bluuebunny/crossref_metadata_2025 huggingface dataset:
One-Pot Synthesis of Selenothioic Acid S-Alkyl Esters by the Reaction of Lithium Alkyneselenolates with Thiols
Authors: Murai Toshiaki , Hayashi Akihiro , Kanda Takahiro , Kato Shinzi
Published: March 2006

The reaction of lithium alkyneselenolates generated from lithium alkynides and selenium powder with a variety of thiols afforded selenothioic acid S-alkyl esters in moderate to high yields. The product yields were highly dependent on the substituents of the starting acetylenes. The formation of unstable S-aryl ester was confirmed by the enolization followed by alkylation.
Oxidation of Cr(III) to Cr(VI) Species During the Thermal Decomposition Process of Zn/Cr-layered Double Hydroxide Carbonate
Authors: Fuda Kiyoshi , Suda Kazuhito , Matsunaga Toshiaki
Published: March 2006

The intermediates obtained from thermal decomposition of Zn/Cr-layered double hydroxide carbonates (Zr/Cr-LDH; Zn0.66Cr0.34(OH)2(CO3)0.170.57H2O) were studied by XRD, TPD, FT-IR, ESCA and chemical analyses. It was found that Cr(III) ions embedded originally in the hydroxide layers were oxidized to Cr(VI) species in the temperature range between 473 and 773 K where the layer structure was lost, and reduced again to Cr(III) in the spinel phase over 773 K.
3-Arylcyclohex-2-en-1-ones and 3,6-Diarylcyclohex-2-en-1-ones. New Liquid Crystalline Compounds
Authors: Brettle Roger , Dunmur David A , Farrand Louise D , Hindley Nigel J , Marson Charles M
Published: March 2006

The cyclohex-2-en-1-one unit flanked by one or more aryl rings is shown to provide a new system which can exhibit liquid crystal properties; these new mesogens contain a chiral centre which is both adjacent to a lateral dipolar carbonyl group and is also located in the central core.
Photocatalytic Decomposition of Propyzamide Using TiO2 Supported on Activated Carbon
Authors: Uchida Hiroyuki , Itoh Shigeyoshi , Yoneyama Hiroshi
Published: March 2006

Utility of activated carbon adsorbate as a support for TiO2 photocatalysts was demonstrated for photomineralization of propyzamide, a typical herbicide, in dilute aqueous solution. High adsorptive activity of the activated carbon support enables the organic pollutant to concentrate around the loaded TiO2, resulting in a high photocatalytic degradation rate.
Redox-Mediated Decarboxylative Photo-Phenylselenenylation of N-Acyloxyphthalimides
Authors: Okada Keiji , Okubo Katsura , Morita Naoto , Oda Masaji
Published: March 2006

Decarboxylative phenylselenenylation of N-acyloxyphthalimides by visible light irradiation in aqueous solvents using catalytic amount of Ru(bpy)3Cl2 as a sensitizer in the presence of one equivalent of BNAH and 0.5 equivalent of diphenyl diselenide efficiently proceeds via redox-mediated radical chain mechanism. The AIBN-induced thermal reaction is also described.
Design and Synthesis of Cyclic Fibronectin Related Peptides, RGDSPASS Containing Cystine Peptides
Authors: Yamamoto Yasuo , Katow Hideki , Sofuku Shosuke
Published: March 2006

Arg-Gly-Asp-Ser (RGDS) is an active site in the cell binding domain of fibronectin (FN). Three types of RGDSPASS containing cystine peptides were designed on the basis of the position of Pro in β turn and synthesized.
Enhanced Quantum Yield in Porphyrin Heterodimer Solar Cells
Authors: Takahashi Kohshin , Nanbu Hideki , Komura Teruhisa , Murata Kazuhiko
Published: March 2006

The Al/porphyrin/Au sandwich-type photovoltaic cell with a heterodimer solid of 5,10,15,20-tetraphenylporphyrinatozinc (Zntpp) and 5,10,15-triphenyl-20-(3-pyridyl)porphyrin (H2pyp3p) exhibits a remarkably large photocurrent quantum yield, compared with the cell with a pure Zntpp or an H2pyp3p solid.
Preparation and Properties of Polyaniline Nitrile-Rubber Copolymers
Authors: Oka Osamu , Kiyohara Osamu , Morita Shigenori , Yoshino Katsumi
Published: March 2006

Graft copolymers of polyaniline and telechelic nitrile rubber have been synthesized. They were soluble in N-methyl-2-pyrrolidone(NMP) and flexible self-supporting films were obtained by casting the solutions. Upon protonic doping, their conductivities rised from 10−8 to 10−2 S/cm. Spectroscopic, electrochemical and mechanical studies demonstrated that the electronic states of copolymer are fundamentally the same as those of the original polyaniline, i.e., they are not much influenced by the grafting, however, the mechanical properties are affected by rubber.
Catalytic Stereoselective Synthesis of α- or β-Ribofuranosides by Combined Use of Silver Salts and Lithium Perchlorate or Diphenyltin Sulfide
Authors: Mukaiyama Teruaki , Shimomura Naoyuki
Published: March 2006

Catalytic stereoselective synthesis of 1,2-cis- or 1,2-trans-ribofuranosides from 1-O-iodoacetylribofuranose and alkyl trimethylsilyl ethers is efficiently promoted by combined use of silver salts and lithium perchlorate or diphenyltin sulfide (Ph2Sn=S) under mild conditions.
One-Pot Preparation of Alcohols from Aromatic Olefins and Acrylic Acid Derivatives by Cobalt(II) Porphyrin-Catalyzed Reductive Oxygenation Followed by Reduction with Trimethyl Phosphite
Authors: Matsusita Yoh-ichi , Sugamoto Kazuhiro , Matsui Takanao
Published: March 2006

Various aromatic olefins and acrylic acid derivatives were converted to benzyl alcohols and α-hydroxyalkanoic acid derivatives in good yields by the reductive oxygenation with oxygen and triethylsilane in the presence of a catalytic amount of cobalt(II) porphyrin followed by treating the reaction mixture with trimethyl phosphite.
Service System Design with Immobile Servers, Stochastic Demand, and Congestion
Authors: Elhedhli Samir
Published: March 2006

The service system design problem seeks to locate a set of service facilities, allocate enough capacity, and assign stochastic customer demand to each of them, so as to minimize the fixed costs of opening facilities and acquiring service capacity, as well as the variable access and waiting costs. This problem is commonly known in the location literature as the facility location problem with immobile servers, stochastic demand, and congestion. It is often set up as a network of M/M/1 queues and modeled as a nonlinear mixed-integer program (MIP). Because of the complexity of the resulting model, the current literature focuses on approximate and/or heuristic solution methods. This paper proposes a linearization based on a simple transformation and piecewise linear approximations and an exact solution method based on cutting planes. This leads to the exact solution of models with up to 100 customers, 20 potential service facilities, and 3 capacity levels.
Extending the Horizons: Environmental Excellence as Key to Improving Operations
Authors: Corbett Charles J. , Klassen Robert D.
Published: March 2006

The view that adopting an environmental perspective on operations can lead to improved operations is in itself not novel; phrases such as “lean is green” are increasingly commonplace. The implication is that any operational system that has minimized inefficiencies is also more environmentally sustainable. However, in this paper we argue that the underlying mechanism is one of extending the horizons of analysis and that this applies to both theory and practice of operations management. We illustrate this through two principal areas of lean operations, where we identify how successive extensions of the prevailing research horizon in each area have led to major advances in theory and practice. First, in quality management, the initial emphasis on statistical quality control of individual operations was extended through total quality management to include a broader process encompassing customer requirements and suppliers’ operations. More recently, the environmental perspective extended the definition of customers to stakeholders and defects to any form of waste. Second, in supply chain management, the horizon first expanded from the initial focus on optimizing inventory control with a single planner to including multiple organizations with conflicting objectives and private information. The environmental perspective draws attention to aspects such as reverse flows and end-of-life product disposal, again potentially improving the performance of the overall supply chain. In both cases, these developments were initially driven by practice, where many of the benefits of adopting an environmental perspective were unexpected. Given that these unexpected side benefits seem to recur so frequently, we refer to this phenomenon as the “law of the expected unexpected side benefits.” We conclude by extrapolating from the developmental paths of total quality management and supply chain management to speculate about the future of environmental research in operations management.
Supply Auctions and Relational Contracts for Procurement
Authors: Tunca Tunay I. , Zenios Stefanos A.
Published: March 2006

We examine the competition between procurement auctions and long-term relational contracts that emerges from the increased usage of electronic marketplaces. Procurement auctions create supply chain efficiencies by selecting the least costly bidder, and long-term relational contracts ensure the quality of the procured products or services when these have nonverifiable attributes. The following two-layer supply chain model is analyzed: Suppliers of an industrial part with nonverifiable quality trade with several manufacturers that utilize that part in the production of an end product. A price-based reverse auction is used for the procurement of low-quality parts, and a relational long-term contract is used for high-quality parts. A formal model of the competition between the two procurement models identifies conditions under which the two coexist, and conditions under which one will push the other out of the market. Market and product parameters that increase the relative economic appeal of the relational contract are determined. It is demonstrated that the competition from the auction market can either facilitate or undermine the relational contract compared with a benchmark case of a monopolist supplier. This implies that competition between the two procurement models plays an important role in the supply of high-quality products.
Development and Validation of an Instrument to Determine Patient Knowledge: The Oral Anticoagulation Knowledge Test
Authors: Zeolla Mario M , Brodeur Michael R , Dominelli Angela , Haines Stuart T , Allie Nicole D
Published: March 2006

Background:

Studies examining the relationship between patient knowledge regarding warfarin therapy and its safe and effective use are limited by the lack of validated knowledge assessment tools.

Objective:

To develop and validate an instrument to assess patient knowledge regarding oral anticoagulation therapy.

Methods:

Four nationally recognized anticoagulation experts participated in the instrument development process to ensure content validity. The Oral Anticoagulation Knowledge (OAK) test was administered to subjects on warfarin and a group of age-matched subjects not on warfarin to assess construct validity. A subgroup of warfarin subjects were retested approximately 2–3 months after initial testing to assess test–retest reliability. Internal consistency reliability was assessed by calculating a Kuder-Richardson 20 value. Item analysis was used to assess performance of individual questions.

Results:

An initial 23 item instrument was pilot tested for readability and comprehension. The OAK test was administered to 74 subjects taking warfarin and 27 age-matched subjects not on warfarin. Thirty-two subjects on warfarin repeated the OAK test an average of 75 days following initial administration. Subjects taking warfarin scored significantly higher than those not on warfarin (72% vs 52%, respectively; p < 0.001), supporting the construct validity of the instrument. Test–retest reliability was acceptable, with a Pearson's correlation coefficient of 0.81. Internal consistency reliability was confirmed by a calculated Kuder–Richardson 20 value of 0.76.

Conclusions:

The OAK test is a brief, valid, and reliable knowledge assessment instrument that may be a useful tool for research and clinical practice to augment patient education programs.
Transfer of Probenecid and Cephalexin into Breast Milk
Authors: Ilett Kenneth F , Hackett L Peter , Ingle Bridget , Bretz Paul J
Published: March 2006

Objective:

To report a case of the transfer of probenecid and cephalexin into human milk.

Case Summary:

A breast-fed infant of a 30-year-old woman being treated with oral probenecid and cephalexin for a breast infection developed severe diarrhea and associated symptoms. To investigate whether the maternal drug treatment was causative, milk was collected over a dose interval at steady-state, and concentrations of probenecid and cephalexin were measured by HPLC. The average concentrations of probenecid and cephalexin in milk were 964 and 745 μg/L, respectively, corresponding to absolute and relative infant doses of 145 μg/kg/day and 0.7% for probenecid and 112 μg/kg/day and 0.5% for cephalexin. The infant's adverse effects were rated as possible for probenecid and probable for cephalexin based on the Naranjo probability scale.

Discussion:

On the basis of the calculated relative infant doses for both probenecid and cephalexin in milk and the notional 10% level of concern for infant exposure, neither drug would be expected to cause significant systemic effects. However, local adverse effects, notably diarrhea, were observed. The Naranjo probability scale rating suggested that cephalexin was more likely than probenecid to be the cause of the infant's diarrhea.

Conclusions:

When using cephalexin/probenecid to treat breast infections in lactating women, clinicians should anticipate the possibility of adverse gastrointestinal effects in the breast-fed infant.
Friends' Influence on Adolescents' First Sexual Intercourse
Authors: Sieving Renee E. , Eisenberg Marla E. , Pettingell Sandra , Skay Carol
Published: March 2006

CONTEXT: Social‐psychological theories of health behavior suggest that adolescents' sexual behaviors are influenced by the sexual attitudes and behaviors of their friends.

METHODS: Data on 2,436 participants in the National Longitudinal Study of Adolescent Health (Add Health) who were sexually inexperienced at Wave 1 (1994–1995) were analyzed to examine whether friend‐related variables predicted initiation of vaginal intercourse by Wave 2 (1996). Analyses also assessed whether predictive relationships varied by level of involvement with friends. Odds ratios were generated by logistic regression analysis.

RESULTS: In the 9–18 months between Waves 1 and 2, 18% of participants initiated intercourse. In analyses controlling for gender, family structure and romantic relationships, the higher the proportion of a youth's friends who were sexually experienced, the greater the odds of sexual debut (odds ratio, 1.01); the odds also were elevated among youth who believed that they would gain their friends' respect by having sex (1.2). Relationships between friend variables and sexual initiation did not vary by level of involvement with friends.

CONCLUSIONS: To maximize the likelihood of success, programs focused on delaying teenage sexual intercourse should address norms for sexual behavior among adolescents' close friends as well as the perceptions, skills and behaviors of individual youth.
Extracellular-Signal Regulated Kinase 1-Dependent Metabotropic Glutamate Receptor 5-Induced Long-Term Depression in the Bed Nucleus of the Stria Terminalis Is Disrupted by Cocaine Administration
Authors: Grueter Brad A. , Gosnell Heather B. , Olsen Christopher M. , Schramm-Sapyta Nicole L. , Nekrasova Tanya , Landreth Gary E. , Winder Danny G.
Published: March 2006

The bed nucleus of the stria terminalis (BNST) is a key component of the CNS stress and reward circuit. Synaptic plasticity in this region could in part underlie the persistent behavioral alterations in generalized anxiety and addiction. Group I metabotropic glutamate receptors (mGluRs) have been implicated in stress, addiction, and synaptic plasticity, but their roles in the BNST are unknown. We find that activation of group I mGluRs in the dorsal BNST induces depression of excitatory synaptic transmission through two distinct mechanisms. First, a combined activation of group I mGluRs (mGluR1 and mGluR5) induces a transient depression that is cannabinoid 1 receptor dependent. Second, as with endocannabinoid-independent group I mGluR long-term depression (LTD) in the adult hippocampus, we find that activation of mGluR5 induces an extracellular signal-regulated kinase (ERK)-dependent LTD. Surprisingly, our data demonstrate that this LTD requires the ERK1 rather than ERK2 isoform, establishing a key role for this isoform in the CNS. Finally, we find that this LTD is dramatically reduced after multiple exposures but not a single exposure to cocaine, suggesting a role for this form of plasticity in the actions of psychostimulants on anxiety and reward circuitries and their emergent control of animal behavior.
Protein Interacting with C-Kinase 1/Protein Kinase Cα-Mediated Endocytosis Converts Netrin-1-Mediated Repulsion to Attraction
Authors: Bartoe Joseph L. , McKenna William L. , Quan Tiffani K. , Stafford Benjamin K. , Moore Jenna A. , Xia Jun , Takamiya Kogo , Huganir Richard L. , Hinck Lindsay
Published: March 2006

In vertebrates, the receptor families deleted in colorectal cancer (DCC) and UNC5 mediate responses to the bifunctional guidance cue netrin-1. DCC mediates attraction, whereas a complex of DCC and UNC5 mediates repulsion. Thus, a primary determinant of the responsiveness of an axon to netrin-1 is the presence or absence of UNC5 family members on the cell surface. Currently, little is known about the role of receptor trafficking in regulating neuronal responses to netrin-1. We show that protein interacting with C-kinase 1 (PICK1) recruits activated protein kinase Cα (PKCα) to MycUNC5A at the plasma membrane, stimulating its endocytosis. We identify two PKCα phosphorylation sites at serines 408 and 587, as well as dileucine internalization motifs, which are required for this endocytosis. We find that PKCα-stimulated internalization of UNC5A alters the functional response of developing hippocampal axons to netrin-1, preventing UNC5A-mediated growth cone collapse and converting netrin-1-stimulated chemorepulsion to attraction. To address whether this conversion in axonal response occurs in neurons expressing endogenous levels of UNC5, we show that mouse cerebellar granule axons exhibit chemorepulsion in a netrin-1 gradient and that this chemorepulsion is converted to chemoattraction after PKCα activation. We demonstrate that this repulsion depends on UNC5A becauseUnc5a−/− axons are not repelled and show this conversion depends on PICK1 becausePICK1−/− axons are not converted to chemoattraction after PKCα activation. Together, these data provide a potential mechanism to explain how developing neurons alter their responsiveness to netrin-1 at intermediate choice points as they navigate to their targets.
Neuregulin 1–erbB Signaling Is Necessary for Normal Myelination and Sensory Function
Authors: Chen Suzhen , Velardez Miguel Omar , Warot Xavier , Yu Zhao-Xue , Miller Shyra J. , Cros Didier , Corfas Gabriel
Published: March 2006

To investigate the role of erbB signaling in the interactions between peripheral axons and myelinating Schwann cells, we generated transgenic mice expressing a dominant-negative erbB receptor in these glial cells. Mutant mice have delayed onset of myelination, thinner myelin, shorter internodal length, and smaller axonal caliber in adulthood. Consistent with the morphological defects, transgenic mice also have slower nerve conduction velocity and defects in their responses to mechanical stimulation. Molecular analysis indicates that erbB signaling may contribute to myelin formation by regulating transcription of myelin genes. Analysis of sciatic nerves showed a reduction in the levels of expression of myelin genes in mutant mice.In vitroassays revealed that neuregulin-1 (NRG1) induces expression of myelin protein zero (P0). Furthermore, we found that the effects of NRG1 on P0 expression depend on the NRG1 isoform used. When NRG1 is presented to Schwann cells in the context of cell–cell contact, type III but not type I NRG1 regulates P0 gene expression. These results suggest that disruption of the NRG1–erbB signaling pathway could contribute to the pathogenesis of peripheral neuropathies with hypomyelination and neuropathic pain.
Receptive Field Properties of Neurons in the Early Visual Cortex Revealed by Local Spectral Reverse Correlation
Authors: Nishimoto Shinji , Ishida Tsugitaka , Ohzawa Izumi
Published: March 2006

We introduce a novel class of white-noise analyses, named local spectral reverse correlation (LSRC), which is capable of revealing various aspects of visual receptive field profiles that were undetectable previously in a single simple measurement. The method is based on spectral analyses in a two-dimensional spatial frequency domain for spatially localized areas within and around their receptive fields. Extracellular single-unit recordings were performed for area 17 and 18 neurons in anesthetized cats. A dynamic dense noise pattern was presented in which the pattern covered an area two to three times larger than the classical receptive field. Spike trains were then cross-correlated with frequency spectra of localized noise pattern to obtain spatially localized selectivity maps in the two-dimensional frequency domain. Our findings are as follows. (1) The new LSRC method allows measurements of two-dimensional frequency tunings and their spatial extent even for cells with substantial nonlinearity. (2) A small subset of neurons shows spatial inhomogeneity in the two-dimensional frequency tunings. (3) In addition to facilitatory response profiles, we can also visualize suppressive profiles localized both in space and spatial frequency domains. Our results suggest that the new analysis technique can be a powerful tool for measuring visual response profiles that contain inhomogeneity in space, as well as for studying neurons with substantial nonlinearities. These features make the method particularly suitable for studying response profiles of neurons in early as well as intermediate extrastriate visual areas.
Notch1 Signaling Regulates Radial Glia Differentiation through Multiple Transcriptional Mechanisms
Authors: Patten Brooke A. , Sardi S. Pablo , Koirala Samir , Nakafuku Masato , Corfas Gabriel
Published: March 2006

Signaling by the Notch1 receptor is critical for the formation of radial glia in the developing nervous system. We have shown previously that Notch1 regulates the molecular and morphological differentiation of radial glia through the transcriptional activation of at least two genes, brain lipid binding protein (BLBP) and the erbB2 receptor tyrosine kinase. However, the mechanisms by which this occurs remained undefined. Here we demonstrate that Notch1 effects on radial glia gene expression are mediated by two downstream mechanisms, one that the depends on Suppressor of Hairless [Su(H)] and the other on Deltex1 (DTX1). These two Notch1-binding proteins contribute to the regulation of BLBP and erbB2 expression, respectively. Importantly, our results suggest that, although these events can occur simultaneously, a hierarchical relationship might exist between DTX1 and Su(H), because overexpression of DTX1 or a dominant-negative form of this protein inhibits Su(H)-mediated events but not vice versa. In contrast to the effects of DTX1 overexpression, interference RNA-mediated knock-down of DTX1 blocks Notch1-induced erbB2 promoter activation and radial glia formation selectively, without affecting Su(H)-dependent pathways, indicating that loss of DTX1 expression and expression of dominant-negative DTX1 result in different alterations in cell differentiation and gene expression. Together, these results show that Notch1 regulates radial glia formation through two distinct transcriptional mechanisms and that the outcomes of Notch1 signaling may depend on the relative expression levels of its coregulators.
Cocaine Increases Dopamine Release by Mobilization of a Synapsin-Dependent Reserve Pool
Authors: Venton B. Jill , Seipel Andrew T. , Phillips Paul E. M. , Wetsel William C. , Gitler Daniel , Greengard Paul , Augustine George J. , Wightman R. Mark
Published: March 2006

Cocaine primarily exerts its behavioral effects by enhancing dopaminergic neurotransmission, amplifying dopamine-encoded sensorimotor integration. The presumed mechanism for this effect is inhibition of the dopamine transporter, which blocks dopamine uptake and prolongs the duration of dopamine in the extracellular space. However, there is growing evidence that cocaine can also augment dopamine release. Here, we directly monitored the actions of cocaine on dopamine release by using electrochemical detection to measure extracellular dopamine in the striatum of anesthetized mice. Cocaine enhanced the levels of striatal dopamine produced by electrical stimulation of dopaminergic neurons. Even after pretreatment with α-methyl-p-tyrosine, which depletes the readily releasable pool of dopamine, cocaine was still capable of elevating dopamine levels. This suggests that cocaine enhances dopamine release by mobilizing a reserve pool of dopamine-containing synaptic vesicles. To test this hypothesis, we examined electrically evoked dopamine release in synapsin I/II/III triple knock-out mice, which have impaired synaptic vesicle reserve pools. Knock-out of synapsins greatly reduced the ability of cocaine to enhance dopamine release with long stimulus trains or after depletion of the newly synthesized pool. We therefore conclude that cocaine enhances dopamine release and does so by mobilizing a synapsin-dependent reserve pool of dopamine-containing synaptic vesicles. This capacity to enhance exocytotic release of dopamine may be important for the psychostimulant actions of cocaine.
Retinoic Acid Receptor-Dependent Survival of Olfactory Sensory Neurons in Postnatal and Adult Mice
Authors: Hägglund Maria , Berghard Anna , Strotmann Jörg , Bohm Staffan
Published: March 2006

To address the hypothesis that retinoids produced by synthesizing enzymes present in the primary olfactory system influence the mouse olfactory sensory map, we expressed a dominant-negative retinoic acid receptor selectively in olfactory sensory neurons. We show that neurons deficient in nuclear retinoid signaling are responsive to odors and form correct odorant receptor-specific axonal projections to target neurons in the olfactory bulb of the brain. Subsequent to the formation of the map, the neurons die prematurely by retrograde-driven caspase-3 activation, which resembles the previously described mechanism of neural death after olfactory bulb ablation. This neurodegenerative event is initiated the second postnatal week and occurs in the adult animal without a compensatory increase of progenitor cell proliferation. In addition, we find that nuclear retinoid signaling is required for the expression of a retinoic acid-degrading enzyme, Cyp26B1, in a small fraction of mature neurons. Collectively, the results provide evidence for a role of locally regulated retinoid metabolism in neuroprotection and in determining population size of neurons at a late stage of neural circuit formation.
Mechanoporation Induced by Diffuse Traumatic Brain Injury: An Irreversible or Reversible Response to Injury?
Authors: Farkas Orsolya , Lifshitz Jonathan , Povlishock John T.
Published: March 2006

Diffuse traumatic brain injury (DTBI) is associated with neuronal plasmalemmal disruption, leading to either necrosis or reactive change without cell death. This study examined whether enduring membrane perturbation consistently occurs, leading to cell death, or if there is the potential for transient perturbation followed by resealing/recovery. We also examined the relationship of these events to calpain-mediated spectrin proteolysis (CMSP). To assess plasmalemmal disruption, rats (n= 21) received intracerebroventricular infusion 2 h before DTBI of a normally excluded 10 kDa fluorophore-labeled dextran. To reveal plasmalemmal resealing or enduring disruption, rats were infused with another labeled dextran 2 h (n= 10) or 6 h (n= 11) after injury. Immunohistochemistry for the 150 kDa spectrin breakdown product evaluated the concomitant role of CMSP. Neocortical neurons were followed with confocal and electron microscopy. After DTBI at 4 and 8 h, 55% of all tracer-flooded neurons contained both dextrans, demonstrating enduring plasmalemmal leakage, with many demonstrating necrosis. At 4 h, 12.0% and at 8 h, 15.7% of the dual tracer-flooded neurons showed CMSP, yet, these demonstrated less advanced cellular change. At 4 h, 39.0% and at 8 h, 24.4% of all tracer-flooded neurons revealed only preinjury dextran uptake, consistent with membrane resealing, whereas 7.6 and 11.1%, respectively, showed CMSP. At 4 h, 35% and at 8 h, 33% of neurons demonstrated CMSP without dextran flooding. At 4 h, 5.5% and at 8 h, 20.9% of tracer-flooded neurons revealed only postinjury dextran uptake, consistent with delayed membrane perturbation, with 55.0 and 35.4%, respectively, showing CMSP. These studies illustrate that DTBI evokes evolving plasmalemmal changes that highlight mechanical and potential secondary events in membrane poration.
Tau Protects Microtubules in the Axon from Severing by Katanin
Authors: Qiang Liang , Yu Wenqian , Andreadis Athena , Luo Minhua , Baas Peter W.
Published: March 2006

Microtubules in the axon are more resistant to severing by katanin than microtubules elsewhere in the neuron. We have hypothesized that this is because of the presence of tau on axonal microtubules. When katanin is overexpressed in fibroblasts, the microtubules are severed into short pieces, but this phenomenon is suppressed by the coexpression of tau. Protection against severing is also afforded by microtubule-associated protein 2 (MAP2), which has a tau-like microtubule-binding domain, but not by MAP1b, which has a different microtubule-binding domain. The microtubule-binding domain of tau is required for the protection, but within itself, provides less protection than the entire molecule. When tau (but not MAP2 or MAP1b) is experimentally depleted from neurons, the microtubules in the axon lose their characteristic resistance to katanin. These results, which validate our hypothesis, also suggest a potential explanation for why axonal microtubules deteriorate in neuropathies involving the dissociation of tau from the microtubules.
Constitutive Activation Drives Compartment-Selective Endocytosis and Axonal Targeting of Type 1 Cannabinoid Receptors
Authors: Leterrier Christophe , Lainé Jeanne , Darmon Michèle , Boudin Hélène , Rossier Jean , Lenkei Zsolt
Published: March 2006

The type 1 cannabinoid receptor (CB1R) is one of the most abundant G-protein-coupled receptors (GPCRs) in the brain, predominantly localized to axons of GABAergic neurons. Like several other neuronal GPCRs, CB1R displays significantin vitroconstitutive activity (i.e., spontaneous activation in the absence of ligand). However, a clear biological role for constitutive GPCR activity is still lacking. This question was addressed by studying the consequences of constitutive activation on the intracellular trafficking of endogenous or transfected CB1Rs in cultured hippocampal neurons using optical and electron microscopy. We found that constitutive activity results in a permanent cycle of endocytosis and recycling, which is restricted to the somatodendritic compartment. Thus, CB1Rs are continuously removed by endocytosis from the plasma membrane in the somatodendritic compartment but not in axons, where CB1Rs accumulate on surface. Blocking constitutive activity by short-term incubation with inverse agonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide (AM281) results in sequestration of recycled CB1Rs on the somatodendritic plasma membrane. Long-term inhibition of endocytosis by cotransfection of dominant-negative proteins results in impaired axonal polarization of surface-bound CB1Rs. Kinetic analysis shows that the majority of newly synthesized CB1Rs arrive first to the somatodendritic plasma membrane, from where they are rapidly removed by AM281-sensitive constitutive endocytosis before being delivered to axons. Thus, constitutive-activity driven somatodendritic endocytosis is required for the proper axonal targeting of CB1R, representing a novel, conformation-dependent targeting mechanism for axonal GPCRs.
Motoneurons Derived from Embryonic Stem Cells Express Transcription Factors and Develop Phenotypes Characteristic of Medial Motor Column Neurons
Authors: Soundararajan Prabakaran , Miles Gareth B. , Rubin Lee L. , Brownstone Robert M. , Rafuse Victor F.
Published: March 2006

Embryonic stem (ES) cells differentiate into functional motoneurons when treated with a sonic hedgehog (Shh) agonist and retinoic acid (RA). Whether ES cells can be directed to differentiate into specific subtypes of motoneurons is unknown. We treated embryoid bodies generated from HBG3 ES cells with a Shh agonist and RA for 5 d in culture to induce motoneuron differentiation. Enhanced green fluorescent protein (eGFP) expression was used to identify putative motoneurons, because eGFP is expressed under the control of theHb9promoter in HBG3 cells. We found that 96 ± 0.7% of the differentiated eGFP+motoneurons expressed Lhx3, a homeobox gene expressed by postmitotic motoneurons in the medial motor column (MMCm), when the treated cells were plated on a neurite-promoting substrate for 5 d. When the treated embryoid bodies were transplanted into stage 17 chick neural tubes, the eGFP+motoneurons migrated to the MMCm, expressed Lhx3, projected axons to the appropriate target for MMCmmotoneurons (i.e., epaxial muscles), and contained synaptic vesicles within intramuscular axonal branches.In ovoandin vitrostudies indicated that chemotropic factors emanating from the epaxial muscle and/or surrounding mesenchyme likely guide Lhx3+motoneurons to their correct target. Finally, whole-cell patch-clamp recordings of transplanted ES cell-derived motoneurons demonstrated that they received synaptic input, elicited repetitive trains of action potentials, and developed passive membrane properties that were similar to host MMCmmotoneurons. These results indicate that ES cells can be directed to form subtypes of neurons with specific phenotypic properties.
Human Astrocytes Are Resistant to Fas Ligand and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis
Authors: Song Jin H. , Bellail Anita , Tse Margaret C. L. , Yong V. Wee , Hao Chunhai
Published: March 2006

Human astrocytes express Fas yet are resistant to Fas-induced apoptosis. Here, we report that calcium/calmodulin-dependent protein kinase II (CaMKII) is constitutively activated in human astrocytes and protects the cells from apoptotic stimulation by Fas agonist. Once stimulated, Fas recruits Fas-associated death domain and caspase-8 for the assembly of the death-inducing signaling complex (DISC); however, caspase-8 cleavage is inhibited in the DISC. Inhibition of CaMKII kinase activity inhibits the expression of phosphoprotein enriched astrocytes-15 kDa/phosphoprotein enriched in diabetes (PEA-15/PED) and cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP), thus releasing their inhibition of caspase-8 cleavage. Inhibition of PEA-15/PED or c-FLIP by small interfering RNA sensitizes human astrocytes to Fas-induced apoptosis. In contrast, inhibition of CaMKII, PEA-15, or c-FLIP does not affect the sensitivity of human astrocytes to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL death receptors (DR4, DR5) are weakly expressed at mRNA, protein, and cell surface levels and thus fail to mediate the assembly of the DISC in human astrocytes. Overexpression of DR5 restores TRAIL signaling pathways and sensitizes the human astrocytes to TRAIL-induced apoptosis if CaMKII kinase activity or expression of PEA-15 and c-FLIP is inhibited; the results suggest that CaMKII-mediated pathways prevent TRAIL-induced apoptosis in human astrocytes under conditions in which TRAIL death receptors are upregulated. This study has therefore identified the molecular mechanisms that protect normal human astrocytes from apoptosis induced by Fas ligand and TRAIL.
Nonallelic Interactions Betweenhet-cand a Polymorphic Locus,pin-c, Are Essential for Nonself Recognition and Programmed Cell Death inNeurospora crassa
Authors: Kaneko Isao , Dementhon Karine , Xiang Qijun , Glass N Louise
Published: March 2006

Nonself recognition in filamentous fungi is conferred by genetic differences at het (heterokaryon incompatibility) loci. When individuals that differ in het specificity undergo hyphal fusion, the heterokaryon undergoes a programmed cell death reaction or is highly unstable. In Neurospora crassa, three allelic specificities at the het-c locus are conferred by a highly polymorphic domain. This domain shows trans-species polymorphisms indicative of balancing selection, consistent with the role of het loci in nonself recognition. We determined that a locus closely linked to het-c, called pin-c (partner for incompatibility with het-c) was required for het-c nonself recognition and heterokaryon incompatibility (HI). The pin-c alleles in isolates that differ in het-c specificity were extremely polymorphic. Heterokaryon and transformation tests showed that nonself recognition was mediated by synergistic nonallelic interactions between het-c and pin-c, while allelic interactions at het-c increased the severity of the HI phenotype. The pin-c locus encodes a protein containing a HET domain; predicted proteins containing HET domains are frequent in filamentous ascomycete genomes. These data suggest that nonallelic interactions may be important in nonself recognition in filamentous fungi and that proteins containing a HET domain may be a key factor in these interactions.
Challenges and Opportunities in Finfish Nutrition
Authors: Trushenski Jesse T. , Kasper Craig S. , Kohler Christopher C.
Published: March 2006

Much of the criticism leveled at aquaculture (e.g., dependency on animal‐derived feedstuffs, nutrient‐laden effluent discharges, and increased organic contamination in edible products) can be traced to the feeds in use. Accordingly, finfish nutritionists are being challenged to formulate feeds that not only meet the nutritional requirements of livestock but also minimize production costs, limit environmental impacts, and enhance product quality. These challenges not only add considerable complexity to finfish nutrition but also afford opportunities to avoid some of the mistakes made by other industries in the past. From a review of the current status of finfish nutrition with respect to major nutrient classes, we comment on future opportunities and promising avenues of research. Alternative protein sources, specifically those derived from marine bycatch, plants, and microbes, are discussed, as well as methods to facilitate their implementation in finfish feeds. Dietary lipid, its role in fish bioenergetics and physiology, and quality of aquaculture products is reviewed with special emphasis on alternative lipid sources and finishing diets. Carbohydrates and fiber are discussed in terms of nutrient‐sparing, least‐cost diet formulation and digestive physiology. Micronutrients are reviewed in terms of current knowledge of requirements and, along with other dietary immunostimulants, are given further consideration in a review of nutriceuticals and application in finfish feeds. The status of nutritional research in new aquaculture species is also outlined. By integrating classical approaches with emerging technologies, dietary formulations, and species, finfish nutritionists may identify means to increase production efficiency and sustainability and provide for the continued success of aquaculture.
Relationships among Feed Intake, Feed Efficiency, and Growth in Juvenile Rainbow Trout
Authors: Silverstein Jeffrey T
Published: March 2006

Improving the efficiency of aquaculture production is important for both economic and environmental sustainability. The purpose of this work was to define the relationships between feed intake, weight gain, and feed efficiency (measured as residual feed intake) in rainbow trout Oncorhynchus mykiss fed either to apparent satiation or a limited ration. The results indicated that under an apparent satiation feeding regime, a weak but significant correlation existed between weight gain and residual feed intake (RFI; r = −0.31, P < 0.04). When fed a limited ration, the correlation between weight gain and RFI was stronger (r = −0.57, P < 0.001). Genetic differences between family groups were detected only under the apparent satiation feeding regime and not under limited feeding. Although these experiments were conducted on different groups of fish, it appears that the variation in RFI was greater in satiation-fed fish than in fish fed a limited ration (coefficient of variation = 174% versus 33%). Estimates of residual feed intake measured on individuals from full-sib families and on groups of individuals from the same families were correlated (r = 0.66, P = 0.03), suggesting that the feed efficiency measured on individually reared fish captures a trait expressed in social groups as well.
Binding Affinities of Hepatic Nuclear Estrogen Receptors for Genistein in Channel Catfish
Authors: Kelly Anita M , Green Christopher C
Published: March 2006

Soybean meal, the major protein source used in commercial feeds for channel catfish Ictalurus punctatus, contains natural phytoestrogens known as isoflavones, many of which have been found to be endocrine disruptors. This study investigated whether genistein (an isoflavone) in a soybean-based diet would increase plasma vitellogenin (Vtg) concentrations and whether it would compete with estradiol (E2) for binding sites on adult channel catfish hepatic estrogen receptors (ERs). Three-year-old channel catfish males and females were fed a casein-based diet (control) or a soybean-based diet. The genistein concentrations were 93.2 ng/g and 415,800 ng/g in the control and soybean diets, respectively. The binding specificity of the ERs was assessed by binding-affinity studies. In order of decreasing binding affinity, ethinylestradiol > E2 > genistein > testosterone, demonstrating that the hepatic ERs in channel catfish bind estrogens and genistein more than androgens. No significant differences in affinity (Kd) were observed for hepatic ERs in male or female catfish fed the soybean diet compared with those fed the control diet. Significant increases in binding capacity (B  max) for males fed the soybean diet (158 ± 15 fmol/mg protein) were evident compared with males fed the control diet (73 ± 4 fmol/mg protein). Genistein competed with [3H]E2 for hepatic ERs in both the male and female channel catfish. The relative binding affinities in male ERs were higher (2.72) than those in female ERs (1.17) for genistein. Because diets of farm-raised channel catfish are routinely composed of high quantities of soybean meal, the findings that genistein stimulates Vtg production in male channel catfish and binds to the ERs in both male and female channel catfish suggest that dietary genistein could alter production traits. However, further research to elucidate the effects of genistein on catfish reproduction is necessary to determine the impact of this phytoestrogen on catfish physiology.
A Three-Dimensional Computational Fluid Dynamics (CFD) Model Analysis of Free Surface Hydrodynamics and Fish Passage Energetics in a Vertical-Slot Fishway
Authors: Khan Liaqat A.
Published: March 2006

A three-dimensional (3-D), computational fluid dynamics model of a vertical-slot fishway was used to characterize fishway hydrodynamics. The computational grid of a seven-pool fishway, consisting of about half a million hexahedral and prism cells, simulates the spatial variations of water surface and velocity in the model domain. Model results indicate a strong 3-D velocity field in the fishway, with eddies, flow separations, vortices, upwellings, and downwellings. Velocities and drag forces encountered by upstream migrating fish and energy expenditures in ascending the fishway are determined from the fishway hydrodynamics. The computed results are consistent with published information. Based on burst swimming speeds, the species of salmon Oncorhynchus spp. capable of migrating through the fishway were identified. Because the upriver spawning migration of adult salmon is energetically expensive, a quantification of energy expenditure in the fishways could be utilized for optimizing the design, operation, and management of fishways. Though this paper presents a model of a vertical-slot fishway, the modeling approach is applicable to other types of fishways.
Electrical Conductivity as Applied to Electrofishing
Authors: Kolz A. Lawrence
Published: March 2006

The electrical power transferred from water to fish when electrofishing is related to the ratio between the electrical conductivity of the water and that of the fish. Measuring the conductivity of water is easily accomplished with a standard conductivity meter, but determining it for fish has been difficult. No other industry standard or biological methodology apparently requires knowledge of the electrical conductivity of an object or fish freely suspended in an electrified volume of water. Therefore, the technology associated with electrofishing is confronted with the dilemma of explaining the seemingly incompatible differences between the static, electrical conductivities measured for immobilized fish and the dynamic, effective conductivities observed with live fish. To resolve this conflict, a new parameter, immersion conductivity, is introduced, accompanied by a proposed technique to measure this parameter for fish or other conductive materials in electrified volumes of water. Electrical principles based on the maximum power theorem are applied to develop relationships between the size of the distorted electrical field surrounding an immersed material and the resultant values of immersion conductivity. The immersion conductivity for fish is demonstrated to be a function of the cross‐sectional area of the water volume relative to that of the fish contained therein; it is not a fixed value. Initially, inwater voltage gradient measurements are recorded for a rubber cylinder of known electrical conductivity to demonstrate the feasibility of the test protocol and produce appropriate power graphs. Immersion conductivity values of 72–204 μS/cm were then measured for sacrificed fish, and this range correlates with effective conductivity values previously reported for live fish. The protocol associated with the measurement of immersion conductivity determines the optimal water conductivity for maximum power transfer, thereby creating research opportunities for comparing the in vivo thresholds of electroshock response among different species of fish or different‐sized fish of the same species.
Evaluation of Alveolar Bone Support of the Permanent Canine in Cleft and Noncleft Patients
Authors: Boyarskiy Simon , Choi Hyung Jun , Park Kitae
Published: March 2006

Objective:

To quantitatively compare the alveolar bone support ratio of the permanent canine in cleft patients who received secondary alveolar bone graft with that of the population without clefts.

Design:

Retrospective study utilizing periapical radiographs of the subjects with and without clefts.

Setting:

Hospital and university based.

Patients:

Eighteen unilateral and 9 bilateral cleft patients who had secondary bone graft procedures.

Main Outcome Measures:

Alveolar bone support of the permanent canine utilizing the ratio of bone height to root length.

Results:

Average bone support for the permanent canine was 88.55% in patients with clefts and 95.59% in patients with no history of clefts. This difference was statistically significant. There was no statistically significant difference in alveolar bone support ratio between the unilateral and bilateral cleft patients.

Conclusions:

Although alveolar bone support was significantly higher in the noncleft control group, a successful level of alveolar bone support was achieved for the permanent canine on the cleft site after secondary bone graft. There was no difference in alveolar bone support achieved for the permanent canine whether the type of the cleft was unilateral or bilateral.