bluuebunny/crossref_metadata_2025 huggingface dataset:
Hume’s Science of Emotions: Feeling Theory without Tears
Authors: Collier Mark
Published: September 2012

We must rethink the status of Hume’s science of emotions. Contemporary philosophers typically dismiss Hume’s account on the grounds that he mistakenly identifies emotions with feelings. But the traditional objections to Hume’s feeling theory are not as strong as commonly thought. Hume makes several important contributions, moreover, to our understanding of the operations of the emotions. His claims about the causal antecedents of the indirect passions receive support from studies in appraisal theory, for example, and his suggestions concerning the social dimensions of self-conscious emotions can help guide future research in this field. His dual-component hypothesis concerning the processing of emotions, furthermore, suggests a compromise solution to a recalcitrant debate in cognitive science. Finally, Hume’s proposals concerning the motivational influences of pride, and the conventional nature of emotional display rules, are vindicated by recent work in social psychology.
Projectivism and Error in Hume’s Ethics
Authors: Olson Jonas
Published: September 2012

This essay argues that while Hume believes both that morality is grounded in our ordinary moral practices, sentiments, and beliefs, and that moral properties are real, he also holds that ordinary moral thinking involves systematically erroneous beliefs about moral properties. These claims, on their face, seem difficult to square with one another but this paper argues that on Hume’s view, they are reconcilable. The reconciliation is effected by making a distinction between Hume’s descriptive metaethics, that is, his account of vulgar moral thought and discourse, and his revisionary metaethics, that is, his account of how vulgar moral thought and discourse could be reformed so as to no longer involve error. This essay concludes that Hume is a projectivist and an error theorist in descriptive metaethics, while he is a projectivist and a subjectivist in revisionary metaethics.
The Role of Political Economy in Hume’s Moral Philosophy
Authors: Wennerlind Carl
Published: September 2012

Hume insisted that property serve as the foundation of society because it best promotes the greatest amount of industry and therefore contributes to public utility. Industry thus plays a central role in Hume’s theory of justice. Given that Hume extensively discussed the social, political, cultural, and moral implications of industry in the Political Discourses , I suggest that Hume’s economic writings should be understood as an integral part of his overall philosophical project. In offering a parallel reading of the Enquiry Concerning the Principles of Morals and the Political Discourses , I argue that Hume’s theory of justice does not resolve into a mere theory of property, as many philosophers complain, but rather, emerges as a rich account of how justice both generates the greatest material affluence and promotes the formation of the most virtuous society.
Extreme Skepticism and Commitment in the Treatise
Authors: Durland Karánn
Published: September 2012

The extreme skepticism that Hume’s dangerous dilemma introduces at the end of the first Book of the Treatise is deeply unsettling, in part because it seems to undermine Hume’s commitments to common life and philosophy, but also because Hume seems not to take its sweeping doubts seriously. He refuses to abandon his daily activities and philosophical pursuits, and he offers no clear account of what entitles him to sustain them. This paper explores a variety of tactics for addressing these opposing elements of his thought. The most radical approach has Hume endorse nothing whatsoever in the Treatise , a maneuver that prevents any conflict between his doubts and his commitments from arising, though at a tremendous cost. A more charitable strategy allows Hume to speak with one consistent voice throughout the text by rejecting, repurposing, or restricting either his doubts or his commitments in a way that resolves the tension between them. Yet a third approach takes Hume to advance incompatible and irreconcilable positions but holds that the inconsistency in his thinking is not as destructive as it initially appears. None of the most promising ways of developing these proposals eliminates or satisfactorily eases the conflict in Hume’s work, and the enormous obstacles that they face give us little reason to hope for something better.
Sherlock Holmes and Game Theory
Authors: Wainwright Michael
Published: September 2012

This essay reanalyzes the game theory interpretation by John von Neumann and Oskar Morgenstern of Arthur Conan Doyle’s “The Final Problem.” The usefulness of this interdisciplinary hermeneutic is then supplemented by lateral and philosophical thinking as prompted by subsequent tales involving Doyle’s detective.
The Ethics of Laughter: David Sedaris and Humour Memoir
Authors: Cardell Kylie , Kuttainen Victoria
Published: September 2012

What is an ethics of autobiography in the context of the humour memoir? This essay examines the work of David Sedaris in order to explore how he uses the composite memoir form, and a comic style, to negotiate the problems of authenticity and authority that have become crucial in recent autobiography.
Thomas the Marvellous: Resurrection and Living-Death in Blanchot and Nancy
Authors: Saghafi Kas
Published: September 2012

Providing an overarching interpretation of Thomas the Obscure and all of Blanchot’s work, Nancy in La Déclosion presents a powerful reading of death and resurrection. It is only by privileging L’Espace littéraire and a certain interpretation of death, I suggest, that Nancy can argue for the mundaneness of resurrection rather than its “fantastic” or “miraculous” nature.
Traumatic Forgetting and Spatial Consciousness in Dionne Brand’s In Another Place, Not Here
Authors: Visvis Vikki
Published: September 2012

By relying on spatial tropes, Brand’s In Another Place, Not Here investigates the competing ideological implications of deliberate traumatic forgetting, suggesting both its productive and problematic dimensions, and thereby complicates current discourses of trauma, particularly by rendering questionable the primacy of remembrance in contemporary discussions.
“cease to exist in order to be”: Worstward Ho between Badiou and Deleuze
Authors: Langlois Christopher
Published: September 2012

In Handbook of Inaesthetics, Alain Badiou develops a disagreement with Gilles Deleuze over the ontology of artistic creation. By contextualizing this disagreement in Beckett’s Worstward Ho, however, we see that it is Deleuze who brings us closer to a position where the difficulties peculiar to artistic thought are better theorized.
Weltgeschichte als Weltgericht : Le corps hétérotopique dans Une tempête
Authors: Chen Chien-Hung
Published: September 2012

Dans Une tempête, le renoncement de Caliban aux habits de Prospero concrétise la Négritude et sert de tourniquet menant au Weltgericht als Weltgeschichte. Le masque donne naissance au corps hétérotopique qui communique la sphère du personnage avec celles de l’acteur et du spectateur, réalisant le désabusement de la mémoire.
Ekphrasis Refigured: Writing Seeing in Siri Hustvedt’s What I Loved
Authors: Grønstad Asbjørn
Published: September 2012

Noting the extensive and sustained engagement with visual media in many contemporary American novels, this essay argues that the notion of ekphrasis as a critical notion must be reconceptualized in order to accommodate the complexity of the relations between new literary expressions and the visual.
Poetry, Polyvocal, Philosophy: A Thought Experiment
Authors: Washington Gene
Published: September 2012

This essay explores the polyvocality between poetry and philosophy. Using an Aristotelian (and Peircean) approach, the author examines how linguistic forms like negation, the “actual,” and the “virtual” inform the polyvocal. Central is the claim that the polyvocal is prior to poetry and philosophy in time, account, and knowledge.
The Remains of Empire and the “Purloined” Philippines: Jessica Hagedorn’s Dream Jungle
Authors: Lee Hsiu-chuan
Published: September 2012

This essay examines Dream Jungle’s intervention into the imaginary configuration of the Philippines. Lacan’s elaboration on “purloin” prompts a reading of the Philippines as not simply “stolen” by imperialism but “prolonged”—via Hagedorn’s fictional creativity—into a community evolving through imperial intrusions, translocal displacements, and encounters.
Creating/Vanishing: The Gypsy Muse in Works by Arnold, Kalda, Janáček, and Vaughan Williams
Authors: Christensen Allan C.
Published: September 2012

A dangerous gypsy muse inspires creativity in the two poems and their musical settings. While enacting their creations, the works perform vanishing acts too, in allusion to their superseding of previous works. Our interest in their vanished origins recalls Darwin’s fascination with the creative sources in Nature, with which the gypsy muse is associated.
Framed Identity: Finding Lucy in Atwood’s “Death by Landscape”
Authors: Raschke Debrah
Published: September 2012

Atwood’s “Death by Landscape” is a multi-layered tale linking a young girl’s disappearance to the death of Tom Thomson, a Canadian painter who inspired the Group of Seven. The paintings from the Group, which frame the camp narrative within which Lucy vanishes, are also associated with the virility ideology that Atwood subverts.
Did Shakespeare’s Company Cut Long Plays Down to Two Hours Playing Time?
Authors: Urkowitz Steven
Published: September 2012

For over 75 years, arguments have been proposed that some unwritten law or commonly followed practice constrained Elizabethan and Jacobean plays to be performed in little more than two hours of playing time. Nevertheless, Shakespeare, Jonson, and others regularly composed plays which if performed as they appear in printed versions would require three or more hours from start to finish. This has led many critics to argue that because of this hypothetical two-hour time limit, many of Shakespeare's plays, along with Jonson's Bartholomew Fair, would never have been acted as written, even in Shakespeare's time and by Shakespeare's own acting company. This article regards such theories, which have led to a skewed perspective on the relationship between so-called cut 'bad quartos' and their 'full length' folio versions, as completely mistaken, and instead offers documentation that casts considerable doubt upon the supposed two-hour limitation on plays performed by Shakespeare's company. By drawing on contemporary accounts of theatre-going, material evidence of cutting practices, laws governing stage playing, and sections of plays that are widely accepted to have been added some time after their initial composition, the essay dismantles the largely unfounded arguments in favour of the 'two-hour theory' posited by critics even today. Ultimately, the article seeks to argue in opposition to the currently fashionable vision of an artistic parsimony that doled out only two-hour tranches of comedies, tragedies, and histories, suggesting instead that Shakespeare and his company, free from arbitrary time constraints, participated fully in bold, risk-taking, and expansive theatrical ventures.
“Posterity is dispossessed”: Laurence Olivier’s Macbeth Manuscripts in 1958 and 2012
Authors: Barnes Jennifer
Published: September 2012

Between December 1955 and July 1958 Laurence Olivier was planning what was to be his fourth and final cinematic Shakespeare adaptation, Macbeth . Despite reaching an advanced stage of production, the project never materialised and Olivier declared posterity to be dispossessed of his Macbeth . Since then a host of cultural commentators, scholars and members of the public have speculated about what exactly Olivier's Macbeth might have looked like. Olivier certainly encouraged such speculation, suggesting that no screenplays relating to the cancelled film project existed. In 2012, however, I discovered thirteen screenplays for Macbeth catalogued in the Laurence Olivier Archive at the British Library. These documents trace Macbeth's development from a first draft through to a final and very detailed shooting script. This essay examines Macbeth both in its own time and today, using the screenplays to detail the specific cultural and industrial reasons as to why Olivier's final cinematic Shakespeare film was never made. I also explore the unmade film in its archival context, asking what Macbeth can tell us about Laurence Olivier's status in our collective cultural memory. Through Macbeth , I argue, Olivier offers us a posthumous performance in the archive.
“Know that I, Ringo the drummer, am”: Shakespeare, YouTube, and the Limits of Performance
Authors: Geddes Louise
Published: September 2012

The Beatles' 1964 performance of the 'Pyramus and Thisbe' playlet from  A Midsummer Night's Dream , originally an oddball product of variety television, has gained a new life as a popular clip on YouTube. This essay explores the video's engagement with online theatrical culture by way of a complex interplay of source and context. As performed by The Beatles, 'Pyramus and Thisbe' mocks classroom Shakespeare while simultaneously drawing on its reputation to position the band in a playful - and lucrative - space between high culture and counterculture. The sketch also locates The Beatles on multiple planes of performance and reality: their deliberately poor performances offer a glimpse of the 'real' Beatles while also recreating Shakespeare's rude mechanicals and highlighting the artificiality, not just of the play, but of 'The Beatles' as an image in itself. Finally, the sketch's presence on YouTube adds another layer of spectator/image recursion, as the online audience appropriates both Shakespeare and The Beatles, while unconsciously mimicking prior audiences of the 1960s and the 1590s.
Quantitative PCR Analysis of DNA, RNAs, and Proteins in the Same Single Cell
Authors: Ståhlberg Anders , Thomsen Christer , Ruff David , Åman Pierre
Published: September 2012

BACKGROUND

The single cell represents the basic unit of all organisms. Most investigations have been performed on large cell populations, but understanding cell dynamics and heterogeneity requires single-cell analysis. Current methods for single-cell analysis generally can detect only one class of analytes.

METHODS

Reverse transcription and the proximity ligation assay were coupled with quantitative PCR and used to quantify any combination of DNA, mRNAs, microRNAs (miRNAs), noncoding RNAs (ncRNAs), and proteins from the same single cell. The method was used on transiently transfected human cells to determine the intracellular concentrations of plasmids, their transcribed mRNAs, translated proteins, and downstream RNA targets.

RESULTS

We developed a whole-cell lysis buffer to release unfractionated DNA, RNA, and proteins that would not degrade any detectable analyte or inhibit the assay. The dynamic range, analytical sensitivity, and specificity for quantifying DNA, mRNAs, miRNAs, ncRNAs, and proteins were shown to be accurate down to the single-cell level. Correlation studies revealed that the intracellular concentrations of plasmids and their transcribed mRNAs were correlated only moderately with translated protein concentrations (Spearman correlation coefficient, 0.37 and 0.31, respectively; P < 0.01). In addition, an ectopically expressed gene affected the correlations between analytes and this gene, which is related to gene regulation.

CONCLUSIONS

This method is compatible with most cell-sampling approaches, and generates output for the same parameter for all measured analytes, a feature facilitating comparative data analysis. This approach should open up new avenues in molecular diagnostics for detailed correlation studies of multiple and different classes of analytes at the single-cell level.
Interaction of methocarbamol and yeast sucrase induces enzyme inhibition
Authors: Minai-Tehrani Dariush , Masoudnia Allaleh , Alavi Sana , Osmani Raheleh , Lotfi Leila , Asghari Mitra , Pirsalehi Mahdi , Sobhani-Damavandifar Zahra
Published: September 2012

Background: Methocarbamol is a skeletal muscle relaxant and is widely used to relieve pain in muscles. Many drugs may have interactions with each other when used at the same time. Yeast sucrase is taken as a drug by patients with congenital sucrase-isomaltase deficiency (CSID).

Methods: In this study, the interaction between methocarbamol and yeast sucrase was investigated.

Results: Our results showed that methocarbamol can inhibit sucrase activity and reduce the maximum reaction velocity (Vmax) of the enzyme by a non-competitive pattern. Measurement of IC50 and Ki of the drug revealed that methocarbamol did not bind the enzyme with high affinity. Fluorescence measurement showed that the drug binds to free enzyme and enzyme-substrate complexes that were accompanied by structural changes on the enzyme. Guaifenesin, which has a similar structure to methocarbamol, does not affect the activity of sucrase.

Conclusions: Methocarbamol inhibits sucrase activity and its carbamate group plays a main role in the binding of drug to sucrase.
Exosomes: the ideal nanovectors for biodelivery
Authors: Fais Stefano , Logozzi Mariantonia , Lugini Luana , Federici Cristina , Azzarito Tommaso , Zarovni Natasa , Chiesi Antonio
Published: September 2012

Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.
Acetylcholinesterase (AChE) inhibitory activity, antioxidant properties and phenolic composition of two Aframomum species
Authors: Adefegha Stephen A. , Oboh Ganiyu
Published: September 2012

Background:
Aframomum species are widely used as a food supplement and remedy in folklore medicine for the management of several diseases. This study was designed to investigate the acetylcholinesterase inhibitory activity and antioxidant properties of phenolic-rich extracts from two Aframomum species: Aframomum danielli (Hook F.) K. Schum (Zingiberaceae) and Aframomum melegueta (Roscoe) K. Schum (Zingiberaceae) seeds.

Methods: Acetylcholinesterase inhibitory activity and antioxidant properties [inhibition of quinolinic acid (QA)-induced lipid peroxidation in rat brain, reducing properties, 2,2-azinobis (3-ethylbenzo-thiazoline-6-sulfonate) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging abilities] using in vitro models were evaluated. Phenolic composition of the seed extracts using reversed phase high performance chromatography (RP-HPLC) and gas chromatography coupled with flame ionization detector (GC-FID) were also assessed.

Results: Both extracts exhibited acetylcholinesterase inhibitory activity in a dose-dependent manner (125–1000 μg/mL); however, A. melegueta extract (IC50=373.33 μg/mL) had a significantly higher (p<0.05) acetylcholinesterase inhibitory activity than A. danielli extract (IC50=417.10 μg/mL). Furthermore, both extracts significantly decreased QA-elevated brain malondialdehyde (MDA) contents, reduced Fe3+ to Fe2+ and scavenged DPPH and ABTS radicals. Phenolic characterization of the seeds by RP-HPLC at 280 nm showed abundance of quercetin and kaempferol in A. melegueta and chlorogenic acid in A. danielli, whereas GC-FID revealed that p-hydroxybenzoic acid was abundant in both seeds.

Conclusions: Inhibitory effect of these extracts on acetylcholinesterase activity and their antioxidant property could be attributed to the combined effect of phenolic and non-phenolic constituents of the seeds. These effects could be part of the possible biochemical mechanism by which these seeds elicit their protection against oxidative stress in brain; however, A. melegueta showed the more promising potential.
Antidepressant Suppression of Non-REM Sleep Spindles and REM Sleep Impairs Hippocampus-Dependent Learning While Augmenting Striatum-Dependent Learning
Authors: Watts Alain , Gritton Howard J. , Sweigart Jamie , Poe Gina R.
Published: September 2012

Rapid eye movement (REM) sleep enhances hippocampus-dependent associative memory, but REM deprivation has little impact on striatum-dependent procedural learning. Antidepressant medications are known to inhibit REM sleep, but it is not well understood if antidepressant treatments impact learning and memory. We explored antidepressant REM suppression effects on learning by training animals daily on a spatial task under familiar and novel conditions, followed by training on a procedural memory task. Daily treatment with the antidepressant and norepinephrine reuptake inhibitor desipramine (DMI) strongly suppressed REM sleep in rats for several hours, as has been described in humans. We also found that DMI treatment reduced the spindle-rich transition-to-REM sleep state (TR), which has not been previously reported. DMI REM suppression gradually weakened performance on a once familiar hippocampus-dependent maze (reconsolidation error). DMI also impaired learning of the novel maze (consolidation error). Unexpectedly, learning of novel reward positions and memory of familiar positions were equally and oppositely correlated with amounts of TR sleep. Conversely, DMI treatment enhanced performance on a separate striatum-dependent, procedural T-maze task that was positively correlated with the amounts of slow-wave sleep (SWS). Our results suggest that learning strategy switches in patients taking REM sleep-suppressing antidepressants might serve to offset sleep-dependent hippocampal impairments to partially preserve performance. State–performance correlations support a model wherein reconsolidation of hippocampus-dependent familiar memories occurs during REM sleep, novel information is incorporated and consolidated during TR, and dorsal striatum-dependent procedural learning is augmented during SWS.
Time-Dependent Cross Talk between Spinal Serotonin 5-HT2AReceptor and mGluR1 Subserves Spinal Hyperexcitability and Neuropathic Pain after Nerve Injury
Authors: Aira Zigor , Buesa Itsaso , Gallego Mónica , García del Caño Gontzal , Mendiable Nahia , Mingo Janire , Rada Diego , Bilbao Juan , Zimmermann Manfred , Azkue Jon Jatsu
Published: September 2012

Emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. Upregulation of the serotonin receptor 2A (5-HT2AR) in dorsal horn neurons promotes spinal hyperexcitation and impairs spinal μ-opioid mechanisms during neuropathic pain. We investigated the involvement of spinal glutamate receptors, including metabotropic receptors (mGluRs) and NMDA, in 5-HT2AR-induced hyperexcitability after spinal nerve ligation (SNL) in rat. High-affinity 5-HT2AR agonist (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2) enhanced C-fiber-evoked dorsal horn potentials after SNL, which was prevented by mGluR1 antagonist AIDA [(RS)-1-aminoindan-1,5-dicarboxylic acid] but not by group II mGluR antagonist LY 341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid] or NMDA antagonistd-AP5 [d-(−)-2-amino-5-phosphonopentanoic acid]. 5-HT2AR and mGluR1 were found to be coexpressed in postsynaptic densities in dorsal horn neurons. In the absence of SNL, pharmacological stimulation of 5-HT2AR with TCB-2 both induced rapid bilateral upregulation of mGluR1 expression in cytoplasmic and synaptic fractions of spinal cord homogenates, which was attenuated by PKC inhibitor chelerythrine, and enhanced evoked potentials during costimulation of mGluR1 with 3,5-DHPG [(RS)-3,5-dihydroxyphenylglycine]. SNL was followed by bilateral upregulation of mGluR1 in 5-HT2AR-containing postsynaptic densities. Upregulation of mGluR1 in synaptic compartments was partially prevented by chronic administration of selective 5-HT2AR antagonist M100907 [(R)-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol], confirming 5-HT2AR-mediated control of mGluR1 upregulation triggered by SNL. Changes in thermal and mechanical pain thresholds following SNL were increasingly reversed over the days after injury by chronic 5-HT2AR blockade. These results emphasize a role for 5-HT2AR in hyperexcitation and pain after nerve injury and support mGluR1 upregulation as a novel feedforward activation mechanism contributing to 5-HT2AR-mediated facilitation.
Striatal Indirect Pathway Contributes to Selection Accuracy of Learned Motor Actions
Authors: Nishizawa Kayo , Fukabori Ryoji , Okada Kana , Kai Nobuyuki , Uchigashima Motokazu , Watanabe Masahiko , Shiota Akira , Ueda Masatsugu , Tsutsui Yuji , Kobayashi Kazuto
Published: September 2012

The dorsal striatum, which contains the dorsolateral striatum (DLS) and dorsomedial striatum (DMS), integrates the acquisition and implementation of instrumental learning in cooperation with the nucleus accumbens (NAc). The dorsal striatum regulates the basal ganglia circuitry through direct and indirect pathways. The mechanism by which these pathways mediate the learning processes of instrumental actions remains unclear. We investigated how the striatal indirect (striatopallidal) pathway arising from the DLS contributes to the performance of conditional discrimination. Immunotoxin targeting of the striatal neuronal type containing dopamine D2receptor in the DLS of transgenic rats resulted in selective, efficient elimination of the striatopallidal pathway. This elimination impaired the accuracy of response selection in a two-choice reaction time task dependent on different auditory stimuli. The impaired response selection was elicited early in the test sessions and was gradually restored as the sessions continued. The restoration from the deficits in auditory discrimination was prevented by excitotoxic lesion of the NAc but not by that of the DMS. In addition, lesion of the DLS mimicked the behavioral consequence of the striatopallidal removal at the early stage of test sessions of discriminative performance. Our results demonstrate that the DLS-derived striatopallidal pathway plays an essential role in the execution of conditional discrimination, showing its contribution to the control of selection accuracy of learned motor responses. The results also suggest the presence of a mechanism that compensates for the learning deficits during the repetitive sessions, at least partly, demanding accumbal function.
Repetition Suppression and Expectation Suppression Are Dissociable in Time in Early Auditory Evoked Fields
Authors: Todorovic Ana , de Lange Floris P.
Published: September 2012

Repetition of a stimulus, as well as valid expectation that a stimulus will occur, both attenuate the neural response to it. These effects, repetition suppression and expectation suppression, are typically confounded in paradigms in which the nonrepeated stimulus is also relatively rare (e.g., in oddball blocks of mismatch negativity paradigms, or in repetition suppression paradigms with multiple repetitions before an alternation). However, recent hierarchical models of sensory processing inspire the hypothesis that the two might be separable in time, with repetition suppression occurring earlier, as a consequence of local transition probabilities, and suppression by expectation occurring later, as a consequence of learnt statistical regularities. Here we test this hypothesis in an auditory experiment by orthogonally manipulating stimulus repetition and stimulus expectation and, using magnetoencephalography, measuring the neural response over time in human subjects. We found that stimulus repetition (but not stimulus expectation) attenuates the early auditory response (40–60 ms), while stimulus expectation (but not stimulus repetition) attenuates the subsequent, intermediate stage of auditory processing (100–200 ms). These findings are well in line with hierarchical predictive coding models, which posit sequential stages of prediction error resolution, contingent on the level at which the hypothesis is generated.
Species Differences in Somatodendritic Dopamine Transmission Determine D2-Autoreceptor-Mediated Inhibition of Ventral Tegmental Area Neuron Firing
Authors: Courtney Nicholas A. , Mamaligas Aphroditi A. , Ford Christopher P.
Published: September 2012

The somatodendritic release of dopamine within the ventral tegmental area (VTA) and substantia nigra pars compacta activates inhibitory postsynaptic D2-receptors on dopaminergic neurons. The proposed mechanisms that regulate this form of transmission differ between electrochemical studies using rats and guinea pigs and electrophysiological studies using mice. This study examines the release and resulting dopamine D2-autoreceptor-mediated IPSCs (D2-IPSCs) in the VTA of mouse, rat, and guinea pig. Robust D2-IPSCs were observed in all recordings from neurons in slices taken from mouse, whereas D2-IPSCs in rat and guinea pig were observed less frequently and were significantly smaller in amplitude. In slices taken from guinea pig, dopamine release was more persistent under conditions of reduced extracellular calcium. The decline in the concentration of dopamine was also prolonged and not as sensitive to inhibition of reuptake by cocaine. This resulted in an increased duration of D2-IPSCs in the guinea pig. Therefore, unlike the mouse or the rat, the time course of dopamine in the extracellular space of the guinea pig determined the duration the D2-IPSC. Functionally, differences in D2-IPSCs resulted in inhibition of dopamine neuron firing only in slices from mouse. The results suggest that the mechanisms and functional consequences of somatodendritic dopamine transmission in the VTA vary among species. This highlights the complexity that underlies dopamine-dependent transmission in one brain area. Differences in somatodendritic transmission would be expectedin vivoto affect the downstream activity of the mesocorticolimbic dopamine system and subsequent terminal release.
Neural Mechanisms for the Abstraction and Use of Pitch Information in Auditory Cortex: Figure 1.
Authors: Wang Xiaoqin , Walker Kerry M. M.
Published: September 2012

Experiments in animals have provided an important complement to human studies of pitch perception by revealing how the activity of individual neurons represents harmonic complex and periodic sounds. Such studies have shown that the acoustical parameters associated with pitch are represented by the spiking responses of neurons in A1 (primary auditory cortex) and various higher auditory cortical fields. The responses of these neurons are also modulated by the timbre of sounds. In marmosets, a distinct region on the low-frequency border of primary and non-primary auditory cortex may provide pitch tuning that generalizes across timbre classes.
Pitch Perception
Authors: Oxenham Andrew J.
Published: September 2012

Pitch is one of the primary auditory sensations and plays a defining role in music, speech, and auditory scene analysis. Although the main physical correlate of pitch is acoustic periodicity, or repetition rate, there are many interactions that complicate the relationship between the physical stimulus and the perception of pitch. In particular, the effects of other acoustic parameters on pitch judgments, and the complex interactions between perceptual organization and pitch, have uncovered interesting perceptual phenomena that should help to reveal the underlying neural mechanisms.
Gender-, strain-, and inheritance-dependent variation in aldosterone secretion in mice
Authors: Spyroglou Ariadni , Sabrautzki Sibylle , Rathkolb Birgit , Bozoglu Tarik , Hrabé de Angelis Martin , Reincke Martin , Bidlingmaier Martin , Beuschlein Felix
Published: September 2012

Arterial hypertension represents one of the most common diseases in developed countries and the rennin–angiotensin–aldosterone system is among the major factors in the regulation of blood pressure and sodium balance. With the exception of rare monogenetic diseases, however, inheritance of aldosterone secretion is widely unknown. In this study, we investigated the aldosterone levels in male and female mice of two inbred strains, C3HeB/FeJ and C57BL/6J, as well as their offspring of the F1 and F2 generation. In all cases, female animals displayed lower aldosterone levels than males. Furthermore, C57BL/6J animals had significantly higher aldosterone levels than C3HeB/FeJ mice of the same age and gender. Depending on the paternal origin of the animal, the F1 offspring showed a tendency toward higher aldosterone values when the paternal side was from the C57BL/6J strain. This observation was confirmed in the F2 generation and over repeated measurements over three consecutive years. Quantification of the aldosterone to renin ratio in the different mouse groups did not show any significant differences, and, similarly, the determination of plasma potassium and kidney parameters did not provide any differences. On the molecular level, investigation of the expression of the enzymes involved in steroidogenesis displayed the same trend as for the aldosterone values, with animals hosting C57BL/6J background in their paternal origin having also the highest expression levels for StAR, cyp11a1, and cyp11b2 enzymes. Taken together, we could demonstrate that the genetic background of the animals plays a significant role modulating their plasma aldosterone levels without clear interference of other parameters in the renin–angiotensin–aldosterone system.
Mechanism of the experimental antithrombotic effect of some apple varieties involves enhanced endogenous thrombolytic activity
Authors: Morishita Mai , Naemura Aki , Tamura Yukinori , Yamaya Hideaki , Tsuda Yuko , Okada Yoshio , Okada Kiyotaka , Matsuo Osamu , Yamamoto Junichiro
Published: September 2012

Prevention of arterial thrombotic diseases has high priority in developed countries. As inappropriate diet is known to enhance the risk for acute thrombotic events, a regular diet with experimentally proven antithrombotic effect might be a beneficial way of prevention. The present study is part of a series of investigations testing fruits and vegetables for antithrombotic activity. The Global Thrombosis Test was used to screen sixteen different apple varieties for antiplatelet and thrombolytic activities. Thein vitroeffective varieties were further investigated using the laser-induced thrombosis model in mice. In order to investigate the mechanism, hemostatometry and flow-mediated vasodilation test (FMV) were performed. Apple varieties were grouped into subclasses according to their antithrombotic activity. AP-2, AP-13, AP-14 and AP-15 showed significant antithrombotic effect bothin vitroandin vivo. AP-8 was antithromboticin vitrobut could not determinein vivobecause of the shortage of the sample. The antithrombotic effect was mainly due to activation of endogenous thrombolytic mechanism. The mechanism of such enhanced thrombolysis was investigated using a synthetic inhibitor highly specific to plasmin, polyclonal IgG to t-PA and u-PA, and testing the antithrombotic effect in t-PA knockout mice. Antithrombotic activity was prevented by the synthetic plasmin inhibitor and IgG against t-PA but not against u-PA. There was no antithrombotic activity in t-PA knockout mice. Intake of antithrombotic apple filtrate did not affect FMV and platelet reactivity. The antithrombotic effect was heat stable at 100 °C for 10 min. These results suggest that the mechanism of antithrombotic activity involves an increased t-PA release from the vascular endothelium and an inhibition of plasminogen activator inhibitor (PAI-1) release from activated platelets. The present findings justify including antithrombotic apple varieties in an antithrombotic diet.
Modulation of hearing related proteins in the brain and inner ear following repeated blast exposures
Authors: Arun Peethambaran , Valiyaveettil Manojkumar , Biggemann Lionel , Alamneh Yonas , Wei Yanling , Oguntayo Samuel , Wang Ying , Long Joseph B. , Nambiar Madhusoodana P.
Published: September 2012

Emerging studies show that blast exposure causes traumatic brain injury (TBI) and auditory dysfunction without rupture of tympanic membrane, suggesting central auditory processing impairment after blast exposure. There is limited information on the mechanisms of blast-induced TBI and associated peripheral and central auditory processing impairments. We utilized a repetitive blast exposure mouse model to unravel the mechanisms of blast TBI and auditory impairment. C57BL/6J mice were exposed to three repeated blasts (20.6 psi) using a shock tube, and the cerebellum was subjected to proteomic analysis. The data showed that calretinin and parvalbumin, two major calcium buffering proteins, were significantly up-regulated after repeated blast exposures, and this was confirmed by Western blotting. Since these proteins are reportedly involved in auditory dysfunction, we examined the inner ear and found both calretinin and parvalbumin were up-regulated, suggesting that modulation of these proteins plays a role in blast-induced peripheral and central auditory processing impairments. Expression of cleaved caspase-3 was also up-regulated in both regions indicating ongoing cellular apoptosis, possibly due to altered calcium homeostasis. These results provide a molecular basis for changes in central and peripheral auditory processing involving abnormal calcium homeostasis resulting in hearing impairment after blast exposure.
Urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in patients with nonalcoholic fatty liver disease
Authors: Tekkeşin Nilgün , Taga Yavuz , İbrişim Duygu , Gündoğan Nilgün
Published: September 2012

Background/Aims

Nonalcoholic fatty liver disease (NAFLD), one of the most common forms of chronic liver disease, is closely associated with obesity and insulin resistance (IR). Adipokines secreted by adipose tissue have recently been implicated in initiating and perpetuating the chronic inflammatory state observed in obesity and NAFLD. Recent studies suggest neutrophil gelatinase-associated lipocalin (NGAL) plays a key role in the pathogenesis of IR. The aims of this study were to determine urinary NGAL levels in patients with ultrasonography proven NAFLD and to correlate these levels with the metabolic profile and fibrosis grade in this population.

Methodology

Our cohort consisted of 65 consecutive patients undergoing abdominal ultrasonography for clinical suspicion of NAFLD. Patients were subsequently divided into two groups: no steatosis (n=20) and steatosis (n=45). The stage of fibrosis was measured using a four-point scale. Urinary NGAL was measured by a specific microparticle enzyme immunoassay. The degree of insulin resistance was determined by the homeostatic model assessment (HOMA). Glucose, insulin, lipid profile, and transaminases were also measured.

Results

Urinary NGAL levels correlated with body mass index, HOMA, fasting glucose, and insulin levels in patients with steatosis. Moreover, uNGAL levels were higher in patients with steatosis compared to those with no steatosis (49.8 ng/mL and 22.7 ng/mL, respectively) with a statistically significant difference (p<0.001). A stepwise increase in uNGAL levels from patients without fibrosis (21.7 ng/mL) to patients with cirrhosis (47.4 ng/mL) was noted (p<0.001).

Conclusions

Our study demonstrates that in adult patients with NAFLD, uNGAL levels correlate with BMI, insulin resistance, and lipid profiles, and identifies a novel association between uNGAL levels and hepatocellular injury in these patients.
Gadolinium-induced fibrosis testing by protein targeting assay and superparamagnetic iron oxide nanoparticle-based magnetic resonance microscopy of skin and kidneys
Authors: Sharma Rakesh
Published: September 2012

Gadolinium-based magnetic resonance imaging (MRI) contrast agents cause undefined fibrosis in kidneys and skin damage. Magnetic resonance microimaging of rat skin and kidney was used first time to identify the physical factors modulating the gadolinium Omniscan®-induced fibrosis by protein targeting. A 500-MHz MR imaging was done to visualize fibrosis in gadolinium-treated animals. Cationic superparamagnetic iron oxide magnetoferritin (SPIOM) was injected in rat to target basement membrane (in rat kidney and different skin structures including epidermis glycolipids and dermis proteins. After MR imaging, excised rat skin and kidneys tissues were imaged by ex vivo 900 MHz MR microimaging to confirm renal fibrosis and skin epidermis thickening. The proton density-weighted images visualized micro details of skin structures and nephron territories while T2-weighted images showed better contrast of tissue structures in both skin and kidney. The gadolinium further enhanced the image contrast and targeted the proteins in renal basement membrane and viable proteins in epidermis. SPIOM enhanced the tissue contrast due to dephasing effect caused by SPIOM on structural changes in nephron and epidermis. Conclusion: Tissue membrane protein and chelate ligand group binding with gadolinium biophysical interaction at molecular level may develop fibrosis. SPIOM injection improved the dephased image contrast of different structures in both skin and nephrons. The epidermis thickening and nephrofibrosis changes may be associated with nephrogenic systemic fibrosis or fibrosing dermatopathy.
Stress magnet ingestion in three children: Endoscopist perspective
Authors: Ozgenc Funda , Yuksekkaya Hasan Ali , Erdemir Gulín , Ecevit Cigdem Omur , Yagci Rasit Vural
Published: September 2012

The widespread use of magnets in toy industry has resulted in increased reports of magnet ingestions and related complications. Ensconcing within plastic covers and manufacturing larger pieces have been forwarded to avoid ingestion. We report 3 cases of magnet ingestion called “stress magnets” which are large to pass the gastric outlet. Endoscopic retrieval of single and double magnets from the stomach is described, and magnet related health hazard as well as the procedure related adversities is discussed.
Ventricular septal rupture complicating acute myocardial infarction following percutaneous coronary intervention
Authors: Rajan Rajesh , Padmaja N. P. , Ramakrishna Pillai V. , Daniel Rachel , Vijayaraghavan Govindan
Published: September 2012

Ventricular septal rupture (VSR) is a rather rare, but at the same time very dreadful complication of acute myocardial infarction in the percutaneous coronary intervention (PCI) era and only limited evidence exist on the optimal treatment of this critical medical condition. VSR is less common following successful early thrombolysis and PCI occurring in myocardium supplied by infarct-related artery (IRA). We report two well-documented cases of successful VSR treatment which will provide valuable information for clinical practice especially due to the long-tem follow-up. Both cases underwent delayed elective surgical closure of VSR. This report clearly describes the incidence, potential risks and timing of occurrence, clinical features, and outcomes of ventricular septal rupture complicating acute myocardial infarction (AMI) after PCI. Hence the topic of this report is of great importance. Although the prognosis of patients who develop VSR is generally grave without immediate surgical repair, both our patients remained hemodynamically stable at discharge and during follow-up of more than 4 years.
Diferenças entre adolescentes do sexo feminino e masculino na vulnerabilidade individual ao HIV
Authors: Anjos Renata Holanda Dutra dos , Silva José Augusto de Souza , Val Luciane Ferreira do , Rincon Laura Alarcon , Nichiata Lucia Yasuko Izumi
Published: September 2012

O objetivo deste estudo foi analisar comparativamente a vulnerabilidade ao HIV/AIDS de homens e mulheres adolescentes, baseada em seus conhecimentos, valores e práticas. Trata-se de um estudo exploratório-descritivo com abordagem quantitativa. Os estudantes responderam a um questionário do qual foram selecionadas questões relevantes para análise. Totalizaram 207 adolescentes, sendo 43,5% do sexo masculino e 56,5% do feminino. A maior parte dos adolescentes declara já ter tido sua primeira relação sexual até o momento do estudo. Observaram-se déficits de conhecimento sobre transmissão do HIV e práticas sexuais seguras. Embora haja conhecimento declarado das técnicas de uso do preservativo, isso não reflete em seu uso constante. Observaram-se valores ligados às representações de gênero, mas percebe-se uma evolução quanto à autonomia e poder de negociação das meninas sobre o uso do preservativo.
O perfil da mulher portadora de HIV/AIDS e sua adesão à terapêutica antirretroviral
Authors: Felix Gabriela , Ceolim Maria Filomena
Published: September 2012

Esse trabalho teve como objetivos caracterizar o perfil sociodemográfico e clínico, os comportamentos em saúde, crenças e atitudes sobre a doença e o tratamento de mulheres com HIV/AIDS atendidas no serviço ambulatorial de um hospital universitário do interior de São Paulo, bem como identificar fatores que interferem na adesão à terapêutica antirretroviral. Os sujeitos do estudo foram 60 mulheres acompanhadas no serviço. Os dados foram colhidos por meio de entrevista semiestruturada. As mulheres tinham idade média de 39,8 (desvio padrão 9,1) anos, baixa escolaridade, condições socioeconômicas insatisfatórias e mantinham relacionamento estável. A relação heterossexual foi a forma mais frequente de infecção; 55% das mulheres já abandonaram o tratamento e alegavam como principais motivos os esquemas terapêuticos impostos, os efeitos colaterais dos antirretrovirais, o enfrentamento psicológico da doença e o pesar iminente da morte; 35% delas não atingiram critérios de adesão considerando-se o uso de 95% da terapêutica antirretroviral prescrita.
Avaliação do nível de esperança de vida de idosos renais crônicos em hemodiálise
Authors: Orlandi Fabiana de Souza , Pepino Barbara Garbelotti , Pavarini Sofia Cristina Iost , Santos Damiana Aparecida dos , Mendiondo Marisa Silvana Zazzetta de
Published: September 2012

O presente estudo teve por objetivo avaliar o nível de esperança dos idosos renais crônicos em hemodiálise, por meio da Escala de Esperança de Herth (EEH). Trata-se de um estudo descritivo transversal, realizado em uma Unidade de Terapia Renal Substitutiva do interior do estado de São Paulo. A amostra foi composta por 50 idosos em tratamento hemodialítico. Após o consentimento em participar da pesquisa, realizou-se entrevistas individuais com os referidos idosos aplicando-se um instrumento de caracterização e a Escala de Esperança de Herth. Todos os preceitos éticos foram respeitados (protocolo 512/2009). Quanto aos resultados, houve predomínio do sexo masculino (60%) e idade média de 70,20 (±6,1) anos. O escore médio obtido com a aplicação da Escala de Esperança de Herth foi de 36,20 (±2,90). Conclui-se que em comparação com o estudo brasileiro de validação da Escala de Esperança de Herth, o nível de esperança dos sujeitos do presente estudo foi mais baixo, indicando a necessidade de intervenção sobre esse sentimento.