bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Haloperidol Promotes Corticostriatal Long-Term Potentiation by Targeting Dopamine D2L Receptors
Authors: Centonze Diego , Usiello Alessandro , Costa Cinzia , Picconi Barbara , Erbs Eric , Bernardi Giorgio , Borrelli Emiliana , Calabresi Paolo
Published: September 2004

Reduced glutamate-mediated synaptic transmission has been implicated in the pathophysiology of schizophrenia. Because antipsychotic agents might exert their beneficial effects against schizophrenic symptoms by strengthening excitatory transmission in critical dopaminoceptive brain areas, in the present study we have studied the effects of acute and chronic haloperidol treatment on striatal synaptic plasticity. Repetitive stimulation of corticostriatal terminals in slices induced either long-term depression or long-term potentiation (LTP) of excitatory transmission in control rats, whereas it invariably induced NMDA receptor-dependent LTP in animals treated chronically with haloperidol. Haloperidol effects were mimicked and occluded in mice lacking both D2L and D2S isoforms of dopamine D2 receptors (D2R-/-), in mice lacking D2L receptors and expressing normal levels of D2S receptors (D2R-/-;D2L-/-), and in mice lacking D2L receptors and overexpressing D2S receptors (D2L-/-). These data indicate that the blockade of D2L receptors was responsible for the LTP-favoring action of haloperidol in the striatum. In contrast, overexpression of D2S receptors uncovered a facilitatory role of this receptor isoform in LTP formation because LTP recorded from D2L-/- mice, but not those recorded from wild-type, D2R-/-, and D2R-/-;D2L-/- mice, was insensitive to the pharmacological blockade of D1 receptors.

The identification of the cellular, molecular, and receptor mechanisms involved in the action of haloperidol in the brain is essential to understand how antipsychotic agents exert their beneficial and side effects.
Alcohol Tolerance in Large-Conductance, Calcium-Activated Potassium Channels of CNS Terminals Is Intrinsic and Includes Two Components: Decreased Ethanol Potentiation and Decreased Channel Density
Authors: Pietrzykowski Andrzej Z. , Martin Gilles E. , Puig Sylvie I. , Knott Thomas K. , Lemos Jose R. , Treistman Steven N.
Published: September 2004

Tolerance is an important element of drug addiction and provides a model for understanding neuronal plasticity. The hypothalamic–neurohypophysial system (HNS) is an established preparation in which to study the actions of alcohol. Acute application of alcohol to the rat neurohypophysis potentiates large-conductance calcium-sensitive potassium channels (BK), contributing to inhibition of hormone secretion. A cultured HNS explant from adult rat was used to explore the molecular mechanisms of BK tolerance after prolonged alcohol exposure. Ethanol tolerance was intrinsic to the HNS and consisted of: (1) decreased BK potentiation by ethanol, complete within 12 min of exposure, and (2) decreased current density, which was not complete until 24 hr after exposure, indicating that the two components of tolerance represent distinct processes. Single-channel properties were not affected by chronic exposure, suggesting that decreased current density resulted from downregulation of functional channels in the membrane. Indeed, we observed decreased immunolabeling against the BK α-subunit on the surface of tolerant terminals. Analysis using confocal microscopy revealed a reduction of BK channel clustering, likely associated with the internalization of the channel.
Role of Purpurin as a Retinol-Binding Protein in Goldfish Retina during the Early Stage of Optic Nerve Regeneration: Its Priming Action on Neurite Outgrowth
Authors: Matsukawa Toru , Sugitani Kayo , Mawatari Kazuhiro , Koriyama Yoshiki , Liu Zhongwu , Tanaka Masayuki , Kato Satoru
Published: September 2004

Unlike mammals, the fish optic nerve can regenerate after injury. So far, many growth or trophic factors have been shown as an axon-regenerating molecule. However, it is totally unknown what substance regulates or triggers the activity of these factors on axonal elongation. Therefore, we constructed a goldfish retina cDNA library prepared from the retina treated with optic nerve transection 5 d previously, when it was just before regrowing optic axons after injury. A cDNA clone for goldfish purpurin for which expression was upregulated during the early stage of optic nerve regeneration was isolated from the retina cDNA library. Purpurin was discovered as a secretory retinol-binding protein in developing chicken retinas. Levels of purpurin mRNA and protein transiently increased and rapidly decreased 2–5 d and 10 d after axotomy, respectively. Purpurin mRNA was localized to the photoreceptor cells, whereas the protein was diffusely found in all of the retinal layers. A recombinant purpurin alone did not affect any change of neurite outgrowth in explant culture of the control retina, whereas a concomitant addition of the recombinant purpurin and retinol first induced a drastic enhancement of neurite outgrowth. Furthermore, the action of retinol-bound purpurin was effective only in the control (untreated) retinas but not in those primed (treated) with a previous optic nerve transection. Thus, purpurin with retinol is the first candidate molecule of priming neurite outgrowth in the early stage of optic nerve regeneration in fish.
Cycling of NMDA Receptors during Trafficking in Neurons before Synapse Formation
Authors: Washbourne Philip , Liu Xiao-Bo , Jones Edward G. , McAllister A. Kimberley
Published: September 2004

The trafficking of glutamate receptors in neurons is of the utmost importance for synapse formation and synaptic plasticity. Recently, we demonstrated that both NMDA and AMPA receptors reside in mobile transport packets that are recruited rapidly and independently to nascent synapses. Here, we show that a large proportion of the glutamate receptor clusters in young cortical neurons are present on the surface of dendrites before synapses are formed and these surface-exposed transport packets are mobile. Exocytosis of glutamate receptors to the dendritic surface occurs via a SNARE [solublen-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor]-dependent SNAP-23-mediated mechanism. Endocytosis occurs rapidly after surface exposure; >50% of surface-labeled NMDA receptors (NMDARs) are endocytosed within 5 min. NMDARs are transported along microtubules on large tubulovesicular organelles, as indicated by immunoelectron microscopy, and are associated with EEA1 (early endosomal antigen 1) and SAP102 (synapse-associated protein 102), as indicated by immunocytochemistry. Most surprisingly, a large proportion of these transport packets cycle through the dendritic plasma membrane before synapse formation. These results suggest a novel model in which NMDARs cycle with the plasma membrane during pauses of movement along microtubules while trafficking.
Entrainment to Video Displays in Primary Visual Cortex of Macaque and Humans
Authors: Williams Patrick E. , Mechler Ferenc , Gordon James , Shapley Robert , Hawken Michael J.
Published: September 2004

Cathode ray tubes (CRTs) display images refreshed at high frequency, and the temporal waveform of each pixel is a luminance impulse only a few milliseconds long. Although humans are perceptually oblivious to this flicker, we show in V1 in macaque monkeys and in humans that extracellularly recorded action potentials (spikes) and visual-evoked potentials (VEPs) align with the video impulses, particularly when high-contrast stimuli are viewed. Of 91 single units analyzed in macaque with a 60 Hz video refresh, 29 cells (32%) significantly locked their firing to a uniform luminance display, but their number increased to 75 (82%) when high-contrast stimuli were shown. Of 92 cells exposed to a 100 Hz refresh, 21 (23%) significantly phase locked to high-contrast stimuli. Phase locking occurred in both input and output layers of V1 for simple and complex cells, regardless of preferred temporal frequency. VEPs recorded in humans showed significant phase locking to the video refresh in all seven observers. Like the monkey neurons, human VEPs more typically phase locked to stimuli containing spatial contrast than to spatially uniform stimuli. Phase locking decreased when the refresh rate was increased. Thus in humans and macaques phase locking to the high strobe frequency of a CRT is enhanced by a salient spatial pattern, although the perceptual impact is uncertain. We note that a billion people worldwide manage to watch TV without obvious distortion of their visual perception despite extraordinary phase locking of their V1s to a 50 or 60 Hz signal.
Aging Results in Reduced Epidermal Growth Factor Receptor Signaling, Diminished Olfactory Neurogenesis, and Deficits in Fine Olfactory Discrimination
Authors: Enwere Emeka , Shingo Tetsuro , Gregg Christopher , Fujikawa Hirokazu , Ohta Shigeki , Weiss Samuel
Published: September 2004

Previous studies demonstrating olfactory interneuron involvement in olfactory discrimination and decreased proliferation in the forebrain subventricular zone with age led us to ask whether olfactory neurogenesis and, consequently, olfactory discrimination were impaired in aged mice. Pulse labeling showed that aged mice (24 months of age) had fewer new interneurons in the olfactory bulb than did young adult (2 months of age) mice. However, the aged mice had more olfactory interneurons in total than their younger counterparts. Aged mice exhibited no differences from young adult mice in their ability to discriminate between two discrete odors but were significantly poorer at performing discriminations between similar odors (fine olfactory discrimination). Leukemia inhibitory factor receptor heterozygote mice, which have less neurogenesis and fewer olfactory interneurons than their wild-type counterparts, performed more poorly at fine olfactory discrimination than the wild types, suggesting that olfactory neurogenesis, rather than the total number of interneurons, was responsible for fine olfactory discrimination. Immunohistochemistry and Western blot analyses revealed a selective reduction in expression levels of epidermal growth factor (EGF) receptor (EGFR) signaling elements in the aged forebrain subventricular zone. Waved-1 mutant mice, which express reduced quantities of transforming growth factor-α, the predominant EGFR ligand in adulthood, phenocopy aged mice in olfactory neurogenesis and performance on fine olfactory discrimination tasks. These results suggest that the impairment in fine olfactory discrimination with age may result from a reduction in EGF-dependent olfactory neurogenesis.
Spectroscopy: Applications
Authors: Serrano‐Andrés Luis , Merchán Manuela
Published: September 2004

Recent years have seen an extraordinary development in the applicability and accuracy ofab initiomethods to compute molecular excited states, which are now generally determined with a precision of 0.1–0.2 eV. The size and character of the problems have increased to make the calculations competitive and complementary to the experimental determinations involving medium and large molecular systems. Many examples can be provided of this new era in the quantum chemistry of the excited state where the multiconfigurational methods, in particular, CASPT2, have been the main protagonists. The present article contains an account of the types and nature of excited states, a compilation of methods, strategies, and problems to be solved in the calculation of molecular excited states, particularly to obtain electronic transition energies and properties, such as band intensities and state lifetimes. Finally, a number of examples and achievements in the field give an overall view of what can be computed nowadays and how the computations can be performed. Illustrative examples include the calculation of dark states, vibrational resolution of electronic bands, novel assignments, interplay between theoretical spectroscopy and experiment, and adiabatic and nonadiabatic photochemical processes.
The Use of N‐Alkyl‐2,2′‐bipyrrolidine Derivatives as Organocatalysts for the Asymmetric Michael Addition of Ketones and Aldehydes to Nitroolefins
Authors: Andrey Olivier , Alexakis Alexandre , Tomassini Axel , Bernardinelli Gerald
Published: September 2004

The direct Michael addition of aldehydes and ketones to nitroolefins, catalyzed by N‐i‐Pr‐2,2′‐bipyrrolidine, is described. The desired 1,4‐adducts are obtained in excellent yields with enantioselectivities up to 95% ee and dr up to 95 : 5 of the syn aldehyde addition product. An unexpected inversion of diastereoselectivity was observed for the addition of α‐hydroxy ketones to β‐arylnitroolefins with enantioselectivities up to 98% ee. The formation of an internal hydrogen bond between the OH group of the α‐hydroxy ketone and the tertiary nitrogen of the catalyst leads to the formation of a rigid cis enamine intermediate that accounts for the inversion of the expected diastereoselectivity and the very high ees.
A New Approach to Axially Chiral Bipyridine N,N′‐Dioxides Bearing Aromatic Substituents and their Use for Catalytic Asymmetric Allylation of Aldehydes with Allyl(trichloro)silane
Authors: Kina Asato , Shimada Toyoshi , Hayashi Tamio
Published: September 2004

Palladium‐catalyzed cross‐coupling of bipyridine N,N′‐dioxide 6,6′‐dichloride (Rnap,Rpyr)‐1 with the aryl Grignard reagents opened a new approach to axially chiral bipyridine N,N′‐dioxides (R)‐2 bearing a variety of aryl groups at the 6 and 6′ positions. One of the N,N′‐dioxides (R)‐2d which is substituted with 3,5‐dimethyl‐4‐methoxy groups was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyl(trichloro)silane. The allylation took place with 0.01–0.1 mol % of (R)‐2d giving homoallyl alcohols of up to 94% ee.
Planar Chiral PHANOLs as Double Hydrogen Bonding Donor Organocatalysts: Synthesis and Catalysis
Authors: Braddock D. Christopher , MacGilp Iain D. , Perry Benjamin G.
Published: September 2004

4,12‐Dihydroxy[2.2]paracyclophanediol (PHANOL; 1), and its para‐substituted derivatives 2, 5 and 7, were found to catalyse Diels–Alder cycloadditions of α,β‐unsaturated aldehydes or ketones with dienes and/or epoxide ring opening reactions with amines. The mode of catalysis by the PHANOLs is via double hydrogen bonding to the two sp2 lone pairs of a carbonyl group or the two lone pairs of the epoxide. The order of activity of the PHANOLs for catalysis of the Diels–Alder reaction essentially correlates with the expected hydrogen‐bond donor strength based on the degree of electron‐withdrawing capability of the group(s) in the para position. In contrast, ortho‐substituted PHANOLs 10, 11 and 14 were not active as catalysts due to steric interference with the double hydrogen bonding mode. 1H NMR and IR spectral data for the various PHANOLs are discussed in support of the proposed double hydrogen bond mode.
The Chiral Diamine Mediated Asymmetric Baylis–Hillman Reaction
Authors: Hayashi Yujiro , Tamura Tomohiro , Shoji Mitsuru
Published: September 2004

A chiral diamine, easily prepared from proline, is an effective, asymmetric organic catalyst for the Baylis–Hillman reaction of aldehydes and methyl vinyl ketone, affording adducts with enantioselectivities up to 75%.
Esterolytic Peptide Dendrimers with a Hydrophobic Core and Catalytic Residues at the Surface
Authors: Clouet Anthony , Darbre Tamis , Reymond Jean‐Louis
Published: September 2004

(3S)‐4‐(9‐Fluorenylmethoxycarbonylamino)‐3‐methyl(allyloxycarbonyl)aminoethyloxyacetic acid (1) was prepared from (R)‐3‐aminopropane‐1,2‐diol and used as branching unit for the synthesis of second generation peptide dendrimers with six individually addressable variable amino acid positions. Three pairs of diastereomeric dendrimers were prepared bearing a common hydrophobic core and permutations of the catalytic triad amino acids aspartate, histidine and serine at the surface. Dendrimers with two surface histidine residues catalyzed the hydrolysis of fluorogenic 8‐acyloxypyrene‐1,3,6‐trisulfonates in aqueous buffer pH 6.0 with rate enhancement kcat/kuncat in the 103 range and Michaelis‐Menten constants KM in the 10−4 M range. Substrate recognition involves electrostatic interactions, as shown by competitive inhibition of catalysis observed with pyrene‐1,3,6,8‐tetrasulfonate. The 4‐fold to 7‐fold lowering in KM between the butyryl and nonanoyl esters in the most active dendrimers provides evidence for a hydrophobic component in substrate binding, which is absent in a closely related, less active diastereomeric peptide dendrimer.
Functionalization of Alkynes Catalyzed byt‐Bu‐P4 Base
Authors: Imahori Tatsushi , Hori Chieko , Kondo Yoshinori
Published: September 2004

The addition of O‐ and N‐nucleophiles to alkynes catalyzed by a phosphazene base,t‐Bu‐P4 base, was investigated. Alkynes were easily transformed to enol ethers and enamines in DMSO by the addition of nucleophiles. When phenylacetylene was reacted with diisopropylamine, a unique head‐to‐head dimerization of phenylacetylene was observed to give the enyne derivative. Terminal proton of phenylacetylene was also catalytically activated byt‐Bu‐P4 base to generate the acetylide anion which was reacted with carbonyl compounds to give phenylpropargylic alcohol derivatives.
Aza‐Baylis–Hillman Reactions of N‐(Arylmethylene)diphenylphosphinamides with Activated Olefins in the Presence of Various Lewis Bases
Authors: Shi Min , Zhao Gui‐Ling
Published: September 2004

The aza‐Baylis–Hillman reactions of N‐(arylmethylene)diphenylphosphinamides with methyl vinyl ketone (MVK), methyl acrylate, acrylonitrile, ethyl vinyl ketone (EVK), phenyl vinyl ketone (PVK), phenyl acrylate, 2‐cyclopenten‐1‐one, 2‐cyclohexen‐1‐one have been systemically investigated in the presence of various Lewis bases. The Lewis base and solvent effects in these reactions have been discussed. A new class of double aza‐Baylis–Hillman reactions (in some cases exclusively) and their further transformations including catalytic, asymmetric version in the presence of chiral nitrogen and phosphine Lewis bases have been disclosed in this paper.
Direct Organocatalytic Ring‐Opening Polymerizations of Lactones
Authors: Casas Jesús , Persson Per Valdemar , Iversen Tommy , Córdova Armando
Published: September 2004

We have developed a novel organocatalytic, direct synthesis of aliphatic polyesters. The synthesis was based on a novel direct organic acid‐catalyzed living ring‐opening polymerization (ROP) of ε‐caprolactone and δ‐valerolactone with benzyl alcohol as the initiator. The organic acid‐catalyzed ROPs were performed without solvent and the catalyst was recovered by precipitation of the polyester products. In addition, they were operationally simple, inexpensive and environmentally benign. Organic acid catalysis provides a new entry for the synthesis of valuable biodegradable materials as well as polyesters for biomedical applications.
Product‐Catalyzed Aldol Reaction between Trimethylsilyl Enolates and Aldehydes
Authors: Fujisawa Hidehiko , Nakagawa Takashi , Mukaiyama Teruaki
Published: September 2004

Aldol reactions between trimethylsilyl ketene acetals and aldehydes by using a catalytic amount of alkoxide anion proceeded smoothly to afford the corresponding aldols in DMF, indicating that the initially‐formed aldolate anion effectively worked to catalyze the reaction. The “product‐catalyzed aldol reaction”, a new class Lewis base‐catalyzed aldol reaction, between trimethylsilyl ketene acetals and aldehydes was performed successfully by the use of aldolate anion as a Lewis base catalyst.
Nucleophilic Phosphine Organocatalysis
Authors: Methot Joey L. , Roush William R.
Published: September 2004

Phosphines have recently become popular choices as nucleophilic catalysts in organic synthesis. The unique reactivity of phosphines compared to amines has allowed the discovery of new nucleophilic addition reactions at the α‐ and γ‐positions of unsaturated carbonyl compounds, as well as novel [3+2] and [4+2] cycloaddition reactions of activated alkynes and alkenes. The accessibility of chiral phosphines has rendered several of these transformations enantioselective and has made possible the kinetic resolution of racemic secondary alcohols by phosphine‐catalyzed acylation. This mini‐review presents recent advances in nucleophilic phosphine organocatalysis for carbon‐carbon bond formation.
First Synthesis of a Highly Basic Dendrimer and its Catalytic Application in Organic Methodology
Authors: Sarkar Arunkanti , Ilankumaran Palanichamy , Kisanga Philip , Verkade John G.
Published: September 2004

Sixteen OCH2CH2N3P(i‐BuNCH2CH2)3N substituents (A) containing the highly basic bicyclic azido‐phosphine moiety shown, have been incorporated into the dendrimer [CH2CH2N[(CH2)3N[(CH2)3NHC(O)‐3,5‐bis‐(A)‐C6H3]2]2]2 in five steps from commercially available starting materials with an overall yield of 22.5%. Also presented are examples of Michael additions, nitroaldol reactions and aryl isocyanate trimerizations that are efficiently catalyzed by the dendrimer.
Thiazolium Ylide‐Catalyzed Intramolecular Aldehyde$\rm{-}$Ketone Benzoin‐Forming Reactions: Substrate Scope
Authors: Hachisu Yoshifumi , Bode Jeffrey W. , Suzuki Keisuke
Published: September 2004

The scope and limitations of intramolecular benzoin‐forming reactions of aldehydes and ketones catalyzed by the combination of a thiazolium salt and a base are described. After optimization of the reaction conditions, five‐ and six‐membered cyclic acyloins were obtained in good to excellent yields and competing reactions such as intramolecular aldol reactions were suppressed. The analogous closure of seven‐membered rings proved difficult.
Bredereck's Reagent Revisited: Latent Anionic Ring‐Opening Polymerization and Transesterification Reactions
Authors: Csihony Szilárd , Beaudette Tristan T. , Sentman Alan C. , Nyce Gregory W. , Waymouth Robert M. , Hedrick James L.
Published: September 2004

The ring‐opening polymerization of lactide with commercially available Bredereck‐type reagents in the presence or absence of alcohol initiators was carried out affording polylactide with controlled molecular weight and narrow polydispersities. An anionic mechanism involving heterolytic cleavage to alkoxides is proposed, where these reagents function as latent anionic initiators for the ring‐opening polymerization of lactide.
N‐Arenesulfonyl‐2‐aminomethylpyrrolidines $\rm{-}$ Novel Modular Ligands and Organocatalysts for Asymmetric Catalysis
Authors: Dahlin Nils , Bøgevig Anders , Adolfsson Hans
Published: September 2004

A novel series of (S)‐N‐arenesulfonyl‐2‐aminomethylpyrrolidines were prepared in high overall yield starting from N‐Boc‐L‐proline. The mono‐sulfonyldiamines were evaluated as organocatalysts in the asymmetric α‐amination of propanal using diethyl azadicarboxylate (DEAD) as the amine source. The initially formed α‐aminated aldehyde was reduced in situ to the corresponding N‐aminooxazolidinone, which was obtained in moderate to high yield in up to 87% ee.
Neutral Coordinate‐Organocatalysts in Organic Synthesis: Allylation of Acylhydrazones with Allyltrichlorosilanes
Authors: Kobayashi Shū , Sugiura Masaharu , Ogawa Chikako
Published: September 2004

N,N‐Dimethylformamide (DMF), sulfoxides, and phosphine oxides, etc., which are neutral, uncharged molecules and coordinate to silicon atoms of organosilicon reagents to activate nucleophilic addition, are defined as neutral coordinate‐organocatalysts (NCOs). In the presence of NCOs, allylation reactions of acylhydrazones, useful imine surrogates, using allyltrichlorosilanes proceed smoothly to afford the synthetically useful racemic and non‐racemic homoallylic amine derivatives in high yields with high diastereoselectivities.
Theoretical Explorations of Enantioselective Alkylation Reactions of Pyrroles and Indoles Organocatalyzed by Chiral Imidazolidinones
Authors: Gordillo Ruth , Carter Jennifer , Houk K. N.
Published: September 2004

The transition structures for MacMillan's alkylations of N‐methylpyrrole by aldehydes catalyzed by chiral amine salts were explored with B3LYP/6‐31G(d) density functional theory. These results provide an explanation of the enantioselectivities observed with these two catalysts.
The Scope of the Direct Proline‐Catalyzed Asymmetric Addition of Ketones to Imines
Authors: Notz Wolfgang , Watanabe Shin‐ichi , Chowdari Naidu S. , Zhong Guofu , Betancort Juan M. , Tanaka Fujie , Barbas Carlos F.
Published: September 2004

A full account of catalytic direct asymmetric Mannich‐type reactions is presented describing the scope of amino acid‐catalyzed additions of unmodified ketones to a large variety of imines. These reactions are performed under very mild, operationally simple, and environmentally friendly and benign conditions employing a one‐pot, three‐component protocol as well as preformed imines. Typically, products were obtained with high regio‐ and diastereoselectivities and excellent enantioselectivities. The methodology developed was applied as a powerful approach toward the synthesis of enantiomerically pure functionalized α‐amino acids, γ‐lactones, oxime‐functionalized amino acids as well as pharmacologically important targets such as (R)‐cyclohexylglycine.
Molecular cytogenetic characterization of ring chromosome 15 in three unrelated patients
Authors: Tümer Z. , Harboe T.L. , Blennow E. , Kalscheuer V.M. , Tommerup N. , Brøndum‐Nielsen K.
Published: September 2004

We report molecular cytogenetic characterization of ring chromosome 15 in three unrelated male patients with the karyotype 46,XY,r(15). One was a stillborn child with several malformations, and the other two cases showed pre‐ and postnatal growth retardation and developmental delay, common features for ring chromosome 15 syndrome. One of these patients also displayed clinical features resembling Prader–Willi syndrome (PWS). To delineate the extent of the deletion on chromosome 15, we have carried out fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs) mapping to the distal long arm of chromosome 15. The deletion breakpoints clustered within a 4.5–6.5 Mb region proximal to the 15q telomere. Two deletions involved the same known genes, while the largest deletion observed in the stillborn child involved three additional genes, including the COUP‐TFII gene, which has been suggested to play a role in heart development. The heart malformations, which are observed in this patient, are thus likely to be due to hemizygosity/haploinsufficiency of the COUP‐TFII gene. In all three patients, the insulin‐like growth factor I receptor gene (IGF1R) gene was deleted supporting the association between IGF1R and growth retardation seen in ring chromosome 15 syndrome. © 2004 Wiley‐Liss, Inc.
Genomewide search and association studies in a Finnish celiac disease population: Identification of a novel locus and replication of the HLA and CTLA4 loci
Authors: Rioux John D. , Karinen Hannele , Kocher Kerry , McMahon Sheila Guschwan , Kärkkäinen Päivi , Janatuinen Esko , Heikkinen Markku , Julkunen Risto , Pihlajamäki Jussi , Naukkarinen Anita , Kosma Veli‐Matti , Daly Mark J. , Lander Eric S. , Laakso Markku
Published: September 2004

It has been reported that celiac disease (CD) is strongly associated with the HLA‐DQ2 alleles DQA1*0501 and DQB1*0201. However, this association only accounts for a portion of the genetic component of CD. Several non‐HLA loci and candidate genes that potentially contribute to CD susceptibility have been reported, but have not been confirmed. The aim of this study was to identify loci that contribute to disease susceptibility in a CD population from Finland. We performed a genomewide linkage scan and identified two regions of significant linkage to CD (6p and 2q23‐32) and one region of suggestive linkage (10p). We also performed targeted typing and analyses that replicated the associations of the HLA and CTLA4 loci. © 2004 Wiley‐Liss, Inc.
Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: A population‐based Swedish cohort study
Authors: Cnattingius Sven , Reilly Marie , Pawitan Yudi , Lichtenstein Paul
Published: September 2004

There is accumulated evidence for genetic influences on preeclampsia. However, no study has been able to separate the effects of maternal and fetal genetic factors from environmental factors, and there are still uncertainties about the origin and magnitude of the genetic effects. We used the population‐based Swedish Birth and Multi‐Generation Registries to identify a cohort of women who gave birth from 1987 through 1997. In order to separate the genetic and environmental contributions to preeclampsia, we analyzed pregnancy outcomes from families joined by full siblings. We included information from 244,564 sibling pairs (62,236 sister pairs, 63,288 brother pairs, and 119,040 sister–brother pairs), who had 701,488 pregnancies. We found that 35% of the variance in liability of preeclampsia was attributable to maternal genetic effects, 20% to fetal genetic effects (with similar contribution of maternal and paternal genetic effects), 13% to the couple effect, less than 1% to shared sibling environment, and 32% to unmeasured factors. Among women and men without a history of preclampsia, partner change reduced the risk of preeclampsia (odds ratio, 0.6; 95 percent confidence interval, 0.4–0.9). Genetic factors account for more than half of the liability of preeclampsia, and maternal genes contribute more than fetal genes. We suggest that the couple effect is due to a genetic interaction between mother and father. © 2004 Wiley‐Liss, Inc.
Monozygotic twins discordant for frontonasal malformation
Authors: Mohammed Shehla N. , Swan Marc C. , Wall Steven A. , Wilkie Andrew O.M.
Published: September 2004

Frontonasal malformation (FNM), also known as the median cleft face syndrome, encompasses a spectrum of phenotypes that are believed to result from a single underlying aetiology. Over the course of two decades, the Craniofacial Unit at the Radcliffe Infirmary, Oxford has been involved in the management of six same‐sex twins where only a single twin is affected. With local ethical committee approval, five sets of twins were traced and consented to participation in this study. Monozygosity of all five twin pairs was confirmed, and the clinical features were reviewed. We discuss the mechanistic relationship between FNM and the twinning process and the genetic implications of this association. © 2004 Wiley‐Liss, Inc.
A case of tangier disease with a novel mutation in the c‐terminal region of ATP‐binding cassette transporter A1
Authors: Guan Jing‐Zhi , Tamasawa Naoki , Brunham Liam R. , Matsui Jun , Murakami Hiroshi , Suda Toshihiro , Ochiai Shigeru , Tsutsui Masahiro , Kudou Kenji , Satoh Kei , Hayden Michael R.
Published: September 2004

Tangier disease (TD), a rare disorder characterized by extremely low levels of high density lipoprotein cholesterol (HDL‐C), is caused by mutations in the ATP‐binding cassette transporter A1 (ABCA1) gene. Here, we describe a new patient with TD. The 42‐year‐old proband had obvious juvenile cataracts, mild hepatosplenomegaly, and an extremely low level of HDL‐C (1 mg/dl), consistent with the diagnosis of TD. The proband was homozygous for a novel CTC6914‐6TT → 2203X mutation in the carboxy terminus of the ABCA1 protein. ApoAI‐mediated cholesterol efflux from patient fibroblasts was markedly decreased compared to control, despite normal levels of protein expression. This indicates that this mutant protein is normally transcribed and exists as a stable product, yet is functionally defective. These results point to a critical role for the intracellular C‐terminal region of the ABCA1 gene product in regulating cholesterol efflux and HDL‐cholesterol levels. © 2004 Wiley‐Liss, Inc.
Clinical variability in KBG syndrome: Report of three unrelated families
Authors: Maegawa Gustavo Henrique Boff , Leite Júlio Cesar Loguercio , Félix Têmis Maria , da Silveira Heraldo Luís Dias , da Silveira Heloísa Emília
Published: September 2004

The KBG syndrome is characterized by short stature, macrodontia, a specific combination of minor anomalies, developmental delay, and/or mental retardation. We reported on four patients from three unrelated families. The most frequent clinical findings were: atypical face, long/flat philtrum, thin upper lip, macrodontia, dental malposition, enamel hypoplasia, and cleft teeth. Skeletal anomalies such as cervical ribs and vertebral abnormalities were also noted. Hand anomalies were observed in three patients. Mental retardation and developmental delay were present in three of the four patients. There is wide clinical variability in the expression of this syndrome. The males are usually more severely affected then the females, suggesting possible X‐linked inheritance in some cases. © 2004 Wiley‐Liss, Inc.
Ocular coloboma and high myopia with Hirschsprung disease associated with a novel ZFHX1B missense mutation and trisomy 21
Authors: Gregory‐Evans C.Y. , Vieira H. , Dalton R. , Adams G.G.W. , Salt A. , Gregory‐Evans K.
Published: September 2004

Syndromic Hirschsprung disease has been associated with mutations in ZFHX1B, a Smad‐interacting transcriptional repressor protein. Tissue in situ hybridization has demonstrated strong expression of ZFHX1B in the developing eye, suggesting that some mutations in this gene may cause visual loss. However, none of the reported mutations have been associated with an ocular phenotype. We describe a patient with Down syndrome and Hirschsprung disease with high myopia and ocular coloboma affecting the iris and retina. In addition to trisomy 21, a novel, de novo heterozygous A to G transition in exon 8 of the ZFHX1B gene was identified, which results in a R953G amino acid substitution. This abnormality was not seen in a screen of 200 chromosomes from ethnically matched, normal controls. The arginine residue at position 953 is an extremely conserved amino acid throughout evolution. This is the first report associating Hirschsprung disease and severe eye defects with a specific genetic mutation and is the first report of a mutation in ZFHX1B causing a developmental ocular anomaly. © 2004 Wiley‐Liss, Inc.
Proteomic studies identified a single nucleotide polymorphism in glyoxalase I as autism susceptibility factor
Authors: Junaid Mohammed A. , Kowal Dagmar , Barua Madhabi , Pullarkat Premila S. , Sklower Brooks Susan , Pullarkat Raju K.
Published: September 2004

Autism is a neurodevelopmental disability characterized by deficits in verbal communications, impairments in social interactions, and repetitive behaviors. Several studies have indicated strong involvement of multigenic components in the etiology of autism. Linkage analyses and candidate gene search approaches so far have not identified any reliable susceptibility genes. We are using a proteomic approach to identify protein abnormalities due to aberrant gene expression in autopsied autism brains. In four of eight autism brains, we have found an increase in polarity (more acidic) of glyoxalase I (Glo1) by two‐dimensional gel electrophoresis. To identify the molecular change resulting in the shift of Glo1 polarity, we undertook sequencing of GLO1 gene. Direct sequencing of GLO1 gene/mRNA in these brains, has identified a single nucleotide polymorphism (SNP), C419A. The SNP causes an Ala111Glu change in the protein sequence. Population genetics of GLO1 C419A SNP studied in autism (71 samples) and normal and neurological controls (49 samples) showed significantly higher frequency for the A419 (allele frequency 0.6 in autism and 0.4 in controls, one‐tailed Fisher's test P < 0.0079). Biochemical measurements have revealed a 38% decrease in Glo1 enzyme activity in autism brains (one‐tailed t‐test P < 0.026). Western blot analysis has also shown accumulation of advanced glycation end products (AGE's) in autism brains. These data suggest that homozygosity for A419 GLO1 resulting in Glu111 is a predisposing factor in the etiology of autism. © 2004 Wiley‐Liss, Inc.
Girl with monosomy 1p36 and Angelman syndrome due to unbalanced der(1) transmission of a maternal translocation t(1;15)(p36.3;q13.1)
Authors: Torisu Hiroyuki , Yamamoto Toshiyuki , Fujiwaki Takehisa , Kadota Mitsutaka , Oshimura Mitsuo , Kurosawa Kenji , Akaboshi Shinjiro , Oka Akira
Published: September 2004

We report on a girl with monosomy 1p36.3 and Angelman syndrome due to an unbalanced transmission of a maternal balanced chromosomal translocation. She manifested monosomy 1p36 and Angelman syndrome including generalized hypopigmentation, ataxic movements, intractable seizures with characteristic electroencephalographic (EEG) abnormality compatible with Angelman syndrome, and other minor anomalies, large anterior fontanelle, severe psychomotor retardation, and seizures due to monosomy 1p36. Her karyotype was 45, XX, der(1) t(1;15)(p36.31;q13.1),−15, derived from maternal translocation. Molecular analysis determined a breakpoint of 1p between D1S243 and D1S468, which suggested that most genes contributing to the common phenotype are in the distal region. © 2004 Wiley‐Liss, Inc.
Neither single‐marker nor haplotype analyses support an association between genetic variation near NOTCH4 and bipolar disorder
Authors: Prathikanti Sridhar , Schulze Thomas G. , Chen Yu‐Sheng , Harr Bettina , Akula Nirmala , Hennessy Kathy , Potluri Suneeta , Lyons Jennifer , Nguyen Tu , McMahon Francis J.
Published: September 2004

Markers near the NOTCH4 locus on chromosome 6p21.3 have been reported to be associated with schizophrenia in some studies. Since schizophrenia and bipolar affective disorder (BPAD) may share genetic determinants, we tested markers in and near NOTCH4 in a sample of 153 parent–offspring triads ascertained through a sibling pair with BPAD for evidence of association. This sample would have 80% power to detect an association at or above a genotype relative risk of 2.4 at the 10−7 level of significance. In addition to the two markers previously showing the most significant association with schizophrenia, three additional nearby markers were studied. The five markers were genotyped using validated methods. Both single‐marker and 3‐marker haplotype data was analyzed using family‐based association methods. No genome‐wide significant association was detected between any of the five SNP‐markers and BPAD in this sample. One marker showed nominal evidence of association (P = 0.049), but this evidence was not supported by haplotype analyses including nearby flanking markers or by case‐control analysis using 93 Caucasian controls. These results do not support an association between genetic variation near NOTCH4 and BPAD in this sample. © 2004 Wiley‐Liss, Inc.
Association study of brain‐derived neurotrophic factor in adults with a history of childhood onset mood disorder
Authors: Strauss J. , Barr C.L. , George C.J. , King N. , Shaikh S. , Devlin B. , Kovacs M. , Kennedy J.L.
Published: September 2004

Brain‐derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant‐like effects in animals. BDNF gene polymorphisms have been associated with bipolar disorder. We tested two genetic polymorphisms of BDNF for their association with childhood‐onset mood disorders (COMD) within the context of a case‐control design. Two BDNF polymorphisms, a dinucleotide repeat (GT)n, and a single nucleotide polymorphism (SNP) in the coding region, val66met, were genotyped in 99 adults with a history of COMD and matched psychiatrically healthy controls. A genomic control (GC) method was used to evaluate population substructure. Alleles at (GT)n were highly associated with COMD in this sample (χ2 = 17.8; d.f. = 5; P = 0.0032). The odds of carrying the 168 bp allele were 3.94 times greater for cases than controls (CI = 1.72–9.04). Alleles of val66met were not significantly associated with COMD. GC analysis suggested population substructure was not a confounder of association. Analysis of haplotypes, in which (GT)n was treated as a binary variable (long vs. short alleles), provided significant evidence that the haplotype val/short contributes to liability to COMD. The BDNF (GT)n marker and the val/short haplotype are associated with COMD in this sample, in accordance with the previously described neurotrophic hypothesis of depression and some previous studies of association for bipolar disorder and neuroticism. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148‐7299:1/suppmat/index.html. © 2004 Wiley‐Liss, Inc.
Titelbild: Methoden zur chemischen Synthese von Fullerenen (Angew. Chem. 38/2004)
Authors: Scott Lawrence T.
Published: September 2004

Viel Energie kostet es, das planare π‐System eines polycyclischen aromatischen Kohlenwasserstoffs zu krümmen. Ohne diesen Kraftakt wäre die erste chemische Synthese von C60 in isolierbaren Mengen undenkbar gewesen. L. T. Scott beschreibt im Aufsatz auf S. 5102 ff. die Anwendungsbreite und die Einschränkungen der leistungsstarken neuartigen Methoden, die bei der Fullerensynthese zum Einsatz kamen und anhand der Synthesen zahlreicher geodätischer Polyarene erprobt wurden.
Cover Picture: Methods for the Chemical Synthesis of Fullerenes (Angew. Chem. Int. Ed. 38/2004)
Authors: Scott Lawrence T.
Published: September 2004

A high price in energy must be paid to impose curvature on the π system of a planar polycyclic aromatic hydrocarbon. This step was essential for the first chemical synthesis of C60 in isolable quantities, which stands as dramatic testimony to the power of the new synthetic methods devised for fullerene synthesis. In his Review on page 4994 ff., L. T. Scott describes the numerous syntheses of geodesic polyarenes reported, which serve to test the scope and limitations of the new methods.
Pervaporation of water/alcohol mixtures through chitosan/cellulose acetate composite hollow‐fiber membranes
Authors: Tsai H. A. , Chen H. C. , Chou W. L. , Lee K. R. , Yang M. C. , Lai J. Y.
Published: September 2004

For the purpose of separating aqueous alcohol by the use of pervaporation technique, a composite membrane of chitosan (CT) dip‐coated cellulose acetate (CA) hollow‐fiber membranes, CT‐d‐CA, was investigated. The effects of air‐gap distance in the spinning of CA hollow‐fiber membranes, chitosan concentration, and sorts of aqueous alcohol solutions on the pervaporation performances were studied. Compared with unmodified CA hollow‐fiber membrane, the CT‐d‐CA composite hollow‐fiber membrane effectively increases the permselectivity of water. The thickness of coating layer increases with an increase in chitosan concentration. As the concentration of chitosan solution increased, the permeation rate decreased and the concentration of water in the permeate increased. In addition, the effects of feed composition and feed solution temperature on the pervaporation performances were also investigated. The permeation rate and water content in permeate at 25°C for a 90 wt % aqueous isopropanol solution through the CT‐d‐CA composite hollow‐fiber membrane with a 5‐cm air‐gap distance spun, 2 wt % chitosan dip‐coated system were 169.5 g/m2 h and 98.9 wt %, respectively. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1562–1568, 2004
Preparation and thermomechanical characterization of poly(vinyl chloride) blends compatible with terpolymer‐containing maleic anhydride
Authors: Boztuğ Ali
Published: September 2004

In this study, I aimed to change the thermomechanical characteristics of poly(vinyl chloride) (PVC), which is widely used in commercial areas. Copolymers containing maleic anhydride (MA) units are commonly used to obtain compatible polymer blends. In our study, PVC blends were also prepared with the terpolymers with and without anhydride units. I assumed that the impact of the terpolymer on the thermomechanical characteristics of the PVC material could be more effectively controlled. For this purpose, two sets of six different blends of PVC with or without MA were synthesized, among which one was pure PVC, but the other five blends contained 2, 4, 6, 8, and 10% terpolymer. In conclusion, I observed that the terpolymer with the MA unit more regularly changed the thermomechanical characteristics of PVC. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1586–1589, 2004
Swelling behavior of thermoreversible poly(N‐isopropylacrylamide‐co‐N‐vinylimidazole) hydrogels
Authors: Işık Belma , Günay Yekta
Published: September 2004

Thermoresponsive hydrogels based on N‐isopropylacrylamide and N‐vinylimidazole were synthesized, and their swelling–deswelling behavior was studied as a function of the total monomer concentration. For copolymeric structures with better thermoresponsive properties with respect to poly(N‐isopropylacrylamide‐co‐N‐vinylimidazole) hydrogels, these hydrogels were protonated with HCl and HNO3, and the copolymer behaviors were compared with those of the unprotonated hydrogels. The temperature was changed from 4 to 70°C at fixed pHs and total ionic strengths. The equilibrium swelling ratio, dynamic swelling ratio, and dynamic deswelling ratio were evaluated for all the hydrogels. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1619–1624, 2004
Mathematical simulation of dynamic coupled heat and liquid moisture transfer in multilayer anisotropic porous polymers
Authors: Li Y. , Wang Z.
Published: September 2004

A one‐dimensional mathematical model describing the dynamic coupled heat and moisture transfer inside multilayered porous polymers and anistropic materials is developed in this reported study. Compared to models published previously, three improvements have been made: (1) the model takes into account the dynamic complex behavior of coupled heat and liquid moisture transfer inside each layer; (2) the model provides different (inter‐) boundary conditions that correspond with the contact situations between neighbored layers and the influences from waterproof fabrics; and (3) the combinations of different types of polymer fibers in each layer and their roles with respect to processes of heat and moisture transfer. Physical experiments for liquid transfer, through the layered fabric assemblies with different construction, were carried out to validate the developed model in terms of dynamic temperature and moisture concentration distribution in the assembly, as well as the initial and final absolute liquid volumetric fractions at the surface of the top layer. Good agreement between the calculated and experimental results was obtained. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1590–1605, 2004
Carboxymethylation of Cassia occidentalis seed gum
Authors: Gupta Sarika , Sharma Pradeep , Soni P. L.
Published: September 2004

The seeds of Cassia occidentalis, an annual weed occurring throughout India, are a rich source of galactomannan gum. The gum derived from seed endosperm can be utilized in a number of industries to replace conventional gums. With a view to utilize the gum for broader applications, carboxymethylation of Cassia occidentalis seed gum was carried out. The reaction conditions were optimized with respect to concentration of monochloroacetic acid, sodium hydroxide, solvent ratio, reaction time, and reaction temperature. Rheological studies of carboxymethyl gum exhibited relatively high viscosity and stability vis‐a‐vis unmodified Cassia occidentalis gum. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1606–1611, 2004
Preparation of cadmium sulfide/poly(methyl methacrylate) composites by precipitation with compressed CO2
Authors: Li Zhonghao , Zhang Jianling , Du Jimin , Mu Tiancheng , Liu Zhimin , Chen Jing , Han Buxing
Published: September 2004

Cadmium sulfide (CdS) nanoparticles and poly(methyl methacrylate) (PMMA) were first synthesized in methyl methacrylate (MMA)/sodium bis(2‐ethylhexyl) sulfosuccinate (AOT) microemulsion, in which MMA acts as the solvent and monomer. Then compressed CO2 was used as an antisolvent to precipitate the CdS and PMMA simultaneously. Using this method, a CdS/PMMA composite was successfully prepared. The CdS nanoparticles dispersed in the polymer matrices were characterized by transmission electron microscopy. The higher pressure is favorable to producing CdS nanoparticles of smaller size. The phase structure of the obtained composite was characterized by X‐ray diffraction, which reveals that cubic CdS particles were formed. The FTIR spectra of the composite showed that there is no chemical bonding or strong interaction between CdS and PMMA. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1643–1648, 2004