bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical localization of Papilio RBP in the eye of butterflies
Authors: Wakakuwa Motohiro , Ozaki Koichi , Arikawa Kentaro
Published: March 2004

We recently identified a novel retinoid binding protein, PapilioRBP, in the soluble fraction of the eye homogenate of the butterfly Papilio xuthus, and demonstrated that the protein is involved in the visual cycle. We now have localized the protein in the Papilio eye by light and electron microscopic immunohistochemistry using a monospecific antiserum produced against artificially expressed Papilio RBP. We found strong immunoreactivity in the primary as well as secondary pigment cells and in the tracheal cells. The pigment cells have long been regarded as an important site of the visual cycle, and this view is further supported by the present result. Interestingly, the cytoplasm and nuclei of these cells were equally labeled, indicating that the protein exists in both the cytoplasm and the nucleus. We conducted a survey for the existence of the Papilio RBP-like proteins in other insects including several species of butterflies, dragonflies, cicadas, grasshoppers and honeybees. Anti-Papilio RBP immunoreactivity was confirmed in the proteins isolated only from butterflies belonging to the superfamily Papilionoidea and not from other species. In all insects tested, however, fluorescing proteins were clearly detected, suggesting that these insects also have similar retinol-binding proteins.
The hydrodynamic trails of Lepomis gibbosus (Centrarchidae), Colomesus psittacus (Tetraodontidae) and Thysochromis ansorgii (Cichlidae) investigated with scanning particle image velocimetry
Authors: Hanke Wolf , Bleckmann Horst
Published: March 2004

The hydrodynamic trails of fish belonging to the families Centrarchidae,Tetraodontidae and Cichlidae were investigated. Water movements were measured in six horizontal planes, spaced 10–12 mm apart, for up to 5 min after the passage of a fish, using a computer controlled array of modulated laser diodes. We measured continuously and non-continuously swimming fish. Water velocities decayed rapidly in the leading seconds after the passage of a fish,but could still be measured for a period considerably longer than that. In still water (median water velocity <0.5 mm s–1), the hydrodynamic trails of Lepomis gibbosus lasted for more than 5 min. The trails of Colomesus psittacus and Thysochromis ansorgiicould be detected for more than 30 s and more than 3 min, respectively. The water disturbance left behind by these fish was sufficient to be sensed by a piscivorous predator at a distance where vision or hearing frequently fail. Acoustic stimuli estimated from a dipole model in a distance that would be covered by the tested fish in 1 min (4–25 m) were 1.5×10–7 to 3.1×10–10 m s–2, while the hearing threshold of a perch is three orders of magnitude above that. By contrast, the fish wakes after 1 min (except for one Colomesus wake) contained water velocities between 0.95 and 2.05 mm s–1, which are within the detection range of hydrodynamic sensory systems. The three species differed with respect to water velocities,the spatial extent of the fish-generated water disturbances and the structure of the wake.
A Facile Approach to 2-CF3-Substituted Seven-membered Oxacycles via Stereoselective Preparation and Cope Rearrangement of 2-CF3-cis-2,3-Bis(alkenyl)oxiranes
Authors: Shimizu Masaki , Fujimoto Takuya , Liu Xinyu , Hiyama Tamejiro
Published: March 2004

Stereoselective preparation and Cope rearrangement of 2-CF3-substituted cis-2,3-bis(alkenyl)oxiranes provides a convenient route to a diverse of 2-CF3-4,5-dihydrooxepins. The reaction sequence followed by reduction or oxidation provides 2-CF3-substituted oxepanes or oxepins, respectively.
A Cationic Diruthenium Amidinate, [(η5-C5Me5)Ru(μ2-i-PrN=C(Me)Ni-Pr)Ru(η5-C5Me5)]+, as an Efficient Catalyst for the Atom-Transfer Radical Reactions
Authors: Motoyama Yukihiro , Gondo Mitsuru , Masuda Satoshi , Iwashita Yuya , Nagashima Hideo
Published: March 2004

A cationic diruthenium amidinate, [(η5-C5Me5)Ru(μ2-i-PrN=C(Me)Ni-Pr)Ru(η5-C5Me5)]+, is generated by treatment of (η5-C5Me5)Ru(μ2-i-PrN=C(Me)Ni-Pr)Ru(Cl)(η5-C5Me5) (3a) with NaPF6 or other metal salts of weakly coordinating anions, which is active towards catalytic atom transfer radical cyclization of N-allyl trichloroacetamides and related reactions.
Syntheses and Structure of a Novel Layered Lanthanide–Zinc Coordination Polymer: [LaZn(HIDA)(IDA)2·0.5H2O]n
Authors: Xu Hongbin , Zhao Yahui , Su Zhongmin , Li Guanghua , Ma Yue , Shao Kuizhan , Zhu Dongxia , Zhang Hengjun , Yue Shumei
Published: March 2004

The hydrothermal reactions of La2O3, Zn(CH3COO)2·2H2O, iminodiacetic acid (H2IDA), and H2O resulted in the formation of a novel coordination polymers [LaZn(HIDA)(IDA)2·0.5H2O]n. X-ray diffraction analyses confirms that in complexe 1 La ions are lined through sharing the O atoms of IDA ligands which the octahedron-coordinated Zn ions are beside alternately to form a 1-D zigzag inorganic chain. And then a 2-D layered coordination polymer is constructed by helix bridging protonated HIDA ligands.
Photochromism of Diarylethene-capped Gold Nanoparticles
Authors: Matsuda Kenji , Ikeda Masumi , Irie Masahiro
Published: March 2004

Diarylethene-capped gold nanoparticles were synthesized by a self-assembled monolayer (SAM) technique and the photochemical behavior was studied. The average diameter of the particles was determined to be 1.1 nm from TEM image. The synthesized nanoparticles showed reversible photochromic reactivity regardless of the presence of the surface plasmon band.
Synthesis and Characterization of the First Organically Templated Layered Cerium Phosphate Fluoride: [(CH2)2(NH3)2]0.5[CeIVF3(HPO4)]
Authors: Yu Ranbo , Wang Dan , Ishiwata Shintaro , Saito Takashi , Azuma Masaki , Takano Mikio , Chen Yunfa , Li Jinghai
Published: March 2004

A novel organically templated layered cerium phosphate fluoride [(CH2)2(NH3)2]0.5[CeIVF3(HPO4)] has been synthesized by hydrothermal synthesis technology, and characterized by means of single-crystal X-ray diffraction. Its unique layered structure is based on a network of novel CeO3F5 polyhedral and PO4 tetrahedral. The [NH3(CH2)2NH3]+ cations contact with the adjacent layers via hydrogen bonds to compensate the negative charge of the inorganic framework.
Synthesis of cis-2-Fluorocyclopropylamine by Stereoselective Cyclopropanation Under Phase-transfer Conditions
Authors: Matsuo Jun-ichi , Tani Yu-ichirou , Hayakawa Yu-ichirou
Published: March 2004

cis-2-Fluorocyclopropylamine is stereoselectively synthesized by cyclopropanation of 3-aryl-2-vinyl-3-(methoxy)isoindol-1-one by treating dibromofluoromethane with saturated aqueous KOH solution in the presence of 18-crown-6 in dichloromethane, followed by removal of a bromine atom of the formed bromofluorocyclopropane derivative with Raney Ni, and successive three steps-deprotection procedures for generating an amino group on the cyclopropane ring.
Leaky termination at premature stop codons antagonizes nonsense-mediated mRNA decay in S. cerevisiae
Authors: KEELING KIM M. , LANIER JESSICA , DU MING , SALAS-MARCO JOE , GAO LIN , KAENJAK-ANGELETTI ANISA , BEDWELL DAVID M.
Published: March 2004

The Nonsense-Mediated mRNA Decay (NMD) pathway mediates the rapid degradation of mRNAs that contain premature stop mutations in eukaryotic organisms. It was recently shown that mutations in three yeast genes that encode proteins involved in the NMD process, UPF1, UPF2, and UPF3, also reduce the efficiency of translation termination. In the current study, we compared the efficiency of translation termination in a upf1Δ strain and a [PSI+] strain using a collection of translation termination reporter constructs. The [PSI+] state is caused by a prion form of the polypeptide chain release factor eRF3 that limits its availability to participate in translation termination. In contrast, the mechanism by which Upf1p influences translation termination is poorly understood. The efficiency of translation termination is primarily determined by a tetranucleotide termination signal consisting of the stop codon and the first nucleotide immediately 3′ of the stop codon. We found that the upf1Δ mutation, like the [PSI+] state, decreases the efficiency of translation termination over a broad range of tetranucleotide termination signals in a unique, context-dependent manner. These results suggest that Upf1p may associate with the termination complex prior to polypeptide chain release. We also found that the increase in readthrough observed in a [PSI+]/upf1Δ strain was larger than the readthrough observed in strains carrying either defect alone, indicating that the upf1Δ mutation and the [PSI+] state influence the termination process in distinct ways. Finally, our analysis revealed that the mRNA destabilization associated with NMD could be separated into two distinct forms that correlated with the extent the premature stop codon was suppressed. The minor component of NMD was a 25% decrease in mRNA levels observed when readthrough was ≥0.5%, while the major component was represented by a larger decrease in mRNA abundance that was observed only when readthrough was ≤0.5%. This low threshold for the onset of the major component of NMD indicates that mRNA surveillance is an ongoing process that occurs throughout the lifetime of an mRNA.
Dim2p, a KH-domain protein required for small ribosomal subunit synthesis
Authors: VANROBAYS EMMANUEL , GÉLUGNE JEAN-PAUL , CAIZERGUES-FERRER MICHÈLE , LAFONTAINE DENIS L.J.
Published: March 2004

Recent proteomic analyses are revealing the dynamics of preribosome assembly. Following cleavage at processing site A2, which generates the 20S pre-rRNA (the immediate precursor to the 18S rRNA), early RRPs (ribosomal RNA processing factors) are released in bulk from the preribosomes, and the resulting pre-40S subunits are left associated with a limited set of proteins that we refer to as the SSU RRP complex. Dim2p, a core constituent of the SSU RRP complex and conserved KH-domain containing protein, is required for pre-rRNA processing and is associated with early nucleolar and late cytoplasmic pre-rRNA species. Consistently, Dim2p shuttles between the nucle(ol)us and the cytoplasm, a trafficking that is tightly regulated by growth. The association of Dim2p with the 18S rRNA dimethyltransferase Dim1p, as well as its requirement for pre-rRNA processing at cleavage sites A1 and A2 and for 18S rRNA dimethylation, suggest that Dim2p may recruit Dim1p to nucleolar pre-rRNAs through its KH domain.
The Saccharomyces cerevisiae TAN1 gene is required for N4-acetylcytidine formation in tRNA
Authors: JOHANSSON MARCUS J.O. , BYSTRÖM ANDERS S.
Published: March 2004

The biogenesis of transfer RNA is a process that requires many different factors. In this study, we describe a genetic screen aimed to identify gene products participating in this process. By screening for mutations lethal in combination with a sup61-T47:2C allele, coding for a mutant form of \batchmode
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, the nonessential TAN1 gene was identified. We show that the TAN1 gene product is required for formation of the modified nucleoside N4-acetylcytidine (ac4C) in tRNA. In Saccharomyces cerevisiae, ac4C is present at position 12 in tRNAs specific for leucine and serine as well as in 18S ribosomal RNA. Analysis of RNA isolated from a tan1-null mutant revealed that ac4C was absent in tRNA, but not rRNA. Although no tRNA acetyltransferase activity by a GST-Tan1 fusion protein was detected, a gel-shift assay revealed that Tan1p binds tRNA, suggesting a direct role in synthesis of ac4C12. The absence of the TAN1 gene in the sup61-T47:2C mutant caused a decreased level of mature \batchmode
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, indicating that ac4C12 and/or Tan1p is important for tRNA stability.
Analysis of the requirement for RNA polymerase II CTD heptapeptide repeats in pre-mRNA splicing and 3′-end cleavage
Authors: ROSONINA EMANUEL , BLENCOWE BENJAMIN J.
Published: March 2004

The carboxyl-terminal domain (CTD) of RNA polymerase II (pol II) plays an important role in coupling transcription with precursor messenger RNA (pre-mRNA) processing. Efficient capping, splicing, and 3′-end cleavage of pre-mRNA depend on the CTD. Moreover, specific processing factors are known to associate with this structure. The CTD is therefore thought to act as a platform that facilitates the assembly of complexes required for the processing of nascent transcripts. The mammalian CTD contains 52 tandemly repeated heptapeptides with the consensus sequence YSPTSPS. The C-terminal half of the mammalian CTD contains mostly repeats that diverge from this consensus sequence, whereas the N-terminal half contains mostly repeats that match the consensus sequence. Here, we demonstrate that 22 tandem repeats, from either the conserved or divergent halves of the CTD, are sufficient for approximate wild-type levels of transcription, splicing, and 3′-end cleavage of two different pre-mRNAs, one containing a constitutively spliced intron, and the other containing an intron that depends on an exon enhancer for efficient splicing. In contrast, each block of 22 repeats is not sufficient for efficient inclusion of an alternatively spliced exon in another pre-mRNA. In this case, a longer CTD is important for counteracting the negative effect of a splicing silencer element located within the alternative exon. Our results indicate that the length, rather than the composition of CTD repeats, can be the major determinant in efficient processing of different pre-mRNA substrates. However, the extent of this length requirement depends on specific sequence features within the pre-mRNA substrate.
Premature termination codons do not affect the rate of splicing of neighboring introns
Authors: LYTLE J. ROBIN , STEITZ JOAN A.
Published: March 2004

Introduction of a premature termination codon (PTC) into an exon of a gene can lead to nonsense-mediated decay of the mRNA, which is best characterized as a cytoplasmic event. However, increasing evidence has suggested that PTCs may also influence the nuclear processing of an RNA transcript, leading to models of nuclear surveillance perhaps involving translating nuclear ribosomes. We used quantitative RT-PCR to measure the in vivo steady-state levels of every exon-intron junction in wild-type, PTC-containing, and missense-containing precursor mRNAs of both the nonrearranging dihydrofolate reductase (DHFR) and the somatically rearranging Ig-μ genes. We find that each exon-intron junction’s abundance and, therefore, the rate of intron removal, is not significantly affected by the presence of a PTC in a neighboring exon in either the DHFR or Ig-μ pre-mRNA. Similarly, the abundance of the uncleaved Ig-μ polyadenylation sites does not differ between wild-type and PTC-containing Ig-μ pre-mRNAs. Our Ig-μ data were confirmed by RNase protection analyses, and multiple cell isolates were examined to resolve differences with previously published data on steady-state pre-mRNA levels. We conclude that the presence of a PTC affects the rate of neither splicing nor the cleavage step of 3′ end formation during pre-mRNA processing in the nucleus. Our results are discussed with respect to existing evidence for nuclear surveillance mechanisms.
Functional dissection of hnRNP D suggests that nuclear import is required before hnRNP D can modulate mRNA turnover in the cytoplasm
Authors: CHEN CHYI-YING A. , XU NIANHUA , ZHU WENMIAO , SHYU ANN-BIN
Published: March 2004

Many shuttling proteins not only function in the nucleus but also control mRNA fates in the cytoplasm. We test whether a link exists between their nuclear association with mRNPs and their cytoplasmic functions using the p37 isoform of hnRNP D, which inhibits the rapid cytoplasmic mRNA decay in NIH3T3 cells. We showed that p37 shuttles between nucleus and cytoplasm, and narrowed down the nuclear import signal to a 50-amino-acid C-terminal domain. A p37 mutant missing this domain, still capable of associating with target mRNAs in vitro, was confined to the cytoplasm, where it was unable to block cytoplasmic mRNA turnover. Introducing heterologous shuttling domains to this mutant, thereby restoring its ability to enter the nucleus, concomitantly restored its cytoplasmic function. Association of p37 with its target mRNAs can only be detected when it can enter the nucleus. Our results suggest that nuclear import of hnRNP D is a prerequisite for it to exert its cytoplasmic function. This study provides a useful model system to elucidate the mechanisms by which “nuclear history” affects cytoplasmic mRNA fates.
Fitting In and Fighting Back: Stigma Management Strategies among Homeless Kids
Authors: Roschelle Anne R. , Kaufman Peter
Published: March 2004

Using data collected during a four‐year ethnographic study, this article examines the stigma management strategies of kids who are homeless in the San Francisco Bay area. We focus specifically on strategies of inclusion and exclusion. Strategies of inclusion are attempts by homeless kids to establish harmonious relationships with both peers and strangers. The most common are forging friendships, passing, and covering. Strategies of exclusion are aggressive and nonconciliatory attempts to gain social acceptance. They include verbal denigration and physical and sexual posturing. Some of these strategies successfully protect the kids’ sense of self, while other strategies had the unintended effect of reinforcing their spoiled identities. We argue that these stigma management strategies are both informed by and interpreted through their disadvantaged social structural location.
A Model of Animal Selfhood: Expanding Interactionist Possibilities
Authors: Irvine Leslie
Published: March 2004

Interaction between people and companion animals provides the basis for a model of the self that does not depend on spoken language. Drawing on ethnographic research in an animal shelter as well as interviews and auto‐ethnography, this article argues that interaction between people and animals contributes to human selfhood. In order for animals to contribute to selfhood in the ways that they do, they must be subjective others and not just the objects of anthropomorphic projection. Several dimensions of subjectivity appear among dogs and cats, constituting a “core” self consisting of agency, coherence, affectivity, and history. Conceptualizing selfhood in this way offers critical access to animals' subjective presence and adds to existing interactionist research on relationships between people and animals.
The Living Gesture and the Signifying Moment
Authors: Halton Eugene
Published: March 2004

Drawing from Peircean semiotics, from the Greek conception of phronesis, and from considerations of bodily awareness as a basis of reasonableness, I attempt to show how the living gesture touches our deepest signifying nature, the self, and public life. Gestural bodily awareness, more than knowledge, connects us with the very conditions out of which the human body evolved into its present condition and remains a vital resource in the face of a devitalizing, rationalistic consumption culture. It may be precisely these deep‐rooted abilities for what I term “self‐originated experience” that can ultimately offset automatism.
Radial Electromechanical Properties of Carbon Nanotubes
Authors: Gómez‐Navarro C. , de Pablo P. J. , Gómez‐Herrero J.
Published: March 2004

The radial electromechanical properties of carbon nanotubes have been measured. The electrical conductance of single‐walled carbon nanotubes (SWNTs) as a function of the loading force and bias voltage applied by an atomic force microscope tip is reported (see Figure). An increase of the conductance due to the tip–SWNT electrical contact formation and a drop of the conductance at high loading forces due to radial molecule deformation are observed (see also inside front cover).
Human personality dimensions of persistence and harm avoidance associated with DRD4 and 5‐HTTLPR polymorphisms
Authors: Szekely A. , Ronai Z. , Nemoda Z. , Kolmann G. , Gervai J. , Sasvari‐Szekely M.
Published: March 2004

The associations of human personality traits as measured by the Temperament and Character Inventory (TCI) with two genetic polymorphisms, the dopamine D4 receptor (DRD4) gene exon III repeat polymorphism (VNTR) and the serotonin transporter‐linked functional polymorphism (5‐HTTLPR) are presented in a population of 157 ethnically homogeneous Caucasians. No association was found between Novelty Seeking and the DRD4 VNTR, but male individuals with a 7‐repeat allele exhibited significantly lower Persistence scores. The 5‐HTTLPR polymorphism itself had no significant effect on any of the temperament dimensions, but a significant DRD4 VNTR × 5‐HTTLPR interaction was observed for Harm Avoidance, the subgroup with a s/s 5‐HTTLPR, 7‐repeat DRD4 genotype showed a higher mean Harm Avoidance score than the other groups. These results are discussed in relation to the recent findings on infant temperament. Association between the DRD4 7‐repeat allele and Persistence can be theoretically linked to the 7‐repeat allele as a risk factor for attention deficit hyperactivity disorder. © 2003 Wiley‐Liss, Inc.
Serotonin transporter polymorphism and depressive‐related symptoms in schizophrenia
Authors: Golimbet V.E. , Alfimova M.V. , Shchebatykh T.V. , Abramova L.I. , Kaleda V.G. , Rogaev E.I.
Published: March 2004

A role for the serotonin transporter (5‐HTT) gene polymorphism in mental illnesses and anxiety‐traits has been implicated. The contribution of genetic factors in personality traits and the manifestation of specific symptoms in psychiatric illnesses have yet to be elucidated. Anxious‐depressive symptoms are a significant component in a pattern of schizophrenic symptoms. This study focused on the relation between 5‐HTT polymorphism and clinical presentations of schizophrenia, specifically those related to the affective spectrum. Using clinical and psychological analyses, we tested the genetic association between the 5‐HTTLPR polymorphism (5‐HTT gene‐linked polymorphic region) and anxiety‐ and depressive‐related symptoms emerged in schizophrenia. In 260 patients with an ICD‐10 diagnosis of schizophrenia (broad definition), we studied the 5‐HTTLPR genotype (insertion‐deletion polymorphism), the Positive and Negative Syndrome Scale (PANSS), and self‐rated inventories (EPI, MMPI, STAI) scores. Patients with the “ss” genotype (deletion variant) scored significantly higher on “Guilt feelings” and “Depression” items, as compared with those of the “ll” genotype (insertion variant) (P = 0.016, 0.039, respectively). The frequency of the “ss” genotype was reduced in patients with no depression or guilt feelings, or in those patients exhibiting questionable symptoms. In contrast, the “ss” genotype carriers prevailed among the patients with mild, moderate, or severe ratings of the symptoms. The scores on all anxiety‐ and depression‐related traits, self‐rated by the patients, did not significantly differ by genotype. Our finding may contribute to understanding of molecular genetic features underlying an appearance of psychopathological symptoms emerged in schizophrenia. © 2003 Wiley‐Liss, Inc.
The gamma amino butyric acid (GABA) receptor alpha‐3 subunit gene polymorphism in unipolar depressive disorder: A genetic association study
Authors: Henkel Verena , Baghai Thomas C. , Eser Daniela , Zill Peter , Mergl Roland , Zwanzger Peter , Schüle Cornelius , Bottlender Ronald , Jäger Markus , Rupprecht Rainer , Hegerl Ulrich , Möller Hans‐Jürgen , Bondy Brigitta
Published: March 2004

There is evidence that genes coding for the gamma aminobutyric acid (GABA) receptor may be involved in the etiology of affective disorders. Recently, an association between a CA‐repeat in the GABRA 3 gene and bipolar disorder had been reported. The present study aimed at investigating the association between this polymorphism and unipolar major depressive disorder. The sample consisted of 201 unipolar depressive patients and 151 healthy subjects. All study participants were unrelated German individuals of the same ethnogeographical origin. No differences in genotype frequencies between unipolar patients and healthy subjects were found for GABRA 3 (P = 0.08). However, a significant difference of allelic frequencies was observed in female patients (n = 128) compared to female controls (n = 81) (P ≤ 0.0001). This effect was not present in the group of male patients (n = 73) compared to male healthy subjects (n = 70) (P = 0.24). The results of our study indicate that GABRA 3 gene might also be involved in the genetic pathophysiology of unipolar major depressive disorder (at least in female patients), even if the findings do not support a predominant role of GABRA 3. © 2003 Wiley‐Liss, Inc.
Polymorphism at codon 469 of the intercellular adhesion molecule‐1 gene is not associated with sporadic Alzheimer's disease
Authors: Rodero Lucía , Infante Jon , Palacio Enrique , Llorca Javier , Berciano José , Combarros Onofre
Published: March 2004

Activation of microglia is a central part of the chronic inflammatory response in Alzheimer's disease (AD). Intercellular adhesion molecule‐1 (ICAM‐1) is a cell surface receptor that may act in AD to adhere microglia to beta amyloid fibrils within senile plaques. Preliminary evidence in an Italian population indicates that a polymorphism at codon 469 of the ICAM‐1 gene is a predisposing factor for sporadic AD. Another group has been unable to replicate this association in a Finnish population. A case‐control study utilizing a clinically well‐defined group of 283 sporadic AD patients and 283 control subjects was performed to test this association in an ethnically homogeneous population from Spain. The current study does not demonstrate any significant difference in E469K genotype or allele frequencies between AD patients and controls. Our study in the Spanish population argues against the hypothesis that polymorphism at codon 469 of the ICAM‐1 gene is causally related to AD. © 2003 Wiley‐Liss, Inc.
Family‐based association studies of α‐adrenergic receptor genes in chromosomal regions with linkage to bipolar affective disorder
Authors: Jamra Rami Abou , Schumacher Johannes , Golla Astrid , Richter Carola , Otte Andreas C.J. , Schulze Thomas G. , Ohlraun Stephanie , Maier Wolfgang , Rietschel Marcella , Cichon Sven , Propping Peter , Nöthen Markus M.
Published: March 2004

Several lines of evidence suggest an involvement of the noradrenergic neurotransmitter system in the pathogenesis of bipolar affective disorder (BPAD). Three genes for α‐adrenergic receptors (ADRA) are located in chromosomal regions that showed evidence for linkage: The α1c‐adrenergic (ADRA‐1C) receptor gene on 8p21, the α2a‐adrenergic (ADRA‐2A) receptor gene on 10q25, and the α2c‐adrenergic (ADRA‐2C) receptor on 4p16. In a BPAD sample of 120 parent‐offspring triads, we genotyped a 492 Cys/Arg variant in exon 2 of the ADRA‐1C gene, a ‐1291 G/C variant in the 5′UTR of the ADRA‐2A gene, and a STR marker (adra2c1) in the 5′UTR of the ADRA‐2C gene. Using the Transmission Disequilibrium Test (TDT), no significant differences in transmissions were observed for any of the three ADRA genes. © 2003 Wiley‐Liss, Inc.
Regional European differences in allele and genotype frequencies of low density lipoprotein receptor‐related protein 1 polymorphism in Alzheimer's disease
Authors: Panza Francesco , D'Introno Alessia , Colacicco Anna M. , Capurso Cristiano , Basile Anna M. , Capurso Sabrina , Capurso Antonio , Solfrizzi Vincenzo
Published: March 2004

The low density lipoprotein receptor‐related protein 1 (LRP1 gene) is a candidate gene for Alzheimer's disease (AD), because it is a ligand for proteins involved in AD pathogenesis, such as apolipoprotein E (APOE), α2‐macroglobulin (A2M), amyloid precursor protein (APP), and is located on chromosome 12, within a region linked with AD. An association between a silent polymorphism (C/T) in exon 3 and late onset AD has been reported, with an increased frequency of the C allele, although with conflicting results. We examined this polymorphism in a cohort of 166 sporadic AD patients and 225 sex‐ and age‐matched nondemented controls from Southern Italy. No statistically significant differences were found in LRP1 genotype and allele frequencies between the whole AD sample and controls, nor in early‐ and late‐onset subsets of AD patients. No statistically significant differences in frequencies between LRP1 alleles and AD among APOE allele, age, or gender strata were found. Finally, comparing our results with the findings from other European populations, the LRP1 C allele frequency showed a statistically significant decreasing trend from Northern to Southern regions of Europe, with a concomitant increase in LRP1 T allele frequency, but in AD patients only. Finally, in the AD sample, a decreasing geographical trend from North to South of Europe was found for LRP1 CC genotype, and an inverse trend for LRP1 CT genotype frequency. We suggest that these regional variations in LRP1 genotype and allele frequencies in AD could be related to the different patterns of association between this polymorphism and the disease in various European studies. © 2003 Wiley‐Liss, Inc.
Modeling AC current conduction through a human tooth
Authors: Križaj Dejan , Jan Janja , Valenčič Vojko
Published: March 2004

Impedance between the electrode inserted in a root canal of a human tooth and the outer electrode placed on the oral mucosa serves as a measure of the root canal length, a vital parameter necessary for efficient endodontic procedure in dentistry. For better understanding of current conduction through the tooth, the impedance has been measured on extracted teeth (in vitro) and further used to develop corresponding electrical lumped element models. For modeling the metal/solution interface and complex structure of the tooth, Fricke's constant phase elements are employed. More detailed insight into current conduction is given by numerical simulation. Numerical simulation demonstrates the influence on the impedance of several important parameters, such as dentin conductance, canal preparation, and solution conductance. Bioelectromagnetics 25:185–195, 2004. © 2004 Wiley‐Liss, Inc.
Studies on microwaves in medicine and biology: From snails to humans
Authors: Lin James C.
Published: March 2004

This d'Arsonval Medal acceptance presentation highlights several research themes selected from Dr. Lin's published works, focusing on the microwave portion of the nonionizing electromagnetic spectrum. The topics discussed include investigation of microwave effects on the spontaneous action potentials and membrane resistance of isolated snail neurons, effects on the permeability of blood brain barriers in rats, the phenomenon and interaction mechanism for the microwave auditory effect (the hearing of microwave pulses by animals and humans), the development of miniature catheter antennas for microwave interstitial hyperthermia treatment of cancer, the application of transcatheter microwave ablation for treatment of cardiac arrhythmias, and the use of noninvasive wireless technology for sensing of human vital signs and blood pressure pulse waves. The paper concludes with some observations on research and other endeavors in the interdisciplinary field of bioelectromagnetics. Bioelectromagnetics 25:146–159, 2004. © 2004 Wiley‐Liss, Inc.
Orientation of DNA on a surface from simulation
Authors: Wong Ka‐Yiu , Pettitt B. Montgomery
Published: March 2004

DNA orientation near surfaces determines many properties related to hybridization efficiency. We performed a 40‐ns molecular dynamics simulation to study the structure and orientation of a 12‐base‐pair DNA duplex tethered to a neutral, epoxide‐coated silica surface. Starting with a canonical B‐form tethered in an up‐right position, normal to the surface, the DNA tilted to over 55° and back. The time scale was a few nanoseconds for tilting events. The linker between the DNA and the surface went from standing upright to tilted, and finally collapsed on the surface. Although the DNA conformation fluctuated, it remained closed to B‐form for the entire 40 ns. Calculations of helical parameters of the DNA show that the tethered end of the DNA changed its conformation noticeably when attracted to the surface. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Strategies for covalent attachment of DNA to beads
Authors: Steinberg Gali , Stromsborg Katie , Thomas Lynette , Barker David , Zhao Chanfeng
Published: March 2004

Several covalent attachment chemistries were tested for the immobilization of DNA onto glass beads. The comparison was based on the ability of these chemistries to produce derivatized beads that give good hybridization signals. Cyanuric chloride, isothiocyanate, nitrophenyl chloroformate, and hydrazone chemistries gave us the best (yet comparable) hybridization signals. We further characterized the cyanuric chloride method for the number of attachment sites, number of hybridizable sites, hybridization kinetics, effect of linker length on hybridization intensity and stability of the derivatized beads. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004
Implementation of a specialist-led service for the management of acute gallstone disease
Authors: Mercer S J , Knight J S , Toh S K C , Walters A M , Sadek S A , Somers S S
Published: March 2004

Background

The ‘gold standard’ treatment for acute cholecystitis and biliary colic requiring hospital admission is urgent laparoscopic cholecystectomy. This is not routinely available in all hospitals.

Methods

A retrospective audit of emergency admissions with acute cholecystitis or biliary colic from January to December 2000 led to the development and implementation of a specialist-led protocol for the urgent management of acute gallstone disease. A second audit was carried out covering the 6 months after implementation.

Results

One hundred and fifty-eight patients were admitted with acute cholecystitis or biliary colic in the first audit period and 110 in the second interval. The rate of cholecystectomy at index admission increased from 37·3 to 67·3 per cent, at a median of 3 days after admission, and the conversion rate to open surgery fell from 32 to 12 per cent. Median hospital stay fell from 9 to 5·5 days, and the unplanned readmission rate decreased from 19·0 to 3·6 per cent.

Conclusion

Urgent cholecystectomy for the management of acute gallstone disease is feasible and achievable in an acute services hospital with a specialist upper gastrointestinal team. It can lead to a reduced conversion rate, shorter hospital stay, fewer unplanned readmissions, an acceptable operating time and a low complication rate. The protocol is recommended for implementation in other hospitals.
Training and patient safety
Authors: Thorpe P
Published: March 2004

Patient Safety Leading Article Series, 2004 Over the rest of 2004 BJS will publish a series of leading articles dealing with issues of patient safety. A personal view of the matter was sought from the perspective of a trainee, Paul Thorpe, British trained but currently working in Australia. The trainee's view, sadly but typically, tends to come last—but not this time. Paul's article starts off the series. He notes that hospitals lag behind the airline industry and it is fitting, therefore, that the second paper is by Manfred Müller of Lufthansa.
Topography and interactions of the arytenoid and cricoid articular facets: Implications for vocal process positional shifts
Authors: Probst Kenneth X. , Schön Ybarra Miguel A. , Kashima Haskin , Crosby Ranice W.
Published: March 2004

Using new computer applications and digital technologies, we provide a rigorous description and realistic illustrations of the arytenoid‐on‐the cricoid rotations. We also provide the articular facet topography and interactions that underlay those rotations and the concomitant vocal process positional shifts. The thyroid cartilage and all soft tissues were removed from three excised, preserved, normal, adult human larynges without disturbing the crico‐arytenoid (CA) articular capsule. Three CA assemblies were thus prepared and used to digitize arytenoid rotations and vocal process positional shifts, and, after disarticulation, also the surface contour of the arytenoid and cricoid facets, and the cricoid lumen margin. The digitized data served to computer generate 2D and 3D graphic visualizations of the vocal process positional shifts, of the topography of the facets, and of the facet motion sequences that show that the anteroposteriorly concave arytenoid facet slides and conjunctly rotates on the anteroposteriorly convex cricoid facet. Visual details of all graphic representations and facet motion sequences were essentially identical across the three assemblies. Then, based on the computer generated data obtained from the largest of the CA assemblies, 3D, realistic, and hand‐drawn images were made that illustrate the directions in which the arytenoids can rotate and the vocal processes concomitantly shift positions. Results indicate that when the arytenoids rotate by sliding from anterior to posterior on the cricoid facets about a primary axis of motion aligned from medial, posterior, and superior, to lateral, anterior, and inferior, their vocal processes shift positions along a plane obliquely oriented from anterior and medial, to posterior and lateral, and from inferior and medial, to superior and lateral. Clin. Anat. 17:206–213, 2004. © 2004 Wiley‐Liss, Inc.
Comparison of clinical and molecular surveillance in patients with advanced nasopharyngeal carcinoma after primary therapy
Authors: Hong Ruey‐Long , Lin Chin‐Yu , Ting Lai‐Lei , Ko Jenq‐Yuh , Hsu Mow‐Ming
Published: March 2004

BACKGROUND

The importance of detecting recurrence at an early stage in patients with malignant disease is well recognized. Circulating Epstein–Barr virus (EBV) DNA can be detected in patients with nasopharyngeal carcinoma (NPC). The objective of the current study was to assess the effectiveness of plasma EBV DNA monitoring in the early detection of NPC recurrence compared with conventional methods.

METHODS

Patients with NPC in two prospective clinical trials who had locoregional recurrences or distant metastases were recruited into the study. Clinical data on these patients were scrutinized for evidence of recurrence. EBV DNA copy numbers in the prospectively collected plasma samples were assayed retrospectively with real‐time quantitative polymerase chain reaction analysis.

RESULTS

At the time of clinical recurrence, 65% of 26 patients with locoregional recurrences and all but 1 of 28 patients with distant failure had circulating EBV DNA. The difference between the time from completion of treatment to positivity for circulating EBV DNA and the time from completion of treatment to the first observed clinical abnormality was not statistically significant for patients with local recurrence (P = 0.84). However, the time to the first detection of circulating EBV DNA was significantly shorter among patients with distant metastases (P < 0.0001). The Kaplan–Meier estimated median time to the emergence of plasma EBV DNA was 190 days, with a 95% confidence interval (CI) of 95–300 days, and the median time to the first observed clinical abnormality was 295 days (95% CI, 276–361 days).

CONCLUSIONS

Monitoring plasma EBV DNA levels surpassed traditional methods for the early detection of distant failure in patients with NPC. The role of this technique should be evaluated in prospective studies that incorporate complementary advanced imaging technology. Cancer 2004;100:1429–37. © 2004 American Cancer Society.
Improvement of Selectivity in Specific Adsorption by the Addition of Acetic Acid during the CVD of Silicon Alkoxide to Form a Silica Overlayer with a Molecular Sieving Property
Authors: Katada N. , Akazawa S. , Niwa M.
Published: March 2004

The CVD of silicon alkoxide was carried out on a tin oxide surface coated with pre‐adsorbed carboxylate anions as templates. During the deposition of alkoxide, acetic acid was added in order to accelerate the formation of siloxane. After removal of the template and acetic acid, both the template molecule itself and the smaller molecule were adsorbed, while the adsorption of larger molecules was almost completely suppressed. The shape‐selective adsorption capacity was thus observed, and the presence of a cavity, the shape and size of which were controlled by the template molecule, is suggested.
Identification and characterisation of mRif1: A mouse telomere‐associated protein highly expressed in germ cells and embryo‐derived pluripotent stem cells
Authors: Adams Ian R. , McLaren Anne
Published: March 2004

We have identified a mouse ortholog of the yeast Rif1 family of telomere‐associated proteins on the basis of its high expression in primordial germ cells and embryo‐derived pluripotent stem cell lines. mRif1 is also highly expressed in totipotent and pluripotent cells during early mouse development, and in male and female germ cells in adult mice. mRif1 expression is induced during derivation of embryonic stem cells and is rapidly down‐regulated upon differentiation of embryonic stem cells in vitro. Furthermore, we show that mRif1 physically interacts with the telomere‐associated protein mTrf2 and can be cross‐linked to telomeric repeat DNA in mouse embryonic stem cells. mRif1 may be involved in the maintenance of telomere length or pluripotency in the germline and during early mouse development. Developmental Dynamics 229:733–744, 2004. © 2004 Wiley‐Liss, Inc.
Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant‐negative mechanism
Authors: Hime Gary R. , Lada Hania , Fietz Michael J. , Gillies Susan , Passmore Abraham , Wicking Carol , Wainwright Brandon J.
Published: March 2004

Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol‐sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C‐terminal truncation that has been characterised previously as a dominant‐negative protein. G509V exhibits vesicular localisation identical to the wild‐type protein, but the C‐terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant‐negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant‐negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant‐negative function. Developmental Dynamics 229:780–790, 2004. © 2004 Wiley‐Liss, Inc.
Genetic background has a major effect on the penetrance and severity of craniofacial defects in mice heterozygous for the gene encoding the nucleolar protein treacle
Authors: Dixon Jill , Dixon Michael James
Published: March 2004

Treacher Collins syndrome (TCS) is a craniofacial disorder that results from mutations in TCOF1, which encodes the nucleolar protein Treacle. The severity of the clinical features exhibits wide variation and includes hypoplasia of the mandible and maxilla, abnormalities of the external ears and middle ear ossicles, and cleft palate. To determine the in vivo function of Treacle, we previously generated Tcof1 heterozygous mice on a mixed C57BL/6 and 129 background. These mice exhibited a lethal phenotype, which included abnormal development of the maxilla, absence of the eyes and nasal passages, and neural tube defects. Here, we show that placing the mutation onto different genetic backgrounds has a major effect on the penetrance and severity of the craniofacial and other defects. The offspring exhibit markedly variable strain‐dependent phenotypes that range from extremely severe and lethal in a mixed CBA/Ca and 129 background, to apparently normal and viable in a mixed BALB/c and 129 background. In the former case, in addition to a profoundly severe craniofacial phenotype, CBA‐derived heterozygous mice also exhibited delayed ossification of the long bones, rib fusions, and digit anomalies. The results of our studies indicate that factors in the different genetic backgrounds contribute extensively to the Tcof1 phenotype. Developmental Dynamics 229:907–914, 2004. © 2004 Wiley‐Liss, Inc.
Alternative processing for MHC class I presentation by immature and CpG‐activated dendritic cells
Authors: Chen Liying , Jondal Mikael
Published: March 2004

Exogenous proteins can be processed by antigen‐presenting cells for the generation of MHC class I‐restricted T cell responses. Where this occurs is not clear, although both transfer of internalized antigen into the cytosol and alternative processing in endolysosomes and phagosomes have been reported. Here we have studied the capacity of bone marrow‐derived mouse myeloid dendritic cells (DC) to process the OVA protein for peptide presentation by H2‐Kb. We have found that immature DC (iDC), both wild‐type and transporter associated with antigen processing (TAP)‐deficient cells, can transiently process OVA in a pathway which is resistant to inhibitors of the classical MHC class I pathway including the Golgi inhibitor Brefeldin A (BFA) and the proteasome inhibitor lactacystin. This alternative pathway is not found in subcultured DC with an intermediate maturity (imDC) or in resting, IL‐3 expanded macrophages but can be re‐expressed in imDC if these are activated byan immunostimulatory CpG oligonucleotide. Both iDC and CpG‐activated DC were found to process OVA by regurgitation. In addition, we found that iDC secrete proteolytic enzymes into the supernatant, which can process OVA in the extracellular phase. These results suggest that multiple pathways exist for the processing of exogenous protein antigens into MHC class I‐binding peptides.
CTLA‐4‐dependent mechanisms prevent T cell induced‐liver pathology during the erythrocyte stage of Plasmodium berghei malaria
Authors: Jacobs Thomas , Plate Tanja , Gaworski Iris , Fleischer Bernhard
Published: March 2004

During the course of malaria several organs develop pathology. Frequently also signs of hepatocyte damage are found. In the present work we studied the mechanisms leading to liver pathology during the erythrocyte stage of Plasmodium berghei malaria. During infection, mice developed an inflammation of the liver, associated with infiltration of T cells, although only little tissuedamage could be observed. Histological analysis revealed the presence of CTL‐associated antigen‐4 (CTLA‐4)‐positive T cells in the liver parenchyma. To study the influence of CTLA‐4 expression on liver inflammation, mice were treated with an antibody against CTLA‐4. Treated mice suffered from a dramatically increased liver pathology. Using cytokine‐deficient mice we found that pathology was dependent on the presence of IL‐12 and IFN‐γ. To further study the mechanisms that lead to an enhanced pathology, we analyzed cytokine production from liver‐derived T cells. In infected mice the frequency of IFN‐γ‐producing cells in the liver was low. In contrast, in anti‐CTLA‐4‐treated mice larger numbers of IFN‐γ‐producing cells were detectable. Our results indicate that activated T cells during the erythrocyte stage of malaria can induce pathology due to secretion of pro‐inflammatory cytokines. Moreover, these results provide evidence that CTLA‐4 expression can restrict T cell function in inflamed organs and might therefore prevent pathology.