bluuebunny/crossref_metadata_2025 huggingface dataset:
`Caucasian and Thai make a good mix'
Authors: Haritaworn Jin
Published: January 2009

This article examines the current celebration of Eur/ Asianness in the media and popular culture. It traces representations of the `mixed race' body, from colonial discourses of degeneracy and monstrosity to capitalist discourses of commercialized exoticism and `beauty'. It then examines how people of Thai and non-Thai parentage interviewed in Britain and Germany in 2001 and 2002 negotiated gendered and racialized readings of their bodies. Narratives of multi-racialized embodiment brim with racism, as the `valuable' or `pathological', `good' or `bad mixes', of unlike body parts grafted onto each other. This necessitates a critical re-evaluation of `hybridity' debates, which treat biological racism as a past phenomenon that can be metaphorized for cultural processes of identification.
Governing through crime as commonsense racism
Authors: Fleury-Steiner Benjamin D. , Dunn Kerry , Fleury-Steiner Ruth
Published: January 2009

This article explores momentous changes to Delaware's death penalty statute in 1991, reforms that made it one of the USA's premier killing states. Reflecting on media coverage of a high profile crime and the legislative debates that led to the law change sheds light on how static conceptions of spaces (i.e. `the dangerous city') and persons (i.e. `non-white invaders from Philadelphia') reveal lawmakers' commonsense racism as inextricably bound to such momentous legislative action. By situating the decision in the context of the intense urgency to act set in motion by a high profile racially charged crime and a taken-for-granted compliance to an aggressive pro-death legal formalism, lawmakers appeared to act in a manner that was racially neutral. However and perhaps most strikingly, the debate lacked any dissenting voices of representatives from racially aggrieved communities long neglected by the state. Such a racially insensitive rush to appear `tough on crime' reveals how Delaware lawmakers acted according to a commonsense of racialized persons, places, and channels that enforced racial hierarchy (i.e. actions that hurt minorities and favor whites). More broadly, we argue that Haney-Lopez's (2003) theory of commonsense racism helps to clarify Simon's (2007) theory of governing through crime as it applies to the `toughening' of already punitive criminal laws at the state level, if not especially the death penalty.
Anger about crime and support for punitive criminal justice policies
Authors: Johnson Devon
Published: January 2009

Previous research on the sources of punitive attitudes has largely focused on the cognitive and demographic factors associated with the desire to punish criminals harshly. This study focuses on the link between affect and punitiveness by examining the relationship between anger about crime and support for punitive criminal penalties. Using national survey data from the USA, this research shows that anger about crime is a significant predictor of punitive attitudes, after controlling for other factors such as racial prejudice, fear of crime, causal attributions for criminal behavior, and political ideology. The findings indicate the need for more research on the relationship between emotions and punitiveness.
Theorizing fines
Authors: O'Malley Pat
Published: January 2009

Given their central place as a sanction in criminal justice, the virtual absence of a theoretical literature on fines is a serious deficit. The article reviews the principal contributions to date, and argues that they suffer from a misleading conviction that sanctions are driven by production relations. To begin with, this seriously underestimates the impact of penal discourses and practice, which can better account for variations in the rise, uneven distribution and recent decline in fines' dominance as a punishment. Equally important is the failure to consider the nexus between the rise of the modern regulatory fine (for example `on the spot' fines) and the rise of consumer societies.
Accountable to what?
Authors: Ward Geoff , Kupchik Aaron
Published: January 2009

Formal philosophical and procedural aspects of American juvenile justice have been transformed over the past half-century by `accountability' movements. Yet the meaning of accountability in juvenile justice — specifically who is to be held accountable and to whom — has varied over time making its present application unclear. In this article, we first describe two models of accountability ideals and how each developed. We discuss how traditional rehabilitative ideals were first displaced by `system accountability' reforms emphasizing fairness and youths' rights, followed by `juvenile accountability' reforms emphasizing punishment and victims' interests. We then explore how juvenile court judges, lawyers and probations officers in four states prioritize these accountability principles. While decision makers in our sample prioritize a system accountability perspective, especially as this relates to rehabilitative ideals, there is considerable diversity in orientation. Professional roles and racial identities of decision makers significantly shape their prioritization of various accountability goals.
Cortical Plasticity Following Motor Skill Learning During Mental Practice in Stroke
Authors: Page Stephen J. , Szaflarski Jerzy P. , Eliassen James C. , Pan Hai , Cramer Steven C.
Published: January 2009

Background and purpose. Mental practice (MP), which involves cognitive rehearsal of physical movements, is a noninvasive, inexpensive method of enabling repetitive, task-specific practice (RTP). Recent, randomized controlled data suggest that MP, when combined with an RTP therapy program, increases affected arm use and function significantly more than RTP only. As a next step, this 10-subject case series examined the possibility that cortical plasticity is a mechanism underlying the treatment effect of MP when combined with RTP. Method. Ten chronic stroke patients (mean = 36.7 months) exhibiting stable, moderate motor deficits received 30-minute therapy sessions for their affected arms, occurring 3 days/week for 10 weeks, and emphasizing valued activities of daily living (ADLs). Directly after therapy, subjects received 30-minute MP sessions, which required MP of the ADLs performed during therapy. Behavioral outcomes were blindly evaluated using the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FM). Functional magnetic resonance imaging (fMRI) was administered before and after intervention to assess cortical changes. Results. Before intervention, subjects exhibited stable motor deficits. After intervention, subjects exhibited ARAT and FM score increases (+5.3 and +4.2, respectively) and clinically significant gains in ADLs. Postintervention fMRI revealed significant increases in activation to wrist flexion and extension of the affected hand in the premotor area and primary motor cortex ipsilateral and contralateral to the affected hand, as well as in superior parietal cortex ipsilateral to the affected hand. Decreased activation was noted in parietal cortex of the hemisphere ipsilateral to the affected hand. These changes correlated with anatomical regions in which behavioral changes were observed in the ARAT and FM. Conclusions. MP is an easy to use, cost-effective strategy that was again shown to improve affected arm outcomes after stroke. This is the first study to demonstrate alteration in the cortical map in response to MP training.
EPIC-DB: a proteomics database for studying Apicomplexan organisms
Authors: Madrid-Aliste Carlos J , Dybas Joseph M , Angeletti Ruth Hogue , Weiss Louis M , Kim Kami , Simon Istvan , Fiser Andras
Published: January 2009

Background

High throughput proteomics experiments are useful for analyzing the protein expression of an organism, identifying the correct gene structure of a genome, or locating possible post-translational modifications within proteins. High throughput methods necessitate publicly accessible and easily queried databases for efficiently and logically storing, displaying, and analyzing the large volume of data.

Description

EPICDB is a publicly accessible, queryable, relational database that organizes and displays experimental, high throughput proteomics data for Toxoplasma gondii and Cryptosporidium parvum. Along with detailed information on mass spectrometry experiments, the database also provides antibody experimental results and analysis of functional annotations, comparative genomics, and aligned expressed sequence tag (EST) and genomic open reading frame (ORF) sequences. The database contains all available alternative gene datasets for each organism, which comprises a complete theoretical proteome for the respective organism, and all data is referenced to these sequences. The database is structured around clusters of protein sequences, which allows for the evaluation of redundancy, protein prediction discrepancies, and possible splice variants. The database can be expanded to include genomes of other organisms for which proteome-wide experimental data are available.

Conclusion

EPICDB is a comprehensive database of genome-wide T. gondii and C. parvum proteomics data and incorporates many features that allow for the analysis of the entire proteomes and/or annotation of specific protein sequences. EPICDB is complementary to other -genomics- databases of these organisms by offering complete mass spectrometry analysis on a comprehensive set of all available protein sequences.
A novel Ecotin-Ubiquitin-Tag (ECUT) for efficient, soluble peptide production in the periplasm of Escherichia coli
Authors: Paal Michael , Heel Thomas , Schneider Rainer , Auer Bernhard
Published: January 2009

Background

Many protocols for recombinant production of peptides and proteins include secretion into the periplasmic space of Escherichia coli, as they may not properly fold in the cytoplasm. If a signal peptide is not sufficient for translocation, a larger secretion moiety can instead be fused to the gene of interest. However, due to the covalent linkage of the proteins, a protease recognition site needs to be introduced in between, altering the N-terminus of the product. In the current study, we combined the ubiquitin fusion technology, which allows production of authentic peptides and proteins, with secretion by the perpiplasmic protease inhibitor ecotin.

Results

Different fusion constructs, composed of ecotin, mouse ubiquitin b and a model peptide, were expressed in E. coli BL21(DE3). The fusion proteins were translocated into the periplasmic space and the ecotin signal peptide was cleaved off. Under the control of the lacUV5 promoter at 24°C we obtained 18 mg periplasmic recombinant protein per gram dry cell weight. However, vigorous expression with the T7 promoter caused outer membrane permeabilization and leakage of the fusion protein into the culture medium. Target peptides were released from hybrid proteins by the deubiquitinating enzyme ubiquitin c-terminal hydrolase-L3 in vitro. MALDI TOF-TOF mass spectroscopy confirmed accurate cleavage.

Conclusion

This newly described method represents a useful technique for the production of authentic soluble peptides in the periplasm of E. coli. In addition, larger proteins might also be produced with the current system by the use of ubiquitin specific proteases, which can cleave off larger C-terminal extensions.
Isotretinoin and psychopathology: a review
Authors: Kontaxakis Vassilis P , Skourides Demetris , Ferentinos Panayotis , Havaki-Kontaxaki Beata J , Papadimitriou George N
Published: January 2009

Isotretinoin, a synthetic oral retinoid that is used against severe nodulocystic acne, has been associated with various psychiatric side effects such as depression, suicidality and psychotic symptoms. A great number of reports on its effects have been published since its introduction into the market. However, a causal relationship has not been established and the link between isotretinoin use and psychiatric events remains controversial. The present paper reviews the available evidence regarding the association of isotretinoin and psychiatric side effects. All published material reporting psychiatric side effects following isotretinoin treatment, including case reports, case series, reports from adverse drug event reporting systems, prospective surveys and retrospective case-control studies, are presented. In addition, the neurobiology of the retinoids and possible biological mechanisms that may lead to psychopathology are described.
A Drosophila systems model of pentylenetetrazole induced locomotor plasticity responsive to antiepileptic drugs
Authors: Mohammad Farhan , Singh Priyanka , Sharma Abhay
Published: January 2009

Background

Rodent kindling induced by PTZ is a widely used model of epileptogenesis and AED testing. Overlapping pathophysiological mechanisms may underlie epileptogenesis and other neuropsychiatric conditions. Besides epilepsy, AEDs are widely used in treating various neuropsychiatric disorders. Mechanisms of AEDs' long term action in these disorders are poorly understood. We describe here aDrosophilasystems model of PTZ induced locomotor plasticity that is responsive to AEDs.

Results

We empirically determined a regime in which seven days of PTZ treatment and seven days of subsequent PTZ discontinuation respectively cause a decrease and an increase in climbing speed ofDrosophilaadults. Concomitant treatment with NaVP and LEV, not ETH, GBP and VGB, suppressed the development of locomotor deficit at the end of chronic PTZ phase. Concomitant LEV also ameliorated locomotor alteration that develops after PTZ withdrawal. Time series of microarray expression profiles of heads of flies treated with PTZ for 12 hrs (beginning phase), two days (latent phase) and seven days (behaviorally expressive phase) showed only down-, not up-, regulation of genes; expression of 23, 2439 and 265 genes were downregulated, in that order. GO biological process enrichment analysis showed downregulation of transcription, neuron morphogenesis during differentiation, synaptic transmission, regulation of neurotransmitter levels, neurogenesis, axonogenesis, protein modification, axon guidance, actin filament organization etc. in the latent phase and of glutamate metabolism, cell communication etc. in the expressive phase. Proteomic interactome based analysis provided further directionality to these events. Pathway overrepresentation analysis showed enrichment of Wnt signaling and other associated pathways in genes downregulated by PTZ. Mining of available transcriptomic and proteomic data pertaining to established rodent models of epilepsy and human epileptic patients showed overrepresentation of epilepsy associated genes in our PTZ regulated set.

Conclusion

Systems biology ultimately aims at delineating and comprehending the functioning of complex biological systems in such details that predictive models of human diseases could be developed. Due to immense complexity of higher organisms, systems biology approaches are however currently focused on simpler organisms. Amenable to modeling, our model offers a unique opportunity to further dissect epileptogenesis-like plasticity and to unravel mechanisms of long-term action of AEDs relevant in neuropsychiatric disorders.
The scavenger receptor CD36 plays a role in cytokine-induced macrophage fusion
Authors: Helming Laura , Winter Julia , Gordon Siamon
Published: January 2009

Multinucleated giant cells, characteristic of granulomatous infections, originate from the fusion of macrophages. Using an antibody screening strategy we found that the scavenger receptor CD36 participates in macrophage fusion induced by the cytokines IL-4 and GM-CSF. Our results demonstrate that exposure of phosphatidylserine on the cell surface and lipid recognition by CD36 are required for cytokine-induced fusion of macrophages. We also show that CD36 acts in a heterotypic manner during giant-cell formation and that the formation of osteoclasts is independent of CD36. The discovery of molecules involved in the formation of multinucleated giant cells will enable us to determine their functional significance. Furthermore, our results suggest that lipid capture by cell surface receptors may be a general feature of cell fusion.
GMC Tests of Competence: the assessment of poorly performing doctors
Authors: Etheridge Lucinda , Sturrock Alison , Conlon Liam , Dacre Jane
Published: January 2009

Objective

This article aims to provide an overview of the current procedures in place by the General Medical Council to assess the fitness to practise of poorly performing doctors.

Method

It outlines the legal background, the structure and the rationale behind the type of assessments used.

Results

Specialty specific Tests of Competence and a workplace-based assessment are carried out by a specially trained and appointed team of assessors. All assessments are designed to the highest standards by expert teams, including trained stakeholders.

Conclusions

Assessments are continually being updated and validated to ensure high standards in this high stakes process.
Small molecule activators of pre-mRNA 3′ cleavage
Authors: Ryan Kevin , Khleborodova Asya , Pan Jingyi , Ryan Xiaozhou P.
Published: January 2009

3′ Cleavage and polyadenylation are obligatory steps in the biogenesis of most mammalian pre-mRNAs. In vitro reconstitution of the 3′ cleavage reaction from human cleavage factors requires high concentrations of creatine phosphate (CP), though how CP activates cleavage is not known. Previously, we proposed that CP might work by competitively inhibiting a cleavage-suppressing serine/threonine (S/T) phosphatase. Here we show that fluoride/EDTA, a general S/T phosphatase inhibitor, activates in vitro cleavage in place of CP. Subsequent testing of inhibitors specific for different S/T phosphatases showed that inhibitors of the PPM family of S/T phosphatases, which includes PP2C, but not the PPP family, which includes PP1, PP2A, and PP2B, activated 3′ cleavage in vitro. In particular, NCI 83633, an inhibitor of PP2C, activated extensive 3′ cleavage at a concentration 50-fold below that required by fluoride or CP. The testing of structural analogs led to the identification of a more potent compound that activated 3′ cleavage at 200 μM. While testing CP analogs to understand the origin of its cleavage activation effect, we found phosphocholine to be a more effective activator than CP. The minimal structural determinants of 3′ cleavage activation by phosphocholine were identified. Our results describe a much improved small molecule activator of in vitro pre-mRNA cleavage, identify the molecular determinants of cleavage activation by phosphoamines such as phosphocholine, and suggest that a PPM family phosphatase is involved in the negative regulation of mammalian pre-mRNA 3′ cleavage.
The SID-1 double-stranded RNA transporter is not selective for dsRNA length
Authors: Shih Joseph D. , Fitzgerald Michael C. , Sutherlin Marie , Hunter Craig P.
Published: January 2009

The double-stranded RNA (dsRNA) transport protein SID-1 enables systemic RNA interference (RNAi) in Caenorhabditis elegans, whereby silencing initiated by local exposure to dsRNA spreads throughout the animal and to its progeny. Previously, we showed that providing dsRNA in the growth medium of Drosophila S2 cells that express C. elegans SID-1 efficiently triggers RNAi. In these experiments long dsRNA proved to be significantly more effective than short dsRNA in silencing the target gene. Here, we show that equivalent masses of long or short dsRNA accumulate in these cells, indicating that size-dependent silencing is not due to size-selective transport through SID-1. Furthermore, using pulse-chase dsRNA uptake experiments, we show that short dsRNA accumulates more rapidly than long dsRNA. We found that import rates are dependent on dsRNA concentration, consistent with energy-independent, diffusion-limited transport through the SID-1 channel. Comparison of silencing efficiencies between Drosophila S2 cells heterologously expressing SID-1 and primary-cultured C. elegans cells shows similar dsRNA concentration and size dependencies, suggesting that C. elegans regulatory proteins do not measurably enhance or restrict dsRNA transport through SID-1. Finally, we find that coexpressing mutant SID-1 with wild-type SID-1 in S2 cells interferes with SID-1 function, indicating that SID-1 may function as a multimer.
Specific roles for the Ccr4-Not complex subunits in expression of the genome
Authors: Azzouz Nowel , Panasenko Olesya O. , Deluen Cécile , Hsieh Julien , Theiler Grégory , Collart Martine A.
Published: January 2009

In this work we used micro-array experiments to determine the role of each nonessential subunit of the conserved Ccr4-Not complex in the control of gene expression in the yeastSaccharomyces cerevisiae. The study was performed with cells growing exponentially in high glucose and with cells grown to glucose depletion. Specific patterns of gene deregulation were observed upon deletion of any given subunit, revealing the specificity of each subunit's function. Consistently, the purification of the Ccr4-Not complex through Caf40p by tandem affinity purification from wild-type cells or cells lacking individual subunits of the Ccr4-Not complex revealed that each subunit had a particular impact on complex integrity. Furthermore, the micro-arrays revealed that the role of each subunit was specific to the growth conditions. From the study of only two different growth conditions, revealing an impact of the Ccr4-Not complex on more than 85% of all studied genes, we can infer that the Ccr4-Not complex is important for expression of most of the yeast genome.
EcI5, a group IIB intron with high retrohoming frequency: DNA target site recognition and use in gene targeting
Authors: Zhuang Fanglei , Karberg Michael , Perutka Jiri , Lambowitz Alan M.
Published: January 2009

We find that group II intron EcI5, a subclass CL/IIB1 intron from an Escherichia coli virulence plasmid, is highly active in retrohoming in E. coli. Both full-length EcI5 and an EcI5-ΔORF intron with the intron-encoded protein expressed separately from the same donor plasmid retrohome into a recipient plasmid target site at substantially higher frequencies than do similarly configured Lactococcus lactis Ll.LtrB introns. A comprehensive view of DNA target site recognition by EcI5 was obtained from selection experiments with donor and recipient plasmid libraries in which different recognition elements were randomized. These experiments suggest that EcI5, like other mobile group II introns, recognizes DNA target sequences by using both the intron-encoded protein and base-pairing of the intron RNA, with the latter involving EBS1, EBS2, and EBS3 sequences characteristic of class IIB introns. The intron-encoded protein appears to recognize a small number of bases flanking those recognized by the intron RNA, but their identity is different than in previously characterized group II introns. A computer algorithm based on the empirically determined DNA recognition rules enabled retargeting of EcI5 to integrate specifically at 10 different sites in the chromosomal lacZ gene at frequencies up to 98% without selection. Our findings provide insight into modes of DNA target site recognition used by mobile group II introns. More generally, they show how the diversity of mobile group II introns can be exploited to provide a large variety of different target specificities and potentially other useful properties for gene targeting.
Phosphorylation of FMRP inhibits association with Dicer
Authors: Cheever Anne , Ceman Stephanie
Published: January 2009

Fragile X syndrome is caused by an absence of the protein product of the fragile X mental retardation gene (FMR1). The fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates translation of associated mRNAs; however, the mechanism for this regulation remains unknown. Constitutively, phosphorylated FMRP (P-FMRP) is found associated with stalled untranslating polyribosomes, and translation of at least one mRNA is down-regulated when FMRP is phosphorylated. Based on our hypothesis that translational regulation by P-FMRP is accomplished through association with the microRNA (miRNA) pathway, we developed a phospho-specific antibody to P-FMRP and showed that P-FMRP associates with increased amounts of precursor miRNAs (pre-miRNA) compared with total FMRP. Furthermore, P-FMRP does not associate with Dicer or Dicer-containing complexes in coimmunoprecipitation experiments or in an in vitro capture assay using a P-FMRP peptide sequence bound to agarose beads. These data show that Dicer-containing complexes bind FMRP at amino acids 496–503 and that phosphorylation disrupts this association with a consequent increase in association with pre-miRNAs. In sum, we propose that in addition to regulating translation, phosphorylation of FMRP regulates its association with the miRNA pathway by modulating association with Dicer.
A realistic evaluation of practice-based commissioning
Authors: Greener Ian , Mannion Russell
Published: January 2009

The tendency of governments to recycle policy from previous periods presents analysts with the opportunity of assessing their likelihood of success in new time periods. This article presents a theoretical and empirical contribution toward this goal. Its theoretical contribution utilises the work of Pawson and Archer by exploring how context from previous and current periods can be compared and separated from generic policy mechanisms that underpin reforms in order to be able to show how outcomes from the past might be reproduced or transformed in current policy. Its empirical contribution applies this framework to the case of GP fundholding from the 1990s and practice-based commissioning of the 2000s, to show how the latter policy both addresses the difficulties of its predecessor but also makes significant errors that jeopardise its potential for success.
Publication Metrics and Record of Pharmacy Practice Chairs
Authors: Thompson Dennis F , Callen Erin C , Nahata Milap C
Published: January 2009

Background:

Scholarship is an essential component of academic pharmacy. Department chairs are considered role models and mentors to junior faculty, but their publication record has not been documented.

Objective:

To quantify publication patterns of pharmacy practice chairs in general and, specifically, at health sciences center (HSC)-based versus non–HSC-based and public versus private colleges of pharmacy.

Methods:

Pharmacy practice chairs were identified using the 2006–2007 roster of faculty from the American Association of Colleges of Pharmacy. Of the 89 colleges of pharmacy in the roster, 11 listed no pharmacy practice chair and 5 listed more than one. Data were collected on the remaining 73 schools by searching each chair's name on PubMed and Web of Science (WoS). Data on total publications, publications per year, total citations, citations per article, h-index, and m quotient were collected.

Results:

A total of 2394 papers published by 73 pharmacy practice chairs were found in a search of PubMed. The mean number of total publications per chair was 33 (95% CI 21 to 44). The mean number of publications per year was 1.4 using PubMed and 1.6 using WoS. Mean h-index was 8.0 (95% CI 6.3 to 9.6). Mean number of total citations was 410 (95% CI 252 to 568). Thirty-three percent (n = 24) had less than 10 lifetime publications and 18% had more than 50 lifetime publications, HSC-based chairs averaged 51.3 papers while non–HSC-based chairs averaged 19.1 (p < 0.01). Similar data were found for total citations (HSC = 673 vs non-HSC = 216; p < 0.001). Public school chairs had an average of 41.5 articles cited on PubMed, versus 15 for private school chairs (p<0.01). Public school chairs had an average h-index of 9.7 versus 4.4 for private school chairs (p < 0.001), and an average of 9.2 citations per article compared with 5.2 for private school chairs (p < 0.001).

Conclusions:

These data provide a normative pattern of publication metrics and record for pharmacy practice chairs and demonstrate marked variability in scholarly productivity.
Human Papillomavirus Vaccine Safety in Pediatric Patients: An Evaluation of the Vaccine Adverse Event Reporting System
Authors: Borja-Hart Nancy L , Benavides Sandra , Christensen Crystal
Published: January 2009

Recent news reports have linked the human papillomavirus (HPV) vaccine to serious adverse events (AEs) in children and adolescents. We used the Vaccine Adverse Event Reporting System (VAERS) database to extract postmarketing AEs reported in patients who received the vaccine. Since approval of the HPV vaccine in the US, 3174 AEs occurring in children and adolescents (aged 6-17 y) have been reported to the VAERS. Of these, 191 (6%) were deemed to be serious. Although these AEs are of significant concern, more research is required before they can be directly correlated with the vaccine.
Spectral background and transmission characteristics of fiber optic imaging bundles
Authors: Udovich Joshua Anthony , Kirkpatrick Nathaniel D. , Kano Angelique , West Rynes Anthony , Utzinger Urs , Gmitro Arthur F.
Published: January 2009

The emission and transmission properties of three commercially produced
coherent fiber optic imaging bundles were evaluated. Full fluorescence
excitation versus emission data were collected from 250 to
650 nm excitation for
high-resolution Sumitomo, Fujikura, and Schott fiber bundles. The
results generated show regions of autofluorescence and inelastic Raman
scattering in the imaging bundles that represent a
wavelength-dependent background signal when these fibers are used for
imaging applications. The high-resolution fiber bundles also exhibit
significant variation in transmission with the angle of illumination,
which affects the overall coupling and transmission efficiency.
Knowledge of these properties allows users of high-resolution imaging
bundles to optimally design systems that utilize such bundles.
Distinctive Neuronal Networks and Biochemical Pathways for Appetitive and Aversive Memory inDrosophilaLarvae
Authors: Honjo Ken , Furukubo-Tokunaga Katsuo
Published: January 2009

Associative strength between conditioned stimulus (CS) and unconditioned stimulus (US) is thought to determine learning efficacy in classical conditioning. Elucidation of the neuronal mechanism that underlies the association between CS and US in the brain is thus critical to understand the principle of memory formation. With a simple brain organization, theDrosophilalarva provides an attractive model system to investigate learning at the neurocircuitry level. Previously, we described a single-odor paradigm for larval associative learning using sucrose as a reward, and showed that larval appetitive memory lasts longer than 2 h. In this work, we describe behavioral and genetic characterization of larval aversive olfactory memory formed in our paradigm, and compare its stability and neurocircuitry with those of appetitive memory. Despite identical training paradigms, larval olfactory memory formed with quinine or NaCl is short-lived to be lost in 20 min. As with appetitive memory, larval aversive memory produced in this paradigm depends on intact cAMP signaling, but neither mutation ofamnesiacnor suppression of CREB activity affects its kinetics. Neurocircuitry analyses suggest that aversive memory is stored before the presynaptic termini of the larval mushroom body neurons as is the case with appetitive memory. However, synaptic output of octopaminergic and dopaminergic neurons, which exhibit distinctive innervation patterns on the larval mushroom body and antennal lobe, is differentially required for the acquisition of appetitive and aversive memory, respectively. These results as a whole suggest that the genetically programmed memory circuitries might provide predisposition in the efficacy of inducing longer-lived memory components in associative learning.
Insulin-Like Growth Factor-1 Promotes G1/S Cell Cycle Progression through Bidirectional Regulation of Cyclins and Cyclin-Dependent Kinase Inhibitors via the Phosphatidylinositol 3-Kinase/Akt Pathway in Developing Rat Cerebral Cortex
Authors: Mairet-Coello Georges , Tury Anna , DiCicco-Bloom Emanuel
Published: January 2009

Although survival-promoting effects of insulin-like growth factor-1 (IGF-1) during neurogenesis are well characterized, mitogenic effects remain less well substantiated. Here, we characterize cell cycle regulators and signaling pathways underlying IGF-1 effects on embryonic cortical precursor proliferationin vitroandin vivo. In vitro, IGF-1 stimulated cell cycle progression and increased cell number without promoting cell survival. IGF-1 induced rapid increases in cyclin D1 and D3 protein levels at 4 h and cyclin E at 8 h. Moreover, p27KIP1and p57KIP2expression were reduced, suggesting downregulation of negative regulators contributes to mitogenesis. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway specifically underlies IGF-1 activity, because blocking this pathway, but not MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase), prevented mitogenesis. To determine whether mechanisms defined in culture relate to corticogenesisin vivo, we performed transuterine intracerebroventricular injections. Whereas blockade of endogenous factor with anti-IGF-1 antibody decreased DNA synthesis, IGF-1 injection stimulated DNA synthesis and increased the number of S-phase cells in the ventricular zone. IGF-1 treatment increased phospho-Akt fourfold at 30 min, cyclins D1 and E by 6 h, and decreased p27KIP1and p57KIP2expression. Moreover, blockade of the PI3K/Akt pathwayin vivodecreased DNA synthesis and cyclin E, increased p27KIP1and p57KIP2expression, and prevented IGF-1-induced cyclin E mRNA upregulation. Finally, IGF-1 injection in embryos increased postnatal day 10 brain DNA content by 28%, suggesting a role for IGF-1 in brain growth control. These results demonstrate a mitogenic role for IGF-1 that tightly controls both positive and negative cell cycle regulators, and indicate that the PI3K/Akt pathway mediates IGF-1 mitogenic signaling during corticogenesis.
Spatiotemporal Patterns of Cortical Activity with Bilateral Cochlear Implants in Congenital Deafness
Authors: Kral Andrej , Tillein Jochen , Hubka Peter , Schiemann Dorrit , Heid Silvia , Hartmann Rainer , Engel Andreas Karl
Published: January 2009

Congenital deafness affects developmental processes in the auditory cortex. In this study, local field potentials (LFPs) were mapped at the cortical surface with microelectrodes in response to cochlear implant stimulation. LFPs were compared between hearing controls and congenitally deaf cats (CDCs). Pulsatile electrical stimulation initially evoked cortical activity in the rostral parts of the primary auditory field (A1). This progressed both in the approximate dorsoventral direction (along the isofrequency stripe) and in the rostrocaudal direction. The dorsal branch of the wavefront split into a caudal branch (propagating in A1) and another smaller one propagating rostrally into the AAF (anterior auditory field). After the front reached the caudal border of A1, a “reflection wave” appeared, propagating back rostrally. In total, the waves took ∼13–15 ms to propagate along A1 and return back. In CDCs, the propagation pattern was significantly disturbed, with a more synchronous activation of distant cortical regions. The maps obtained from contralateral and ipsilateral stimulation overlapped in both groups of animals. Although controls showed differences in the latency–amplitude patterns, cortical waves evoked by contralateral and ipsilateral stimulation were more similar in CDCs. Additionally, in controls, LFPs with contralateral and ipsilateral stimulation were more similar in caudal A1 than in rostral A1. This dichotomy was lost in deaf animals. In conclusion, propagating cortical waves are specific for the contralateral ear, they are affected by auditory deprivation, and the specificity of the cortex for stimulation of the contralateral ear is reduced by deprivation.
Propagation of Sinusoidal Electrical Waves along the Spinal Cord during a Fictive Motor Task
Authors: Cuellar Carlos A. , Tapia Jesus A. , Juárez Victoria , Quevedo Jorge , Linares Pablo , Martínez Lourdes , Manjarrez Elias
Published: January 2009

We present for the first time direct electrophysiological evidence of the phenomenon of traveling electrical waves produced by populations of interneurons within the spinal cord. We show that, during a fictive rhythmic motor task, scratching, an electrical field potential of spinal interneurons takes the shape of a sinuous wave, “sweeping” the lumbosacral spinal cord rostrocaudally with a mean speed of ∼0.3 m/s. We observed that traveling waves and scratching have the same cycle duration and that duration of the flexor phase, but not of the extensor phase, is highly correlated with the cycle duration of the traveling waves. Furthermore, we found that the interneurons from the deep dorsal horn and the intermediate nucleus can generate the spinal traveling waves, even in the absence of motoneuronal activity. These findings show that the sinusoidal field potentials generated during fictive scratching could be a powerful tool to disclose the organization of central pattern generator networks.
TRPV1 Expression Defines Functionally Distinct Pelvic Colon Afferents
Authors: Malin Sacha A. , Christianson Julie A. , Bielefeldt Klaus , Davis Brian M.
Published: January 2009

Changes in primary sensory neurons are likely to contribute to the emergence of chronic visceral pain. An important step in understanding visceral pain is the development of comprehensive phenotypes that combines functional and anatomical properties for these neurons. We developed a novelex vivophysiology preparation in mice that allows intracellular recording from colon sensory neurons during colon distension, in the presence and absence of pharmacologic agents. This preparation also allows recovery of functionally characterized afferents for histochemical analysis. Recordings obtained from L6 dorsal root ganglion cells in C57BL/6 mice identified two distinct populations of distension-responsive colon afferents: high-firing frequency (HF) and low-firing frequency (LF) cells. Fluid distension of the colon elicited rapid firing (>20 Hz) in HF cells, whereas LF cells seldom fired >5 Hz. Distension response thresholds were significantly lower in HF cells (LF, 17.5 ± 1.1 cmH2O; HF, 2.6 ± 1.0 cmH2O). Responses of most LF afferents to colon distension were sensitized by luminal application of capsaicin (1 μm; 8 of 9 LF cells), mustard oil (100 μm; 10 of 12 LF cells), and low pH (pH 4.0; 5 of 6 LF cells). In contrast, few HF afferents were sensitized by capsaicin (3 of 9), mustard oil (2 of 7), or low pH (1 of 6) application. Few HF afferents (4 of 23) expressed the capsaicin receptor, TRPV1. In contrast, 87% (25 of 29) of LF afferents expressed TRPV1. TRPV1 has been shown to be required for development of inflammatory hyperalgesia. These results suggest a unique functional role of TRPV1-positive colon afferents that could be exploited to design specific therapies for visceral hypersensitivity.
Non-Nuclear WldSDetermines Its Neuroprotective Efficacy for Axons and SynapsesIn Vivo
Authors: Beirowski Bogdan , Babetto Elisabetta , Gilley Jon , Mazzola Francesca , Conforti Laura , Janeckova Lucie , Magni Giulio , Ribchester Richard R. , Coleman Michael P.
Published: January 2009

Axon degeneration contributes widely to neurodegenerative disease but its regulation is poorly understood. The Wallerian degeneration slow (WldS) protein protects axons dose-dependently in many circumstances but is paradoxically abundant in nuclei. To test the hypothesis that WldSacts within nucleiin vivo, we redistributed it from nucleus to cytoplasm in transgenic mice. Surprisingly, instead of weakening the phenotype as expected, extranuclear WldSsignificantly enhanced structural and functional preservation of transected distal axons and their synapses. In contrast to native WldSmutants, distal axon stumps remained continuous and ultrastructurally intact up to 7 weeks after injury and motor nerve terminals were robustly preserved even in older mice, remaining functional for 6 d. Moreover, we detect extranuclear WldSfor the first timein vivo, and higher axoplasmic levels in transgenic mice with WldSredistribution. Cytoplasmic WldSfractionated predominantly with mitochondria and microsomes. We conclude that WldScan act in one or more non-nuclear compartments to protect axons and synapses, and that molecular changes can enhance its therapeutic potential.
Mood Influences Supraspinal Pain Processing Separately from Attention
Authors: Villemure Chantal , Bushnell M. Catherine
Published: January 2009

Studies show that inducing a positive mood or diverting attention from pain decreases pain perception. Nevertheless, induction manipulations, such as viewing interesting movies or performing mathematical tasks, often influence both emotional and attentional states. Imaging studies have examined the neural basis of psychological pain modulation, but none has explicitly separated the effects of emotion and attention. Using odors to modulate mood and shift attention from pain, we previously showed that the perceptual consequences of changing mood differed from those of altering attention, with mood primarily altering pain unpleasantness and attention preferentially altering pain intensity. These findings suggest that brain circuits involved in pain modulation provoked by mood or attention are partially separable. Here we used functional magnetic resonance imaging to directly compare the neurocircuitry involved in mood- and attention-related pain modulation. We manipulated independently mood state and attention direction, using tasks involving heat pain and pleasant and unpleasant odors. Pleasant odors, independent of attentional focus, induced positive mood changes and decreased pain unpleasantness and pain-related activity within the anterior cingulate (ACC), medial thalamus, and primary and secondary somatosensory cortices. The effects of attentional state were less robust, with only the activity in anterior insular cortex (aIC) showing possible attentional modulation. Lateral inferior frontal cortex [LinfF; Brodmann's area (BA) 45/47] activity correlated with mood-related modulation, whereas superior posterior parietal (SPP; BA7) and entorhinal activity correlated with attention-related modulation. ACC activity covaried with LinfF and periacqueductal gray activity, whereas aIC activity covaried with SPP activity. These findings suggest that separate neuromodulatory circuits underlie emotional and attentional modulation of pain.
Encoding of Gustatory Working Memory by Orbitofrontal Neurons
Authors: Lara Antonio H. , Kennerley Steven W. , Wallis Jonathan D.
Published: January 2009

The content model regarding the functional organization of working memory in prefrontal cortex (PFC) states that different PFC areas encode different types of information in working memory depending on their afferent connections with other brain areas. Previous studies that tested this model focused on visual, auditory and somatosensory information. However, posterior areas processing this information project to widespread and overlapping regions of lateral PFC, making it difficult to establish the veracity of the model. In contrast, gustatory information enters PFC via orbitofrontal cortex (OFC), and so the content model would argue that OFC should be responsible for maintaining gustatory information in working memory. To test this, we recorded the activity of single neurons throughout PFC and gustatory cortex (GUS) from two subjects while they performed a gustatory delayed-match-to-sample task with intervening gustatory distraction. Neurons that encoded the identity of the gustatory stimulus across the delay, consistent with a role in gustatory working memory, were most prevalent in OFC and GUS compared with dorsolateral PFC and ventrolateral PFC. Gustatory information in OFC was more resilient to intervening distraction, paralleling previous findings regarding visual working memory processes in PFC and posterior sensory cortex. Our findings provide support for the content model of working memory organization. Maintaining gustatory information may be one aspect of a wider function for OFC in reward working memory that could contribute to its role in decision-making.
Receptive Fields of Retinal Bipolar Cells Are Mediated by Heterogeneous Synaptic Circuitry
Authors: Zhang Ai-Jun , Wu Samuel M.
Published: January 2009

Center-surround antagonistic receptive field (CSARF) organization is the basic synaptic circuit that serves as elementary building blocks for spatial information processing in the visual system. Cells with such receptive fields converge into higher-order visual neurons to form more complex receptive fields. Retinal bipolar cells (BCs) are the first neurons along the visual pathway that exhibit CSARF organization. BCs have been classified according to their response polarities and rod/cone inputs, and they project signals to target cells at different sublaminae of the inner plexiform layer. On the other hand, CSARFs of various types of BCs have been assumed be organized the same way. Here we examined center and surround responses of over 250 salamander BCs, and demonstrated that different types of BCs exhibit different patterns of dye coupling, receptive field center size, surround response strength, and conductance changes associated with center and surround responses. We show that BC receptive field center sizes varied with the degree of BC–BC coupling, and that surround responses of different BCs are mediated by different combinations of five lateral synaptic pathways mediated by the horizontal cells and amacrine cells. The finding of heterogeneous receptive field circuitry fundamentally challenges the common assumption that CSARFs of different subtypes of visual neurons are mediated by the same synaptic pathways. BCs carrying different visual signals use different synaptic circuits to process spatial information, allowing shape and contrast computation be differentially modulated by various lighting and adaptation conditions.
Endogenous Truncated TrkB.T1 Receptor Regulates Neuronal Complexity and TrkB Kinase Receptor FunctionIn Vivo
Authors: Carim-Todd Laura , Bath Kevin G. , Fulgenzi Gianluca , Yanpallewar Sudhirkumar , Jing Deqiang , Barrick Colleen A. , Becker Jodi , Buckley Hannah , Dorsey Susan G. , Lee Francis S. , Tessarollo Lino
Published: January 2009

Pathological orin vitrooverexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific physiological functions and its effect on endogenous TrkB kinase signalingin vivo. We found that TrkB.T1-deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and long-term potentiation.In vivoreduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our results suggest that, at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signalingin vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.