bluuebunny/crossref_metadata_2025 huggingface dataset:
Personal Morality and Professional Obligations: Rights of Conscience and Informed Consent
Authors: May Thomas , Aulisio Mark P.
Published: January 2009

This article examines the issue of expanding rights of conscience for health-care professionals to include rights grounded in claims of complicity. Our concerns relate to the nature of professional expertise, on the one hand, and an individual’s right to live by his or her values, on the other. The fact that a patient is dependent on a physician’s counseling about treatment options requires limiting conscience-based refusal to provide information, since allowing refusal would deprive patients of even knowing the options that exist for them. Sanctioning such claims of conscience not only would supplant one person’s moral judgment with another’s, it would also allow professional standing to be used as a justification for imposing one person’s moral views on another.
Kawasaki Disease in India: Increasing Awareness or Increased Incidence?
Authors: Kushner Howard I. , Macnee Rupert P. , Burns Jane C.
Published: January 2009

Reports of Kawasaki disease (KD) throughout India are increasing. This article addresses the question of whether the increased diagnosis of KD in India represents the emerging recognition of an illness that had been previously obscured by misdiagnosis, or whether KD is new to India and is increasing in incidence.Whichever answer turns out to be correct, the burden of KD is likely to pose a significant challenge to the health-care system in India in the coming years, due to the high cost of treatment and the potential for lifelong cardiovascular sequelae.Moreover, elucidating the factors that have contributed to the increased recognition of KD in India may provide useful insights for the continuing search for the etiology of KD worldwide.
Darwinism and the Cultural Evolution of Sports
Authors: De Block Andreas , Dewitte Siegfried
Published: January 2009

This article outlines a Darwinian approach to sports that takes into account its profoundly cultural character and thereby overcomes the traditional nature-culture dichotomies in the sociology of sport. We argue that there are good reasons to view sports as culturally evolved signaling systems that serve a function similar to (biological) courtship rituals in other animals. Our approach combines the insights of evolutionary psychology, which states that biological adaptations determine the boundaries for the types of sport that are possible, and pure cultural theories, which describe the mechanism of cultural evolution without referring to sport’s biological bases. Several biological and cultural factors may moderate the direct effect that signaling value has on a sport’s viability or popularity. Social learning underlies many aspects of the cultural control of sports, and sports have evolved new cultural functions more-or-less unrelated to mate choice as cultural evolution itself became important in humans.
Creating Reflective Spaces: Interactions Between Philosophers and Biomedical Scientists
Authors: De Melo-Martin Inmaculada
Published: January 2009

New science policy initiatives are encouraging multidisciplinary collaborations between social scientists, humanists, biomedical scientists, and engineers. Although these policy initiatives are not always clear about how such interactions should take place, the idea is that social scientists and humanists can bring a broader perspective to the table, as well as highlight a variety of matters that are often not addressed by natural scientists and engineers. This article focuses on collaborations between philosophers and biomedical scientists in order to discuss how interdisciplinary collaborations may address ethical, social, and environmental concerns in ways that lead to improvements in people’s health and quality of life. The article concludes with a consideration of some of the challenges that such collaborations face.
Who Is Dürer’s “Syphilitic Man”?
Authors: Eisler Colin
Published: January 2009

Among Albrecht Dürer’s first known woodcuts is one showing a syphilitic man. The Nuremberg artist’s image is the earliest known depiction of an individual suffering from this illness. Syphilis was probably brought by Conquistadores from the New World to Naples in the later 1490s and was then transmitted throughout Western Europe by Northern mercenaries ( Landsknechten ) returning from Italy to their native Germany and Switzerland. The attire worn by Dürer’s Syphilitic Man is exactly that of the Landsknecht . This makes the image important not only as a very early work by the artist and the earliest image of a syphilitic, but also as a depiction of the agent of the disease. The young Dürer had ample opportunity to study such mercenaries during his journeyman years in present-day Switzerland and Strasbourg, since most of them came from precisely the same impoverished territories.
The Threat That Dare Not Speak Its Name: Human Extinction
Authors: Epstein Richard J. , Zhao Y.
Published: January 2009

The end of the human race is not imminent, but it is both inevitable and important. Judging by the scarcity of relevant publications, however, there seems little public or professional concern about this prospect. We submit that this striking disinterest reflects a combination of ignorance and denial that is putting the long-term interests of society in jeopardy. With the pace of change now outstripping that of adaptation, it is no longer alarmist for academics to raise awareness about the approach of human extinction and to design strategies by which time to extinction might be prolonged. By making complacent and anthropocentric thinking less politically correct than it is at present, such awareness could motivate the world community to reformulate social norms in a way that benefits our descendants as much as possible for as long as possible.

The face of Death is toward the sun of Life His shadow darkens Earth.

—Tennyson, “The Death of the Duke of Clarence and Avondale” (1892)
Death, Mourning, and Medical Progress
Authors: Callahan Daniel
Published: January 2009

A number of changes can be observed in the way people are coming to think about death, mourning, and medical progress. The palliative care movement was initiated some 30 years ago to respond to widespread ignorance or neglect of pain relief for the dying, which was then coming to public attention and becoming a key part of the nascent hospice movement. Yet if an important feature of the latter movement was acceptance of the reality of death, in recent years there has emerged a blending of clinical treatment and hospice care, a kind of compromise with the idea of death as an inevitability. Meanwhile, the combination of real progress in forestalling death and the matching medical and media hype about past and coming victories over mortality mean that death itself is coming to be seen as a biological accident, a contingent event, not a fixed given. People die now because of bad luck, indifference to good living habits, unfortunate genetics, and the like, or because they have the misfortune of dying before a cure for their fatal disease is at hand. Mourning likewise is changing. The old custom of the deceased being laid out in their living rooms, followed by a funeral, has long given way to a movement away from public funerals to private ones followed later by a memorial ceremony. No more dead bodies on display to grieve over, but soothing ceremonies of remembrance.
Medical Education and the Tyranny of Competency
Authors: Brooks Michael A.
Published: January 2009

Those who educate medical students and physicians work in a world suffused with the concept of competency. This article examines the intellectual origins and hidden assumptions of this concept and argues that it is an inadequate, and even harmful, concept to use as a guiding motif for professional education. The competency model—which tends to be top-down and prescriptive—does not provide the framework for objective educational assessment that it claims to provide. The alternative apprenticeship model is more appropriate for professional education and is more consistent with what psychological research has shown about the acquisition of expertise.
Poetry and the Brain: Cajal’s Conjectures on the Psychology of Writers
Authors: Triarhou Lazaros C. , Vivas Ana B.
Published: January 2009

In 1902, Santiago Ramón y Cajal (1852–1934), the father of modern neuroscience and a 1906 Nobel laureate, contributed a preface to a book of poems by his fellow countryman, Spanish poet and dramatist Marcos Zapata (1844–1914). In that uncustomary—for his neuroscience followers—essay, Cajal unfolds his ideas on the literary genres of drama and comedy in relation to the workings of the human mind and sentiments. The same text was reissued almost half a century later in Spain and in Argentina under the title The Psychology of Artists . We present an English version of Cajal’s essay, which may be of interest to both humanists and biologists, and which further denotes the celebrated neuroanatomist’s attempt at understanding the mystery of the human mind.
Down with Natural Selection?
Authors: Pigliucci Massimo
Published: January 2009

Biologists are increasingly reexamining the conceptual structure of evolutionary theory, which dates back to the so-called Modern Synthesis of the 1930s and 1940s. Calls for an Extended Evolutionary Synthesis (EES) cite a number of empirical and theoretical advances that need to be accounted for, including evolvability, evolutionary novelties, capacitors of phenotypic evolution, developmental plasticity, and phenotypic attractors. In Biological Emergences , however, Robert Reid outlines a theory of evolution in which natural selection plays no role or—worse—actually impedes evolution by what Reid calls “natural experimentation.” For Reid, biological complexity emerges because of intrinsic mechanisms that work in opposition to natural selection, a view that would reopen old questions of orthogenesis and Lamarckism. This review outlines why we do need an EES, but also why it is unlikely to take the shape that Reid advocates.
The Stem-Cell Century: A New Epoch and Fresh Challenge
Authors: McCormick Jennifer B. , Scott Christopher Thomas
Published: January 2009

Stem-cell research is still a prominent part of the political, scientific, and public discourse. Scientific advances are being made at a rapid rate, while debates on the moral status of the embryo continue. In the United States, President George W. Bush has twice vetoed legislation that some maintain would be an improvement over the current funding environment; others argue the solution is not optimal for thoroughly exploiting the potential of this exciting new area of research. In addition, we face a number of additional policy and legal challenges, including such issues as intellectual property, oocyte procurement, and informed consent of egg donors. We review Russell Korobkin’s Stem Cell Century in the context of recent additions to the literature on stem-cell research and policy.
Edward Bancroft’s “Torporific Eels”
Authors: Finger Stanley
Published: January 2009

Edward Bancroft was a medical apprentice in Connecticut before running off to Guiana in 1763. While in South America, he practiced medicine and collected material for a lengthy book on the region, which he published after he settled in London. Bancroft’s Essay (1769) contains a description of the “torporific eels” found in the warm rivers of Guiana, along with a series of experiments suggesting that the eel’s powers are electrical. It also calls for studies to determine whether saltwater torpedo rays might demonstrate the same properties, which Bancroft expected would be the case. Today, Bancroft is best remembered for serving Benjamin Franklin and the American delegation in France during the War of Independence, and for being a double agent. But what this colorful man wrote about the South American eels helped to make an early case for animal electricity and stimulated Franklin to encourage John Walsh to conduct his landmark electrical experiments on torpedoes and electric eels in the 1770s. These efforts led to new way of thinking about the physiology of the nervous and muscular systems, even in nonspecialized fish.
Science Without Laws
Authors: Schweber Silvan S.
Published: January 2009

During the 1970s, something deeply consequential happened in the cultural, economic, and social relationships between science and technology. Paul Forman has proposed that the abrupt reversal of the culturally ascribed primacy in the science-technology relationship circa 1980 be taken as a demarcation of postmodernity from modernity. Modernity’s most basic cultural presuppositions—the superiority of theory to practice, the elevation of the public over the private and that of the disinterested over the interested, and the belief that the means sanctify the ends—were ascribed to science. In postmodernity, science is subsumed under technology, and the status of technology relative to science reflects our pragmatic-utilitarian subordination of means to ends. These cultural changes have resonated with deep epistemological and ontological changes within the sciences themselves, and all these have manifested themselves in universities becoming entrepreneurial, and the consequences thereof. Science Without Laws insightfully illustrates some of the changes within the life and human sciences by analyzing the role played by model systems and case studies.
Welcome Home, Descartes! Rethinking the Anthropology of the Body
Authors: Ecks Stefan
Published: January 2009

For many scholars, the Cartesian mind/body split is one of the fundamental mistakes of the Western scientific tradition. Anthropologists who study notions of the body in cultures around the world regularly take Descartes as their point of departure. Many also suggest that breaking free from Descartes is politically liberating: if the mindful body could be rediscovered, society could move away from its materialist, positivist, and commodity-fetishizing ways. Beyond the Body Proper is anthropology’s best and most comprehensive anti-Cartesian manifesto to date. This volume brings together some of the finest studies on the cultural and historical diversity of bodies and minds. Yet anthropologists’ blanket rejection of the mind/body dualism seems politically self-defeating. If anthropologists want to criticize racism, gender hierarchies, or discrimination against disabled people, they need to believe that the mind is independent from the body. In other words, they need to uphold the Cartesian split.
Silence, Rape and Politics in Measure for Measure : Close Readings in Theatre History
Authors: Aebischer Pascale
Published: January 2009

This article builds on Philip McGuire's work on the silences in Measure for Measure to re-examine them in the light of scholarship in theatre history (in particular Tiffany Stern's work on rehearsal and Scott McMillin's reflections on the sharer-apprentice relationship) to suggest that the cue-script and apprenticeship systems combined to put the boy performer playing Isabella in a position which would highlight his momentary embarrassment at being unable to respond to the Duke's proposal. The article produces close readings of the encounters between Isabella and Angelo in the centre of the play and relates those to their silence at the end to argue that the Duke's marriage proposal in act 5 is a replay of Angelo's attempted rape of Isabella in act 2. This observation becomes a springboard for looking at present-day performance practices and arguing that six RSC productions staged between 1970 and 1998 (directed by John Barton (1970), Barry Kyle (1978), Adrian Noble (1983), Steven Pimlott (1994) and Michael Boyd (1998)) each engage with contemporary politics in their respective stagings of Isabella's silence. A complex understanding of the relationship between silence, rape and politics underpins each staging, whether it ends on stunned unresponsiveness, a kiss, or a cathartic slap in the face.
“[H]urt in that service”: The Norwich Affray and Early Modern Reactions to Injuries during Dramatic Performances
Authors: Northway Kara
Published: January 2009

The extravagant pageantry and sheer mass of bodies involved in Early Modern processional drama frequently caused physical and economic damage to property and people. The normalisation of such violence, along with the processions' employment of professional actors, ordinary workers and members of the audience as part of the drama, obscured the boundaries of stage and real action. This led to cases such as the Norwich affray, in which a few actors and a spectator, Henry Brown, chased down and murdered a gatecrasher. This essay focuses on the complex agency of injured workers and audience-actors in processions, especially examining Brown at the affray, arguing that violent movement had competing interpretations by contemporaries during and after the procession - meanings that, depending on how they defined acceptable violence, they rewarded or misinterpreted and punished.
Portable Power: Inventor Samuel Ruben and the Birth of Duracell
Authors: Hintz Eric S.
Published: January 2009

This article explores the invention and commercialization of mercury and alkaline batteries by independent inventor Samuel Ruben and his licensee, the P. R. Mallory Company, known today as Duracell. During World War II, the Army Signal Corps turned to the National Inventors Council to help them solve operational problems with zinc-carbon batteries; Ruben invented a more reliable mercury battery, which Mallory manufactured. Ruben and Mallory then adapted the cells for peacetime applications like hearing aids, watches, and pacemakers, placing miniature batteries at the vanguard of the postwar miniaturization movement alongside the more heralded transistor. The company later developed cheaper alkaline batteries and modified its marketing strategy, transforming the battery from a component of other products to a consumer product in its own right. Mallory effectively pursued a “mixed innovation strategy,” relying on long-term consulting relationships with outside inventors like Ruben while simultaneously investing in its own scientific research laboratories.
Michael of Rhodes: A Fifteenth-Century Mariner and His Book
Authors: Long Pamela O.
Published: January 2009

This essay concerns the cover illustration of the issue of

Technology and Culture

(a drawing of a Venetian galley) and the manuscript in which it is found. The codex was written and illustrated by a fifteenth-century oarsman, Michael of Rhodes, who worked his way up to officer positions in a forty-year career on Venetian galleys. The essay describes the manuscript and the complex process of making a three-volume facsimile edition, edited by Pamela O. Long, David McGee, and Alan M. Stahl, published by MIT Press in 2009. Michael’s remarkable, illustrated codex of more than 400 pages, created c. 1435–1436, contains the first extant treatise on shipbuilding in the world, an extensive tract on commercial mathematics, calendrical and astrological material, portolans (i.e., sailing directions), and Michael’s own autobiographical service record.
Bell and Gray: Just a Coincidence?
Authors: Finn Bernard S.
Published: January 2009

This essay review examines Seth Shulman's

The Telephone Gambit

, A. Edward Evenson's

The Telephone Patent Conspiracy of 1876

, Burton Baker's

The Gray Matter: The Forgotten Story of the Telephone

, and Charlotte Gray's

Reluctant Genius: Alexander Graham Bell and the Passion for Invention

. Baker, Evenson, and Shulman argue that Bell inserted a clause in his 1876 patent application describing a variable-resistance (liquid) transmitter that he had improperly learned about from Elisha Gray's caveat application. Although Finn agrees with their basic claim, he contends it was irrelevant to the patent's validity. The liquid transmitter was worthless. Bell received no patent credit for it or for the broader claim to a variable resistance transmitter. He was, however, granted sweeping credit for voice transmission by “undulating” electrical currents. Finn praises amateur historians (Baker and Evenson) for research efforts, and popularizers (Shulman and Gray) for helping to disseminate the work of professional historians. He criticizes Shulman (in particular) and Gray for errors and for not giving proper acknowledgment to predecessors. He proposes steps that professional historians of technology might take to improve the quality of popular writings through guidelines for writers and publishers.
The Mechanization of Brickmaking
Authors: Holley I. B.
Published: January 2009

Brickmaking for millennia—BC down to the early nineteenth century—was a highly labor-intensive undertaking. Early attempts to reduce this burden involved wooden stamping presses, none notably successful. Not until the metal-working industry developed did more effective mechanization of brickmaking arrive. Late in the century a new concept, extrusion through a die, brought greater success. Later kilns and improved knowledge of clays brought mechanization to its culmination. In the United States, much of this development took place in Philadelphia.
From Lab to iPod: A Story of Discovery and Commercialization in the Post–Cold War Era
Authors: McCray W. Patrick
Published: January 2009

The 1988 discovery, made simultaneously in two European laboratories, of giant magnetoresistance (GMR) became the basis for the Nobel prize in physics two decades later. Companies like IBM rapidly commercialized the discovery, which paved the way for major advances in data storage commonly seen in computers and portable music players. GMR also helped catalyze a new field of research known as “spintronics” and provided a rationale for a major global investment in nanotechnology. This article examines the process through which a basic physics discovery was made and then commercialized. In this narrative, military agencies and commercial firms acting as “institutional entrepreneurs” fostered the growth of spintronics (and nanotechnology) in the post-Cold War environment. Finally, it concludes by exploring the validity of the linear model for research and the shifting boundaries between contemporary science and technology.
On the Side: Car Culture in the USSR, 1960s–1980s
Authors: Siegelbaum Lewis H.
Published: January 2009

Accommodating itself to private ownership of automobiles relatively late in the twentieth century, the Soviet government did not make it easy for motorists to obtain what they needed to keep their cars in working order. In fact, it was almost impossible for them to do so without violating the canons of Communist morality, to say nothing of Soviet law. The shortage of spare parts, fuel, repair services, legally sanctioned garage space, and other accoutrements of an automobile-based society—plus the resort to the second, gray, shadow (a.k.a. “on-the-side”) economy—defined the specificity of Soviet car culture. Based on a wide range of sources that includes interviews, contemporary Soviet newspapers, magazines, and social science literature, belles letters and film comedies, as well as Western research, this article explores Soviet car culture in terms of its spatial dimensions and the kinds of relationships that occurred within them. It concludes with observations about the culture’s internal contradictions and dynamics.
The Historian of Technology and Her True Country
Authors: Usselman Steven W.
Published: January 2009

This address, presented in Lisbon at the Fiftieth Annual Meeting of the Society for the History of Technology (SHOT), reflects upon questions of nationalism and technology that have persistently informed scholarship in the discipline. Drawing upon the work of Flannery O’Connor, a Southerner writer whose stories and prose addressed themes of region, race, and technological progress at the height of the so-called American Century, the essay contemplates how historians of technology structure stories about the past in ways that respect both universal tendencies and the particulars of specific times and places. In exploring relations between technology and culture, historians have derived especially useful insights from focusing upon the practice of governance, often by deploying techniques from political economy and economic history. Such an approach holds great promise in an age characterized by a new wave of globalization marked by significant innovation in communications and information technology.
The COP9 Signalosome Is Required for Light-Dependent Timeless Degradation andDrosophilaClock Resetting
Authors: Knowles Alyson , Koh Kyunghee , Wu June-Tai , Chien Cheng-Ting , Chamovitz Daniel A. , Blau Justin
Published: January 2009

The ubiquitin–proteasome system plays a major role in the rhythmic accumulation and turnover of molecular clock components. In turn, these ∼24 h molecular rhythms drive circadian rhythms of behavior and physiology. InDrosophila, the ubiquitin–proteasome system also plays a critical role in light-dependent degradation of the clock protein Timeless (TIM), a key step in the entrainment of the molecular clocks to light–dark cycles. Here, we investigated the role of the COP9 signalosome (CSN), a general regulator of protein degradation, in fly circadian rhythms. We found that null mutations in the genes encoding the CSN4 and CSN5 subunits prevent normal TIM degradation by light in the pacemaker lateral neurons (LNs) as does LN-specific expression of a dominant-negativeCSN5transgene. These defects are accompanied by strong reductions in behavioral phase shifts of adult flies lacking normal CSN5 activity in LNs. Defects in TIM degradation and resetting of behavioral phases were rescued by overexpression of Jetlag (JET), the F-box protein required for light-mediated TIM degradation. Flies lacking normal CSN activity in all clock neurons are rhythmic in constant light, a phenotype previously associated withjetmutants. Together, these data indicate that JET and the CSN lie in a common pathway leading to light-dependent TIM degradation. Surprisingly, we found that manipulations that strongly inhibit CSN activity had minimal effects on circadian rhythms in constant darkness, indicating a specific role for the CSN in light-mediated TIM degradation.
Head Direction Cell Activity in Mice: Robust Directional Signal Depends on Intact Otolith Organs
Authors: Yoder Ryan M. , Taube Jeffrey S.
Published: January 2009

The head direction (HD) cell signal is a representation of an animal's perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice with that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficienttiltedmice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified intiltedmice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells intiltedmice were controlled by landmark rotation but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared with rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues.
Connectivity-Based Parcellation of Human Cingulate Cortex and Its Relation to Functional Specialization
Authors: Beckmann Matthias , Johansen-Berg Heidi , Rushworth Matthew F. S.
Published: January 2009

Whole-brain neuroimaging studies have demonstrated regional variations in function within human cingulate cortex. At the same time, regional variations in cingulate anatomical connections have been found in animal models. It has, however, been difficult to estimate the relationship between connectivity and function throughout the whole cingulate cortex within the human brain. In this study, magnetic resonance diffusion tractography was used to investigate cingulate probabilistic connectivity in the human brain with two approaches. First, an algorithm was used to search for regional variations in the probabilistic connectivity profiles of all cingulate cortex voxels with the whole of the rest of the brain. Nine subregions with distinctive connectivity profiles were identified. It was possible to characterize several distinct areas in the dorsal cingulate sulcal region. Several distinct regions were also found in subgenual and perigenual cortex. Second, the probabilities of connection between cingulate cortex and 11 predefined target regions of interest were calculated. Cingulate voxels with a high probability of connection with the different targets formed separate clusters within cingulate cortex. Distinct connectivity fingerprints characterized the likelihood of connections between the extracingulate target regions and the nine cingulate subregions. Last, a meta-analysis of 171 functional studies reporting cingulate activation was performed. Seven different cognitive conditions were selected and peak activation coordinates were plotted to create maps of functional localization within the cingulate cortex. Regional functional specialization was found to be related to regional differences in probabilistic anatomical connectivity.
Dynamical Response Properties of Neocortical Neuron Ensembles: Multiplicative versus Additive Noise
Authors: Boucsein Clemens , Tetzlaff Tom , Meier Ralph , Aertsen Ad , Naundorf Björn
Published: January 2009

To understand the mechanisms of fast information processing in the brain, it is necessary to determine how rapidly populations of neurons can respond to incoming stimuli in a noisy environment. Recently, it has been shown experimentally that an ensemble of neocortical neurons can track a time-varying input current in the presence of additive correlated noise very fast, up to frequencies of several hundred hertz. Modulations in the firing rate of presynaptic neuron populations affect, however, not only the mean but also the variance of the synaptic input to postsynaptic cells. It has been argued that such modulations of the noise intensity (multiplicative modulation) can be tracked much faster than modulations of the mean input current (additive modulation). Here, we compare the response characteristics of an ensemble of neocortical neurons for both modulation schemes. We injected sinusoidally modulated noisy currents (additive and multiplicative modulation) into layer V pyramidal neurons of the rat somatosensory cortex and measured the trial and ensemble-averaged spike responses for a wide range of stimulus frequencies. For both modulation paradigms, we observed low-pass behavior. The cutoff frequencies were markedly high, considerably higher than the average firing rates. We demonstrate that modulations in the variance can be tracked significantly faster than modulations in the mean input. Extremely fast stimuli (up to 1 kHz) can be reliably tracked, provided the stimulus amplitudes are sufficiently high.
Dramatically Decreased Cocaine Self-Administration in Dopamine But Not Serotonin Transporter Knock-Out Mice
Authors: Thomsen Morgane , Hall F. Scott , Uhl George R. , Caine S. Barak
Published: January 2009

There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT−/−), the serotonin transporter (SERT−/−), or both (DAT−/−SERT−/−) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarly affected. We used a broad range of experimental conditions that included acquisition without previous training, behavior established with food training and subsequent testing with food, cocaine or a direct dopamine agonist as reinforcers, fixed ratio and progressive ratio schedules of reinforcement, and a reversal procedure. Wild-type mice readily acquired cocaine self-administration and showed dose–response curves characteristic of the schedule of reinforcement that was used. While some DAT−/−mice appeared to acquire cocaine self-administration transiently, almost all DAT−/−mice failed to self-administer cocaine reliably. Food-maintained behaviors were not decreased by the DAT mutation, and IV self-administration of a direct dopamine agonist was robust in the DAT−/−mice. In contrast to those mice, cocaine's reinforcing effects were not diminished in SERT−/−mice under any of the conditions tested, except for impaired initial acquisition of both food- and cocaine-maintained behavior. These findings support the notion that the DAT, but not the SERT, is critical in mediating the reinforcing effects of cocaine.
The Rheb–mTOR Pathway Is Upregulated in Reactive Astrocytes of the Injured Spinal Cord
Authors: Codeluppi Simone , Svensson Camilla I. , Hefferan Michael P. , Valencia Fatima , Silldorff Morgan D. , Oshiro Masakatsu , Marsala Martin , Pasquale Elena B.
Published: January 2009

Astrocytes in the CNS respond to tissue damage by becoming reactive. They migrate, undergo hypertrophy, and form a glial scar that inhibits axon regeneration. Therefore, limiting astrocytic responses represents a potential therapeutic strategy to improve functional recovery. It was recently shown that the epidermal growth factor (EGF) receptor is upregulated in astrocytes after injury and promotes their transformation into reactive astrocytes. Furthermore, EGF receptor inhibitors were shown to enhance axon regeneration in the injured optic nerve and promote recovery after spinal cord injury. However, the signaling pathways involved were not elucidated. Here we show that in cultures of adult spinal cord astrocytes EGF activates the mTOR pathway, a key regulator of astrocyte physiology. This occurs through Akt-mediated phosphorylation of the GTPase-activating protein Tuberin, which inhibits Tuberin's ability to inactivate the small GTPase Rheb. Indeed, we found that Rheb is required for EGF-dependent mTOR activation in spinal cord astrocytes, whereas the Ras–MAP kinase pathway does not appear to be involved. Moreover, astrocyte growth and EGF-dependent chemoattraction were inhibited by the mTOR-selective drug rapamycin. We also detected elevated levels of activated EGF receptor and mTOR signaling in reactive astrocytesin vivoin an ischemic model of spinal cord injury. Furthermore, increased Rheb expression likely contributes to mTOR activation in the injured spinal cord. Interestingly, injured rats treated with rapamycin showed reduced signs of reactive gliosis, suggesting that rapamycin could be used to harness astrocytic responses in the damaged nervous system to promote an environment more permissive to axon regeneration.
Neuropeptide Y Fragments Derived from Neprilysin Processing Are Neuroprotective in a Transgenic Model of Alzheimer's Disease
Authors: Rose John B. , Crews Leslie , Rockenstein Edward , Adame Anthony , Mante Michael , Hersh Louis B. , Gage Fred H. , Spencer Brian , Potkar Rewati , Marr Robert A. , Masliah Eliezer
Published: January 2009

The endopeptidase neprilysin (NEP) is a major amyloid-β (Aβ) degrading enzyme and has been implicated in the pathogenesis of Alzheimer's disease. Because NEP cleaves substrates other than Aβ, we investigated the potential role of NEP-mediated processing of neuropeptides in the mechanisms of neuroprotectionin vivo. Overexpression of NEP at low levels in transgenic (tg) mice affected primarily the levels of neuropeptide Y (NPY) compared with other neuropeptides.Ex vivoandin vivostudies in tg mice and in mice that received lentiviral vector injections showed that NEP cleaved NPY into C-terminal fragments (CTFs), whereas silencing NEP reduced NPY processing. Immunoblot and mass spectrometry analysis showed that NPY 21–36 and 31–36 were the most abundant fragments generated by NEP activityin vivo. Infusion of these NPY CTFs into the brains of APP (amyloid precursor protein) tg mice ameliorated the neurodegenerative pathology in this model. Moreover, the amidated NPY CTFs protected human neuronal cultures from the neurotoxic effects of Aβ. This study supports the possibility that the NPY CTFs generated during NEP-mediated proteolysis might exert neuroprotective effectsin vivo. This function of NEP represents a unique example of a proteolytic enzyme with dual action, namely, degradation of Aβ as well as processing of NPY.
Morphine Enhances Microglial Migration through Modulation of P2X4Receptor Signaling
Authors: Horvath Ryan J. , DeLeo Joyce A.
Published: January 2009

Opioids, although fundamental to the treatment of pain, are limited in efficacy by side effects including tolerance and hyperalgesia. Using anin vitroculture system, we report that morphine increased microglial migration via a novel interaction between μ-opioid and P2X4receptors, which is dependent upon PI3K/Akt pathway activation. Morphine at 100 nmenhanced migration of primary microglial cells toward adenosine diphosphate by 257, 247, 301, 394, and 345% following 2, 6, 12, 24, and 48 h of stimulation, respectively. This opioid-dependent migration effect was inhibited by naloxone and confirmed to be μ-opioid receptor-dependent through the use of selective agonists and antagonists. PPADS [pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid)], a P2X1–3,5–7antagonist, had no effect on microglial migration; however, TNP-ATP [2′,3′-O-(2,4,6-trinitrophenyl)-ATP], a P2X1–7antagonist, inhibited morphine-induced migration, suggesting a P2X4receptor-mediated effect. The PI3K inhibitors wortmannin and LY294002 decreased morphine-induced microglial migration. Iba1 protein, a microglial marker, and P2X4receptor expression were significantly increased after 6, 12, 24, and 48 h of morphine stimulation. Together, these results provide evidence for two phases of morphine effects on microglia. The initial phase takes place in minutes, involves PI3K/Akt pathway activation and leads to acutely enhanced migration. The longer-term phase occurs on the order of hours and involves increased expression of Iba1 and P2X4receptor protein, which imparts a promigratory phenotype and is correlated with even greater migration. These data provide the first necessary step in supporting microglial migration as an attractive target for the prevention or attenuation of morphine-induced side effects including tolerance and hyperalgesia.
Contrasting Activity Profile of Two Distributed Cortical Networks as a Function of Attentional Demands
Authors: Popa Daniela , Popescu Andrei T. , Paré Denis
Published: January 2009

Recent human functional MRI (fMRI) studies have revealed that two widely distributed groups of cortical areas display inverse changes in activity when attentional demands increase, with one group showing higher (task-on) and the second lower (task-off) blood oxygen level-dependent (BOLD) signals. Moreover, task-on and task-off regions also exhibit slow (<0.2 Hz) inversely correlated fluctuations in BOLD signal at rest. However, the neuronal correlates of these reciprocal BOLD signal fluctuations are unknown. Here, we addressed this question using simultaneous recordings of unit activity and local field potentials (LFPs) in the cat homologues of task-on and task-off regions. In all states of vigilance, LFP power was lower in task-off than task-on regions with no difference in firing rates. Both sets of regions displayed slow (0.5–0.15 Hz) cyclical modulations in LFP power in all frequency bands but with large and variable phase differences such that task-on and task-off regions were often anticorrelated. Inversely correlated LFP power fluctuations were state-dependent in that they were much more frequent in waking and paradoxical sleep than in slow-wave sleep. Moreover, consistent with fMRI findings, when attentional demands increased, LFP power in task-on and task-off regions changed in opposite directions, further augmenting and decreasing, respectively. At odds with previous fMRI studies, however, the decreased LFP power in task-off regions was associated with increased firing rates, suggesting that the engagement of task-off regions might not be reduced but in fact enhanced during attention.
Parallels and Nonparallels between Language and Music
Authors: Jackendoff Ray
Published: January 2009

THE PARALLELS BETWEEN LANGUAGE AND MUSIC CAN BE explored only in the context of (a) the differences between them, and (b) those parallels that are also shared with other cognitive capacities. The two differ in many aspects of structure and function, and, with the exception of the metrical grid, all aspects they share appear to be instances of more general capacities.
Travelling Through Pitch Space Speeds up Musical Time
Authors: Firmino Érico Artioli , Bueno José Lino Oliveira , Bigand Emmanuel
Published: January 2009

SEVERAL MODELS OF TIME ESTIMATION HAVE BEEN developed in psychology; a few have been applied to music. In the present study, we assess the influence of the distances travelled through pitch space on retrospective time estimation. Participants listened to an isochronous chord sequence of 20-s duration. They were unexpectedly asked to reproduce the time interval of the sequence. The harmonic structure of the stimulus was manipulated so that the sequence either remained in the same key (CC) or travelled through a closely related key (CFC) or distant key (CGbC). Estimated times were shortened when the sequence modulated to a very distant key. This finding is discussed in light of Lerdahl's Tonal Pitch Space Theory (2001), Firmino and Bueno's Expected Development Fraction Model (in press), and models of time estimation.
Can Birth Weight Standards Based on Healthy Populations Improve the Identification of Small-for-Gestational-Age Newborns at Risk of Adverse Neonatal Outcomes?
Authors: Ferdynus Cyril , Quantin Catherine , Abrahamowicz Michal , Platt Robert , Burguet Antoine , Sagot Paul , Binquet Christine , Gouyon Jean-Bernard
Published: January 2009

OBJECTIVES. To develop neonatal growth standards based on (1) the entire population of live births and (2) a healthy subpopulation and compare them in identifying infants as small for gestational age and at risk of adverse neonatal outcomes.

PATIENTS AND METHODS. We included all births, between 28 and 41 weeks of gestation, reported in Burgundy (France) from 2000 to 2006. Fetal deaths, multiple births, and chromosomal aberrations were excluded. We first estimated separate birth weight distributions at each week of gestation for (1) all neonates and (2) only infants born from women without maternal diseases. Small for gestational age was defined as a birth weight below the 10th percentile of the corresponding standard. We assessed the associations of small for gestational age on the basis of the alternative definitions, with mortality and major neonatal outcomes.

RESULTS. We included 127 584 live births. For term newborns, small for gestational age was significantly associated with an increased risk of death with both standards. In contrast, for preterm newborns (32–36 weeks), small for gestational age was not significantly associated with mortality and morbidity. Very preterm infants (28–31 weeks) identified as small for gestational age according to the healthy-population standard were at higher risk of chronic lung disease and intraventricular hemorrhage. When using the entire-population standard, small for gestational age was associated with chronic lung disease but not intraventricular hemorrhage. The area under the receiver operating characteristic for predicting an intraventricular hemorrhage was significantly greater for small for gestational age defined with the healthy-population standard compared with small for gestational age classified with the entire-population standard.

CONCLUSIONS. Neonatal growth standards based on healthy populations could improve the identification of very preterm neonates as small for gestational age and at risk of intraventricular hemorrhage.
Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children
Authors: Mosholder Andrew D. , Gelperin Kate , Hammad Tarek A. , Phelan Kathleen , Johann-Liang Rosemary
Published: January 2009

OBJECTIVES. To gain a better understanding of the capacity of psychostimulant medications to induce adverse psychiatric reactions and determine the frequency of such reactions, we analyzed postmarketing surveillance data and clinical trial data for drugs, either approved or under development, for the treatment of attention-deficit/hyperactivity disorder.

METHODS. The US Food and Drug Administration requested manufacturers of drugs approved for attention-deficit/hyperactivity disorder or with active clinical development programs for that indication to search their electronic clinical trial databases for cases of psychosis or mania using prespecified search terms. The manufacturers supplied descriptions of clinical trials, numbers of patients exposed to study drug, and duration of exposure to permit calculations of incidence rates. Independently, cases of psychosis or mania in children and adults for drugs used to treat attention-deficit/hyperactivity disorder from the Food and Drug Administration Adverse Event Reporting System safety database were analyzed. Manufacturers were asked to conduct similar analyses of their postmarketing surveillance databases.

RESULTS. We analyzed data from 49 randomized, controlled clinical trials in the pediatric development programs for these products. A total of 11 psychosis/mania adverse events occurred during 743 person-years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person-years of placebo exposure in the same trials. The rate per 100 person-years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In ∼90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children.

CONCLUSIONS. Patients and physicians should be aware that psychosis or mania arising during drug treatment of attention-deficit/hyperactivity disorder may represent adverse drug reactions.