In the News: ART and Premature Twins; A Pair of College Presidents; Twins in Real Estate; Tribute to a Twin
Authors: Segal Nancy L. , Blandón-Gitlin Iris
Published: February 2010

Monozygotic (MZ) twins switched at birth represent a rare class of twins who are reared apart and reunited (MZA). Background data and descriptive findings from a case study of such a pair, born thirty-six years ago in the Canary Islands, are presented. The next section reviews a twin study of materialism and an essay addressing relations between MZ twinning and human reproductive cloning. This article concludes with summaries of several newsworthy, twin-related items. They include the multiple birth consequences of artificial reproductive technology, the friendly rivalry between identical twin college presidents, a joint venture in real estate and a tribute to a deceased twin.
Phenotypic and Genetic Relations Between the HEXACO Dimensions and Trait Emotional Intelligence
Authors: Veselka Livia , Petrides K. V. , Schermer Julie Aitken , Cherkas Lynn F. , Spector Tim D. , Vernon Philip A.
Published: February 2010

The present study investigated the location of trait emotional intelligence (trait EI or trait emotional self-efficacy) within the context of the HEXACO model — a more comprehensive personality framework than the conventional Big Five structure. A total of 666 MZ and 526 DZ adult twin pairs from the United Kingdom completed the short form of the Trait Emotional Intelligence Questionnaire (TEIQue-SF) and the short form of the HEXACO Personality Inventory (HEXACO-60). Many significant phenotypic correlations between the TEIQue-SF and the HEXACO-60 were obtained, which were strongest for HEXACO Extraversion, and weakest for HEXACO Honesty–Humility. As was expected, Emotionality was the only HEXACO dimension to correlate negatively with TEIQue-SF scores. Bivariate behavioral genetic analyses revealed that all phenotypic correlations were attributable to common genetic and common nonshared environmental factors. The study confirms the validity of trait EI as a constellation of emotional self-perceptions located at the lower levels of personality.
Dion Chen-Loung Chen (1930–2009)
Authors: Rosenau Thomas , Potthast Antje , Capanema Ewellyn , Balakshin Mikhail
Published: February 2010

No abstract available
A Probabilistic Strategy for Understanding Action Selection
Authors: Kim Byounghoon , Basso Michele A.
Published: February 2010

Brain regions involved in transforming sensory signals into movement commands are the likely sites where decisions are formed. Once formed, a decision must be read out from the activity of populations of neurons to produce a choice of action. How this occurs remains unresolved. We recorded from four superior colliculus neurons simultaneously while monkeys performed a target selection task. We implemented three models to gain insight into the computational principles underlying population coding of action selection. We compared the population vector average (PVA)/optimal linear estimator (OLE) and winner-takes-all (WTA) models and a Bayesian model, maximum a posteriori estimate (MAP), to determine which predicted choices most often. The probabilistic model predicted more trials correctly than both the WTA and the PVA. The MAP model predicted 81.88%, whereas WTA predicted 71.11% and PVA/OLE predicted the least number of trials at 55.71 and 69.47%. Recovering MAP estimates using simulated, nonuniform priors that correlated with monkeys' choice performance, improved the accuracy of the model by 2.88%. A dynamic analysis revealed that the MAP estimate evolved over time and the posterior probability of the saccade choice reached a maximum at the time of the saccade. MAP estimates also scaled with choice performance accuracy. Although there was overlap in the prediction abilities of all the models, we conclude that movement choice from populations of neurons may be best understood by considering frameworks based on probability.
Mental Hoop Diaries: Emotional Memories of a College Basketball Game in Rival Fans
Authors: Botzung Anne , Rubin David C. , Miles Amanda , Cabeza Roberto , LaBar Kevin S.
Published: February 2010

The rivalry between the men's basketball teams of Duke University and the University of North Carolina–Chapel Hill (UNC) is one of the most storied traditions in college sports. A subculture of students at each university form social bonds with fellow fans, develop expertise in college basketball rules, team statistics, and individual players, and self-identify as a member of a fan group. The present study capitalized on the high personal investment of these fans and the strong affective tenor of a Duke–UNC basketball game to examine the neural correlates of emotional memory retrieval for a complex sporting event. Male fans watched a competitive, archived game in a social setting. During a subsequent functional magnetic resonance imaging session, participants viewed video clips depicting individual plays of the game that ended with the ball being released toward the basket. For each play, participants recalled whether or not the shot went into the basket. Hemodynamic signal changes time locked to correct memory decisions were analyzed as a function of emotional intensity and valence, according to the fan's perspective. Results showed intensity-modulated retrieval activity in midline cortical structures, sensorimotor cortex, the striatum, and the medial temporal lobe, including the amygdala. Positively valent memories specifically recruited processing in dorsal frontoparietal regions, and additional activity in the insula and medial temporal lobe for positively valent shots recalled with high confidence. This novel paradigm reveals how brain regions implicated in emotion, memory retrieval, visuomotor imagery, and social cognition contribute to the recollection of specific plays in the mind of a sports fan.
Serotonin Modulates Fast-Spiking Interneuron and Synchronous Activity in the Rat Prefrontal Cortex through 5-HT1Aand 5-HT2AReceptors
Authors: Puig M. Victoria , Watakabe Akiya , Ushimaru Mika , Yamamori Tetsuo , Kawaguchi Yasuo
Published: February 2010

Alterations of the serotonergic system in the prefrontal cortex (PFC) are implicated in psychiatric disorders such as schizophrenia and depression. Although abnormal synchronous activity is observed in the PFC of these patients, little is known about the role of serotonin (5-HT) in cortical synchrony. We found that 5-HT, released by electrical stimulation of the dorsal raphe nucleus (DRN) in anesthetized rats, regulates the frequency and the amplitude of slow (<2 Hz) waves in the PFC via 5-HT2Areceptors (5-HT2ARs). 5-HT also modulates prefrontal gamma (30–80 Hz) rhythms through both 5-HT1ARs and 5-HT2ARs, but not 5-HT2CRs, inducing an overall decrease in the amplitude of gamma oscillations. Because fast-spiking interneurons (FSi) are involved in the generation of gamma waves, we examined serotonergic modulation of FSi activityin vivo. Most FSi are inhibited by serotonin through 5-HT1ARs, while a minority is activated by 5-HT2ARs, and not 5-HT2CRs.In situhybridization histochemistry confirmed that distinct populations of FSi in the PFC express 5-HT1ARs and 5-HT2ARs, and that the number of FSi expressing 5-HT2CRs is negligible. We conclude that 5-HT exerts a potent control on slow and gamma oscillations in the PFC. On the one hand, it shapes the frequency and amplitude of slow waves through 5-HT2ARs. On the other hand, it finely tunes the amplitude of gamma oscillations through 5-HT2AR- and 5-HT1AR-expressing FSi, although it primarily downregulates gamma waves via the latter population. These results may provide insight into impaired serotonergic control of network activity in psychiatric illnesses such as schizophrenia and depression.
Integration of Vibrotactile Signals for Whisker-Related Perception in Rats Is Governed by Short Time Constants: Comparison of Neurometric and Psychometric Detection Performance
Authors: Stüttgen Maik C. , Schwarz Cornelius
Published: February 2010

Rats explore environments by sweeping their whiskers across objects and surfaces. Both sensor movement and repetitive sweeping typical for this behavior require that vibrotactile signals are integrated over time. While temporal integration properties of neurons along the whisker somatosensory pathway have been studied extensively, the consequences for behavior are unknown. Here, we investigate the ability of head-fixed rats to integrate information over time for the detection of near-threshold pulsatile deflection sequences applied to a single whisker. Psychometric detection performance was assessed with whisker stimuli composed of different numbers of pulses (1-31) delivered at varying frequencies (10, 20, 100 Hz). Detection performance indeed improved with increasing number and frequency of pulses, albeit this improvement was much lower than predicted by probabilistic combination, suggesting highly sublinear integration of pulses. This behavioral observation was reflected in the firing properties of concomitantly recorded barrel cortex neurons, which showed substantial response adaptation to repetitive whisker deflection. To estimate the integration time with which barrel cortex neuronal activity must be read out to match behavior, we constructed a model monitoring spiking activity of simulated neuronal pools, where spike trains were channeled through a leaky integrator with exponential decay. Detection was accomplished by simple threshold crossings. This simple model gave an excellent match of neurometric and psychometric data at surprisingly small time constants τ of 5–8 ms, thus limiting integration largely to <25 ms. This result carries important implications regarding sensory processing for whisker-mediated perception.
CD200R1 Agonist Attenuates Mechanisms of Chronic Disease in a Murine Model of Multiple Sclerosis
Authors: Liu Yingru , Bando Yoshio , Vargas-Lowy David , Elyaman Wassim , Khoury Samia J. , Huang Tao , Reif Karin , Chitnis Tanuja
Published: February 2010

To assess the effects and mechanisms of a CD200R1 agonist administered during the progressive stage of a multiple sclerosis model, we administered CD200R1 agonist (CD200Fc) or control IgG2a during the chronic phase of disease (days 10–30) in mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55) peptide. We found that administration of CD200Fc during the chronic stages of EAE reduced disease severity, demyelination, and axonal damage, through the modulation of several key disease mechanisms. CD200Fc treatment suppressed macrophage and microglial accumulation within the CNS, in part through downregulation of adhesion molecules VLA-4 and LFA-1, which are necessary for macrophage migration. Additionally, expression of activation markers MHC-II and CD80 and production of proinflammatory cytokines IL-6, tumor necrosis factor-α, and nitric oxide by CD11b+cells were decreased in both the spleen and CNS in CD200Fc-treated animals. Antigen-presenting cell function in the spleen and CNS was suppressed in CD200Fc-treated mice, but there were no significant alterations on T cell activation or phenotype. CD200Fc increased apoptosis of CD11b+cells but not astrocytes. In contrast, addition of CD200Fc treatment protected oligodendrocytes from apoptosisin vitroandin vivo. Our results demonstrate that CD200R1 agonists modulate both myeloid- and non-myeloid-related mechanisms of chronic disease in the EAE model and may be effective in the treatment of progressive multiple sclerosis and other neurodegenerative diseases.
A Genetic Model of Chronic Rhinosinusitis-Associated Olfactory Inflammation Reveals Reversible Functional Impairment and Dramatic Neuroepithelial Reorganization
Authors: Lane Andrew P. , Turner Justin , May Lindsey , Reed Randall
Published: February 2010

Inflammatory sinus and nasal disease is a common cause of human olfactory loss. To explore the mechanisms underlying rhinosinusitis-associated olfactory loss, we have generated a transgenic mouse model of olfactory inflammation, in which tumor necrosis factor α (TNF-α) expression is induced in a temporally controlled manner specifically within the olfactory epithelium (OE). Like the human disease, TNF-α expression leads to a progressive infiltration of inflammatory cells into the OE. Using this model, we have defined specific phases of the pathologic process. An initial loss of sensation without significant disruption is observed, followed by a striking reorganization of the sensory neuroepithelium. An inflamed and disrupted state is sustained chronically by continued induction of cytokine expression. After prolonged maintenance in a deficient state, there is a dramatic recovery of function and a normal histologic appearance when TNF-α expression is extinguished. Although obstruction of airflow is also a contributing factor in human rhinosinusitis, thisin vivomodel demonstrates for the first time that direct effects of inflammation on OE structure and function are important mechanisms of olfactory dysfunction. These features mimic essential aspects of chronic rhinosinusitis-associated olfactory loss, and illuminate underlying cellular and molecular aspects of the disease. This manipulable model also serves as a platform for developing novel therapeutic interventions.
A Surface-Based Analysis of Hemispheric Asymmetries and Folding of Cerebral Cortex in Term-Born Human Infants
Authors: Hill Jason , Dierker Donna , Neil Jeffrey , Inder Terrie , Knutsen Andrew , Harwell John , Coalson Timothy , Van Essen David
Published: February 2010

We have established a population average surface-based atlas of human cerebral cortex at term gestation and used it to compare infant and adult cortical shape characteristics. Accurate cortical surface reconstructions for each hemisphere of 12 healthy term gestation infants were generated from structural magnetic resonance imaging data using a novel segmentation algorithm. Each surface was inflated, flattened, mapped to a standard spherical configuration, and registered to a target atlas sphere that reflected shape characteristics of all 24 contributing hemispheres using landmark constrained surface registration. Population average maps of sulcal depth, depth variability, three-dimensional positional variability, and hemispheric depth asymmetry were generated and compared with previously established maps of adult cortex. We found that cortical structure in term infants is similar to the adult in many respects, including the pattern of individual variability and the presence of statistically significant structural asymmetries in lateral temporal cortex, including the planum temporale and superior temporal sulcus. These results indicate that several features of cortical shape are minimally influenced by the postnatal environment.
Distinct Roles of GABAergic Interneurons in the Regulation of Striatal Output Pathways
Authors: Gittis Aryn H. , Nelson Alexandra B. , Thwin Myo T. , Palop Jorge J. , Kreitzer Anatol C.
Published: February 2010

Striatal GABAergic microcircuits are critical for motor function, yet their properties remain enigmatic due to difficulties in targeting striatal interneurons for electrophysiological analysis. Here, we use Lhx6-GFP transgenic mice to identify GABAergic interneurons and investigate their regulation of striatal direct- and indirect-pathway medium spiny neurons (MSNs). We find that the two major interneuron populations, persistent low-threshold spiking (PLTS) and fast spiking (FS) interneurons, differ substantially in their excitatory inputs and inhibitory outputs. Excitatory synaptic currents recorded from PLTS interneurons are characterized by a small, nonrectifying AMPA receptor-mediated component and a NMDA receptor-mediated component. In contrast, glutamatergic synaptic currents in FS interneurons have a large, strongly rectifying AMPA receptor-mediated component, but no detectable NMDA receptor-mediated responses. Consistent with their axonal morphology, the output of individual PLTS interneurons is relatively weak and sparse, whereas FS interneurons are robustly connected to MSNs and other FS interneurons and appear to mediate the bulk of feedforward inhibition. Synaptic depression of FS outputs is relatively insensitive to firing frequency, and dynamic-clamp experiments reveal that these short-term dynamics enable feedforward inhibition to remain efficacious across a broad frequency range. Surprisingly, we find that FS interneurons preferentially target direct-pathway MSNs over indirect-pathway MSNs, suggesting a potential mechanism for rapid pathway-specific regulation of striatal output pathways.
VGLUT3 (Vesicular Glutamate Transporter Type 3) Contribution to the Regulation of Serotonergic Transmission and Anxiety
Authors: Amilhon Bénédicte , Lepicard Ève , Renoir Thibault , Mongeau Raymond , Popa Daniela , Poirel Odile , Miot Stéphanie , Gras Christelle , Gardier Alain M. , Gallego Jorge , Hamon Michel , Lanfumey Laurence , Gasnier Bruno , Giros Bruno , El Mestikawy Salah
Published: February 2010

Three different subtypes of H+-dependent carriers (named VGLUT1–3) concentrate glutamate into synaptic vesicles before its exocytotic release. Neurons using other neurotransmitter than glutamate (such as cholinergic striatal interneurons and 5-HT neurons) express VGLUT3. It was recently reported that VGLUT3 increases acetylcholine vesicular filling, thereby, stimulating cholinergic transmission. This new regulatory mechanism is herein designated as vesicular-filling synergy (or vesicular synergy). In the present report, we found that deletion of VGLUT3 increased several anxiety-related behaviors in adult and in newborn mice as early as 8 d after birth. This precocious involvement of a vesicular glutamate transporter in anxiety led us to examine the underlying functional implications of VGLUT3 in 5-HT neurons. On one hand, VGLUT3 deletion caused a significant decrease of 5-HT1A-mediated neurotransmission in raphe nuclei. On the other hand, VGLUT3 positively modulated 5-HT transmission of a specific subset of 5-HT terminals from the hippocampus and the cerebral cortex. VGLUT3- and VMAT2-positive serotonergic fibers show little or no 5-HT reuptake transporter. These results unravel the existence of a novel subset of 5-HT terminals in limbic areas that might play a crucial role in anxiety-like behaviors. In summary, VGLUT3 accelerates 5-HT transmission at the level of specific 5-HT terminals and can exert an inhibitory control at the raphe level. Furthermore, our results suggest that the loss of VGLUT3 expression leads to anxiety-associated behaviors and should be considered as a potential new target for the treatment of this disorder.
Postnatal Development of a Segmental Switch Enables Corticospinal Tract Transmission to Spinal Forelimb Motor Circuits
Authors: Chakrabarty Samit , Martin John H.
Published: February 2010

Development of skilled movements and the corticospinal tract (CST) begin prenatally and continue postnatally. Because the CST is required for skilled movements in maturity, it is accepted that motor skills cannot occur until the CST develops a mature organization. We recently showed that the CST plays an essential role in postnatal development of interneurons comprising the spinal circuits it engages. We proposed that CST signals are more effectively transmitted to ventral motor circuits after interneuron maturation, thereby enabling expression of CST motor functions, suggesting development of a segmental switch promoting transmission. We tested this by recording CST-evoked focal synaptic potentials, extracellularly, in the cervical enlargement of cats before and after interneuron maturation [postnatal week 5 (PW5) to PW7]. We compared monosynaptic CST amplitude input to segmental circuits with oligosynaptic ventral horn responses, as a measure of CST-evoked segmental response transmission from input to output. The M1 primary motor cortex was unilaterally inactivated between PW5 and PW7 to determine activity dependence. CST interneuron contacts were identified using confocal microscopy. CST terminals contact diverse interneuron classes. CST stimulation strongly activated ventral motor circuits at the ages when both interneurons and CST spinal terminations have developed a mature phenotype, supporting development of segmental transmission of CST signals. CST activity blockade impeded development of effective segmental transmission by the inactivated CST and created a novel path for transmission from the ipsilateral, unaffected, CST. Our findings show that development of segmental CST signal transmission regulates nascent CST motor control functions and provide insight into systems-level mechanisms for protracted motor skill development.
Ecto-5′-Nucleotidase (CD73) Inhibits Nociception by Hydrolyzing AMP to Adenosine in Nociceptive Circuits
Authors: Sowa Nathaniel A. , Taylor-Blake Bonnie , Zylka Mark J.
Published: February 2010

Ecto-5′-nucleotidase (NT5E, CD73) is a membrane-anchored protein that hydrolyzes extracellular adenosine 5′-monophosphate (AMP) to adenosine in diverse tissues but has not been directly studied in nociceptive neurons. We found that NT5E was located on peptidergic and nonpeptidergic nociceptive neurons in dorsal root ganglia (DRG) and on axon terminals in lamina II (the substantia gelatinosa) of spinal cord. NT5E was also located on epidermal keratinocytes, cells of the dermis, and on nociceptive axon terminals in the epidermis. Following nerve injury, NT5E protein and AMP histochemical staining were coordinately reduced in lamina II. In addition, AMP hydrolytic activity was reduced in DRG neurons and spinal cord ofNt5e−/−mice. The antinociceptive effects of AMP, when combined with the adenosine kinase inhibitor 5-iodotubericidin, were reduced by ∼50% inNt5e−/−mice and were eliminated inAdenosine A1receptor(A1R, Adora1) knock-out mice. Additionally,Nt5e−/−mice displayed enhanced sensitivity in the tail immersion assay, in the complete Freund's adjuvant model of inflammatory pain and in the spared nerve injury model of neuropathic pain. Collectively, our data indicate that the ectonucleotidase NT5E regulates nociception by hydrolyzing AMP to adenosine in nociceptive circuits and represents a new molecular target for the treatment of chronic pain. Moreover, our data suggest NT5E is well localized to regulate nucleotide signaling between skin cells and sensory axons.
Loss of Retrograde Endocannabinoid Signaling and Reduced Adult Neurogenesis in Diacylglycerol Lipase Knock-out Mice
Authors: Gao Ying , Vasilyev Dmitry V. , Goncalves Maria Beatriz , Howell Fiona V. , Hobbs Carl , Reisenberg Melina , Shen Ru , Zhang Mei-Yi , Strassle Brian W. , Lu Peimin , Mark Lilly , Piesla Michael J. , Deng Kangwen , Kouranova Evguenia V. , Ring Robert H. , Whiteside Garth T. , Bates Brian , Walsh Frank S. , Williams Gareth , Pangalos Menelas N. , Samad Tarek A. , Doherty Patrick
Published: February 2010

Endocannabinoids (eCBs) function as retrograde signaling molecules at synapses throughout the brain, regulate axonal growth and guidance during development, and drive adult neurogenesis. There remains a lack of genetic evidence as to the identity of the enzyme(s) responsible for the synthesis of eCBs in the brain. Diacylglycerol lipase-α (DAGLα) and -β (DAGLβ) synthesize 2-arachidonoyl-glycerol (2-AG), the most abundant eCB in the brain. However, their respective contribution to this and to eCB signaling has not been tested. In the present study, we show ∼80% reductions in 2-AG levels in the brain and spinal cord in DAGLα−/−mice and a 50% reduction in the brain in DAGLβ−/−mice. In contrast, DAGLβ plays a more important role than DAGLα in regulating 2-AG levels in the liver, with a 90% reduction seen in DAGLβ−/−mice. Levels of arachidonic acid decrease in parallel with 2-AG, suggesting that DAGL activity controls the steady-state levels of both lipids. In the hippocampus, the postsynaptic release of an eCB results in the transient suppression of GABA-mediated transmission at inhibitory synapses; we now show that this form of synaptic plasticity is completely lost in DAGLα−/−animals and relatively unaffected in DAGLβ−/−animals. Finally, we show that the control of adult neurogenesis in the hippocampus and subventricular zone is compromised in the DAGLα−/−and/or DAGLβ−/−mice. These findings provide the first evidence that DAGLα is the major biosynthetic enzyme for 2-AG in the nervous system and reveal an essential role for this enzyme in regulating retrograde synaptic plasticity and adult neurogenesis.
Reevaluation of Neurodegeneration inlurcherMice: Constitutive Ion Fluxes Cause Cell Death with, Not by, Autophagy
Authors: Nishiyama Jun , Matsuda Keiko , Kakegawa Wataru , Yamada Nobuaki , Motohashi Junko , Mizushima Noboru , Yuzaki Michisuke
Published: February 2010

Thelurcher(Lc) mice have served as a valuable model for neurodegeneration for decades. Although the responsible mutation was identified in genes encoding δ2 glutamate receptors (GluD2s), which are predominantly expressed in cerebellar Purkinje cells, how the mutant receptor (GluD2Lc) triggers cell death has remained elusive. Here, taking advantage of recent knowledge about the domain structure of GluD2, we reinvestigated Lc-mediated cell death, focusing on the “autophagic cell death” hypothesis. Although autophagy and cell death were induced by the expression of GluD2Lcin heterologous cells and cultured neurons, they were blocked by the introduction of mutations in the channel pore domain of GluD2Lcor by removal of extracellular Na+. In addition, although GluD2Lcis reported to directly activate autophagy, mutant channels that are not associated with n-PIST (neuronal isoform of protein-interacting specifically with TC10)–Beclin1 still caused autophagy and cell death. Furthermore, cells expressing GluD2Lcshowed decreased ATP levels and increased AMP-activated protein kinase (AMPK) activities in a manner dependent on extracellular Na+. Thus, constitutive currents were likely necessary and sufficient to induce autophagy via AMPK activation, regardless of the n-PIST–Beclin1 pathwayin vitro. Interestingly, the expression of dominant-negative AMPK suppressed GluD2Lc-induced autophagy but did not prevent cell death in heterologous cells. Similarly, the disruption ofAtg5, a gene crucial for autophagy, did not prevent but rather aggravated Purkinje-cell death inLcmice. Furthermore, calpains were specifically activated inLcPurkinje cells. Together, these results suggest that Lc-mediated cell death was not caused by autophagy but necrosis with autophagic features bothin vivoandin vitro.
NME1 at the human maternal–fetal interface downregulates titin expression and invasiveness of trophoblast cells via MAPK pathway in early pregnancy
Authors: Xie Ke-Ming , Hou Xiao-Fan , Li Ming-Qing , Li Da-Jin
Published: February 2010

Nometastatic gene 23-H1 (NME1, also known as nm23-H1) is a wide-spectrum tumor metastasis suppressor gene that plays an important role in suppressing the invasion and metastasis of tumor cells. It has been demonstrated thatNME1is also expressed in human first-trimester placenta, but its function at maternal–fetal interface is not clear. The present study aimed to elucidate the biological function of NME1 at the maternal–fetal interface, especially on invasion of the human extravillous cytotrophoblasts (EVCTs). NME1 has been identified in both human trophoblast cells and decidual stromal cells (DSCs) in early pregnancy. We have proved thatNME1silencingin vitroincreases the titin protein translation in the invasive EVCTs. Moreover, NME1 can inactivate the phospho-extracellular signal-regulated kinase 1/2 (P-ERK1/2) in trophoblasts in a time-dependent manner, and U0126, an inhibitor of MAPK/ERK, can inhibit partly the enhanced invasiveness and titin expression in trophoblasts induced byNME1silencing. Interestingly, the expression of NME1 in either villi or decidua is higher significantly in miscarriage than that of the normal early pregnancy. These findings first reveal that the NME1 expressed in trophoblasts and DSCs controls the inappropriate invasion of human first-trimester trophoblast cells via MAPK/ERK1/2 signal pathway, and the overexpression of NME1 at maternal–fetal interface leads to pregnancy wastage.
Promoting and Avoiding Recombination: Contrasting Activities of the Escherichia coli RuvABC Holliday Junction Resolvase and RecG DNA Translocase
Authors: Zhang Jing , Mahdi Akeel A , Briggs Geoffrey S , Lloyd Robert G
Published: February 2010

RuvABC and RecG are thought to provide alternative pathways for the late stages of recombination in Escherichia coli. Inactivation of both blocks the recovery of recombinants in genetic crosses. RuvABC resolves Holliday junctions, with RuvAB driving branch migration and RuvC catalyzing junction cleavage. RecG also drives branch migration, but no nuclease has been identified that might act with RecG to cleave junctions, apart from RusA, which is not normally expressed. We searched for an alternative nuclease using a synthetic lethality assay to screen for mutations causing inviability in the absence of RuvC, on the premise that a strain without any ability to cut junctions might be inviable. All the mutations identified mapped to polA, dam, or uvrD. None of these genes encodes a nuclease that cleaves Holliday junctions. Probing the reason for the inviability using the RusA Holliday junction resolvase provided strong evidence in each case that the RecG pathway is very ineffective at removing junctions and indicated that a nuclease component most probably does not exist. It also revealed new suppressors of recG, which were located to the ssb gene. Taken together with the results from the synthetic lethality assays, the properties of the mutant SSB proteins provide evidence that, rather than promoting recombination, a major function of RecG is to curb potentially pathological replication initiated via PriA protein at sites remote from oriC.
Impact of Labor on Outcomes in Transient Tachypnea of the Newborn: Population-Based Study
Authors: Tutdibi Erol , Gries Katharina , Bücheler Monika , Misselwitz Bjorn , Schlosser Rolf L. , Gortner Ludwig
Published: February 2010

OBJECTIVE:

Our aim was to assess the effect of labor on the risk and course of transient tachypnea of the newborn (TTN) in term neonates from a contemporary, population-based cohort.

METHODS:

We analyzed perinatal characteristics of term singleton newborns (gestational age [GA] of ≥37 completed weeks) who were born between January 2001 and December 2005 in the federal states of Hesse and Saarland (Germany). TTN was diagnosed on the basis of International Classification of Diseases, 10th Revision codes.

RESULTS:

Of a total of 275 459 births, 239 971 fulfilled the inclusion criteria of GA of ≥37 completed weeks and singleton live birth. Among those, 13 346 term infants were admitted for neonatal care and 1423 were diagnosed as having TTN. The overall incidence of TTN was 5.9 cases per 1000 singleton live births in our study cohort. Elective cesarean section, low GA, male gender, and low birth weight were associated with TTN. The duration of oxygen supplementation for newborns with TTN was associated inversely with the duration of labor (r = −0.151; P = .028).

CONCLUSIONS:

Our study indicates that TTN is strongly related to elective cesarean section and low GA. Furthermore, the absence of exposure to labor contractions is associated with increased risk and severe course of TTN at term, with longer duration of oxygen supplementation.
Importance of Colonization Site in the Current Epidemic of Staphylococcal Skin Abscesses
Authors: Faden Howard , Lesse Alan J. , Trask Jennifer , Hill January A. , Hess Donavon J. , Dryja Diane , Lee Yi-Horng
Published: February 2010

OBJECTIVE:

The goal was to compare rectal and nasal Staphylococcus aureus colonization rates and S aureus pulsed-field types (PFTs) for children with S aureus skin and soft-tissue abscesses and normal control subjects.

METHODS:

Sixty consecutive children with S aureus skin and soft-tissue abscesses that required surgical drainage and 90 control subjects were enrolled. Cultures of the nares and rectum were taken in both groups. S aureus isolates from all sites were characterized through multiple-locus, variable-number, tandem-repeat analysis, pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec typing for methicillin-resistant S aureus isolates, and determination of the presence of Panton-Valentine leukocidin genes.

RESULTS:

S aureus was detected significantly more often in the rectum of children with abscesses (47%) compared with those in the control group (1%; P = .0001). Rates of nasal colonization with S aureus were equivalent for children with abscesses (27%) and control subjects (20%; P = .33). S aureus recovered from the rectum was identical to S aureus in the abscess in 88% of cases, compared with 75% of nasal isolates. PFT USA300, staphylococcal cassette chromosome mec type IV, and Panton-Valentine leukocidin genes were significantly increased in the S aureus isolates from children with abscesses compared with those from control subjects.

CONCLUSIONS:

Skin and soft-tissue abscesses in the current epidemic of community-associated staphylococcal disease are strongly associated with rectal colonization by PFT USA300. Nasal colonization in children does not seem to be a risk factor.