bluuebunny/crossref_metadata_2025 huggingface dataset:
Hermeneutic resistance: Four test cases for the notion of literary uninterpretability
Authors: Orr Leonard
Published: October 2007

What does it mean to say that a given text is uninterpretable? While there are always the examples of accidental uninterpretability (cases of works that have suffered severe physical damage, texts in real languages not known by readers, references and allusions that were not kept alive as intertexts for other groups), this is not the focus of criticism or hermeneutics. There is a long and important history of purposeful obscurity, of authors who, for whatever reasons, made their texts difficult and challenging for any reader they constructed. Others did this without regard for the readers' responses, or so it would seem, following their own private visions, compositional or generative rules and constraints, or because they were in some sense writing-under-the influence (to cover a group from Plato's poets to the mescaline-induced writing and art of Henri Michaux). The test cases for this article will be drawn from works by authors with a developed aesthetics of functional indeterminacy (such as Gertrude Stein, James Joyce's Finnegans Wake, Samuel Beckett's later fiction), practitioners of Dadaism, OULIP0, Surrealism, automatic writing, aleatory approaches, as well as visionary, drug-influenced, and insane authors. My argument will take issue with the idea that any texts remain uninterpretable by critics even if these works have a high degree of indeterminacy or completeness, no matter what rules or motives were being followed by the authors.
The genres speak: Using large corpora to profile generic registers
Authors: Dillon George L
Published: October 2007

This article shows how useful the evidence retrievable from large and easily available corpora can be in identifying the distinguishing lexical and phrasal characteristics of generic registers. Here attention is directed toward the lexical register of two genres of “disposable writing”: news writing (in Part I) and romance fiction (in Part II, where it is contrasted with its near neighbour, “sexy” fiction). But use of corpus evidence on register profiling is still at a relatively early stage, so that a number of large topics merit further discussion here: What words and phrases are characteristic of individual genres and how much more common are they in the genres than in other writings? Are there national differences in the “style” of genres? What is the functional basis or rationale for these genre “styles”? These questions are explored along the way to proposing that registers be viewed as genres' fashions of speaking. The study also uncovers one distinctive aspect of romance writing not widely recognised, namely its extremely heavy and varied use of inquit tags.
Spinal Astrocyte Glutamate Receptor 1 Overexpression after Ischemic Insult Facilitates Behavioral Signs of Spasticity and Rigidity
Authors: Hefferan Michael P. , Kucharova Karolina , Kinjo Kiyohiko , Kakinohana Osamu , Sekerkova Gabriella , Nakamura Seiya , Fuchigami Tatsuya , Tomori Zoltan , Yaksh Tony L. , Kurtz Neil , Marsala Martin
Published: October 2007

Using a rat model of ischemic paraplegia, we examined the expression of spinal AMPA receptors and their role in mediating spasticity and rigidity. Spinal ischemia was induced by transient occlusion of the descending aorta combined with systemic hypotension. Spasticity/rigidity were identified by simultaneous measurements of peripheral muscle resistance (PMR) and electromyography (EMG) before and during ankle flexion. In addition, Hoffman reflex (H-reflex) and motor evoked potentials (MEPs) were recorded from the gastrocnemius muscle. Animals were implanted with intrathecal catheters for drug delivery and injected with the AMPA receptor antagonist NGX424 (tezampanel), glutamate receptor 1 (GluR1) antisense, or vehicle. Where intrathecal vehicle had no effect, intrathecal NGX424 produced a dose-dependent suppression of PMR [ED50of 0.44 μg (0.33–0.58)], as well as tonic and ankle flexion-evoked EMG activity. Similar suppression of MEP and H-reflex were also seen. Western blot analyses of lumbar spinal cord tissue from spastic animals showed a significant increase in GluR1 but decreased GluR2 and GluR4 proteins. Confocal and electron microscopic analyses of spinal cord sections from spastic animals revealed increased GluR1 immunoreactivity in reactive astrocytes. Selective GluR1 knockdown by intrathecal antisense treatment resulted in a potent reduction of spasticiy and rigidity and concurrent downregulation of neuronal/astrocytic GluR1 in the lumbar spinal cord. Treatment of rat astrocyte cultures with AMPA led to dose-dependent glutamate release, an effect blocked by NGX424. These data suggest that an AMPA/kainate receptor antagonist can represent a novel therapy in modulating spasticity/rigidity of spinal origin and that astrocytes may be a potential target for such treatment.
Weber's Law in Decision Making: Integrating Behavioral Data in Humans with a Neurophysiological Model
Authors: Deco Gustavo , Scarano Leandro , Soto-Faraco Salvador
Published: October 2007

Recent single-cell studies in monkeys (Romo et al., 2004) show that the activity of neurons in the ventral premotor cortex covaries with the animal's decisions in a perceptual comparison task regarding the frequency of vibrotactile events. The firing rate response of these neurons was dependent only on the frequency differences between the two applied vibrations, the sign of that difference being the determining factor for correct task performance. We present a biophysically realistic neurodynamical model that can account for the most relevant characteristics of this decision-making-related neural activity. One of the nontrivial predictions of this model is that Weber's law will underlie the perceptual discrimination behavior. We confirmed this prediction in behavioral tests of vibrotactile discrimination in humans and propose a computational explanation of perceptual discrimination that accounts naturally for the emergence of Weber's law. We conclude that the neurodynamical mechanisms and computational principles underlying the decision-making processes in this perceptual discrimination task are consistent with a fluctuation-driven scenario in a multistable regime.
Aging in Binaural Hearing Begins in Mid-Life: Evidence from Cortical Auditory-Evoked Responses to Changes in Interaural Phase
Authors: Ross Bernhard , Fujioka Takako , Tremblay Kelly L. , Picton Terence W.
Published: October 2007

Older adults often have difficulty understanding speech in a noisy environment or with multiple speakers. In such situations, binaural hearing improves the signal-to-noise ratio. How does this binaural advantage change with increasing age? Using magnetoencephalography, we recorded cortical activity evoked by changes in interaural phase differences of amplitude-modulated tones. These responses occurred for frequencies up to 1225 Hz in young subjects but only up to 940 Hz in middle-aged and 760 Hz in older adults. Behavioral thresholds also decreased with increasing age but were more variable, likely because some older adults make effective use of compensatory mechanisms. The reduced frequency range for binaural hearing became significant in middle age, before decline in hearing sensation and the morphology of cortical responses, which became apparent only in the older subjects. This study provides evidence from human physiological data for the early onset of biological aging in binaural hearing.
Myosin Va Controls Oligodendrocyte Morphogenesis and Myelination
Authors: Sloane Jacob A. , Vartanian Timothy K.
Published: October 2007

A product of myosin Va mutations, Griscelli's syndrome type 1 (GS1) is characterized by several neurologic deficits including quadraparesis, mental retardation, and seizures. Although multiple studies have not clearly established a cause for the neurologic deficits linked with GS1, a few reports suggest that GS1 is associated with abnormal myelination, which could cause the neurologic deficits seen with GS1. In this report, we investigate whether myosin Va is critical to oligodendrocyte morphology and to myelinationin vivo. We found that myosin Va-null mice exhibit significantly impaired myelination of the brain, optic nerve, and spinal cord. Oligodendrocytes express myosin Va and loss of myosin Va function resulted in significantly smaller lamellas and decreased process number, length, and branching of oligodendrocytes. Loss of myosin Va function also blocked distal localization of vesicle-associated membrane protein 2 (VAMP2), which is known to associate with myosin Va. When VAMP2 function was disrupted, oligodendrocytes exhibited similar morphologic deficits to what is seen with functional ablation of myosin Va. Our findings establish a role for both myosin Va and VAMP2 in oligodendrocyte function as it relates to myelination.
The Marginal Zone/Layer I as a Novel Niche for Neurogenesis and Gliogenesis in Developing Cerebral Cortex
Authors: Costa Marcos R. , Kessaris Nicoletta , Richardson William D. , Götz Magdalena , Hedin-Pereira Cecilia
Published: October 2007

The cellular diversity of the cerebral cortex is thought to arise from progenitors located in the ventricular zone and subventricular zone in the telencephalon. Here we describe a novel source of progenitors located outside these two major germinative zones of the mouse cerebral cortex that contributes to neurogenesis and gliogenesis. Proliferating cells first appear in the preplate of the embryonic cerebral cortex and further increase in the marginal zone during mid and late neurogenesis. The embryonic marginal zone progenitors differ in their molecular characteristics as well as the size and identity of their clonal progeny from progenitors isolated from the ventricular zone and subventricular zone. Time-lapse video microscopy and clonal analysisin vitrorevealed that the marginal zone progenitor pool contains a large fraction of oligodendrocyte or astrocyte progenitors, as well as neuronal and bipotent progenitors. Thus, marginal zone progenitors are heterogenous in regard to their fate specification, as well as in regard to their region of origin (pallial and subpallial) as revealed byin vivofate mapping. The local environment in the marginal zone tightly regulates the size of this novel progenitor pool, because both basement membrane defects in lamininγ1−/−mice or alterations in the cellular composition of the marginal zone in Pax6Small Eyemutant mice lead to an increase in the marginal zone progenitor pool. In conclusion, we have identified a novel source of neuronal and glial progenitors in the marginal zone of the developing cerebral cortex with properties notably distinct from those of ventricular zone and subventricular zone progenitors.
Methamphetamine Self-Administration and Voluntary Exercise Have Opposing Effects on Medial Prefrontal Cortex Gliogenesis
Authors: Mandyam Chitra D. , Wee Sunmee , Eisch Amelia J. , Richardson Heather N. , Koob George F.
Published: October 2007

Psychostimulant abuse produces deficits in prefrontal cortex (PFC) function, whereas physical activity improves PFC-dependent cognition and memory. The present study explored the vulnerability of medial PFC (mPFC) precursor proliferation and survival to methamphetamine self-administration and voluntary exercise, factors that may have opposing effects on mPFC plasticity to facilitate functional consequences. Intermittent 1 h access to methamphetamine (I-ShA) increased, but daily 1 and 6 h access decreased, proliferation and survival, with dose-dependent effects on mature cell phenotypes. All groups showed increased cell death. Voluntary exercise enhanced proliferation and survival but, in contrast to methamphetamine exposure, did not alter cell death or mature phenotypes. Furthermore, enhanced cell survival by I-ShA and voluntary exercise had profound effects on gliogenesis with differential regulation of oligodendrocytes versus astrocytes. In addition, new cells in the adult mPFC stain for the neuronal marker neuronal nuclear protein, although enhanced cell survival by I-ShA and voluntary exercise did not result in increased neurogenesis. Our findings demonstrate that mPFC gliogenesis is vulnerable to psychostimulant abuse and physical activity with distinct underlying mechanisms. The susceptibility of mPFC gliogenesis to even modest doses of methamphetamine could account for the pronounced pathology linked to psychostimulant abuse.
Intraburst and Interburst Signaling by Climbing Fibers
Authors: Maruta Jun , Hensbroek Robert A. , Simpson John I.
Published: October 2007

Although cerebellar Purkinje cell complex spikes occur at low frequency (∼1/s), each complex spike is often associated with a high-frequency burst (∼500/s) of climbing fiber spikes. We examined the possibility that signals are present within the climbing fiber bursts. By intracellularly recording from depolarized, nonspiking Purkinje cells in anesthetized pigmented rabbits, climbing fiber burst patterns were investigated by determining the number of components in the induced compound EPSPs during spontaneous activity and during visual stimulation. For our sample of 43 cells, >70% of all EPSPs were of the compound type composed of two or three EPSPs. During spontaneous activity, the number of components in each compound EPSP was not related to the latency to the succeeding compound EPSP. Conversely, the number of components in each compound EPSP was related to its latency after the preceding compound EPSP. This latency increased from 0.62 s for one-component EPSPs to 1.69 s for compound EPSPs with four or more components. The effect of visual stimulation on the climbing fiber activity was studied in 19 floccular Purkinje cells whose low-frequency interburst climbing fiber response was modulated by movement about the vertical axis. During sinusoidal oscillation (0.1 Hz, ±10°), compound EPSPs with a larger number of components tended to be more prevalent during movement in the excitatory direction than in the inhibitory direction. Thus, climbing fibers can, in addition to modulation of their low interburst frequency, transmit signals in the form of the number of spikes within each high-frequency burst.
Aberrant Hippocampal Activity Underlies the Dopamine Dysregulation in an Animal Model of Schizophrenia
Authors: Lodge Daniel J. , Grace Anthony A.
Published: October 2007

Evidence supports a dysregulation of subcortical dopamine (DA) system function as a common etiology of psychosis; however, the factors responsible for this aberrant DA system responsivity have not been delineated. Here, we demonstrate in an animal model of schizophrenia that a pathologically enhanced drive from the ventral hippocampus (vHipp) can result in aberrant dopamine neuron signaling. Adult rats in which development was disrupted by prenatal methylazoxymethanol acetate (MAM) administration display a significantly greater number of spontaneously firing ventral tegmental DA neurons. This appears to be a consequence of excessive hippocampal activity because, in MAM-treated rats, vHipp inactivation completely reversed the elevated DA neuron population activity and also normalized the augmented amphetamine-induced locomotor behavior. These data provide a direct link between hippocampal dysfunction and the hyper-responsivity of the DA system that is believed to underlie the augmented response to amphetamine in animal models and psychosis in schizophrenia patients.
Subsecond Changes in Top–Down Control Exerted by Human Medial Frontal Cortex during Conflict and Action Selection: A Combined Transcranial Magnetic Stimulation–Electroencephalography Study
Authors: Taylor Paul C. J. , Nobre Anna C. , Rushworth Matthew F. S.
Published: October 2007

Action selection requires choosing one of all the possible conflicting action plans that are available. There is currently a debate as to whether the dorsal medial frontal cortex (dMFC) merely detects or actively resolves response conflict. We used combined on-line transcranial magnetic stimulation and electroencephalographic recording (TMS–EEG) to test whether human dMFC plays a critical causal role in conflict resolution, and whether the mechanism for such a function is via interactions with primary motor cortex. In an Eriksen flanker task, subjects discriminated the direction of the centermost arrow in an array of five, responding with the left or right hand. The lateralized readiness potential (LRP), a measure of relative levels of activity in left and right motor cortices, was also recorded. Reaction times and error rates were higher on incongruent than congruent trials, and incongruent trials produced a positive LRP deflection reflecting initial partial activation of the incorrect response. On one-half of trials, repetitive TMS was applied to left dMFC starting 100 ms before visual stimulus onset and ending 100 ms afterward. TMS disrupted performance by selectively increasing error rates on contralateral (right hand) incongruent trials. TMS also only modulated the LRP on incongruent trials, causing an increased positive deflection (associated with preparation of the incorrect response) starting 180 ms after visual stimulus onset. TMS of a control site did not interfere with behavior or motor cortical activity. dMFC has a direct causal role in resolving conflict during action selection, and the mechanism involves the top–down modulation of primary motor cortical activity.
Top–Down Attentional Deficits in Macaques with Lesions of Lateral Prefrontal Cortex
Authors: Rossi Andrew F. , Bichot Narcisse P. , Desimone Robert , Ungerleider Leslie G.
Published: October 2007

Brain imaging, electrical stimulation, and neurophysiological studies have all implicated the prefrontal cortex (PFC) in the top–down control of attention. Specifically, feedback from PFC has been proposed to bias activity in visual cortex in favor of attended stimuli over irrelevant distracters. To identify which attentional functions are critically dependent on PFC, we removed PFC unilaterally in combination with transection of the corpus callosum and anterior commissure in two macaques. In such a preparation, the ipsilesional hemisphere is deprived of top–down feedback from PFC to visual cortex, and the contralesional hemisphere can serve as an intact normal control. Monkeys were trained to fixate a central cue and discriminate the orientation of a colored target grating presented among colored distracter gratings in either the hemifield affected by the PFC lesion or the normal control hemifield. Locations of the targets and distracters were varied, and the color of the central cue specified the color of the target on each trial. The behavioral response was a bar release, and thus attentional impairments could be distinguished from impaired oculomotor control. When the cue was held constant for many trials, task performance in the affected hemifield was nearly normal. However, the monkeys were severely impaired when the cue was switched frequently across trials. The monkeys were unimpaired in a pop-out task with changing targets that did not require top–down attentional control. The PFC thus appears to play a critical role in the ability to flexibly reallocate attention on the basis of changing task demands.
Activations in Visual and Attention-Related Areas Predict and Correlate with the Degree of Perceptual Learning
Authors: Mukai Ikuko , Kim David , Fukunaga Masaki , Japee Shruti , Marrett Sean , Ungerleider Leslie G.
Published: October 2007

Repeated experience with a visual stimulus can result in improved perception of the stimulus, i.e., perceptual learning. To understand the underlying neural mechanisms of this process, we used functional magnetic resonance imaging to track brain activations during the course of training on a contrast discrimination task. Based on their ability to improve on the task within a single scan session, subjects were separated into two groups: “learners” and “nonlearners.” As learning progressed, learners showed progressively reduced activation in both visual cortex, including Brodmann's areas 18 and 19 and the fusiform gyrus, and several cortical regions associated with the attentional network, namely, the intraparietal sulcus (IPS), frontal eye field (FEF), and supplementary eye field. Among learners, the decrease in brain activations in these regions was highly correlated with the magnitude of performance improvement. Unlike learners, nonlearners showed no changes in brain activations during training. Learners showed stronger activation than nonlearners during the initial period of training in all these brain regions, indicating that one could predict from the initial activation level who would learn and who would not. In addition, over the course of training, the functional connectivity between IPS and FEF in the right hemisphere with early visual areas was stronger for learners than nonlearners. We speculate that sharpened tuning of neuronal representations may cause reduced activation in visual cortex during perceptual learning and that attention may facilitate this process through an interaction of attention-related and visual cortical regions.
Prefrontal Dysfunction in Schizophrenia Involves Mixed-Lineage Leukemia 1-Regulated Histone Methylation at GABAergic Gene Promoters
Authors: Huang Hsien-Sung , Matevossian Anouch , Whittle Catheryne , Kim Se Young , Schumacher Armin , Baker Stephen P. , Akbarian Schahram
Published: October 2007

Alterations in GABAergic mRNA expression play a key role for prefrontal dysfunction in schizophrenia and other neurodevelopmental disease. Here, we show that histone H3-lysine 4 methylation, a chromatin mark associated with the transcriptional process, progressively increased atGAD1and other GABAergic gene promoters (GAD2,NPY,SST) in human prefrontal cortex (PFC) from prenatal to peripubertal ages and throughout adulthood. Alterations in schizophrenia included decreasedGAD1expression and H3K4-trimethylation, predominantly in females and in conjunction with a risk haplotype at the 5′ end ofGAD1. Heterozygosity for a truncated, lacZ knock-in allele of mixed-lineage leukemia 1 (Mll1), a histone methyltransferase expressed in GABAergic and other cortical neurons, resulted in decreased H3K4 methylation at GABAergic gene promoters. In contrast,Gad1H3K4 (tri)methylation and Mll1 occupancy was increased in cerebral cortex of mice after treatment with the atypical antipsychotic, clozapine. These effects were not mimicked by haloperidol or genetic ablation of dopamine D2and D3receptors, suggesting that blockade of D2-like signaling is not sufficient for clozapine-induced histone methylation. Therefore, chromatin remodeling mechanisms at GABAergic gene promoters, including MLL1-mediated histone methylation, operate throughout an extended period of normal human PFC development and play a role in the neurobiology of schizophrenia.
Orbital Prefrontal Cortex Is Required for Object-in-Place Scene Memory But Not Performance of a Strategy Implementation Task
Authors: Baxter Mark G. , Gaffan David , Kyriazis Diana A. , Mitchell Anna S.
Published: October 2007

The orbital prefrontal cortex is thought to be involved in behavioral flexibility in primates, and human neuroimaging studies have identified orbital prefrontal activation during episodic memory encoding. The goal of the present study was to ascertain whether deficits in strategy implementation and episodic memory that occur after ablation of the entire prefrontal cortex can be ascribed to damage to the orbital prefrontal cortex. Rhesus monkeys were preoperatively trained on two behavioral tasks, the performance of both of which is severely impaired by the disconnection of frontal cortex from inferotemporal cortex. In the strategy implementation task, monkeys were required to learn about two categories of objects, each associated with a different strategy that had to be performed to obtain food reward. The different strategies had to be applied flexibly to optimize the rate of reward delivery. In the scene memory task, monkeys learned 20 new object-in-place discrimination problems in each session. Monkeys were tested on both tasks before and after bilateral ablation of orbital prefrontal cortex. These lesions impaired new scene learning but had no effect on strategy implementation. This finding supports a role for the orbital prefrontal cortex in memory but places limits on the involvement of orbital prefrontal cortex in the representation and implementation of behavioral goals and strategies.
Activity-Dependent Development of Callosal Projections in the Somatosensory Cortex
Authors: Wang Chun-Lei , Zhang Lei , Zhou Yang , Zhou Jing , Yang Xiu-Juan , Duan Shu-min , Xiong Zhi-Qi , Ding Yu-Qiang
Published: October 2007

The corpus callosum is the largest commissural system in the mammalian brain, but the mechanisms underlying its development are not well understood. Here we report that neuronal activity is necessary for the normal development and maintenance of callosal projections in the mouse somatosensory cortex. We labeled a subpopulation of layer II/III callosal neurons viain uteroelectroporation and traced their axons in the contralateral cortex at different postnatal stages. Callosal axons displayed region- and layer-specific projection patterns within the first 2 weeks postnatally. Prenatal suppression of neuronal excitation was achieved via electroporation-induced overexpression of the inward rectifying potassium channel Kir2.1 in layer II/III cortical neurons. This resulted in abnormal callosal projections with many axons extending beyond layers II–III to terminate in layer I. Others failed to terminate at the border between the primary and secondary somatosensory cortices. Blocking synaptic transmission via expression of the tetanus toxin light chain (TeNT-LC) in these axons produced a more pronounced reduction in the projections to the border region, and the eventual disappearance of callosal projections over the entire somatosensory cortex. When Kir2.1 and TeNT-LC were coexpressed, callosal axon targeting exhibited a more severe phenotype that appeared to represent the addition of the effects produced by individual expression of Kir2.1 and TeNT-LC. These results underscore the importance of activity in regulating the developing neural connections and suggest that neuronal and synaptic activities are involved in regulating different aspects of the development of callosal projection.
Role of Kinase Suppressor of Ras-1 in Neuronal Survival Signaling by Extracellular Signal-Regulated Kinase 1/2
Authors: Szatmari Erzsebet , Kalita Katarzyna B. , Kharebava Giorgi , Hetman Michal
Published: October 2007

Scaffolding proteins including kinase suppressor of Ras-1 (KSR1) determine specificity of signaling by extracellular signal-regulated kinase 1/2 (ERK1/2), enabling it to couple diverse extracellular stimuli to various cellular responses. The scaffolding protein(s) that contributes to ERK1/2-mediated neuronal survival has not yet been identified. In cultured rat cortical neurons, BDNF activates ERK1/2 to enhance neuronal survival by suppressing DNA damage- or trophic deprivation-induced apoptosis. Here we report that in this system, BDNF increased KSR1 association with activated ERK1/2, whereas KSR1 knockdown with a short hairpin (sh) RNA reduced BDNF-mediated activation of ERK1/2 and protection against a DNA-damaging drug, camptothecin (CPT). In contrast, BDNF suppression of trophic deprivation-induced apoptosis was unaffected by shKSR1 although blocked by shERK1/2. Also, overexpression of KSR1 enhanced BDNF protection against CPT. Therefore, KSR1 is specifically involved in antigenotoxic activation of ERK1/2 by BDNF. To test whether KSR1 contributes to ERK1/2 activation by other neuroprotective stimuli, we used a cAMP-elevating drug, forskolin. In cortical neurons, ERK1/2 activation by forskolin was protein kinase A (PKA) dependent but TrkB (receptor tyrosine kinase B) independent and was accompanied by the increased association between KSR1 and active ERK1/2. Forskolin suppressed CPT-induced apoptosis in a KSR1 and ERK1/2-dependent manner. Inhibition of PKA abolished forskolin protection, whereas selective PKA activation resulted in an ERK1/2- and KSR1-mediated decrease in apoptosis. Hence, KSR1 is critical for the antiapoptotic activation of ERK1/2 by BDNF or cAMP/PKA signaling. In addition, these novel data indicate that stimulation of cAMP signaling is a candidate neuroprotective strategy to intervene against neurotoxicity of DNA-damaging agents.
The Heat Shock Response and Chaperones/Heat Shock Proteins in Brain Tumors: Surface Expression, Release, and Possible Immune Consequences
Authors: Graner Michael W. , Cumming R. Ian , Bigner Darell D.
Published: October 2007

The heat shock response is a highly conserved “stress response” mechanism used by cells to protect themselves from potentially damaging insults. It often involves the upregulated expression of chaperone and heat shock proteins (HSPs) to prevent damage and aggregation at the proteome level. Like most cancers, brain tumor cells often overexpress chaperones/HSPs, probably because of the stressful atmosphere in which tumors reside, but also because of the benefits of HSP cytoprotection. However, the cellular dynamics and localization of HSPs in either stressed or unstressed conditions has not been studied extensively in brain tumor cells. We have examined the changes in HSP expression and in cell surface/extracellular localization of selected brain tumor cell lines under heat shock or normal environments. We herein report that brain tumor cell lines have considerable heat shock responses or already high constitutive HSP levels; that those cells express various HSPs, chaperones, and at least one cochaperone on their cell surfaces; and that HSPs may be released into the extracellular environment, possibly as exosome vesicular content. In studies with a murine astrocytoma cell line, heat shock dramatically reduces tumorigenicity, possibly by an immune mechanism. Additional evidence indicative of an HSP-driven immune response comes from immunization studies using tumor-derived chaperone protein vaccines, which lead to antigen-specific immune responses and reduced tumor burden in treated mice. The heat shock response and HSPs in brain tumor cells may represent an area of vulnerability in our attempts to treat these recalcitrant and deadly tumors.
An Ion Channel Essential for Sensing Chemical Damage
Authors: Macpherson Lindsey J. , Xiao Bailong , Kwan Kelvin Y. , Petrus Matt J. , Dubin Adrienne E. , Hwang SunWook , Cravatt Benjamin , Corey David P. , Patapoutian Ardem
Published: October 2007

Tissue damage and its downstream consequences are experimentally assayed by formaldehyde application, which indiscriminately modifies proteins and is presumed to cause pain through broadly acting mechanisms. Here we show that formaldehyde activates the ion channel TRPA1 and that TRPA1-deficient mice exhibit dramatically reduced formaldehyde-induced pain responses. 4-Hydroxynonenal, a reactive chemical produced endogenously during oxidative stress, and other related aldehydes also activate TRPA1in vitro. Furthermore, painful responses to iodoacetamide, a nonspecific cysteine-alkylating compound, are abolished in TRPA1-deficient mice. Therefore, although these reactive chemicals modify many proteins, the associated pain appears mainly dependent on a single ion channel.
Jambes arquées. Huwawa és Bész közös inspirációs forrása, az afrikai törpe
Authors: Nagy Adrienn
Published: October 2007

Az egyiptomi Bész isten
ismert alak az ókorral foglalkozó kutatók körében, legyen az egyiptológus,
assziriológus vagy klasszika archeológus. A mezopotámiai Huwawa/Humbaba is
hasonlóképpen népszerű i_0
Development of a mercury speciation, fate, and biotic uptake (BIOTRANSPEC) model: Application to Lahontan Reservoir (Nevada, USA)
Authors: Gandhi Nilima , Bhavsar Satyendra P. , Diamond Miriam L. , Kuwabara James S. , Marvin-DiPasquale Mark , Krabbenhoft David P.
Published: October 2007

A mathematically linked mercury transport, speciation, kinetic, and simple biotic uptake (BIOTRANSPEC) model has been developed. An extension of the metal transport and speciation (TRANSPEC) model, BIOTRANSPEC estimates the fate and biotic uptake of inorganic (Hg(II)), elemental (Hg(0)) and organic (MeHg) forms of mercury and their species in the dissolved, colloidal (e.g., dissolved organic matter [DOM]), and particulate phases of surface aquatic systems. A pseudo-steady state version of the model was used to describe mercury dynamics in Lahontan Reservoir (near Carson City, NV, USA), where internal loading of the historically deposited mercury is remobilized, thereby maintaining elevated water concentrations. The Carson River is the main source of total mercury (THg), of which more than 90% is tightly bound in a gold-silver-mercury amalgam, to the system through loadings in the spring, with negligible input from the atmospheric deposition. The speciation results suggest that aqueous species are dominated by Hg-DOM, Hg(OH)2, and HgClOH. Sediment-to-water diffusion of MeHg and Hg-DOM accounts for approximately 10% of total loadings to the water column. The water column acts as a net sink for MeHg by reducing its levels through two competitive processes: Uptake by fish, and net MeHg demethylation. Although reservoir sediments produce significant amounts of MeHg (4 g/d), its transport from sediment to water is limited (1.6 g/d), possibly because of its adsorption on metal oxides of iron and manganese at the sediment-water interface. Fish accumulate approximately 45% of the total MeHg mass in the water column, and 9% of total MeHg uptake by fish leaves the system because of fishing. Results from this new model reiterate the previous conclusion that more than 90% of THg input is retained in sediment, which perpetuates elevated water concentrations.
Bioassays with cagedHyalella aztecato determine in situ toxicity downstream of two Saskatchewan, Canada, uranium operations
Authors: Robertson Erin L. , Liber Karsten
Published: October 2007

The main objectives of this in situ study were to evaluate the usefulness of an in situ bioassay to determine if downstream water bodies at the Key Lake and Rabbit Lake uranium operations (Saskatchewan, Canada) were toxic to Hyalella azteca and, if toxicity was observed, to differentiate between the contribution of surface water and sediment contamination to in situ toxicity. These objectives were achieved by performing 4-d in situ bioassays with laboratory-reared H. azteca confined in specially designed, paired, surface water and sediment exposure chambers. Results from the in situ bioassays revealed significant mortality, relative to the respective reference site, at the exposure sites at both Key Lake (p ≤ 0.001) and Rabbit Lake (p = 0.001). No statistical differences were found between survival in surface water and sediment exposure chambers at either Key Lake (p = 0.232) or Rabbit Lake (p = 0.072). This suggests that surface water (the common feature of both types of exposure chambers) was the primary cause of in situ mortality of H. azteca at both operations, although this relationship was stronger at Key Lake. At Key Lake, the primary cause of aquatic toxicity to H. azteca did not appear to be correlated with the variables measured in this study, but most likely with a pulse of organic mill-process chemicals released during the time of the in situ study — a transient event that was caused by a problem with the mill's solvent extraction process. The suspected cause of in situ toxicity to H. azteca at Rabbit Lake was high levels of uranium in surface water, sediment, and pore water.
Benzotriazole is antiestrogenic in vitro but not in vivo
Authors: Harris Catherine A. , Routledge Edwin J. , Schaffner Christian , Brian Jayne V. , Giger Walter , Sumpter John P.
Published: October 2007

Benzotriazole (BT) is an anticorrosive agent well known for its use in aircraft deicing and antifreeze fluids but also used in dishwasher detergents. It is highly persistent in the environment; therefore, BT is frequently found in runoff emanating from large airports as well as in the surrounding groundwater. In addition, BT has recently been found to be ubiquitous in Swiss wastewater treatment plant effluents and their receiving waters; however, very little chronic toxicity data is available on which to base a sound ecological risk assessment of this chemical. In vitro assays conducted using a recombinant yeast (anti-) estrogen assay indicated that BT possessed clear antiestrogenic properties. This chemical was approximately 100-fold less potent than Tamoxifen, which was used as a positive control. A subsequent in vivo study, however, involving analysis of vitellogenin induction and somatic indices in adult fathead minnows (Pimephales promelas) exposed to BT at concentrations of 10, 100, and 1,000 μg/L for two weeks showed no evidence of antiestrogenic activity by this compound. The possibility exists that higher concentrations of BT may yet induce the type of activity observed in vitro, although the concentrations used here already far exceed those reported in surface-water samples. Furthermore, adverse effects may be observed in fish or other organisms exposed to BT for a longer period than employed here, although such studies are costly and unlikely to be included in standard risk assessment procedures. A rigorous investigation of the chronic toxicity of BT is imperative.
Chlorinated hydrocarbons in pelagic forage fishes and squid of the Southern California Bight
Authors: Jarvis Erica , Schiff Kenneth , Sabin Lisa , Allen M. James
Published: October 2007

Large quantities of DDT and polychlorinated biphenyls (PCBs) have been historically discharged to the Southern California Bight (SCB). While these contaminants have bioaccumulated in sediment-associated fishes, little data exist on concentrations of these compounds in pelagic forage species that are the likely food source for larger predatory mammals and birds. The goal of the present study was to assess the extent and magnitude of DDT and PCB bioaccumulation in the four major pelagic species of the SCB: Pacific sardine (Sardinops sagax), Pacific chub mackerel (Scomber japonicus), northern anchovy (Engraulis mordax), and California market squid (Loligo opalescens). A total of 99 composite samples were collected from commercial landing docks along the southern California coast from July 2003 to February 2004. Whole fish were homogenized and analyzed for total DDT (ortho- and para-isomers of DDT and its degradation products) and 41 PCB congeners. Virtually all of the samples of Pacific sardine, northern anchovy, and Pacific chub mackerel had detectable levels of total DDT. Only 50% of the California market squid samples had detectable total DDT. Northern anchovy had the highest total DDT concentrations (60 ± 38 μg/kg wet wt), followed by Pacific chub mackerel (41 ± 40 μg/kg wet wt), Pacific sardine (34 ± 29 μg/kg wet wt), and California market squid (0.8 ± 1.2 μg/kg wet wt). In general, concentrations were highest in the central SCB. An estimated 99% of northern anchovy, 83% of Pacific sardine, 33% of Pacific chub mackerel, and 0% of California market squid landings exceeded wildlife risk screening values for total DDT. Virtually none of the landings were estimated to exceed wildlife risk screening values for PCBs.
Toxicity versus accumulation for barley plants exposed to copper in the presence of metal buffers: Progress towards development of a terrestrial biotic ligand model
Authors: Antunes Paula M.C. , Hale Beverley A. , Ryan Adam C.
Published: October 2007

Development of a terrestrial biotic ligand model (TBLM) for higher plants requires a root-Cu accumulation value that corresponds to the 50% inhibitory concentration (IC50). However, it is not yet known which of the two previously reported Cubinding ligands on the root is associated with Cu toxicity. The aim of the present study was therefore to investigate the relationship between Cu binding to each ligand group and toxicity, so that the key toxicological site could be identified. To obtain accumulation and toxicity data that were not biased by limited Cu supply to the root, 2-d-old barley seedlings were exposed for 48 h to a range of free Cu ion activities (i.e., {Cu2+}) in simple exposure media buffered by nitrilotriacetic acid (NTA) or ethylenediaminetetraacetic acid (EDTA). Comparison of the amount of predicted root-bound Cu (calculated with the aqueous geochemical program PHREEQC) with root elongation data showed that toxicity likely resulted from Cu binding to low-affinity ligands, as the high-affinity ligands were approximately 99% saturated when a reduction in root elongation was first observed. For plants exposed to both NTA- and the EDTA-buffered {Cu2+} solutions, the root-Cu accumulation value corresponding to the IC50 was approximately 80 μg/g root dry weight, which is similar to the value obtained from previous work with wheat. The linear relationship between the amount of Cu bound to the low-affinity ligands and the percent root growth inhibition suggests that this relationship will be a robust predictor of Cu toxicity when incorporated into the TBLM, and applied to varied exposure scenarios. For the simple solutions used here, the TBLM-predicted and measured IC50 values were statistically indistinguishable.
Occurrence and estrogenicity of phenolics in paper-recycling process water: Pollutants originating from thermal paper in waste paper
Authors: Terasaki Masanori , Shiraishi Fujio , Fukazawa Hitoshi , Makino Masakazu
Published: October 2007

Eight phenolics were detected in samples collected from areas where paper-recycling process water is discharged. The detected concentration levels were up to 270 μg/L and 230 μg/g in water samples and sediment samples, respectively, obtained from both the outfall of the paper-recycling process water and its downstream areas. In particular, totarol (compound 4), 2,4-bis(1-phenylethyl)phenol (compound 6), 4,4′-butylidenebis(6-t-butyl-m-cresol) (compound 7), 2,4-bis(1-phenylethyl)-6-chlorophenol (compound 8), and 4-hydroxy-4′-isopropoxydiphenyl sulfone (compound 9) were identified for the first time as environmental pollutants. The estrogenicities of the identified compounds were assessed by yeast two-hybrid assays incorporating either the human or medaka fish (Oryzias latipes) estrogen receptor a (hERα and medERα, respectively) and an estrogen receptor competitive enzyme-linked immunosorbent assay (ER-ELISA) both with and without metabolic activation by a rat liver S9 mix. Bisphenol A (compound 3) and 2-naphthol (compound 1) exhibited activity in the assays of both hERα and medERα without the S9 mix. The relative activity (%) to 17β-estradiol was 0.0015% for compound 3 and 0.0009% for compound 1 in the hERα assay and 0.027% for compound 3 and 0.0093% for compound 1 in the medERα assay. These compounds were attenuated by the S9 mix. The binding affinity was evaluated using an ER-ELISA. Compounds 3, 4, 6, and 7 exhibited affinity without the S9 mix. After exposure to the S9 mix, however, the binding affinity of compound 7 was eliminated by the S9 mix; those of compounds 3, 4, and 6 were attenuated; and that of compound 8 exhibited affinity. A comprehensive assessment of the estrogenicities of the phenolics originating from thermal paper and their implications for an aquatic environment may require an examination of the components of the phenolics, as in the present study.
Transferable properties of multi-biological toxicity caused by cobalt exposure inCaenorhabditis elegans
Authors: Wang Yang , Xie Wei , Wang Dayong
Published: October 2007

Cobalt is widespread in the environment and excess dietary Co exposure can result in toxic effects in many organisms. However, whether the multi-biological toxicities caused by Co exposure can be transferred from parents to progeny has not been clarified. In the present study, we analyzed the multiple toxicities of Co to the nematode Caenorhabditis elegans and its progeny. Endpoints of life span, body size, vulva development, brood size, generation time, body bend, head thrash, and chemotaxis plasticity were used for toxicity testing. Our results indicate that Co induced multi-biological defects by affecting the life span, development, reproduction, behavior, and behavioral plasticity. Moreover, we found that most of these multi-biological defects could be transferred from parents to the filial generation (F1 and F2) progenies, and that this transmission could only be partially recovered. Certain specific phenotypes in the progeny exhibited even more severe defects than in the parents, such as chemotaxis plasticity. We classified the defects caused by Co exposure into four groups according to their transferable properties. Furthermore, the stress responses were investigated in embryos using a stable transgenic line, hsp16-2-gfp. Our data suggest that the multi-biological defects caused by Co exposure can be transferred from parents to progeny, and that Co toxicity might be accumulated in the eggs of nematodes.
Use of δ13C, δ15N, and carbon to nitrogen ratios to evaluate the impact of sewage-derived particulate organic matter on the benthic communities of the Southern California Bight
Authors: Ramírez-Álvarez Nancy , Macías-Zamora José Vinicio , Burke Roger A. , Rodríguez-Villanueva Lúz Verónica
Published: October 2007

We measured stable isotope ratios (δ13Cand δ15N) of particulate organic matter (POM) sources and benthic organic matter compartments as well as sediment C to N ratios from the coastal area of the southern end of the Southern California Bight (SCB). We used the isotopic values to evaluate the relative importance of the major POM sources to the sediment and two benthic macroinvertebrates. Application of a simple model to sediment δ13C values suggested that sewage-derived POM (SDPOM) supplies an average of 48% of the organic C to study area sediments. Application of a similar model to Spiophanes duplex δ13C values suggested that SDPOM from wastewater treatment plants discharging into the SCB could supply up to 57% of the C assimilated by this important benthic macroinvertebrate in areas as far away as 26 km from SDPOM inputs. The stable isotope data for Amphiodia urtica were more difficult to interpret because of the complex feeding habits of this organism.
Evaluation of sources and loading of pesticides to the Sacramento River, California, USA, during a storm event of winter 2005
Authors: Guo Lei , Kelley Kevin , Goh Kean S.
Published: October 2007

A monitoring study was conducted in the tributaries and main stem of the Sacramento River, California, USA, during the storm event of January 26 to February 1, 2005. The purpose of the study was to evaluate the sources and loading of pesticides in the Sacramento River watershed during the winter storm season. A total of 26 pesticides or pesticide degradates were analyzed, among which five pesticides and one triazine degradate were detected. Diuron, diazinon, and simazine were found in all streams with a total load of 110.4, 15.4, and 15.7 kg, respectively, in the Sacramento River over the single storm event. Bromacil, hexazinone, and the triazine degradate diaminochlorotriazine were only detected in two smaller drainage canals with a load ranged from 0.25 to 7 kg. The major source of pesticides detected in the main stem Sacramento River was from the most upstream subbasin, the Sacramento River above Colusa, where detected pesticides either exceeded or were close to those at the main outlet of the Sacramento River at Alamar Marina. The higher precipitation in this subbasin was partly responsible for the greater contribution of pesticides observed. Diazinon was the only pesticide with concentrations above water quality criteria, indicating that additional mitigation measures may be needed to reduce its movement to surface water.