bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic and Structural Characterization of Formazanyl Copper Complexes
Authors: Kawamura Yoshiko , Yamauchi Jun , Ohya-Nishiguchi Hiroaki
Published: August 2006

1-(o-Substituted phenyl)-3,5-diphenyl-5-formazans form various kinds of complexes. The copper(II) complexes of 1,3,5-triphenyl-5-formazan and 1-(p-Cl and o-CH3)-3,5-diphenyl-5-formazans (Group I) showed about 0.012 cm−1 of the parallel component of the copper(II) ESR splitting constant; those of the copper(II) complexes of 1-(o-Cl and o-Br)phenyl-3,5-diphenyl-5-formazans (Group II) were 0.018 cm−1. The f-values in the near-infrared region of the former complexes were almost 10-times larger than those of the latter complexes. The difference was attributed to a tetrahedral distortion of about 65—70 degrees from the planar structure in Group I; the complexes of Group II, however, were almost planar. The complexes of 1-(o-OH and o-COOH)phenyl-3,5-diphenyl-5-formazans (Group III) showed exchange interactions between two copper(II) ions with exchange energies of −375 and +33.5 cm−1 for the former and the latter complexes of Group III, respectively. Referring to the exchange and dipolar interactions, the Cu–Cu distances and the Cu–O–Cu bridging angles are discussed.
Theoretical Studies of the Reactions of Hydrogen Sulfide and Methanethiol with the H, F, and O(3P) Atoms. Possibilities of the Bimolecular Homolytic Substitution (SH2) Reactions
Authors: Takane Shin-ya , Fueno Takayuki
Published: August 2006

Potential energy profiles of the radical substitution reactions of H2S with some atomic radicals X (X = H, O, F) and of CH3SH with the hydrogen atom have been investigated by ab initio molecular orbital calculations employing the 6-31G** basis sets. All the reactions studied have proved to be elementary reactions with no intermediate adducts involved. At the MRD-CI level using the 6-31G** plus the Rydberg s and p orbitals on sulfur, the activation energies of the homolytic substitution reactions H2S + X → H + HSX are calculated to be 50, 127, and 104 kJ mol−1 for X = H, O, and F, respectively, which are uniformly higher than those calculated for the hydrogen abstraction reactions H2S + X → SH + XH. For the substitution reaction CH3SH + H → CH3 + H2S, however, the activation energy calculated is as low as 19 kJ mol−1, which is even slightly lower than that for the abstraction CH3SH + H → CH3S + H2. The predicted prevalence of the homolytic substitution reaction of CH3SH over the hydrogen abstraction is qualitatively in harmony with observations.
Complexation Behavior of Heterocyclic Hydrazones. I. Structure and Acid-Base Equilibria for Heterocyclic Hydrazones
Authors: Taya Toshiki , Sakamoto Tsukasa , Doi Kunio , Otomo Makoto
Published: August 2006

The acid-base equilibria of twenty-one hydrazones substituted by phenyl, pyridyl and/or quinolyl groups have been investigated in aqueous solutions over the region of H− to H0 acidity function by a spectrophotometric method at 25 °C. For 2-pyridinecarbaldehyde 2-(5-substituted)pyridylhydrazones, although the proton dissociation of the neutral species (HL) satisfied a Hammett correlation, those of H2L+ and H3L2+ did not. The thermodynamic parameters for the proton dissociations of H2L+ and H3L2+ of seven representative liqands were determined by a temperature-coefficient method at 25 °C and an ionic strength of 0.1 (KCl). The enthalpy and entropy changes for the proton dissociations of H3L2+ and H2L+ were influenced by the steric effects of the methyl group and/or the introduced quinolyl ring. An analysis of the pH dependence of the 1H NMR signals for three hydrazones in an acetone-d6–D2O solution gave more profitable information concerning the fine structures of HL, H2L+, and H3L2+. Each 1H and 13C NMR chemical shift of some ring-substituted methyl derivatives (HL form) in a dioxane–D2O solution has been briefly assigned. On the other hand, a single-crystal X-ray analysis, 1H NMR data in chloroform-d and thermodynamic data for di-2-pyridyl ketone 2-pyridylhydrazone (DPPH) suggested that the intramolecular hydrogen bond in the DPPH molecule is broken by the addition of a proton to the H2L+ species in an aqueous solution.
Mechanism of Silica Gel Dissolution in Water in the Presence of Pyrocatechol
Authors: Mizutani Tadashi , Takahashi Koji , Kato Tsutomu , Yamamoto Jiro , Ueda Nasuo , Nakashima Ruka
Published: August 2006

The rates of dissolution of silica gel in aqueous alkaline solutions containing pyrocatechol were measured. At pH 10, all of the silica gel was dissolved in the presence of pyrocatechol at 25 °C for 48 h (SiO2 0.3 g and pyrocatechol 0.04 mol in 15 ml of water). The rates of silica-gel dissolution increased with increasing pyrocatechol concentration. Four moles of pyrocatechol were needed to dissolve one mole of SiO2. The rate of dissolution was first order in solid SiO2 concentration. Langmuir-type adsorption of pyrocatechol to the silica-gel surface was assumed to explain the rate dependence on the pyrocatechol concentration.
Preparation and Crystal Structure of Aqua(ethanol)tetrakis(μ-salicylato-O,O′)dicopper(II)–Ethanol–Water (1/1/1)
Authors: Yoneda Kimio , Uchiyama Khoichi , Boettcher Barry , Inouye Yoshinobu
Published: August 2006

A new dinuclear copper(II) salicylate, [Cu2(C7H5O2)4]·2C2H5OH·2H2O, was prepared from copper(II) hydroxide and excess salicyclic acid in 80% ethanol. The structure was clarified by a single crystal X-ray analysis.
Synthesis of 5,15-Diaryl-Substituted Oxochlorins from 5,15-Diaryloctaethylporphyrin
Authors: Osuka Atsuhiro , Marumo Shinji , Maruyama Kazuhiro
Published: August 2006

5,15-Diaryl-substituted oxochlorins were prepared from osmium tetraoxide oxidation of 5,15-diaryloctaethylporphyrin followed by acid-catalyzed pinacol rearrangement. Optical and electrochemical properties of this macrocyclic ring are studied by measuring the absorption and fluorescence spectra, fluorescence lifetimes, and one-electron oxidation and reduction potentials.
Facile Alkoxyl Exchange of 2-Methoxybenzoates via Nucleophilic Aromatic Substitution with Sodium Alkoxides in Dimethylformamide
Authors: Hattori Tetsutaro , Satoh Seiichi , Miyano Sotaro
Published: August 2006

Methyl 2-methoxybenzoate undergoes facile nuclear-methoxyl displacement by treatment with sodium butoxide or isopropoxide in dimethylformamide.
Extraordinary rates of transition metal ion-mediated ribozyme catalysis
Authors: Roychowdhury-Saha Manami , Burke Donald H.
Published: August 2006

In pre-steady-state, fast-quench kinetic analysis, the tertiary-stabilized hammerhead ribozyme “RzB” cleaves its substrate RNA with maximal measured kobs values of ∼3000 min−1 in 1 mM Mn2+ and ∼780 min−1 in 1 mM Mg2+ at 37°C (pH 7.4). Apparent pKa for the catalytic general base is ∼7.8–8.5, independent of the corresponding metal hydrate pKa, suggesting potential involvement of a nucleobase as general base as suggested previously from nucleobase substitution studies. The pH-rate profile is bell-shaped for Cd2+, for which the general catalytic acid has a pKa of 7.3 ± 0.1. Simulations of the pH-rate relation suggest a pKa for the general catalytic acid to be ∼9.5 in Mn2+ and >9.5 in Mg2+. The acid pKa's follow the trend in the pKa of the hydrated metal ions but are displaced by ∼1–2 pH units in the presence of Cd2+ and Mn2+. One possible explanation for this trend is direct metal ion coordination with a nucleobase, which then acts as general acid.
Increased Adverse Drug Reactions to Antimicrobials and Anticonvulsants in Patients with HIV Infection
Authors: Lin Daren , Tucker M Jane , Rieder Michael J
Published: August 2006

Objective:

To review the incidence, signs, symptoms, and mechanisms of adverse drug reactions (ADRs) to sulfonamides, anticonvulsants, and antimycobacterial medications among people with HIV.

Data Sources:

Searches of MEDLINE/PubMed (1980–November 2005) and National Library of Medicine Meeting Abstracts (1989–November 2005), as well as hand searches of journals and abstracts, were conducted to identify primary literature. Reference lists were reviewed to identify additional relevant reports.

Study Selection and Data Extraction:

Relevant articles and abstracts, particularly of in vitro experiments and clinical studies, were compiled and reviewed.

Data Synthesis:

ADRs, especially in HIV-infected patients, are a cause for concern. Sulfonamides, anticonvulsants, and antimycobacterial drugs are commonly used to prevent and treat complications of HIV, including seizures and opportunistic infections. Patients with HIV have a much greater rate of ADRs to these drug classes, including severe and life-threatening hypersensitivity reactions. Several mechanisms of these ADRs have been postulated. Sulfamethoxazole and anticonvulsant hypersensitivity may involve the increased formation and decreased detoxification of reactive metabolites. The mechanisms for the marked increase in hypersensitivity ADRs to antimycobacterial drugs may be related to an altered immune profile in patients infected with both tuberculosis and HIV.

Conclusions:

ADRs to antimicrobial and anticonvulsant therapy cause markedly increased morbidity and mortality in HIV-positive patients. Further research involving the interaction between HIV and the increased ADRs to these drugs is required.
Choosing the Appropriate Antithrombotic Agent for the Prevention and Treatment of VTE: A Case-Based Approach
Authors: Nutescu Edith A , Wittkowsky Ann K , Dobesh Paul P , Hawkins David W , Dager William E
Published: August 2006

Objective:

To review the risk of venous thromboembolism (VTE) in various patient populations and evaluate the agents available for the prevention and treatment of VTE using a case-based approach.

Data Sources:

A MEDLINE search (1995–July 2006) was conducted to identify relevant literature. Additional references were reviewed from selected articles.

Study Selection and Data Extraction:

Articles related to the prevention of VTE in orthopedic surgery, general surgery, and medically ill patients, as well as the treatment of VTE, were reviewed.

Data Synthesis:

Pharmacologic options for the prevention and treatment of VTE include warfarin, unfractionated heparin (UFH), low-molecular-weight heparins (LMWH), and fondaparinux. Current guidelines support the use of warfarin, LMWH, or fondaparinux for VTE prophylaxis following lower limb major orthopedic surgery. For VTE prophylaxis in hospitalized medical patients or patients undergoing general surgery, use of UFH and LMWH is supported; however, recent data on fondaparinux suggest that it is also effective in these patient populations. The use of UFH or LMWH (both in conjunction with warfarin) for treatment of acute deep venous thrombosis or nonmassive pulmonary embolism is recommended. Recent data suggest that fondaparinux (in conjunction with warfarin) is also effective for the treatment of VTE. A variety of pharmacokinetic, pharmacodynamic, and pharmacoeconomic factors differentiate each agent for the various indications.

Conclusions:

Currently, a “one-size-fits-all” anticoagulant is not available for treatment of VTE. A variety of patient factors, including type of surgery, medical indication, thrombotic risk factors, bleeding risk, history of heparin-induced thrombocytopenia, and a variety of comorbid conditions can affect the safety, efficacy, and selection of appropriate VTE therapy.
An Update on Evidence of Clinical Pharmacy Services’ Impact on Health-Related Quality of Life
Authors: Pickard A Simon , Hung Shih-Ying
Published: August 2006

Objective:

To describe and critique recent studies of clinical pharmacy services that have evaluated impact on health-related quality of life (HRQL) and to determine whether studies that lacked a control group were more likely to report a statistically significant impact on HRQL.

Data Sources:

MEDLINE, EMBASE and International Pharmaceutical Abstracts were searched (March 1999–December 2004) using terms for HRQL and clinical pharmacy services.

Study Selection and Data Extraction:

All original research articles in English identified from the data sources were examined. Abstracts were screened by 2 reviewers, and studies were included if a clinical pharmacy service was evaluated and pre-/post-HRQL outcomes were reported.

Data Synthesis:

Of 1152 citations identified by the literature search, 36 articles met the inclusion criteria. Twenty-two studies had a condition-specific focus. Fifteen studies incorporated a generic HRQL measure (primarily the short-form-36 items), 13 studies used a condition-specific measure, and 8 studies included both. Significant impact on one or more domains of HRQL was predominantly demonstrated in interventions relating to asthma, hypertension, and chronic heart failure. Statistically significant change in HRQL was reported in 8 of 21 studies that used a randomized controlled design (38%), in 2 of 5 studies with a nonrandomized design with control group (40%), and in 6 of 8 studies without a control group (75%; χ2 2.00; p = 0.16).

Conclusions:

Since 1999, the number of published studies of clinical pharmacy services that evaluated HRQL as an endpoint has more than tripled. Study designs have improved in terms of longer length of follow-up, and a wider breadth of clinical services has been evaluated. Certain pharmacy services, such as asthma management, appear to offer the most convincing evidence for the value of clinical pharmacy services in terms of measurable short-term HRQL benefit.
Poly-L-lactic Acid for Facial Lipoatrophy in HIV
Authors: El-Beyrouty Claudine , Huang Vanthida , Darnold Courtney J , Clay Patrick G
Published: August 2006

Objective:

To review the clinical data for poly-L-lactic acid, a synthetic polymer used as an intradermal injection for the treatment of HIV associated facial fat loss (lipoatrophy).

Data Sources:

A literature search was performed using MEDLINE (1966–August 2006). The search was limited to articles published in English and used the key words polylactic acid, polylactides, degradation, lipodystrophy, lipoatrophy, and HIV/AIDS. Dermik Laboratories was contacted to obtain unpublished information. Additional articles were retrieved from citations of selected references.

Study Selection and Data Extraction:

Relevant information on the pharmacology, pharmacokinetics, safety, and efficacy of poly-L-lactic acid from clinical trials were selected.

Data Synthesis:

Poly-L-lactic acid (Sculptra) is a biocompatible, biodegradable, synthetic polymer able to be tailored into various desired morphologic features. It is approved by the Food and Drug Administration for the correction of facial lipoatrophy in people with HIV. Six clinical trials have evaluated the use of intradermal injections of poly-L-lactic acid. Results showed that cutaneous thickness is improved in patients receiving poly-L-lactic acid. Adverse effects included nodule and hematoma formation, as well as pain at the injection site.

Conclusions:

Poly-L-lactic acid offers a treatment alternative for patients with HIV-associated lipoatrophy. Further research is required in nonwhite populations.
Laccase-catalysed functionalisation of TMP with tyramine
Authors: Grönqvist Stina , Rantanen Kari , Alén Raimo , Mattinen Maija-Liisa , Buchert Johanna , Viikari Liisa
Published: August 2006

Modified wood fibres open new perspectives to create value-added products based on renewable raw materials. An interesting option is the targeted modification of fibre surfaces by oxidative enzymes. This two-stage functionalisation method consists of enzymatic activation of fibre surfaces followed by addition of radicalised compounds reacting preferentially by radical coupling. In this work, the activation of bleached and unbleached softwood TMPs with laccase isolated from Trametes hirsuta was studied. The formation and stability of the radicals were studied by EPR spectroscopy. The reaction of the radicals with 3-hydroxytyramine hydrochloride and the type of chemical linkages were investigated. EPR, ESCA and FTIR spectroscopy were used for analysis. Bleached TMP was radicalised more efficiently than unbleached TMP. The radicals were unstable, as 90% of them were quenched within a few hours. Their lifetime was, however, found to be adequately long for performing coupling reactions. Bonding of new compounds to pulps via radical reactions thus seems to be possible.
Influences of hot pressing temperature and surface structure on VOC emissions from OSB made of Scots pine
Authors: Makowski Mathias , Ohlmeyer Martin
Published: August 2006

Oriented strand board (OSB) made of Scots pine (Pinus sylvestris L.) releases high amounts of terpenes and aldehydes. These volatile organic compound (VOC) emissions are clearly affected by the manufacturing parameters. As a consequence of high temperatures during hot pressing, terpene emissions from OSB are reduced. Aldehyde emissions are initially lowered after pressing at a high temperature (260°C). Furthermore, emissions are influenced by the surface structure. If the surface consists of fine particles, terpene emissions are lowered and the course of aldehyde formation is altered. Nevertheless, a reduction in VOC emissions by adjustment of the parameters investigated in this work seems to be restricted to terpenes. Aldehyde emissions from all panels converge during emission testing and in the final stages no clear distinction is possible according to the pressing temperature or surface structure.
Evaluating growth strain of Eucalyptus globulus Labill. from SilviScan measurements
Authors: Yang Jun Li , Baillères Henri , Evans Robert , Downes Geoff
Published: August 2006

Longitudinal surface strain was measured or estimated using three different methods along the stems of nine trees of 10-year-old Eucalyptus globulus Labill. Wood samples were collected close to the location where the strain was measured or estimated. Microfibril angle (MFA), cellulose crystallite width (Wcryst), microdensity and Young's modulus along the grain (EL) were determined using the SilviScan-2 technology at high spatial resolution. Relationships of measured strain and estimated strain to wood properties were established. The quality of the relationships depends on a particular wood property. Strain was more closely related to mean Wcryst than to any other wood properties. Its relationship with MFA was the next closest. Based on the results of regression analysis, we propose that Wcryst may be suitable for the prediction of surface strain at a moderate level of reliability. Adding measurement of MFA, microdensity and EL does not significantly improve the prediction quality. The strain measurement method also affects the results. The best relationships were obtained with longitudinal displacement measured by the CIRAD method. Strain measured by the strain gauge method gave weak relationships, possibly owing to variation in the cambium age of the specimens.
Dynamic Regulation of Synaptic GABA Release by the Glutamate-Glutamine Cycle in Hippocampal Area CA1
Authors: Liang Shu-Ling , Carlson Gregory C. , Coulter Douglas A.
Published: August 2006

Vesicular GABA and intraterminal glutamate concentrations are in equilibrium, suggesting inhibitory efficacy may depend on glutamate availability. Two main intraterminal glutamate sources are uptake by neuronal glutamate transporters and glutamine synthesized through the astrocytic glutamate-glutamine cycle. We examined the involvement of the glutamate-glutamine cycle in modulating GABAergic synaptic efficacy. In the absence of neuronal activity, disruption of the glutamate-glutamine cycle by blockade of neuronal glutamine transport with α-(methylamino) isobutyric acid (MeAIB; 5 mm) or inhibition of glutamine synthesis in astrocytes with methionine sulfoximine (MSO; 1.5 mm) had no effect on miniature IPSCs recorded in hippocampal area CA1 pyramidal neurons. However, after a period of moderate synaptic activity, application of MeAIB, MSO, or dihydrokainate (250 μm;an astrocytic glutamate transporter inhibitor) significantly reduced evoked IPSC (eIPSC) amplitudes. The MSO effect could be reversed by exogenous application of glutamine (5 mm), whereas glutamine could not rescue the eIPSC decreases induced by the neuronal glutamine transporter inhibitor MeAIB. The activity-dependent reduction in eIPSCs by glutamate-glutamine cycle blockers was accompanied by an enhanced blocking effect of the low-affinity GABAAreceptor antagonist, TPMPA [1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid], consistent with diminished GABA release. We further corroborated this hypothesis by examining MeAIB effects on minimal stimulation-evoked quantal IPSCs (meIPSCs). We found that, in MeAIB-containing medium, moderate stimulation induced depression in potency of meIPSCs but no change in release probability, consistent with reduced vesicular GABA content. We conclude that the glutamate-glutamine cycle is a major contributor to synaptic GABA release under physiological conditions, which dynamically regulates inhibitory synaptic strength.
Active and Passive Membrane Properties and Intrinsic Kinetics Shape Synaptic Inhibition in Hippocampal CA1 Pyramidal Neurons
Authors: Hardie Jason B. , Pearce Robert A.
Published: August 2006

The impact of synaptic inhibition depends on the passive and active properties of the neuronal membrane as well as on the characteristics of the underlying synaptic conductances. Here, we evaluated the contributions of these different factors to the IPSPs produced by two kinetically and anatomically distinct inhibitory synapses onto hippocampal CA1 pyramidal neurons: somatic GABAA,fastand dendritic GABAA,slow. Using combined current-clamp and voltage-clamp recordings from neurons in hippocampal brain slices, we found that despite pronounced differences in kinetics and only weak voltage dependence of the underlying synaptic conductances, there were much smaller differences in duration but strong voltage dependence of IPSPs arising from somatic and dendritic synapses. Pharmacologic tests and compartmental modeling showed that these effects were produced by the hyperpolarization-activated cation current,IH, which accelerated IPSP decay over a broad range of membrane potentials and reduced IPSP amplitudes at hyperpolarized potentials, and the persistent sodium current,INaP, which prolonged and amplified IPSPs at depolarized subthreshold potentials. The relative magnitudes of their influences depended on the kinetics of the underlying synaptic conductances: the effect on duration was greater for GABAA,fastand on amplitude was greater for GABAA,slow. Passive and active factors thus influence the impact of synaptic inhibition in a location- and voltage-dependent manner.
Arginase 1 Regulation of Nitric Oxide Production Is Key to Survival of Trophic Factor-Deprived Motor Neurons
Authors: Estévez Alvaro G. , Sahawneh Mary Anne , Lange Philipp S. , Bae Narae , Egea Mariela , Ratan Rajiv R.
Published: August 2006

When deprived of trophic factors, the majority of cultured motor neurons undergo nitric oxide-dependent apoptosis. However, for reasons that have remained unclear, 30–50% of the motor neurons survive for several days without trophic factors. Here we hypothesize that the resistance of this motor neuron subpopulation to trophic factor deprivation can be attributed to diminished nitric oxide production resulting from the activity of the arginine-degrading enzyme arginase. When incubated with nor-NG-hydroxy-nor-l-arginine (NOHA), the normally resistant trophic factor-deprived motor neurons showed a drop in survival rates, whereas trophic factor-treated neurons did not. NOHA-induced motor neuron death was inhibited by blocking nitric oxide synthesis and the scavenging of superoxide and peroxynitrite, suggesting that peroxynitrite mediates NOHA toxicity. When we transfected arginase 1 into motor neurons to see whether it alone could abrogate trophic factor deprivation-induced death, we found that its forced expression did indeed do so. The protection afforded by arginase 1 expression is reversed when cells are incubated with NOHA or with low concentrations of nitric oxide. These results reveal that arginase acts as a central regulator of trophic factor-deprived motor neuron survival by suppressing nitric oxide production and the consequent peroxynitrite toxicity. They also suggest that the resistance of motor neuron subpopulations to trophic factor deprivation may result from increased arginase activity.
Corticofugal Output from the Primary Somatosensory Cortex Selectively Modulates Innocuous and Noxious Inputs in the Rat Spinothalamic System
Authors: Monconduit Lénaïc , Lopez-Avila Alberto , Molat Jean-Louis , Chalus Maryse , Villanueva Luis
Published: August 2006

Sensory maps for pain can be modified by deafferentation or injury, and such plasticity has been attributed mainly to changes in the convergence of projections in “bottom-up” mechanisms. We addressed the possible contribution of “top-down” mechanisms by investigating the functional significance of corticofugal influences from the primary somatosensory cortex (S1) to the ventroposterolateral thalamic nucleus (VPL). The strong convergence of spinal and lemniscal afferents to the VPL and the close correspondence between afferents and efferents within the VPL–S1 network suggest the existence of functionally related thalamocortical circuits that are implicated in the detection of innocuous and noxious inputs. Functional characterization of single nociceptive, wide dynamic range, and non-nociceptive VPL neurons and labeling the axons and terminal fields with the juxtacellular technique showed that all three types of cells project to a restricted area, within S1. The convergence of the terminal trees of axons from VPL neurons activated by innocuous, noxious, or both inputs suggests that their inputs are not segregated into anatomically distinct regions. Microinjections within S1 were performed for pharmacological manipulation of corticofugal modulation. Glutamatergic activation of corticofugal output enhanced noxious-evoked responses and affected in a biphasic way tactile-evoked responses of VPL cells. GABAA-mediated depression of corticofugal output concomitantly depressed noxious and enhanced innocuous-evoked responses of VPL neurons. Microinjections of a GABAAantagonist on corticofugal cells enhanced noxious-evoked responses of VPL cells. Our findings demonstrate that corticofugal influences from S1 contribute to selectively modulate somatosensory submodalities at the thalamic level.
Scaffolding Protein INAD Regulates Deactivation of Vision by Promoting Phosphorylation of Transient Receptor Potential by Eye Protein Kinase C inDrosophila
Authors: Popescu Daniela C. , Ham Amy-Joan L. , Shieh Bih-Hwa
Published: August 2006

Drosophilavisual signaling is one of the fastest G-protein-coupled transduction cascades, because effector and modulatory proteins are organized into a macromolecular complex (“transducisome”). Assembly of the complex is orchestrated by inactivation no afterpotential D (INAD), which colocalizes the transient receptor potential (TRP) Ca2+channel, phospholipase Cβ, and eye protein kinase C (eye-PKC), for more efficient signal transduction. Eye-PKC is critical for deactivation of vision. Moreover, deactivation is regulated by the interaction between INAD and TRP, because abrogation of this interaction inInaDp215results in slow deactivation similar to that ofinaCp209lacking eye-PKC. To elucidate the mechanisms whereby eye-PKC modulates deactivation, here we demonstrate that eye-PKC, via tethering to INAD, phosphorylates TRPin vitro. We reveal that Ser982of TRP is phosphorylated by eye-PKCin vitroand, importantly, in the fly eye, as shown by mass spectrometry. Furthermore, transgenic expression of modified TRP bearing an Ala substitution leads to slow deactivation of the visual response similar to that ofInaDp215. These results suggest that the INAD macromolecular complex plays an essential role in termination of the light response by promoting efficient phosphorylation at Ser982of TRP for fast deactivation of the visual signaling.
Dynamics and Effective Topology Underlying Synchronization in Networks of Cortical Neurons
Authors: Eytan Danny , Marom Shimon
Published: August 2006

Cognitive processes depend on synchronization and propagation of electrical activity within and between neuronal assemblies.In vivomeasurements show that the size of individual assemblies depends on their function and varies considerably, but the timescale of assembly activation is in the range of 0.1–0.2 s and is primarily independent of assembly size. Here we use anin vitroexperimental model of cortical assemblies to characterize the process underlying the timescale of synchronization, its relationship to the effective topology of connectivity within an assembly, and its impact on propagation of activity within and between assemblies. We show that the basic mode of assembly activation, “network spike,” is a threshold-governed, synchronized population event of 0.1–0.2 s duration and follows the logistics of neuronal recruitment in an effectively scale-free connected network. Accordingly, the sequence of neuronal activation within a network spike is nonrandom and hierarchical; a small subset of neurons is consistently recruited tens of milliseconds before others. Theory predicts that scale-free topology allows for synchronization time that does not increase markedly with network size; our experiments with networks of different densities support this prediction. The activity of early-to-fire neurons reliably forecasts an upcoming network spike and provides means for expedited propagation between assemblies. We demonstrate this capacity by observing the dynamics of two artificially coupled assembliesin vitro, using neuronal activity of one as a trigger for electrical stimulation of the other.
Cytoskeleton Regulation of Glycine Receptor Number at Synapses and Diffusion in the Plasma Membrane
Authors: Charrier Cécile , Ehrensperger Marie-Virginie , Dahan Maxime , Lévi Sabine , Triller Antoine
Published: August 2006

Lateral diffusion of neurotransmitter receptors in and out of synapses has been postulated as a core mechanism for rapid changes in receptor number at synapses during plastic processes. In this study, we have used single particle tracking to investigate how changes in glycine receptor (GlyR) lateral diffusion properties might account for changes in receptor number at synapses after disruption of the cytoskeleton in dissociated spinal cord neurons. We found that pharmacological disruption of F-actin and microtubules decreased the amount of GlyR and gephyrin, the backbone of the inhibitory postsynaptic scaffold, at synapses. F-actin and microtubule disruption increased GlyR exchanges between the synaptic and extrasynaptic membranes and decreased receptor dwell time at synapses. GlyR lateral diffusion was predominantly controlled by microtubules in the extrasynaptic membrane and by actin at synapses. Both diffusion coefficients and confinement at synapses were affected after F-actin disruption. Our results indicate that receptor exchanges between the synaptic and extrasynaptic compartments depend on the properties of both the postsynaptic differentiation and the extrasynaptic membrane. Consequently, GlyR number at synapses may be rapidly modulated by the cytoskeleton through the regulation of lateral diffusion in the plasma membrane and of receptor stabilization at synapses.
Artemin Overexpression in Skin Enhances Expression of TRPV1 and TRPA1 in Cutaneous Sensory Neurons and Leads to Behavioral Sensitivity to Heat and Cold
Authors: Elitt Christopher M. , McIlwrath Sabrina L. , Lawson Jeffery J. , Malin Sacha A. , Molliver Derek C. , Cornuet Pamela K. , Koerber H. Richard , Davis Brian M. , Albers Kathryn M.
Published: August 2006

Artemin, a neuronal survival factor in the glial cell line-derived neurotrophic factor family, binds the glycosylphosphatidylinositol-anchored protein GFRα3 and the receptor tyrosine kinase Ret. Expression of the GFRα3 receptor is primarily restricted to the peripheral nervous system and is found in a subpopulation of nociceptive sensory neurons of the dorsal root ganglia (DRGs) that coexpress the Ret and TrkA receptor tyrosine kinases and the thermosensitive channel TRPV1. To determine how artemin affects sensory neuron properties, transgenic mice that overexpress artemin in skin keratinocytes (ART-OE mice) were analyzed. Expression of artemin caused a 20.5% increase in DRG neuron number and increased the level of mRNA encoding GFRα3, TrkA, TRPV1, and the putative noxious cold-detecting channel TRPA1. Nearly all GFRα3-positive neurons expressed TRPV1 immunoreactivity, and most of these neurons were also positive for TRPA1. Interestingly, acid-sensing ion channel (ASIC) 1, 2a, 2b, and 3 mRNAs were decreased in the DRG, and this reduction was strongest in females. Analysis of sensory neuron physiological properties using anex vivopreparation showed that cutaneous C-fiber nociceptors of ART-OE mice had reduced heat thresholds and increased firing rates in response to a heat ramp. No change in mechanical threshold was detected. Behavioral testing of ART-OE mice showed that they had increased sensitivity to both heat and noxious cold. These results indicate that the level of artemin in the skin modulates gene expression and response properties of afferents that project to the skin and that these changes lead to behavioral sensitivity to both hot and cold stimuli.
Stimulation of Nicotinamide Adenine Dinucleotide Biosynthetic Pathways Delays Axonal Degeneration after Axotomy
Authors: Sasaki Yo , Araki Toshiyuki , Milbrandt Jeffrey
Published: August 2006

Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.
Estradiol-Induced Increase in the Magnitude of Long-Term Potentiation Is Prevented by Blocking NR2B-Containing Receptors
Authors: Smith Caroline C. , McMahon Lori L.
Published: August 2006

Estradiol, through activation of genomic estrogen receptors, induces changes in synaptic morphology and function in hippocampus, a brain region important for memory acquisition. Specifically, this hormone increases CA1 pyramidal cell dendritic spine density, NMDA receptor (NMDAR)-mediated transmission, and the magnitude of long-term potentiation (LTP) at CA3–CA1 synapses. We recently reported that the estradiol-induced increase in LTP magnitude occurs only when there is a simultaneous increase in the fractional contribution of NMDAR-mediated transmission relative to AMPA receptor transmission, suggesting a direct role for the increase in NMDAR transmission to the heightened LTP magnitude. Estradiol has been shown to increase expression of the NMDAR subunit NR2B, but whether this translates into an increase in function of NR2B-containing receptors remains to be determined. Here we show that not only is the estradiol-induced increase in NMDAR transmission mediated by NR2B-containing receptors, but blocking these receptors using RO25-6981 [R-(R,S)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidine propranol] (0.5 μm), an NR2B selective antagonist, prevents the estradiol-induced increase in LTP magnitude. Thus, our data show a causal link between the estradiol-induced increase in transmission mediated by NR2B-containing NMDARs and the increase in LTP magnitude.
Measurement of thermal neutron cross sections of the reactions 126Sn(n, γ)127g,127mSn
Authors: Zhang Sheng-Dong , Yang Lei , Guo Jingru , Wang Fangding , Cui An-Zhi , Diao Lijun
Published: August 2006

The thermal neutron cross sections of the reactions 126Sn(n, γ)127gSn and 126Sn(n, γ)127mSn were measured for the first time. A radiochemical carrier-free separation procedure of 126Sn from high level liquid waste (HLLW) is based on the anion exchange and PbS co-precipitation. The (n, γ) reactions on 197Au and 55Mn were used as monitors of thermal neutron flux in irradiation of 126Sn samples. The radionuclides 126Sn, 127gSn, 127Sb, 198Au and 56Mn were detected by HPGe γ-ray spectrometry. The experimentally obtained thermal neutron cross sections of the 126Sn(n, γ)127mSn and 126Sn(n, γ)127gSn reactions are: 126Sn(n, γ)127gSn: σg = 0.200 ± 0.039 b 126Sn(n, γ)127mSn: σm = 0.39 ± 0.10 b The total cross section of the reaction 126Sn(n, γ)127(m+g)Sn is 0.59 ± 0.14 b.
Electrochemical behavior of uranium(VI) in 1-butyl-3-methylimidazolium chloride and in 0.05 M aliquat-336/chloroform
Authors: Giridhar P. , Venkatesan K. A. , Subramaniam S. , Srinivasan T. G. , Vasudeva Rao P. R.
Published: August 2006

Alkali metal uranyl chloride (M2UO2Cl4 (M = Na or Cs)) was dissolved in 1-butyl-3-methylimidazolium chloride (bmimCl) and the redox behavior of uranyl ion present in the resultant solution was investigated by cyclic voltammetry at 343 K. The cyclic voltammogram consisted of a reduction wave occurring at the peak potential of −0.85 V, due to the reduction of U(VI) and two oxidation waves occurring at the peak potentials of −0.6 V and +0.2 V. Controlled potential electrolysis of uranium(VI) loaded bmimCl gave a black deposit, which was characterized as uranium oxide by EDXRF and XRD analysis. Extraction of uranium(VI) from nitric acid medium by 0.05 M tri-n-octylmethylammonium chloride (TOMAC) in chloroform was studied and the cyclic voltammogram of uranyl ion present in the extracted phase exhibited a single reduction (−0.8 V) and an oxidation wave (0.06 V) at 298 K. Controlled potential electrolysis of uranium(VI) loaded TOMAC at −1.0 V also gave a black uranium oxide deposit similar to that observed in the previous case. The results indicated that uranyl ion in organic phase undergoes a single step two electron quasi-reversible reduction at the working electrode, which can be conveniently exploited for the direct recovery of uranium from the spent fuel or from high level liquid wastes.
[201Tl](III)-bleomycin for tumor imaging
Authors: Jalilian A. R. , Akhlaghi M. , Shirazi B. , Aboudzadeh R. , Raisali Gholamreza , Salouti M. , Babaii M.
Published: August 2006

Due to interesting physical properties and wide availability of thallium-201 as a SPECT radionuclide, the idea of incorporation of this nuclide into biologically active compounds was targeted. Thallium-201 (T
1/2 = 3.04 d) in Tl+ form was converted to Tl3+ cation in presence of O3 in 6 M HCl controlled by RTLC/gel electrophoresis methods. The final evaporated activity was reacted with bleomycin in normal saline to yield [201Tl]BLM at room temperature after 0.5 h (radiochemical yield > 99%) followed by HPLC analysis. The studies showed that thallic ion is mostly incorporated into bleomycin A2 while other species in the pharmaceutical sample almost remain unlabeled. Radiochemical purity of more than 99% was obtained using RTLC, HPLC with specific activity of about 7 Ci/mmol. The stability of the tracer was checked in the final product in presence of human serum at 37 °C up to 3 d. The tracer accumulated in tumors of fibrosarcoma-bearing mice after 72 h.
Hemostasis and fibrinolysis in non-diabetic overweight and obese men and women. Is there still a role for leptin?
Authors: Mertens Ilse , Considine Robert V , Van der Planken Marc , Van Gaal Luc F
Published: August 2006

Objective: Leptin has been associated with disturbances in hemostasis and fibrinolysis, with inconsistent results on the influence of fat mass. However, the influence of the amount of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) has not yet been studied. In this study, we investigated the relationship between leptin and fibrinogen, von Willebrand factor antigen (vWF:Ag), and plasminogen-activator inhibitor-1 (PAI-1) activity and determined the influence of associated metabolic variables and VAT versus SAT.

Methods: Fibrinogen, vWF:Ag, PAI-1,VAT and SAT (CT-scan), and insulin resistance (homeostasis model assessment; HOMA-IR) were measured in 199 women and 81 men with overweight or obesity visiting the weight management clinic of a university hospital.

Results: Leptin did not relate to fibrinogen (r = 0.11 and 0.13 in women and men respectively; P > 0.05), a relationship with vWF:Ag was only found in men (r = 0.31; P = 0.005), while leptin related to PAI-1 activity in both men (r = 0.36; P < 0.001) and women (r = 0.23; P < 0.001). Further analysis showed leptin to have an effect on the variation of PAI-1 independent of VAT and HOMA-IR in women, but not in men. Multiple regression showed HOMA-IR to be the most important determinant of PAI-1, both in men and women, but leptin also showed an independent effect. As for vWF:Ag, leptin was an independent determinant in men only.

Conclusions: PAI-1 related to leptin levels independent of fat mass percentage, HOMA-IR, and the amount of VAT and SAT. For vWF:Ag this relationship was found only in men, and not in women, while a relationship with fibrinogen could not be demonstrated.
Sustained endogenous glucose production, diminished lipolysis and non-esterified fatty acid appearance and oxidation in non-obese women at high risk of type 2 diabetes
Authors: Forbes Shareen , Robinson Stephen , Dungu Jason , Anyaoku Victor , Bannister Peter , Forster David , Dissanayake Sujata , McCarthy Mark I , MacDonald Ian A , Venkatesan Soundararajan , Johnston Desmond G
Published: August 2006

Objective: To evaluate early defects in glucose production, lipolysis and fatty acid oxidation in non-obese, normally glucose tolerant women, who are nevertheless at risk of type 2 diabetes.

Methods: Ten women with previous gestational diabetes (pGDM) and ten controls were studied in two 4 h infusions of stable isotopes 6,6-2H2-glucose, 1-13C-palmitate, and 1,1,2,3,3-2H5-glycerol with and without infusion of adrenaline. Fatty acid oxidation was quantified using indirect calorimetry and13CO2measurements. Insulin sensitivity was evaluated using the short insulin tolerance test.

Results: The pGDM and control women were non-obese and carefully matched for body mass index and fat mass. Whole body insulin sensitivity and basal insulin concentrations did not differ significantly but basal glucose concentrations were increased in women with pGDM. During a 0.9% saline infusion, glucose appearance was not significantly different at the first (90–120 min) and second (210–240 min) steady states. However, glucose appearance decreased in controls but was maintained in the pGDM women (−0.33 ± 0.02 vs −0.03 ± 0.08 mg/kg per min;P= 0.004). Basal glycerol appearance (0.27 ± 0.02 vs 0.38 ± 0.03 mg/kg per min;P= 0.02), palmitate appearance (0.74 ± 0.09 vs 1.05 ± 0.09 mg/kg per min;P= 0.03) and palmitate oxidation (0.07 ± 0.01 vs 0.10 ± 0.01 mg/kg per min;P= 0.03) were lower in the pGDM women. During the adrenaline infusion, changes in glucose, glycerol and palmitate concentrations and kinetics were similar in both groups.

Conclusions: Sustained glucose production during fasting is an early abnormality in non-obese subjects at risk of type 2 diabetes. Lipolysis and non-esterified fatty acid appearance and oxidation are diminished, suggesting an increased tendency to store fat. The observations are not readily attributable to differences in insulin or catecholamine sensitivity.
The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study
Authors: Mohr Beth A , Bhasin Shalender , Link Carol L , O’Donnell Amy B , McKinlay John B
Published: August 2006

Objective: Changes in adiposity affecting total testosterone (TT) and free testosterone (FT) levels have not been examined in a population-based survey. We aimed to determine whether changes in adiposity predict follow-up levels and rates of change in TT, FT and sex hormone-binding globulin (SHBG) in men.

Design: The Massachusetts Male Aging Study is a randomly sampled, population-based cohort interviewed at baseline (T1, 1987–1989; n = 1709; aged 40–70 years) and followed-up approximately 9 years later (T2, 1995–1997; n = 1156). Men were categorized as overweight (body mass index (BMI) ≥ 25 kg/m2) or having obesity (BMI ≥ 30 kg/m2), waist obesity (waist circumference ≥ 102 cm), or waist-to-hip ratio (WHR) obesity (WHR>0.95). For each adiposity group, we constructed four categories to represent changes between T1 and T2: overweight (or obese, etc.) at neither wave, T1 only, T2 only, or both waves.

Results: After adjustment for confounding variables, men who were overweight at T2 only, or at both waves, had significantly lower mean T2 TT and SHBG levels than men in the neither group (P<0.05). Mean FT did not differ between any overweight group and the neither group. Men who were obese at both times, had the highest mean BMI, the highest fraction of severely obese men, and significantly greater rate of decline in FT than the neither group.

Conclusions: In men who become overweight, the greater rate of decline in TT, but not FT, is related mostly to a lesser age-related increase in SHBG. Since weight gain is highly prevalent in older men, over-reliance on TT levels in the diagnosis of androgen deficiency could result in substantial misclassification.
Distribution of Toxocara infection in the environment and in definitive and paratenic hosts in Estonia
Authors: Talvik Heli , Moks Epp , Mägi Erika , Järvis T. , Miller Illa
Published: August 2006

The aim of the study was to elucidate the distribution and possible transmission routes of Toxocara spp. infection in Estonia. Out of 454 faecal and sand samples collected from park lawns and sandpits in the town of Tartu, 19 were Toxocara positive (4.2%). Out of the 45 sandpit samples 17.8% were Toxocara positive. Cat faeces was found in 21 sandpit samples. Parasitological necropsies were performed on 41 euthanised stray dogs and 27 cats in the Tallinn Dog Home. Additionally, 13 wild free-roaming brown rats (Rattus norvegicus) were captured from the Tallinn Dog Home territory, necropsied and studied for the presence of Toxocara larvae. Toxocara canis adults were found in 14.6% of the dogs and Toxocara cati (syn. mystax) adults in the small intestines of 48.2% of the cats examined. Larval infection was detected in the kidney and liver in 5 dogs (12.2%). Our study demonstrated only low-level larval Toxocara infections in adult dogs. Toxocara larvae were not found in cats and brown rats. According to the results of this study, cats more often carry Toxocara infection than dogs. Under our conditions, stray and free-roaming cats are the main contaminators of the environment with Toxocara eggs. Children playing in sandpits are the main risk group for larval toxocarosis.