bluuebunny/crossref_metadata_2025 huggingface dataset:
A default mechanism of spindle orientation based on cell shape is sufficient to generate cell fate diversity in polarisedXenopusblastomeres
Authors: Strauss Bernhard , Adams Richard J. , Papalopulu Nancy
Published: August 2006

The process of oriented divisions of polarised cells is a recurrent mechanism of cell fate diversification in development. It is commonly assumed that a specialised mechanism of spindle alignment into the axis of polarity is a prerequisite for such systems to generate cell fate diversity. Oriented divisions also take place in the frog blastula, where orientation of the spindle into the apicobasal axis of polarised blastomeres generates inner and outer cells with different fates. Here, we show that, in this system, the spindle orients according to the shape of the cells, a mechanism often thought to be a default. We show that in the embryo, fatedifferentiative,perpendicular divisions correlate with a perpendicular long axis and a small apical surface, but the long axis rather then the size of the apical domain defines the division orientation. Mitotic spindles in rounded, yet polarised,isolated Xenopus blastula cells orient randomly, but align into an experimentally introduced long axis when cells are deformed early in the cell cycle. Unlike other systems of oriented divisions, the spindle aligns at prophase, rotation behaviour is rare and restricted to small angle adjustments. Disruption of astral microtubules leads to misalignment of the spindle. These results show that a mechanism of spindle orientation that depends on cell shape rather than cortical polarity can nevertheless generate cell fate diversity from a population of polarised cells.
Tsukushi cooperates with VG1 to induce primitive streak and Hensen's node formation in the chick embryo
Authors: Ohta Kunimasa , Kuriyama Sei , Okafuji Tatsuya , Gejima Ryu , Ohnuma Shin-ichi , Tanaka Hideaki
Published: August 2006

Three classes of signaling molecule, VG1, WNT and BMP, play crucial roles in axis formation in the chick embryo. Although VG1 and WNT signals have a pivotal function in inducing the primitive streak and Hensen's node in the embryo midline, their action is complemented by that of BMP antagonists that protect the prospective axial tissue from the inhibitory influence of BMPs secreted from the periphery. We have previously reported that a secreted factor, chick Tsukushi (TSK), is expressed in the primitive streak and Hensen's node, where it works as a BMP antagonist. Here, we describe a new crucial function for TSK in promoting formation of the primitive streak and Hensen's node by positively regulating VG1 activity. We provide evidence that TSK directly binds VG1 in vitro, and that TSK and VG1 functionally interact in axis formation, as shown by biological assays performed in chick and Xenopus embryos. Furthermore, we show that alternative splicing of TSK RNA leads to the formation of two isoforms (TSKA,originally designated as TSK, and TSKB) that differ in their C-terminal region. Biochemical and biological assays indicate that TSKB is a much weaker BMP antagonist than TSKA, although both isoforms efficiently interact with VG1. Remarkably, although both TSKA and TSKBare expressed throughout the early extending primitive streak, their expression patterns diverge during gastrulation. TSKA expression concentrates in Hensen's node, a well-known source of anti-BMP signals,whereas TSKB accumulates in the middle primitive streak (MPS), a region known to work as a node-inducing center where VG1 expression is also specifically localized. Loss-of-function experiments demonstrate that TSKB, but not TSKA, function is required in the MPS for induction of Hensen's node. Taken together, these results indicate that TSK isoforms play a crucial role in chick axis formation by locally modulating VG1 and BMP activities during gastrulation.
The presbycusis component in occupational hearing loss
Authors: Lebo Charles P. , Reddell Rayford C.
Published: August 2006

In the evaluation of suspected occupational hearing losses, an expanding part of current otologic practice, the otologist is expected to differentiate noise sequelae from other types of ear pathology and to estimate the extent to which each abnormality contributes to the total hearing disability. The audiometric identification of acoustic trauma is possible only in early cases. When the noise effects are more advanced and when they are combined with aging, the pure tone curves are nonspecific. The standard battery of audiologic tests does not help in the quantitative separation of acoustic trauma from presbycusis. Most authorities consider that when acoustic trauma and presbycusis are concomitant, the effects of each are independent and that the influences of each upon auditory acuity are simply additive.

There are significant individual differences in susceptibility to acoustic trauma and in the degree of hearing deterioration which occurs with aging. While it is not yet possible to make retrospective determinations of these variances, it is feasible to make age corrections of noise‐induced hypoacusis if one averages acoustic vulnerability and aging effects. Such averaging results in some inequalities in individual cases, but the validity of this approach in large numbers of cases is justifiable because of the absence of alternatives.

The authors have modified the prebycusic data of Spoor (which combine several important hearing surveys conducted in the United States and in western Europe) by changing the calibration from ASA‐1954 to ANSI‐1969 and have prepared curves which demonstrate mean aggregate hearing levels at specified frequencies according to age and sex.

Two formulae for age correction are presented along with examples of each formula and the authors' evaluation.
Cristo ocular and cristo spinal reflexes: A review after 1,000 cases of vertigo
Authors: Dolowitz David A.
Published: August 2006

Vertigo and dizziness may be considered spatial disorientation. This disorientation follows malfunction (following disease or injury) of the computer‐like action of the eyes, ears, proprioceptive sense, cervical spine, cerebrum, cerebellum, autonomic system or the master control in the reticular substance.

It is felt that changes in nystagmus would follow injury or disease to any of these components. Studies have been reported of the establishment of parameters of cristo ocular and cristo spinal reflexes in persons with good spatial orientation. The differential diagnosis of 1,000 cases of patients with vertigo will be compared with “normals,” establishing, where possible, a differential diagnosis.
Results in labyrinthine cryosurgery monitored by evoked response
Authors: Tabor James R. , Best Lavar , Donohoe Robert W.
Published: August 2006

Cryosurgery is one conservative approach for Ménière's disease designed to control vertigo without adversely affecting the hearing in most cases. Report is made of 47 consecutive cases of cryosurgery. All patients were unresponsive to medical therapy. During the surgical procedure, the hearing is monitored at 2,000 cycles per second, and the vestibular function is monitored by evoked response to a loud click stimuli. Initial testing for threshold at 2,000 cycles and to a click stimulus is done by the evoked response. An initial freeze at —160°C. for two minutes is done, and the vestibular and auditory function is retested. A repeat freeze is completed unless there is a definite hearing change or the vestibular recording changes as evinced by the evoked response. If necessary, a third freeze is done, depending upon vestibular and auditory threshold changes. By this method a significant improvement of vertiginous symptoms resulted in 76 to 80 percent of the patients. The results of postoperative electronystagmography suggest an increase in unilateral weakness, but all cases showed a caloric response. In general, the hearing postoperatively continued to fluctuate as before surgery, accompanied by tinnitus, fullness, and recruitment. Morbidity in the way of hearing loss and temporary facial paralysis occurs in approximately 10 percent of the patients treated in this manner. Until a more knowledgeable approach to Ménière's disease is forthcoming, cryosurgery to the lateral semicircular canal still holds a position in the armamentarium for the treatment of patients who have incapacitating vertigo.
Carcinoma of the tongue: Review of 220 cases
Authors: Schleuning Alexander J. , Summers Gordon W.
Published: August 2006

Two hundred twenty cases of carcinoma of the tongue were reviewed. The three‐year determinant survival of 178 cases was 32.5 percent. The five‐year determinant survival of 169 cases was 29 percent. Only five patients of 41 who developed late node metastasis survived five years. Sixtynine of 79 patients treated for cure by X‐ray therapy developed recurrence. Thirteen were salvaged by secondary treatment. Twenty‐eight of 44 patients treated surgically developed recurrences. Eight were saved by secondary treatment. Because of a high percentage of recurrences at the primary site and a poor salvage of these recurrences, combined therapy is felt to offer the best hope for improved survivals.
Das slowenische Strafrecht zum Zeitpunkt des Beitritts Sloweniens zur EU (am 1. Mai 2004)
Authors: Korošec Damjan , Ambrož Matjaž
Published: August 2006

A. Einleitende Bemerkungen

Das slowenische Strafgesetzbuch (StGB) wurde im September 1994 vom Parlament verabschiedet und trat am 1. Januar 1995 in Kraft. Im Jahr 1999 erfuhr es relativ unwesentliche Änderungen und Ergänzungen, jüngste Änderungen fanden im Jahr 2004 statt. Sie traten am 5. Mai 2004 in Kraft und betreffen hauptsächlich den besonderen Teil des StGB. Es handelt sich vor allem um die Verschärfung und Erweiterung der typischen Straftatbestände für die organisierte Kriminalität, die Korruption, den Terrorismus und den Menschenhandel im weiteren Sinn und die Neugestaltung einiger Sexualstraftatbestände, vor allem bezüglich der Prostitution und sexueller Angriffe auf Minderjährige. Einige dieser Neuerungen, insbesondere auf dem Gebiet der völkerrechtlichen Verbrechen, werden als Annäherung Sloweniens an den so genannten europäischen Strafrechtsraum verstanden (und in der Literatur bereits überwiegend als übereilt kritisiert) und verdienen damit am Ende dieser Darstellung besondere Aufmerksamkeit.
Extinction Training in Conjunction with a Partial Agonist of the Glycine Site on the NMDA Receptor Erases Memory Trace
Authors: Mao Sheng-Chun , Hsiao Ya-Hsin , Gean Po-Wu
Published: August 2006

Much evidence indicates that extinction training does not erase memory traces but instead forms inhibitory learning that prevents the expression of original memory. Fear conditioning induces long-term potentiation and drives synaptic insertion of AMPA receptors into the amygdala. Here we show that extinction training applied 1 h after training reversed the conditioning-induced increase in surface glutamate receptor subunit 1 (GluR1) in parallel with the inhibition of startle potentiation. However, if applied 24 h after training, extinction training reduced startle potentiation without influencing the GluR1 increase. We infusedd-cycloserine (DCS), a partial agonist of the glycine site on the NMDA receptor, bilaterally into the amygdala 30 min before extinction training. This augmented the extinction training-elicited reduction in startle and reversed the conditioning-induced increase in GluR1. Delivery of five sets of tetanic stimulation (TS) to the external capsule produced a robust enhancement of synaptic responses in the lateral amygdala neurons that persisted for >2 h. Low-frequency stimulation applied 1 h after TS had no long-lasting effect on synaptic responses. The same treatments, however, induced depotentiation in the presence of DCS and reversed TS-induced increase in surface GluR1. Together, this study has two important findings: (1) whether a memory trace remains intact or is erased depends on the interval between conditioning and extinction training and (2) DCS facilitates the reversal of memory trace. DCS-induced augmentation of extinction and reversal of GluR1 surface expression are likely mediated by DCS-facilitated endocytosis of AMPA receptors.
Transient Receptor Potential Vanilloid 1 Is Required for Intrinsic Osmoreception in Organum Vasculosum Lamina Terminalis Neurons and for Normal Thirst Responses to Systemic Hyperosmolality
Authors: Ciura Sorana , Bourque Charles W.
Published: August 2006

Recent studies have indicated that members of the transient receptor potential vanilloid (TRPV) family of cation channels are required for the generation of normal osmoregulatory responses, yet the mechanism of osmosensory transduction in primary osmoreceptor neurons of the CNS remains to be defined. Indeed, despite ample evidence suggesting that the organum vasculosum lamina terminalis (OVLT) serves as the primary locus of the brain for the detection of osmotic stimuli, evidence that neurons in the OVLT are intrinsically osmosensitive has remained elusive. Here we show that murine OVLT neurons are intrinsically sensitive to increases in the osmolality of the extracellular fluid. Hypertonic conditions provoked increases in membrane cation conductance that resulted in the generation of an inward current, depolarizing osmoreceptor potentials, and enhanced action potential discharge. Moreover, we found that this osmosensory signal transduction cascade was absent in OVLT neurons from TRPV1 knock-out (TRPV1−/−) mice and that responses of wild type (WT) OVLT neurons could be blocked by ruthenium red, an inhibitor of TRPV channels. Finally,TRPV1−/−mice showed significantly attenuated water intake in response to systemic hypertonicity compared with WT controls. These findings indicate that OVLT neurons act as primary osmoreceptors and that a product of thetrpv1gene is required for osmosensory transduction.
Social Context-Dependent Singing-Regulated Dopamine
Authors: Sasaki Aya , Sotnikova Tatyana D. , Gainetdinov Raul R. , Jarvis Erich D.
Published: August 2006

Like the mammalian striatum, the songbird striatum receives dense dopaminergic input from the midbrain ventral tegmental area–substantia nigra pars compacta complex. The songbird striatum also contains a unique vocal nucleus, Area X, which has been implicated in song learning and social context-dependent song production. Area X shows increased neural firing and activity-dependent gene expression when birds sing, and the level of activation is higher and more variable during undirected singing relative to directed singing to other birds. Here we show in the first report ofin vivomicrodialysis in awake, behaving songbirds that singing is associated with increased dopamine levels in Area X. Dopamine levels are significantly higher with directed relative to undirected singing. This social context-dependent difference in dopamine levels requires the dopamine transporter, because localin vivoblockade of the transporter caused dopamine levels for undirected singing to increase to levels similar to that for directed singing, eliminating the social context-dependent difference. The increase in dopamine is presumably depolarization and vesicular release dependent, because adding of high K+increased and removal of Ca2+increased and decreased extracellular DA levels. Our findings implicate DA and molecules that control DA kinetics in singing behavior and social context-dependent brain function.
Accumulation of Amyloid Precursor Protein in the Mitochondrial Import Channels of Human Alzheimer’s Disease Brain Is Associated with Mitochondrial Dysfunction
Authors: Devi Latha , Prabhu Badanavalu M. , Galati Domenico F. , Avadhani Narayan G. , Anandatheerthavarada Hindupur K.
Published: August 2006

Mitochondrial dysfunction is one of the major intracellular lesions of Alzheimer’s disease (AD). However, the causative factors involved in the mitochondrial dysfunction in human AD are not well understood. Here we report that nonglycosylated full-length and C-terminal truncated amyloid precursor protein (APP) accumulates exclusively in the protein import channels of mitochondria of human AD brains but not in age-matched controls. Furthermore, in AD brains, mitochondrially associated APP formed stable ∼480 kDa complexes with the translocase of the outer mitochondrial membrane 40 (TOM40) import channel and a super complex of ∼620 kDa with both mitochondrial TOM40 and the translocase of the inner mitochondrial membrane 23 (TIM23) import channel TIM23 in an “Nin mitochondria–Cout cytoplasm” orientation. Accumulation of APP across mitochondrial import channels, which varied with the severity of AD, inhibited the entry of nuclear-encoded cytochromecoxidase subunits IV and Vb proteins, which was associated with decreased cytochromecoxidase activity and increased levels of H2O2. Regional distribution of mitochondrial APP showed higher levels in AD-vulnerable brain regions, such as the frontal cortex, hippocampus, and amygdala. Mitochondrial accumulation of APP was also observed in the cholinergic, dopaminergic, GABAergic, and glutamatergic neuronal types in the category III AD brains. The levels of translocationally arrested mitochondrial APP directly correlated with mitochondrial dysfunction. Moreover, apolipoprotein genotype analysis revealed that AD subjects with the E3/E4 alleles had the highest content of mitochondrial APP. Collectively, these results suggest that abnormal accumulation of APP across mitochondrial import channels, causing mitochondrial dysfunction, is a hallmark of human AD pathology.
EphB Receptors and Ephrin-B3 Regulate Axon Guidance at the Ventral Midline of the Embryonic Mouse Spinal Cord
Authors: Kadison Stephanie R. , Mäkinen Taija , Klein Rüdiger , Henkemeyer Mark , Kaprielian Zaven
Published: August 2006

EphB receptors and their ephrin-B ligands are required for midline guidance decisions at several rostrocaudal levels of the developing CNS. In the embryonic vertebrate spinal cord, ephrin-B3 is localized to the floor plate (FP) at the ventral midline (VM), ephrin-B1 and ephrin-B2 are expressed in the dorsal spinal cord, and decussated EphB receptor-bearing commissural axons navigate between these ventral and dorsal ephrin-B domains. Despite these compelling expression patterns, thein vivorole(s) for EphB and ephrin-B proteins in regulating the guidance of spinal commissural axons has not been established. Here, we use DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate) labeling to assess the pathfinding of commissural axons in the spinal cords of ephrin-B and EphB mutant mouse embryos. In mice lacking ephrin-B3 or multiple EphB receptors, a significant number of axons followed aberrant trajectories in the immediate vicinity of the VM. Furthermore, forked transverse commissural (FTC) axons, a unique class of commissural axons that continues to project in the transverse plane on the contralateral side of the FP, were present at a markedly higher frequency in ephrin-B3 and EphB mutants, compared with wild-type embryos. Neither the midline guidance errors nor excessive numbers of FTC axons were observed in the spinal cords ofephrin-B3laczmice that express a truncated form of ephrin-B3, which is capable of forward but not reverse signaling. In contrast to the midline guidance defects observed in EphB and ephrin-B3 mutant embryos, wild-type-like contralateral projections were observed in mice lacking ephrin-B1 and/or ephrin-B2.
Activation of Pedunculopontine Tegmental Protein Kinase A: A Mechanism for Rapid Eye Movement Sleep Generation in the Freely Moving Rat
Authors: Bandyopadhya Ram S. , Datta Subimal , Saha Subhash
Published: August 2006

Cells in the pedunculopontine tegmentum (PPT) play a key role in the generation of rapid eye movement (REM) sleep, but its intracellular signaling mechanisms remain unknown. In the current studies, the role of PPT intracellular protein kinase A (PKA) in the regulation of REM sleep was evaluated by comparing PKA subunit [catalytic (PKACα) and regulatory (PKARI, PKARIIα, and PKARIIβ) types] expression and activity in the PPT at normal, high, and low REM sleep conditions. To compare anatomical specificity, REM sleep-dependent expressions of these PKA subunits were also measured in the medial pontine reticular formation (mPRF), medial prefrontal cortex (mPFC), and anterior hypothalamus (AHTh). The results of these PKA subunit expression and activity studies demonstrated that the expression of PKACαand PKA activity in the PPT increased and decreased during high and low REM sleep, respectively. Conversely, PKACαexpression and PKA activity decreased with high REM sleep in the mPRF. Expression of PKACαalso decreased in the mPFC and remained unchanged in the AHTh with high REM sleep. These subunit expression and PKA activity data reveal a positive relationship between REM sleep and increased PKA activity in the PPT. To test this molecular evidence, localized activation of cAMP-dependent PKA activity was blocked using a pharmacological technique. The results of this pharmacological study demonstrated that the localized inhibition of cAMP-dependent PKA activation in the PPT dose-dependently suppressed REM sleep. Together, these results provide the first evidence that the activation of the PPT intracellular PKA system is involved in the generation of REM sleep.
Altered Hippocampal Synaptic Potentiation in P2X4Knock-Out Mice
Authors: Sim Joan A. , Chaumont Séverine , Jo Jihoon , Ulmann Lauriane , Young Mark T. , Cho Kwangwook , Buell Gary , North R. Alan , Rassendren Francois
Published: August 2006

P2X4purinergic receptors are calcium-permeable, ATP-activated ion channels. In the CA1 area of the hippocampus, they are located at the subsynaptic membrane somewhat peripherally to AMPA receptors. The possible role of P2X4receptors has been difficult to elucidate because of the lack of selective antagonists. Here we report the generation of a P2X4receptor knock-out mouse and show that long-term potentiation (LTP) at Schaffer collateral synapses is reduced relative to that in wild-type mice. Ivermectin, which selectively potentiates currents at P2X4, was found to increase LTP in wild-type mice but had no effect in P2X4knock-out mice. We suggest that calcium entry through subsynaptic P2X4receptors during high-frequency stimulation contributes to synaptic strengthening.
Encoding Difficulty Promotes Postlearning Changes in Sleep Spindle Activity during Napping
Authors: Schmidt Christina , Peigneux Philippe , Muto Vincenzo , Schenkel Maja , Knoblauch Vera , Münch Mirjam , de Quervain Dominique J.-F. , Wirz-Justice Anna , Cajochen Christian
Published: August 2006

Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep EEG activity after declarative learning of unrelated word pairs. At weekly intervals, 13 young male volunteers spent three 24 h sessions in the laboratory under carefully controlled homeostatic and circadian conditions. At approximately midday, subjects performed either one of two word-pair learning tasks or a matched nonlearning control task, in a counterbalanced order. The two learning lists differed in the level of concreteness of the words used, resulting in an easier and a more difficult associative encoding condition, as confirmed by performance at immediate cued recall. Subjects were then allowed to sleep for 4 h; afterward, delayed cued recall was tested. Compared with the control condition, sleep EEG spectral activity in the low spindle frequency range and the density of low-frequency sleep spindles (11.25–13.75 Hz) were both significantly increased in the left frontal cortex after the difficult but not after the easy encoding condition. Furthermore, we found positive correlations between these EEG changes during sleep and changes in memory performance between pre-nap and post-nap recall sessions. These results indicate that, like during nocturnal sleep, daytime sleep EEG oscillations including spindle activity are modified after declarative learning of word pairs. Furthermore, we demonstrate here that the nature of the learning material is a determinant factor for sleep-related alterations after declarative learning.
Involvement of Protein Kinase C-ε in Activity-Dependent Potentiation of Large Dense-Core Vesicle Exocytosis in Chromaffin Cells
Authors: Park Yong-Soo , Hur Eun-Mi , Choi Bo-Hwa , Kwak Eunyee , Jun Dong-Jae , Park Su-Jin , Kim Kyong-Tai
Published: August 2006

Neurotransmitter release is modulated in an activity-dependent manner. We showed previously that repetitive stimulation of nicotinic acetylcholine receptor (nAChR) induced activity-dependent potentiation (ADP) of large dense-core vesicle (LDCV) exocytosis in chromaffin cells. Here we report that protein kinase C (PKC)-ε is critically involved in ADP. Stimulation of nAChR induced activation of PKC-ε, and inhibition of PKC-ε by expression of the dominant-negative mutant of PKC-ε (DN-PKC-ε) or short interfering (siRNA) against PKC-ε abolished ADP via decreasing the frequency and quantal size of fused vesicles without affecting basal exocytosis, suggesting that PKC-ε is specifically involved in ADP. Electron microscopy revealed that inhibition of PKC-ε disrupts activity-induced vesicle translocation required for ADP. We also suggest the involvement of myristoylated alanine-rich C kinase substrate (MARCKS), which is known as a downstream target of PKC-ε, in ADP of LDCV exocytosis. The level of phospho-MARCKS correlated with the time course of ADP and was reduced by transfection with DN-PKC-ε. Actin filament disassembly induced by MARCKS phosphorylation was also significantly blocked by transfection of DN-PKC-ε. Furthermore, knockdown of MARCKS by siRNA resulted in inhibition of ADP and reduction of the number of fused vesicles. Together, we provide evidence that ADP of LDCV exocytosis is regulated by PKC-ε and its downstream target MARCKS via modulating vesicle translocation.
Amygdala Response to Facial Expressions Reflects Emotional Learning
Authors: Hooker Christine I. , Germine Laura T. , Knight Robert T. , D’Esposito Mark
Published: August 2006

The functional role of the human amygdala in the evaluation of emotional facial expressions is unclear. Previous animal and human research shows that the amygdala participates in processing positive and negative reinforcement as well as in learning predictive associations between stimuli and subsequent reinforcement. Thus, amygdala response to facial expressions could reflect the processing of primary reinforcement or emotional learning. Here, using functional magnetic resonance imaging, we tested the hypothesis that amygdala response to facial expressions is driven by emotional association learning. We show that the amygdala is more responsive to learning object–emotion associations from happy and fearful facial expressions than it is to the presentation of happy and fearful facial expressions alone. The results provide evidence that the amygdala uses social signals to rapidly and flexibly learn threatening and rewarding associations that ultimately serve to enhance survival.
Transgenic Mice Overexpressing Glycogen Synthase Kinase 3β: A Putative Model of Hyperactivity and Mania
Authors: Prickaerts Jos , Moechars Dieder , Cryns Kim , Lenaerts Ilse , van Craenendonck Hansfried , Goris Ilse , Daneels Guy , Bouwknecht J. Adriaan , Steckler Thomas
Published: August 2006

Lithium is used as treatment for bipolar disorder with particular efficacy in the treatment of mania. Lithium inhibits glycogen synthase kinase 3β (GSK-3β) directly or indirectly via stimulation of the kinase Akt-1. We therefore investigated the possibility that transgenic mice overexpressing GSK-3β could be of relevance to model bipolar disorder. Transgenic mice showed hypophagia, an increased general locomotor activity, and decreased habituation as assessed in an open field, an increased acoustic startle response, and again decreased habituation. The forced swim test revealed a reduced immobility in transgenic mice, but this is probably related to the hyperactivity of the animals. There were no differences in baseline and stress-induced increases of plasma adrenocorticotrophic hormone and corticosterone levels. Molecular analysis suggests compensatory mechanisms in the striatum of these transgenic mice for the overload of active GSK-3β by dimming the endogenous GSK-3β signaling pathway via upregulation of Akt-1 expression. Brain-derived neurotrophic factor protein levels were increased in the hippocampus of the transgenic mice. This suggests some kind of compensatory mechanism to the observed reduction in brain weight, which has been related previously to a reduced size of the somatodendritic compartment. Together, in mice overexpressing GSK-3β, specific intracellular signaling pathways are affected, which is accompanied by altered plasticity processes and increased activity and reactivity, whereas habituation processes seem to be decreased. The behavioral observations led to the suggestion that the model at hand recapitulates hyperactivity as observed in the manic phase of bipolar disorder.
Increased Expression of the 5-HT Transporter Confers a Low- Anxiety Phenotype Linked to Decreased 5-HT Transmission
Authors: Jennings Katie A. , Loder Merewyn K. , Sheward W. John , Pei Qi , Deacon Robert M. J. , Benson Matthew A. , Olverman Henry J. , Hastie Nicholas D. , Harmar Anthony J. , Shen Sanbing , Sharp Trevor
Published: August 2006

A commonly occurring polymorphic variant of the human 5-hydroxytryptamine (5-HT) transporter (5-HTT) gene that increases 5-HTT expression has been associated with reduced anxiety levels in human volunteer and patient populations. However, it is not known whether this linkage between genotype and anxiety relates to variation in 5-HTT expression and consequent changes in 5-HT transmission. Here we test this hypothesis by measuring the neurochemical and behavioral characteristics of a mouse genetically engineered to overexpress the 5-HTT. Transgenic mice overexpressing the human 5-HTT (h5-HTT) were produced from a 500 kb yeast artificial chromosome construct. These transgenic mice showed the presence of h5-HTT mRNA in the midbrain raphe nuclei, as well as a twofold to threefold increase in 5-HTT binding sites in the raphe nuclei and a range of forebrain regions. The transgenic mice had reduced regional brain whole-tissue levels of 5-HT and, in microdialysis experiments, decreased brain extracellular 5-HT, which reversed on administration of the 5-HTT inhibitor paroxetine. Compared with wild-type mice, the transgenic mice exhibited a low-anxiety phenotype in plus maze and hyponeophagia tests. Furthermore, in the plus maze test, the low-anxiety phenotype of the transgenic mice was reversed by acute administration of paroxetine, suggesting a direct link between the behavior, 5-HTT overexpression, and low extracellular 5-HT.In toto, these findings demonstrate that associations between increased 5-HTT expression and anxiety can be modeled in mice and may be specifically mediated by decreases in 5-HT transmission.
Movements of Adult Radio‐Tagged Bighead Carp in the Illinois River
Authors: Peters Lindsay M. , Pegg Mark A. , Reinhardt Ulrich G.
Published: August 2006

Populations of invasive bighead carp Hypophthalmichthys nobilis in the Mississippi River basin are rapidly increasing in size and range. However, the rate of expansion is not well understood. We used radiotelemetry to document movements of bighead carp within the LaGrange Reach of the Illinois River, Illinois, where populations have been documented since 1993. We surgically implanted radio transmitters into 42 adults in June 2003 and May–July 2004. Successful relocation of individuals decreased over time and ended in August of both years. We analyzed 132 observations from 23 adults and found a mean (±SE) movement rate of 1.70 ± 0.74 km/d. The highest movement rate was 14.33 km/d. The maximum distance traveled by an individual was 163 km upstream in 35 d, and the top 10% of movements as observed by boat were between 26.5 and 56.5 km within 3–10 d. Forty‐three percent of fish died or dropped transmitters for unknown reasons, but handling, environmental conditions, or both may have contributed to the loss. Our study is the first to document the movement rates and patterns of bighead carp within the United States and shows that adults are capable of moving considerable distances in a short time. Immediate actions to prevent or control their spread are warranted.
Seasonal and Diel Movements and Habitat Use of Robust Redhorses in the Lower Savannah River, Georgia and South Carolina
Authors: Grabowski Timothy B. , Isely J. Jeffery
Published: August 2006

The robust redhorseMoxostoma robustumis a large riverine catostomid whose distribution is restricted to three Atlantic Slope drainages. Once presumed extinct, this species was rediscovered in 1991. Despite being the focus of conservation and recovery efforts, the robust redhorse's movements and habitat use are virtually unknown. We surgically implanted pulse‐coded radio transmitters into 17 wild adults (460–690 mm total length) below the downstream‐most dam on the Savannah River and into 2 fish above this dam. Individuals were located every 2 weeks from June 2002 to September 2003 and monthly thereafter to May 2005. Additionally, we located 5–10 individuals every 2 h over a 48‐h period during each season. Study fish moved at least 24.7 ± 8.4 river kilometers (rkm; mean ± SE) per season. This movement was generally downstream except during spring. Some individuals moved downstream by as much as 195 rkm from their release sites. Seasonal migrations were correlated to seasonal changes in water temperature. Robust redhorses initiated spring upstream migrations when water temperature reached approximately 12°C. Our diel tracking suggests that robust redhorses occupy small reaches of river (∼1.0 rkm) and are mainly active diurnally. Robust redhorses were consistently found in association with woody debris and gravel streambed sediments along the outer edge of river bends. Fish exhibited a high degree of fidelity to both overwintering and spawning areas. Our observations of long‐distance seasonal migrations suggest that successful robust redhorse conservation efforts may require an ecosystem management approach.
Effects of Physical Habitat and Ontogeny on Lentic Habitat Preferences of Juvenile Chinook Salmon
Authors: Sergeant Christopher J. , Beauchamp David A.
Published: August 2006

We experimentally tested the habitat preferences of juvenile Chinook salmon Oncorhynchus tshawytscha to evaluate whether habitat availability was limited for a lake‐rearing population in Lake Washington (Seattle, Washington). A segment of this population resides in shallow (<1 m deep), nearshore areas of the lake during January–May and migrates to saltwater at age 0. During the shallow, nearshore phase, fish are exposed to varying degrees of bottom slope, substrate, and cover (e.g., overhead docks and woody debris) formed by the natural and modified shorelines of this highly urbanized system. The effects of these three habitat variables on patch use or electivity were tested in combination with ontogeny and the presence or absence of piscivores. Fry and presmolts avoided steeper bottom slopes, but presmolt responses were strongest. Responses to substrate and cover options were weak, although fry exhibited some coherent preference for finer substrates. The habitat preferences displayed by both life stages corroborated the observations from nearshore field surveys in Lake Washington. No direct effects on habitat preference from diel period or piscivore presence were evident. These results, combined with field observations, suggest that juvenile Chinook salmon may risk exposure to predation in order to utilize preferred habitat and to forage at a high rate. Therefore, nearshore habitat restoration projects aimed at increasing preferred juvenile Chinook salmon habitat should consider this risk‐prone behavior. Future experiments in larger experimental arenas could clarify the importance of heterogeneous nearshore habitat and further examine predation effects on the productivity of lake‐rearing juvenile Chinook salmon.
Characterization of the Physiological Stress Response in Lingcod
Authors: Milston Ruth H. , Davis Michael W. , Parker Steven J. , Olla Bori L. , Clements Shaun , Schreck Carl B.
Published: August 2006

The goal of this study was to describe the duration and magnitude of the physiological stress response in lingcod Ophiodon elongatus after exposure to brief handling and sublethal air stressors. The response to these stressors was determined during a 24‐h recovery period by measuring concentrations of plasma cortisol, lactate, glucose, sodium, and potassium. Lingcod were subjected to brief handling followed by either a 15‐min or a 45‐min air stressor in the laboratory. After the 15‐min stressor, an increase in cortisol or glucose could not be detected until after 5 min of recovery. Peak concentrations were measured after 30 min for cortisol and after 60 min for glucose and lactate. Glucose and lactate had returned to basal levels after 12 h, whereas cortisol did not return to basal levels until after 24 h of recovery. Immediately following a 45‐min air stressor, all measured parameters were significantly elevated over levels in prestressor control fish. Cortisol concentrations tended to increase and reached a measured peak after 8 h of recovery, whereas glucose and lactate reached a measured peak after 1 h of recovery. Cortisol and lactate returned to basal levels within 24 h. Glucose, however, remained elevated even after 24 h of recovery. Plasma ions initially increased during the first hour of recovery, and the concentrations then declined to a level below that measured in control fish for the remainder of the 24‐h recovery period. In addition, we evaluated the effect of fish size on the stress response. There was no significant difference between the stress response of smaller (41–49‐cm [total length] and larger (50–67‐cm) lingcod after 45 min air exposure. In general, both the magnitude and duration of the primary and secondary stress responses in lingcod are comparable to those of salmonids.
Outcomes and Humanistic Issues Related to Treatment of Acute Bronchospasm
Authors: Okamoto Lynn J.
Published: August 2006

Because of emergency department visits and hospitalizations, the economic costs associated with asthma, chronic obstructive pulmonary disease (COPD), and bronchospasm are a significant portion of total overall treatment costs. A small proportion of patients account for most of the costs, due to disease severity and acute exacerbations. Disease management programs, sponsored by insurance groups and employers, are lowering health and disability costs and reducing days missed from work and school because of exacerbations. Quality‐of‐life patient assessments are available to assist practitioners in evaluating disease status. Evidenced‐based medicine analysis can show that less expensive therapies are not necessarily cost‐effective. A study of the rate of hospital admissions from the emergency department showed that although levalbuterol therapy in the emergency department was more costly than racemic albuterol therapy, total overall treatment costs were reduced because of decreased hospitalizations in the levalbuterol‐treated patients. Thus, providers, payers, and patients should examine all the scientific evidence (safety, efficacy or effectiveness, economics, and humanistic benefits) to make the most informed health care decision.
An in situ assay with the microalgaPhaeodactylum tricornutumfor sediment-overlying water toxicity evaluations in estuaries
Authors: Moreira Susana Maria , Guilhermino Lúcia , Ribeiro Rui
Published: August 2006

Given the urgent need for ecologically relevant toxicity tools specific to estuarine systems, the main goal of the present study was to develop and evaluate the potential of an in situ algal assay for estuarine sediment-overlying water toxicity evaluations using the microalga Phaeodactylum tricornutum immobilized in alginate beads. With its simple and cost-effective design, the assay apparatus, coupled with the use of microalgae immobilized in alginate beads, allowed rapid and easy deployment as well as retrieval of assay chambers. The effectiveness of the proposed in situ assay was investigated by deploying it at two reference and six contaminated Portuguese estuaries. By deploying open chambers both with and without an artificial nutrient source and closed chambers with an artificial seawater medium, it was possible to discriminate toxic effects from those caused by differences in temperature, light, and nutrient conditions across sites. A reduction in algal growth was found at contaminated sites relative to reference sites. The strontium alginate beads used for microalgae immobilization were found to be appropriate to perform in situ assays, showing no signs of disruption or dissolution after up to 8 d of exposure in estuarine sediment-overlying waters. The proposed in situ assay was shown to be a useful tool for estuarine sediment-overlying water toxicity testing to provide relevant data concerning primary production to estuarine ecological risk assessment studies.
Determining stressor presence in streams receiving urban and agricultural runoff: Development of a benthic in situ toxicity identification evaluation method
Authors: Custer Kevin W. , Burton G. Allen , Coelho Ricardo S. , Smith Preston R.
Published: August 2006

Determining toxicity in streams during storm-water runoff can be highly problematic because of the fluctuating exposures of a multitude of stressors and the difficulty of linking these dynamic exposures with biological effects. An underlying problem with assessing storm-water quality is determining if toxicity exists and then which contaminant is causing the toxicity. The goal of this research is to provide an alternative to standard toxicity testing methods by incorporating an in situ toxicity identification evaluation (TIE) approach. A benthic in situ TIE bioassay (BiTIE) was developed for separating key chemical classes of stressors in streams during both low- and high-flow events to help discern between point and nonpoint sources of pollution. This BiTIE method allows for chemical class fractionation through the use of resins, and these resins are relatively specific for removing nonpolar organics (Dowex™ Optipore™), ammonia (zeolite), and polywool (control). Three indigenous aquatic insects, a mayfly (Isonychia spp.), a caddisfly (Hydropsyche spp.), and a water beetle (Psephenus herricki), were placed in BiTIE chambers that were filled with natural substrates. Acute 96-h exposures were conducted at Honey Creek, New Carlisle, Ohio, USA (reference site), and Little Beavercreek, Beavercreek, Ohio, USA (impaired site). At both sites, significant (p < 0.025) stressor responses were observed using multiple species with polywool or no resin (control) treatments exhibiting <80% survival and resin treatments with >80% survival. The BiTIE method showed stressor–response relationships in both runoff and base flow events during 96-h exposures. The method appears useful for discerning stressors with indigenous species in situ.
Effects of pesticides on soil invertebrates in laboratory studies: A review and analysis using species sensitivity distributions
Authors: Frampton Geoff K. , Jänsch Stephan , Scott-Fordsmand Janeck J. , Römbke Jörg , van den Brink Paul J.
Published: August 2006

Species sensitivity distributions (SSD) and 5% hazardous concentrations (HC5) are distribution-based approaches for assessing environmental risks of pollutants. These methods have potential for application in pesticide risk assessments, but their applicability for assessing pesticide risks to soil invertebrate communities has not been evaluated. Using data obtained in a systematic review, the present study investigates the relevance of SSD and HC5 for predicting pesticide risks to soil invertebrates. Altogether, 1,950 laboratory toxicity data were obtained, representing 250 pesticides and 67 invertebrate taxa. The majority (96%) of pesticides have toxicity data for fewer than five species. Based on a minimum of five species, the best available endpoint data (acute mortality median lethal concentration) enabled SSD and HC5 to be calculated for 11 pesticides (atrazine, carbendazim, chlorpyrifos, copper compounds, diazinon, dimethoate, γ-hexachlorocyclohexane, lambda-cyhalothrin, parathion, pentachlorophenol, and propoxur). Arthropods and oligochaetes exhibit pronounced differences in their sensitivity to most of these pesticides. The standard test earthworm species, Eisenia fetida sensu lato, is the species that is least sensitive to insecticides based on acute mortality, whereas the standard Collembola test species, Folsomia candida, is among the most sensitive species for a broad range of toxic modes of action (biocide, fungicide, herbicide, and insecticide). These findings suggest that soil arthropods should be tested routinely in regulatory risk assessments. In addition, the data indicate that the uncertainty factor for earthworm acute mortality tests (i.e., 10) does not fully cover the range of earthworm species sensitivities and that acute mortality tests would not provide the most sensitive risk estimate for earthworms in the majority (95%) of cases.
Effects of dibutylphthalate and ethynylestradiol on liver peroxisomes, reproduction, and development of zebrafish (Danio rerio)
Authors: Ortiz-Zarragoitia Maren , Trant John M. , Cajaraville Miren P.
Published: August 2006

The aim of the present work was to study the effects of the peroxisome proliferator dibutylphthalate (DBP) and the xenoestrogen 17α-ethynylestradiol (EE2) on liver peroxisomes, reproduction, and development of zebrafish (Danio rerio). In experiment 1, newly fertilized zebrafish eggs were exposed for five weeks, covering the entire period of sexual determination, to nominal concentrations of 25 and 100 μg/L of DBP and 5 μg/L of EE2. In experiment 2, adult female zebrafish were exposed for 15 d to 100 and 500 μg/L of DBP and 5 μg/L of EE2, and afterward, they were paired with untreated males to study the effects in the resultant offspring. Ethynylestradiol provoked marked mortality (∼50%) and delayed development of larvae as well as sterility of adult females, possibly related to alterations in aromatase gene expression. Ethynylestradiol up-regulated vitellogenin expression in the early life stages and increased vitellogenin synthesis and accumulation in adult females. Ethynylestradiol caused liver peroxisome proliferation in early life stages but not in adult females. Dibutylphthalate caused teratogenic effects in early life stages and mortality of the larvae obtained from exposed females. Dibutylphthalate provoked liver peroxisome proliferation and up-regulation of cytochrome P450A1 in early life stages at the end of the exposure and in adult females. Dibutylphthalate also up-regulated the expression of aromatase genes. In conclusion, the xenoestrogen EE2 caused liver peroxisome proliferation in early life stages of zebrafish, but the peroxisome proliferator DBP did not behave as a typical xenoestrogen. Overall, changes in gene expression were more marked during early life stages than in adult female zebrafish.
In situ on-line toxicity biomonitoring in water: Recent developments
Authors: Gerhardt Almut , Ingram Mary Kate , Kang Ik Joon , Ulitzur Shimon
Published: August 2006

—In situ on-line biomonitoring is an emerging branch of aquatic biomonitoring. On-line biomonitoring systems use behavioral and/or physiological stress responses of caged test organisms exposed in situ either in a bypass system or directly instream. Sudden pollution waves are detected by several existing single-species on-line biomonitors, which until now have been placed mostly in streamside laboratories. However, recent achievements have been multispecies biomonitors, mobile biomonitors for direct in-stream use, development of new instruments, new methods for data analysis and alarm generation, biomonitors for use in soil and sediment, and scientific research supporting responses as seen in on-line biomonitors by linking them to other biological and ecological effects. Mobile on-line monitoring platforms containing an array of biomonitors, biosensors, and chemical monitoring equipment might be the future trend, especially in monitoring transboundary rivers at country borders as well as in coastal zones.