bluuebunny/crossref_metadata_2025 huggingface dataset:
Ems and Nkx6 are central regulators in dorsoventral patterning of the Drosophila brain
Authors: Seibert Janina , Volland Dagmar , Urbach Rolf
Published: November 2009

In central nervous system development, the identity of neural stem cells (neuroblasts) critically depends on the precise spatial patterning of the neuroectoderm in the dorsoventral (DV) axis. Here, we uncover a novel gene regulatory network underlying DV patterning in the Drosophila brain, and show that the cephalic gap gene empty spiracles (ems) and the Nk6 homeobox gene (Nkx6) encode key regulators. The regulatory network implicates novel interactions between these and the evolutionarily conserved homeobox genes ventral nervous system defective (vnd), intermediate neuroblasts defective (ind) and muscle segment homeobox (msh). We show that Msh cross-repressively interacts with Nkx6 to sustain the boundary between dorsal and intermediate neuroectoderm in the tritocerebrum (TC) and deutocerebrum (DC), and that Vnd positively regulates Nkx6 by suppressing Msh. Remarkably, Ems is required to activate Nkx6, ind and msh in the TC and DC, whereas later Nkx6 and Ind act together to repress ems in the intermediate DC. Furthermore, the initially overlapping expression of Ems and Vnd in the ventral/intermediate TC and DC resolves into complementary expression patterns due to cross-repressive interaction. These results indicate that the anteroposterior patterning gene ems controls the expression of DV genes, and vice versa. In addition, in contrast to regulation in the ventral nerve cord, cross-inhibition between homeodomain factors (between Ems and Vnd, and between Nkx6 and Msh) is essential for the establishment and maintenance of discrete DV gene expression domains in the Drosophila brain. This resembles the mutually repressive relationship between pairs of homeodomain proteins that pattern the vertebrate neural tube in the DV axis.
Two populations of endochondral osteoblasts with differential sensitivity to Hedgehog signalling
Authors: Hammond Christina Lindsey , Schulte-Merker Stefan
Published: November 2009

Hedgehog (Hh) signalling has been implicated in the development of osteoblasts and osteoclasts whose balanced activities are critical for proper bone formation. As many mouse mutants in the Hh pathway are embryonic lethal, questions on the exact effects of Hh signalling on osteogenesis remain. Using zebrafish, we show that there are two populations of endochondral osteoblasts with differential sensitivity to Hh signalling. One, formed outside the cartilage structure, requires low levels of Hh signalling and fails to differentiate in Indian hedgehog mutants. The other derives from chondrocytes and requires higher levels of Hh signalling to form. This latter population develops significantly earlier in mutants with increased Hh signalling, leading to premature endochondral ossification, and also fails to differentiate in Indian hedgehog mutants, resulting in severely delayed endochondral ossification. Additionally, we demonstrate that the timing of first osteoclast activity positively correlates to Hh levels in both endochondral and dermal bone.
Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development
Authors: Seifert Ashley W. , Bouldin Cortney M. , Choi Kyung-Suk , Harfe Brian D. , Cohn Martin J.
Published: November 2009

Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans.
Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons
Authors: Chi Xian Xuan , Schmutzler Brian S. , Brittain Joel M. , Wang Yuying , Hingtgen Cynthia M. , Nicol Grant D. , Khanna Rajesh
Published: November 2009

Collapsin response mediator proteins (CRMPs) mediate signal transduction of neurite outgrowth and axonal guidance during neuronal development. Voltage-gated Ca2+ channels and interacting proteins are essential in neuronal signaling and synaptic transmission during this period. We recently identified the presynaptic N-type voltage-gated Ca2+ channel (Cav2.2) as a CRMP-2-interacting partner. Here, we investigated the effects of a functional association of CRMP-2 with Cav2.2 in sensory neurons. Cav2.2 colocalized with CRMP-2 at immature synapses and growth cones, in mature synapses and in cell bodies of dorsal root ganglion (DRG) neurons. Co-immunoprecipitation experiments showed that CRMP-2 associates with Cav2.2 from DRG lysates. Overexpression of CRMP-2 fused to enhanced green fluorescent protein (EGFP) in DRG neurons, via nucleofection, resulted in a significant increase in Cav2.2 current density compared with cells expressing EGFP. CRMP-2 manipulation changed the surface levels of Cav2.2. Because CRMP-2 is localized to synaptophysin-positive puncta in dense DRG cultures, we tested whether this CRMP-2-mediated alteration of Ca2+ currents culminated in changes in synaptic transmission. Following a brief high-K+-induced stimulation, these puncta became loaded with FM4-64 dye. In EGFP and neurons expressing CRMP-2–EGFP, similar densities of FM-loaded puncta were observed. Finally, CRMP-2 overexpression in DRG increased release of the immunoreactive neurotransmitter calcitonin gene-related peptide (iCGRP) by ∼70%, whereas siRNA targeting CRMP-2 significantly reduced release of iCGRP by ∼54% compared with control cultures. These findings support a novel role for CRMP-2 in the regulation of N-type Ca2+ channels and in transmitter release.
ArabidopsisRab-E GTPases exhibit a novel interaction with a plasma-membrane phosphatidylinositol-4-phosphate 5-kinase
Authors: Camacho Luísa , Smertenko Andrei P. , Pérez-Gómez José , Hussey Patrick J. , Moore Ian
Published: November 2009

Rab GTPases of the Arabidopsis Rab-E subclass are related to mammalian Rab8 and are implicated in membrane trafficking from the Golgi to the plasma membrane. Using a yeast two-hybrid assay, Arabidopsis phosphatidylinositol-4-phosphate 5-kinase 2 (PtdIns(4)P 5-kinase 2; also known as PIP5K2), was shown to interact with all five members of the Rab-E subclass but not with other Rab subclasses residing at the Golgi or trans-Golgi network. Interactions in yeast and in vitro were strongest with RAB-E1d[Q74L] and weakest with the RAB-E1d[S29N] suggesting that PIP5K2 interacts with the GTP-bound form. PIP5K2 exhibited kinase activity towards phosphatidylinositol phosphates with a free 5-hydroxyl group, consistent with PtdIns(4)P 5-kinase activity and this activity was stimulated by Rab binding. Rab-E proteins interacted with PIP5K2 via its membrane occupancy and recognition nexus (MORN) domain which is missing from animal and fungal PtdIns(4)P 5-kinases. In plant cells, GFP:PIP5K2 accumulated at the plasma membrane and caused YFP:RAB-E1d to relocate there from its usual position at the Golgi. GFP:PIP5K2 was rapidly turned over by proteasomal activity in planta, and overexpression of YFP:PIP5K2 caused pleiotropic growth abnormalities in transgenic Arabidopsis. We propose that plant cells exhibit a novel interaction in which PIP5K2 binds GTP-bound Rab-E proteins, which may stimulate temporally or spatially localized PtdIns(4,5)P2 production at the plasma membrane.
Eeyarestatin I inhibits Sec61-mediated protein translocation at the endoplasmic reticulum
Authors: Cross Benedict C. S. , McKibbin Craig , Callan Anna C. , Roboti Peristera , Piacenti Michela , Rabu Catherine , Wilson Cornelia M. , Whitehead Roger , Flitsch Sabine L. , Pool Martin R. , High Stephen , Swanton Eileithyia
Published: November 2009

Production and trafficking of proteins entering the secretory pathway of eukaryotic cells is coordinated at the endoplasmic reticulum (ER) in a process that begins with protein translocation via the membrane-embedded ER translocon. The same complex is also responsible for the co-translational integration of membrane proteins and orchestrates polypeptide modifications that are often essential for protein function. We now show that the previously identified inhibitor of ER-associated degradation (ERAD) eeyarestatin 1 (ESI) is a potent inhibitor of protein translocation. We have characterised this inhibition of ER translocation both in vivo and in vitro, and provide evidence that ESI targets a component of the Sec61 complex that forms the membrane pore of the ER translocon. Further analyses show that ESI acts by preventing the transfer of the nascent polypeptide from the co-translational targeting machinery to the Sec61 complex. These results identify a novel effect of ESI, and suggest that the drug can modulate canonical protein transport from the cytosol into the mammalian ER both in vitro and in vivo.
The integrin adhesion complex changes its composition and function during morphogenesis of an epithelium
Authors: Delon Isabelle , Brown Nicholas H.
Published: November 2009

Cell adhesion to the extracellular matrix (ECM) is mediated by the integrin family of transmembrane receptors. Integrins link ECM ligands to the cytoskeleton, providing strong attachment to enable cell-shape change and tissue integrity. This connection is made possible by an intracellular complex of proteins, which links to actin filaments and controls signalling cascades that regulate cytoskeletal rearrangements. We have identified stress-fibre-associated focal adhesions that change their composition during tissue morphogenesis. Early expression of αPS1βPS integrin decreases the levels of the actin-nucleating factors Enabled, Diaphanous and profilin, as well as downregulating the amount of F-actin incorporated into the stress fibres. As follicle cells mature in their developmental pathway and become squamous, the integrin in the focal adhesions changes from αPS1βPS to αPS2βPS. During the switch, stress fibres increase their length and change orientation, first changing by 90° and then reorienting back. The normal rapid reorientation requires new expression of αPS2βPS, which also permits recruitment of the adaptor protein tensin. Unexpectedly, it is the extracellular portion of the αPS2 subunit that provides the specificity for intracellular recruitment of tensin. Molecular variation of the integrin complex is thus a key component of developmentally programmed morphogenesis.
Colchicine for the Primary and Secondary Prevention of Pericarditis: An Update
Authors: Kuo I fan , Pearson Glen J , Koshman Sheri L
Published: November 2009

Objective:

To review the efficacy and safety of colchicine as primary and secondary prophylaxis for pericarditis.

Data Sources:

We searched MEDLINE, EMBASE, PubMed, BSOSIS Previews. International Pharmaceutical Abstracts. Web of Science, and CENTRAL for controlled studies from database inception date to July 2009. Search terms included colchicine, pericarditis, and postpericardiotomy syndrome (PPS).

Study Selection and Data Extraction:

Prospective, randomized, controlled trials investigating the use of colchicine in preventing pericarditis were included. Data extracted included design, inclusion criteria, demographics, interventions, background therapy, and pericarditis-related clinical outcomes.

Data Synthesis:

Data were synthesized qualitatively, given variable study designs. Three trials were identified. A single trial examining primary prevention evaluated the use of colchicine versus placebo for preventing PPS in patients undergoing cardiopulmonary bypass grafting. No significant reduction in PPS was found. Two studies examined secondary prevention of pericarditis, comparing colchicine plus aspirin versus aspirin alone. One study examined using these comparators to treat a first episode of pericarditis. After 3 months, there was a significant reduction in recurrent pericarditis with colchicine plus aspirin (11.7% vs 33%; p = 0,009). Another study examined this same regimen in recurrent pericarditis, finding a significant reduction in recurrence after 6 months (21% vs 45%;p = 0.02).

Conclusions:

Despite limitations in study designs, current evidence suggests a role for colchicine in the secondary prophylaxis for recurrent pericarditis. The evidence for use of colchicine as primary prophylaxis in PPS is indeterminate; therefore, colchicine cannot be recommended routinely. While colchicine should be recommended for the prevention of recurrent pericarditis, questions regarding the optimal regimen and long-term safety profile need to be further elucidated.
Association Between Exposure to Topical Tacrolimus or Pimecrolimus and Cancers
Authors: Hui Rita L , Lide William , Chan James , Schottinger Joanne , Yoshinaga Monica , Millares Mirta
Published: November 2009

Background:

The Food and Drug Administration has issued a public health advisory regarding cancer risk from topical calcineurin inhibitors.

Objective:

To compare the rates of cancer among patients with common dermatologic conditions who were exposed or not exposed to topical calcineurin inhibitors.

Methods:

A retrospective cohort observational study used data from an integrated healthcare delivery system on 953,064 subjects with diagnoses of atopic dermatitis or eczema between 2001 and December 2004. The main endpoint was initial cancer diagnosis. Chart review was performed to confirm cancer diagnosis in the subjects exposed to topical calcineurin inhibitors when any particular cancer rate was at least 3 times higher than that in unexposed subjects. Data were analyzed using the Cox proportional hazards model.

Results:

Age- and sex-adjusted hazard ratios for all cancers were 0.93 (95% CI 0.81 to 1.07; p = 0.306) for tacrolimus-exposed versus -unexposed subjects and 1.15 (95% CI 0.99 to 1.31; p = 0.054) for pimecrolimus-exposed versus -unexposed subjects. T-cell lymphoma was the only cancer associated with a significantly increased risk among subjects exposed to tacrolimus (HR = 5.04, 95% CI 2.39 to 10.63; p < 0.001) or pimecrolimus (HR = 3.76, 95% CI 1.71 to 8.28; p = 0.010). Subsequent chart review of subjects in the exposed group with T-cell lymphoma found that 4 of 16 had skin lesions that were suspected to be the early lesions of T-cell lymphoma prior to exposure to tacrolimus or pimecrolimus. After these 4 cases were excluded, the age and sex hazard ratio for T-cell lymphoma was 5.44 (95% CI 2.51 to 11.79; p < 0.001) for tacrolimus and 2.32 (95% CI 0.89 to 6.07; p = 0.086) for pimecrolimus. There was no statistically significantly increased risk for other subgroups of cancer, including melanoma.

Conclusions:

Exposure to topical tacrolimus or pimecrolimus was not associated with an increase in the overall cancer rate. Use of topical tacrolimus may be associated with an increased risk of T-cell lymphoma.
Students' approaches to learning and their experiences of the teaching–learning environment in different disciplines
Authors: Parpala Anna. , Lindblom‐Ylänne Sari. , Komulainen Erkki. , Litmanen Topi. , Hirsto Laura.
Published: November 2009

Background

There is evidence of disciplinary variation in students' approaches to learning. Furthermore, previous research has shown that students' approaches are related to their perceptions of the learning environment.

Aim

The overall objective of the study was to analyse combinations of approaches to learning among undergraduates in different disciplines. More precisely, the aim was to cluster students on the basis of their scores on different items measuring approaches to learning, and to explore the relationship between the clusters and both the disciplines of the students and their perceptions of the teaching–learning environment.

Sample

A total of 2,509 students participated in the study.

Methods

The students were asked to complete an on‐line questionnaire, which was a revised version of the Experience of Teaching and Learning Questionnaire. It included items covering approaches to learning and perceptions of the teaching–learning environment.

Results

The students were classified in four clusters. There were significant differences in how the respondents from the 10 faculties were represented in these clusters. There were also differences in their perceptions of the teaching–learning environment in the different faculties.

Conclusions

It appears that there is disciplinary variation in approaches to learning. Furthermore, the results indicate that both approaches to learning and the discipline have an effect on students' experiences of the teaching–learning environment.
Parental and school effects on children's political attitudes in Northern Ireland
Authors: Stringer Maurice. , Irwing Paul. , Giles Melanie. , McClenahan Carol. , Wilson Ronnie. , Hunter John.
Published: November 2009

Background

Recent research has suggested that intergroup contacts with out‐group members can both reduce prejudice and is associated with attitude change.

Aim

This study extends prior work in Northern Ireland to examine parental and schooling effects on children's attitudes in a post‐conflict environment.

Sample

A large‐scale cross‐sectional survey of secondary schoolchildren (N = 1,732) and their parents (N = 800) in Northern Ireland assessed the effects of in‐school and out‐of‐school intergroup contacts on intergroup attitudes.

Method

Multivariate analysis of variance was employed to examine associations between children's political attitudes and parental, group membership, school, and contact variables.

Conclusions

The results suggest that parental attitudes, group membership, and cross‐group contacts explain the majority of variance (58%) in children's political attitudes. The findings provide a comprehensive account of the factors that influence children's political attitudes within a deeply divided society and offer teachers and educationalists a way to improve community relations in a segregated society.
Espacios vedados y hroes desvalidos: La nia de luto y el cine espaol de los aos sesenta
Authors: Sotomayor Carmen
Published: November 2009

Forbidden spaces and helpless heroes: The Girl in Mourning and 1960s Spanish cinema examines Manuel Summers' second film, La nia de luto, released in 1964. It argues that Summers' popular narrative frame goes beyond its apparent tipismo (typical story in picturesque settings)
to present its viewers with the angst of youth. Through a humorous portrait of life in an Andalusian village, Summers reveals the lack of personal freedom and choice experienced by young people during the sixties in Francoist Spain, as well as the constraining social forces around them.
Public service radio facing the new competitive environment in Catalonia
Authors: Bonet Montse , Fernndez-Quijada David
Published: November 2009

The European digitization and technological convergence process has served to deepen the crisis that all public broadcasters have been experiencing in Europe over the last 20 years. Yet, when the transition to digital broadcasting is discussed, this has mainly referred to the medium
of television. Radio on the other hand, a medium with greater capillarity (in the sense of having deeper local roots and networks), has been dealing with its own crisis. This article outlines the main characteristics and problems of public service radio in Catalonia, arising from a study carried
out on its structure and the programming it offers.1

1This research was commissioned by the General Secretary for Media in the Department of Culture and Media of the Catalan Autonomous
Government, the Generalitat de Catalunya, passed on to the authors via the Institut de la Comunicaci (InCom, Communication Institute) of the Universitat Autnoma de Barcelona (UAB, Autonomous University of Barcelona). 
Amrica en Sevilla: la materializacin del espritu neoimperial en la Exposicin Iberoamericana de 1929
Authors: Souto Ana
Published: November 2009

This article considers the representation of the relationships between Spain and its former colonies at the Ibero-American Exhibition in Seville in 1929. The analysis provides two main arguments. First, it will be argued that the styles of the Plaza de Amrica named neoplateresque,
neomudejar and neogthic were chosen to stand for a new form of imperialism based on a Hispanoamerican identity, with Spain once again as the leader, although this time spiritual rather than political. Second, the article discusses how this neo-imperialist spirit was reinforced by
the pavilions of the Latin American countries by underlining the common cultural elements with Spain based on language, religion and the cultural idea of race, by creating buildings in the colonial baroque style, either in a neo-colonial or neomestizo way, thereby stating their affiliation
to the pan-hispanist spirit.
St. James the Moor-slayer, a new challenge to Spanish national discourse in the twenty-first century
Authors: Garca Javier Domnguez
Published: November 2009

The arguments presented on the following pages will explore the debate that revolves around the relationship between St. James (Santiago, patron saint of Spain) and Spanish contemporary political discourses. The author critiques appropriations and re-enactments of St. James made by
the dominant hegemonic practices while focusing on the recent polemic surrounding the removal of the statue of the Moor-slayer (Santiago Matamoros) from the entrance to the cathedral of Santiago de Compostela. This timely debate could potentially lead to a new critical view of postmodern
appropriations of medieval iconology, as it argues that hegemonic discourses in Spain emphasize particular narratives, both discursive or symbolic in form, in order to relegate others to oblivion.
Mapping a beautiful voice: theoretical considerations
Authors: Himonides Evangelos
Published: November 2009

The prime purpose of this article is to draw on a range of diverse literatures to clarify those elements that are perceived to constitute a beautiful sung performance. The text rehearses key findings from existing literatures in order to determine the extent to which particular elements might appear the most salient for an individual listener and also quantifiable (in the sense of being open to empirical study). The article concludes with a theoretical framework for the elements that are likely to construct and shape our responses to particular sung performances.
Some features of children's composing in a computer-based environment: the influence of age, task familiarity and formal instrumental music instruction
Authors: Hewitt Allan
Published: November 2009

760 children aged 8 to 12 years old composed 1,696 short melodies using a computer-based software application. As well as providing an appropriate composing environment, the software maintained a detail event-driven log of all user interactions. Session logs were used as the basis of
a detailed behavioural analysis of children's composing processes, exploring the influence of three variables (age, task familiarity and formal instrumental music tuition) on composing processes. Results suggested that older children tended to engage in less exploratory composing behaviour
in comparison to younger participants, such as listening to their emerging melodies or trying out different notes. Participants receiving formal instrumental music tuition were far less likely to use the exploratory functions of the software in comparison to their non-expert peers. Older children
worked faster than younger children, and were more efficient in their use of the software functions. Increased familiarity with the software was accompanied by greater speed in interaction, regardless of instrumental expertise. Implications for music composition pedagogy and future research
in musical creativity are discussed.
Peer learning in the music studio
Authors: Jones Christopher , King Andrew
Published: November 2009

This paper sets out the findings of a pilot study for implementing a peer tutoring scheme within the recording studio. It examines peer learning in different contexts and relates this to recording studio practice. It outlines the current problems students face during out-of-hours access to the recording studios and suggests that the implementation of a peer tutoring scheme could provide a valuable support tool for staff and students. A purposive sample of twelve students (nine first-year and three third-year undergraduates), were selected after a preliminary studio test in which the data were ranked. The participants were subsequently divided into three mentoring groups, each containing three first-year students accompanied by one third-year student who acted as a peer tutor. This study identifies how peer learning may help foster collaborative learning and what issues arise for those involved. It also investigates the dynamics between a student mentor (tutor) and student peer (tutee), and provides signposts for a follow-up study.
Reviews
Authors: Daynes Helen
Published: November 2009

Recorded Music: Philosophical and Critical Reflections, M. Doantan-Dack (ed.) (2008), London: Middlesex University Press, p. 374, ISBN: 978 1 904750 277. Paperback. 30.00
Reviews
Authors: Moore Adrian
Published: November 2009

Understanding the Art of Sound Organization,
Leigh Landy, (2007), London: MIT Press, pp. 203303, ISBN 978-0-262-12292-4, Softback, 24
Reviews
Authors: Himonides Evangelos
Published: November 2009

From Pac-Man to Pop Music: Interactive Audio in Games and New Media (Ashgate Popular and Folk Music Series). Published May 2008, ISBN: 978-0-7546-6200-6 (Hardback), 49.50
Alejandro Gonzlez Irritu: director without borders
Authors: Tierney Dolores
Published: November 2009

This article seeks to question and revise the boundaries of Mexican National Cinema, in order to make it possible to look at films made by Mexican directors in the United States and elsewhere as part of the project of the country's national cinema. The article looks specifically at
Alejandro Gonzlez Irritu's trilogy (Amores perros, 21 Grams, Babel) exploring not only how these films, although made in different countries and political contexts, share many of the same visual, stylistic and narrative strategies, but also what this might suggest about the possibilities
of a resistant and contestatory cinema, made in the United States but still broadly adherent to the concepts of a Third Worldist, and specifically Mexican, culture and ideology.
Imagining Englishness: the mapping of identity in My Summer of Love (2004) by Pawel Pawlikowski
Authors: Rydzewska Joanna
Published: November 2009

This article will look at the way in which the thematic and aesthetic discourses of My Summer of Love imagine and problematize the notion of a British/English identity. As an allegorical story of Sapphic love and conflict between two teenage girls, working-class Mona and upper-class
Tamsin, My Summer of Love explores an English identity by mapping it onto the British class system. As an outsider to British/English culture by dint of his Polish origin, Pawlikowski negotiates his perception of British/English identity by extrapolating the myths that contribute to
the creation of the imagined British community (mainly the South/North divide of England) and conventions of British cinema (mainly the British social realism with its emblematic That Long Shot of Our Town from That Hill). However, the prominence of authorial discourse in this phenomenological
project of getting to the heart of English identity as well as realist aesthetic discourses also hint at his nomadic sensibility and the allegiance to various European New Waves.
Nothing counts: shot and event in Werckmeister Harmonies
Authors: Marchant Steven
Published: November 2009

This essay examines the nature of the shot in Bla Tarr'sWerckmeister Harmonies(2000), asking what is achieved in Tarr's decision to stage the film as a series of sequence shots. It considers the shot as an event and argues that the distinctive quality of the Werckmeister shot rests in its being simultaneously concrete and void. It contrasts Tarr's film with the work of Michelangelo Antonioni, who is understood as a key precursor. Is there a pure form of the event? A solar eclipse, a glass of water thrown on hot coals, a walk through the town at midnight the variety of events is infinite, yet the occurrence, the happening, is that the same in every case? Can we separate the pure form of the event from what happens in a given instance? Is the happening different from what happens? Whether sunrise or dice throw, planetary movement or drunken stumble, is the occurrence always the same? Is there one event repeated in every event?
Review
Authors: Gleghorn Charlotte
Published: November 2009

The Persistence of Whiteness: Race and Contemporary Hollywood Cinema (2008), Daniel Bernardi (ed.), Abingdon: Routledge, xxvi + 390 pp., ISBN13: 978-0-415-77413-0, Paperback, 18.99
Hyperdopaminergic Tone Erodes Prefrontal Long-Term Potential via a D2Receptor-Operated Protein Phosphatase Gate
Authors: Xu Tai-Xiang , Sotnikova Tatyana D. , Liang Chengyu , Zhang Jingping , Jung Jae U. , Spealman Roger D. , Gainetdinov Raul R. , Yao Wei-Dong
Published: November 2009

Dopamine (DA) plays crucial roles in the cognitive functioning of the prefrontal cortex (PFC), which, to a large degree, depends on lasting neural traces formed in prefrontal networks. The establishment of these permanent traces requires changes in cortical synaptic efficacy. DA, via the D1-class receptors, is thought to gate or facilitate synaptic plasticity in the PFC, with little role recognized for the D2-class receptors. Here we show that, when significantly elevated, DA erodes, rather than facilitates, the induction of long-term potentiation (LTP) in the PFC by acting at the far less abundant cortical D2-class receptors through a dominant coupling to the protein phosphatase 1 (PP1) activity in postsynaptic neurons. In mice with persistently elevated extracellular DA, resulting from inactivation of the DA transporter (DAT) gene, LTP in layer V PFC pyramidal neurons cannot be established, regardless of induction protocols. Acute increase of dopaminergic transmission by DAT blockers or overstimulation of D2receptors in normal mice have similar LTP shutoff effects. LTP in mutant mice can be rescued by a singlein vivoadministration of D2-class antagonists. Suppression of postsynaptic PP1 mimics and occludes the D2-mediated rescue of LTP in mutant mice and prevents the acute erosion of LTP by D2agonists in normal mice. Our studies reveal a mechanistically unique heterosynaptic PP1 gate that is constitutively driven by background DA to influence LTP induction. By blocking prefrontal synaptic plasticity, excessive DA may prevent storage of lasting memory traces in PFC networks and impair executive functions.
Differential Activity-Dependent Secretion of Brain-Derived Neurotrophic Factor from Axon and Dendrite
Authors: Matsuda Naoto , Lu Hui , Fukata Yuko , Noritake Jun , Gao Hongfeng , Mukherjee Sujay , Nemoto Tomomi , Fukata Masaki , Poo Mu-ming
Published: November 2009

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and differentiation during development and for synaptic function and plasticity in the mature brain. BDNF-containing vesicles are widely distributed and bidirectionally transported in neurons, and secreted BDNF can act on both presynaptic and postsynaptic cells. Activity-dependent BDNF secretion from neuronal cultures has been reported, but it remains unknown where the primary site of BDNF secretion is and whether neuronal activity can trigger BDNF secretion from axons and dendrites with equal efficacy. Using BDNF fused with pH-sensitive green fluorescent protein to visualize BDNF secretion, we found that BDNF-containing vesicles exhibited markedly different properties of activity-dependent exocytic fusion at the axon and dendrite of cultured hippocampal neurons. Brief spiking activity triggered a transient fusion pore opening, followed by immediate retrieval of vesicles without dilation of the fusion pore, resulting in very little BDNF secretion at the axon. On the contrary, the same brief spiking activity induced “full-collapse” vesicle fusion and substantial BDNF secretion at the dendrite. However, full vesicular fusion with BDNF secretion could occur at the axon when the neuron was stimulated by prolonged high-frequency activity, a condition neurons may encounter during epileptic discharge. Thus, activity-dependent axonal secretion of BDNF is highly restricted as a result of incomplete fusion of BDNF-containing vesicles, and normal neural activity induces BDNF secretion from dendrites, consistent with the BDNF function as a retrograde factor. Our study also revealed a novel mechanism by which differential exocytosis of BDNF-containing vesicles may regulate BDNF–TrkB signaling between connected neurons.
Neural Activity in the Middle Temporal Area and Lateral Intraparietal Area during Endogenously Cued Shifts of Attention
Authors: Herrington Todd M. , Assad John A.
Published: November 2009

We measured the behavioral time course of endogenously cued attentional shifts while recording from neurons in the middle temporal area (MT) and lateral intraparietal area (LIP) of two macaque monkeys. The monkeys were required to detect a subtle speed change of one of two continuously moving stimuli. The likely location of the speed change was cued throughout each trial but could switch at an unpredictable time. Attention was evident as an improvement in detection ability and reaction time at the cued location, and the focus of attention shifted over a 400 ms period in response to a switch of the cued stimulus. Attention modulated the ongoing neural response in both MT and LIP, and the sign of this modulation also rapidly shifted after a cue switch. Our data provide a framework for understanding the link between the neural and behavioral effects of attention. The responses of single neurons to the test stimulus in MT and LIP were correlated with stimulus detection and reaction time and, at the population level, a spike-rate threshold model was able to account for the effect of attention on detection rate and reaction time. In this view, the time course of the attentional shift can be understood as an interaction between the emerging attentional modulation and the neural response to the test stimulus in LIP. We also present evidence that the threshold model is not wholly explained by sensory (feedforward) information but may also be influenced by cognitive (feedback) processes at the time of stimulus detection.
Aβ Immunotherapy Protects Morphology and Survival of Adult-Born Neurons in Doubly Transgenic APP/PS1 Mice
Authors: Biscaro Barbara , Lindvall Olle , Hock Christoph , Ekdahl Christine T. , Nitsch Roger M.
Published: November 2009

The hippocampus is heavily affected by progressive neurodegeneration and β-amyloid pathology in Alzheimer's disease (AD). The hippocampus is also one of the few brain regions that generate new neurons throughout adulthood. Because hippocampal neurogenesis is regulated by both endogenous and environmental factors, we determined whether it benefits from therapeutic reduction of β-amyloid peptide (Aβ)-related toxicity induced by passive Aβ immunotherapy. Aβ immunotherapy of 8–9-month-old mice expressing familial AD-causing mutations in the amyloid precursor protein and presenilin-1 genes with an antibody against Aβ decreased compact β-amyloid plaque burden and promoted survival of newly born neurons in the hippocampal dentate gyrus. As these neurons matured, they exhibited longer dendrites with more complex arborization compared with newly born neurons in control-treated transgenic littermates. The newly born neurons showed signs of functional integration indicated by expression of the immediate-early geneZif268in response to exposure to a novel object. Aβ immunotherapy was associated with higher numbers of synaptophysin-positive synaptic boutons. Labeling dividing progenitor cells with a retroviral vector encoding green fluorescent protein (GFP) showed that Aβ immunotherapy restored the impaired dendritic branching, as well as the density of dendritic spines in new mature neurons. The presence of cellular prion protein (PrPc) on the dendrites of the GFP+newly born neurons is compatible with a putative role of PrPcin mediating Aβ-related toxicity in these cells. In addition, passive Aβ immunotherapy was accompanied by increased angiogenesis. Our data establish that passive Aβ immunotherapy can restore the morphological maturation of the newly formed neurons in the adult hippocampus and promote angiogenesis. These findings provide evidence for a role of Aβ immunotherapy in stimulating neurogenesis and angiogenesis in transgenic mouse models of AD, and they suggest the possibility that Aβ immunotherapy can recover neuronal and vascular functions in brains with β-amyloidosis.
The Synaptic Representation of Sound Source Location in Auditory Cortex
Authors: Chadderton Paul , Agapiou John P. , McAlpine David , Margrie Troy W.
Published: November 2009

A key function of the auditory system is to provide reliable information about the location of sound sources. Here, we describe how sound location is represented by synaptic input arriving onto pyramidal cells within auditory cortex by combining free-field acoustic stimulation in the frontal azimuthal plane within vivowhole-cell recordings. We found that subthreshold activity was panoramic in that EPSPs could be evoked from all locations in all cells. Regardless of the sound location that evoked the largest EPSP, we observed a slowing in the EPSP slope along the contralateral–ipsilateral plane that was reflected in a temporal sequence of peak EPSP times. Contralateral sounds evoked EPSPs with earlier peak times and consequently generated action potential firing with shorter latencies than ipsilateral sounds. Thus, whereas spiking probability reflected the region of space evoking the largest EPSP, across the population, synaptic inputs enforced a gradient of spike latency and precision along the horizontal axis. Therefore, within auditory cortex and regardless of preferred location, the time window of synaptic integration reflects sound source location and ensures that spatial acoustic information is represented by relative timings of pyramidal cell output.
Brain Control of Movement Execution Onset Using Local Field Potentials in Posterior Parietal Cortex
Authors: Hwang Eun Jung , Andersen Richard A.
Published: November 2009

The precise control of movement execution onset is essential for safe and autonomous cortical motor prosthetics. A recent study from the parietal reach region (PRR) suggested that the local field potentials (LFPs) in this area might be useful for decoding execution time information because of the striking difference in the LFP spectrum between the plan and execution states (Scherberger et al., 2005). More specifically, the LFP power in the 0–10 Hz band sharply rises while the power in the 20–40 Hz band falls as the state transitions from plan to execution. However, a change of visual stimulus immediately preceded reach onset, raising the possibility that the observed spectral change reflected the visual event instead of the reach onset. Here, we tested this possibility and found that the LFP spectrum change was still time locked to the movement onset in the absence of a visual event in self-paced reaches. Furthermore, we successfully trained the macaque subjects to use the LFP spectrum change as a “go” signal in a closed-loop brain-control task in which the animals only modulated the LFP and did not execute a reach. The execution onset was signaled by the change in the LFP spectrum while the target position of the cursor was controlled by the spike firing rates recorded from the same site. The results corroborate that the LFP spectrum change in PRR is a robust indicator for the movement onset and can be used for control of execution onset in a cortical prosthesis.
Dynorphin Opioid Peptides Enhance Acid-Sensing Ion Channel 1a Activity and Acidosis-Induced Neuronal Death
Authors: Sherwood Thomas W. , Askwith Candice C.
Published: November 2009

Acid-sensing ion channel 1a (ASIC1a) promotes neuronal damage during pathological acidosis. ASIC1a undergoes a process called steady-state desensitization in which incremental pH reductions desensitize the channel and prevent activation when the threshold for acid-dependent activation is reached. We find that dynorphin A and big dynorphin limit steady-state desensitization of ASIC1a and acid-activated currents in cortical neurons. Dynorphin potentiation of ASIC1a activity is independent of opioid or bradykinin receptor activation but is prevented in the presence of PcTx1, a peptide which is known to bind the extracellular domain of ASIC1a. This suggests that dynorphins interact directly with ASIC1a to enhance channel activity. Inducing steady-state desensitization prevents ASIC1a-mediated cell death during prolonged acidosis. This neuroprotection is abolished in the presence of dynorphins. Together, these results define ASIC1a as a new nonopioid target for dynorphin action and suggest that dynorphins enhance neuronal damage following ischemia by preventing steady-state desensitization of ASIC1a.
Why Sex Matters: Brain Size Independent Differences in Gray Matter Distributions between Men and Women
Authors: Luders Eileen , Gaser Christian , Narr Katherine L. , Toga Arthur W.
Published: November 2009

The different brain anatomy of men and women is both a classic and continuing topic of major interest. Among the most replicated and robust sex differences are larger overall brain dimensions in men, and relative increases of global and regional gray matter (GM) in women. However, the question remains whether sex-typical differences in brain size (i.e., larger male and smaller female brains) or biological sex itself account for the observed sex effects on tissue amount and distribution. Exploring cerebral structures in men and women with similar brain size may clarify the true contribution of biological sex. We thus examined a sample of 24 male and 24 female subjects with brains identical in size, in addition to 24 male and 24 female subjects with considerable brain size differences. Using this large set of brains (n= 96), we applied a well validated and automated voxel-based approach to examine regional volumes of GM. While we revealed significant main effects of sex, there were no significant effects of brain size (and no significant interactions between sex and brain size). When conductingpost hoctests, we revealed a number of regions where women had larger GM volumes than men. Importantly, these sex effects remained evident when comparing men and women with the same brain size. Altogether, our findings suggest that the observed increased regional GM volumes in female brains constitute sex-dependent redistributions of tissue volume, rather than individual adjustments attributable to brain size.
Cerebral and Cerebrospinal Processes Underlying Counterirritation Analgesia
Authors: Piché Mathieu , Arsenault Marianne , Rainville Pierre
Published: November 2009

Pain is a complex experience involving extensive interactions between brain and spinal cord processes. Various interventions that modulate pain, such as the application of a competing noxious stimulus (counterirritation), are thought to involve cerebrospinal regulation through diffuse noxious inhibitory controls (DNICs). However, no study has yet examined the relation between brain and spinal cord activity during counterirritation analgesia in humans. This fMRI study investigates brain responses to phasic painful electrical stimulation administered to the sural nerve to evoke a spinal nociceptive response (RIII reflex) before, during and after counterirritation induced by the immersion of the left contralateral foot in cold water. Responses are compared with a control condition without counterirritation. As expected, counterirritation produced robust pain inhibition with residual analgesia persisting during the recovery period. In contrast, RIII reflex amplitude was significantly decreased by counterirritation only in a subset of subjects. Modulatory effects of counterirritation on pain perception and spinal nociception were paralleled by decreased shock-evoked activity in pain-related areas. Individual changes in shock-evoked brain activity were specifically related to analgesia in primary somatosensory cortex (SI), anterior cingulate cortex and amygdala, and to RIII modulation in supplementary motor area and orbitofrontal cortex (OFC). Moreover, sustained activation induced by the counterirritation stimulus in the OFC predicted shock-pain decrease while sustained activity in SI and the periaqueductal gray matter predicted RIII modulation. These results provide evidence for the implication of at least two partly separable neural mechanisms underlying the effects of counterirritation on pain and spinal nociception in humans.
Brn3a and Nurr1 Mediate a Gene Regulatory Pathway for Habenula Development
Authors: Quina Lely A. , Wang Shirong , Ng Lydia , Turner Eric E.
Published: November 2009

The habenula is a dorsal diencephalic structure consisting of medial and lateral subnuclei and a principal output tract, the fasciculus retroflexus, which together form a link between the limbic forebrain and ventral midbrain. Here, we have used microarray and bioinformatic approaches in the mouse to show that the habenula is a distinctive molecular territory of the CNS, with a unique profile of neurotransmitter, ion channel, and regulatory factor expression. Neurons of the medial habenula and part of the lateral habenula express the transcription factor Brn3a/Pou4f1, and Brn3a-expressing habenular neurons project exclusively to the interpeduncular nucleus in the ventral midbrain. In Brn3a mutant embryos, the fasciculus retroflexus is directed appropriately, but habenular neurons fail to innervate their targets. Microarray analysis of Brn3a null embryos shows that this factor regulates an extensive program of habenula-enriched genes, but not generic neural properties. The orphan nuclear receptor Nurr1/Nr4a2 is coexpressed with Brn3a in the developing habenula, is downstream of Brn3a, and mediates expression of a subset of Brn3a-regulated transcripts. Together, these findings begin to define a gene regulatory pathway for habenula development in mammals.