bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping glutamate responses in immunocytochemically identified neurons of the mouse retina
Authors: Sun Daniel , Kalloniatis Michael
Published: December 2005

The mammalian retina contains as many as 50–60 unique cell types, many of which have been identified using various neurochemical markers. Retinal neurons express N‐methyl‐D‐aspartate (NMDA), α‐amino‐3‐hydroxyl‐5‐methylisoxazole‐4‐propionic acid (AMPA), and kainic acid (KA) receptor subunits in various mixtures, densities, and spatial distributions. Ionotropic glutamatergic drive in retinal neurons can be mapped using a cation channel permeant guanidinium analog called agmatine (1‐amino‐4‐guanidobutane; AGB). This alternative approach to physiologically characterize neurons in the retina was introduced by Marc (1999, J Comp Neurol 407:47–64, 407:65–76), and allows the simultaneous mapping of responses of glutamate receptor‐gated channels from an entire population of neurons. Unlike previous AGB studies, we colocalized AGB with various macromolecular markers using direct and indirect immunofluorescence to characterize the glutamate agonist sensitivities of specific cell types. Activation with NMDA, AMPA, and KA resulted in AGB entry into neurons in a dose‐dependent manner and was consistent with previous receptor subunit localization studies. Consistent with the various morphological phenotypes encompassed by the calbindin and calretinin immunoreactive cells, we observed various functional phenotypes revealed by AGB labeling. Not all calbindin or calretinin immunoreactive cells showed ligand‐evoked AGB permeation. A small proportion either did not possess functional glutamate receptors, required higher activation thresholds, or express functional channels impermeable to AGB. AMPA and KA activation of bipolar cells resulted in AGB permeation into the hyperpolarizing variety only. We also studied the glutamate ligand‐gating properties of 3[α1‐3]‐fucosyl‐N‐acetyl‐lactosamine (CD15) immunoreactive cells and show functional responses consistent with receptor subunit gene expression patterns. CD15‐immunoreactive bipolar cells only responded to AMPA but not KA. The CD15 immunoreactive amacrine cells demonstrated an identical selectivity to AMPA activation, but were also responsive to NMDA. Finally, localization of AGB secondary to glutamate receptor activation was visualized with a permanent reaction product. J. Comp. Neurol. 494:686–703, 2006. © 2005 Wiley‐Liss, Inc.
A phylotypic stage in vertebrate brain development: GABA cell patterns in zebrafish compared with mouse
Authors: Mueller Thomas , Vernier Philippe , Wullimann Mario F.
Published: December 2005

A recent comparison of early forebrain gene expression in mouse and zebrafish revealed highly comparable expression patterns of developmentally relevant genes, for example, of proneural (Neurogenin1, NeuroD, Mash1/Zash1a) genes involved in neurogenesis at a particular time window (mouse: embryonic day 12.5/13.5; zebrafish: 3 days). Here we extend this analysis to the description of γ‐aminobutyric acid (GABA) cell patterns in the early postembryonic zebrafish brain (i.e., during early secondary neurogenesis). We find again an astonishing degree of correspondences of GABA cell patterns between zebrafish and mouse during this previously established critical time window, for example, regarding absence of GABA cells in certain forebrain regions (pallium, dorsal thalamus, eminentia thalami) or with respect to the spatiotemporal occurrence of GABA cells (e.g., late cerebellar GABA cells). Furthermore, there is perfect correlation with previously established proneural gene expression patterns (i.e., absence of Mash1/Zash1a gene expression in GABA‐cell‐free forebrain regions) between mouse and zebrafish. The available information in additional vertebrate species, especially in Xenopus, is also highly consistent with our analysis here and suggests that a “phylotypic stage” of neurogenesis during vertebrate brain development may be present. J. Comp. Neurol. 494:620–634, 2006. © 2005 Wiley‐Liss, Inc.
Estrogen receptor‐α distribution in male rodents is associated with social organization
Authors: Cushing Bruce S. , Wynne‐Edwards Katherine E.
Published: December 2005

It has been hypothesized that site‐specific reduction of estrogen receptor‐α (ERα) is associated with the expression of male prosocial behaviors. Specifically, highly social males are predicted to express significantly lower levels of ERα than females and less social males in brain regions associated with prosocial behavior including the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This hypothesis was tested by comparing ERα immunoreactivity (IR) in three species of microtines, the polygynous montane (Microtus montanus) and meadow (M. pennsylvanicus) voles and the monogamous pine vole (M. pinetorum), and two species of cricetines that differ in the extent of social pair‐bond formation, Siberian (Phodopus sungorus) and Djungarian (P. campbelli) hamsters. As predicted, ERα‐IR was sexually dimorphic in the BST and MeA of the highly social species, with females expressing more ERα‐IR cells than males. Male and female montane voles did not differ. Male and female meadow voles differed in the ventromedial hypothalamus, with females expressing more ERα‐IR cells. Male pine voles expressed lower levels of ERα‐IR in the MeA than male montane and meadow voles and in the BST relative to montane males. Male Djungarian hamsters, which show higher levels of parental care, had fewer ERα‐IR cells in the BST than male Siberian hamsters. Results indicate that the distribution of ERα differs relative to the continuum of species‐typical affiliative behavior and supports the hypothesis that ERα has a significant role in regulating species‐specific social organization. J. Comp. Neurol. 494:595–605, 2006. © 2005 Wiley‐Liss, Inc.
Ommatidial type‐specific interphotoreceptor connections in the lamina of the swallowtail butterfly, Papilio xuthus
Authors: Takemura Shin‐Ya , Arikawa Kentaro
Published: December 2005

The eye of the butterfly Papilio xuthus contains a random array of three types of ommatidia (types I–III), each bearing nine photoreceptors, R1–R9. Of the six spectral classes of photoreceptors identified, types I, II, and III ommatidia contain four, three, and two classes, respectively: the ommatidia are thus spectrally heterogeneous. The photoreceptors send their axons to the lamina where, together with some large monopolar cells (LMCs), the nine from a single ommatidium contribute to a module called a lamina cartridge. We recently reported that among different photoreceptor axon terminals visualized by confocal microscopy, the number and length of axon collaterals differ for different spectral receptors, suggesting that lamina circuits are specific for each ommatidial type. Here we studied the distribution of synapse‐like structures in the cartridges, first characterizing a photoreceptor by measuring its spectral sensitivity and then injecting Lucifer yellow (LY). We subsequently histologically identified the type of ommatidium to which the injected photoreceptor belonged, cut serial ultrathin sections of the entire lamina, labeled these with anti‐LY immunocytochemistry, and then localized synapse‐like structures. We found numerous interphotoreceptor contacts both within and between cartridges, the combination of which was again specific for the ommatidial type. R3 and R4, which are green‐sensitive photoreceptors in all ommatidia, have thick axons lacking collaterals. We found that these cells exclusively make contacts with LMCs and not with photoreceptors. We therefore presume that R3 and R4 construct a system for motion vision, whereas other randomly distributed spectral types provide inputs for color vision. J. Comp. Neurol. 494:663–672, 2006. © 2005 Wiley‐Liss, Inc.
Expression pattern of calcitonin gene‐related peptide in the superior colliculus during postnatal development: Demonstration of its intrinsic nature and possible roles
Authors: Gerrikagoitia Inmaculada , del Caño Gontzal García , Canudas Jesús , Sarasa Manuel , Martínez‐Millán Luis
Published: December 2005

Calcitonin gene‐related peptide (CGRP) is a widespread neuropeptide with multiple central and peripheral targets. In an analysis on the expression of this peptide throughout the rat brain during postnatal development, we observed a discrepancy between results obtained by immunohistochemistry and by in situ hybridization. In the superior colliculus (SC), only the immunohistochemical signal could be detected (Terrado et al. [1997] Neuroscience 80:951–970). Here we focus our attention on this structure because the temporal pattern of CGRP immunoreactivity observed in the SC suggested the participation of this peptide in the postnatal maturation of the SC. In the present study, we describe in detail the postnatal development of collicular CGRP‐immunoreactive structures and their spatiotemporal relationship with cholinergic modules and definitively demonstrate the local expression of CGRP in the SC. CGRP‐immunopositive axons and neurons were distributed within the most ventral part of superficial strata and in the intermediate strata of the SC, showing a peak in staining intensity and density at the end of the first postnatal week. At P14, CGRPergic terminal fibers are arranged in small, clearly defined patches in a complementary manner with respect to the cholinergic modules, which start forming at this stage. By using Western blot and RT‐PCR analyses, and by means of injections of antisense oligonucleotides, both the presence of CGRP peptide in the SC and the local expression of α‐CGRP transcripts in collicular neurons were demonstrated. A possible role of CGRP is discussed in the context of postnatal modular compartmentalization of collicular afferents. J. Comp. Neurol. 494:721–737, 2006. © 2005 Wiley‐Liss, Inc.
Water deprivation activates a glutamatergic projection from the hypothalamic paraventricular nucleus to the rostral ventrolateral medulla
Authors: Stocker Sean D. , Simmons Johnny R. , Stornetta Ruth L. , Toney Glenn M. , Guyenet Patrice G.
Published: December 2005

Elevated sympathetic outflow contributes to the maintenance of blood pressure in water‐deprived rats. The neural circuitry underlying this response may involve activation of a pathway from the hypothalamic paraventricular nucleus (PVH) to the rostral ventrolateral medulla (RVLM). We sought to determine whether the PVH‐RVLM projection activated by water deprivation is glutamatergic and/or contains vasopressin‐ or oxytocin‐neurophysins. Vesicular glutamate transporter 2 (VGLUT2) mRNA was detected by in situ hybridization in the majority of PVH neurons retrogradely labeled from the ipsilateral RVLM with cholera toxin subunit B (CTB; 85% on average, with regional differences). Very few RVLM‐projecting PVH neurons were immunoreactive for oxytocin‐ or vasopressin‐associated neurophysin. Injection of biotinylated dextran amine (BDA) into the PVH produced clusters of BDA‐positive nerve terminals within the ipsilateral RVLM that were immunoreactive (ir) for the VGLUT2 protein. Some of these terminals made close appositions with tyrosine‐hydroxylase‐ir dendrites (presumptive C1 cells). In water‐deprived rats (n = 4), numerous VGLUT2 mRNA‐positive PVH neurons retrogradely labeled from the ipsilateral RVLM with CTB were c‐Fos‐ir (16–40%, depending on PVH region). In marked contrast, few glutamatergic, RVLM‐projecting PVH neurons were c‐Fos‐ir in control rats (n = 3; 0–3%, depending on PVH region). Most (94% ± 4%) RVLM‐projecting PVH neurons activated by water deprivation contained VGLUT2 mRNA. In summary, most PVH neurons that innervate the RVLM are glutamatergic, and this population includes the neurons that are activated by water deprivation. One mechanism by which water deprivation may increase the sympathetic outflow is activation of a glutamatergic pathway from the PVH to the RVLM. J. Comp. Neurol. 494:673–685, 2006. © 2005 Wiley‐Liss, Inc.
Astrocytic and neuronal localization of the scaffold protein Na+/H+ exchanger regulatory factor 2 (NHERF‐2) in mouse brain
Authors: Paquet Maryse , Kuwajima Masaaki , Yun C. Chris , Smith Yoland , Hall Randy A.
Published: December 2005

The Na+/H+ exchanger regulatory factor 2 (NHERF‐2) is a scaffold protein that regulates cellular signaling by forming protein complexes. Several proteins known to interact with NHERF‐2 are abundantly expressed in the central nervous system, but little is known about NHERF‐2 localization in the brain. By using immunohistochemistry combined with light and electron microscopy, we found that many populations of astrocytes, as well as some populations of neurons, were immunopositive for NHERF‐2 throughout the mouse brain. Quantitative analysis of the subcellular distribution of NHERF‐2 immunostaining in four brain structures, cerebral cortex, hippocampus, striatum, and cerebellar cortex, showed that NHERF‐2 was expressed mainly in astrocytic processes but was also sometimes observed in both pre‐ and postsynaptic neuronal elements. NHERF‐2 immunostaining was associated mainly with the plasma membrane of neurons and astrocytes. However, NHERF‐2 immunoreactivity was also observed in association with synaptic vesicles in putative glutamatergic axon terminals. The subcellular localization of NHERF‐2 in brain is consistent with a role for NHERF‐2 in forming complexes between cell surface and cytosolic proteins, and the preferential expression of NHERF‐2 in astrocytes suggests that this scaffold protein may play an important role in astrocytic physiology. J. Comp. Neurol. 494:752–762, 2006. © 2005 Wiley‐Liss, Inc.
New Insights into the Redox Chemistry of Ruthenium Metallopharmaceuticals: The Electrochemical Behaviour of [LH][trans‐RuIIICl4L2] (L = imidazole or indazole) Complexes
Authors: Ravera Mauro , Cassino Claudio , Baracco Sara , Osella Domenico
Published: December 2005

Here we report the findings from a study on the electrochemical behaviour of two RuIII complexes [LH][trans‐RuIIICl4L2] (L = imidazole, ICR, or indazole, IndCR) in aqueous solution at different pH values. An electrochemically reversible and chemically quasi‐reversible one‐electron reduction is observed for both compounds. Despite the similarity of the structures, the fate of the electrogenerated RuII species is different; in the case of ICR, imidazole, followed by a chloride ion, is released as the consequence of the reduction, while for IndCR two subsequent water for chloride substitutions take place. Our measurements suggests that the RuIII complexes under study may serve as pro‐drugs, being activated by reduction in a suitable aqueous environment and, therefore, binding biomolecules more rapidly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Entrapment of a Hexamer of Nitrobenzene Molecules between the Layers of (4,4)‐Coordination Networks Containing Intra‐β‐Sheet Hydrogen Bonds
Authors: Sarkar Madhushree , Biradha Kumar
Published: December 2005

Two exo‐bidentate pyridyl ligands containing diamides as spacers were shown to form non‐interpenetrated 2D‐coordination networks of (4,4)‐geometry upon treatment with Cu(NO3)2 and NaSCN. The crystal structures reveal that both structures contain intralayer β‐sheet hydrogen bonds. In one of these structures nitrobenzene occupies 60 % of the crystal volume included between the coordination networks. The nitrobenzene molecules form a layer which has the hexameric C–H···O hydrogen bonded aggregate as a basic building block. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Crystal Structure and Optical Properties of a Lanthanum(III) Complex of the Solvatochromic Dye “Nile Red” (Eur. J. Inorg. Chem. 1/2006)
Authors: Døssing Anders , Magnussen Magnus , Frey Anne Mette
Published: December 2005

The cover picture shows that addition of lanthanum(III) triflate to the red solution of a fluorescent “Nile Red” derivative results in a bathochromic shift of the intense charge‐transfer band due to the formation of a chelate lanthanum(III) complex, as shown by a structure determination of crystals isolated from the resulting blue solution. details are discussed in the Short Communication by A. Døssing et al. on p. 43 ff.
Synthetic and Structural Studies of Silver(I)‐ and Gold(I)‐ContainingN‐Heterocyclic Carbene Metallacrown Ethers
Authors: Wang Jun‐Wen , Li Qing‐Shan , Xu Feng‐Bo , Song Hai‐Bin , Zhang Zheng‐Zhi
Published: December 2005

The ligands bis(imidazolium) hexafluorophosphate [RHimy‐(CH2OCH2)n‐HimyR][PF6]2 [Himy = –C3N2H3–, imidazolium; R = 1‐naphthylmethyl, n = 2 (1a), 3 (2a); R = 9‐anthracenylmethyl, n = 2 (1b), 3 (2b)] with a highly flexible polyether chain were easily prepared by the reaction of substituted imidazole with the corresponding polyglycol diiodide, followed by exchange of the anions with PF6–. Ligands 1a,b and 2a,b react with Ag2O to give monometallic AgI‐containing N‐heterocyclic carbene (NHC) metallacrown ethers 3a,b and 4a,b with a long and highly flexible bridging chain (CH2OCH2)n (n = 2, 3) between the two imidazolium units. Complexes 3a,b and 4a,b react with [Au(SMe2)Cl] in a transmetalation reaction to give AuI analogues 5a,b and 6a,b. Complexes 3a,b–6a,b are novel examples of a metallacrown ether with NHCs. In contrast to the use of a high‐dilution technique in the preparation of polyether chain phosphane‐containing metallacrown ethers, the new trans‐metallacrown ethers can be prepared in concentrated solution. The structures of 3a–6a were confirmed by X‐ray diffraction determination. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Moore Cyclizations: Rearrangements of 3‐Heteroatom‐pent‐1‐en‐4‐yn‐1‐ones – A Computational Search for New Reactions
Authors: Schreiner Peter R. , Bui Binh H.
Published: December 2005

The thermal rearrangements of 3‐heteroatom‐pent‐1‐en‐4‐yn‐1‐ones were studied at the BLYP/6‐311+G*//BLYP/6‐31G* level of theory. While cyclizations to oxo‐hetero‐cyclopentadien‐di‐yl are most favorable and predicted to be experimentally feasible for X = CH–, NH, O, and S, protonation of these substituents raises the corresponding 2,6‐cyclization barriers. Cyclizations to oxacyclohexadienediyl are highly improbable due to competition with other low‐lying alternative pathways. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Polystyrene‐Supported 1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene as an Efficient and Reusable Catalyst for the Thiolysis of 1,2‐Epoxides under Solvent‐Free Conditions
Authors: Fringuelli Francesco , Pizzo Ferdinando , Vittoriani Carla , Vaccaro Luigi
Published: December 2005

Polystyrene‐supported 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (PS‐TBD) is an effective basic catalyst for the thiolysis of the 1,2‐epoxides 1a–e by the aryl‐ and alkyl‐substituted thiols 2A–E under solvent‐free conditions while its activity is remarkably reduced in MeCN. The reactions are totally anti‐diastereoselective and generally highly C‐β regioselective. The corresponding hydroxy sulfides have been isolated in excellent yields and the catalyst has been easily recovered and reused with no loss in terms of efficiency and selectivity of the process. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Family‐based association test for time‐to‐onset data with time‐dependent differences between the hazard functions
Authors: Jiang Hongyu , Harrington David , Raby Benjamin A. , Bertram Lars , Blacker Deborah , Weiss Scott T. , Lange Christoph
Published: December 2005

In genetic association studies, the differences between the hazard functions for the individual genotypes are often time‐dependent. We address the non‐proportional hazards data by using the weighted logrank approach by Fleming and Harrington [1981]:Commun Stat‐Theor M 10:763–794. We introduce a weighted FBAT‐Logrank whose weights are based on a non‐parametric estimator for the genetic marker distribution function under the alternative hypothesis. We show that the computation of the marker distribution under the alternative does not bias the significance level of any subsequently computed FBAT‐statistic. Hence, we use the estimated marker distribution to select the Fleming‐Harrington weights so that the power of the weighted FBAT‐Logrank test is maximized. In simulation studies and applications to an asthma study, we illustrate the practical relevance of the new methodology. In addition to power increases of 100% over the original FBAT‐Logrank test, we also gain insight into the age at which a genotype exerts the greatest influence on disease risk. Genet. Epidemiol. 2006. © 2006 Wiley‐Liss, Inc.
Upregulation of the stress‐associated gene p8 in mouse models of demyelination and in multiple sclerosis tissues
Authors: Plant Sheila R. , Wang Ying , Vasseur Sophie , Thrash J. Cameron , Mcmahon Eileen J. , Bergstralh Daniel T. , Arnett Heather A. , Miller Stephen D. , Carson Monica J. , Iovanna Juan L. , Ting Jenny P‐Y.
Published: December 2005

Cuprizone‐induced demyelination is a mouse model of multiple sclerosis (MS) as cuprizone‐fed mice exhibit neuroinflammation and demyelination in the brain. Upon removal of cuprizone from the diet, inflammation is resolved and reparative remyelination occurs. In an Affymetrix GeneChip analysis, the stress‐associated gene p8 was strongly upregulated (>10×) during cuprizone‐induced demyelination but not remyelination. We verified this upregulation (>15×) of p8 in the CNS during demyelination by real‐time polymerase chain reaction (PCR). This upregulation is brain‐specific, as p8 is not elevated in the liver, lung, kidney, spleen, and heart of cuprizone‐treated mice. We also localized the cellular source of p8 during cuprizone treatment, and further found elevated expression during embryogenesis but not in normal adult brain. Compared with wild‐type controls, the death of oligodendrocytes in p8−/− mice is delayed, as is microglial recruitment to areas of demyelination. The corpus callosum of p8−/− mice demyelinates at a slower rate than wild‐type mice, suggesting that p8 exacerbates CNS inflammation and demyelination. Enhanced expression of p8 is also observed in the spinal cords of mice with acute experimental autoimmune encephalomyelitis (EAE) induced by PLP139‐151 peptide (10×). Increased expression is detected during disease onset and expression wanes during the remission phase. Finally, p8 is found upregulated (8×) in post‐mortem tissue from MS patients and is higher in the plaque tissue compared with adjacent normal‐appearing white and gray matter. Thus, p8 is an excellent candidate as a novel biomarker of demyelination. © 2005 Wiley‐Liss, Inc.
Non‐PKC DAG/Phorbol‐Ester receptor(s) inhibit complement receptor‐3 and nPKC inhibit scavenger receptor‐AI/II‐mediated myelin phagocytosis but cPKC, PI3k, and PLCγ activate myelin phagocytosis by both
Authors: Cohen Goni , Makranz Chen , Spira Maya , Kodama Tatsuhiko , Reichert Fanny , Rotshenker Shlomo
Published: December 2005

Complement‐receptor‐3 (CR3/MAC‐1), scavenger‐receptor‐AI/II (SRAI/II), and Fcγ‐receptor (FcγR) can mediate myelin phagocytosis in macrophages and microglia. Paradoxically, after injury to CNS axons these receptors are expressed but myelin is not phagocytosed, suggesting that phagocytosis is subject to regulation between efficient and inefficient states. In the present work, we focus on CR3/MAC‐1 and SRAI/II‐mediated myelin phagocytosis. Phagocytosis by CR3/MAC‐1 and SRAI/II was inhibited by cPKC inhibitor Go‐6976, general‐PKC inhibitors Ro‐318220 and calphostin‐C, and BAPTA/AM, which chelates intracellular Ca2+ required for cPKC activation. Signaling/activation by cPKC are thus suggested. PMA, which mimics diacylglycerol (DAG) as an activator of cPKC, novel‐PKC (nPKC), and non‐PKC DAG‐driven molecule(s), produced a dose‐dependent dual effect on phagocytosis by CR3/MAC‐1 and SRAI/II, i.e., augmentation at low concentrations and inhibition at high concentrations. Inhibition of phagocytosis by CR3/MAC‐1 was enhanced by combining inhibiting concentrations of PMA with PKC inhibitors Go‐6976 or Ro‐318220, suggesting inhibition by PMA/DAG‐driven non‐PKC molecule(s). In contrast, inhibition of phagocytosis by SRAI/II was enhanced by combining inhibiting concentrations of PMA with cPKC inhibitor Go‐6976 but not with general‐PKC inhibitor Ro‐318220, suggesting inhibition by nPKC. Phagocytosis by CR3/MAC‐1 and SRAI/II was further inhibited by PI3K inhibitors wortmannin and LY‐294002 and PLCγ inhibitor U‐73122. Altogether, our observations suggest that CR3/MAC‐1 and SRAI/II‐mediated myelin phagocytosis share activation by PI3K, PLCγ and cPKC. The two differ, however, in that non‐PKC DAG‐driven molecule(s) inhibit CR3/MAC‐1‐mediated phagocytosis, whereas nPKC inhibit SRAI/II‐mediated phagocytosis. Each of these signaling steps may be targeted for regulating CR3/MAC‐1 and/or SRAI/II‐mediated phagocytosis between efficient and inefficient states. © 2005 Wiley‐Liss, Inc.
Selectively increased expression of the astrocytic/endothelial glucose transporter protein GLUT1 in acute liver failure
Authors: Bélanger Mireille , Desjardins Paul , Chatauret Nicolas , Butterworth Roger F.
Published: December 2005

Acute liver failure (ALF) is consistently accompanied by alterations in brain energy metabolites and recent nuclear magnetic resonance (NMR) studies suggest disturbances in brain oxidative metabolism in experimental ALF. Glucose transport across the blood‐brain barrier is essential to sustain brain energy metabolism and is accomplished by the facilitative glucose transporter GLUT1. To investigate alterations in brain glucose uptake in acute liver failure further, GLUT1 expression and [14C]‐2‐deoxy‐D‐glucose uptake were measured in the brains of rats with hepatic devascularization. RT‐PCR and Western blot analyses showed significant increases in steady‐state levels of GLUT1 mRNA and protein in frontal cortex as early as 6 h following hepatic devascularization, (prior to the onset of brain edema and encephalopathy) which remained elevated at coma stages of encephalopathy. Expression of the astrocytic (45‐kDa) and endothelial (55‐kDa) forms of GLUT1 was increased as a result of hepatic devascularization. Exposure of cultured astrocytes to pathophysiologically relevant concentrations of ammonia resulted in increased GLUT1 expression, suggesting that elevated ammonia levels are responsible for GLUT1 upregulation in ALF. Increased GLUT1 expression in ALF was selective, since expression of the neuronal glucose transporter GLUT3 and other glucose‐regulated proteins (GRP‐78 and GRP‐94) was unaltered. [14C]‐2‐deoxy‐D‐glucose autoradiography revealed increases in cerebral glucose uptake following the induction of GLUT1 in ALF. These results suggest that ammonia‐induced increases of GLUT1 expression resulting in increased cerebral glucose uptake occur in ALF and could contribute to the pathophysiological mechanisms responsible for the neurological complications of this condition. © 2005 Wiley‐Liss, Inc.
Synthesis of multi‐labeled [14C]Aripiprazole
Authors: Bonacorsi Samuel J. , Waller Stephen C. , Kent Rinehart J.
Published: December 2005

Development of Aripiprazole as an oral treatment of schizophrenia required the synthesis of a suitably labeled drug product for use in human metabolism and pharmacokinetic studies. Due to the potential metabolic degradation of the molecule, a multi‐labeled approach utilizing 14C was adopted. The synthesis of [14C]Aripiprazole was accomplished in separate syntheses from 2,3‐dichloro[U‐14C]aniline and [3‐14C]‐cinnamic acid, respectively. Labeled versions were combined on the basis of molar radioactivity giving a final product with a radiochemical purity of 99.9% and a specific activity of 15.5 µCi/mg. Copyright © 2005 John Wiley & Sons, Ltd.
The no‐carrier‐added synthesis of bromine‐76 labeled alkenyl and alkynyl bromides using organotrifluoroborates
Authors: Kabalka George W. , Mereddy Arjun R. , Green James F.
Published: December 2005

A straightforward radiobromination procedure has been developed for the construction of radiobrominated alkenyl and alkynyl bromides. The organotrifluoroborates used as the reactive intermediates are unique in that they are quite polar and thus readily separated from the desired products. Copyright © 2005 John Wiley & Sons, Ltd.
Syntheses and radiofluorination of two derivatives of 5‐cyano‐indole as selective ligands for the dopamine subtype‐4 receptor
Authors: Tietze Rainer , Hocke Carsten , Löber Stefan , Hübner Harald , Kuwert Torsten , Gmeiner Peter , Prante Olaf
Published: December 2005

Two fluoroethoxy substituted derivatives, namely 2‐[4‐(2‐(2‐fluoroethoxy)phenyl)‐piperazin‐1‐ylmethyl]indole‐5‐carbonitrile (5a) and 2‐[4‐(4‐(2‐fluoroethoxy)‐phenyl)piperazin‐1‐ylmethyl]indole‐5‐carbonitrile (5b) were synthesized as analogs of the selective D4receptor ligand 2‐[4‐(4‐fluorophenyl)piperazin‐1‐ylmethyl]indole‐5‐carbonitrile (FAUC 316).In vitrocharacterization using CHO‐cells expressing different dopamine receptor subtypes gaveKivalues of 2.1 (5a) and 9.9 nM (5b) for the dopamine D4subtype and displayed a 420‐fold D4‐selectivity over D2receptors for5b. The para‐fluoroethoxy substituted candidate5brevealed substantially reducedα1and serotoninergic binding affinities in comparison to the ortho‐fluoroethoxy substituted compound. In order to provide potential positron emission tomography (PET) imaging probes for the dopamine D4receptor,18F‐labelling conditions using [18F]fluoroethyl tosylate were optimized and led to radiochemical yields of 81 ± 5% ([18F]5a) and 47 ± 4% ([18F]5b) (n= 3, decay‐corrected and referred to labelling agent), respectively. Thus,18F‐fluoroethylation favourably at the para position of the phenylpiperazine moiety of the 5‐cyano‐indole framework proved to be tolerated by D4receptors and could also be applied to alternative scaffolds in order to develop D4radioligand candidates for PET with improved D4receptor affinity and selectivity. Copyright © 2005 John Wiley & Sons, Ltd.
Homogenous Synthesis of Hydroxyethylcellulose in NaOH/Urea Aqueous Solution
Authors: Zhou Jinping , Qin Ye , Liu Shilin , Zhang Lina
Published: December 2005

Summary: Hydroxyethylcellulose (HEC) was synthesized by a fully homogenous method from cellulose in 7.5 wt.‐% NaOH/11 wt.‐% urea aqueous solutions under mild conditions. HEC samples were characterized with NMR, SEC‐LLS, solubility, and viscosity measurements. The MS and DS values of the obtained HEC samples are in the range from 0.54 to 1.44 and 0.45 to 1.14, respectively, and the relative DS values at C‐2 and C‐6 hydroxyl groups are slightly higher than those at C‐3 hydroxyl groups. HEC samples are soluble in water starting from a MS of 0.57 and DS of 0.49, which display high viscosity in aqueous solutions. Moreover, a NaOH/urea aqueous solution is a stable system for cellulose etherification. In this way, we could provide a simple, pollution‐free, and homogeneous aqueous solution system for synthesizing cellulose ethers.

13C NMR spectra of acetylated HEC (a) in CDCl3 at 40 °C and (b) in DMSO‐d6 at 100 °C.

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13C NMR spectra of acetylated HEC (a) in CDCl3 at 40 °C and (b) in DMSO‐d6 at 100 °C.
Preparation and Characterization of Novel Bone Scaffolds Based on Electrospun Polycaprolactone Fibers Filled with Nanoparticles
Authors: Wutticharoenmongkol Patcharaporn , Sanchavanakit Neeracha , Pavasant Prasit , Supaphol Pitt
Published: December 2005

Summary: Novel bone‐scaffolding materials were successfully fabricated by electrospinning from polycaprolactone (PCL) solutions containing nanoparticles of calcium carbonate (CaCO3) or hydroxyapatite (HA). The diameters of the as‐spun fibers were found to increase with the addition and increasing amounts of the nanoparticles. The observed increase in the diameters of the as‐spun fibers with the addition and increasing amounts of the nanoparticulate fillers was responsible for the observed increase in the tensile strength of the obtained fiber mats. An increase in the concentration of the base PCL solution caused the average diameter of the as‐spun PCL/HA composite fibers to increase. Increasing applied electrical potential also resulted in an increase in the diameters of the obtained PCL/HA composite fibers. Lastly, indirect cytotoxicity evaluation of the electrospun mats of PCL, PCL/CaCO3, and PCL/HA fibers based on human osteoblasts (SaOS2) and mouse fibroblasts (L929) revealed that these as‐spun mats posed no threat to the cells, a result that implied their potential for utilization as bone‐scaffolding materials.

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Materials for Peripheral Nerve Regeneration
Authors: Ciardelli Gianluca , Chiono Valeria
Published: December 2005

Summary: Recent efforts in scientific research in the field of peripheral nerve regeneration have been directed towards the development of artificial nerve guides. We have studied various materials with the aim of obtaining a biocompatible and biodegradable two layer guide for nerve repair. The candidate materials for use as an external layer for the nerve guides were poly(caprolactone) (PCL), a biosynthetic blend between PCL and chitosan (CS) and a synthesised poly(ester‐urethane) (PU). Blending PCL, which is a biocompatible synthetic polymer, with a natural polymer enhanced the system biocompatibility and biomimetics, fastened the degradation rates and reduced the production costs. Various novel block poly(ester‐urethane)s are being synthesised by our group with tailored properties for specific tissue engineering applications. One of these poly(ester‐urethane)s, based on a low molecular weight poly(caprolactone) as the macrodiol, cycloesandimethanol as the chain extender and hexamethylene diisocyanate as the chain linker, was investigated for the production of melt extruded nerve guides. We studied natural polymers such as gelatin (G), poly(L‐lysine) (PL) and blends between chitosan and gelatin (CS/G) as internal coatings for nerve guides. In vitro and in vivo tests were performed on PCL guides internally coated either with G or PL to determine the differences in the quality of nerve regeneration associated with the type of adhesion protein. CS/G natural blends combined the good cell adhesion properties of the protein phase with the ability to promote nerve regeneration of the polysaccharide phase. Natural blends were crosslinked both by physical and chemical crosslinking methods. In vitro neuroblast adhesion tests were performed on CS/G film samples, PCL/CS and PU guides internally coated with G to evaluate the ability of such materials towards nerve repair.

SEM image of a fractured section of a PCL melt extruded guide.

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SEM image of a fractured section of a PCL melt extruded guide.
Adsorption of Biopolyester Depolymerase on Silicon Wafer and Poly[(R)‐3‐hydroxybutyric acid] Single Crystal Revealed by Real‐Time AFM
Authors: Numata Keiji , Kikkawa Yoshihiro , Tsuge Takeharu , Iwata Tadahisa , Doi Yoshiharu , Abe Hideki
Published: December 2005

Summary: The adsorption behavior of PHB depolymerase from R. pickettii T1 on a silicon wafer and on P(3HB) single crystals has been studied by real‐time and AFM in air and a buffer solution. First, the morphology of PHB depolymerase adsorbed on a silicon wafer was characterized to show that one molecule of PHB depolymerase has dimensions of 2.2 ± 0.7 nm height and 16 ± 5 nm width. The observation of PHB depolymerase adsorbed on a P(3HB) single crystal indicated that the dimensions of enzyme on the crystalline surface in air were 1.2 ± 0.5 nm high and 28 ± 7 nm wide, while enzyme molecules with dimensions of 2.1 ± 0.6 nm height and 16 ± 7 nm width were detected in a buffer solution. Comparison of the dimensions of PHB depolymerase in air with those in a buffer solution showed that the enzyme was squashed in air, but not in a buffer solution. In addition, the influence of enzymatic adsorption on the molecular state of the P(3HB) crystalline surface was investigated. The AFM images of P(3HB) single crystals after enzymatic adsorption and washing with ethanol indicated that the adhesion of PHB depolymerase changed the molecular state and generated holes on the crystalline surface.

Illustration and AFM images of the adsorption process of PHB depolymerase on PHB single crystals.

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Illustration and AFM images of the adsorption process of PHB depolymerase on PHB single crystals.
Preparation of Nano‐Structured Polyaniline Composite Film via “Carbon Nanotubes Seeding” Approach and its Gas‐Response Studies
Authors: Ma Xingfa , Zhang Xiaobin , Li Yu , Li Guang , Wang Mang , Chen Hongzheng , Mi Yuhong
Published: December 2005

Summary: Polyaniline composite film with nano‐structure was prepared through a chemical oxidation method by adding carbon nanotubes (CNTs) as nano‐fiber seeds. Spin‐coating or casting method was employed on the interdigital electrodes of carbon and the composite film was formed with an in‐situ polymerization approach. The gas‐response to trimethylamine was also examined at room temperature. It was found that the difference was not only in the morphology, but also in the value of gas‐sensitivity. Comparing with films without the CNTs, the value of gas‐sensitivity decreased dramatically, while the baseline current of the sensor increased remarkably. This method can be an effective way to adjust the gas‐sensitivity of sensors made from polyaniline composite film by adding a small amount of carbon nanotube. XRD data showed that the degree of orientation of polyaniline was increased greatly with the addition of CNTs.

Morphology and reproducibility (inset) of polyaniline composite film containing carbon nanotubes.

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Morphology and reproducibility (inset) of polyaniline composite film containing carbon nanotubes.
Mechanical and Thermal Properties of Flexible Poly(propylene) Composites
Authors: Houshyar Shadi , Shanks Robert A.
Published: December 2005

Summary: The melting temperature difference between poly(propylene) (PP) fibre and random poly(propylene‐co‐ethylene) (PPE) was exploited to establish processing conditions for all‐PP composite. Under these conditions, the matrix must be liquid to ensure good wetting and impregnation of fibres, though temperatures must be low enough to avoid melting of fibres. The high chemical compatibility of the two components allowed creation of strong physico‐chemical interactions, favouring strong interfacial adhesion. Static and dynamic mechanical properties and morphology of all‐PP composites were investigated according to method of preparation and compared with the behaviour of hot compacted composites, prepared under different moulding conditions. The composites were compacted with varying pressure and time, and mechanical and thermal properties of the resulting sheets were measured. With increased moulding time, more fibres melted or their original properties deteriorated. Fast cooling or quenching caused imperfect morphology. Moulding pressure played an important role. Morphology of the optimum hot compacted composite was investigated using scanning electron microscopy before and after tensile testing. Tensile fracture surfaces showed a melted phase epitaxially crystallised onto the remaining orientated phase. Compacted composites showed fibre shapes under a thin layer of PPE with all of the gaps between fibres filled by melted PPE matrix.

SEM of compacted all‐PP composite without quenching.

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SEM of compacted all‐PP composite without quenching.
Multipass membrane protein structure prediction using Rosetta
Authors: Yarov‐Yarovoy Vladimir , Schonbrun Jack , Baker David
Published: December 2005

We describe the adaptation of the Rosetta de novo structure prediction method for prediction of helical transmembrane protein structures. The membrane environment is modeled by embedding the protein chain into a model membrane represented by parallel planes defining hydrophobic, interface, and polar membrane layers for each energy evaluation. The optimal embedding is determined by maximizing the exposure of surface hydrophobic residues within the membrane and minimizing hydrophobic exposure outside of the membrane. Protein conformations are built up using the Rosetta fragment assembly method and evaluated using a new membrane‐specific version of the Rosetta low‐resolution energy function in which residue–residue and residue–environment interactions are functions of the membrane layer in addition to amino acid identity, distance, and density. We find that lower energy and more native‐like structures are achieved by sequential addition of helices to a growing chain, which may mimic some aspects of helical protein biogenesis after translocation, rather than folding the whole chain simultaneously as in the Rosetta soluble protein prediction method. In tests on 12 membrane proteins for which the structure is known, between 51 and 145 residues were predicted with root‐mean‐square deviation <4 Å from the native structure. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Pressure perturbation calorimetry of helical peptides
Authors: Barrett Devin G. , Minder C. Michael , Mian Michelle U. , Whittington Shelly J. , Cooper W. John , Fuchs Kristin M. , Tripathy Ashutosh , Waters Marcey L. , Creamer Trevor P. , Pielak Gary J.
Published: December 2005

Pressure perturbation calorimetry quantifies the temperature dependence of a solute's thermal expansion coefficient, providing information about solute–solvent interactions. We tested the idea that pressure perturbation calorimetry can provide information about solvent‐accessible surface area by studying peptides with different secondary structures. The peptides comprised two host–guest series: one predominately an α‐helix, the other predominately a polyproline II helix. In aqueous buffer, we find a correlation between the amount of secondary structure as assessed by circular dichroism spectropolarimetry and the pressure perturbation calorimetry data. We conclude that pressure perturbation calorimetry can provide information about the exposure of polar and nonpolar surface area. Data acquired in a buffered urea solution, however, are not as easily interpreted. Proteins 2006. © 2005 Wiley‐Liss, Inc.
A topology‐constrained distance network algorithm for protein structure determination from NOESY data
Authors: Huang Yuanpeng Janet , Tejero Roberto , Powers Robert , Montelione Gaetano T.
Published: December 2005

This article formulates the multidimensional nuclear Overhauser effect spectroscopy (NOESY) interpretation problem using graph theory and presents a novel, bottom‐up, topology‐constrained distance network analysis algorithm for NOESY cross peak interpretation using assigned resonances. AutoStructure is a software suite that implements this topology‐constrained distance network analysis algorithm and iteratively generates structures using the three‐dimensional (3D) protein structure calculation programs XPLOR/CNS or DYANA. The minimum input for AutoStructure includes the amino acid sequence, a list of resonance assignments, and lists of 2D, 3D, and/or 4D‐NOESY cross peaks. AutoStructure can also analyze homodimeric proteins when X‐filtered NOESY experiments are available. The quality of input data and final 3D structures is evaluated using recall, precision, and F‐measure (RPF) scores, a statistical measure of goodness of fit with the input data. AutoStructure has been tested on three protein NMR data sets for which high‐quality structures have previously been solved by an expert, and yields comparable high‐quality distance constraint lists and 3D protein structures in hours. We also compare several protein structures determined using AutoStructure with corresponding homologous proteins determined with other independent methods. The program has been used in more than two dozen protein structure determinations, several of which have already been published. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Blast wave propagation in city streets—an overview
Authors: Smith Peter D , Rose Timothy A
Published: December 2005

This paper presents an overview of research conducted by the authors and others both experimentally and analytically in the area of blast wave interactions with buildings and structures in an urban landscape. Empirical tools for the assessment of blast wave resultants for simple‐geometry situations are first presented before the confining effects of buildings along a street are discussed. Street layouts such a T‐junctions and crossroads are then introduced and the way that blast wave characteristics are affected by street width and the height of buildings along the street is assessed. The influence of the location of the explosive charge within the street layout on the blast load experienced by buildings is also reviewed. It is likely that building façades closest to the explosion will fail and the effect on the loading experienced further from the detonation is therefore assessed. A complementary study of the loads developed inside a building whose façade has failed is also discussed. Apart from the blast loads on buildings in a street in which there is an explosion, buildings in adjacent streets will also experience blast loading. Studies concerned with the phenomena of ‘channelling’ and ‘shielding’ are presented and the extent to which both processes occur in any given situation discussed. The various studies reported throughout the paper indicate that simple tools are often inappropriate and the development of empirical rules for more complex geometries may not be reliable. This view is supported by studying blast wave propagation in a realistic cityscape comprising streets of different widths with several layout features all bounded by buildings of different size, shape and height. Such studies conclude that computational fluid dynamics analyses may sometimes be the only satisfactory approach for the engineer seeking a reliable assessment of blast loads experienced by buildings in an urban landscape.
Differentiation of fluoronitroaniline isomers by negative‐ion electrospray mass spectrometry
Authors: Gierczyk Blażej , Grajewski Jakub , Zalas Maciej
Published: December 2005

Tetra‐ and trifluoronitroanilines were studied by electrospray ionization mass spectrometry. These compounds gave signals only in the negative‐ion mode. It was found that the so‐called ‘in‐source’ fragmentation, induced by cone voltage increase, enables differentiation of isomers. For para‐nitroanilines, in contrast to ortho derivatives, the loss of NO2 was the most favored process and other fragment ions were characterized by low abundances. For trifluoro conjugates the substitution pattern of aromatic ring by fluorine atoms also affected their fragmentation patterns. For example, in 2,3,6‐trifluoro‐4‐nitroaniline, in contrast to 2,3,5‐trifluoro‐4‐nitroaniline, efficient NO loss, followed by HF loss, took place. Copyright © 2005 John Wiley & Sons, Ltd.
Young, black, and male in foster care: Relationship of negative social contextual experiences to factors relevant to mental health service delivery
Authors: Scott Lionel D. , Davis Larry E.
Published: December 2005

Among a small, cross‐sectional sample of young Black males transitioning from foster care (), this study explored the relationship of their negative social contextual experiences to two factors relevant to the delivery of mental health services to them: cultural mistrust of mental health professionals and attitudes toward seeking professional help. Three domains of young Black male's negative social contextual experiences were measured: proximal negative experiences, distal negative experiences, and negative imagery experiences. Results of multivariate analysis of covariance (MANCOVA) controlling for custody status, counselling status and history, and psychiatric history showed that young Black males reporting a high frequency of negative social contextual experiences reported significantly greater cultural mistrust of mental health professionals and significantly less positive attitudes toward seeking professional help for mental health problems than young Black males reporting a low frequency of negative social contextual experiences. Implications and future research directions are discussed.