bluuebunny/crossref_metadata_2025 huggingface dataset:
Central ventilatory and cardiovascular actions of calcitonin gene-related peptide in unanesthetized trout
Authors: Le Mével Jean-Claude , Lancien Frédéric , Mimassi Nagi , Kermorgant Marc , Conlon J. Michael
Published: May 2012

Calcitonin gene-related peptide (CGRP) and its receptors are widely distributed in the tissues of teleost fish, including the brain, but little is known about the ventilatory and cardiovascular effects of the peptide in these vertebrates. The present study was undertaken to compare the central and peripheral actions of graded doses (5–50 pmol) of trout CGRP on ventilatory and cardiovascular variables in unanesthetized rainbow trout. Compared with vehicle, intracerebroventricular injection of CGRP significantly elevated the ventilation frequency (fV) and the ventilation amplitude (VAMP) and, consequently, the total ventilation (VTOT). The maximum hyperventilatory effect of CGRP (VTOT: +300%), observed at a dose of 50 pmol, was mostly due to its stimulatory action on VAMP (+200%) rather than fV (+30%). In addition, CGRP produced a significant and dose-dependent increase in mean dorsal aortic blood pressure (PDA) (50 pmol: +40%) but the increase in heart rate (fH) was not significant. Intra-arterial injections of CGRP were without effect on the ventilatory variables but significantly and dose-dependently elevated PDA (50 pmol: +36%) without changing fH. At the highest dose tested, this hypertensive phase was preceded by a rapid and transient hypotensive response. In conclusion, our study suggests that endogenous CGRP within the brain of the trout may act as a potent neurotransmitter and/or neuromodulator in the regulation of cardio-ventilatory functions. In the periphery, endogenous CGRP may act as a local and/or circulating hormone preferentially involved in vasoregulatory mechanisms.
The use of trypsin to confirm the presence of macrocreatine kinase on isoenzyme electrophoresis
Authors: George Roanna , Wallage Michael , Goodall Roberta
Published: May 2012

Background

Macrocreatine kinase (MCK) type 1 is a high molecular weight form of CK that is non-pathological. Identification of MCK is beneficial in preventing unnecessary investigations that may follow a persistently elevated CK of unknown origin. Currently, gel filtration chromatography can be used as a confirmatory technique, but it is laborious, time-consuming and expensive. The aim of this work, carried out as part of a larger investigation into the prevalence of MCK, was to determine whether trypsin can be used as an alternative to confirm the presence of MCK on isoenzyme electrophoresis.

Methods

Five samples found to have bands running in the MCK region on isoenzyme electrophoresis were treated with trypsin. Electrophoresis was carried out using the Helena Biosciences Sas-1 Plus system. These samples were also analysed by the confirmatory technique of gel filtration chromatography.

Results

Of the five samples treated with trypsin, three were found to be MCK-positive and two MCK-negative. These results correlated with those obtained by the reference method of gel filtration chromatography.

Conclusions

There appears to be a potential use of trypsin in confirming the presence of MCK following isoenzyme electrophoresis. If these findings were verified, this would provide a less labour-intensive, less time-consuming and more cost-effective confirmatory technique. Further study is required, which needs to be expanded to include a larger number of patients, before this method can be adopted routinely.
Collaboration between Health Services Managers and Researchers: Making a Difference?
Authors: Bullock Alison , Morris Zoë Slote , Atwell Christine
Published: May 2012

Objectives

Our aim was to evaluate whether the involvement of health care managers in research projects improves the quality and relevance of research, and whether collaboration builds capacity in the managerial community.

Methods

The NIHR Service Delivery and Organization Management Fellowship programme supports the direct involvement of health care managers in research projects. Data were collected from face-to-face interviews with management fellows and chief investigators of research projects at 10 case study sites. Data were analysed thematically using an adapted Kirkpatrick framework for programme evaluation.

Results

Management fellows improved the relevance and quality of research through enhancing its validity, efficiency and credibility. This was achieved by: using their contextual understanding to enable and support access and recruitment participants, data collection tools, processes and analysis; supporting dissemination activities; and undertaking additional work which was complementary to the main project. Capacity was developed through formal courses and exposure to new knowledge, ideas and practices. Factors found to enable or impede improvements in research included management fellows' knowledge and experience of the NHS, their background and personal characteristics, mutual respect, timing and flexibility. Consequences were not always predictable. Costs for management fellows included foregone opportunities, specifically for promoted posts. Researchers reported time-costs associated with administering the fellowship.

Conclusions

Collaborations between managers and researchers can improve research relevance and quality and research capacity development. Factors critical to success relate to the fit between the project and the management fellow and how clearly the purpose is understood.
Financial and Clinical Risk in Health Care Reform: A View from Below
Authors: Smith Pam , Mackintosh Maureen , Ross Fiona , Clayton Julie , Price Linnie , Christian Sara , Byng Richard , Allan Helen
Published: May 2012

Objectives

This paper examines how the interaction between financial and clinical risk at two critical phases of health care reform in England has been experienced by frontline staff caring for vulnerable patients with long term conditions.

Methods

The paper draws on contracting theory and two interdisciplinary and in-depth qualitative research studies undertaken in 1995 and 2007. Methods common to both studies included documentary analysis and interviews with managers and front line professionals. The 1995 study employed action-based research and included observation of community care; the 2007 study used realistic evaluation and included engagement with service user groups.

Results

In both reform processes, financial risk was increasingly devolved to frontline practitioners and smaller organizational units such as GP commissioning groups, with payment by unit of activity, aimed at changing professionals' behaviour. This financing increased perceived clinical risk and fragmented the delivery of health and social care services requiring staff efforts to improve collaboration and integration, and created some perverse incentives and staff demoralisation.

Conclusions

Health services reform should only shift financial risk to frontline professionals to the extent that it can be efficiently borne. Where team work is required, contracts should reward collaborative multi-professional activity.
Tensions in Commissioning: Services for Children's Speech, Language and Communication Needs in One English Region
Authors: Davies Karen , Davies Peter
Published: May 2012

Objectives

To investigate the tensions faced in commissioning services for children's speech, language and communication needs and to identify variation in commissioning practice in response to these tensions.

Methods

Quantitative and qualitative evidence from a review of speech, language and communication services in one English region, focused on three case studies.

Results

The case studies reveal variation in practice in relation to commissioning tensions generated by: low incidence/high needs cases, blurred boundaries between health and education, multi-agency working, parental voice and service development. The introduction of commissioning and models of practice such as ‘the commissioning cycle’ has left huge variation between localities in levels and type of provision for these services.

Conclusion

Large variation in commissioning practice is associated with commissioners' adoption of one of three models: a market model, an integrated model and a top-up model.
Partnership Working in Public Health: The Implications for Governance of a Systems Approach
Authors: Hunter David , Perkins Neil
Published: May 2012

Objectives

Most of the research on partnerships has centred on health and social care, and while many of the findings remain relevant, public health partnerships concerned with ‘wicked issues’ give rise to a different and more complex set of issues which merit exploration. The study aimed to identify those factors promoting effective partnership working for health improvement; to assess the extent to which partnership governance and incentive arrangements were commensurate with the complexities of the problem; and to explore how far local partnerships contributed to better outcomes for individuals and populations.

Methods

A three-year study of public health partnerships (2007-10) in nine localities across England involving semi-structured interviews at strategic and operational levels.

Results

Successful partnerships shared a number of characteristics:they were clear about goals and purpose; they were aware of partners' roles and responsibilities; and they had a clear strategic overview of performance through robust monitoring and evaluation. In many cases, partnerships were facades with a ‘silo mentality’ prevailing - there was an unwillingness to share information or resources, or to accord partnership working sufficient priority or support. Despite enthusiasm for partnerships and an insistence that they were essential, it was impossible to establish evidence of their impact on health outcomes. While the focus on partnerships tends to be on structures, relational factors, including high levels of trust and goodwill, were important ingredients of a well-functioning partnership. Less formal and more organic, operational partnerships were more effective than more formal, strategic level ones which were driven by targets. Finally, partnerships were, in part, shaped by the national policy context, with constant policy and organizational churn making it difficult to sustain long-term relationships.

Conclusions

Future partnerships might be undertaken differently, adopting a complex adaptive systems perspective. This advocates an approach to partnership working that is less focused on rigid structures and much more on relational factors like trust and goodwill.
Bell's palsy in pregnancy: underlying HELLP syndrome or pre-eclampsia?
Authors: Pourrat O , Neau J-P , Pierre F
Published: May 2012

Bell's palsy is not uncommon during pregnancy. An association with pre-eclampsia (PE) has been reported previously. Furthermore, it has even been suggested that Bell's palsy could be a predictor of PE. We report three cases illustrating various possible aspects of this association, one of them including the features of HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome.
Weight gain in pregnancy: is less truly more for mother and infant?
Authors: Barbour Linda A
Published: May 2012

SUMMARY

Although more than 50% of women gain weight above the Institute of Medicine (IOM) guidelines for weight gain in pregnancy and excessive weight gain is an independent risk factor for significant maternal and neonatal morbidity and offspring obesity, there is little consensus over the ideal weight gain during pregnancy. Surprisingly, the 2009 IOM guidelines varied minimally from the 1990 IOM guidelines, and many critics advocate lower weight gain recommendations. This review explores the energy costs of pregnancy, the relationship between gestational weight gain and birth weight, and considers what gestational weight gain minimizes both large-for-gestational age as well as small-for-gestational age infants. An extensive examination of the current data leads this author to question whether the current weight gain recommendations are too liberal, especially for obese pregnant women.
A case of recurrent severe pre-eclampsia associated with essential cryofibrinogenaemia
Authors: Chau Katrina , Henderson Christopher , Adno Alan , Spicer Timothy , Cleland Bruce , Makris Angela
Published: May 2012

Essential cryofibrinogenaemia is a rare disorder characterized by cryofibrinogens without cryoglobulins. Connective tissue disorders and thrombophilia are known to increase risk of pre-eclampsia, but pre-eclampsia has not previously been reported in association with cryofibrinogenaemia. We report the case of a 32-year-old woman with recurrent severe pre-eclampsia diagnosed with essential cryofibrinogenaemia.
Risk of Venous Thromboembolism in Patients with Chronic Liver Disease and the Utility of Venous Thromboembolism Prophylaxis
Authors: Pincus Kathleen J , Tata Asha L , Watson Kristin
Published: May 2012

OBJECTIVE:

To review the current literature on the risk of venous thromboembolism (VTE) in patients with chronic liver disease (CLD).

DATA SOURCES:

Literature was accessed through MEDLINE/PubMed (1996-December 2011) using the search terms liver disease, cirrhosis, venous thromboembolism, deep vein thrombosis, and pulmonary embolism.

STUDY SELECTION AND DATA EXTRACTION:

Relevant observational and population-based studies were included to present background information. Bibliographies of all relevant articles were reviewed for additional citations.

DATA SYNTHESIS:

Liver disease affects the synthesis of procoagulants and anticoagulants, resulting in hemostatic alterations and abnormal laboratory values. Retrospective studies characterized the VTE incidence to be 0.5-6.3%. Population-based studies reported VTE relative risks of 1.74-2.10 in patients with CLD compared with population controls and VTE odds ratios of 0.9-1.39 for hospitalized patients with CLD compared with controls without liver disease. There is a paucity of data on the use of pharmacologic prophylaxis in patients with CLD.

CONCLUSIONS:

Patients with CLD should be assessed for VTE risk and given VTE prophylaxis when the benefits outweigh the risks. Diagnoses of CLD or elevated international normalized ratio do not confer protection against development of VTE and do not justify withholding pharmacologic prophylaxis based on this diagnosis.
Burkholderia cepacia Septicemia in a Pediatric Oncology Patient: A Pharmacotherapy Challenge
Authors: Durham Spencer H , Lee Amy E , Assanasen Chatchawin
Published: May 2012

OBJECTIVE:

To discuss pharmacotherapy challenges encountered during treatment of a pediatric oncology patient with Burkholderia cepacia septicemia.

CASE SUMMARY:

An 11-year-old male with a history of aplastic anemia presented to the emergency department with a 1-day history of cough and purulent nasal discharge 6 months after undergoing bone marrow transplant. Blood cultures obtained from the patient's Broviac catheter revealed gram-negative rods. Piperacillin/tazobactam and tobramycin were administered, but the patient worsened clinically, with fever and chills. B. cepacia was identified as the offending pathogen, and the therapy was changed to meropenem and ciprofloxacin, as piperacillin/ tazobactam and tobramycin are ineffective against Burkholderia spp. Intravenous trimethoprim/sulfamethoxazole, the drug of choice for Burkholderia spp. infections, was unavailable as it had been placed on national manufacturer backorder. The patient improved initially, but he later experienced recurrence of fever, and blood culture results were positive for Burkholderia spp. Infection was eradicated after removal of the central line and administration of ceftazidime and oral minocycline.

DISCUSSION:

Literature reveals few cases of B. cepacia in pediatric oncology patients, and to our knowledge, no cases have been reported in bone marrow transplant patients in the US. Burkholderia spp. is highly resistant to many antibiotics, and commonly used agents for the empiric treatment of febrile neutropenia are not active against this organism. This indicates that most oncology patients who present with this infection would not receive appropriate initial treatment. In addition, antibiotic therapy may need to be modified, based on drug availability.

CONCLUSIONS:

B. cepacia is an emerging multidrug-resistant pathogen that can produce severe infection in immunocompromised patients. It is pertinent to consider this organism in oncology patients who do not improve with standard therapy, as prompt use of correct pharmacotherapy is necessary to avoid serious morbidity as well as mortality in this population.
Real life
Authors: Paul Colette
Published: May 2012

Colette Paul’s story explores, in a humorous way, how the stuff of ‘real life’ is transformed by the writer into ‘material’ for fiction. It also address some anxieties about teaching Creative Writing. However, while these concerns frame ‘Real life’
as explicitly metafictional, the way in which class politics are engaged with is of equal importance to the author.
Choreographic and somatic strategies for navigating bodyscapes and tensegrity schemata
Authors: Hawksley Sue
Published: May 2012

This article reflects upon the psychophysical patterning and layered nature of phenomenal experience, and the interconnectedness of bodymind and environment. These are conceptualized as ‘bodyscape’ and ‘tensegrity schema’ and explored by engaging the principles
of tensegrity (tensional integrity) with reference to dance, performance and somatic practices. In some performance environments, performers may be called on to bring in and out of focus, or simultaneously hold in attention, multiple layers and shifting perspectives of bodily experience. Giving
examples I suggest that such situations, together with some choreographic and somatic practices, may facilitate an attitude of embodied reflection and skills of perceptual alertness. These can develop awareness of and capacity to ‘navigate’ bodyscape and tensegrity schema, and
support the performer to better cope with the often conflicting multisensory and polyattentional demands of complex environments, whether highly specialized performance modes or everyday. The discussion derives theoretical flavour from dance and performance studies, phenomenology, somaesthetics
and cognitive science, and is informed by my current practice-led Ph.D. research in dance and choreography enquiring into notions of embodiment.
‘Emergence of form’: A recollection
Authors: Münker Katja
Published: May 2012

‘The emergence of form’ was an experimental framework that scrutinized ‘the emergence of form’ in the context of an intertwined exploration of different somatic practices and time-space-related reflections for an extended period of time: the duration of the complete
conference. The framework was facilitated by the Aesthetic Practice and Embodiment Research Group of the Inter-University Centre for Dance Berlin – HZT represented by Professor Alex Arteaga, Elisabeth Molle, Katja Münker and Ka Rustler. Whilst the creation and realization of the
project during the conference was a collective process, I have individually composed the text while being and moving on the floor. Passing through stages of the experiment and its embedment in the conference, I was listening and bringing into language with, in and from many layers of my living
human system. Time-flow and time experience within the long-term experiment was particular not only because it was long, but because time-flow felt multi-layered and overlapping. The writing is trying to give that resonance. The intention behind this writing was to bridge and connect memory,
experience, (sensuous and cognitive) reflection and evaluation without separating this subsequent act from the experiential-experimental setting of the framework itself.
A conversation about choreographic thinking tools
Authors: DeLahunta Scott , Clarke Gill , Barnard Phil
Published: May 2012

This article aims to draw the reader into an interdisciplinary conversation between the co-authors about the use of imagery in dance creation placed under very different disciplinary lenses. The conversation has two points of departure. First, for nearly a decade the choreographer Wayne
McGregor has engaged in an interdisciplinary collaborative research with cognitive scientists with the aim to develop new understandings of the choreographic process. A large percentage of this research has focused on imagery in creativity and has resulted in the development of the Choreographic
Thinking Tools, currently in use by McGregor and his dance company. One third of this article is dedicated to a description of these developments combined with figures that illustrate the scientific theory lying behind them. The second point of departure and second third of this article brings
these ideas into conjunction with somatic practices, as reflected in the writing of an expert practitioner invited to introduce somatics to McGregor’s dance company in the framework of the Choreographic Thinking Tools. The final section that concludes the article reintroduces scientific
theory with the goal to articulate some of the contrasts and overlaps between the different approaches represented in this conversation.
everything is at once: Reflections on embodied photography and collaborative process
Authors: Brown Natalie Garrett , Kipp Christian , Pollard Niki , Voris Amy
Published: May 2012

In discussion with his co-collaborators, dance artists Natalie Garrett Brown and Amy Voris, this interview explores the photographic process of Christian Kipp, landscape and dance photographer, as he reflects on his experience of working on the Enter & Inhabit project. The questions
asked by Garrett Brown and Voris were generated through movement and reflective writing in response to the photographic collection exhibited as part of the 2011 Dance and Somatic Practices Conference, Coventry, UK. In particular, the article explores the interrelationship between the somatic-informed
movement practices and performance score creation of Garrett Brown and Voris and the sensorial play of Kipp’s photography. Co-authored by Garrett Brown, Kipp and Voris, this collection of questions and responses seeks to continue rather than merely document the Enter & Inhabit collaborative
process.
Coming to our senses: Perceptual performance and fields of intensities
Authors: Wood Becca
Published: May 2012

This article examines new methods and practices for the performance of interrelational spaces and perceptions in choreography and sound technologies. The series of works discussed, strategically solicit somatic-informed choreography to question attentiveness to space, time and body
in intermodal arrangements. The critical spatial practice examines the potential for ubiquitous technologies to disrupt perceptions of time and place in live performance situations towards new methods of performance encounter.
Finding a Home for Products We Love: How Buyer Usage Intent Affects the Pricing of Used Goods
Authors: Brough Aaron R. , Isaac Mathew S.
Published: May 2012

Consumers often dispose of used products by selling them in a secondary market (e.g., classified advertisements, Craigslist, eBay). When consumers must dispose of products to which they feel emotionally attached, they often expect to sell the product at a price in excess of its market value. However, the authors identify a condition in which product attachment can decrease rather than increase the minimum price sellers are willing to accept. Specifically, they propose that due to concern for how products are used following a transaction, strongly attached sellers may be more willing than weakly attached sellers to provide discounts to potential buyers whose usage intentions are deemed appropriate. Whereas prior research has focused primarily on one particular consequence of attachment, namely, the intensified reluctance of consumers to part with their possessions, this research identifies a novel consequence of attachment: a heightened sensitivity to the manner in which the product will be used following a transaction. Four empirical studies provide converging evidence that sellers’ product attachment determines the extent to which their minimum acceptable sales price is influenced by buyer usage intent.
Developing General Equilibrium Benefit Analyses for Social Programs: An Introduction and Example
Authors: Klaiber H. Allen , Smith V. Kerry
Published: May 2012

Benefit-Cost analyses of social programs often involve complex interactions between market and non-market goods. In this paper we outline one conceptual framework for incorporating the general equilibrium effects into benefit-cost analyses of changes in social programs. The goal is to develop models that are capable of capturing the interactions that take place between decisions involving marketed goods together with their effects on non-market goods and the reverse –changes in non-market goods that cause induce changes in decisions about marketed goods. These types of feedback effects are likely to result from large changes in social programs. These effects are compounded by the potential for endogenous realized outcomes that arise as a result of household actions taken in response to proposed policies. To demonstrate the importance of our conceptual discussion of these general equilibrium effects, we present an empirical example of our general equilibrium framework using teacher cuts in response to budget pressures in Maricopa County, Arizona. We find substantial differences in willingness to pay measures between models which account for endogenous education outcomes in a general equilibrium setting and those which ignore the linkages between market (housing) and non-market (education) goods in a partial equilibrium setting
Accounting for Nonmarket Impacts in a Benefit-Cost Analysis of Underground Coal Mining in New South Wales, Australia
Authors: Gillespie Rob , Kragt Marit E.
Published: May 2012

Strategic inquiries into coal mining by Australian Governments advocate increased use of comprehensive benefit cost analyses and nonmarket valuation studies when assessing individual project proposals. The study reported in this paper addresses these Government concerns, by integrating results of a choice experiment into a benefit cost analysis undertaken for a Colliery in the Southern Coalfield of New South Wales, Australia. Results of the study were used to aid the State government in evaluating proposals for continued underground coal mining. We show that impacts of mine subsidence on streams, swamps, and Aboriginal sites negatively affect community wellbeing. Social welfare increases with the length of time that the mine provides direct employment. We demonstrate how implicit price estimates from the choice experiment can be incorporated into a benefit cost analysis of continued mining. Benefit cost analyses were carried out for a range of policy scenarios—including policies that would restrict mining activities at the Colliery and protect environmental and cultural features in the Southern Coalfield. Notwithstanding the environmental impacts generated by mining operations, continued mining is shown to be a more economically efficient course of action.
A Recursive Algorithm for a Non-uniform Amplitude Beam Propagating Through a Sub-wavelength Grating
Authors: Li Jianlong , Wang Pu
Published: May 2012

A recursive algorithm for a non-uniform
amplitude beam propagating through a
sub-wavelength grating is proposed in this
paper. This method is based on Maxwell's
equations and the continuity of the tangential
components of the electric and magnetic field
vectors, and gives an exact complete
solution. And we illustrate a propagation of a
Gaussian beam through a grating in detail.
Development of a New Class of Zero Cross Correlation Codes for Optical CDMA Systems
Authors: Rashidi Che Bin Mohd , Aljunid S. A. , Ghani F. , Anuar M. S.
Published: May 2012

The paper presents a method for the development of a new class of zero cross correlation optical code for Optical Code Division Multiple Access (OCDMA) system using Spectral Amplitude Coding. The proposed code is called Modified Zero Cross Correlation Code (MZCC). The code has minimum length and can be constructed quite simply for any number of users and for any code weights. The code has better spectrum slicing properties and noise performance in term of Bit Error Rate. The Modified Zero Cross Correlation Code will be demonstrated in simulation using OptiSys. 6.0 to observe noise performance which is better as compared to the existing Zero Cross Correlation Code.
Photo Parametric Amplifier Using Up & Down Converter Configuration for Optical Receiver
Authors: Abdullah Mohammad Faiz Liew , Elbireki Majdi Farag Mohammed
Published: May 2012

A fundamental requirement in the design of
an optical receiver is the achievement of high
sensitivity and broad bandwidth. These two
features are very important in getting
reliable system. In this project a receiver
circuit based on Photo parametric Amplifier
(PPA), which is suggested as one of the
alternative for receiver detection and
amplification techniques is fully
described. The PPA mode of operation involves
optical detection and amplification within a
single device. It is able to provide
selectivity and sensitivity at the same time,
as required for wireless optical
communications. The most common problem that
any communication system might face is the
noise which must be eliminated or at least
reduce it. In order to reduce the noise,
filters have been implemented before the
signal is passes through an amplifier. In this
project an Up converter has been placed at the
transmitter circuit in order to obtain high
frequency, while at the receiver circuit,
filters has been placed with Down converter to
obtain the desired frequency. Photo diode, PIN
type has been used to detect any incoming
signal at the receiver circuit. Results showed
that the output signal has been improved; with
addition power strength and noise reduction
which showed that photo parametric amplifier
is more reliable and suitable to be used in
wireless optical communication system.
Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain
Authors: Volkow Nora D. , Tomasi Dardo , Wang Gene-Jack , Telang Frank , Fowler Joanna S. , Logan Jean , Benveniste Helene , Kim Ron , Thanos Panayotis K. , Ferré Sergi
Published: May 2012

Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [11C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([11C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [11C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.
Calcium-Permeable AMPA Receptors Provide a Common Mechanism for LTP in Glutamatergic Synapses of Distinct Hippocampal Interneuron Types
Authors: Szabo Andras , Somogyi Jozsef , Cauli Bruno , Lambolez Bertrand , Somogyi Peter , Lamsa Karri P.
Published: May 2012

Glutamatergic synapses on some hippocampal GABAergic interneurons exhibit activity-induced long-term potentiation (LTP). Interneuron types within the CA1 area expressing mutually exclusive molecular markers differ in LTP responses. Potentiation that depends on calcium-permeable (CP) AMPA receptors has been characterized in oriens-lacunosum moleculare (O-LM) interneurons, which express parvalbumin and somatostatin (SM). However, it is unknown how widely CP-AMPAR-dependent plasticity is expressed among different GABAergic interneuron types. Here we examine synaptic plasticity in rat hippocampal O-LM cells and two other interneuron types expressing either nitric oxide synthase (NOS) or cholecystokinin (CCK), which are known to be physiologically and developmentally distinct. We report similar CP-AMPAR-dependent LTP in NOS-immunopositive ivy cells and SM-expressing O-LM cells to afferent fiber theta burst stimulation. The potentiation in both cell types is induced at postsynaptic membrane potentials below firing threshold, and induction is blocked by intense spiking simultaneously with afferent stimulation. The strong inward rectification and calcium permeability of AMPARs is explained by a low level of GluA2 subunit mRNA expression. LTP is not elicited in CCK-expressing Schaffer collateral-associated cells, which lack CP-AMPARs and express high levels of the GluA2 subunit. The results show that CP-AMPAR-mediated synaptic potentiation is common in hippocampal interneuron types and occurs in interneurons of both feedforward and feedback inhibitory pathways.
R6/2 Huntington's Disease Mice Develop Early and Progressive Abnormal Brain Metabolism and Seizures
Authors: Cepeda-Prado Efrain , Popp Susanna , Khan Usman , Stefanov Dimitre , Rodríguez Jorge , Menalled Liliana B. , Dow-Edwards Diana , Small Scott A. , Moreno Herman
Published: May 2012

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated usingin vivofunctional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [14C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used asin vivobiomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.
Photochemical Inactivation Analysis of Temporal Dynamics of Postsynaptic Native AMPA Receptors in Hippocampal Slices
Authors: Kamiya Haruyuki
Published: May 2012

Postsynaptic expression of AMPA-type glutamate receptors (AMPAR) is more mobile than previously thought. Much evidence suggests that AMPAR are delivered from intracellular reserved pools to postsynaptic sites in a constitutive, as well as activity-dependent manner by exocytosis, lateral diffusion, or diffusional trapping. These notions were supported by optical monitoring of AMPAR subunits labeled with macromolecular tags such as GFP or Immunobeads, although it remains uncertain whether the mode and rate of synaptic delivery are similar to native “unlabeled” receptors. To reveal the real-time dynamics of native AMPARin situ, photochemical inactivation of surface receptors using 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX), a photoreactive AMPAR blocker, was adopted for acute hippocampal slices of mice. Because of the irreversible block due to cross-link formation between ANQX and surface AMPAR, recovery of EPSPs after photoinactivation reflects the time course of synaptic delivery of intracellular AMPAR. Brief UV illumination with fast application of ANQX resulted in persistent suppression of EPSPs for a prolonged period of up to 3 h, suggesting minimal synaptic delivery of AMPAR by exocytosis in the resting condition. Kinetic analysis of EPSP recovery clarified that the supply of postsynaptic AMPAR from the intracellular pool is dominated in the initial, but not in the later, phase of long-term potentiation (LTP). These results suggest that constitutive synaptic delivery is minimal in the resting condition at intact hippocampal synapses in a time scale of hours, while postsynaptic AMPAR are replaced with those in intracellular pools almost exclusively in an activity-dependent manner, typically shortly after LTP induction.
Age-DependentIn VivoConversion of Mouse Cochlear Pillar and Deiters' Cells to Immature Hair Cells by Atoh1 Ectopic Expression
Authors: Liu Zhiyong , Dearman Jennifer A. , Cox Brandon C. , Walters Brandon J. , Zhang Lingli , Ayrault Olivier , Zindy Frederique , Gan Lin , Roussel Martine F. , Zuo Jian
Published: May 2012

Unlike nonmammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair cells (HCs) after damage, thus causing permanent deafness. Here, we achievedin vivoconversion of two SC subtypes, pillar cells (PCs) and Deiters' cells (DCs), into HCs by inducing targeted expression of Atoh1 at neonatal and juvenile ages using novel mouse models. The conversion only occurred in ∼10% of PCs and DCs with ectopic Atoh1 expression and started with reactivation of endogenous Atoh1 followed by expression of 11 HC and synaptic markers, a process that took approximately 3 weeksin vivo. These new HCs resided in the outer HC region, formed stereocilia, contained mechanoelectrical transduction channels, and survived for >2 monthsin vivo; however, they surprisingly lacked prestin and oncomodulin expression and mature HC morphology. In contrast, adult PCs and DCs no longer responded to ectopic Atoh1 expression, even after outer HC damage. Finally, permanent Atoh1 expression in endogenous HCs did not affect prestin expression but caused cell loss of mature HCs. Together, our results demonstrate thatin vivoconversion of PCs and DCs into immature HCs by Atoh1 is age dependent and resembles normal HC development. Therefore, combined expression of Atoh1 with additional factors holds therapeutic promise to convert PCs and DCs into functional HCsin vivofor regenerative purposes.
Electrophysiological Abnormalities in Both Axotomized and Nonaxotomized Pyramidal Neurons following Mild Traumatic Brain Injury
Authors: Greer John E. , Povlishock John T. , Jacobs Kimberle M.
Published: May 2012

Mild traumatic brain injury (mTBI) often produces lasting detrimental effects on cognitive processes. The mechanisms underlying neurological abnormalities have not been fully identified, in part due to the diffuse pathology underlying mTBI. Here we employ a mouse model of mTBI that allows for identification of both axotomized and intact neurons in the living cortical slice via neuronal expression of yellow fluorescent protein. Both axotomized and intact neurons recorded within injured cortex are healthy with a normal resting membrane potential, time constant (τ), and input resistance (Rin). In control cortex, 25% of cells show an intrinsically bursting action potential (AP) firing pattern, and the rest respond to injected depolarizing current with a regular-spiking pattern. At 2 d postinjury, intrinsic bursting activity is lost within the intact population. The AP amplitude is increased and afterhyperpolarization duration decreased in axotomized neurons at 1 and 2 d postinjury. In contrast, intact neurons also show these changes at 1 d, but recover by 2 d postinjury. Two measures suggest an initial decrease in excitability in axotomized neurons followed by an increase in excitability within intact neurons. The rheobase is significantly increased in axotomized neurons at 1 d postinjury. The slope of the plot of AP frequency versus injected current is larger for intact neurons at 2 d postinjury. Together, these results demonstrate that intact and axotomized neurons are both affected by mTBI, resulting in different changes in neuronal excitability that may contribute to network dysfunction following TBI.
Neuronal Learning of Invariant Object Representation in the Ventral Visual Stream Is Not Dependent on Reward
Authors: Li Nuo , DiCarlo James J.
Published: May 2012

Neurons at the top of primate ventral visual stream [inferior temporal cortex (IT)] have selectivity for objects that is highly tolerant to variation in the object's appearance on the retina. Previous nonhuman primate (Macaca mulatta) studies suggest that this neuronal tolerance is at least partly supported by the natural temporal contiguity of visual experience, because altering that temporal contiguity can robustly alter adult IT position and size tolerance. According to that work, it is the statistics of the subject's visual experience, not the subject's reward, that instruct the specific images that IT treats as equivalent. But is reward necessary for gating this type of learning in the ventral stream? Here we show that this is not the case—temporal tolerance learning proceeds at the same rate, regardless of reward magnitude and regardless of the temporal co-occurrence of reward, even in a behavioral task that does not require the subject to engage the object images. This suggests that the ventral visual stream uses autonomous, fully unsupervised mechanisms to constantly leverage all visual experience to help build its invariant object representation.
Long-Distance Amplitude Correlations in the High Gamma Band Reveal Segregation and Integration within the Reading Network
Authors: Vidal Juan R. , Freyermuth Samson , Jerbi Karim , Hamamé Carlos M. , Ossandon Tomas , Bertrand Olivier , Minotti Lorella , Kahane Philippe , Berthoz Alain , Lachaux Jean-Philippe
Published: May 2012

Reading sentences involves a distributed network of brain regions acting in concert surrounding the left sylvian fissure. The mechanisms of neural communication underlying the extraction and integration of verbal information across subcomponents of this reading network are still largely unknown. We recorded intracranial EEG activity in 12 epileptic human patients performing natural sentence reading and analyzed long-range corticocortical interactions between local neural activations. During a simple task contrasting semantic, phonological, and purely visual processes, we found process-specific neural activity elicited at the single-trial level, characterized by energy increases in a broad gamma band (40–150 Hz). Correlation analysis between task-induced gamma-band activations revealed a selective fragmentation of the network into specialized subnetworks supporting sentence-level semantic analysis and phonological processing. We extend the implications of our results beyond reading, to propose that gamma-band amplitude correlations might constitute a fundamental mechanism for large-scale neural integration during high-level cognition.
Atoh1 Directs the Formation of Sensory Mosaics and Induces Cell Proliferation in the Postnatal Mammalian CochleaIn Vivo
Authors: Kelly Michael C. , Chang Qing , Pan Alex , Lin Xi , Chen Ping
Published: May 2012

Hearing impairment due to the loss of sensory hair cells is permanent in humans. Considerable interest targets the hair cell differentiation factor Atoh1 as a potential tool with which to promote hair cell regeneration. We generated a novel mouse model to direct the expression of Atoh1 in a spatially and temporally specific manner in the postnatal mammalian cochlea to determine the competency of various types of cochlear epithelial cells for hair cell differentiation. Atoh1 can generate cells in young animals with morphological, molecular, and physiological properties reminiscent of hair cells. This competency is cell type specific and progressively restricted with age. Significantly, Atoh1 induces ectopic sensory patches through Notch signaling to form a cellular mosaic similar to the endogenous sensory epithelia and expansion of the sensory mosaic through the conversion of supporting cells and nonautonomous supporting cell production. Furthermore, Atoh1 also activates proliferation within the normally postmitotic cochlear epithelium. These results provide insight into the potential and limitations of Atoh1-mediated hair cell regeneration.
Perceptual Learning Evidence for Tuning to Spectrotemporal Modulation in the Human Auditory System
Authors: Sabin Andrew T. , Eddins David A. , Wright Beverly A.
Published: May 2012

Natural sounds are characterized by complex patterns of sound intensity distributed across both frequency (spectral modulation) and time (temporal modulation). Perception of these patterns has been proposed to depend on a bank of modulation filters, each tuned to a unique combination of a spectral and a temporal modulation frequency. There is considerable physiological evidence for such combined spectrotemporal tuning. However, direct behavioral evidence is lacking. Here we examined the processing of spectrotemporal modulation behaviorally using a perceptual-learning paradigm. We trained human listeners for ∼1 h/d for 7 d to discriminate the depth of spectral (0.5 cyc/oct; 0 Hz), temporal (0 cyc/oct; 32 Hz), or upward spectrotemporal (0.5 cyc/oct; 32 Hz) modulation. Each trained group learned more on their respective trained condition than did controls who received no training. Critically, this depth-discrimination learning did not generalize to the trained stimuli of the other groups or to downward spectrotemporal (0.5 cyc/oct; −32 Hz) modulation. Learning on discrimination also led to worsening on modulation detection, but only when the same spectrotemporal modulation was used for both tasks. Thus, these influences of training were specific to the trained combination of spectral and temporal modulation frequencies, even when the trained and untrained stimuli had one modulation frequency in common. This specificity indicates that training modified circuitry that had combined spectrotemporal tuning, and therefore that circuits with such tuning can influence perception. These results are consistent with the possibility that the auditory system analyzes sounds through filters tuned to combined spectrotemporal modulation.