bluuebunny/crossref_metadata_2025 huggingface dataset:
Mean Streets, Bad Boys, Drugs and Rock ‘n’ Roll: Morocco’s Urban Legends of the 21 st Century
Authors: Orlando Valérie K.
Published: May 2011

In the past decade, Moroccan filmmaking has documented the transitions taking place in contemporary society. Whether the films are made in French, Arabic, Berber, or a mixture of all three, language becomes secondary to the images that filmmakers seek to convey to their audiences. For the most part, films made since 1999, the year marking the end of the “Lead Years” ( Les Années de plomb , 1963–1999) under the dogmatic and repressive rule of King Hassan II, are socially engaging. Made in a social-realist style that seeks not only to entertain but also to educate audiences about the sociocultural and political transitions that are taking place in society, Moroccan filmmakers depict a culture on the move. History is being reviewed and retold to remind and educate Moroccans of and about the atrocities that took place during the Lead Years. Human rights’ abuses, torture, women’s emancipation, freedom of speech, poverty, unemployment, and the plight of urban street children in Casablanca are the themes of today’s Moroccan cinema. No stone is left unturned, as filmmakers push the envelope of social consciousness to expose the challenges of contemporary Moroccan society. In the past decade, the films Casanegra (Nourredine Lakhmari, 2008), L’Os de fer (Hicham Lasri, The Iron Bone, 2007), Les Anges de Satan (Ahmed Boulane, Satan’s Angels, 2007), and Casablanca (Farida Benlyazid, 2002) reveal that in the era of intense globalization, urban spaces in Morocco have become conflicted, fragmented spaces. The modern city is for these filmmakers a corrupted human space that rejects the laws of traditional life, dislocates the individual from his/her clan, and leads to the dissolution of the social contract between man and his community. In the films analyzed in this article, the urban space is one that fosters reflection on the price of modernity, technology and the hypothetical Western advances of the globalized age.
Burning the Past: Moroccan Cinema of Illegal Immigration
Authors: Smolin Jonathan
Published: May 2011

Since the early 1990s, illegal immigration through the Strait of Gibraltar has become one of the most pressing social, cultural, and political challenges confronting Morocco. Illegal immigration is also a highly controversial subject because it suggests that those who undertake the dangerous journey would rather risk death and an uncertain future than remain in Morocco. Illegal immigrants typically burn their passports before setting off, a highly symbolic act that implies a burning of their past and a total rejection of the present. Not surprisingly, the phenomenon of illegal immigration has served as a rich theme for Moroccan writers and filmmakers since the mid-1990s. This article examines two films that focus on illegal immigration through the Strait of Gibraltar, Jilali Ferhati’s Horses of Fortune (1995) and Mohamed Ismail’s And After (2001). It argues that Ferhati’s film deconstructs the motives behind the phenomenon by focusing on the lead character’s deception, compulsion, and addiction. Ismail’s film, on the other hand, targets the importance of local exploitation in compelling Moroccans to burn their past. In both films, events in the lives of the main characters force them to burn their past before they even arrive at the beach to set out on the perilous crossing. Ultimately, this article argues that both films provide powerful alternative views on the phenomenon of Moroccan illegal immigration that differ from critics’ typical emphasis on the fantasy of Europe or attempts to flee economic misery.
The Tamer as Shrewd in John Fletcher's The Woman's Prize : Or, The Tamer Tam'd
Authors: Crocker Holly A.
Published: May 2011

Fletcher's play utilizes the close domestic connection between shrews and tyrants to critique Petruchio's absolutist marital authority. Yet, in recasting Petruchio as a tyrant, Fletcher also rewrites the role of shrew; rather than stage a showdown between unruly partners, Fletcher valorizes feminine "shrewdness" as an everyday safeguard against masculine misgovernment. By vesting Maria with the rational control required to bring order to the domestic body, The Woman's Prize makes room for women's power over household relations.
Richard II and the Book of Life
Authors: Estill Laura
Published: May 2011

The Tragedy of Richard II is the only play by Shakespeare in which the phrase "book of life" or "book of heaven" occurs. The book of life is a register of names of those who will get into heaven. Richard's deposition is "[m]ark'd with a blot, damn'd in the book of heaven" (IV.i.236). This paper argues that the tragedy is Richard's realization that anyone, even a divinely anointed king, can be blotted from the book of life and denied access to heaven.
Citizens, Gentry, and the Double Ending of Rowley and Middleton's A Fair Quarrel
Authors: Nicol David
Published: May 2011

Studies of William Rowley and Thomas Middleton's A Fair Quarrel have overlooked the significance of the class identity of the characters to the play's structure. The play is often viewed through the lens of Middleton's satirical city comedies, even though most of it was written by Rowley whose more romantic comedies often celebrate the citizenry. This article examines the play's much-debated generic structure using Walter Cohen's and Lawrence Manley's methods of categorizing the London comedies of the period according to their representation of class divisions. It demonstrates that in its depiction of the interactions between citizens and gentry, A Fair Quarrel is rather more sympathetic toward the values that it attributes to citizens than those it attributes to the gentry. This attitude is especially apparent in the play's ending, which stages two forms of comic resolution in parallel, contrasting a climax that is harmonious and inclusive with another that is awkward and socially exclusive to the gentry.
Adoption and the Language of Horticulture in All's Well That Ends Well
Authors: Ellerbeck Erin
Published: May 2011

This article examines the horticultural lexicon used by Shakespeare to describe adoptive familial bonds. As an example of the ways in which early modern gardeners manipulated the natural world, the practice of grafting collapses any rigid distinction perceived to exist between nature and culture. It serves in All's Well That Ends Well as a metaphor for the combination of families, in which a child belonging genetically to one family is adopted by another. Shakespeare's use of the grafting metaphor suggests, within the context of the play, that legitimate families might be synthetically produced, or based on nonbiological ties.
Ovid and Women's Pastoral in Lady Mary Wroth's Love's Victory
Authors: MacDonald Joyce Green
Published: May 2011

This paper seeks to place Lady Mary Wroth's Love's Victory within the context of Ovidian pastoral. Unlike the pastoral models offered by Virgil or Theocritus, which have been suggested as templates for Wroth's play, Ovid's portraits of withdrawal and separation from civil society often focus on women. Ovid's pastorals also emphasize that the topics of courtship and marriage that feature so prominently in Renaissance pastoral can imply sexual anxiety and even danger for women. This paper argues that Wroth's engagement with Ovidian models of female community challenges trends in the recovery and reconstruction of her authorship by feminist scholarship.
Purgation, Exorcism, and the Civilizing Process in Macbeth
Authors: Hampton Bryan Adams
Published: May 2011

This essay explores the national obsession with purgation in early modern English house-holding theory as it contributes to the building of national identity and the civilizing process. Macbeth provides a window on this obsession, for the imagery and conceptual presence of purgation, in both their natural and supernatural matrices, dominates the play. Via the cultural phenomena of possession and exorcism, the essay interrogates the binaries of the sacred and the profane in Macbeth , arguing that Macbeth's brutal actions are both fair and foul because they are inscribed within a near-fungible economy, flexible ideology, and a politics of the holy and unholy.
Henry VIII, Shakespeare, and the Jacobean Royal Court
Authors: Rankin Mark
Published: May 2011

Early Stuart history plays by William Shakespeare and Samuel Rowley join an ongoing debate over the continued cultural relevance of Henry VIII to the Stuart Court. In anachronistic representations of the Tudor king, both playwrights lodge typological arguments designed to flatter the perceived interests and agendas of their respective patrons, King James and Prince Henry Frederick. This evidence raises larger implications concerning the potential of Shakespearean-era plays to offer royal counsel and shape opinion. At stake are competing narratives of the Henrician Reformation that could legitimate differing ideological commitments concerning history and English Protestant orthodoxy.
Recent Studies in Tudor and Stuart Drama
Authors: Harris Jonathan Gil
Published: May 2011

An assessment of recent scholarly work treating the literature of Tudor and Stuart drama and some general observations on the state of the profession. A full bibliography and price list of the works received by SEL for consideration follow.
Jacobean Politics of Interpretation in Jonson's Masque of Blacknesse
Authors: Odom Glenn A.
Published: May 2011

The difference between Ben Jonson's symbology in Masque of Blacknesse and the symbology expressed by King James's political writing is a form of resistance. The encyclopedias of emblems in the period postulate a clear, universally accessible, direct Neo-Platonic connection of symbol and meaning. King James insists that this connection is not readily apparent and that the symbols require skilled interpretation in order to generate their fixed meaning. Jonson creates symbols that are not bound by a single fixed meaning despite interpretive efforts. This attention to differences in symbology provides fresh ways of understanding recent scholarship on issues of performance, race, and religion.
Ben Jonson's Legal Imagination in Volpone
Authors: Klotz Lisa
Published: May 2011

Jonson habitually used legal procedure to structure his plots and broaden his satire beyond the easy targets of corrupt judges or inane judgment. Examining the avocatori in relation to the entities on which they are modeled, the Venetian avogadori and the English justices of the peace, shows them to be more competent than previously thought. They are duped because the conspirators present a more rational case, in contrast to the implausible and uncorroborated accusations of Celia and Bonario. The satire is not of naive judges, or Venetian or English justice, but of reason's limits in discerning truth and plausibility.
The Transformation of Grief in Ovid's Metamorphoses
Authors: Gentilcore Roxanne M.
Published: May 2011

In Ovid's Metamorphoses women suffer from pathological grief and undergo metamorphosis as a result of this emotional state much more frequently than men. In these narratives depicting women's all-consuming grief, Ovid focuses on spontaneous transformation rather than divine intervention. This is in contrast to Ovid's depiction of masculine grief. The metamorphosis of the female mourner represents the power of grief to transform and subsume the individual while making her permanent sorrow a feature of the physical landscape. Voicelessness, tears, and petrifaction are common distinguishing features of those women whose grief has alienated them from society and rendered them unable to communicate with the living. In contrast to these stories, there are four individuals who grieve but are not transformed. They are depicted as sharing their grief and stories with others. All-encompassing grief is a prevalent characteristic of women in the Metamorphoses that narrative alone has the possibility of alleviating.
Saving the Life of a Foolish Poet: Tacitus on Marcus Lepidus, Thrasea Paetus, and Political Action under the Principate
Authors: Strunk Thomas E.
Published: May 2011

This paper explores Tacitus' representation of Thrasea Paetus. Preliminary to analyzing this portrayal, I discuss two passages often cited when exploring Tacitus' political thought, Agricola 42.4 and Annales 4.20. I reject the former's validity with regard to Thrasea and accept the latter as a starting point for comparing Tacitus' depictions of Marcus Lepidus and Thrasea. Tacitus' characterizations of Thrasea and Lepidus share the greatest resemblance in the trials of Antistius Sosianus and Clutorius Priscus, both of whom wrote verses offensive to the regime. Thrasea and Lepidus both came to the defense of their respective poet in an attempt to spare the poet's life. In light of these trials, I conclude that Tacitus sought to reclaim the legacy of Thrasea and to cast him anew as a principled moderate rather than a reckless dissident.
Heraclean Historians
Authors: Ring Abram
Published: May 2011

The rhetorical use of Heracles, well recognized in poetry and philosophy, also occurs in historiography, not only to praise various historical figures but even to flatter the historians themselves since they saw their work as a "labor" for the benefaction of mankind. This conceit seems to have been particularly important for universal historians as shown by the examples of Diodorus, Pompeius Trogus, and Nicolaus of Damascus. Surely philosophers such as Prodicus were influential in the historians' use of Heracles, and most likely Heracles was first explicitly compared with historians by one of Diodorus' predecessors in universal history.
The Logic of Opportunity: Philip II, Demosthenes, and the Charismatic Imagination
Authors: Butler Margaret E.
Published: May 2011

Demosthenes' characterization of Philip II of Macedon as a charismatic leader and talented opportunist has framed the historical narrative of the fourth century BCE in terms of what Philip did right and the Greek poleis did wrong. An analysis of Philip's early campaigns, drawing on sociological approaches to the study of opportunity, suggests that his "charismatic imagination" was his open-ended, high-risk, and relentless pursuit of new opportunities for growth. Examination of the opportunities open to the Athenians and the Macedonians helps reframe the debate in terms of the overarching constraints affecting the strategic decisions of both states.
Catullus 8 and Catullan Iambos
Authors: Lavigne Donald E.
Published: May 2011

In this paper, I account for Catullus' use of the choliambic meter in poem 8 and show how his redeployment of this iambic meter impacts our understanding of genre. Seeing meter as an integral formal feature of the genre of Iambos , I argue that Catullus' use of this meter encodes generic features. In poem 8, those features are seen to be iambic distance and the concomitant iambic voice, characterized by a self-conscious multiplicity.
Generation of artificial channels by multimerization of β-strands from natural porin
Authors: Lolicato Marco , Reina Simona , Messina Angela , Guarino Francesca , Winterhalter Mathias , Benz Roland , De Pinto Vito
Published: June 2011

General diffusion porins are passive transmembrane channels. We have explored the possibility to create artificial nanopores starting from natural β-barrel structures. Structural elements of bacterial porins were used to build a series of artificial nanopores. The basic module was selected by multi-alignment of general diffusion porins. The sequence corresponded to a highly conserved motif containing two β-strands, which was obtained fromEscherichia coliOmpF. Dimeric to octameric repeats were obtained through cDNA recombinant technology. The hexameric repeat was used to test its properties. This protein was expressed, purified and reconstituted in the planar bilayer membranes. It was able to form channels in membranes with a conductance of 300 pS in 150 mmKCl and did not show any relevant voltage-dependence.
Novel neutrophil inhibitory factor homologue in the buccal gland secretion of Lampetra japonica
Authors: Xue Zhuang , Bai Jie , Sun Jing , Wu Yu , Yu Shui Yan , Guo Ren Yong , Liu Xin , Li Qing Wei
Published: June 2011

To identify the functional gene fragment, a neutrophil inhibitory factor (NIF) like protein was found in the buccal gland ofLampetra japonica, suggesting that this related lamprey protein represents a novel class of integrin receptor antagonists. The recombinantLampetra japonica-NIF like (rLj-NIF) was identified by SDS-PAGE and purified by using His·Bind affinity chromatography. Effect of rLj-NIF on neutrophil migration suggested that rLj-NIF can act as a neutrophil inhibitory factor. Besides that, oxidative burst activity of neutriphil was tested by flow cytometry using dihydrorhodamine (DHR123) as a fluorogenic substrate, and the data suggested that the mean fluorescence intensity significantly decreased compared with positive controls (p<0.01). All above results indicated that rLj-NIF could also prevent the binding of β2 integrins to the surface of PMN and its FITC-labeled monoclonal antibodies (p<0.05). These data suggest thatLampetra japonica-NIF like protein is secreted by the stage of the parasite at the site of attachment. rLj-NIF plays an essential role in physiological reaction of neutrophil by a novel class of β2 integrin receptor antagonists. The activity of immunosuppressant ofL.japonica-NIF could have potential medicinal value in anti-inflammation and therapy of autoimmune diseases.
Impact of aryl hydrocarbon receptor (AhR) knockdown on cell cycle progression in human HaCaT keratinocytes
Authors: Kalmes Michaela , Hennen Jenny , Clemens Judith , Blömeke Brunhilde
Published: June 2011

While activation of the aryl hydrocarbon receptor (AhR) by exogenous ligands is well investigated, its physiological function is less understood. By extending research in AhR biology, evidence appeared that the receptor generally plays an important role in cell physiology. In keratinocytes, little is known about endogenous functions of the AhR. In order to expand this knowledge, we analyzed the impact of AhR knockdown on cell cycle progression in HaCaT cells and showed that proliferation of siAhR HaCaT cells was significantly decreased. In line with that result, western blot analysis revealed that protein level of the cyclin dependent kinase inhibitor p27KIP1 was increased, whereas protein level of the cyclin dependent kinase (CDK) 2 was reduced. CDK4 and CDK6 protein levels remained unchanged, whereas protein level of the retinoblastoma protein (pRB) was reduced. By measuring ethoxyresorufin-O-deethylase (EROD) activity we showed that endogenous cytochrome P450 1 (CYP1), especially CYP1A1 is required for normal cell cycle in HaCaT cells, as well. To the best of our knowledge, we provide evidence for the first time in human skin cells, that in the absence of exogenous ligands, the AhR promotes cell cycle progression in HaCaT cells and one can speculate that this is the physiological function of this receptor in keratinocytes.
Laboratory assessment of iron status in pregnancy
Authors: Walsh Thomas , O'Broin Sean D. , Cooley Sharon , Donnelly Jennifer , Kennedy John , Harrison Robert F. , McMahon Corinna , Geary Michael
Published: June 2011

Background: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies.

Methods: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered.

Results: A high occurrence iron deficiency (ID) at first booking (SF<12 μg/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia “cut-off” (Hb<110 g/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 μg/L) which were mostly associated with much higher Hb levels.

Conclusions: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.
Calcium pyrophosphate and monosodium urate crystals in synovial fluid as a cause of pseudoeosinophilia
Authors: Robier Christoph , Neubauer Manfred , Quehenberger Franz , Stettin Mariana , Rainer Franz
Published: June 2011

Background: Synovial fluid (SF) leukocytes can be counted microscopically in a Neubauer chamber or by automated procedures using haematology analysers. Knowledge of laboratory artefacts is crucial for the correct interpretation of results obtained using automated methods. SF pseudoeosinophilia has recently been described as a new artefact in patients with crystal-related arthropathies. We investigated whether pseudoeosinophilia of SF is restricted to crystal-related disorders, or if it may also occur in other arthropathies.

Methods: We compared the percentages of eosinophils in 120 crystal containing SF samples with 185 crystal-free specimens using the Wilcoxon test. Crystal positive samples, determined by polarised microscopy, contained at least two monosodium urate or calcium pyrophosphate crystals per 10 high power fields (630× magnification). True SF eosinophilia was ruled out by microscopic examination of stained slides.

Results: Crystal positive samples had significantly higher percentages of eosinophils than the controls (p<0.0001). No significant differences between the two crystal types were found (p=0.693). Thus, pseudoeosinophilia was significantly correlated with the presence of crystals, and none of the distinct crystal types was more likely to be associated with pseudoeosinophilia.

Conclusions: In this study, SF pseudoeosinophilia was confirmed as a crystal-related laboratory artefact which has to be considered in the interpretation of automated SF leukocyte differential counts.
Global uniqueness in determining electric potentials for a system of strongly coupled Schrödinger equations with magnetic potential terms
Authors: Liu Shitao , Triggiani Roberto
Published: June 2011

We consider the inverse problem of determining simultaneously two unknown electric potential coefficients for a system of two general strongly coupled Schrödinger equations, with magnetic potential terms, and with Neumann boundary conditions, from single Dirichlet measurements on a portion Γ1 of the boundary. Under suitable geometrical assumptions on the complementary unobserved portion Γ0 of the boundary, we show that one can uniquely determine the two unknown potential coefficients in one shot, from respective Dirichlet boundary measurements on Γ1 over an arbitrarily short time interval. The proof is based on a recent Carleman estimate in [Lasiecka, Triggiani and Zhang, J. Inv. Ill-Posed Problems 12: 43–123, 2004] for single Schrödinger equations. It also takes advantage of a convenient route “post-Carleman estimates” suggested by [Isakov, Inverse Problems for Partial Differential Equations, Springer, 2006, Theorem 8.2.2, p. 231].
Estimation of accuracy of finite-dimensional methods of regularization
Authors: Tanana Vitaly P. , Yaparova Natalya M.
Published: June 2011

We consider the estimation of the accuracy of finite dimensional approximations of regularized solutions for inverse problems in a separable Hilbert space. A connection of the regularization parameter with the estimates of error for these approximations and with the estimates of initial date is obtained. For the establishment method the estimation of error of the finite-dimensional approximation is obtained. This estimate is exact with respect to the order.
Neto2 Modulation of Kainate Receptors with Different Subunit Compositions
Authors: Straub Christoph , Zhang Wei , Howe James R.
Published: June 2011

Kainate receptors are less well understood than other glutamate receptors, and synaptic kainate receptors display properties that differ from recombinant receptors. In particular, the slow decay of kainate receptor synaptic currents contrasts with the rapid deactivation and desensitization of receptors expressed in heterologous cells. We recently identified Neuropilin and Tolloid like-2 (Neto2) as a novel accessory subunit of kainate receptors and showed that Neto2 modulates the gating kinetics of GluK2 receptors. However, the kainate receptor family consists of five different subunits (GluK1–5) that can form homomeric and heteromeric receptors with different functional properties. Here, we tested whether Neto2 modulation varies with subunit composition. Rapid application techniques were used to apply glutamate to outside–out patches that contained GluK1, GluK1/5, or GluK2/5 kainate receptors. Coexpression of Neto2 slowed desensitization to varying degrees. Responses to 1 ms pulses of glutamate were also slowed by Neto2, especially for receptors containing GluK5, as were postsynaptic currents in neurons expressing recombinant kainate receptors. In addition, Neto2 markedly increased the rate at which some receptors recovered from desensitization. These results suggest that Neto2 modulates the function of most kainate receptors.
Cognitive Effort Drives Workspace Configuration of Human Brain Functional Networks
Authors: Kitzbichler Manfred G. , Henson Richard N. A. , Smith Marie L. , Nathan Pradeep J. , Bullmore Edward T.
Published: June 2011

Effortful cognitive performance is theoretically expected to depend on the formation of a global neuronal workspace. We tested specific predictions of workspace theory, using graph theoretical measures of network topology and physical distance of synchronization, in magnetoencephalographic data recorded from healthy adult volunteers (N= 13) during performance of a working memory task at several levels of difficulty. We found that greater cognitive effort caused emergence of a more globally efficient, less clustered, and less modular network configuration, with more long-distance synchronization between brain regions. This pattern of task-related workspace configuration was more salient in the β-band (16–32 Hz) and γ-band (32–63 Hz) networks, compared with both lower (α-band; 8–16 Hz) and higher (high γ-band; 63–125 Hz) frequency intervals. Workspace configuration of β-band networks was also greater in faster performing participants (with correct response latency less than the sample median) compared with slower performing participants. Processes of workspace formation and relaxation in relation to time-varying demands for cognitive effort could be visualized occurring in the course of task trials lasting <2 s. These experimental results provide support for workspace theory in terms of complex network metrics and directly demonstrate how cognitive effort breaks modularity to make human brain functional networks transiently adopt a more efficient but less economical configuration.
Short-Term Facilitation Modulates Size and Timing of the Synaptic Response at the Inner Hair Cell Ribbon Synapse
Authors: Goutman Juan D. , Glowatzki Elisabeth
Published: June 2011

Inner hair cells (IHCs) in the mammalian cochlea are able to continuously release neurotransmitter in the presence of constant stimuli. Nonetheless, strong synaptic depression is observed over the first few milliseconds of stimulation. This process most likely underlies adaptation in the auditory nerve. In the present study we demonstrate that under certain conditions of stimulation, facilitation can occur at the IHC ribbon synapse. Using simultaneous whole-cell, voltage-clamp recordings from IHCs and afferent fiber endings in excised postnatal rat cochleae, we stimulated IHCs with 2 ms long test depolarizations from a holding potential of −89 mV. Synaptic currents in afferent fibers occurred with high failure rates of ∼50%. However, when a pre-depolarization to values of −55 to −49 mV was implemented before the test pulse, success rates of the synaptic response increased to 100%, the strength of the synaptic response increased ∼2.8-fold, and synaptic latency was reduced by ∼50%. When calcium influx was minimized during pre-depolarization, none of these effects were found, suggesting that calcium influx during pre-depolarizations is required for synaptic conditioning. Similarly, in response to paired-pulse protocols, short term facilitation occurred. The response to the second stimulus increased up to ∼5-fold, and its latency was reduced by up to 35% compared to the response to the first stimulus. We propose that at the IHC resting membrane potential, the ribbon synapse operates in a constantly facilitated mode caused by Ca2+influx, optimizing the size and timing of the postsynaptic response in auditory nerve fibers.
Long-Term Imaging Reveals Dynamic Changes in the Neuronal Composition of the Glomerular Layer
Authors: Adam Yoav , Mizrahi Adi
Published: June 2011

The mammalian olfactory bulb (OB) contains a rich and highly heterogeneous network of local interneurons (INs). These INs undergo continuous turnover in the adult OB in a process known as “adult neurogenesis.” Although the overall magnitude of adult neurogenesis has been estimated, the detailed dynamics of the different subpopulations remains largely unknown. Here we present a novel preparation that enables long-termin vivotime-lapse imaging in the mouse OB through a chronic cranial window in a virtually unlimited number of sessions. Using this preparation, we followed the turnover of a specific neuronal population in the OB, the dopaminergic (DA) neurons, for as long as 9 months. By following the same population over long periods of time, we found clear addition and loss of DA neurons in the glomerular layer. Both cell addition and loss increased over time. The numbers of new DA cells were consistently and significantly higher than lost DA cells, suggesting a net increase in the size of this particular population with age. Over a 9 month period of adult life, the net addition of DA neurons reached ∼13%. Our data argue that the fine composition of the bulbar IN network changes throughout adulthood rather than simply being replenished.
Sparse But Highly Efficient Kv3 Outpace BKCaChannels in Action Potential Repolarization at Hippocampal Mossy Fiber Boutons
Authors: Alle Henrik , Kubota Hisahiko , Geiger Jörg R. P.
Published: June 2011

Presynaptic elements of axons, in which action potentials (APs) cause release of neurotransmitter, are sites of high densities and complex interactions of proteins. We report that the presence of Kv3 channels in addition to Kv1 at glutamatergic mossy fiber boutons (MFBs) in rat hippocampal slices considerably limits the number of fast, voltage-activated potassium channels necessary to achieve basal presynaptic AP repolarization. The ∼10-fold higher repolarization efficacy per Kv3 channel compared with presynaptic Kv1 results from a higher steady-state availability at rest, a better recruitment by the presynaptic AP as a result of faster activation kinetics, and a larger single-channel conductance. Large-conductance calcium- and voltage-activated potassium channels (BKCa) at MFBs give rise to a fast activating/fast inactivating and a slowly activating/sustained K+current component during long depolarizations. However, BKCacontribute to MFB–AP repolarization only after presynaptic Kv3 have been disabled. The calcium chelators EGTA and BAPTA are equally effective in preventing BKCaactivation, suggesting that BKCaare not organized in nanodomain complexes with presynaptic voltage-gated calcium channels. Thus, the functional properties of Kv3 channels at MFBs are tuned to both promote brevity of presynaptic APs limiting glutamate release and at the same time keep surface protein density of potassium channels low. Presynaptic BKCachannels are restricted to limit additional increases of the AP half-duration in case of Kv3 hypofunction, because rapid membrane repolarization by Kv3 combined with distant calcium sources prevent BKCaactivation during basal APs.
Spinning versus Wobbling: How the Brain Solves a Geometry Problem
Authors: Laurens Jean , Strauman Dominik , Hess Bernhard J.
Published: June 2011

Oscillating an animal out-of-phase simultaneously about the roll and pitch axes (“wobble”) changes continuously the orientation of the head relative to gravity. For example, it may gradually change from nose-up, to ear-down, nose-down, ear-down, and back to nose-up. Rotations about the longitudinal axis (“spin”) can change the orientation of the head relative to gravity in the same way, provided the axis is tilted from vertical. During both maneuvers, the otolith organs in the inner ear detect the change in head orientation relative to gravity, whereas the semicircular canals will only detect oscillations in velocity (wobble), but not any rotation at constant velocity (spin). Geometrically, the whole motion can be computed based on information about head orientation relative to gravity and the wobble velocity. We subjected monkeys (Macaca mulatta) to combinations of spin and wobble and found that the animals were always able to correctly estimate their spin velocity. Simulations of these results with an optimal Bayesian model of vestibular information processing suggest that the brain integrates gravity and velocity information based on a geometrically coherent three-dimensional representation of head-in-space motion.
Scratching Beneath the Surface: New Insights into the Functional Properties of the Lateral Occipital Area and Parahippocampal Place Area
Authors: Cant Jonathan S. , Goodale Melvyn A.
Published: June 2011

We used fMRI on neurologically intact humans to investigate whether or not there are different neural substrates for the different kinds of information that a visual surface signals (shape from texture vs material properties from texture). Participants attended to differences in the shape (flat/convex), texture and color (wood/rock), or material properties (soft/hard) of a set of circular surfaces. Attending to shape activated the contour-sensitive lateral occipital (LO) area, and attending to texture activated a region of the collateral sulcus (CoS) that overlaps with the parahippocampal place area (PPA). Interestingly, attending to material properties activated the same texture-sensitive region in the CoS. These results demonstrate the existence of different neural substrates for the different types of information that a visual surface signals. With regard to object shape, the organization of the LO area may be complex, with neurons tuned not only to the outline shape of objects, but also to their surface curvature independent of contour. Moreover, to our knowledge, this is the first study to demonstrate that processing surface texture, which occurs within the scene-sensitive PPA, is a route to accessing knowledge about an object's material properties. With this in mind, we propose that models of visual cortical organization should focus not only on the particular stimulus category to which a region maximally responds (e.g., objects, scenes), but also on the stimulus attributes that best support the processing of that category (e.g., shape, texture, material properties).
NMDA Receptor Activation Suppresses Microtubule Growth and Spine Entry
Authors: Kapitein Lukas C. , Yau Kah Wai , Gouveia Susana Montenegro , van der Zwan Wouter A. , Wulf Phebe S. , Keijzer Nanda , Demmers Jeroen , Jaworski Jacek , Akhmanova Anna , Hoogenraad Casper C.
Published: June 2011

Dynamic microtubules are important to maintain neuronal morphology and function, but whether neuronal activity affects the organization of dynamic microtubules is unknown. Here, we show that a protocol to induce NMDA-dependent long-term depression (LTD) rapidly attenuates microtubule dynamics in primary rat hippocampal neurons, removing the microtubule-binding protein EB3 from the growing microtubule plus-ends in dendrites. This effect requires the entry of calcium and is mediated by activation of NR2B-containing NMDA-type glutamate receptor. The rapid NMDA effect is followed by a second, more prolonged response, during which EB3 accumulates along MAP2-positive microtubule bundles in the dendritic shaft. MAP2 is both required and sufficient for this activity-dependent redistribution of EB3. Importantly, NMDA receptor activation suppresses microtubule entry in dendritic spines, whereas overexpression of EB3-GFP prevents NMDA-induced spine shrinkage. These results suggest that short-lasting and long-lasting changes in dendritic microtubule dynamics are important determinants for NMDA-induced LTD.
Presynaptic α2-GABAAReceptors in Primary Afferent Depolarization and Spinal Pain Control
Authors: Witschi Robert , Punnakkal Pradeep , Paul Jolly , Walczak Jean-Sébastien , Cervero Fernando , Fritschy Jean-Marc , Kuner Rohini , Keist Ruth , Rudolph Uwe , Zeilhofer Hanns Ulrich
Published: June 2011

Spinal dorsal horn GABAAreceptors are found both postsynaptically on central neurons and presynaptically on axons and/or terminals of primary sensory neurons, where they mediate primary afferent depolarization (PAD) and presynaptic inhibition. Both phenomena have been studied extensively on a cellular level, but their role in sensory processingin vivohas remained elusive, due to inherent difficulties to selectively interfere with presynaptic receptors. Here, we address the contribution of a major subpopulation of GABAAreceptors (those containing the α2 subunit) to spinal pain control in mice lacking α2-GABAAreceptors specifically in primary nociceptors (sns-α2−/−mice).sns-α2−/−mice exhibited GABAAreceptor currents and dorsal root potentials of normal amplitudein vitro, and normal response thresholds to thermal and mechanical stimulationin vivo, and developed normal inflammatory and neuropathic pain sensitization. However, the positive allosteric GABAAreceptor modulator diazepam (DZP) had almost completely lost its potentiating effect on PAD and presynaptic inhibitionin vitroand a major part of its spinal antihyperalgesic action against inflammatory hyperalgesiain vivo. Our results thus show that part of the antihyperalgesic action of spinally applied DZP occurs through facilitated activation of GABAAreceptors residing on primary nociceptors.
The Benefit of Object Interactions Arises in the Lateral Occipital Cortex Independent of Attentional Modulation from the Intraparietal Sulcus: A Transcranial Magnetic Stimulation Study
Authors: Kim Jiye G. , Biederman Irving , Juan Chi-Hung
Published: June 2011

Our visual experience is generally not of isolated objects, but of scenes, where multiple objects are interacting. Such interactions (e.g., a watering can positioned to pour water toward a plant) have been shown to facilitate object identification compared with when the objects are depicted as not interacting (e.g., a watering can positioned away from the plant) (Green and Hummel, 2004, 2006). What is the neural basis for this advantage? Recent fMRI studies have identified the lateral occipital cortex (LO) as a potential neural origin of this behavioral benefit, as LO showed greater responses to object pairs depicted as interacting compared with when they are not (Kim and Biederman, 2010; Roberts and Humphreys, 2010). However, it is possible that LO was modulated by an attention-sensitive region, the intraparietal sulcus (IPS), which sometimes showed a similar pattern of responses as that of LO in the Kim and Biederman (2010) investigation. To test this hypothesis, we delivered transcranial magnetic stimulation (TMS) to human subjects' LO and IPS while they detected a target object that was or was not interacting with another object to form a scene. TMS delivered to LO but not IPS abolished the facilitation in identifying interacting objects compared with noninteracting depictions observed in the absence of TMS, suggesting that it is LO and not IPS that is critical for the coding of object interactions.
Apraxia Impairs Intentional Retrieval of Incidentally Acquired Motor Knowledge
Authors: Dovern Anna , Fink Gereon R. , Saliger Jochen , Karbe Hans , Koch Iring , Weiss Peter H.
Published: June 2011

Apraxia caused by left hemispheric stroke typically impairs skilled sequential movements. After stroke, apraxic patients need to reacquire motor skills by motor learning. The current study assessed for the first time incidental motor sequence learning in apraxic patients. Forty-eight human subjects (henceforth called “patients”) with left hemispheric stroke affecting the middle cerebral artery territory (18 with apraxia and 30 without apraxia) and 17 age-matched healthy controls were tested on a visuomanual serial reaction time task. Subjects performed four blocks consisting of repetitions of a complex six element sequence containing ambiguous pairwise transitions before a new and unfamiliar sequence was introduced in block 5. Reaction time (RT) disadvantages in this fifth block indicated incidental sequence-specific motor learning. The intentional retrieval of the learned motor knowledge was assessed subsequently with a free recall task. Voxel-based lesion-symptom mapping (VLSM) was performed to investigate for the first time the lesion correlates of deficits in learning and retrieving sequential motor knowledge. Despite generally prolonged RTs, apraxic patients showed sequence-specific motor learning as could be observed in nonapraxic patients and healthy controls. However, apraxic patients showed reduced intentional retrieval of the learned sequence. VLSM revealed that impaired intentional retrieval of motor sequence knowledge resulted from dorsal premotor cortex lesions. Apraxic patients showed a dissociation of preserved incidental motor (sequence) learning and deficient intentional retrieval of this incidentally learned motor knowledge. The data suggest that novel approaches for treating apraxia should focus on incidental motor learning, but that automatic rather than intentional retrieval strategies should be enforced.
Canonical Notch Signaling Is Not Necessary for Prosensory Induction in the Mouse Cochlea: Insights from a Conditional Mutant ofRBPjκ
Authors: Basch Martín L. , Ohyama Takahiro , Segil Neil , Groves Andrew K.
Published: June 2011

The mammalian organ of Corti consists of a highly organized array of hair cells and supporting cells that originate from a common population of prosensory progenitors. Proper differentiation of this complex cellular mosaic requires lateral inhibition mediated by Notch signaling. Several studies have implicated Notch signaling in the earlier induction of the prosensory domain that lies along the length of the cochlear duct, and which forms before the onset of hair cell and supporting cell differentiation. To investigate the role of Notch signaling in prosensory domain formation, we conditionally inactivated the transcriptional mediator of canonical Notch signaling,RBPjκ, throughout the inner ear. AlthoughRBPjκ mutants have severe vestibular defects and a shortened cochlear duct, markers of the prosensory domain appear at the normal time and location in the cochlea of RBPjκ mutants. Despite the lack ofRBPjκ, hair cell and supporting cell markers also appear at appropriate times in the cochlea, suggesting thatRBPjκ is dispensable for differentiation of the cochlear sensory epithelium. However, we also observed that differentiating hair cells and supporting cells rapidly die inRBPjκ mutants, suggesting a requirement ofRBPjκ for cell survival in this tissue. Finally, in contrast to the chick basilar papilla, ectopic activation of Notch signaling did not induce ectopic sensory patches in nonsensory regions of the cochlea. Our results indicate that canonical Notch signaling is not necessary for prosensory specification in the mouse cochlea, suggesting that other signaling pathways may specify this highly derived sensory organ.
Historical Perspectives
Authors: Toubas Paul-Louis
Published: June 2011

The end of World War II brought peace, optimism, and unequaled opportunities for women, lifting barriers and generating a world of babies. The demand for physicians to man crowded nurseries increased the need to put order to the chaotic nature of the “Baby Boom.” Women physicians, still facing frustrating discrimination, focused on their work. Virginia Apgar designed a score to triage the condition of the newly born and prepare for action, if necessary. Lula Lubchenco's growth curves identified the abnormalities of growth that could affect brain development. Murdina Desmond organized intensive care to prepare for the fight against staphylococcal infections plaguing the nurseries. Mildred Stahlman transformed the intensive care unit into a laboratory to study the cardiopulmonary functions of the newborn and develop approaches to attack “hyaline membrane disease” using assisted ventilation. These women physicians, among others, had adamant observer qualities. Their work ethic, compassion, and creativity stimulated a generation of medical students who were eager to do their best to solve the newly apparent multitude of problems. They prepared for the following decades of medical technology that burst forth in the 1960s.
Palatal Development and Orofacial Function: Possible Effects of Preterm Care
Authors: Tighe David , Tighe Reiltin , Petrick Laima , Cobourne Martyn T. , Rabe Heike
Published: June 2011

Understanding of the impact of disordered palatal and orofacial development on preterm neonatal survivors is increasing. Optimal clinical assessment and management requires neonatologists to have a sound knowledge of: normal palatal development; potential causes for disordered development, including iatrogenic causes; factors to assess on newborn examination; and optimal multidisciplinary follow-up for feeding, orthodontic, and speech-language development. Key findings quantify harmful effects of intubation on palatal shape, tooth eruption/morphology, and speech; further studies are required to delineate the effect on swallowing. The evidence base is discussed for preterm care and palatal and orofacial development in preterm and low-birthweight infants. Current knowledge is limited by lack of uniformity of definition and measurement tools. Guidance is summarized for practical management and follow-up of preterm and low-birthweight infants requiring intubation.
Red, Scaly Babies: Neonatal Erythroderma
Authors: Bedocs Laleh A. , O'Regan Grainne M. , Bruckner Anna L.
Published: June 2011

Erythroderma is defined as generalized skin erythema affecting at least 90% of the body. This skin reaction is not specific for one diagnosis. Neonatal erythroderma is potentially life-threatening and presents unique therapeutic and diagnostic challenges. The differential diagnosis is broad, and many of the potential diagnoses are exceedingly rare. Additional clinical or laboratory findings may point to the underlying primary disease, and understanding these clues can expedite establishing the diagnosis. Irrespective of the underlying cause, neonates who have erythroderma have a compromised skin barrier, which can lead to dehydration, electrolyte imbalances, temperature instability, protein losses, and increased risk for infection. This review focuses on an approach to managing erythroderma and reviews the features of several causes of erythroderma.