bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron Status in Toddlerhood Predicts Sensitivity to Psychostimulants in Children
Authors: Turner Catharyn A. , Xie Diqiong , Zimmerman Bridget M. , Calarge Chadi A.
Published: October 2010

Objective: Iron deficiency is associated with impaired dopaminergic signaling and externalizing behavior. The authors examine, whether iron stores in toddlerhood influence later response to psychostimulants. Method: Youth participating in a study monitoring the long-term safety of risperidone were included in this analysis if they had received psychostimulant monotherapy for at least 3 weeks and had a complete blood count obtained before psychostimulant treatment. Sensitivity to psychostimulants was defined based on the weight-adjusted dose during the 1st year of treatment. Regression analysis examined whether the hematological tests based on the characteristics of red blood cells were associated with sensitivity to psychostimulants. Results: A total of 29 participants (93% men; 76% Whites), primarily with ADHD (93%), comprised the current sample. The hematological tests were obtained, on average, 3 years before the initiation of psychostimulants monotherapy that occurred at 5.8 years of age and continued for a median of 0.85 years, at an average daily dose of 0.98 mg/kg ( SD = 0.38) in methylphenidate equivalent. Compared with those who were poorly sensitive to psychostimulants, after adjusting for age, mean corpuscular volume was significantly higher in the highly and moderately psychostimulants sensitive groups. Conclusions: If replicated, these findings suggest that more attention should be paid to optimizing body iron in early childhood.
Cellular Automata Simulations on a FPGA cluster
Authors: Murtaza S. , Hoekstra A.G. , Sloot P.M.A.
Published: October 2010

The emergence of multicore architectures and the chip industry’s plan to roll out hundreds of cores per die sometime in the near future might have triggered the evolution of von Neumann architectures towards a parallel processing paradigm. The capability to have hundreds of cores per die is exciting, but how optimally we are able to utilize such a resource remains a challenge. Since there are no straightforward solutions we seek inspiration from relevant scientific processes. Cellular automata which are inherently decentralized and spatially extended structures provide a potential candidate among parallel processing alternatives. The availability of spatial parallelism on field programmable gate arrays make them the ideal platform to investigate cellular automata systems as potential parallel processing paradigms on multicore architectures. This article presents a massively parallel implementation for a floating-point-based cellular automata using special purpose hardware such as Field Programmable Gate Array (FPGAs). The challenge is to best map an application to the underlying many-core architecture and address issues such as inter-core communication, scalability, and flexibility both in terms of hardware and software. Maxwell — a 64-node FPGA supercomputer, is used for accelerator implementations that range from a single to a multiple FPGA-enabled system. A performance model is proposed and demonstrated to closely reproduce measured execution times. The performance model enables identification of the main sources of overhead and suggests improvements to the architecture and implementation of the lattice Boltzmann method and compute-bound cellular automata in general. Further, a 2 million cell 2DQ9 lattice Boltzmann method lattice with periodic boundary conditions, simulated using a multiple FPGA chip accelerator implementation, is presented. The performance model shows how the FPGA-enabled PC cluster is the preferred multiple FPGA organization over the multiple FPGA-based PC setup. Latency hiding is fully exploited for PC cluster-based system implementations and demonstrated using system profiling.
A Strategy for Diversity Training
Authors: Madera Juan M. , Neal Jack A. , Dawson Mary
Published: October 2010

The purpose of this study was to test the effectiveness of a diversity training exercise using perspective taking to increase positive attitudes toward non-English-speaking individuals. Ninety-six participants were given a pretest (survey) followed by the training and a posttest. Participants were randomly assigned as a “manager” or an “employee.” The managers were provided with a recipe and instructions in English, and the managers’ employees provided with the recipe and instruction in an abstract, non-English language. The results of a repeated-measures ANOVA showed a significant effect of perspective-taking training on attitudes toward non-English speakers, such that attitudes were more positive posttraining than pretraining. The effect of the training on the attitudes toward non-English-speaking individuals was moderated by the status role (i.e., manager or employee). In addition, participants’ empathy mediated the relationship between the perspective-taking training and attitudes, such that perspective taking induced empathy, resulting in more positive attitudes.
Grounding Evaluations in Culture
Authors: Samuels Maurice , Ryan Katherine
Published: October 2010

The emergence of and the attention given to culture in the evaluation field over the last decade has created a heightened awareness of and need for evaluators to understand the complexity and multidimensionality of evaluations within multicultural, multiracial, and cross-cultural contexts. In this article, the authors discuss how cultural considerations can be incorporated within other evaluation approaches (e.g., school-based evaluation). The authors begin with a selective review on the rapidly growing literature on culture and evaluation, with particular attention to culturally responsive evaluation. After sketching the foundations and implementation of this approach, designated as culturally relevant democratic inquiry (CDI), the authors present an excerpt from a CDI pilot the authors have conducted. The article concludes with an analysis of the potential benefits and current challenges to implementing CDI and integrating culture into evaluations in general.
Disease progression in multiple sclerosis: combining physicians’ and patients’ perspectives?
Authors: Kragt JJ , Nielsen JM , van der Linden FAH , Polman CH , Uitdehaag BMJ
Published: October 2010

Background: To assess disease progression in multiple sclerosis (MS) several outcome measures are available. The interrelation of changes on different scales has not been studied extensively and the concept of combining scales has only recently been introduced in MS.

Objective: To explore combining different clinical outcome measures in the evaluation of disease progression in MS.

Methods: In 553 patients we studied the presence of relevant changes according to standard definitions on the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (9HPT), Timed 25-Foot Walk (T25FW) and the Multiple Sclerosis Impact Scale (MSIS-29). We examined ‘exclusive worsening’ (worsening on one measure while not worsening on any other measure) and ‘opposing changes’ (worsening on one measure while improving on another measure). Finally, we investigated the impact of combining assessments.

Results: Based on the EDSS alone, 140 patients progressed. However, almost twice as many (275) showed worsening on any of the clinical outcome measures. Exclusive worsening was observed in 37 patients on the EDSS, 13 on the 9HPT, 39 on the T25FW and 44 on the MSIS physical. Of all worsened patients 76 (28%) showed opposing changes, a phenomenon predominantly observed when combining physician-based and patient-derived outcome measures.

Conclusion: When assessing disease progression in MS, sensitivity to change can be increased by combining different outcome measures. The added value is especially present when combining measures from different perspectives. However, further research is needed to evaluate the optimal way to combine outcome measures before implementing this strategy in clinical studies.
The globalized state: Measuring and monitoring governance
Authors: Buduru Bogdan , Pal Leslie A.
Published: October 2010

In the last 20 years, there has been an explosion of ‘governance indicators’ purporting to measure and track the quality of governance (especially public administration) among states. These indicators are sponsored by international agencies such as the World Bank, NGOs such as Transparency International and Freedom House, and private sector risk assessors. We argue that this web of standards marks a distinctive feature of globalized, if loose, coordination among states and an increase in monitoring and auditing functions. The article reviews the major governance indicators, their characteristics and limitations. We conclude that these indicators are a little noticed, but supremely powerful mechanism of discordant control and discipline on state systems around the world.
DNA and the politics of truth in socially organized life
Authors: Gustavs Julie , Clegg Stewart R.
Published: October 2010

We apply a representation of the double helix to explain how truth is managed in the social organization of life. One chain, representing context, is made up of the three materialities through which we move — discourses, time and space. The other chain, representing agency, comprises identity, distinct capitals and practices. The chains are fused by horizontal rods, which represent capillaries of power relating the elemental chains by binding, winding and tangling them together in various ways. The model offers an innovative tool for theorization of socially organized truth relations.
Power: A ‘family resemblance’ concept
Authors: Haugaard Mark
Published: October 2010

While Lukes’ view of power as an ‘essentially contested concept’ is a move in the right direction, it does not go far enough because it falls short of arguing for a plural view of power. Power constitutes a ‘family resemblance concept’, with family members forming complex relationships within overlapping language games. Members include, among others: episodic power, dispositional power, systemic power, power to, power over, empowerment, legitimate power and domination. This argument does not entail relativism or that ‘anything goes’, as all usages have to be justified as ‘conceptual tools’, whereby pragmatic criteria of usefulness, rather than essence, define better or worse usage. When moving language games, the relationship between signifier and referent changes, which leads to confusion, unless the family resemblance nature of power is understood. In the literature, the most significant confusion has taken place between sociological analytic and normative political theory language games.
Agency and power: The contractual illusion
Authors: Sulkunen Pekka
Published: October 2010

Many forms of governance today stress the contractual form. This article asks if this phenomenon is real or just an illusion. The contract is analysed in light of Steven Lukes’ power theory. The contractual form avoids everything that the Lukesian or Foucauldian ‘third dimension’ of power seeks to establish. Contracts aim to make power visible, transparent, accountable and based on conscious, informed consent. The article argues, on the basis of the theory of justification developed by Boltanski and Thévenot, that contractual power is a response to the principle of justification in contemporary society, where agency is a measure of human dignity and worth. Contractual power explains the tendency to exclude people who are incapable of assuming agency. The contractual form is literally an illusion, but has real consequences in society.
Assessment of Mean Platelet Volume of Pregnant Women with Gestational Diabetes Mellitus and Impaired Glucose Tolerance as a Marker of Future Cardiovascular Disease Risk
Authors: Köşüş Aydin , Köşüş Nermin , Duran Müzeyyen , Turhan Nilgün Öztürk
Published: October 2010

Objective To assess the platelet count and mean platelet volume (MPV) of pregnant women with gestational diabetes mellitus (GDM) or gestational impaired glucose tolerance (GIGT) to find out whether GDM and GIGT are risk factors for future development of cardiovascular disease. Study design A 50-g oral glucose load (OGL) was administered to all participants and heamotologic parameters were studied at 24–28 gestational weeks. When plasma glucose ≥ 140 mg/dl (7.8 mmol/L) was measured following the OGL, a 100 g-3-h oral glucose tolerance test was undertaken. Results A significant difference was observed for MPV values between the GDM and normal OGL groups.

Conclusion Presence of a high MPV in GDM could demonstrate an increase in the risk for current and future thrombotic complications.
Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia
Authors: Kawatani Yukie , Suzuki Takafumi , Shimizu Ritsuko , Kelly Vincent P. , Yamamoto Masayuki
Published: October 2010

Reactive oxygen species (ROS) are highly destructive toward cellular macromolecules. However, moderate levels of ROS can contribute to normal cellular processes including signaling. Herein we evaluate the consequence of a pro-oxidant environment on hematopoietic homeostasis. The NF-E2 related factor 2 (Nrf2) transcription factor regulates genes related to ROS scavenging and detoxification. Nrf2 responds to altered cellular redox status, such as occurs with loss of antioxidant selenoproteins after deletion of the selenocysteine-tRNA gene (Trsp). Conditional knockout of the Trsp gene using Mx1-inducible Cre-recombinase leads to selenoprotein deficiency and anemia on a wild-type background, whereas Trsp:Nrf2 double deficiency dramatically exacerbates the anemia and increases intracellular hydrogen peroxide levels in erythroblasts. Results indicate that Nrf2 compensates for defective ROS scavenging when selenoproteins are lost from erythroid cells. We also observed thymus atrophy in single Trsp-conditional knockout mice, suggesting a requirement for selenoprotein function in T-cell differentiation within the thymus. Surprisingly, no changes were observed in the myelomonocytic or megakaryocytic populations. Therefore, our results show that selenoprotein activity and the Nrf2 gene battery are particularly important for oxidative homeostasis in erythrocytes and for the prevention of hemolytic anemia.
Genome-wide identification and evolution of ATP-binding cassette transporters in the ciliate Tetrahymena thermophila: A case of functional divergence in a multigene family
Authors: Xiong Jie , Feng Lifang , Yuan Dongxia , Fu Chengjie , Miao Wei
Published: October 2010

Background

In eukaryotes, ABC transporters that utilize the energy of ATP hydrolysis to expel cellular substrates into the environment are responsible for most of the efflux from cells. Many members of the superfamily of ABC transporters have been linked with resistance to multiple drugs or toxins. Owing to their medical and toxicological importance, members of the ABC superfamily have been studied in several model organisms and warrant examination in newly sequenced genomes.

Results

A total of 165 ABC transporter genes, constituting a highly expanded superfamily relative to its size in other eukaryotes, were identified in the macronuclear genome of the ciliateTetrahymena thermophila. Based on ortholog comparisons, phylogenetic topologies and intron characterizations, each highly expanded ABC transporter family ofT.thermophilawas classified into several distinct groups, and hypotheses about their evolutionary relationships are presented. A comprehensive microarray analysis revealed divergent expression patterns among the members of the ABC transporter superfamily during different states of physiology and development. Many of the relatively recently formed duplicate pairs within individual ABC transporter families exhibit significantly different expression patterns. Further analysis showed that multiple mechanisms have led to functional divergence that is responsible for the preservation of duplicated genes.

Conclusion

Gene duplications have resulted in an extensive expansion of the superfamily of ABC transporters in theTetrahymenagenome, making it the largest example of its kind reported in any organism to date. Multiple independent duplications and subsequent divergence contributed to the formation of different families of ABC transporter genes. Many of the members within a gene family exhibit different expression patterns. The combination of gene duplication followed by both sequence divergence and acquisition of new patterns of expression likely plays a role in the adaptation ofTetrahymena to its environment.
Dissociation of μ- and δ-opioid Inhibition of Glutamatergic Synaptic Transmission in Superficial Dorsal Horn
Authors: Wrigley Paul J , Jeong Hyo-Jin , Vaughan Christopher W
Published: October 2010

Background:

There is anatomical and behavioural evidence that μ- and δ-opioid receptors modulate distinct nociceptive modalities within the superficial dorsal horn. The aim of the present study was to examine whether μ- and δ-opioid receptor activation differentially modulates TRP sensitive inputs to neurons within the superficial dorsal horn. To do this, whole cell patch clamp recordings were made from lamina I – II neurons in rat spinal cord slices in vitro to examine the effect of opioids on TRP agonist-enhanced glutamatergic spontaneous miniature excitatory postsynaptic currents (EPSCs).

Results:

Under basal conditions the μ-opioid agonist DAMGO (3 μM) reduced the rate of miniature EPSCs in 68% of neurons, while the δ- and κ-opioid agonists deltorphin-II (300 nM) and U69593 (300 nM) did so in 13 – 17% of neurons tested. The TRP agonists menthol (400 μM) and icilin (100 μM) both produced a Ca2+-dependent increase in miniature EPSC rate which was unaffected by the voltage dependent calcium channel (VDCC) blocker Cd2+. The proportion of neurons in which deltorphin-II reduced the miniature EPSC rate was enhanced in the presence of icilin (83%), but not menthol (0%). By contrast, the proportion of DAMGO and U69593 responders was unaltered in the presence of menthol (57%, 0%), or icilin (57%, 17%).

Conclusions:

These findings demonstrate that δ-opioid receptor activation selectively inhibits inputs activated by icilin, whereas μ-opioid receptor activation has a more widespread effect on synaptic inputs to neurons in the superficial dorsal horn. These findings suggest that δ-opioids may provide a novel analgesic approach for specific, TRPA1-like mediated pain modalities.
Bromocriptine Mesylate for Glycemic Management in Type 2 Diabetes Mellitus
Authors: Kerr Jessica L , Timpe Erin M , Petkewicz Katherine A
Published: October 2010

Objective:

To review the pharmacologic characteristics, safety, and efficacy of bromocriptine mesylate for glycemic control in patients with type 2 diabetes mellitus.

Data Sources:

A Scopus and MEDLINE search (1950–June 2010) was conducted using the key words bromocriptine, diabetes, and circadian rhythm. Data were also received from the manufacturer.

Study Selection and Data Extraction:

Available abstracts, studies, and review articles published in English with human data discussing bromocriptine treatment for type 2 diabetes mellitus were reviewed.

Data Synthesis:

Bromocriptine is an ergot derivative available for treatment of type 2 diabetes. The mechanism of action of this agent is unclear; however, activity as a dopamine D2 receptor agonist seems to provide the primary mechanism for utility in resetting the circadian rhythm in patients with type 2 diabetes. Other mechanisms, including α-1 antagonist, α-2 agonist, and serotonin and prolactin modulator, may also help to explain bromocriptine's glucose-lowering effects. Studies with bromocriptine have included 4328 patients with type 2 diabetes. The majority of available trials conducted enrolled patients for a study duration of 6–24 weeks. One trial evaluating the safety and efficacy of bromocriptine concluded after 52 weeks of follow-up. Endpoints of hemoglobin A1c (A1C) reduction and plasma glucose concentrations were the primary focus of all studies, with statistically significant differences found. Bromocriptine use resulted in a mean A1C reduction of 0.27% (range 0.1–0.6), while placebo resulted in a mean A1C increase of 0.48% (range 0.3–1.1), Incidence of adverse effects of nausea, vomiting, headache, and rhinitis was greater than that of placebo in clinical trials. Cardiovascular endpoints did not differ from those of placebo.

Conclusions:

Bromocriptine has demonstrated efficacy as an adjunctive agent in the management of type 2 diabetes. Caution may be warranted in the elderly population or patients at risk for suspected drug-drug interactions. Further studies of longer duration may help to define the role of bromocriptine in the management of diabetes.
Nicotine Replacement Therapy Effect on Pregnancy Outcomes
Authors: Forinash Alicia B , Pitlick Jamie M , Clark Kylie , Alstat Valerie
Published: October 2010

Objective:

To review data assessing the effects of nicotine replacement therapy (NRT) during pregnancy on fetal, neonatal, and maternal outcomes.

Data Sources:

A literature search of PubMed (1966-Jufy 2010) was performed using the terms smoking, smoking cessation, pregnancy, and nicotine replacement therapy. Bibliographies and the Cochrane Database were reviewed to identify additional relevant articles.

Study Selection and Data Extraction:

All studies including humans and published in English with data describing NRT effects on pregnancy outcomes or malformations as a primary or secondary outcome were evaluated.

Data Synthesis:

Currently, behavior modification therapy is recommended for smoking cessation in pregnancy as first-line treatment, but NRT should be offered to patients who are not successful. NRT is currently a pregnancy category D medication. Pregnancy outcomes and malformation rates for NRT in pregnancy were evaluated as either primary or secondary outcomes in several trials. Four studies examined pregnancy outcomes after a full course of nicotine gum or patch therapy. NRT use significantly decreased the risk of preterm delivery and low birth weight compared to that of smokers. Only 1 study evaluated the risk of malformations after exposure to the NRT patch during the first trimester. In a retrospective analysis, NRT users had an increased risk for any fetal malformation but not for major or musculoskeletal ones. However, no adjustments were made for many known factors associated with malformations.

Conclusions:

Behavior modification therapy should always be the first method tried for smoking cessation in the pregnant population. If behavior modification therapy is attempted without success, NRT should be offered because of decreased risk for low birth weight and preterm delivery compared to continued smoking. Additionally, NRT does not appear to increase the risk for malformations.
Sepsis Bundles: Just Do It
Authors: Micek Scott T , Sawyer Amber M
Published: October 2010

The initial management of patients with septic shock appears to be critical in terms of determining outcome; a standardized systematic approach for the management of patients with severe infections appears to consistently improve the delivery of recommended therapies and, as a result, may improve patient outcomes. With minimal-to-no risk or acquisition costs, severe sepsis bundle implementation should become the standard of care for the management of septic shock. A multifaceted approach may aid in the success of implementation of sepsis bundles in teaching and nonteaching institutions. Bundle implementation should change clinical practice by including surveillance, feedback reporting, and staff education to organize the target interventions into packages that must be implemented in strict compliance, for every patient, to ensure uniformity and provide practical applicability. Quality improvement via utilization of protocols can be achieved, regardless of institution size or academic status, and should continue to be promoted in the intensive care unit setting.
Arts research as a triptych installation: A framework for interpreting and rendering enquiry
Authors: Sinner Anita
Published: October 2010

This article explores how a triptych installation serves as a framework for interpreting and rendering enquiry and for expanding notions of arts research. The triptych format brings rigour to enquiry by focusing attention on the properties of the art form, organizing practice openly
and transparently, and demonstrating how it relates to the broad field of arts research. My purpose in invoking this architecture extends to iconographic methods of framing whereby visual representation is a way of teaching about social and cultural activities. In this case pre-service teachers
represented their experiences visually as unfolding, unexpected and uncertain. As an ensemble, the three panels of the triptych featured in this study represent processes, practices and products.
Insight on OutReach: Towards a critical practice
Authors: Sagan Olivia , Candela Emily , Frimodig Bess
Published: October 2010

This article touches on several kinds of arts practices and activities that bear upon debates concerning the social role of the arts. This then informs our main argument that a re-examination needs to take place of the arts outreach activities undertaken by institutions of higher arts
education (HAE). We suggest that the boundaries between socially engaged contemporary art practice, community arts and the arts outreach activities of institutions, with their contested terms and multiple perspectives, are more porous than often suggested and would benefit from a fluidity
of debate in and through them. We also argue that the theory, socio-political motivation and ensuing practice which powers arts outreach should, in many instances, be re-energized with a radicalization in line with twenty-first century polyphonic concerns. These ideas are explored through
the lens of Insight on OutReach, an outreach project at University of the Arts London.
Engaging in reflective practices: investigating pupils' experiences of art from a phenomenological perspective
Authors: Tam Cheung-On
Published: October 2010

This article reports on three cases of primary and secondary schoolteachers investigating their pupils' experiences of art from a phenomenological perspective. Using the three cases as illustrations, the article discusses how these teachers, having limited knowledge of research and
aesthetics, selected study topics, determined the scope and method of data collection, conducted conversational interviews and interpreted the data collected. The article reveals the ways in which small-scale phenomenological studies can be carried out in a school context, with the ultimate
aim of improving teachers' own practices. The article concludes with an analysis of phenomenological studies as a form of professional reflective practice.
The Other side of the easel: questioning art education through a postcolonial frame
Authors: Ashton Linda
Published: October 2010

In this article I combine a researcher voice (reflective practitioner, Schon 1983) with the neo-narrative reporting strategy of Stewart (1996) to blend and blur a researchteaching nexus. I elaborate on a four-pronged strategy that encourages my pre-service primary teachers to recognize
and challenge some of the western art world's longstanding exclusive discourses. The teaching approaches are informed directly by my post-structuralist doctoral research and postmodern art education alignment (Ashton 1999a, 2008).
Book Reviews
Authors: Houghton Nicholas , Stears Derek
Published: October 2010

Artist Teacher: A Philosophy for Creating and Teaching, G. James Daichendt (2010) Bristol: Intellect, ISBN 978-1-81450-313-4 (hbk) 29.95

Understanding Art Education: Engaging Refl exively with Practice, Nicholas Addison, Lesley Burgess, John Steers, and Jane
Trowell (2010) London and New York: Routledge, 174 pp., ISBN 978-0-415-36740-0 (pbk) 22.99, ISBN 978-0-415-36739-4 (hbk) 80.00
Antifungal activities of three supercritical fluid extracted cedar oils
Authors: Du Tianchuan , Shupe Todd F. , Hse Chung Y.
Published: October 2010

Port-Orford cedar (Chamaecyparis lawsoniana), Alaska yellow cedar (Chamaecyparis nootkatensis), and Eastern red cedar (Juniperus virginiana) were submitted to supercritical fluid extraction with CO2 (SCC) and Soxhlet extracted (SE) with hexane. The components in the extracted oils were identified by GC-MS. The oils were evaluated against two common wood decay fungi, brown-rot fungus (Gloeophyllum trabeum) and white-rot fungus (Trametes versicolor). The SCC extraction yields of J. virginiana, C. nootkatensis, and C. lawsoniana were 3.27%, 3.22%, and 3.29%, respectively. The SE yields of J. virginiana, C. nootkatensis, and C. lawsoniana were 0.80%, 0.71%, and 1.52%, respectively. The statistical analysis showed that SCC extracted cedar oils had higher antifungal activities than SE cedar oils against both fungi. In vitro studies showed that C. nootkatensis oils have the strongest antifungal activity, followed by C. lawsoniana, and J. virginiana oil.
Oligodendrocyte Myelin Glycoprotein Does Not Influence Node of Ranvier Structure or Assembly
Authors: Chang Kae-Jiun , Susuki Keiichiro , Dours-Zimmermann Maria T. , Zimmermann Dieter R. , Rasband Matthew N.
Published: October 2010

Oligodendrocyte myelin glycoprotein (OMgp) is expressed by both neurons and oligodendrocytes in the CNS. It has been implicated in growth cone collapse and neurite outgrowth inhibition by signaling through the Nogo receptor and paired Ig-like receptor B (PirB). OMgp was also reported to be an extracellular matrix (ECM) protein surrounding CNS nodes of Ranvier and proposed to function as (1) an inhibitor of nodal collateral sprouting and (2) an important contributor to proper nodal and paranodal architecture. However, we show here that the anti-OMgp antiserum used in previous studies to define the functions of OMgp at nodes is not specific. Among all reported nodal ECM components, the antiserum exhibited strong cross-reactivity against versican V2 isoform, a chondroitin sulfate proteoglycan. Furthermore, the OMgp antiserum labeled OMgp-null nodes, but not nodes from versican V2-deficient mice, and preadsorption of the OMgp antiserum with recombinant versican V2 blocked nodal labeling. Analysis of CNS nodes in OMgp-null mice failed to reveal any nodal or paranodal defects, or increased nodal collateral sprouting, indicating that OMgp does not participate in CNS node of Ranvier assembly or maintenance. We successfully identified a highly specific anti-OMgp antibody and observed OMgp staining in white matter only after initiation of myelination. OMgp immunoreactivity decorated the surface of mature myelinated axons, but was excluded from compact myelin and nodes. Together, our results strongly argue against the nodal localization of OMgp and its proposed functions at nodes, and reveal OMgp's authentic localization relative to nodes and myelin.
The Parafascicular Thalamic Nucleus Concomitantly Influences Behavioral Flexibility and Dorsomedial Striatal Acetylcholine Output in Rats
Authors: Brown Holden D. , Baker Phillip M. , Ragozzino Michael E.
Published: October 2010

Recent evidence suggests that a circuit involving the centromedian–parafascicular (Pf) thalamus and basal ganglia is critical for a shift away from biased actions. In particular, excitatory input from the Pf onto striatal cholinergic neurons may facilitate behavioral flexibility. Accumulating evidence indicates that an endogenous increase in dorsomedial striatal acetylcholine (ACh) output enhances behavioral flexibility. The present experiments investigated whether the rat (Rattus norvegicus) Pf supports flexibility during reversal learning, in part, by modifying dorsomedial striatal ACh output. This was determined first by examining the effects of Pf inactivation, through infusion of the GABA agonists baclofen and muscimol, on place acquisition and reversal learning. Additional experiments examined Pf inactivation on dorsomedial striatal ACh output during reversal learning and a resting condition. Behavioral testing was performed in a cross-maze.In vivomicrodialysis combined with HPLC/electrochemical detection was used to sample ACh from the dorsomedial striatum. Pf inactivation selectively impaired reversal learning in a dose-dependent manner. A subsequent study showed that an increase in dorsomedial striatal ACh efflux (∼30% above basal levels) during reversal learning was blocked by Pf inactivation, which concomitantly impaired reversal learning. In the resting condition, a dose of baclofen and muscimol that blocked a behaviorally induced increase in dorsomedial striatal ACh output did not reduce basal ACh efflux. Together, the present findings indicate that the Pf is an intralaminar thalamic nucleus critical for behavioral flexibility, in part, by directly affecting striatal ACh output under conditions that require a shift in choice patterns.
Two Distinct Modes of PERIOD Recruitment onto dCLOCK Reveal a Novel Role for TIMELESS in Circadian Transcription
Authors: Sun Woo Chul , Jeong Eun Hee , Jeong Hyun-Jeong , Ko Hyuk Wan , Edery Isaac , Kim Eun Young
Published: October 2010

Negative transcriptional feedback loops are a core feature of eukaryotic circadian clocks and are based on rhythmic interactions between clock-specific repressors and transcription factors. InDrosophila, the repression of dCLOCK (dCLK)-CYCLE (CYC) transcriptional activity by dPERIOD (dPER) is critical for driving circadian gene expression. Although growing lines of evidence indicate that circadian repressors such as dPER function, at least partly, as molecular bridges that facilitate timely interactions between other regulatory factors and core clock transcription factors, how dPER interacts with dCLK-CYC to promote repression is not known. Here, we identified a small conserved region on dPER required for binding to dCLK, termed CBD (for dCLKbindingdomain). In the absence of the CBD, dPER is unable to stably associate with dCLK and inhibit the transcriptional activity of dCLK-CYC in a simplified cell culture system. CBD is situated in close proximity to a region that interacts with other regulatory factors such as the DOUBLETIME kinase, suggesting that complex architectural constraints need to be met to assemble repressor complexes. Surprisingly, when dPER missing the CBD (dPER(ΔCBD)) was evaluated in flies the clock mechanism was operational, albeit with longer periods. Intriguingly, the interaction between dPER(ΔCBD) and dCLK is TIM-dependent and modulated by light, revealing a novel and unanticipatedin vivorole for TIM in circadian transcription. Finally, dPER(ΔCBD) does not provoke the daily hyperphosphorylation of dCLK, indicating that direct interactions between dPER and dCLK are necessary for the dCLK phosphorylation program but are not required for other aspects of dCLK regulation.
Decision Threshold Modulation in the Human Brain
Authors: Domenech Philippe , Dreher Jean-Claude
Published: October 2010

Perceptual decisions are made when sensory evidence accumulated over time reaches a decision threshold. Because decisions are also guided by prior information, one important factor that is likely to shape how a decision is adaptively tuned to its context is the predictability of forthcoming events. However, little is known about the mechanisms underlying this contextual regulation of the perceptual decision-making process. Mathematical models of decision making predict two possible mechanisms supporting this regulation: an adjustment of the distance to the decision threshold, which leads to a change in the amount of accumulated evidence required to make a decision, or a gain control of the sensory evidence, leading to a change in the slope of the sensory evidence accumulation. Here, we show that predictability of the forthcoming event reduces the distance to the threshold of the decision. Then, combining model-driven fMRI and the framework of information theory, we show that the anterior cingulate cortex (ACC) adjusts the distance to the decision threshold in proportion to the current amount of predictive information and that the dorsolateral cortex (DLPFC) codes the accumulation of sensory evidence. Moreover, the information flow from the ACC to the DLPFC region that accumulates sensory evidence increases when optimal adjustment of the distance to the threshold requires more complex computations, reflecting the increased weight of ACC's regulation signals in the decision process. Our results characterize the respective contributions of the ACC and the DLPFC to contextually optimized decision making.
Thermally Active TRPV1 Tonically Drives Central Spontaneous Glutamate Release
Authors: Shoudai Kiyomitsu , Peters James H. , McDougall Stuart J. , Fawley Jessica A. , Andresen Michael C.
Published: October 2010

Central synapses spontaneously release neurotransmitter at low rates. In the brainstem, cranial visceral afferent terminals in caudal solitary tract nucleus (NTS) display pronounced, activity-dependent, asynchronous release of glutamate and this extra release depends on TRPV1 receptors (TRPV1+). Asynchronous release is absent for afferents lacking TRPV1 (TRPV1−) and resting EPSC frequency was greater in TRPV1+. Here, we studied this basal activity difference by assessing thermal sensitivity of spontaneous and miniature synaptic events in TRPV1+ and TRPV1− second-order NTS neurons. The spontaneous EPSC rate decreased when temperature was decreased, increased steeply between 30 and 42°C only in TRPV1+ neurons, and was calcium-dependent. TRPV1-specific antagonist SB366791, but not TTX, strongly attenuated thermal responses. Temperature changes failed to alter EPSC frequency in TRPV1− neurons. EPSC amplitudes and decay kinetics changed little with temperature. IPSCs in these second-order NTS neurons were unaltered by temperature. Such results suggest that activated, presynaptic TRPV1+ receptors trigger continuous resting release of glutamate vesicles at physiological temperatures only in capsaicin-responsive terminals. In mechanically isolated individual neurons harvested from medial NTS, increases in temperature increased the rate of glutamate release only in TRPV1+ neurons, whereas IPSC rates were unaffected. Cadmium failed to block thermal increases in glutamate release, suggesting that calcium entry through TRPV1 channels may trigger glutamate release independently of voltage-activated calcium channels. Together, our findings indicate a new form of afferent signaling in which TRPV1 channels within central terminals of peripheral afferents tonically generate glutamate release in NTS at 37°C in the absence of afferent action potentials.
Activity of Red Nucleus Neurons in the Cat during Postural Corrections
Authors: Zelenin Pavel V. , Beloozerova Irina N. , Sirota Mikhail G. , Orlovsky Grigori N. , Deliagina Tatiana G.
Published: October 2010

The dorsal-side-up body posture in standing quadrupeds is maintained by the postural system, which includes spinal and supraspinal mechanisms driven by somatosensory inputs from the limbs. A number of descending tracts can transmit supraspinal commands for postural corrections. The first aim of this study was to understand whether the rubrospinal tract participates in their transmission. We recorded activity of red nucleus neurons (RNNs) in the cat maintaining balance on the periodically tilting platform. Most neurons were identified as rubrospinal ones. It was found that many RNNs were profoundly modulated by tilts, suggesting that they transmit postural commands. The second aim of this study was to examine the contribution of sensory inputs from individual limbs to posture-related RNN modulation. Each RNN was recorded during standing on all four limbs, as well as when two or three limbs were lifted from the platform and could not signal platform displacements. By comparing RNN responses in different tests, we found that the amplitude and phase of responses in the majority of RNNs were determined primarily by sensory input from the corresponding (fore or hind) contralateral limb, whereas inputs from other limbs made a much smaller contribution to RNN modulation. These findings suggest that the rubrospinal system is primarily involved in the intralimb postural coordination, i.e., in the feedback control of the corresponding limb and, to a lesser extent, in the interlimb coordination. This study provides a new insight into the formation of supraspinal motor commands for postural corrections.
Locus Ceruleus and Anterior Cingulate Cortex Sustain Wakefulness in a Novel Environment
Authors: Gompf Heinrich S. , Mathai Christine , Fuller Patrick M. , Wood David A. , Pedersen Nigel P. , Saper Clifford B. , Lu Jun
Published: October 2010

Locus ceruleus (LC) neuronal activity is correlated with the waking state, yet LC lesions produce only minor alterations in daily wakefulness. Here, we report that sustained elevations in neurobehavioral and EEG arousal in response to exposure to an environment with novel stimuli, including social interaction, are prevented by selective chemical lesions of the LC in rats. Similar results are seen when the anterior cingulate cortex (ACC), which receives especially dense LC innervation, is selectively denervated of LC input or is ablated by the cell-specific neurotoxin ibotenic acid. Anterograde tracing combined with tyrosine hydroxylase immunohistochemistry demonstrates ACC terminals in apposition with the distal dendrites of LC neurons. Our data implicate the ACC as both a source of input to the LC as well as one of its targets and suggests that the two structures engage in a dialog that may provide a critical neurobiological substrate for sustained attention.
Distinct Functions of Glial and Neuronal Dystroglycan in the Developing and Adult Mouse Brain
Authors: Satz Jakob S. , Ostendorf Adam P. , Hou Shangwei , Turner Amy , Kusano Hajime , Lee Jane C. , Turk Rolf , Nguyen Huy , Ross-Barta Susan E. , Westra Steve , Hoshi Toshinori , Moore Steven A. , Campbell Kevin P.
Published: October 2010

Cobblestone (type II) lissencephaly and mental retardation are characteristic features of a subset of congenital muscular dystrophies that include Walker–Warburg syndrome, muscle-eye-brain disease, and Fukuyama-type congenital muscular dystrophy. Although the majority of clinical cases are genetically undefined, several causative genes have been identified that encode known or putative glycosyltransferases in the biosynthetic pathway of dystroglycan. Here we test the effects of brain-specific deletion of dystroglycan, and show distinct functions for neuronal and glial dystroglycan. Deletion of dystroglycan in the whole brain produced glial/neuronal heterotopia resembling the cerebral cortex malformation in cobblestone lissencephaly. In wild-type mice, dystroglycan stabilizes the basement membrane of the glia limitans, thereby supporting the cortical infrastructure necessary for neuronal migration. This function depends on extracellular dystroglycan interactions, since the cerebral cortex developed normally in transgenic mice that lack the dystroglycan intracellular domain. Also, forebrain histogenesis was preserved in mice with neuron-specific deletion of dystroglycan, but hippocampal long-term potentiation was blunted, as is also the case in theLargemydmouse, in which dystroglycan glycosylation is disrupted. Our findings provide genetic evidence that neuronal dystroglycan plays a role in synaptic plasticity and that glial dystroglycan is involved in forebrain development. Differences in dystroglycan glycosylation in distinct cell types of the CNS may contribute to the diversity of dystroglycan function in the CNS, as well as to the broad clinical spectrum of type II lissencephalies.
Visual Representations by Cortical Somatostatin Inhibitory Neurons—Selective But with Weak and Delayed Responses
Authors: Ma Wen-pei , Liu Bao-hua , Li Ya-tang , Josh Huang Z. , Zhang Li I. , Tao Huizhong W.
Published: October 2010

Somatostatin-expressing inhibitory (SOM) neurons in the sensory cortex consist mostly of Martinotti cells, which project ascending axons to layer 1. Due to their sparse distribution, the representational properties of these neurons remain largely unknown. By two-photon imaging guided cell-attached recordings, we characterized visual response and receptive field (RF) properties of SOM neurons and parvalbumin-expressing inhibitory (PV) neurons genetically labeled in the mouse primary visual cortex. In contrast to PV neurons, SOM neurons exhibit broader spikes, lower spontaneous firing rates, smaller On/Off subfields, and broader ranges of basic RF properties such as On/Off segregation, orientation and direction tunings. Notably, the level of orientation and direction selectivity is comparable to that of excitatory neurons, from weakly-tuned to highly selective, whereas PV neurons are in general unselective. Strikingly, the evoked spiking responses of SOM cells are ∼3- to 5-fold weaker and 20–25 ms delayed compared with those of PV neurons. The onset latency of the latter is consistent with that of inhibitory input to excitatory neurons. These functional differences between SOM and PV neurons exist in both layer 2/3 and 4. Our results suggest that SOM and PV neurons engage in cortical circuits in different manners: while PV neurons provide fast, strong but untuned feedforward inhibition to excitatory neurons, likely serving as a general gain control for the processing of ascending inputs, SOM neurons with their selective but delayed and weak inhibition may provide more specific gating of later arriving intracortical excitatory inputs on the distal dendrites.
Presynaptic BDNF Promotes Postsynaptic Long-Term Potentiation in the Dorsal Striatum
Authors: Jia Yousheng , Gall Christine M. , Lynch Gary
Published: October 2010

Brain-derived neurotrophic factor (BDNF) facilitates the formation of long-term potentiation (LTP) in hippocampus, but whether this involves release from presynaptic versus postsynaptic pools is unclear. We therefore tested whether BDNF is essential for LTP in dorsal striatum, a structure in which the neurotrophin is present only in afferent terminals. Whole-cell recordings were collected from medium spiny neurons in striatal slices prepared from adult mice. High-frequency stimulation (HFS) of neocortical afferents produced a rapid and stable NMDA receptor-dependent potentiation. The ratio of AMPA to NMDA receptor-mediated components of the EPSPs was substantially increased after inducing potentiation, suggesting that the response enhancement involved postsynaptic changes. In accord with this, paired-pulse response ratios, a measure of transmitter release kinetics, were reduced by elevated calcium but not by LTP. Infusion of the BDNF scavenger TrkB-Fc blocked the formation of potentiation, beginning with the second minute after HFS, without reducing responses to HFS. These results suggest that presynaptic pools of BDNF can act within 2 min of HFS to support the formation of a postsynaptic form of LTP in striatum.
Brain-Derived Neurotrophic Factor Mediates Non-Cell-Autonomous Regulation of Sensory Neuron Position and Identity
Authors: Wright Melissa A. , Ribera Angeles B.
Published: October 2010

During development, neurons migrate considerable distances to reside in locations that enable their individual functional roles. Whereas migration mechanisms have been extensively studied, much less is known about how neurons remain in their ideal locations. We sought to identify factors that maintain the position of postmigratory dorsal root ganglion neurons, neural crest derivatives for which migration and final position play an important developmental role. We found that an early developing population of sensory neurons maintains the position of later born dorsal root ganglia neurons in an activity-dependent manner. Further, inhibiting or increasing the function of brain-derived neurotrophic factor induces or prevents, respectively, migration of dorsal root ganglia neurons out of the ganglion to locations where they acquire a new identity. Overall, the results demonstrate that neurotrophins mediate non-cell-autonomous maintenance of position and thereby the identity of differentiated neurons.