bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinically benign multiple sclerosis despite large T2 lesion load: Can we explain this paradox?
Authors: Strasser-Fuchs S. , Enzinger C. , Ropele S. , Wallner M. , Fazekas F.
Published: November 2007

Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 ± 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 ± 6 years) matched for disease duration. The magnetization transfer ratio (MTR), magnetization transfer rate ( kfor), brain parenchymal fraction (BPF) and brain metabolite concentrations from proton MRS were determined. BMS patients were significantly less disabled than their SPMS counterparts (mean expanded disability status score: 2.1 ± 1.1 versus 6.2 ± 1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2 ± 27.1 versus 27.9 ± 24.8 cm3; P = 0.19). Normal appearing brain tissue histogram metrics for MTR and kfor, mean MTR and kfor of MS lesions and mean BPF were similar in BMS and SPMS patients. Levels of N-acetyl-aspartate, choline and myoinositol were comparable between groups. This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the brain parenchyma. Functional compensation must come from other mechanisms such as brain plasticity. Multiple Sclerosis 2008; 14: 205—211. http://msj.sagepub.com
PAI and TPA gene polymorphisms in multiple sclerosis
Authors: Lovrečić Luca , Ristić Smiljana , Starčević-Čizmarević Nada , Brajenović-Milic Bojana , Saša Sega Jazbec  , Sepčić Juraj , Kapović Miljenko , Peterlin Borut
Published: November 2007

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system. It manifests as acute focal inflammatory demyelination and axonal loss with limited remyelination and results in the chronic multifocal sclerotic plaques. Previously published data showed impaired fibrinolysis in MS. Tissue plasminogen activator t-PA is a serine protease that catalyses the activation of plasmin, which mediates the effects of fibrinolytic system. Alu insertion/deletion (I/D) genetic polymorphism in TPA gene in MS patients has not been analysed previously. The major inhibitor of t-PA is plasminogen activator inhibitor-1 (PAI-1). Its gene expression is modulated by functional genetic polymorphism in the promoter (4G/5G). In the present study, an association of two genetic polymorphisms with MS, its progression and subtype were analysed. TPA DD/PAI-1 4G4G genotype combination has reached a borderline significance for reduced risk for MS (OR = 0.543, 95% CI 0.301—0.978, P = 0.04), suggesting a gene—gene interaction. The explanation for this interaction may be a complex interplay between these two pleiotropic proteins within the brain tissue and in plasma. Multiple Sclerosis 2008; 14: 243—247. http://msj.sagepub.com
Chronic myeloid leukemia associated with mitoxantrone treatment in a patient with MS
Authors: Sadiq Saud A. , Rammal Mustapha , Sara Gabriel
Published: November 2007

We report the first case of chronic myeloid leukemia (CML) in a patient with multiple sclerosis (MS) diagnosed within two years of receiving mitoxantrone therapy. Previously only acute forms of leukemia particularly acute promyelocytic leukemia (APL) have been associated with mitoxantrone treatment in MS. This underscores the need for only using mitoxantrone in severe treatment-unresponsive cases of MS. Multiple Sclerosis 2008; 14: 272—273. http://msj.sagepub.com
Implementing Europe
Authors: Jensen Christian B.
Published: November 2007

This article shows that member state governments' ability rather than their willingness to implement directives drives uneven implementation of European Union labor policy. Analysis of 186 labor policy infringement cases against 15 member states between 1978 and 2000 shows that administrative oversight mechanisms that concentrate authority in the hands of government and exclude interest group participation enhance governments' ability to resolve conflicts with the Commission over implementation. Mechanisms that depend on cooperation with interest groups inhibit the resolution of these conflicts. This finding undermines the common prescription that increasing interest group involvement should improve member state governments' implementation of EU laws.
Analysing Roll Calls of the European Parliament
Authors: Han Jeong-Hun
Published: November 2007

This article explores the performance of a Bayesian application of spatial voting models to the roll calls of the Fifth European Parliament (EP). Focusing on two distinct voting behaviours of members of the EP (MEPs) — high absenteeism and the defection from majority alternatives caused by the influence of national parties — it shows that the Bayesian method is complementary to the standard NOMINATE method. In general, the two methods produce very similar estimates and work as robustness checks for the results from each other. However, the Bayesian method enables us to measure the uncertainty of estimates resulting from the estimation with a large number of missing data and some random-appearing roll calls. In this way, it helps us draw more confident inferences about MEPs' voting behaviour.
Advancing Work—Life Integration in Individuals, Organizations, and Communities
Authors: Morris Michael Lane , Madsen Susan R.
Published: November 2007

The problem and the solution. Working adults report they experience greater challenges today in their ability to be productive employees, experience personal and interpersonal health and well-being, and make meaningful contributions as citizens to their respective communities. By better understanding work—life theory and research, human resource development professionals can contribute to the strategic development of policies, practices, programs, and interventions that appear to alleviate or ameliorate demands fostering greater work—life integration. Integration is a solution representing a holistic strategy including effective and efficient coordination of efforts and energies among all stakeholders sharing interest and benefits from workers being able to fulfill their personal, work, family, and community obligations.
Rethinking the ClockWork of Work: Why Schedule Control May Pay Off at Work and at Home
Authors: Kelly Erin L. , Moen Phyllis
Published: November 2007

The problem and the solution. Many employees face work—life conflicts and time deficits that negatively affect their health, well-being, effectiveness on the job, and organizational commitment. Many organizations have adopted flexible work arrangements but not all of them increase schedule control, that is, employees' control over when, where, and how much they work. This article describes some limitations of flexible work policies, proposes a conceptual model of how schedule control impacts work—life conflicts, and describes specific ways to increase employees' schedule control, including best practices for implementing common flexible work policies and Best Buy's innovative approach to creating a culture of schedule control.
Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia
Authors: Visco Carlo , Ruggeri Marco , Laura Evangelista Maria , Stasi Roberto , Zanotti Roberta , Giaretta Ilaria , Ambrosetti Achille , Madeo Domenico , Pizzolo Giovanni , Rodeghiero Francesco
Published: November 2007

The prevalence, clinical characteristics, and prognostic significance of immune thrombocytopenia (IT) in patients with chronic lymphocytic leukemia (CLL) have not been clearly determined. To clarify this, we retrospectively analyzed 1278 consecutive newly diagnosed patients with CLL. Criteria for IT diagnosis included the following: rapid (< 2 weeks) and severe fall (half of the initial level and below 100 × 109/L) in platelet count; normal or augmented megakaryocytes in bone marrow; no or limited (not palpable) splenomegaly; no cytotoxic treatment in the preceding month. Sixty-four patients (5%) were diagnosed with IT. The median time to IT from CLL diagnosis was 13 months (range, 0-81 months), and median platelet count at IT diagnosis was 14 × 109/L (range, 1-71 × 109/L). Fifty-six of the 64 patients (87%) received treatment for IT. The probability of responding to treatment for IT was significantly higher for patients receiving chemotherapy with or without steroids than for patients treated with intravenous immunoglobulins with or without steroids (P = .01). The development of IT was significantly associated with unmutated IgVh, a positive direct antiglobulin test, and the occurrence of autoimmune hemolytic anemia. Patients with CLL and IT had poorer survival than other patients with CLL (5-year overall survival 64% vs 82%, P < .001), and this effect was independent from common clinical prognostic variables.
Composite signet-ring cell/neuroendocrine carcinoma of the stomach with a metastatic neuroendocrine carcinoma component: a better prognosis entity
Authors: Nugent Summer L , Cunningham Steven C , Alexiev Borislav A , Bellavance Emily , Papadimitriou John C , Hanna Nader
Published: November 2007

Background

Mixed (composite) exocrine-neuroendocrine cell carcinomas are defined as an intimate admixture of neoplastic glandular exocrine and neuroendocrine cell types. Although gastric adenocarcinoma containing a small number of neuroendocrine cells is a relatively frequent occurrence, gastric neoplasms containing equal proportions of both cell types are rare.

Case Presentation

We present a case of composite exocrine (signet-ring cell)-neuroendocrine cell carcinoma, in which the neoplastic signet-ring cell exocrine and neuroendocrine constituents occurred in fairly equivalent amounts, whereas only the neuroendocrine carcinoma portion of the tumor represented the metastatic component. Light microscopy, immunohistochemical and electron microscopic findings are described, and the literature is reviewed.

Conclusion

This study confirms the ability of pluripotent precursor cells to differentiate into either adenocarcinoma or neuroendocrine tumor and, justifying the designation of composite exocrine-neuroendocrine cell carcinoma as the appropriate classification for this tumor. The protracted clinical course further supports the notion that composite signet-ring cell/neuroendocrine carcinoma tumors behave relatively less aggressively than the pure forms of the former cell type.
Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial
Authors: Jimenez Juan J , Iribarren Jose L , Lorente Leonardo , Rodriguez Jose M , Hernandez Domingo , Nassar Ibrahim , Perez Rosalia , Brouard Maitane , Milena Antonio , Martinez Rafael , Mora Maria L
Published: November 2007

Introduction

Extracorporeal circulation induces hemostatic alterations that lead to inflammatory response (IR) and postoperative bleeding. Tranexamic acid (TA) reduces fibrinolysis and blood loss after cardiopulmonary bypass (CPB). However, its effects on IR and vasoplegic shock (VS) are not well known and elucidating these effects was the main objective of this study.

Methods

A case control study was carried out to determine factors associated with IR after CPB. Patients undergoing elective CPB surgery were randomly assigned to receive 2 g of TA or placebo (0.9% saline) before and after intervention. We performed an intention-to-treat analysis, comparing the incidence of IR and VS. We also analyzed several biological parameters related to inflammation, coagulation, and fibrinolysis systems. We used SPSS version 12.2 for statistical purposes.

Results

In the case control study, 165 patients were studied, 20.6% fulfilled IR criteria, and the use of TA proved to be an independent protective variable (odds ratio 0.38, 95% confidence interval 0.18 to 0.81; P < 0.01). The clinical trial was interrupted. Fifty patients were randomly assigned to receive TA (24) or placebo (26). Incidence of IR was 17% in the TA group versus 42% in the placebo group (P = 0.047). In the TA group, we observed a significant reduction in the incidence of VS (P = 0.003), the use of norepinephrine (P = 0.029), and time on mechanical ventilation (P = 0.018). These patients showed significantly lower D-dimer, plasminogen activator inhibitor 1, and creatine-kinase levels and a trend toward lower levels of soluble tumor necrosis factor receptor and interleukin-6 within the first 24 hours after CPB.

Conclusion

The use of TA attenuates the development of IR and VS after CPB.

Trial registration number

ISRCTN05718824.
Salmonellainfection of afferent lymph dendritic cells
Authors: Chan Simon S M , Mastroeni Pietro , McConnell Ian , Blacklaws Barbara A
Published: November 2007

The interactions of Salmonella enterica subspecies I serotype Abortusovis (S. Abortusovis) with ovine afferent lymph dendritic cells (ALDCs) were investigated for their ability to deliver Maedi visna virus (MVV) GAG p25 antigens to ALDCs purified from afferent lymph. Salmonellae were found to enter ALDC populations by a process of cell invasion, as confirmed by electron and confocal microscopy. This led to phenotypical changes in ALDC populations, as defined by CD1b and CD14 expression. No differences in the clearance kinetics of intracellular aroA-negative Salmonella from CD1b+ CD14lo and CD1b+ CD14− ALDC populations were noted over 72 h. ALDCs were also shown to present MVV GAG p25 expressed by aroA-negative S. Abortusovis to CD4+ T lymphocytes. Thus, the poor immune responses that Salmonella vaccines elicited in large animal models compared with mice are neither a result of an inability of Salmonella to infect large animal DCs nor an inability of these DCs to present delivered antigens. However, the low efficiency of infection of ALDC compared with macrophages or monocyte-derived DCs may account for the poor immune responses induced in large animal models.
Serum Retinol-Binding Protein-4, Leptin, and Adiponectin Concentrations Are Related to Ectopic Fat Accumulation
Authors: Perseghin Gianluca , Lattuada Guido , De Cobelli Francesco , Esposito Antonio , Belloni Elena , Canu Tamara , Ragogna Francesca , Scifo Paola , Del Maschio Alessandro , Luzi Livio
Published: November 2007

Context: Serum retinol-binding protein 4 (RBP-4), leptin, and adiponectin concentrations identify insulin resistance in varied conditions, but their relationships with insulin sensitivity and ectopic fat accumulation are unclear.

Objective: Our objective was to establish how these adipokines are related with intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content.

Design and Setting: We assessed retrospectively serum fasting RBP-4 concentrations in 1) 53 nondiabetic individuals in which insulin sensitivity and IMCL content were assessed by means of the insulin clamp and of 1H magnetic resonance spectroscopy of the calf muscles, and 2) 140 nondiabetic individuals in which insulin sensitivity and the IHL content were assessed by means of the updated homeostasis model assessment and of 1H magnetic resonance spectroscopy. In both experiments, serum leptin and adiponectin concentrations were measured.

Results: Fasting serum RBP-4, adiponectin, and leptin were associated with peripheral insulin sensitivity, were abnormal in the first-degree relatives of type 2 diabetic parents, and correlated with the soleus IMCL content and with the IHL content. The association of RBP-4 and adiponectin with insulin sensitivity was age, sex, and body mass index independent, but stepwise regression analysis suggested that RBP-4, but not adiponectin and leptin, was independently associated with insulin sensitivity. Adiponectin was independently associated with the IHL content, RBP-4, and leptin with the soleus IMCL content.

Conclusion: Serum RBP-4 was a robust marker of insulin resistance. Serum RBP-4, leptin, and adiponectin concentrations reflected ectopic fat accumulation in humans.
Serum 25-Hydroxyvitamin D and Bone Mineral Density in a Racially and Ethnically Diverse Group of Men
Authors: Hannan Marian T. , Litman Heather J. , Araujo Andre B. , McLennan Christine E. , McLean Robert R. , McKinlay John B. , Chen Tai C. , Holick Michael F.
Published: November 2007

Context: Although racial and ethnic differences in vitamin D status and bone mineral density (BMD) are recognized, less is known about how differences in vitamin D status impact BMD, especially among men.

Objective: Our objective was to examine the relation between serum 25-hydroxyvitamin D [25(OH)D] and BMD by race and ethnic group.

Design: We conducted a population-based, observational survey.

Participants: Participants included 1114 Black, Hispanic, and White men, 30–79 yr of age.

Outcomes: We assessed 25(OH)D by a competitive protein binding assay and BMD by dual-energy x-ray absorptiometry.

Results: Mean age ± sd of the 331 Black, 362 Hispanic, and 421 White men was 48 ± 12.8 yr. Mean 25(OH)D was lower among Black (25.0 ± 14.7 ng/ml) and Hispanic (32.9 ± 13.9 ng/ml) men compared with White men (37.4 ± 14.0 ng/ml, P < 0.01). A higher percentage of both Black (44%) and Hispanic (23%) men had levels of 25(OH)D in the lowest quartile, compared with 11% of White men (P < 0.001). After adjusting for age, height, and weight, only White men showed significant positive correlation between 25(OH)D and BMD (range of correlations, 0.00–0.14). Serum 25(OH)D was not associated with BMD in Black or Hispanic men at any bone site. Results were similar when adjusted for age only.

Conclusions: Our findings confirm substantial racial and ethnic group differences in BMD and serum 25(OH)D in men. Serum 25(OH)D and BMD are significantly related to one another in White men only. This may have implications for evaluation of bone health and supplementation in men with low levels of 25(OH)D. Further understanding of the biological mechanisms for these differences between race and ethnic groups is needed.
A cool look at the structural changes in kinesin motor domains
Authors: Amos Linda A. , Hirose Keiko
Published: November 2007

Recently, several 3D images of kinesin-family motor domains interacting with microtubules have been obtained by analysis of electron microscope images of frozen hydrated complexes at much higher resolutions (9-12 Å) than in previous reports (15-30 Å). The high-resolution maps show a complex interaction interface between kinesin and tubulin, in which kinesin's switch II helix α4 is a central feature. Differences due to the presence of ADP, as compared with ATP analogues, support previously determined crystal structures of kinesins alone in suggesting that α4 is part of a pathway linking the nucleotide-binding site and the neck that connects to cargo. A 3D structure of the microtubule-bound Kar3 motor domain in a nucleotide-free state has revealed dramatic changes not yet reported for any crystal structure, including melting of the switch II helix, that may be part of the mechanism by which information is transmitted. A nucleotide-dependent movement of helix α6, first seen in crystal structures of Kif1a, appears to bring it into contact with tubulin and may provide another communication link. A microtubule-induced movement of loop L7 and a related distortion of the central β-sheet, detected only in the empty state, may also send a signal to the region of the motor core that interacts with the neck. Earlier images of a kinesin-1 dimer in the empty state, showing a close interaction between the two motor heads, can now be interpreted in terms of a communication route from the active site of the directly bound head via its central β-sheet to the tethered head.
Statin Treatment of Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage
Authors: Trimble Jason L , Kockler Denise R
Published: November 2007

Objective:

To evaluate the evidence for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for (he prevention and management of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).

Data Sources:

Literature searches were conducted using MEDLINE (1966–July 2007) and the Cochrane Database (2007, Issue 2). Search terms included HMG-CoA reductase inhibitors, statins, subarachnoid hemorrhage, and vasospasm. Other data sources were identified from select bibliographies.

Study Selection and Data Extraction:

All controlled trials evaluating statins for the prevention and management of cerebral vasospasm after aSAH and published in the English language were included for review. Clinical and surrogate markers for cerebral vasospasm and outcomes were assessed.

Data Synthesis:

Cerebral vasospasm, which may occur after aSAH, is associated with serious morbidity and significant mortality. Evidence suggests that statins have noteworthy biochemical effects through inhibition of nicotinamide adenine dinucleotide phosphate oxidase and superoxide production and up regulation and activation of endothelial nitric oxidase synthase and nitric oxidase production via inhibition of geranylgeranylation of RhoA and Rac1 guanosine triphosphatases. Researchers have proposed that these effects may have a role in preventing or reducing vasospasm after aSAH. One matched control study and 3 placebo-con trolled trials (1 with an additional post hoc analysis) have described use of statins for the prevention and management of cerebral vasospasm after aSAH. These data focused on differing primary endpoints; however, reductions in clinical vasospasm and middle cerebral artery transcranial doppler velocity, improved functional outcomes, enhanced autoregulation indices incidence, improvements in duration and time of impaired cerebral autoregulation, and reductions in rescue therapy have been reported.

Conclusions:

Current data suggest that statins may be a reasonable treatment option for the prevention and management of cerebral vasospasm after aSAH. However, results from large, well-controlled trials have not been published.
On Statins, Strokes, Meta-Analyses, Competing Risks, and the Onward March of Science
Authors: Belloto Robert J
Published: November 2007

A comment on the conduct of a meta-analysis analyzing the effects of statins on cardiovascular and cerebrovascular outcomes is presented in this editorial. Competing risk and risk-stratified analysis models that may be more appropriate for the analysis of clinical trials in general and statin trials in particular are introduced. The avoidance of these more complicated models seems to be paradoxical when other models that clinicians have used for some time and are using today are seen to contain more patient variables than the proposed models. Certainty, one way these competing risk and general mathematical models will be used is to have the data readily available for other researchers to duplicate the calculations or use in entirely new ways. This aids in the learning process and helps students, reviewers, editors, and others who wish to research and judge the clinical trials.
Factors Influencing Supplier Share Allocations in an Overseas Chinese Context
Authors: Brush Gregory J. , Rexha Nexhmi
Published: November 2007

Recent international attention has been drawn to marketing opportunities in Asia and the important role of customer relationships in supplier performance. However, empirical research on industrial buying behavior in Asia is sparse, and the extant literature indicates that buyer behavior may differ in non-Western industrial marketing relationships. Drawing on transaction cost economics and relational exchange theory, the authors develop a model that provides new insights into how international supplier behaviors affect manufacturer trust–performance perceptions and their business share allocation in a Chinese-dominated business environment. The results from 340 industrial relationships indicate the significant role of communications and adaptations in relationship development. Moreover, trust in suppliers and their performance are equally important factors in a manufacturer's business share allocation. The study contributes to the generalizability of relationship marketing theory and practice through empirical evidence on the transferability of Western business concepts.
Assessing Measurement Invariance of Export Market Orientation: A Study of Chinese and Non-Chinese Firms in China
Authors: Murray Janet Y. , Gao Gerald Yong , Kotabe Masaaki , Zhou Nan
Published: November 2007

In response to numerous calls for the cross-cultural validation of measures used in international research, the authors assess measurement invariance of the export market orientation (EMO) and export performance (EP) constructs using 491 Chinese and non-Chinese export ventures in China. The results show that both the EMO and the EP scales are invariant between Chinese and non-Chinese export ventures. In addition, different EMO components have differential effects on EP for Chinese versus non-Chinese firms. To achieve higher EP, Chinese firms should focus on export intelligence responsiveness, and non-Chinese firms should concentrate their efforts on export intelligence generation. The authors discuss implications and suggest directions for further research.
Prion Protein Regulates Glutamate-Dependent Lactate Transport of Astrocytes
Authors: Kleene Ralf , Loers Gabriele , Langer Julia , Frobert Yveline , Buck Friedrich , Schachner Melitta
Published: November 2007

Prion-related protein (PrP) is a neural cell adhesion molecule involved in neurite outgrowth, neuronal survival, and synaptic function. In search of novel binding partners for PrP, we identified the α2/β2-Na+/K+-ATPase and showed that this astroglial ATPase interacts directly with the immunoglobulin superfamily adhesion molecule basigin. In cultured astrocytes, PrP is involved in regulating lactate transport via the astroglial monocarboxylate transporter 1 (MCT1) and in conjunction with α2/β2-ATPase and basigin. Lactate transport via MCT1 is glutamate dependent and regulated by glutamate receptor 2 (GluR2)-containing AMPA receptors with which PrP interacts. The functional interplay between PrP, GluR2, α2/β2-ATPase, basigin, and MCT1 in regulating lactate transport of astrocytes may be functional in the metabolic cross talk between astrocytes and neurons, most likely under stress.
Single-Unit Firing in Rat Perirhinal Cortex Caused by Fear Conditioning to Arbitrary and Ecological Stimuli
Authors: Furtak Sharon C. , Allen Timothy A. , Brown Thomas H.
Published: November 2007

Pretraining lesions of rat perirhinal cortex (PR) severely impair pavlovian fear conditioning to a 22 kHz ultrasonic vocalization (USV) cue. However, PR lesions are without significant effect when the cue is a continuous tone at the same or a lower frequency. Here we examined fear-conditioning-produced changes in single-unit firing elicited in rat PR by a 22 kHz tone cue or a 22 kHz USV cue. Chronic recording electrodes were introduced from the lateral surface of the skull. Altogether, 200 well isolated units were studied in 28 rats. Overall, 73% of the recorded single units (145 of 200 units) evidenced statistically significant firing changes in response to the tone or USV conditional stimulus (CS) after it had been paired several times with an aversive unconditional stimulus (US). Interestingly, 33% of units (66 of 200 units) that were initially CS-unresponsive became CS-responsive after conditioning. After conditioning, there were two notable differences between single-unit responses elicited by the USV cue and those elicited by the tone cue. First, 11% of the units (14 of 123 units) recorded from the USV-conditioned group displayed a precisely timed increase in firing rate during the 260 ms interval in which the US had previously occurred. This US-timed response was unique to the USV-conditioned group. Second, the mean latency of cue-elicited firing was ∼30 ms longer in the USV-conditioned group than in the tone-conditioned group. These cue-specific differences in acquired firing latencies and acquired firing patterns suggest that spectrotemporal properties of a CS can control the essential circuitry or neurophysiological mechanisms underlying fear conditioning.
Trade-Off between Object Selectivity and Tolerance in Monkey Inferotemporal Cortex
Authors: Zoccolan Davide , Kouh Minjoon , Poggio Tomaso , DiCarlo James J.
Published: November 2007

Object recognition requires both selectivity among different objects and tolerance to vastly different retinal images of the same object, resulting from natural variation in (e.g.) position, size, illumination, and clutter. Thus, discovering neuronal responses that have object selectivity and tolerance to identity-preserving transformations is fundamental to understanding object recognition. Although selectivity and tolerance are found at the highest level of the primate ventral visual stream [the inferotemporal cortex (IT)], both properties are highly varied and poorly understood. If an IT neuron has very sharp selectivity for a unique combination of object features (“diagnostic features”), this might automatically endow it with high tolerance. However, this relationship cannot be taken as given; although some IT neurons are highly object selective and some are highly tolerant, the empirical connection of these key properties is unknown. In this study, we systematically measured both object selectivity and tolerance to different identity-preserving image transformations in the spiking responses of a population of monkey IT neurons. We found that IT neurons with high object selectivity typically have low tolerance (and vice versa), regardless of how object selectivity was quantified and the type of tolerance examined. The discovery of this trade-off illuminates object selectivity and tolerance in IT and unifies a range of previous, seemingly disparate results. This finding also argues against the idea that diagnostic conjunctions of features guarantee tolerance. Instead, it is naturally explained by object recognition models in which object selectivity is built through AND-like tuning mechanisms.
Activity-Dependent Synaptic Plasticity in Retinal Ganglion Cells
Authors: Xia Yingqiu , Nawy Scott , Carroll Reed C.
Published: November 2007

At many excitatory synapses, AMPA-type receptors (AMPARs) are not statically situated in the membrane, but undergo continuous rounds of endocytosis and exocytosis, referred to as rapid cycling. AMPAR cycling is believed to play a role in certain forms of synaptic plasticity, but the link between cycling and synaptic function is not well understood. We have previously demonstrated that AMPARs cycle in neurons of the inner retina, including amacrine and ganglion cells, and that cycling is inhibited by synaptic activity. Recording from cultured neurons and ON ganglion cells in the flat-mount retina, we now show that rapid cycling is primarily, perhaps exclusively, restricted to AMPARs that contain the GluR2 subunit, and that cycle is confined to extrasynaptic receptors. We also demonstrate a form of plasticity at the ON bipolar cell–ON ganglion cell synapse, whereby synaptic quiescence drives a change in the composition of AMPARs from predominantly GluR2-containing to GluR2-lacking. Finally, we provide evidence linking synaptic receptor composition and cycling, showing that disruption of cycling leads increases the number of GluR2-containing receptors in the ON bipolar–ON ganglion cell synapse. We propose that cycling lowers the number of GluR2-containing receptors at the surface and, consequently, within the synapse. After increased levels of synaptic activity, cycling ceases, and all GluR2-containing receptors are free to go to the surface, where they can be delivered to synapses. Our results suggest that by regulating the cycling of AMPARs, ambient light can modulate the composition of synaptic receptors in ON ganglion cells.
Human Motor Corpus Callosum: Topography, Somatotopy, and Link between Microstructure and Function
Authors: Wahl Mathias , Lauterbach-Soon Birgit , Hattingen Elke , Jung Patrick , Singer Oliver , Volz Steffen , Klein Johannes C. , Steinmetz Helmuth , Ziemann Ulf
Published: November 2007

The corpus callosum (CC) is the principal white matter fiber bundle connecting neocortical areas of the two hemispheres. Although an object of extensive research, important details about the anatomical and functional organization of the human CC are still largely unknown. Here we focused on the callosal motor fibers (CMFs) that connect the primary motor cortices (M1) of the two hemispheres. Topography and somatotopy of CMFs were explored by using a combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure. CMF microstructure was assessed by fractional anisotropy (FA), and CMF functional connectivity between the hand areas of M1 was measured by interhemispheric inhibition using paired-pulse transcranial magnetic stimulation. CMFs mapped onto the posterior body and isthmus of the CC, with hand CMFs running significantly more anteriorly and ventrally than foot CMFs. FA of the hand CMFs but not FA of the foot CMFs correlated linearly with interhemispheric inhibition between the M1 hand areas. Findings demonstrate that CMFs connecting defined body representations of M1 map onto a circumscribed region in the CC in a somatotopically organized manner. The significant and topographically specific positive correlation between FA and interhemispheric inhibition strongly suggests that microstructure can be directly linked to functional connectivity. This provides a novel way of exploring human brain function that may allow prediction of functional connectivity from variability of microstructure in healthy individuals, and potentially, abnormality of functional connectivity in neurological or psychiatric patients.
The Temporal Sequence of Gut Peptide–CNS Interactions TrackedIn Vivoby Magnetic Resonance Imaging
Authors: Kuo Yu-Ting , Parkinson James R. C. , Chaudhri Owais B. , Herlihy Amy H. , So Po-Wah , Dhillo Waljit S. , Small Caroline J. , Bloom Stephen R. , Bell Jimmy D.
Published: November 2007

Hormonal satiety signals secreted by the gut play a pivotal role in the physiological control of appetite. However, therapeutic exploitation of the gut–brain axis requires greater insight into the interaction of gut hormones with CNS circuits of appetite control. Using the manganese ion (Mn2+) as an activity-dependent magnetic resonance imaging (MRI) contrast agent, we showed an increase in signal intensity (SI) in key appetite-regulatory regions of the hypothalamus, including the arcuate, paraventricular, and ventromedial nuclei, after peripheral injection of the orexigenic peptide ghrelin. Conversely, administration of the anorexigenic hormone peptide YY3–36caused a reduction in SI. In both cases, the changes in SI recorded in the hypothalamic arcuate nucleus preceded the effect of these peptides on food intake. Intravenous Mn2+itself did not significantly alter ghrelin-mediated expression of the immediate early gene product c-Fos, nor did it cause abnormalities of behavior or metabolic parameters. We conclude that manganese-enhanced MRI constitutes a powerful tool for the future investigation of the effects of drugs, hormones, and environmental influences on neuronal activity.
Double Dissociation of Attentional Resources: Prefrontal Versus Cingulate Cortices
Authors: Ng Chi-Wing , Noblejas Maria I. , Rodefer Joshua S. , Smith Christina B. , Poremba Amy
Published: November 2007

Efficient attention to our environment facilitates the decisions that need to be executed in daily life. Filtering critical from noncritical information may require the neural organization of multiple brain regions. Combining lesion techniques and the rodent version of the Wisconsin card sorting task in humans, we show at least two types of attentional processing systems reside in the cingulate and prefrontal cortices depending on task demands requiring shifts of attention within or between sets of meaningful cues, respectively. This neural organization for shifting attention either within or between perceptual dimensions is task dependent, and this type of organization provides evidence of attentional systems that transcend separate modality processing systems while subdividing executive control of attention. The results suggest that the anterior and posterior cingulate cortices are critical when shifting attention to closely related meaningful cues (i.e., within a perceptual dimension or attentional set) by suppressing interference of irrelevant background information, whereas the prefrontal cortex is critical when shifting attention between disparate sets of meaningful cues (i.e., between perceptual dimensions or attentional sets) (Dias et al., 1996a,b; Birrell and Brown, 2000). Based on the theories of Mackintosh (1965, 1975; Sutherland and Mackintosh, 1971), it is suggested that the cingulate cortex may be important for decreasing attention to irrelevant information. In general, attention deficit disorders affect both children and adults, and current medications may affect the prefrontal and associated parietal cortical systems more or less than the cingulate cortical system.
A Domain Linking the AMPA Receptor Agonist Binding Site to the Ion Pore Controls Gating and CauseslurcherProperties when Mutated
Authors: Schmid Sabine M. , Körber Christoph , Herrmann Solveig , Werner Markus , Hollmann Michael
Published: November 2007

Ionotropic, AMPA-type glutamate receptors (GluRs) critically shape excitatory synaptic signals in the CNS. Ligand binding induces conformational changes in the glutamate-binding domain of the receptors that are converted into opening of the channel pore via three short linker sequences, a process referred to as gating. Although crystallization of the glutamate-binding domain and structural models of the ion pore advanced our understanding of ligand-binding dynamics and pore movements, the allosteric coupling of both events by the short linkers has not been described in detail. To study the role of the linkers in gating GluR1, we transplanted them between different GluRs and examined the electrophysiological properties of the resulting chimeric receptors inXenopus laevisoocytes and HEK293 cells. We found that all three linkers decisively affect receptor functionality, agonist potency, and desensitization. One linker chimera was nondesensitizing and exhibited strongly increased agonist potencies, while fluxing ions even in the absence of agonist, similar to properties reported for the GluR1lurchermutation. Combining this newlurcher-like linker chimera with the originallurchermutation allowed us to reassess the effect oflurcheron GluR1 gating properties. The observed differential but interdependent influence of linker andlurchermutations on receptor properties suggests that the linkers are part of a fine-tuned structural element that normally stabilizes the closed ion pore. We propose thatlurcher-like mutations act by disrupting this element such that ligand-induced conformational changes are not necessarily required to gate the channel.
Reconfiguration of a Vertebrate Motor Network: Specific Neuron Recruitment and Context-Dependent Synaptic Plasticity
Authors: Li Wen-Chang , Sautois Bart , Roberts Alan , Soffe Stephen R.
Published: November 2007

Motor networks typically generate several related output patterns or gaits where individual neurons may be shared or recruited between patterns. We investigate how a vertebrate locomotor network is reconfigured to produce a second rhythmic motor pattern, defining the detailed pattern of neuronal recruitment and consequent changes in the mechanism for rhythm generation. HatchlingXenopustadpoles swim if touched, but when held make slower, stronger, struggling movements. In immobilized tadpoles, a brief current pulse to the skin initiates swimming, whereas 40 Hz pulses produce struggling. The classes of neurons active during struggling are defined using whole-cell patch recordings from hindbrain and spinal cord neurons during 40 Hz stimulation of the skin. Some motoneurons and inhibitory interneurons are active in both swimming and struggling, but more neurons are recruited within these classes during struggling. In addition, and in contrast to a previous study, we describe two new classes of excitatory interneuron specifically recruited during struggling and define their properties and synaptic connections. We then explore mechanisms that generate struggling by building a network model incorporating these new neurons. As well as the recruitment of new neuron classes, we show that reconfiguration of the locomotor network to the struggling central pattern generator (CPG) reveals a context-dependent synaptic depression of reciprocal inhibition: the result of increased inhibitory neuron firing frequency during struggling. This provides one possible mechanism for burst termination not seen in the swimming CPG. The direct demonstration of depression in reciprocal inhibition confirms a key element of Brown's (1911) hypothesis for locomotor rhythmogenesis.
Stereotypical Bouton Clustering of Individual Neurons in Cat Primary Visual Cortex
Authors: Binzegger Tom , Douglas Rodney J. , Martin Kevan A. C.
Published: November 2007

In all species examined, with the exception of rodents, the axons of neocortical neurons form boutons in multiple separate clusters. Most descriptions of clusters are anecdotal, so here we developed an objective method for identifying clusters. We applied a mean-shift cluster-algorithm to three-dimensional reconstructions of 39 individual neurons and three thalamic afferents from the cat primary visual cortex. Both spiny (20 of 26) and smooth (7 of 13) neurons formed at least two distinct ellipsoidal clusters (range, 2–7). For all cell types, cluster formation is heterogenous, but is regulated so that cluster size and the number of boutons allocated to a cluster equalize with increasing number of clusters formed by a neuron. The bouton density within a cluster is inversely related to the spatial scale of the axon, resulting in a four times greater density for smooth neurons than for spiny neurons. Thus, the inhibitory action of the smooth neurons is much more concentrated and focal than the excitatory action of spiny neurons. The cluster with the highest number of boutons (primary cluster) was typically located around or above the soma of the parent neuron. The distance to the next cluster was proportional to the diameter of the primary cluster, suggesting that there is an optimal distance and spatial focus of the lateral influence of a neuron. The lateral spread of clustered axons may thus support a spoke-like network architecture that routes signals to localized sites, thereby reducing signal correlation and redundancy.
Neural Ensembles in CA3 Transiently Encode Paths Forward of the Animal at a Decision Point
Authors: Johnson Adam , Redish A. David
Published: November 2007

Neural ensembles were recorded from the CA3 region of rats running on T-based decision tasks. Examination of neural representations of space at fast time scales revealed a transient but repeatable phenomenon as rats made a decision: the location reconstructed from the neural ensemble swept forward, first down one path and then the other. Estimated representations were coherent and preferentially swept ahead of the animal rather than behind the animal, implying it represented future possibilities rather than recently traveled paths. Similar phenomena occurred at other important decisions (such as in recovery from an error). Local field potentials from these sites contained pronounced theta and gamma frequencies, but no sharp wave frequencies. Forward-shifted spatial representations were influenced by task demands and experience. These data suggest that the hippocampus does not represent space as a passive computation, but rather that hippocampal spatial processing is an active process likely regulated by cognitive mechanisms.
Flexible Coding for Categorical Decisions in the Human Brain
Authors: Li Sheng , Ostwald Dirk , Giese Martin , Kourtzi Zoe
Published: November 2007

Despite the importance of visual categorization for interpreting sensory experiences, little is known about the neural representations that mediate categorical decisions in the human brain. Here, we used psychophysics and pattern classification for the analysis of functional magnetic resonance imaging data to predict the features critical for categorical decisions from brain activity when observers categorized the same stimuli using different rules. Although a large network of cortical and subcortical areas contain information about visual categories, we show that only a subset of these areas shape their selectivity to reflect the behaviorally relevant features rather than simply physical similarity between stimuli. Specifically, temporal and parietal areas show selectivity for the perceived form and motion similarity, respectively. In contrast, frontal areas and the striatum represent the conjunction of spatiotemporal features critical for complex and adaptive categorization tasks and potentially modulate selectivity in temporal and parietal areas. These findings provide novel evidence for flexible neural coding in the human brain that translates sensory experiences to categorical decisions by shaping neural representations across a network of areas with dissociable functional roles in visual categorization.
The Healing Religions
Authors: Dericquebourg Regis
Published: November 2007

Many religions are concerned with the problem of illness. They organize healing pilgrimages and benedictions for sick people, but the cure of sickness is not their main preoccupation. They are primarily concerned with the salvation of souls. At the other extreme, groups such as Christian Science, Antoinism (which emerged in Belgium in 1910) Invitation to Life (emerging in France in 1983), and the followers of the Christ of Montfavet (founded by a French spiritual healer in the mid-20th century) are directly concerned with the treatment of illness. Those religions refer to poverty, physical and mental difficulties, and all kinds of misfortunes. Healing religions consider that suffering is not a normal condition of humanity insofar as God provides the spiritual tools to enable health and well-being. The results of my empirical studies let me to propose an ideal-type of healing religions. Doing so, I am showing that the healing churches which are minority religious groups constitute an original unit in the social field of religions.
Brand of Choice
Authors: McIntyre E.H.
Published: November 2007

Amid current competing ideologies and priorities, Hillsong has found a formula that fuses aspects of secular consumerism and individualism with Pentecostal religious fervour. This paper will examine the ways Hillsong music is used to constitute religious experience and how religious experience is (re)packaged and sold by the lucrative Hillsong Music label. This paper looks at musical and lyrical examples from two popular artists on the Hillsong Music label, Hillsong United and Darlene Zschech and examines how and why their songs are used in worship. Data is taken from observation of Hillsong church services and from the recorded music available on CD. The paper concludes that Hillsong music actively appropriates mainstream popular music styles and utilises their appeal to the modern religious consumer. Hillsong music emphasises feeling and experience over doctrine by placing the ultimate authority and control over an individual’s religious practice into their own hands. Hillsong promotion includes a lucrative music label that extends the Pentecostal emphasis on personal experience beyond the space of the church itself and recreates it in the marketable form of the CD. It is recommended that this paper acts as a step towards a wider scale study of the popularity of Hillsong and its music, and the way it shapes and reflects Australian religiosity.