bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen‐bonding and Proton Transfer Interactions between Harmane and Trifluoroethanol in the Ground and Excited Singlet States
Authors: Balón Manuel , Carmona Carmen , Guardado Pilar , Muñoz Maria A.
Published: January 2008

A study of the hydrogen‐bonding and proton transfer reactions of the ground and excited states of harmane (1‐methyl‐9H‐pyrido/3,4‐b/indole) and its N9‐methyl derivative with 2,2,2‐trifluoroethanol in cyclohexane is reported. Spectral measurements (UV–visible, Fourier trans‐form IR, steady‐state and time‐resolved fluorescence) show the formation of fluorescent ground‐state hydrogen‐bonded complexes. The results have been interpreted assuming a tautomeric equilibrium between a 1:1 hydrogen‐bonded complex and its 1:2 proton transfer tautomer (hydrogen‐bonding ion pair). Upon excitation to its singlet excited state, the proton transfer tautomer of harmane reacts with an additional 2,2,2‐trifluoroethanol molecule to give a zwitterionic exciplex, which fluoresces at longer wavelength.
Molecular Mechanisms of Photoaging in Human Skin In Vivo and Their Prevention by All‐Trans Retinoic Acid
Authors: Fisher Gary J. , Talwar Harvinder S. , Lin Jiayuh , Voorhees John J.
Published: January 2008

Abstract— Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (MMP) that degrade skin collagen. We find that pretreatment of human skin with all‐trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV‐induced collagen destruction and may therefore be able to lessen the effects of photoaging. The tRA prevents UV‐induced accumulation of c‐Jun protein, which is required for MMP gene expression. Activation of c‐Jun transcriptional activity requires N‐terminal phosphorylation. The majority of c‐Jun in human skin in vivo is Nterminal phosphorylated. Topically applied tRA does not inhibit N‐terminal phosphorylation by UV‐induced c‐Jun kinase activity in human skin. The tRA likely acts to reduce UV induction of c‐Jun protein by stimulating its breakdown through the ubiquitin‐proteasome pathway.
Inhibition of Peroxyoxalate Chemiluminescence by Intercalation of Fluorescent Acceptors between DMA Bases
Authors: Alba F. Javier , Daban Joan‐Ramon
Published: January 2008

Abstract— We have examined the ability of different fluorescent DNA dyes to become chemically excited by the peroxyoxalate chemiluminescent reaction. The intercalating dyes ethidium bromide and propidium iodide, and the bis‐intercalating dyes ethidium homodimer‐1, benzoxazolium‐4‐pyridinium dimer‐1 and benzoxazolium‐4‐quinolinium dimer‐1, exhibit an intense Chemiluminescence when they are excited by the bis(2,4,6‐trichlorophenyl)oxalate (TCPO)‐H2O2 reaction in the absence of DNA. However, the Chemiluminescence of these dyes is very low when they are bound to double‐stranded DNA (dsDNA). In contrast, the minor groove‐binding dye Hoechst 33258 excited by the TCPO‐H2O2 reaction shows approximately the same Chemiluminescence intensity when it is free in solution or complexed with dsDNA. Structural alterations or partial dissociation of dsDNA‐bis‐intercalating dye complexes produced by the addition of acetone, NaCl, MgCl2 or the cationic surfactant cetyltrimethylammonium bromide increases the Chemiluminescence intensity. A moderate Chemiluminescence intensity is observed when bis‐intercalating dyes are complexed with single‐stranded DNA. Our results indicate that the energy from the intermediates produced in the peroxyoxalate chemiluminescent reaction cannot be efficiently transferred to fluorescent dyes complexed with DNA; chemiexcitation is almost completely inhibited when dyes are buried in the dsDNA structure by intercalation between the base pairs.
Fluorescence Spectral Properties of the Anticancer Drug Topotecan by Steady‐State and Frequency Domain Fluorometry with One‐Photon and Multi‐Photon Excitation
Authors: Gryczynski Ignacy , Gryczynski Zygmunt , Lakowicz Joseph R. , Yang Danzhou , Burke Thomas G.
Published: January 2008

Abstract— Topotecan is an antitumor agent with activity against a variety of cancers. We examined the steady‐state and time‐resolved fluorescence spectral properties of topote‐can with one‐and two‐photon excitation. Topotecan was found to display a high two‐photon cross section near 20 GM for wavelengths within the fundamental output of a Ti: sapphire laser, 800–880 nm. In frozen solution the anisotropies of topotecan are near the theoretical maxima for one‐photon and two‐photon excitation with colinear electronic transitions. The intensity and anisotropy decays of topotecan fluorescence were found to be homogeneous (single exponentials) in phosphate‐buffered saline and propylene glycol. The steady‐state and time‐resolved data indicate that topotecan binds to a double‐helical DNA oligomer d(AT)10 resulting in increased anisotropies and multiexponential intensity and anisotropy decays. Subnanosecond components in the anisotropy decay of the DNA‐topotecan complex suggest loose binding of the drug to DNA. Loose binding of topotecan to DNA is also revealed by accessibility of topotecan to collisional quenching by iodide.
Photophysics of Hypericin and Hypocrellin A in Complex with Subcellular Components: Interactions with Human Serum Albumin
Authors: Das Kaustuv , Smirnov Alexandra V. , Wen Jin , Miskovsky Pavol , Petrich Jacob W.
Published: January 2008

Abstract— Time‐resolved fluorescence and absorption measurements are performed on hypericin complexed with human serum albumin, HSA (1:4, 1:1 and ∼5:1 hypericin: HSA complexes). Detailed comparisons with hypocrellin A/HSA complexes (1:4 and 1:1) are made. Our results are consistent with the conclusions of previous studies indicating that hypericin binds to HSA by means of a specific hydrogen‐bonded interaction between its carbon‐yl oxygen and the N1‐H of the tryptophan residue in the HA subdomain of HSA. (They also indicate that some hypericin binds nonspecifically to the surface of the protein.) A single‐exponential rotational diffusion time of 31 ns is measured for hypericin bound to HSA, indicating that it is very rigidly held. Energy transfer from the tryptophan residue of HSA to hypericin is very efficient and is characterized by a critical distance of 94 Å, from which we estimate a time constant for energy transfer of ∼3 × 10–15 s. Although it is tightly bound to HSA, hypericin is still capable of executing excited‐state intramolecular proton (or hydrogen atom) transfer in the ∼5:1 complex, albeit to a lesser extent than when it is free in solution. It appears that the proton transfer process is completely impeded in the 1:1 complex. The implications of these results for hypericin (and hypocrellin A) are discussed in terms of the mechanism of intramolecular excited‐state proton transfer, the mode of binding to HSA and the light‐induced antiviral and antitumor activity.
Ultraviolet‐B‐Induced Damage to Escherichia coli Fpg Protein
Authors: Sidorkina O. M. , Kuznetsov S. V. , Blais J. C. , Bazin M. , Laval J. , Santus R.
Published: January 2008

Abstract— We investigated the effect of UVB light (290 ≤δ≤ 320 nm) on the structure and enzymatic activities of Escherichia coli Fpg protein (2,6‐diamino‐4‐hydroxy‐5N‐methylformamidopyrimidine‐DNA glycosylase), a DNA repair enzyme containing a zinc finger motif and five chromophoric Trp residues. Irradiation with UVB light of air‐saturated pH 7.4 buffered aqueous solutions of Fpg induces the formation of polymers as shown by sodium dodecyl sulfate polyaerylamide gel electrophoretic analysis. In argon‐saturated solutions, polymer formation produces a precipitate. The polymerization quantum yield is 0.07 ± 0.01 and 0.15 ± 0.02 in air‐and argon‐saturated solutions, respectively. In the polymerized Fpg protein, second‐derivative absorption spectroscopy indicates that three and one Trp residues are destroyed in air‐and argon‐saturated solutions, respectively. Polymers are devoid of all three activities of the Fpg protein, whereas the unpolymerized protein retains full activities. Matrix‐assisted laser desorption/ionization experiments demonstrate that polymer formation is accompanied by the formation of short polypeptides containing the first 32 or 33 residues of the N‐terminal domain. Theses polypeptides are most probably formed by the photolytic cleavage of Fpg protein induced by light absorption by the adjacent Trp‐34 residue.
Alterations of Hairless Mouse Skin Exposed to Chronic UV Irradiation and Its Prevention by Hydrocortisone
Authors: Mitani Hiroaki , Koshiishi Ichiro , Toyoda Hidenao , Toida Toshihiko , Imanari Toshio
Published: January 2008

Abstract— Ultraviolet‐induced alterations of skin were investigated in a murine animal model. Groups of hairless mice were exposed to UV (black light, Λmax 352 nm; UV distribution: 300–310 nm, 0.9%; 310–320 nm, 2.0%; 320–420 nm, 97.1%) for 20 weeks at a dose of 16.3 J/cm2 five times weekly on weekdays. At the end of 20 weeks irradiation, the dorsal skins were biochemically and histologically examined. Ultraviolet caused remarkable increases in amounts of hyaluronan, chondroitin sulfates and dermatan sulfates in skin (μg/cm2). Interestingly, a significant change in a collagen content (hydroxyproline, μg/g of dry powder) caused by UV irradiation was not observed, whereas the amount of collagen (hydroxy‐proline, μg/cm2) increased remarkably. Histologically, no distinguishable thickening was observed in both upper dermis and lower dermis, but thickening of the epidermis was observed. Furthermore, the histological study indicated that UV irradiation caused a disappearance of crowds of adipocytes, alternative appearance of numerous fibroblasts and accumulation of collagen bundles and hyaluronan in lower dermis. Hydrocortisone, an anti‐inflammatory agent, prevented both the fibrosis of lower dermis and the accumulation of the extracellular matrix components. Based on these results, it seems reasonable that UV penetrates into the lower dermis and causes fibrosis there, resulting from the inflammatory responses.
Protoporphyrin IX Fluorescence Photobleaching during ALA‐Mediated Photodynamic Therapy of UVB‐Induced Tumors in Hairless Mouse Skin
Authors: Robinson Dominic J. , de Bruijn Henriëtte S. , van der Veen Nynke , Stringer Mark R. , Brown Stanley B. , Star Willem M.
Published: January 2008

Abstract— Fluorescence photobleaching of protoporphyrin IX (PpIX) during superficial photodynamic therapy (PDT), using 514 nm excitation, was studied in UVB‐induced tumor tissue in the SKH‐HR1 hairless mouse. The effects of different irradiance and light fractionation regimes upon the kinetics of photobleaching and the PDT‐induced damage were examined. Results show that the rate of PpIX photobleaching (i.e. fluorescence intensity vs fluence) and the PDT damage both increase with decreasing irradiance. We have also detected the formation of fluorescent PpIX photoproducts in the tumor during PDT, although the quantity recorded is not significantly greater than generated in normal mouse skin, using the same light regime. The subsequent photobleaching of the photoproducts also occurs at a rate (vs fluence) that increases with decreasing irradiance. In the case of light fractionation, the rate of photobleaching increases upon renewed exposure after the dark period, and there is a corresponding increase in PDT damage although this increase is smaller than that observed with decreasing irradiance. The effect of fractionation is greater in UVB‐induced tumor tissue than in normal tissue and the damage is enhanced when fractionation occurs at earlier time points. We observed a variation in the distribution of PDT damage over the irradiated area of the tumor: at high irradiance a ring of damage was observed around the periphery. The distribution of PDT damage became more homogeneous with both lower irradiance and the use of light fractionation. The therapeutic dose delivered during PDT, calculated from an analysis of the fluorescence photobleaching rate, shows a strong correlation with the damage induced in normal skin, with and without fractionation. The same correlation could be made with the data obtained from UVB‐induced tumor tissue using a single light exposure. However, there was no such correlation when fractionation schemes were employed upon the tumor tissue.
Anion‐lnduced Fluorescence Quenching of a New Zwitterionic Biacridine Derivative
Authors: Werner Tobias , Fahnrich Karsten , Huber Christian , Wolfbeis Otto S.
Published: January 2008

The effect of halides and different buffer anions on the quenching of the fluorescence of the new probe 10,10′‐bis(3‐sulfopropyl)‐9,9′‐biacridine (SPBA) has been studied using fluorescence and decay time measurements. The linearity of the Stern‐Volmer plot indicates that fluorescence quenching by halides can be described reasonably well by a single‐exponential decay with a K of 4.06 times 106M‐1s‐1for chloride, 7.83 times 106M‐1s‐1for bromide and 1.12 times 107M‐1s‐1for iodide. We have found that SPBA is collisionally quenched also by the buffers 3‐(N‐mor‐pholino)propanesulfonic acid (MOPS) and N‐2‐hydroxy‐ethylpiperazine‐N′‐ethansulfonic acid (HEPES). The bi‐molecular rate constants are 1.67 × 106M‐ls‐1for HEPES and 1.44 times 106M‐1s‐1for MOPS.
Apoptosis Induction in Nonirradiated Human HL‐60 and Murine NSO/2 Tumor Cells by Photoproducts of lndole‐3‐acetic Acid and Riboflavin
Authors: Edwards A. M. , Barredo F. , Silva E. , De Ioannes A. E. , Becker M. I.
Published: January 2008

The effect of the photoproducts of indole‐3‐acetic acid sensitized by riboflavin on nonirradiated human HL‐60 and murine NSO/2 tumor cells was studied. Severe damage with a dose‐response effect was observed on both cell types. The effect was greater than that previously described for the tryptophan riboflavin photoproducts. Electron microscopy studies and flow cytometry analysis of DNA fragmentation allowed us to conclude that the photoproducts studied in this work induce cell death by an apoptotic mechanism.
Optical Sensing of Cesium Using 1,3‐Alternate Calix[4]‐mono‐ and Di(anthrylmethyl)aza‐crown‐6
Authors: Ji Hai‐Feng , Hettich Robert L. , Brown Gilbert M. , Dabestani Reza
Published: January 2008

We have synthesized two derivatives of alkylanthracene covalently bonded to 1,3‐alternate calix[4]aza‐crown‐6 at the nitrogen position to study the effect of alkali metal ion complexation on the emission properties of anthracene fluorophore. The mono‐ and dianthryl‐substituted probes are weakly fluorescent because their emission is partially quenched by photoinduced electron transfer (PET) from the nitrogen lone pair to the excited singlet state of anthracene. Upon complexation of alkali metal ions (e.g. K+, Cs+) by the crown moiety, the nitrogen lone pair can no longer participate in the PET process causing an enhancement in the emission of anthracene fluorophore (fluorescent turn on). The maximum fluorescence enhancement observed upon complexation of cesium ions by mono‐ and dianthryl‐substituted calix[4]aza‐crown‐6 relative to the uncomplexed form was 8.5‐ and 11.6‐fold, respectively.
Oxidation of Human Catalase by Singlet Oxygen in Myeloid Leukemia Cells‡
Authors: Lledías Fernando , Hansberg Wilhelm
Published: January 2008

Catalases are oxidized by singlet oxygen giving rise to more acidic conformers detected in zymograms after electrophoresis in polyacrylamide gels. This shift in catalase mobility can be indicative of singlet oxygen production in vivo. Catalase from human cells, as from many organisms, is susceptible to in vitro modification by singlet oxygen. Human myeloid leukemia (U937) cells were treated under different stress conditions and catalase activity and its electrophoretic mobility was monitored. The U937 cells were found to have high levels of catalase activity, as compared to cultured fibroblasts, and to be very resistant to oxidative stress. Hydrogen peroxide did not modify the electrophoretic mobility of catalase, even at doses that produced cell damage. Conditions that primarily generate superoxide, such as treatment with paraquat or heat shock, also failed to modify the enzyme. In contrast, photosensitization reactions using rose Bengal gave rise to a more acidic conformer of catalase. Singlet oxygen quenchers prevented catalase modification by rose Bengal and light. The growth medium had a photosensitizing activity. Catalase was not modified in cells illuminated in phosphate buffer but was modified in cells illuminated in phosphate buffer containing riboflavin. Intense light per se also generated a slight shift in the electrophoretic mobility of catalase. Ultraviolet light (350 or 366 nm) did cause a change in catalase, but to a less acidic catalase conformer, indicating other modifications of the enzyme. The main effect of photosensitization with methylene blue was crosslinking of the enzyme, although some shift to acidic conformers was observed at a low concentration of the photoactive compound. Results indicate that catalase can be modified by singlet oxygen generated intracellulary, even though the enzyme is predominantly inside peroxisomes. Under some photosensitization conditions, catalase modification can be used as a marker to detect intracellular singlet oxygen.
Spectral Irradiance in Pond Water: Influence of Water Chemistry
Authors: Crump D. , Lean D. , Berrill M. , Coulson D. , Toy L.
Published: January 2008

Knowing the depth of UV penetration in ponds and the chemical variables that control underwater spectral irradiance is a prerequisite to predicting the influence of UV on amphibians and other pond organisms. The present study found that over 99% of UVB (280–315 nm) radiation was attenuated in the top 10–20 cm of ponds sampled on the edge of the Canadian Shield near Peterborough, Ontario. While the principal attenuating substance was, as in lakes, dissolved organic carbon (DOC), neither DOC nor DOC fluorescence were useful predictors of the attenuation coefficients other than the observation that all values of DOC were high and all attenuation coefficients were also high. The lack of a reliable relationship between DOC and attenuation resulted from differences throughout the season in the fraction of the DOC capable of absorbing radiation (chromophores) and the fraction capable of fluorescing (fluorophores). Attenuation was higher than predicted from DOC during springtime when amphibians lay their eggs. Absorbance coefficients measured using a spectrophotometer proved to be reliable predictors of both UVB and UVA attenuation coefficients measured in the ponds with a spectro‐radiometer. While DOC provides an effective sun screen against the direct damage of UV radiation, the high attenuation means that the photochemical activity spread over at least 15 m in the ocean is confined to only a few centimeters in ponds.
POINTERLESS IMPLEMENTATION OF HIERARCHICAL SIMPLICIAL MESHES AND EFFICIENT NEIGHBOR FINDING IN ARBITRARY DIMENSIONS
Authors: ATALAY F. BETUL , MOUNT DAVID M.
Published: January 2008

We describe a pointerless representation of hierarchical regular simplicial meshes, based on a bisection approach proposed by Maubach. We introduce a new labeling scheme, called an LPT code, which uniquely encodes the geometry of each simplex of the hierarchy, and we present rules to compute the neighbors of a given simplex efficiently through the use of these codes. In addition, we show how to traverse the associated tree and how to answer point location and interpolation queries. Our system works in arbitrary dimensions.
Activation of Epidermal Akt by Diverse Mouse Skin Tumor Promoters
Authors: Lu Jerry , Rho Okkyung , Wilker Erik , Beltran Linda , DiGiovanni John
Published: January 2008

Akt is a serine/threonine kinase involved in a variety of cellular responses, including cell proliferation and cell survival. Recent studies from our laboratory suggest that Akt signaling may play an important role in skin tumor promotion. To explore this premise, we examined epidermal Akt activation and signaling in response to chemically diverse skin tumor promoters. Mice received single or multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA), okadaic acid, or chrysarobin. All three tumor promoters were able to activate epidermal Akt as early as 1 h after treatment. Activation of Akt following tumor promoter treatment led to enhanced downstream signaling, including hyperphosphorylation of glycogen synthase kinase-3β and Bad. Structure activity studies with phorbol ester analogues revealed that the magnitude of activation paralleled tumor-promoting activity. In cultured primary keratinocytes, TPA treatment also led to activation of Akt. Activation of the epidermal growth factor receptor (EGFR) seemed to underlie the ability of TPA to activate Akt as both PD153035, an inhibitor of EGFR, and GW2974, a dual-specific inhibitor of both EGFR and erbB2, were able to effectively reduce TPA-induced Akt phosphorylation as well as TPA-stimulated EGFR and erbB2 tyrosine phosphorylation in a dose-dependent manner. Furthermore, inhibition of protein kinase C (PKC) activity blocked TPA-stimulated heparin-binding EGF production and EGFR transactivation. Inhibition of PKC also led to a decreased association of Akt with the PP2A catalytic subunit, leading to increased Akt phosphorylation. However, combination of EGFR inhibitor and PKC inhibitor completely abrogated TPA-induced activation of Akt. Collectively, the current results support the hypothesis that elevated Akt activity and subsequent activation of downstream signaling pathways contribute significantly to skin tumor promotion. In addition, signaling through the EGFR via EGFR homodimers or EGFR/erbB2 heterodimers may be the primary event leading to Akt activation during tumor promotion in mouse skin. (Mol Cancer Res 2007;5(12):1342–52)
Ataxia-Telangiectasia Mutated Is Not Required for p53 Induction and Apoptosis in Irradiated Epithelial Tissues
Authors: Gurley Kay E. , Kemp Christopher J.
Published: January 2008

The ataxia-telangiectasia mutated (Atm) protein kinase is a central regulator of the cellular response to DNA damage. Although Atm can regulate p53, it is not known if this Atm function varies between tissues. Previous studies showed that the induction of p53 and apoptosis by whole-body ionizing radiation varies greatly between tissue and tumor types, so here we asked if Atm also had a tissue-specific role in the ionizing radiation response. Irradiated Atm-null mice showed impaired p53 induction and apoptosis in thymus, spleen, and brain. In contrast, radiation-induced p53, apoptosis, phosphorylation of Chk2, and G2-M cell cycle arrest were slightly delayed in Atm−/− epithelial cells of the small intestine but reached wild-type levels by 4 h. Radiation-induced p53 and apoptosis in Atm−/− hair follicle epithelial cells were not impaired at any of the time points examined. Thus, Atm is essential for radiation-induced apoptosis in lymphoid tissues but is largely dispensable in epithelial cells. This indicates that marked differences in DNA damage signaling pathways exist between tissues, which could explain some of the tissue-specific phenotypes, especially tumor suppression, associated with Atm deficiency. (Mol Cancer Res 2007;5(12):1312–8)
Genetic Regulatory Network Models of Biological Clocks: Evolutionary History Matters
Authors: Knabe Johannes F. , Nehaniv Chrystopher L. , Schilstra Maria J.
Published: January 2008

We study the evolvability and dynamics of artificial genetic regulatory networks (GRNs), as active control systems, realizing simple models of biological clocks that have evolved to respond to periodic environmental stimuli of various kinds with appropriate periodic behaviors. GRN models may differ in the evolvability of expressive regulatory dynamics. A new class of artificial GRNs with an evolvable number of complex cis-regulatory control sites—each involving a finite number of inhibitory and activatory binding factors—is introduced, allowing realization of complex regulatory logic. Previous work on biological clocks in nature has noted the capacity of clocks to oscillate in the absence of environmental stimuli, putting forth several candidate explanations for their observed behavior, related to anticipation of environmental conditions, compartmentation of activities in time, and robustness to perturbations of various kinds or to unselected accidents of neutral selection. Several of these hypotheses are explored by evolving GRNs with and without (Gaussian) noise and blackout periods for environmental stimulation. Robustness to certain types of perturbation appears to account for some, but not all, dynamical properties of the evolved networks. Unselected abilities, also observed for biological clocks, include the capacity to adapt to change in wavelength of environmental stimulus and to clock resetting.
Glycinergic “Inhibition” Mediates Selective Excitatory Responses to Combinations of Sounds
Authors: Sanchez Jason Tait , Gans Donald , Wenstrup Jeffrey J.
Published: January 2008

In the mustached bat's inferior colliculus (IC), combination-sensitive neurons display time-sensitive facilitatory interactions between inputs tuned to distinct spectral elements in sonar or social vocalizations. Here we compare roles of ionotropic receptors to glutamate (iGluRs), glycine (GlyRs), and GABA (GABAARs) in facilitatory combination-sensitive interactions. Facilitatory responses to 36 single IC neurons were recorded before, during, and after local application of antagonists to these receptors. The NMDA receptor antagonist CPP [(±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid], alone (n= 14) or combined with AMPA receptor antagonist NBQX (n= 22), significantly reduced or eliminated responses to best frequency (BF) sounds across a broad range of sound levels, but did not eliminate combination-sensitive facilitation. In a subset of neurons, GABAAR blockers bicuculline or gabazine were applied in addition to iGluR blockers. GABAAR blockers did not “uncover” residual iGluR-mediated excitation, and only rarely eliminated facilitation. In nearly all neurons for which the GlyR antagonist strychnine was applied in addition to iGluR blockade (22 of 23 neurons, with or without GABAAR blockade), facilitatory interactions were eliminated. Thus, neither glutamate nor GABA neurotransmission are required for facilitatory combination-sensitive interactions in IC. Instead, facilitation may depend entirely on glycinergic inputs that are presumed to be inhibitory. We propose that glycinergic inputs tuned to two distinct spectral elements in vocal signals each activate postinhibitory rebound excitation. When rebound excitations from two spectral elements coincide, the neuron discharges. Excitation from glutamatergic inputs, tuned to the BF of the neuron, is superimposed onto this facilitatory interaction, presumably mediating responses to a broader range of acoustic signals.
Mutations in aDrosophilaα2δ Voltage-Gated Calcium Channel Subunit Reveal a Crucial Synaptic Function
Authors: Dickman Dion K. , Kurshan Peri T. , Schwarz Thomas L.
Published: January 2008

Voltage-dependent calcium channels regulate many aspects of neuronal biology, including synaptic transmission. In addition to their α1subunit, which encodes the essential voltage gate and selective pore, calcium channels also contain auxiliary α2δ, β, and γ subunits. Despite progress in understanding the biophysical properties of calcium channels, thein vivofunctions of these auxiliary subunits remain unclear. We have isolated mutations in the gene encoding an α2δ calcium channel subunit (dα2δ-3) using a forward genetic screen inDrosophila. Null mutations in this gene are embryonic lethal and can be rescued by expression in the nervous system, demonstrating that the essential function of this subunit is neuronal. The photoreceptor phenotype ofdα2δ-3 mutants resembles that of the calcium channel α1mutantcacophony(cac), suggesting shared functions. We have examined in detail genotypes that survive to the third-instar stage. Electrophysiological recordings demonstrate that synaptic transmission is severely impaired in these mutants. Thus the α2δ calcium channel subunit is critical for calcium-dependent synaptic function. As such, thisDrosophilaisoform is the likely partner to the presynaptic calcium channel α1subunit encoded by thecaclocus. Consistent with this hypothesis, cacGFP fluorescence at the neuromuscular junction is reduced indα2δ-3 mutants. This is the first characterization of an α2δ-3 mutant in any organism and indicates a necessary role for α2δ-3 in presynaptic vesicle release and calcium channel expression at active zones.
Internet Use and Abuse in an Adolescent Population in Athens: Associations with Psychological Profile and Lifestyle of Users
Authors: Tripodaki Elli , Kormas Georgios , Konstantoulaki Eleftheria , Andrie Elisabeth , Nassis Georgios , Freskou Aliki , Sfiri Maria , Georgouli Helen , Tsitsika Artemis , Constantopoulos Andreas
Published: January 2008

INTRODUCTION:

Use of the Internet has become very popular among youth, but phenomena of Web abuse with negative physical and psychosocial consequences have emerged.

OBJECTIVE:

The researchers' goal was to study Internet use and abuse by Greek adolescents and to identify the psychological profile and lifestyle of users. Intervention attempts will also be designed and discussed.

METHODS:

An Athens adolescent population representative sample of 315 (164 boys, 151 girls) high school students (mean age: 15 years) were included in the study. For Internet-addiction diagnosis, an international tool (Young's Internet Addiction Test questionnaire) was used. The Strengths and Difficulties Questionnaire was applied to screen for emotional and behavioral problems. Physical activity and physical fitness were also assessed with appropriate questions. Correlation and x2 statistics were performed by using SPSS (SPSS Inc, Chicago, IL).

RESULTS:

According to the results, 167 (53.4%) of 315 adolescents were using the Internet for >1 year, 82 (26%) of 315 reported daily use, and 25 (8%) of 315 reported >20 hours' use weekly. Boys were spending significantly more time using the Internet than girls (P < .05). According to Young's Questionnaire scoring, no youngster in our sample was addicted. However, in 28 (9.4%) of 315 adolescents, Young's Questionnaire scoring was suggestive of occasional or frequent problems of Internet overuse. The most frequent reason for using the Internet was games (P < .05), and 18 (5.8%) of 315 children in our sample were cyberbullying victims. There was a positive correlation of Internet use and hyperactivity according to the Strengths and Difficulties Questionnaire results (P < .05). Positive correlations were also noted for Internet use and delinquency (P < .001) as well as dysfunctional peer relationships (P < .001).

CONCLUSIONS:

Use of the Internet is popular among Greek youth, and it can be related to psychosocial problems if overused.
DETECTION AND MOLECULAR SEROTYPING OF GROUP B STREPTOCOCCUS IN FATAL NEONATAL PNEUMONIA IN CHINA
Authors: Deng Jianghong , Yang Yonghong
Published: January 2008

INTRODUCTION: Group B Streptococcus (GBS) has been recognized as an important pathogen in neonatal infectious disease. However, there are few data on the prevalence of neonatal GBS infection in China.

OBJECTIVE: Our aim was to estimate the infection rate of GBS in neonatal pneumonia in China and identify distribution of the GBS serotype.

METHODS: We retrospectively studied 200 children with fatal neonatal pneumonia who died between 1953 and 2004; 34 fatal neonatal cases without any infectious disease were used as a control group. Paraffin-embedded lung tissues were collected for total genomic DNA extraction. Polymerase chain reaction (PCR) and Southern blotting were used for GBS detection and molecular serotyping.

RESULTS: (1) The positive rate of GBS in the pneumonia group was significantly higher than that in the control group (PCR: 26% vs 3% [P < .01]; Southern blot: 65% vs 18% [P < .01]). (2) The positive rate in neonates younger than 7 days was significantly higher than that in neonates older than 7 days (PCR: 37% vs 13% [P < .01]; Southern blot: 72% vs 52% [P < .05]). (3) Risk factors were identifiable for most GBS-positive cases. (4) In the pneumonia group, 22 GBS-positive cases were serotypeable: 7 cases were identified as serotype Ia, 6 cases were serotype III, 5 cases were serotype II, and 1 case was serotype Ib.

CONCLUSIONS: In China, GBS is an important pathogen in fatal neonatal pneumonia, especially in early-onset cases. Serotypes Ia, III, and II were the most common serotypes identified.
ASSESSMENT OF BONE MINERAL DENSITY AND MARKERS OF BONE TURNOVER IN CHILDREN UNDERGOING LONG-TERM ORAL ANTICOAGULANT THERAPY
Authors: Avgeri Maria , Platokouki Helen , Papadopoulou Anna , Douros Kostas , Rammos Spyridon , Nicolaidou Polyxeni , Aronis Sophia
Published: January 2008

INTRODUCTION: Oral anticoagulants antagonize vitamin K action and potentially impair the carboxylation of osteocalcin, a protein that is essential for normal bone matrix formation.

OBJECTIVE: Our aim was to evaluate bone mineral density (BMD) and bone-turnover markers in 23 children who were undergoing long-term oral anticoagulant therapy (median age: 4 years) and 25 age- and gender-matched controls.

METHODS: BMD (characterized as a z score) of the lumbar spine was assessed by using dual energy radiograph absorptiometry. Osteoblast (bone alkaline phosphatase, osteocalcin, and amino-terminal procollagen 1 extension peptide) and osteoclast (urinary calcium and deoxypyridinoline and serum cross-linked C telopeptide) activity markers were measured. Vitamin D (25-hydroxy vitamin D, parathyroid hormone, whole and ionized calcium, phosphorus, and magnesium) and vitamin K (factors II, VII, IX, and X, protein C, protein S, and undercarboxylated osteocalcin [Glu-Oc]) statuses were determined.

RESULTS: Patients presented with higher levels of Glu-Oc, parathyroid hormone, and bone-resorption markers and lower levels of bone-formation markers and 25-hydroxy vitamin D; 52% of them showed signs of osteopenia (−1.0 > BMD z score > −2.5). Statistical analysis demonstrated that anticoagulant therapy was an independent predictor of alterations in Glu-OC, osteocalcin, bone alkaline phosphatase, amino-terminal procollagen 1 extension peptide, and serum cross-linked C telopeptide levels.

CONCLUSIONS: Long-term use of coumarin derivatives may cause osteopenia in children with the risk of developing osteoporosis later in life.
HIGH SEROPREVALENCE OF HUMAN METAPNEUMOVIRUS INFECTION IN CHILDREN IN THE CHONGQING, CHINA, AREA
Authors: Zhao Xiaodong , Qin Zhang
Published: January 2008

INTRODUCTION: Human metapneumovirus (hMPV), first isolated in 2001 in the Netherlands, was identified as a respiratory etiologic agent in a variety of regions. A number of reports have described evidence of hMPV infection on mainland China. However, the description of the seroepidemiology of hMPV infection remains limited.

OBJECTIVE: We aimed to define the seropositivity of hMPV immunoglobulin G (IgG) antibodies in different age groups of children in Chongqing, China.

METHODS: The specificity of the enzyme-linked immunosorbent assay was first validated by using respiratory syncytial virus (RSV)-infected cell lysates subtracted sera and Western blotting based on anti-hMPV animal serum. This assay was subsequently used to determine the presence of IgG antibodies to hMPV and RSV in 325 serum samples from children aged 0 to 6 years.

RESULTS: There was no cross-reaction between the hMPV and RSV enzyme-linked immunosorbent assays observed in our system. Seropositivity of anti-hMPV IgG antibodies in children aged 0 to 5 months was 74.5%, 64% for children aged 6 to 11 months, 72.7% for children aged 12 to 23 months, 87.1% for children aged 24 to 35 months, and 90.3% for children 3 to 6 years old, respectively. The seropositivity of hMPV and RSV was considerably similar in almost all age groups.

CONCLUSIONS: hMPV seems to be a common and important respiratory pathogen in Chongqing's children. Almost all individuals had been exposed to hMPV by the age of 6 years.
Transsphenoidal surgery in a patient with acromegaly and McCune–Albright syndrome: application of neuronavigation
Authors: Dou Wanchen , Lin Ning , Ma Wenbin , Yang Yi , Zhu Huijuan , Sun Juan , Lian Wei , Yang Zhong , Li Wuyi , Wang Renzhi
Published: January 2008

✓The McCune–Albright syndrome (MAS) is characterized by a clinical triad of polyostotic fibrous dysplasia, café-au-lait hyperpigmented macules, and hypersecretory endocrinopathies. Acromegaly is an uncommon manifestation of the endocrine disturbance associated with MAS, and the role of surgery in managing these cases has been a topic of debate. The authors present the case of a 35-year-old man with MAS who was also diagnosed with acromegaly, hyperprolactinemia, and pituitary macroadenoma. The patient had an 18-year history of fibrous dysplasia involving the right frontal bone and ribs as well as multiple endocrinopathies, but no cutaneous hyperpigmented macules. An oral glucose tolerance test demonstrated partial suppression of plasma levels of growth hormone (GH). The patient underwent transsphenoidal resection of the pituitary tumor, performed with assistance of neuronavigation, and tolerated the procedure well. After the surgery, both prolactin and GH levels returned to normal. These results suggest that neuronavigation-assisted transsphenoidal surgery can safely remove pituitary adenomas associated with MAS and successfully treat the underlying endocrine abnormalities.
Analysis of neuronal cell death in the cerebral cortex of H-Tx rats with compensated hydrocephalus
Authors: Nonaka Yasuomi , Miyajima Masakazu , Ogino Ikuko , Nakajima Madoka , Arai Hajime
Published: January 2008

Object

Some cases of compensatory hydrocephalus have been reported in which cognitive deficiency progresses despite the absence of progressive ventricular dilation. In this study, the differentially expressed genes in compensated hydrocephalic H-Tx rat cortices were determined. A molecular mechanism that induces neuronal death in the cerebral cortex of compensated hydrocephalus is proposed.

Methods

The cerebral cortices of 8-week-old H-Tx rats with spontaneously arrested hydrocephalus (hH-Tx) and nonhydrocephalic H-Tx (nH-Tx) control rats were subjected to cDNA microarray analysis followed by canonical pathway analysis.

Results

In the hH-Tx rats, many genes in the amyloidal processing pathway showed altered expression, including Akt3 and p38 MAPK. These latter genes are involved in tau protein phosphorylation, and their increased expression in hydrocephalus was confirmed by real-time polymerase chain reaction analysis. Immunohistological and immunoblot analysis revealed elevated phosphorylated tau expression in the cerebral cortex neurons of the hH-Tx rats.

Conclusions

The accumulation of phosphorylated tau protein in the cerebral cortex may be one of the mechanisms by which later cognitive dysfunction develops in patients with compensated hydrocephalus. More work needs to be done to determine if the accumulation of phosphorylated tau in the cortex can help predict which patients may decompensate thus requiring more aggressive treatment for compensated hydrocephalus.
Endovascular remodeling technique for vein of Galen aneurysmal malformations––angiographic confirmation of a connection between the median prosencephalic vein and the deep venous system
Authors: Iizuka Yuo , Kakihara Takanori , Suzuki Mitimasa , Komura Shinji , Azusawa Hiroyuki
Published: January 2008

✓ It is commonly believed that in vein of Galen aneurysmal malformations (VGAMs) venous structures normally constituting the deep or Galenic venous system, such as the internal cerebral vein (ICV) and the basal vein of Rosenthal, are not connected to the vein of Galen. In this report, the authors describe 2 cases of successfully treated VGAM in which drainage of an ICV into the vein of Galen was confirmed by follow-up angiography. Two mural types of VGAM were treated using transarterial glue embolization when 1 child was 5 months and the other was 6 months old. The postoperative outcomes for these babies were complete cures. Follow-up digital subtraction angiography obtained after 12 months (Case 1) and 6 months (Case 2) confirmed that the shrunken median prosencephalic vein connects with the deep venous system. The possibility of normal deep Galenic venous drainage must be considered in endovascular management of VGAM. The goal of endovascular intervention is to close only the ventral component of the dilated median prosencephalic vein.
Multiple horizons and information in USDA production forecasts
Authors: Sanders Dwight R. , Manfredo Mark R.
Published: January 2008

United States Department of Agriculture (USDA) livestock production forecasts are evaluated for their information content across multiple forecast horizons using the direct test developed by Vuchelen and Gutierrez (2005). Forecasts are explicitly tested for rationality (unbiased and efficient) as well as for incremental information out to three‐quarters ahead. The results suggest that although the forecasts are often not rational, they typically do provide the forecast user with unique information at each horizon. Turkey and milk production forecasts are found to provide the most consistent performance, while beef production forecasts provide little information beyond the two‐quarter horizon. [C53, Q13] © 2008 Wiley Periodicals, Inc.
Evaluating animal welfare with choice experiments: an application to Swedish pig production
Authors: Liljenstolpe Carolina
Published: January 2008

In this study, the demand for animal welfare attributes when buying pork fillet is investigated among Swedish respondents. The issue is of importance in order to ensure an economically viable pig industry while applying an increasing number of animal friendly practices. In order to obtain information about consumer demand, an indirect utility function and willingness to pay (WTP) for animal welfare attributes are estimated. The attributes are solely associated with animal friendly practices. An investigation of numerous housing and managerial practices of pig production has not yet been performed. The indirect utility function is estimated using a random parameter logit model. A realistic approach when modeling consumer choice is to allow for heterogeneity in preferences. The relevance of assuming randomness of some of the parameters is evaluated by using a specification test developed by McFadden and Train (2000). The WTP is also estimated at the individual level. The results indicate that WTP for animal welfare attributes may be negative or positive. The preferences are also heterogeneous among respondents, which may be explained by a segmentation of preferences. Finally, the WTP estimates for animal welfare practices are compared with cost estimates for such production systems. [Econlit subject codes: C010, C500, Q100] © 2008 Wiley Periodicals, Inc.
CC Coupling Reactions of Superstrong CF3 Groups with C(sp2)–H Bonds: Reactivity and Synthetic Utility of Zero‐Valent Niobium Catalyst
Authors: Fuchibe Kohei , Mitomi Ken , Suzuki Ryo , Akiyama Takahiko
Published: January 2008

It was found that zero‐valent niobium is an efficient catalyst for the intramolecular CC coupling reactions of o‐aryl and o‐alkenyl α,α,α‐trifluorotoluene derivatives. The superstrong CF bonds of CF3 groups and neighboring C(sp2)H bonds were doubly activated, and fluorenes and indenes were obtained in good yields. The niobium fluorocarbenoid species is proposed to be the key intermediate.
Chemiluminescence of 4‐styrylphthal‐hydrazides with crown ether as ionophore
Authors: Motoyoshiya Jiro , Hotta Masanori , Nishii Yoshinori , Aoyama Hiromu
Published: January 2008

Two 4‐styrylphthalhydrazides bearing crown ether moieties as ionophores were prepared and their chemiluminescence (CL) behaviour was investigated. Their aerobic oxidation in the presence of excess tert‐BuOK in DMSO provided the CL with much shorter emission wavelengths than those of the corresponding phthalate dianions, indicating that the emission arose from the excited phthalates incorporated with potassium ions at the ionophore sites. Such incorporation of potassium ions with the crown sites also reduced the fluorescence intensities of the phthalate dianions which caused an energy transfer CL, resulting in the additional emissions of the phthalhydrazide monoanions in much longer wavelength regions. On the other hand, only the emission from the excited phthalate dianion was detected under aqueous conditions using aqueous hydrogen peroxide in acetonitrile as the oxidant, but no meaningful difference in the CL intensity depending on the kind of metal cations was observed. Copyright © 2008 John Wiley & Sons, Ltd.
Photochemical Generation and Structure of Vinyl Radicals (Eur. J. Org. Chem. 3/2008)
Authors: Goumans Theodorus P. M. , van Alem Kaj , Lodder Gerrit
Published: January 2008

The cover picture shows how the structure of an α‐CN vinyl radical is elucidated through the photolysis of stereoisomeric vinyl halide precursors. The vinyl radical intermediates react with the solvent to form stereoisomeric styrenes. Analysis of the yields of the styrenes as a function of temperature establishes the α‐CN vinyl radical as a rapidly inverting bent, and not linear, species. The photolyses of α‐Me, α‐C(H)=O and α‐F substituted bromostyrenes indicate that the α‐Me vinyl radical is also rapidly inverting, while the α‐C(H)=O and α‐F vinyl radicals are stable bent species. The experimental results are supported by quantum chemical computations. Details are discussed in the article by T. P. M. Goumans et al. on p. 435 ff. Patty Nieuwenburg is acknowledged for the background photo of the dunes of Harlech, Wales.
An investigation of the effect of immediate and extended release venlafaxine on nocturnal melatonin and cortisol release in healthy adult volunteers
Authors: Hallam Karen T. , Begg Denovan P. , Olver James S. , Norman Trevor R.
Published: January 2008

The secretion of the hormone melatonin is particularly robust to the effect of pharmacological agents. Medications may alter melatonin levels through either altering adrenergic activity or affecting liver enzymes involved in melatonin metabolism. The aim of this study was to investigate the effect of venlafaxine, a third generation antidepressant with known adrenergic properties on melatonin secretion. A further aim of the study was to investigate the correlation between plasma and salivary measures on this medication. Eight healthy adult participants (four males, four females) took part in this double blind placebo controlled randomised trial. Participants were tested on 3 nights after taking venlafaxine XR (75 mg), venlafaxine IR (75 mg) or placebo. Participants were placed in a darkened room between 1900 and 0300 h and regular temperature readings, blood and saliva samples were drawn to assess melatonin and cortisol secretion in each condition. There was no significant effect of venlafaxine IR or XR on melatonin concentrations in plasma or saliva and no effects on other circadian parameters including cortisol and temperature. It was notable that the correlation between plasma and salivary melatonin levels became poor after drug treatment. These results indicate that at low doses the mixed serotonergic and noradrenergic drug venlafaxine has no effect on nocturnal melatonin concentrations. Copyright © 2008 John Wiley & Sons, Ltd.