bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of Nav 1.6a Na+ channels affects zebrafish motoneuron development
Authors: Pineda Ricardo H. , Svoboda Kurt R. , Wright Melissa A. , Taylor Alison D. , Novak Alicia E. , Gamse Joshua T. , Eisen Judith S. , Ribera Angeles B.
Published: August 2006

In addition to rapid signaling, electrical activity provides important cues to developing neurons. Electrical activity relies on the function of several different types of voltage-gated ion channels. Whereas voltage-gated Ca2+ channel activity regulates several aspects of neuronal differentiation, much less is known about developmental roles of voltage-gated Na+ channels, essential mediators of electrical signaling. Here, we focus on the zebrafish Na+ channel isotype, Nav1.6a,which is encoded by the scn8a gene. A restricted set of spinal neurons, including dorsal sensory Rohon-Beard cells, two motoneuron subtypes with different axonal trajectories, express scn8a during embryonic development. CaP, an early born primary motoneuron subtype with ventrally projecting axons expresses scn8a, as does a class of secondary motoneurons with axons that project dorsally. To test for developmental roles of scn8a, we knocked down Nav1.6a protein using antisense morpholinos. Na+ channel protein and current amplitudes were reduced in neurons that express scn8a. Furthermore,Nav1.6a knockdown altered axonal morphologies of some but not all motoneurons. Dorsally projecting secondary motoneurons express scn8aand displayed delayed axonal outgrowth. By contrast, CaP axons developed normally, despite expression of the gene. Surprisingly, ventrally projecting secondary motoneurons, a population in which scn8a was not detected,displayed aberrant axonal morphologies. Mosaic analysis indicated that effects on ventrally projecting secondary motoneurons were non cell-autonomous. Thus,voltage-gated Na+ channels play cell-autonomous and non cell-autonomous roles during neuronal development.
N-cadherinis required for the polarized cell behaviors that drive neurulation in the zebrafish
Authors: Hong Elim , Brewster Rachel
Published: August 2006

Through the direct analysis of cell behaviors, we address the mechanisms underlying anterior neural tube morphogenesis in the zebrafish and the role of the cell adhesion molecule N-cadherin (N-cad) in this process. We demonstrate that although the mode of neurulation differs at the morphological level between amphibians and teleosts, the underlying cellular mechanisms are conserved. Contrary to previous reports, the zebrafish neural plate is a multi-layered structure, composed of deep and superficial cells that converge medially while undergoing radial intercalation, to form a single cell-layered neural tube. Time-lapse recording of individual cell behaviors reveals that cells are polarized along the mediolateral axis and exhibit protrusive activity. In N-cad mutants, both convergence and intercalation are blocked. Moreover, although N-cad-depleted cells are not defective in their ability to form protrusions, they are unable to maintain them stably. Taken together, these studies uncover key cellular mechanisms underlying neural tube morphogenesis in teleosts, and reveal a role for cadherins in promoting the polarized cell behaviors that underlie cellular rearrangements and shape the vertebrate embryo.
The treatment of paranasal sinusitis with aerosol bacitracin
Authors: Hopp Eugene S. , Mcgarvey William K.
Published: August 2006

The background of the treatment of sinusitis with aerosols is outlined. The experience of more than 10 years with aerosol Bacitracin is presented. The advantages over other methods of treatment will be discussed.
Tympanoplasty: Should grafts be placed medial or lateral to the tympanic membrane?
Authors: Doyle Patrick J. , Schleuning Alexander J. , Echevarria John
Published: August 2006

Since the introduction of tympanoplasty, there have been enthusiastic reports describing the use of skin, vein, fascia and perichondrium in repairing the tympanic membrane. Both endaural and postauricular techniques have been used. In the last few years most surgeons have concluded that fascia or perichondrium are the most suitable materials available for grafting. These materials have been placed either medial or lateral to the tympanic membrane.
A new technique for the correction of orbital hypertelorism
Authors: Converse John Marquis , Wood‐Smith Donald
Published: August 2006

Orbital hypertelorism is one of the most severe congenital deformities, frequently achieving monstrous proportions because of the wide divergence between the ocular globes. It is complicated by ocular anomalies; prominent among which are strabismus and amblyopia. The etiology is for the most part congenital although traumatic hypertelorism is seen and careful differentiation must be made between the true and false varieties of the deformity. The basis of intercanthal distance is a poor criterion of hypertelorism and we prefer the use of the distance between the anterior lacrimal crests as a more reliable means of measurement and have checked all our cases by the use of anterior‐posterior skull laminagrams.

The surgical technique used is based on that developed by Tessier and his associates in 1967; the original two‐stage procedure has been replaced by a one‐stage modification of this operation introduced by us (Converse, et al., 1970) with preservation of olfaction. The operation consists of raising a large scalp flap through a coronal incision with removal of a major portion of the frontal bone which is subsequently replaced. The frontal lobes are raised from the anterior cranial fossa exposing the roof of each orbit and the subperiosteal elevation is extended over the lower portion of the frontal bone and contiguous orbital rims. Combined with an incision through the lower eyelid, exposure of the entire orbit on its inner aspect just anterior to the optic foramen is obtained and lines of osteotomy are made through the orbital walls and combined with resection of an appropriate central portion of bone to enable medial motion of the orbits. The bony defects are grafted with autogenous bone grafts and the soft tissues are replaced in position.

Twenty‐five cases of orbital hypertelorism involving bilateral and unilateral hypertelorism are presented without unusual complications being observer. The orbits have been mobilized medially for a distance up to 40 millimeters without complications, and the operative procedures are all performed in collaboration with the neurosurgeon.

Most patients have required subsequent extraocular muscle balancing surgery and correction of medial canthal deformities.
Osteoplastic obliteration of the frontal sinuses. A review of 100 patients
Authors: Bosley William R.
Published: August 2006

One hundred consecutive osteoplastic frontal sinus operations were reviewed. The obliteration of the frontal sinus was achieved by natural bony obliteration instead of by operative fat obliteration. The operation was performed for 6 cases of trauma, 13 cases for an osteoma, 56 cases for frontal sinusitis without previous frontal sinus surgery and 25 cases for frontal sinusitis with previous frontal sinus surgery. Headaches were the presenting chief complaint of all cases, and 93 of them had some degree of frontal sinusitis. Localized osteomyelitis of the frontal sinus was present in 42 cases. Although 85 patients were completely satisfied with the results of the operation, 15 continued to have frontal headaches. Complete bony obliteration of the frontal sinus occurred in 93 cases. The seven patients who had incomplete bony obliteration of the frontal sinus are being followed closely for signs and symptoms of recurrent frontal sinus disease.
The histopathological changes in the temporal bone resulting from acute smallpox and chickenpox infection
Authors: Bordley John E. , Kapur Y. P.
Published: August 2006

Twenty‐two pairs of temporal bones collected through a collaborative program arranged between the Christian Medical College, Vellore, South India, and The Johns Hopkins University, were processed in the Temporal Bone Laboratory at the Johns Hopkins University. They have been reviewed and are reported here. Otological examinations were obtained on all cases, and simple hearing tests were carried out in the majority of them. Eighteen of the patients died of smallpox and four of chickenpox. The principal lesions have been found in the middle ears of both groups. In many ears the changes resemble acute necrotizing otitis media. There is much round cell infiltration, and, in a number of sections, inclusion bodies have been found, including one Guarnieri body. Such changes relate closely to lesions found elsewhere in the body in the presence of a virus invasion. There are no previous histopathological studies of changes in the ear in acute smallpox or chickenpox infection, that can be found in the literature.
Acute periorbital swelling
Authors: Healy Gerald B. , Stuart Strong M.
Published: August 2006

The origin of acute periorbital swelling is not always evident. Careful attention to the history, physical findings in the nose and adjacent areas and X‐ray appearances should lead to a correct diagnosis in each case.

Infections of the frontal, ethmoid and maxillary sinuses, the tear sac and nasal vestibule as well as fractures of the nasal and zygomatic bones account for most of the cases.
VIIIth nerve round window action potentials masked by high frequency noise in rats and guinea pigs: A comparative study
Authors: Bone Robert C. , Crowley David , Rauchbach Erol
Published: August 2006

Theoretical and experimental evidence supports the hypothesis that the VIIIth nerve action potential is a precise summation of individual neuron responses. Based on this concept, the action potential, as measured at the round window was altered in a predictably reproducible manner, by the addition of narrow frequency bands of masking noise. Rat and guinea pig cochleas were studied by means of an analytic method described by Teas, Eldredge and Davis. The latency and amplitude of the VIIIth nerve action potential were compared by analysis of variants for variable stimulus intensity and noise band frequency; in addition, interspecies variability was characterized. Results are discussed in light of known anatomic and behavioral data. Applications to human electrocochleography are discussed.
Radical surgery for carcinoma of the middle ear
Authors: Mccrea R. S.
Published: August 2006

Six cases of carcinoma of the middle ear are described, and the problems of radical surgery are discussed. Three of the six cases are alive and free from neoplasm, one for eight years and two for three years.

The difficulty in assessing the extent of a carcinoma of the middle ear is emphasized.

Classical en bloc resection of the temporal bone is unsatisfactory, because of the difficulty in controlling venous bleeding, and because the protympanum is opened if the internal carotid artery is preserved. A modification of this operation is described.

The author recommends pre‐operative studies of the cerebro‐vascular cross‐circulation, and radical surgery followed by radiotherapy for residual or recurrent growth.
Presurgical internal maxillary artery embolization in juvenile angiofibroma
Authors: Roberson Glenn H. , Biller Hugh , Sessions Donald G. , Ogura Joseph H.
Published: August 2006

Embolization of the internal maxillary artery with barium impregnated silastic spheres was performed in four patients with juvenile angiofibroma of the nasopharynx. Three of the cases were done prior to the initial surgical resection to reduce operative hemorrhage. The fourth case was a postoperative recurrence, and embolization was performed to evaluate the clinical response of the tumor. The technical aspects of the procedure, the rationale for embolization and pertinent literature are reviewed.
Cationic changes in endolymph during hypoglycemia
Authors: Mendelsohn Melvin , Roderique Jim
Published: August 2006

Experimentally induced hypoglycemia, using insulin as the hypoglycemic agent, was carried out, using three groups of guinea pigs. The differentiating factor was the time sequence. After the animals had been hypoglycemic for periods of time ranging from one to three hours, the cochlear endolymph. was collected and the sodium and potassium measured. It was found that there was a change in potassium/sodium ratio in the endolymph with the potassium concentration falling, and the sodium concentration rising. The magnitude of the change was quite time‐dependent with the most marked changes occurring after the longest period of hypoglycemia. The results point to the fact that the high potassium/sodium ratio is maintained by an active transport process which ultimately utilizes glucose as an energy source.
Cerebral abscess — A recurrent otologic problem
Authors: Kornblut Alan D.
Published: August 2006

Cerebral abscess represents one of the more serious complications of chronic ear disease. Patient morbidity and mortality is dependent on prompt diagnosis and treatment. The pathogenesis, diagnosis and treatment of cerebral abscesses have been reviewed in order to refamiliarize the otolaryngologist with the management of this clinical problem.
Haus ohne Hüter? Die Justizgrundrechte im Mehr-Ebenen-System von EG-/EU-Vertrag, EMRK und Europäischem Verfassungsvertrags-Entwurf
Authors: Paeffgen Hans-Ullrich
Published: August 2006

Der nachfolgende Aufsatz vergleicht anhand der Justizgrundrechte in den drei vorhandenen bzw. geplanten völkerrechtlichen Verträgen den existenten, den werdenden und den sinnvollen Grund-/Menschenrechtsschutz des EU-Bürgers. Ausgangs- und Mittelpunkt sind dabei die Grundrechtecharta 2000 und der Entwurf eines Verfassungsvertrages für Europa. Dabei befasst er sich besonders mit dem Problem von Rechtsprechungs-Unterschieden und dem Verhältnis der Jurisdiktionsgewalt der jeweils in den Verträgen vorgesehenen Gerichte zueinander. Zugleich möchte er ein wenig in die für das Strafrecht zunehmend bedeutender werdenden, aber dem traditionellen deutschsprachigen Rechtsdenken nicht immer nahestehenden Mechanismen des Europarechtes, namentlich die Rechtsprechung des EuGH, einführen.
Die Übertragbarkeit der Judikatur des Bundesverfassungsgerichts zur akustischen Wohnraumüberwachung auf die Telekommunikationsüberwachung und andere verdeckte Ermittlungsmaßnahmen
Authors: Löffelmann Markus
Published: August 2006

Mit seinem Urteil vom 3. März 2004, 1 BvR 2378/98, hatte das Bundesverfassungsgericht die Verfassungsmäßigkeit der Verankerung der akustischen Wohnraumüberwachung in Art. 13 Abs. 3 GG bestätigt, zugleich aber ihre einfachgesetzliche Ausgestaltung in der Strafprozessordnung in weiten Teilen für verfassungswidrig erklärt und dem Gesetzgeber aufgetragen, bis 30. Juni 2005 einen verfassungsgemäßen Zustand herzustellen. Am 1. Juli 2005 ist nach kontroversen rechtswissenschaftlichen und politischen Diskussionen das Gesetz zur Umsetzung des Urteils des Bundesverfassungsgerichts vom 3. März 2004 (akustische Wohnraumüberwachung) in Kraft getreten. Obwohl im wissenschaftlichen und politischen Diskurs die Frage aufgeworfen wurde, ob und inwieweit das gegenständliche Urteil Auswirkungen auf das Recht anderer heimlicher Ermittlungsmaßnahmen hat und auch dort einen entsprechenden Reformbedarf zeitigt, verhält sich das neue Gesetz nicht zu dieser Problematik. Hier liegt ein Schwerpunkt der noch zu führenden rechtswissenschaftlichen Debatte.
Die Rolle der Staatsanwaltschaft im Strafverfahren: Objektives Organ der Rechtspflege oder doch „parteiischer“ Anwalt des Staates?
Authors: Kelker Brigitte
Published: August 2006

I. Einführung in das Thema und Überblick über den Gang der Darstellung

Wer sich mit der Rolle der Staatsanwaltschaft im Strafverfahren befasst, beschäftigt sich mit einem Thema, das nicht nur bereits Gegenstand zahlreicher Vorarbeiten ist, sondern immer auch mit Implikationen für die anderen am Strafverfahren Beteiligten verbunden ist.
Die Konsensmaxime in der Hauptverhandlung: Zur Rekonstruktion des Amtsermittlungsgrundsatzes in § 244 Abs. 2 StPO unter Berücksichtigung der aktuellen Gesetzesentwürfe zur Verständigung im Strafverfahren
Authors: Jahn Matthias
Published: August 2006

I. Blitzlichter, Schlaglichter, Wetterzeichen

Gäbe es einen Wettbewerb um das strafprozessuale Foto des Jahres, wäre 2005 eine Aufnahme aussichtsreicher Kandidat für den ersten Platz gewesen. Es zeigt den Vizepräsidenten und Vorsitzenden der 10. Strafkammer des Landgerichts Augsburg, den „mittlerweile legendären Richter“ Maximilian Hofmeister, wie er einem auf der Grundlage einer prozessualen Absprache soeben zu zwei Jahren und drei Monaten Haft verurteilten Ex-Staatssekretär im Bundesverteidigungsministerium die Hand schüttelt. Die Körperhaltung des Richters ist dezent nach vornüber gebeugt, während der so mit besonderer Wohlerzogenheit konfrontierte Ludwig-Holger Pfahls sein Gegenüber nicht ansieht, sondern professionell in Richtung der Agenturfotografen feixt. Die Situation ist durchwirkt von einer fundamentalen Misskonzeption zwischen einem auf die Kommunikation zwischen zwei Menschen berechneten Höflichkeitsritual und die jede Intimität dementierende Strahlkraft der öffentlichen Person Pfahls.
Strafrechtsgeschichte
Authors: Jerouschek Günter , Rüping Hinrich
Published: August 2006

I. Ältere Abteilung

von Moos, Peter: Der Fehltritt. Vergehen und Versehen in der Vormoderne. Köln/Weimar/Wien: Böhlau 2001. Norm und Struktur Bd. 15 XXIV, 468 S. (Studien zum sozialen Wandel im Mittelalter und früher Neuzeit).
Gesprengte Ketten? Zur Zukunft des Guidelines Sentencing im US-amerikanischen Strafzumessungsrecht
Authors: Meyer Frank
Published: August 2006

I. Einleitung

Fragt man Strafrechtler hierzulande nach kennzeichnenden Elementen des US-amerikanischen Strafjustizsystems, wird die Antwort regelmäßig jury trial oder plea bargaining lauten. Weitaus weniger bekannt ist ein Institut, das die Strafrechtspflege der Vereinigten Staaten in den letzten 20 Jahren besonders nachhaltig geprägt hat. Die Rede ist vom guidelines sentencing. Anders als es eine wörtliche Übersetzung nahe legt, handelt es sich dabei nicht um informelle Richtlinien, wie sie auch in Deutschland vor allem für Verkehrs- und Steuerstrafsachen existieren. Sie sind vielmehr in der Regel als rechtlich verbindliche Vorschriften ausgestaltet. Dies galt bis zum 13. Januar 2005 auch für die in Bundesstrafverfahren geltenden Federal Sentencing Guidelines (im Folgenden: FSG). An besagtem Tag entschied der U.S. Supreme Court in United States v. Booker, dass deren rechtlich verbindliche Natur mit dem 6. Amendment (right to a jury trial) unvereinbar ist. Die FSG sollten nur noch „beratend“ (advisory) bei der Strafzumessung herangezogen werden. Die Tragweite dieser Entscheidung lässt sich kaum überschätzen. Trotz fortlaufender Kritik am guidelines-Regime war dieses doch integraler Bestandteil des bundesrechtlichen Verfahrensalltags. Mit „Booker“ ist dieses System nicht nur weggefallen, sondern durch ein neues ersetzt worden, über dessen genaue Ausgestaltung und Implikationen Unklarheit herrscht. Ziel des Beitrags ist es daher nicht nur, in die Welt des guidelines sentencing einzuführen, sondern auch Fragestellungen aufzuzeigen, die aus der jüngsten Rechtsprechung des Supreme Court folgen und das US-Strafrecht künftig stark beschäftigen werden. Dazu werden zunächst Geschichte (II.) und Funktionsweise (III.) der FSG skizziert. Überleitend erfolgt eine Schilderung der Kritik, die bezüglich der Anwendungspraxis der FSG sowie ihrer strukturellen Mängel seit Jahren geäußert wird (IV.). Nur vor diesem Hintergrund lässt sich die Entscheidungsserie des Supreme Court, die mit Jones v. United States ihren Ausgang nahm und schließlich in United States v. Booker kulminierte, darstellen (V.). Abschließend wird die Adaption dieser Rechtsprechung durch die Instanzgerichte (VI.) beleuchtet sowie das rechtliche und politische Spannungsfeld erörtert, in dem sich die Zukunft des guidelines sentencing entscheiden wird (VII.).
Decoding Stimulus Variance from a Distributional Neural Code of Interspike Intervals
Authors: Lundstrom Brian Nils , Fairhall Adrienne L.
Published: August 2006

The spiking output of an individual neuron can represent information about the stimulus via mean rate, absolute spike time, and the time intervals between spikes. Here we discuss a distinct form of information representation, the local distribution of spike intervals, and show that the time-varying distribution of interspike intervals (ISIs) can represent parameters of the statistical context of stimuli. For many sensory neural systems the mapping between the stimulus input and spiking output is not fixed but, rather, depends on the statistical properties of the stimulus, potentially leading to ambiguity. We have shown previously that for the adaptive neural code of the fly H1, a motion-sensitive neuron in the fly visual system, information about the overall variance of the signal is obtainable from the ISI distribution. We now demonstrate the decoding of information about variance and show that a distributional code of ISIs can resolve ambiguities introduced by slow spike frequency adaptation. We examine the precision of this distributional code for the representation of stimulus variance in the H1 neuron as well as in the Hodgkin–Huxley model neuron. We find that the accuracy of the decoding depends on the shapes of the ISI distributions and the speed with which they adapt to new stimulus variances.
Cooperative Astrocyte and Dendritic Spine Dynamics at Hippocampal Excitatory Synapses
Authors: Haber Michael , Zhou Lei , Murai Keith K.
Published: August 2006

Accumulating evidence is redefining the importance of neuron–glial interactions at synapses in the CNS. Astrocytes form “tripartite” complexes with presynaptic and postsynaptic structures and regulate synaptic transmission and plasticity. Despite our understanding of the importance of neuron–glial relationships in physiological contexts, little is known about the structural interplay between astrocytes and synapses. In the past, this has been difficult to explore because studies have been hampered by the lack of a system that preserves complex neuron–glial relationships observed in the brain. Here we present a system that can be used to characterize the intricate relationship between astrocytic processes and synaptic structuresin situusing organotypic hippocampal slices, a preparation that retains the three-dimensional architecture of astrocyte–synapse interactions. Using time-lapse confocal imaging, we demonstrate that astrocytes can rapidly extend and retract fine processes to engage and disengage from motile postsynaptic dendritic spines. Surprisingly, astrocytic motility is, on average, higher than its dendritic spine counterparts and likely relies on actin-based cytoskeletal reorganization. Changes in astrocytic processes are typically coordinated with changes in spines, and astrocyte–spine interactions are stabilized at larger spines. Our results suggest that dynamic structural changes in astrocytes help control the degree of neuron–glial communication at hippocampal synapses.
Firing Properties of Anatomically Identified Neurons in the Medial Septum of Anesthetized and Unanesthetized Restrained Rats
Authors: Pascale Simon Axelle , Poindessous-Jazat Frédérique , Dutar Patrick , Epelbaum Jacques , Bassant Marie-Hélène
Published: August 2006

Cholinergic and GABAergic neurons in the medial septum-diagonal band of Broca (MS-DB) project to the hippocampus where they are involved in generating theta rhythmicity. So far, the functional properties of neurochemically identified MS-DB neurons are not fully characterized. In this study, MS-DB neurons recorded in urethane anesthetized rats and in unanesthetized restrained rats were labeled with neurobiotin and processed for immunohistochemistry against glutamic acid decarboxylase (GAD), parvalbumin (PV), and choline acetyltransferase (ChAT). The majority of the 90 labeled neurons (75.5%) were GAD+. Among them, 34.0% were also PV+, but none were ChAT+. Only 8.8% of the labeled neurons were found ChAT+. Remaining neurons (15.5%) were not identified. In anesthetized rats, all of the PV/GAD+ and 65% of GAD+ neurons exhibited burst-firing activity at the theta frequency. PV/GAD+ neurons displayed higher discharge rate and longer burst duration compared with GAD+ neurons. At variance, all of the ChAT+ neurons were slow-firing. Cluster-firing and tonic-firing were observed in GAD+ and unidentified neurons. In unanesthetized rats, during wakefulness or rapid eye movement sleep with hippocampal theta, the bursting neurons were PV/GAD+ or GAD+, whereas all of the ChAT+ neurons were slow-firing. Across the sleep–wake cycle, the GABAergic component of the septohippocampal pathway was always more active than the cholinergic one. The fact that cholinergic MS-DB neurons do not display theta-related bursting or tonic activity but have a very low firing rate questions how acetylcholine exerts its activating role in the septohippocampal system.
Enhanced Presynaptic Neurotransmitter Release in the Anterior Cingulate Cortex of Mice with Chronic Pain
Authors: Zhao Ming-Gao , Ko Shanelle W , Wu Long-Jun , Toyoda Hiroki , Xu Hui , Quan Jessica , Li Jianguo , Jia Yongheng , Ren Ming , Xu Zao C. , Zhuo Min
Published: August 2006

The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in learning and memory. Recent studies show that painful stimuli activate the prefrontal cortex and that brain chemistry is altered in this area in patients with chronic pain. Components of the CNS that are involved in pain transmission and modulation, from the spinal cord to the ACC, are very plastic and undergo rapid and long-term changes after injury. Patients suffering from chronic pain often complain of memory and concentration difficulties, but little is known about the neural circuitry underlying these deficits. To address this question, we analyzed synaptic transmission in the ACC from mice with chronic pain induced by hindpaw injection of complete Freund's adjuvant (CFA).In vitrowhole-cell patch-clamp recordings revealed a significant enhancement in neurotransmitter release probability in ACC synapses from mice with chronic pain. Trace fear memory, which requires sustained attention and the activity of the ACC, was impaired in CFA-injected mice. Using knock-out mice, we found that calmodulin-stimulated adenylyl cyclases, AC1 and/or AC8, were crucial in mediating the long-lasting enhanced presynaptic transmitter release in the ACC of mice with chronic pain. Our findings provide strong evidence that presynaptic alterations caused by peripheral inflammation contribute to memory impairments after injury.
Temporal Coding Mediates Discrimination of “Bitter” Taste Stimuli by an Insect
Authors: Glendinning John I. , Davis Adrienne , Rai Meelu
Published: August 2006

The mechanisms that mediate discriminative taste processing in insects are poorly understood. We asked whether temporal patterns of discharge from the peripheral taste system of an insect (Manduca sextacaterpillars; Sphingidae) contribute to the discrimination of three “bitter” taste stimuli: salicin, caffeine, and aristolochic acid. The gustatory response to these stimuli is mediated exclusively by three pairs of bitter-sensitive taste cell, which are located in the medial, lateral, and epipharyngeal sensilla. We tested for discrimination by habituating the caterpillars to salicin and then determining whether the habituation generalized to caffeine or aristolochic acid. We ran habituation-generalization tests in caterpillars with their full complement of taste sensilla (i.e., intact) and in caterpillars with ablated lateral sensilla (i.e., lat-ablated). The latter perturbation enabled us to examine discrimination in caterpillars with a modified peripheral taste profile. We found that the intact and lat-ablated caterpillars both generalized the salicin-habituation to caffeine but not aristolochic acid. Next, we determined whether this pattern of stimulus-generalization could be explained by salicin and aristolochic acid generating distinct ensemble, rate, temporal, or spatiotemporal codes. To this end, we recorded excitatory responses from the bitter-sensitive taste cells and then used these responses to formulate predictions about whether the salicin-habituation should generalize to caffeine or aristolochic acid, separately for each coding framework. We found that the pattern of stimulus generalization in both intact and lat-ablated caterpillars could only be predicted by temporal coding. We conclude that temporal codes from the periphery can mediate discriminative taste processing.
Glucocorticoids Increase Amyloid-β and Tau Pathology in a Mouse Model of Alzheimer’s Disease
Authors: Green Kim N. , Billings Lauren M. , Roozendaal Benno , McGaugh James L. , LaFerla Frank M.
Published: August 2006

Various environmental and genetic factors influence the onset and progression of Alzheimer’s disease (AD). Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, which controls circulating levels of glucocorticoid hormones, occurs early in AD, resulting in increased cortisol levels. Disturbances of the HPA axis have been associated with memory impairments and may contribute to the cognitive decline that occurs in AD, although it is unknown whether such effects involve modulation of the amyloid β-peptide (Aβ) and tau. Usingin vitroandin vivoexperiments, we report that stress-level glucocorticoid administration increases Aβ formation by increasing steady-state levels of amyloid precursor protein (APP) and β-APP cleaving enzyme. Additionally, glucocorticoids augment tau accumulation, indicating that this hormone also accelerates the development of neurofibrillary tangles. These findings suggest that high levels of glucocorticoids, found in AD, are not merely a consequence of the disease process but rather play a central role in the development and progression of AD.
Mutations in the K+/Cl−Cotransporter Genekazachoc(kcc) Increase Seizure Susceptibility inDrosophila
Authors: Hekmat-Scafe Daria S. , Lundy Miriam Y. , Ranga Rakhee , Tanouye Mark A.
Published: August 2006

During a critical period in the developing mammalian brain, there is a major switch in the nature of GABAergic transmission from depolarizing and excitatory, the pattern of the neonatal brain, to hyperpolarizing and inhibitory, the pattern of the mature brain. This switch is believed to play a major role in determining neuronal connectivity via activity-dependent mechanisms. The GABAergic developmental switch may also be particularly vulnerable to dysfunction leading to seizure disorders. The developmental GABA switch is mediated primarily by KCC2, a neuronal K+/Cl−cotransporter that determines the intracellular concentration of Cl−and, hence, the reversal potential for GABA. Here, we report thatkazachoc(kcc) mutations that reduce the level of the sole K+/Cl−cotransporter in the fruitflyDrosophila melanogasterrender flies susceptible to epileptic-like seizures.Drosophilakcc protein is widely expressed in brain neuropil, and its level rises with developmental age. Youngkccmutant flies with low kcc levels display behavioral seizures and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. Thekccmutation enhances a series of otherDrosophilaepilepsy mutations indicating functional interactions leading to seizure disorder. Both genetic and pharmacological experiments suggest that the increased seizure susceptibility ofkccflies occurs via excitatory GABAergic signaling. Thekccmutants provide an excellent model system in which to investigate how modulation of GABAergic signaling influences neuronal excitability and epileptogenesis.
Lighter or Heavier Than Predicted: Neural Correlates of Corrective Mechanisms during Erroneously Programmed Lifts
Authors: Jenmalm Per , Schmitz Christina , Forssberg Hans , Ehrsson H. Henrik
Published: August 2006

A central concept in neuroscience is that the CNS signals the sensory discrepancy between the predicted and actual sensory consequences of action. It has been proposed that the cerebellum and parietal cortex are involved in this process. A discrepancy will trigger preprogrammed corrective responses and update the engaged sensorimotor memories. Here we use functional magnetic resonance imaging with an event-related design to investigate the neuronal correlates of such discrepancies. Healthy adults repeatedly lifted an object between their right index fingers and thumbs, and on some lifting trials, the weight of the object was unpredictably changed between light (230 g) and heavy (830 g). Regardless of whether the weight was heavier or lighter than predicted, activity was found in the right inferior parietal cortex (supramarginal gyrus). This suggests that this region is involved in the comparison of the predicted and actual sensory input and the updating of the sensorimotor memories. When the object was lighter or heavier than predicted, two different types of preprogrammed force corrections occurred. There was a slow force increase when the weight of the object was heavier than predicted. This corrective response was associated with activity in the left primary motor and somatosensory cortices. The fast termination of the excessive force when the object was lighter than predicted activated the right cerebellum. These findings show how the parietal cortex, cerebellum, and motor cortex are involved in the signaling of the discrepancy between predicated and actual sensory feedback and the associated corrective mechanisms.
The Relationship between Body and Scale Growth Proportions and Validation of Two Back‐Calculation Methods Using Individually Tagged and Recaptured Wild Atlantic Salmon
Authors: Heidarsson Thorkell , Antonsson Thorolfur , Snorrason Sigurður S.
Published: August 2006

Using individually tagged wild Atlantic salmon Salmo salar from two Icelandic rivers, we evaluated scale growth in relation to body growth and validated smolt length estimates derived from the Dahl–Lea and Fraser–Lee back‐calculation models. Smolts were measured and individually tagged during their seaward migration, and scale samples were taken. The scale reader's accuracy was tested, and the bias was found to be less than 5% on average. Spring freshwater growth measurements (i.e., riverine growth during the spring before seaward migration) were validated using scales from smolts and again from the same individuals as adults. Spring growth was largely underestimated (average = 31–34%) when back‐calculated from adult scales. Isometry in body growth and scale growth depended on the fish growth rate. The Dahl–Lea back‐calculation model overestimated smolt lengths in both populations (average = 0.76–1.43 cm). Use of the Fraser–Lee back‐calculation model resulted in slightly more extensive overestimation of smolt length (average = 1.36–1.71 cm). The overestimation decreased with increased smolt size, especially in the Vesturdalsá. The results indicate that the accuracy of the Dahl–Lea back‐calculation model is acceptable and that this model is less biased than the Fraser–Lee model for back‐calculating smolt length. The effect of over‐ or underestimating freshwater growth in spring should be kept in mind when back‐calculating from adult scales, even if the final error will be proportionally small.
Review of Guidelines and the Literature in the Treatment of Acute Bronchospasm in Asthma
Authors: Blake Kathryn
Published: August 2006

Asthma is a common chronic condition that disproportionately affects persons younger than 45 years. Asthma exacerbations can be sudden and severe, requiring treatment in the emergency department or hospitalization. Children younger than 15 years are 2–4 times more likely to have asthma as the first‐listed hospital discharge diagnosis compared with those in other age groups. An estimated 12.8 million missed school days and 24.5 million lost work days due to asthma occurred in 2003. Drugs used in the treatment of acute asthma include inhaled β2‐agonists, oral corticosteroids, and inhaled anticholinergics. Levalbuterol was evaluated in several recent trials for treatment of asthma in the emergency department, for its effect in improving pulmonary function and on hospitalization rate. Theophylline, intravenous β2‐agonists, intravenous magnesium sulfate, and inhaled anesthetics have not been proven useful in the emergency management of asthma. The effectiveness of inhalation devices is dependent on age, cooperation of the patient, and technique.
Review of Guidelines and the Literature in the Treatment of Acute Bronchospasm in Chronic Obstructive Pulmonary Disease
Authors: Pleasants Roy A.
Published: August 2006

In 2002, an estimated 11.2 million adults in the United States had chronic obstructive pulmonary disease (COPD). Guidelines for the management of the disease have been published by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and the American Thoracic Society–European Respiratory Society. Several other organizations are in the process of preparing guidelines for COPD, most based on the GOLD report. The most important pharmacologic intervention in COPD is treatment with bronchodilator drugs. This intervention applies not only to stable COPD, but also to exacerbations (flares) of the disease. Prevention strategies have been developed for acute exacerbations, and management strategies include using short‐acting β2‐agonists, systemic corticosteroids, and antibiotics, in both at‐home and hospital settings.
Risk versus Benefit Considerations for the β2‐Agonists
Authors: Kelly H. William
Published: August 2006

Short‐acting β2‐agonists are the mainstay of therapy for acute bronchospasm associated with asthma and chronic obstructive pulmonary disease, whereas long‐acting β2‐agonists are used in maintaining disease control in these respiratory disorders. This review describes and compares the pharmacology of the β2‐agonists and explains how these differences translate into differences in efficacy and β2‐adrenergic‐mediated adverse effects. Questions commonly asked by clinicians regarding the efficacy and safety of short‐ and long‐acting β2‐agonists include issues about cardiovascular effects, tolerance to their bronchodilator and bronchoprotective effects, blunting of albuterol response by long‐acting β2‐agonists, potential masking of worsening asthma control, and the role of long‐acting β2‐agonists as adjunctive therapy with inhaled corticosteroids in maintaining asthma control. Pharmacogenetics may play a role in determining which patients may be at risk for a reduced response to a β2‐agonist. The continued use of racemic albuterol, which contains a mixture of R‐albuterol and S‐albuterol, has been questioned because of data from preclinical and clinical studies suggesting that S‐albuterol causes proinflammatory effects and may increase bronchial hyperreactivity. The preclinical and clinical effects of these two stereoisomers are reviewed. Data describing the efficacy and safety of levalbuterol (R‐albuterol) and racemic albuterol are presented.
Acute Bronchospasm from the Patient's Perspective: Role of Patient Education
Authors: Williams Dennis
Published: August 2006

Patient education is a vital tool for managing patients with acute broncho‐spasm arising from both asthma and chronic obstructive pulmonary disease (COPD). Both are serious chronic diseases, and lack of patient education usually results in lack of patients' adherence to their therapies. Several surveys indicate that a tremendous disparity exists between physicians and patients with asthma in how they perceive control of the patient's lung disease. A high proportion of physicians report that they provide patient education, and a low proportion of patients claim to have received adequate education. Management plans for both asthma and COPD are outlined, including instructions for the use of peak‐flow meters and profiles of inhalation devices. Although inhalation devices will continue to be the most common delivery systems for airway diseases that cause acute bronchospasm, their proper use can be both complex and diverse. Patient education, therefore, is essential for optimal benefit from therapy.
Treatment Algorithms from the Pharmacist Perspective
Authors: Wittbrodt Eric , Koval Peter , Raissy Hengameh H. , Nichols Jake
Published: August 2006

Hospitals across the United States develop treatment algorithms for acute bronchospasm, asthma, and chronic obstructive pulmonary disease by following several different pathways. Some institutions use established national guidelines and protocols, some revise national guidelines to apply to their particular environment, and others create specific institution‐related treatment algorithms with input from various departments, such as emergency medicine, respiratory therapy, and pharmacy. Although some institutions track outcomes on either a formal or an informal basis, others have not yet implemented outcomes‐based programs.
Long-term exposure to environmentally relevant doses of methyl-tert-butyl ether causes significant reproductive dysfunction in the zebrafish (Danio rerio)
Authors: Moreels David , van Cauwenberghe Karen , Debaere Bruno , Rurangwa Eugène , Vromant Nico , Bastiaens Leen , Diels Ludo , Springael Dirk , Merckx Roel , Ollevier Frans
Published: August 2006

Methyl-tert-butyl ether (MTBE), an anthropogenic chemical used as a gasoline additive, is being detected at an increasing frequency in the environment. The acute lethal concentration that kills 50% of the fish test population and the chronic effects of exposure to MTBE were investigated in the zebrafish (Danio rerio). Chronic exposure over three weeks to effective MTBE concentrations as low as 0.11 mg/L induced a significant increase in the vitellogenin concentration of male fish. The impact of a chronic, eight-week exposure at effective concentrations ranging from 0.44 to 220 mg/L had no significant effect on fecundity, fertilization, or hatch rate but highly significant impacts on sperm motility. Spermatozoa of all MTBE-exposure groups showed a significantly lower straight-line velocity and lower average path velocity compared to those of the nonexposed group. These results suggest that chronic exposure to MTBE negatively affects fish sperm motility at concentrations that are environmentally relevant and several orders of magnitude lower than concentrations inducing acute effects.
Atmospheric dry deposition of trace metals in the coastal region of Los Angeles, California, USA
Authors: Sabin Lisa D. , Lim Jeong Hee , Stolzenbach Keith D. , Schiff Kenneth C.
Published: August 2006

Emissions of trace metals to the atmosphere and subsequent deposition, either directly to a waterbody surface or indirectly to the watershed as washoff during rainfall, represents a potential source of contamination to surface waters near urban centers. The present study provides measurements of atmospheric concentrations of particle-bound trace metals, and it estimates the dry deposition mass loading of trace metals in coastal watersheds in the Los Angeles, California, USA, air basin. Coarse-particle atmospheric concentrations of metals were measured seasonally using a Noll Rotary Impactor at six urban sites and one nonurban site. Dry deposition fluxes were calculated by summing the product of air concentration and the theoretical deposition velocity for each particle size fraction. Mean fluxes at urban sites ranged from 3.2 to 9.1, 11 to 34, 3.8 to 8.8, 8.3 to 29, and 69 to 228 μg/m2/d for chromium, copper, nickel, lead, and zinc, respectively. Mean concentrations and fluxes were significantly higher at urban sites compared with the nonurban site, although differences between urban and nonurban sites were reduced when sampling took place within 5 d after rainfall. Dry deposition to watershed land surfaces was substantial, representing a potentially large source of trace metals based on comparisons with load estimates from stormwater runoff.
Effects of pulp and paper mill discharges on caged rainbow trout (Oncorhynchus mykiss): Biomarker responses along a pollution gradient in the Biobio River, Chile
Authors: Orrego Rodrigo , Burgos Abed , Moraga-Cid Gustavo , Inzunza Barbara , Gonzalez Margarita , Valenzuela Ariel , Barra Ricardo , Gavilán Juan F.
Published: August 2006

Caging experiments were conducted using hatchery-reared, immature, female rainbow trout (Oncorhynchus mykiss) in three previously defined areas of the Biobio River (south central Chile) representing a pollution gradient from the pulp and paper mill discharges area: a pre-impact area (upstream area, reference location), an impact area (area directly influenced), and a postimpact area (downstream area, less influenced). No significant changes were observed in the physiological index as represented by condition factor (K) and liver somatic index during different sampling times (after 11, 21, and 30 d of exposure). Ethoxyresorufin-O-deethylase activities were significantly higher in trout caged at the impact and postimpact discharges areas (two- to fourfold) compared with the reference (pre-impact) area, and a strong inhibition of acetylcholinesterase activity, reaching 50%, was observed mainly in fish caged at the impact area. A significant endocrine–disrupting effect (reproductive level) was evidenced by significant increments in gonad somatic index and plasma vitellogenin levels combined with an induction of gonad maturation (presence of vitellogenic oocytes) in trout caged at the impact and postimpact areas. These results, generated by an in situ approach, confirmed our group's findings for trout exposed to sediment in the laboratory: discharges of pulp mill effluent in the Biobio River are associated with the effects evaluated at different biological levels.
Uptake, removal, accumulation, and phytotoxicity of phenol in willow trees (Salix viminalis)
Authors: Ucisik Ahmed Suheyl , Trapp Stefan
Published: August 2006

Phenol is an intermediate in the metabolism of plants, but it also is a high-volume production compound frequently found in the environment. The relation between removal, uptake, accumulation, and toxicity of phenol in willow trees (Salix viminalis) was determined. Willows were exposed to phenol levels up to 1,000 mg/L in hydroponic solution and sand, respectively. The change on water transpiration of the trees was used to determine toxic effects. In both hydroponic solution and sand, only small inhibition of transpiration was detected up to phenol concentrations of 250 mg/L. For concentrations of 500 mg/L or greater, transpiration fell to 50% or less, and the trees wilted. The trees exposed to 1,000 mg/L wilted and eventually died. For initial nominal concentrations of 1,000 mg/L, a significantly higher amount of phenol remained at the end of the experiment compared to the amount remaining with all other concentrations. Phenol loss was approximately 90% for the trees that survived, except for trees exposed to the lowest concentration (10 mg/L). The loss of phenol was only 15 to 18% in experiments performed without trees. The results demonstrate a clear relation between removal, accumulation, and toxic effects of phenol in trees. Phenol levels of less than 250 mg/L could be degraded by “in planta” metabolism; therefore, no significant buildup of phenol nor any toxic effects in plants occurred. With higher levels, phenol was still degraded quickly, but an accumulation in trees accompanied by severe toxic effects occurred. Phytoremediation of phenol would be best with concentrations in water or soil solution of less than 250 mg/L, at which the degradation of phenol by willows or associated bacteria is rapid and efficient and the toxic effects on trees are negligible.