bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers
Authors: Nicolau G. , Feighner J.P. , Stout R. , Hlavka J. , Gutierrez M. , Ciric S. , Freed J.
Published: August 2005

The purpose of this study was to evaluate the safety and pharmacokinetics of nemifitide, a synthetic antidepressant pentapeptide, following its subcutaneous (s.c.) administration by standard needle injection or by a needle‐free (Bioject™) injection and to compare these two routes of administration for systemic exposure. This small‐scale, randomized, single‐dose, parallel design, open‐label pilot study consisted of three treatment groups of four subjects each dosed as follows: group 1: 40 mg of nemifitide administered by standard needle/syringe and groups 2 and 3: 40 and 80 mg nemifitide, respectively, administered by using a needle‐free (Bioject™) injection delivery system. Plasma concentrations of nemifitide were determined by LC/MS/MS in blood samples collected at 10 min and 0.5, 1, 2, 4, 6 and 24 h after dosing. PK parameters, including observed Cmax, Tmax and AUC0−24, were calculated and statistical analysis of the data was conducted. Safety assessments (dosing site evaluations) were done at 0.5, 1, 5 and 24 h after dosing. Vital signs and clinical laboratory tests were taken on day 1 prior to dosing and at 24 h post‐dose. Adverse experiences in all subjects were observed only as drug‐related local reactions at the injection sites. All were considered mild in severity and transient (resolved by 24 h after dosing). Tmax was observed at 10 min after dose and was the same in all subjects. In the three dosing groups, 1 (40 mg), 2 (40 mg) and 3 (80 mg), observed Cmax values were 226, 245 and 440 ng/ml, respectively, and AUC0−24 values were 108, 106 and 205 ng·h/ml, respectively. Ratios of AUC0−24 and observed Cmax for nemifitide in plasma between groups 1 and 2 were within the 80%–125% range, indicating that the two modes of drug administration resulted in similar systemic exposure to nemifitide. Pharmacokinetic parameters (AUC0−24 and Cmax) indicate dose‐proportionality between the doses of 40 and 80 mg. Copyright © 2005 John Wiley & Sons, Ltd.
Influence of sucrose and water content on molecular mobilityin starch‐based glasses as assessed through structureand secondary relaxation
Authors: Poirier‐Brulez Fabienne , Roudaut Gaëlle , Champion Dominique , Tanguy Marie , Simatos Denise
Published: August 2005

Molecular mobility is known to be a key parameter in controlling the physical properties of materials and thus their quality and performance. Beyond glass transition related changes, attention should be called to the impact of local motions remaining in the glassy state. Gelatinized waxy maize starch at different sucrose contents (0–20% solids) was equilibrated between 0 and 14% water and sorption isotherms determined at 25°C. The effect of water and sucrose content on the molecular mobility of glassy starch was investigated by differential scanning calorimetry through enthalpy relaxation studies and dynamical mechanical thermal analysis. The existence of sucrose–starch interactions was suggested by the sorption isotherms not following the expected additivity of the single component sorption curves. Contrary to the glass transition or associated α relaxation, water and sucrose affected differently the secondary relaxations. Indeed, the β relaxation observed around −15°C was shifted to lower temperature upon increasing hydration, and to higher temperature when sucrose content increased, suggesting a hindering of these local motions. Enthalpy relaxation of the ternary mixtures was studied following aging up to 668 h at Tg −15°C. Ternary mixtures exhibited an enthalpy relaxation upon aging lower than starch alone as a sign of lower polymer mobility in the presence of small molecules, contrary to the free volume theory. Relaxation kinetics were characterized with the Cowie–Ferguson model and compared to literature data. The extent of the enthalpy relaxation appeared to be controlled by the distance between the aging temperature and the β relaxation temperature. © 2005 Wiley Periodicals, Inc. Biopolymers 81: 63–73, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Interaction of heme proteins with poly(propyleneimine) dendrimers in layer‐by‐layer assembly films under different pH conditions
Authors: He Pingli , Li Min , Hu Naifei
Published: August 2005

With the isoelectric point at pH 7.4, hemoglobin (Hb) has net positive surface charges at pH 5.0 and overall negative charges at pH 9.0, and is essentially neutral at pH 7.0. The fifth‐generation poly(propyleneimine) (PPI) dendrimer is usually positively charged in aqueous solution. The {PPI/Hb}n films under different pH conditions have been successfully fabricated on various solid surfaces by the layer‐by‐layer assembly technique, and the growth of films was monitored by ultraviolet‐visible (UV‐vis) spectroscopy, quartz crystal microbalance (QCM), and cyclic voltammetry (CV). Not only was the negatively charged Hb at pH 9.0 alternately adsorbed with positively charged PPI onto solid substrates by electrostatic attraction between them, but the positively charged Hb at pH 5.0 was also successfully assembled with like charged PPI into layer‐by‐layer {PPI/Hb(pH 5.0)}n films. For the latter, the localized electrostatic interaction or the charge reversal of proteins on PPI surface may be the main driving force. For {PPI/Hb(pH 7.0)}n films, however, the hydrophobic/hydrophilic interaction may play a more important role in the assembly, making the amount of adsorbed Hb even less than that of {PPI/Hb(pH 5.0)}n films. For comparison, negatively charged catalase (Cat) at pH 8.0 was used to assemble layer‐by‐layer films with positive PPI, but {PPI/Cat}n films showed quite different properties from {PPI/Hb}n films. UV‐vis and infrared (IR) spectroscopy, QCM, ellipsometry, and voltammetry were utilized to characterize the {PPI/protein}n films. The results suggest that the proteins in the multilayer films retain their near‐native structure and display good voltammetric response for heme Fe(III)/Fe(II) redox couples at underlying pyrolytic graphite (PG) electrodes. Electrocatalysis of oxygen and hydrogen peroxide based on direct electrochemistry of heme proteins at {PPI/protein}n film electrodes was also demonstrated. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 310–323, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Improvement of domain linker prediction by incorporating loop‐length‐dependent characteristics
Authors: Tanaka Takanori , Yokoyama Shigeyuki , Kuroda Yutaka
Published: August 2005

Protein dissection into structural domains that can fold in isolation is an important issue in both functional and structural proteomics. Here, we analyzed inter‐ and intradomain loop sequences (respectively named domain linker and nonlinker loops) and computed a domain linker likelihood score, which was used for developing a domain boundary prediction protocol. The analysis confirmed our previous results indicating that the amino acid composition in terms of glycine, proline, aspartic acid, asparagine, lysine, and histidine significantly differs between linker and nonlinker loops. However, a detailed examination revealed that the amino acid composition bias actually depends on the loop length. Indeed, significant frequency deviations were observed for glycine, proline, and aspartic acid in short linker and nonlinker loops, whereas deviations were observed for aspartic acid, proline, asparagine, and lysine in long linker and nonlinker loops. Finally, we incorporated this loop‐length‐dependent amino acid composition bias in a simple linker prediction protocol, which predicted linkers with a 40.6% specificity and a 36.1% sensitivity. These figures are 4.4 and 2.4% higher than those obtained with our former prediction protocol that does not incorporate loop‐length‐dependent characteristics. This result should have practical significance for experimental protein dissection, since the probability of obtaining a stably folding structural domain by randomly dissecting a protein sequence is estimated to be 12.6%. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 161–168, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Monte Carlo simulation of protein folding in the presence of residue‐specific binding sites
Authors: Rossinsky E. , Srebnik S.
Published: August 2005

Ensemble growth Monte Carlo (EGMC) and dynamic Monte Carlo (DMC) simulations are used to study sequential folding and thermodynamic stability of hydrophobic–polar (HP) chains that fold to a compact structure. Molecularly imprinted cavities are modeled as hard walls having sites that are attractive to specific polar residues on the chain. Using EGMC simulation, we find that the folded conformation can be stabilized using a small number of carefully selected residue‐specific sites while a random selection of surface‐bound residues may only slightly contribute toward stabilizing the folded conformation, and in some cases may hinder the folding of the chain. DMC simulations of the surface‐bound chain confirm increased stability of the folded conformation over a free chain. However, a different trend of the equilibrium population of folded chains as a function of residue‐external site interactions is predicted with the two simulation methods. © 2005 Wiley Periodicals, Inc. Biopolymers 79: 259–268, 2005

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Prospective analysis of patients with adenocarcinoma of the gastric cardia and lymph node metastasis in the proximal field of the chest
Authors: Lagarde S M , Cense H A , Hulscher J B F , Tilanus H W , Ten Kate F J W , Obertop H , van Lanschot J J B
Published: August 2005

Background

The extent to which adenocarcinoma of the cardia with lymph node metastasis in the upper mediastinum is amenable to cure by radical surgery is open to debate. It remains unclear whether these relatively distant metastases have an effect on long-term survival. The aim of this study was to identify the incidence of such positive nodes and evaluate their prognostic significance.

Methods

Some 50 patients with adenocarcinoma of the gastric cardia and substantial invasion of the oesophagus (junctional type II), who underwent an extended transthoracic oesophagectomy as part of a prospective randomized trial between 1994 and 2000, were studied.

Results

Eleven patients (22 per cent) had lymph node metastasis in the proximal field of the chest. These patients had more positive nodes overall (P = 0·020) and a shorter median survival (P = 0·009) than those without such metastasis. Multivariate analysis identified positive nodes in the proximal field as an independent predictor of poor survival.

Conclusion

Lymph node metastasis in the proximal field of the chest is common and is an indicator of poor prognosis in patients with adenocarcinoma of the cardia.
The Mechanism of Formamide Hydrolysis in Water from Ab Initio Calculations and Simulations
Authors: Gorb Leonid , Asensio Amparo , Tuñón Iñaki , Ruiz‐López Manuel F.
Published: August 2005

The neutral hydrolysis of formamide in water is a suitable reference to quantify the efficiency of proteolytic enzymes. However, experimental data for this reaction has only very recently been obtained and the kinetic constant determined experimentally is significantly higher than that predicted by previous theoretical estimations. In this work, we have investigated in detail the possible mechanisms of this reaction. Several solvent models have been considered that represent a considerable improvement on those used in previous studies. Density functional and ab initio calculations have been carried out on a system which explicitly includes the first solvation shell of the formamide molecule. Its interaction with the bulk has been treated with the aid of a dielectric continuum model. Molecular dynamics simulations at the combined density functional/molecular mechanics level have been carried out in parallel to better understand the structure of the reaction intermediates in aqueous solution. Overall, the most favored mechanism predicted by our study involves two reaction steps. In the first step, the carbonyl group of the formamide molecule is hydrated to form a diol intermediate. The corresponding transition structure involves two water molecules. From this intermediate, a water‐assisted proton transfer occurs from one of the hydroxy groups to the amino group. This reaction step may lead either to the formation of a new reaction intermediate with a marked zwitterionic character or to dissociation of the system into ammonia and formic acid. The zwitterionic intermediate dissociates quite easily but its lifetime is not negligible and it could play a role in the hydrolysis of substituted amides or peptides. The predicted pseudo‐first‐order kinetic constant for the rate‐limiting step (the first step) of the hydrolysis reaction at 25 °C (3.9×10−10 s−1) is in excellent agreement with experimental data (1.1×10−10 s−1).
Triple Hydrogen Bonds Direct Crystal Engineering of Metal‐Assembled Complexes: The Effect of a Novel Organic–Inorganic Module on Supramolecular Structure
Authors: Adachi Keiichi , Sugiyama Yuichi , Yoneda Ko , Yamada Koichi , Nozaki Koichi , Fuyuhiro Akira , Kawata Satoshi
Published: August 2005

Novel triply hydrogen bonded suprastructures based on [M(tdpd)2(L)2]2− (H2tdpd=1,4,5,6‐tetrahydro‐5,6‐dioxo‐2,3‐pyrazinedicarbonitrile, L=solvent) and melamine‐analogous cations have been synthesized and characterized. The use of anions containing two AAA sets from [M(tdpd)2(L)2]2− together with cations containing one DDD set (A=hydrogen‐bond acceptor, D=hydrogen‐bond donor) leads to the formation of complementary triply hydrogen bonded modules in the solid state. In all cases, the building module is further extended via additional hydrogen‐bonding interactions to produce a tape, and tapes are assembled into sheets. These results show that a hydrogen‐bonded module consisting of different kinds of building blocks, one of which is a metal complex that includes hydrogen‐bond acceptor sites and the other is a hydrogen‐bond donor molecule, will be attractive for constructing metal‐containing supramolecular systems by the self‐assembly technique.
Rh‐Catalyzed Asymmetric Hydrogenation of Prochiral Olefins with a Dynamic Library of Chiral TROPOS Phosphorus Ligands
Authors: Monti Chiara , Gennari Cesare , Piarulli Umberto , de Vries Johannes G. , de Vries André H. M. , Lefort Laurent
Published: August 2005

A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P‐bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium‐catalyzed asymmetric hydrogenation of dehydro‐α‐amino acids, dehydro‐β‐amino acids, enamides and dimethyl itaconate. ee values up to 98 % were obtained for the dehydro‐α‐amino acids, by using the best combination of ligands, a phosphite [4‐P(O)2O] and a phosphoramidite [13‐P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4‐P(O)2O] and phosphoramidite [13‐P(O)2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2‐acetamidoacrylate and methyl 2‐acetamidocinnamate faster than the mixture of the same phosphite with the phosphoramidite, while the phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/phosphoramidite ratio is also presented.
A Highly Directional Fourfold Hydrogen‐Bonding Motif for Supramolecular Structures through Self‐Assembly of Fullerodendrimers
Authors: Hahn Uwe , González Juan J. , Huerta Elisa , Segura Margarita , Eckert Jean‐François , Cardinali François , de Mendoza Javier , Nierengarten Jean‐François
Published: August 2005

Supramolecular dendrimers resulting from the dimerization of fullerene‐functionalized dendrons through a quadruple hydrogen‐bonding motif were prepared. The synthetic strategy is based on the esterification of a tert‐butoxycarbonyl (Boc)‐protected 2‐ureido‐4‐[1H]pyrimidinone precursor possessing an alcohol function with fullerodendrons bearing a carboxylic acid unit at the focal point. Subsequent acidic treatment to cleave the protecting group and reaction of the resulting amine with octylisocyanate affords the targeted compounds. As demonstrated by the results of MALDI‐TOF mass spectrometry and 1H NMR spectroscopy, both of the 2‐ureido‐4‐[1H]pyrimidinone derivatives form self‐assembled dimers spontaneously through hydrogen‐bonding interactions, thus leading to supramolecular structures containing two or ten fullerene moieties.
Incidence of chemotherapy‐induced, long‐term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane
Authors: Fornier Monica N. , Modi Shanu , Panageas Katherine S. , Norton Larry , Hudis Clifford
Published: August 2005

BACKGROUND

Twenty‐five percent of all women with breast carcinoma are premenopausal and are at risk for chemotherapy‐induced menopause with long‐term side effects. Although there is considerable documentation of the rates of chemotherapy‐induced amenorrhea with classic adjuvant regimens, there are inadequate data that address the impact of taxanes on menstrual function in this setting. The objective of this analysis was to determine the incidence of long‐term amenorrhea (≥ 12 mos) in women with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane‐based chemotherapy, with or without subsequent tamoxifen.

METHODS

The authors identified 235 premenopausal women with breast carcinoma age 40 years or younger who were treated with adjuvant anthracycline and taxane‐based chemotherapy at Memorial Sloan‐Kettering Cancer Center from January 1997 to June 2003.

RESULTS

One hundred sixty‐six patients met all eligibility criteria and had sufficient follow‐up for evaluation. The median age of patients at diagnosis was 36 years (range, 27–40 yrs). All patients had regular pretreatment menses, 25 patients (15%) developed long‐term amenorrhea, and 141 patients (85%) resumed menstruation. Eighty‐two patients (49%) also received tamoxifen: The incidence of amenorrhea among them was 17%. There was a statistically significant association between age and the development of amenorrhea, with older women at higher risk. (P < 0.01)

CONCLUSIONS

The sequential addition of a taxane to standard adjuvant anthracycline‐based chemotherapy did not appear to produce a high rate of chemotherapy‐related amenorrhea compared with historic controls. To increase the information available to assist young patients who are considering adjuvant therapy, prospective studies should incorporate menstrual function ascertainment by patient‐reported history and assays of ovarian function. Cancer 2005. © 2005 American Cancer Society.
DNA methylation of genes linked with retinoid signaling in gastric carcinoma
Authors: Shutoh Mariko , Oue Naohide , Aung Phyu Phyu , Noguchi Tsuyoshi , Kuraoka Kazuya , Nakayama Hirofumi , Kawahara Katsunobu , Yasui Wataru
Published: August 2005

BACKGROUND

Hypermethylation of CpG islands has been associated with silencing of various tumor suppressor genes, and the retinoid acid receptor β (RARβ), cellular retinol‐binding protein 1 (CRBP1), and tazarotene‐induced gene 1 (TIG1) genes have been associated with retinoic acid signaling. To the authors' knowledge, little is known regarding the involvement of these three genes in gastric carcinoma (GC). In this study, the authors investigated the methylation status of these genes and analyzed the role of their DNA methylation in GC.

METHODS

DNA methylation of 3 retinoic acid‐associated genes was analyzed in 42 samples of GC from 42 patients and in 8 GC cell lines by methylation‐specific polymerase chain reaction (PCR) analysis. The mRNA expression levels for these three genes were measured by quantitative reverse transcription‐PCR.

RESULTS

In 7 of 8 GC cell lines, the CRBP1 gene was hypermethylated, and CRBP1 transcription was inactive. In 6 of 8 GC cell lines, the TIG1 gene was hypermethylated, and TIG1 transcription was inactive. Treatment with demethylating agent 5‐aza‐2′‐deoxycytidine restored both CRBP1 and TIG1 transcription. DNA methylation of the RARβ, CRBP1, and TIG1 genes was detected in 15 of 42 GC samples (36%), 14 of 42 GC samples (33%), and 4 of 42 GC samples (10%), respectively, and in 6 of 30 samples (20%), 0 of 30 samples (0%), and 1 of 30 samples (3%) of corresponding nonneoplastic mucosa. None of the 10 normal gastric mucosa samples from young, healthy individuals demonstrated hypermethylation of any of these genes. DNA methylation of each gene was associated significantly with low mRNA expression of the respective gene. Twenty‐four of 42 GC samples (57%) demonstrated hypermethylation of at least 1 of the 3 genes. However, no significant, concordant hypermethylation of these genes was observed.

CONCLUSIONS

The results suggested that gastric carcinogenesis involves transcriptional inactivation by aberrant DNA methylation of genes related to retinoid signaling. Cancer 2005. © 2005 American Cancer Society.
A phase I trial of protracted oral fixed‐dose temozolomide
Authors: Jones Suzanne F. , Greco F. Anthony , Gian Victor G. , Miranda Fernando T. , Raefsky Eric L. , Hainsworth John D. , Willcutt Noel T. , Beschorner Aurelia F. , Kennerly Glyndon , Burris Howard A.
Published: August 2005

BACKGROUND

The current Phase I trial was conducted to determine the dose‐limiting toxicity (DLT), maximum tolerated dose, and recommended Phase II dose of oral fixed‐dose temozolomide when administered for 5 of every 7 days on a continuous basis.

METHODS

Patients received a fixed dose of temozolomide daily for 5 of every 7 days continuously. Four weeks of treatment were considered 1 treatment cycle. Patients were accrued at 7 different dose levels ranging from 100 mg/day to 360 mg/day.

RESULTS

Forty‐six patients received 111 cycles of therapy. DLT consisted of myelosuppression, particularly thrombocytopenia. The primary nonhematologic toxicities were nausea and emesis, which were easily controlled with antiemetics.

CONCLUSIONS

Protracted administration of temozolomide at a fixed dose of 300 mg/day for 5 of every 7 days continuously was well tolerated and allowed greater dose intensity compared with various other schedules. This regimen could potentially increase antitumor activity as protracted temozolomide schedules inhibit DNA repair by depletion of the repair protein O6‐methylguanine‐DNA methyltransferase. Cancer 2005. © 2005 American Cancer Society.
Subbarrel domains in rat somatosensory (S1) cortex
Authors: Land Peter W. , Erickson Susan L.
Published: August 2005

We used cytochrome oxidase (CO) histochemistry in conjunction with other histological methods to investigate the histochemoarchitecture of barrel hollows in rat somatosensory cortex. We found that individual large barrels in the posteromedial barrel subfield encompass two or three discrete subbarrel domains. Detailed analysis revealed, further, that subbarrel domains are relatively consistent in size, each having average dimensions that approximate those of large barrels in mouse S1. Unexpectedly, subbarrel domains are organized into a few distinct, repeated patterns. The small barrels in rat anterolateral barrel subfield and all barrel hollows in mouse S1 appear to consist of single CO domains. Subbarrel domains revealed here by CO are columnar entities that correspond with cyto‐ and myeloarchitectonic inhomogeneities within the barrels and are enriched in thalamocortical axon terminals. The present findings together with existing data indicate that barrels in rat posteromedial barrel subfield are structurally and functionally heterogeneous. J. Comp. Neurol. 490:414–426, 2005. © 2005 Wiley‐Liss, Inc.
Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice
Authors: Stack Edward C. , Kubilus James K. , Smith Karen , Cormier Kerry , Del Signore Steven J. , Guelin Emmanuel , Ryu Hoon , Hersch Steven M. , Ferrante Robert J.
Published: August 2005

Genetic murine models play an important role in the study of human neurological disorders by providing accurate and experimentally accessible systems to study pathogenesis and to test potential therapeutic treatments. One of the most widely employed models of Huntington's disease (HD) is the R6/2 transgenic mouse. To characterize this model further, we have performed behavioral and neuropathological analyses that provide a foundation for the use of R6/2 mice in preclinical therapeutic trials. Behavioral analyses of the R6/2 mouse reveal age‐related impairments in dystonic movements, motor performance, grip strength, and body weight that progressively worsen until death. Significant neuropathological sequela, identified as increasing marked reductions in brain weight, are present from 30 days, whereas decreased brain volume is present from 60 days and decreased neostriatal volume and striatal neuron area, with a concomitant reduction in striatal neuron number, are present at 90 days of age. Huntingtin‐positive aggregates are present at postnatal day 1 and increase in number and size with age. Our findings suggest that the R6/2 HD model exhibits a progressive HD‐like behavioral and neuropathological phenotype that more closely corresponds to human HD than previously believed, providing further assurance that the R6/2 mouse is an appropriate model for testing potential therapies for HD. J. Comp. Neurol. 490:354–370, 2005. © 2005 Wiley‐Liss, Inc.
Synaptic ultrastructure of Drosophila Johnston's organ axon terminals as revealed by an enhancer trap
Authors: Sivan‐Loukianova Elena , Eberl Daniel F.
Published: August 2005

The role of auditory circuitry is to decipher relevant information from acoustic signals. Acoustic parameters used by different insect species vary widely. All these auditory systems, however, share a common transducer: tympanal organs as well as the Drosophila flagellar ears use chordotonal organs as the auditory mechanoreceptors. We here describe the central neural projections of the Drosophila Johnston's organ (JO). These neurons, which represent the antennal auditory organ, terminate in the antennomechanosensory center. To ensure correct identification of these terminals we made use of a β‐galactosidase‐expressing transgene that labels JO neurons specifically. Analysis of these projection pathways shows that parallel JO fibers display extensive contacts, including putative gap junctions. We find that the synaptic boutons show both chemical synaptic structures as well as putative gap junctions, indicating mixed synapses, and belong largely to the divergent type, with multiple small postsynaptic processes. The ultrastructure of JO fibers and synapses may indicate an ability to process temporally discretized acoustic information. J. Comp. Neurol. 491:46–55, 2005. © 2005 Wiley‐Liss, Inc.
Differential distribution of voltage‐gated calcium channel alpha‐2 delta (α2δ) subunit mRNA‐containing cells in the rat central nervous system and the dorsal root ganglia
Authors: Cole Rebecca L. , Lechner Sandra M. , Williams Mark E. , Prodanovich Pat , Bleicher Leo , Varney Mark A. , Gu Guibao
Published: August 2005

Voltage‐gated calcium channels (VGCCs) play an essential role in controlling neurotransmitter release, neuronal excitability, and gene expression in the nervous system. The distribution of cells that contain mRNAs encoding the auxiliary α2δ‐1, α2δ‐2, and α2δ‐3 subunits of the VGCCs in the central nervous system (CNS) and the dorsal root ganglia (DRG) was examined in rats by using in situ hybridization. Specific labeling of α2δ‐1, α2δ‐2, and α2δ‐3 mRNAs appeared to be largely confined to neurons and was widely, although differentially, distributed in the brain, the spinal cord, and the DRG. Importantly, α2δ‐2 mRNA was found to be expressed in interneurons in the cortex, the hippocampus, the striatum, and in regions that contain dense cholinergic neurons. Our results suggest that different α2δ subunits may exert distinctive functions in the CNS. The α2δ‐1 subunit mRNA is localized in brain regions known to be involved in cortical processing, learning and memory, defensive behavior, neuroendocrine secretion, autonomic activation, primary sensory transmission, and general arousal. The α2δ‐2 subunit mRNA is present in brain regions known to modulate the overall activities of the cortex, the hippocampus, and the thalamus. The α2δ‐2 subunit is also found in brain regions known to be involved in olfaction, somatic motor control, fluid homeostasis, ingestive and defensive behaviors, neuroendocrine functions, and circadian rhythm. In addition to being localized in brain regions that express α2δ‐1 and α2δ‐2 subunit mRNAs, α2δ‐3 subunit mRNA is highly expressed in regions involved in auditory information processing and somatic movement. J. Comp. Neurol. 491:246–269, 2005. © 2005 Wiley‐Liss, Inc.
Organization of Kenyon cells in subdivisions of the mushroom bodies of a lepidopteran insect
Authors: Sjöholm Marcus , Sinakevitch Irina , Ignell Rickard , Strausfeld Nicholas J. , Hansson Bill S.
Published: August 2005

The mushroom bodies are paired structures in the insect brain involved in complex functions such as memory formation, sensory integration, and context recognition. In many insects these centers are elaborate, sometimes comprising several hundred thousand neurons. The present account describes the mushroom bodies of Spodoptera littoralis, a moth extensively used for studies of olfactory processing and conditioning. The mushroom bodies of Spodoptera consist of only about 4,000 large‐diameter Kenyon cells. However, these neurons are recognizably similar to morphological classes of Kenyon cells identified in honey bees, Drosophila, and cockroaches. The spodopteran mushroom body is equipped with three major divisions of its vertical and medial lobe, one of which, the gamma lobe, is supplied by clawed class II Kenyon cells as in other described taxa. Of special interest is the presence of a discrete tract (the Y tract) of axons leading from the calyx, separate from the pedunculus, that innervates lobelets above and beneath the medial lobe, close to the latter's origin from the pedunculus. This tract is comparable to tracts and resultant lobelets identified in cockroaches and termites. The article discusses possible functional roles of the spodopteran mushroom body against the background of olfactory behaviors described from this taxon and discusses the possible functional relevance of mushroom body structure, emphasizing similarities and dissimilarities with mushroom bodies of other species, in particular the fruit fly, Drosophila melanogaster. J. Comp. Neurol. 491:290–304, 2005. © 2005 Wiley‐Liss, Inc.
Development of Hsp25 expression compartments is not constrained by Purkinje cell defects in the Lurcher mouse mutant
Authors: Armstrong Carol L. , Vogel M.W. , Hawkes Richard
Published: August 2005

Four transverse zones can be distinguished in the adult mouse cerebellar cortex based on differential expression of cell‐specific antigens, termination patterns of mossy fiber afferents, and phenotypes of mouse mutants with cerebellar defects: the anterior zone (AZ), central zone (CZ), posterior zone (PZ), and nodular zone (NZ). In the heterozygous Lurcher (Lc/+) mouse a zonally restricted abnormality in Purkinje cell development is seen. The Purkinje cell‐specific antigen zebrin II is normally differentially expressed in all four zones of the adult cerebellum, but in the Lc/+ mutant is confined to the PZ and NZ, caudal to a transverse boundary in the dorsal aspect of lobule VIII. In this study we wanted to understand why zebrin II expression is arrested at this boundary and whether the Lc mutation affects the differentiation of additional Purkinje cell antigens in a similar manner. To determine this, we took advantage of the dynamic developmental timetable of another Purkinje cell antigen, the small heat shock protein Hsp25. Using immunohistochemistry we demonstrate that cerebellar maturation anterior to the CZ/PZ transverse boundary appears to be unaffected by the Lc allele, in that initial progression of Hsp25 expression in the Lc/+ cerebellum was similar to controls. Double‐labeling experiments with anti‐Hsp25 and anti‐calbindin suggest that characteristic banding patterns of Hsp25 in Lc/+ cerebellum develop and are preserved despite cell loss. Thus, since simple temporal or spatial models cannot account for the zonal restriction seen during Lc/+ cerebellar development, the abnormality may be zebrin II‐specific. J. Comp. Neurol. 491:69–78, 2005. © 2005 Wiley‐Liss, Inc.
Expression of nestin–green fluorescent protein transgene marks oval cells in the adult liver
Authors: Gleiberman Anatoli S. , Encinas Juan M. , Mignone John L. , Michurina Tatyana , Rosenfeld Michael G. , Enikolopov Grigori
Published: August 2005

Oval cells, which become apparent in the liver after chronic injury, serve as bipotent progenitors for differentiated hepatocytes and cholangiocytes. We found that, in the liver of adult transgenic mice in which expression of green fluorescent protein (GFP) is driven by regulatory elements of the nestin gene, the GFP signal marks a subpopulation of small epithelial cells that meet the criteria for oval cells, including morphology, localization, antigenic profile, and reactivity in response to injury. In the regenerating and developing liver, we also found nestin‐GFP–positive cells that express hepatocyte markers; such cells may correspond to transiently appearing differentiating progeny of oval cells. During development, GFP‐expressing cells in the liver emerge relatively late, after the appearance of differentiated hepatocytes and cholangiocytes. Our results suggest that nestin‐GFP cells in the liver correspond to a specialized cell type whose primary function may be to serve as a reserve for adult liver epithelial cell types. Development Dynamics 234:413–421, 2005. © 2005 Wiley‐Liss, Inc.
GATA‐4:FOG interactions regulate gastric epithelial development in the mouse
Authors: Jacobsen Christina M. , Mannisto Susanna , Porter‐Tinge Susan , Genova Elena , Parviainen Helka , Heikinheimo Markku , Adameyko Igor I. , Tevosian Sergei G. , Wilson David B.
Published: August 2005

Transcription factor GATA‐4 is a key participant in cytodifferentiation of the mouse hindstomach. Here we show that GATA‐4 cooperates with a Friend‐of‐GATA (FOG) cofactor to direct gene expression in this segment of gut. Immunohistochemical staining revealed that GATA‐4 and FOG‐1 are co‐expressed in hindstomach epithelial cells from embryonic days (E) 11.5 to 18.5. The other member of the mammalian FOG family, FOG‐2, was not detected in gastric epithelium. To show that GATA‐4:FOG interactions influence stomach development, we analyzed Gata4ki/ki mice, which express a mutant GATA‐4 that cannot bind FOG cofactors. Sonic Hedgehog, an endoderm‐derived signaling molecule normally down‐regulated in the distal stomach, was over‐expressed in hindstomach epithelium of E11.5 Gata4ki/ki mice, and there was a concomitant decrease in fibroblast growth factor‐10 in adjacent mesenchyme. We conclude that functional interaction between GATA‐4 and a member of the FOG family, presumably FOG‐1, is required for proper epithelial‐mesenchymal signaling in the developing stomach. Developmental Dynamics 234:355–362, 2005. © 2005 Wiley‐Liss, Inc.
Preparation of Gold Nanoparticles on Ultrathin Films of Polythiophene and Polythiophene Derivatives
Authors: Intelmann Carl Matthias , Dietz Hartmut , Plieth Waldfried
Published: August 2005

Two different methods were used to immobilise gold nanoparticles on ultrathin films of polythiophene and polythiophene derivatives. The first method utilised ultrathin films of polythiophene to prepare gold nanoparticles by direct reduction of HAuCl4. A uniform coverage of the polythiophene films with randomly distributed gold nanopraticles possesing a polydisperse size distribution was obtained. Size and size distribution of the gold nanoparticles could be controlled by time, concentration of Au3+, and the addition of a cosolvent. With the second method, ultrathin films of polythiophene derivatives were esterified with thioctic acid, using either Steglich or Yamaguchi conditions. The dithiolane moiety of the thioctic acid was utilised to immobilise gold nanoparticles from a monodisperse gold sol. The gold nanoparticles were adhesive on the polymer films and were not removed by scotch tape tests. The samples with the obtained gold nanoparticles of both methods were analysed by scanning electron microscopy (SEM). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Stereoselective Synthesis of Polysubstituted Tetrahydropyrans by Radical Cyclization of Epoxides using a Transition‐Metal Radical Source
Authors: Banerjee Biplab , Roy Subhas Chandra
Published: August 2005

Epoxyalkyl propargyl ethers 3a–f and allyl epoxyalkyl ethers 6a–c smoothly undergo radical cyclization reactions using a titanium(III) species (Cp2TiCl) as the radical initiator to form polysubstituted tetrahydropyrans 4a–f and 7a–c in good yields and with high diastreoselectivity. The titanium(III) species was prepared in situ from commercially available titanocene dichloride and Zn dust in THF. On the other hand, the epoxyalkyl propargyl ethers 3g and 3h furnished the spirocyclic ethers 4g and 4h, respectively, on radical cyclization reaction as the sole products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Heat production profiles from batch aerobic thermophilic processing of high strength swine waste
Authors: Blackburn J. W. , Cheng J.
Published: August 2005

The literature reports several cases where biological wastewater solids or swine wastes have been aerobically oxidized at thermophilic temperatures. Although the heat generated is reported, little information is given about the heat production profiles with time and average values reported for the overall runs. These studies have also generally been in the medium‐to‐low concentration ranges for swine processes. This paper reports on work done in a laboratory batch reactor with the objectives of generating the actual heat release time profiles in higher strength swine wastes (6 to nearly 10% total solids). Significant amounts of heat were generated, and the amounts generated were determined by two methods [total solids removal calorimetry and chemical oxygen demand (COD) removal] with good agreement. Linear models were constructed showing that the biological heat production is strongly related to the specific air flow rates through the reactors and the interaction between air flow rate and solids or COD concentrations. At 55° C, nitrification was not detected and the nitrogen in the waste was converted to ammonia, which subsequently strips into the exhaust air. In some cases, ammonia was recovered with acid absorbers. In the 2.0‐L reactor with 1.2 L of reaction mixture, energy production rates ranged from 0.7 to 2.43 W and COD removal ranged from 28.5 to 62.7% with a common residence time of 6 days. © 2005 American Institute of Chemical Engineers Environ Prog, 2005
Modelling water erosion in the Sahel: application of a physically based soil erosion model in a gentle sloping environment
Authors: Visser S. M. , Sterk G. , Karssenberg D.
Published: August 2005

Water is a major limiting factor in arid and semi‐arid agriculture. In the Sahelian zone of Africa, it is not always the limited amount of annual rainfall that constrains crop production, but rather the proportion of rainfall that enters the root zone and becomes plant‐available soil moisture. Maximizing the rain‐use efficiency and therefore limiting overland flow is an important issue for farmers. The objectives of this research were to model the processes of infiltration, runoff and subsequent erosion in a Sahelian environment and to study the spatial distribution of overland flow and soil erosion.

The wide variety of existing water erosion models are not developed for the Sahel and so do not include the unique Sahelian processes. The topography of the Sahelian agricultural lands in northern Burkina Faso is such that field slopes are generally low (0–5°) and overland flow mostly occurs in the form of sheet flow, which may transport large amounts of fine, nutrient‐rich particles despite its low sediment transport capacity. Furthermore, pool formation in a field limits overland flow and causes resettlement of sediment resulting in the development of a surface crust.

The EUROSEM model was rewritten in the dynamic modelling code of PCRaster and extended to account for the pool formation and crust development. The modelling results were calibrated with field data from the 2001 rainy season in the Katacheri catchment in northern Burkina Faso. It is concluded that the modified version of EUROSEM for the Sahel is a fully dynamic erosion model, able to simulate infiltration, runoff routing, pool formation, sediment transport, and erosion and deposition by inter‐rill processes over the land surface in individual storms at the scale of both runoff plots and fields. A good agreement is obtained between simulated and measured amounts of runoff and sediment discharge. Incorporating crust development during the event may enhance model performance, since the process has a large influence on infiltration capacity and sediment detachment in the Sahel. Copyright © 2005 John Wiley & Sons, Ltd.
Rates of erosion and topographic evolution of the Sierra Nevada, California, inferred from cosmogenic 26Al and 10Be concentrations
Authors: Stock Greg M. , Anderson Robert S. , Finkel Robert C.
Published: August 2005

Concentrations of cosmogenic 26Al and 10Be in cave sediments and bedrock surfaces, combined with studies of landscape morphology, elucidate the topographic history of the southern Sierra Nevada over the past 5 Ma. Caves dated by 26Al/10Be in buried sediments reveal that river incision rates were moderate to slow between c. 5 and 3 Ma (≤0·07 mm a−1), accelerated between 3 and 1·5 Ma (c. 0·3 mm a−1), and then have subsequently become much slower (c. 0·02 mm a−1). Although the onset of accelerated incision coincides in time with both postulated Pliocene tectonism and pronounced global climate change, we argue that it primarily represents the response to a discrete tectonic event between 3 and 5 Ma. Dated cave positions reveal that, prior to 3 Ma, river canyons displayed up to 1·6 km of local relief, suggesting that Pliocene rock uplift elevated pre‐existing topography. Renewed incision beginning c. 3 Ma deepened canyons by up to 400 m, creating narrow inner gorges. Tributary streams exhibit strong convexities, indicating that the transient erosional response to Pliocene uplift has not yet propagated into upland surfaces. Concentrations of 26Al and 10Be in bare bedrock show that upland surfaces are eroding at slow rates of c. 0·01 mm a−1. Over the past c. 3 Ma, upland surfaces eroded slowly while adjacent rivers incised rapidly, increasing local relief. Although relief production probably drove at least modest crestal uplift, considerable pre‐Pliocene relief and low spatially averaged erosion rates suggest that climatically driven rock uplift is not sufficient to explain all uplift implied by tilted markers at the western edge of the range. Despite the recent pulse of erosion, spatially averaged erosion rates are low, and have probably acted to preserve the broad topographic form of the Sierra Nevada throughout much of the late Cenozoic. Copyright © 2005 John Wiley & Sons, Ltd.
Measuring middle Pleistocene erosion rates with cosmic‐ray‐produced nuclides in buried alluvial sediment, Fisher Valley, southeastern Utah
Authors: Balco Greg , Stone John O. H.
Published: August 2005

Cosmic‐ray‐produced 10Be and 26Al in riverborne quartz sediment are commonly used to estimate average catchment‐scale erosion rates. Likewise, the concentrations of these nuclides in ancient sediments, stored in a depositional basin, carry a record of past erosion rates in the sediment source area. This is important because such a record could be compared to records of climate change or tectonic events to elucidate relationships between climate, tectonics and erosion. If the sediments are shielded from the cosmic‐ray flux after deposition, for example in deep water, their nuclide concentrations need only be corrected for radioactive decay since deposition in order to determine past erosion rates. Where sediment is deposited subaerially and buried relatively slowly, on the other hand, the additional nuclide concentration that builds up during sediment accumulation and storage must be reconstructed and subtracted in order to recover the initial nuclide concentrations in the sediment and thence the past erosion rates. We describe an example of this process for an early to middle Pleistocene section of alluvial sediment in Fisher Valley, Utah. We use stratigraphic observations as well as an independently known age model for the sediment section to: (a) subtract post‐depositional nuclide concentrations and reconstruct past erosion rates between 0·7 and 0·6 Ma; and (b) estimate the uncertainty in the results that arises from imperfect dating of the section and the natural variability in accumulation rates. The present basin‐averaged erosion rate in Fisher Valley is near 125 m Ma−1, and middle Pleistocene basin‐averaged erosion rates varied between 80 and 220 m Ma−1. Changes in the erosion rate over time do not appear to be connected to glacial–interglacial climate changes, but may be related to episodic subsidence of the basin. Uncertainties are small in the case of low erosion rates and high sediment accumulation rates, and large in the opposite situation. In this example, we could reduce the uncertainties by increasing the sampling density or by better relating our sample locations to the small‐scale stratigraphy of the sedimentary section. In general, future attempts to reconstruct past erosion rates from cosmogenic‐nuclide concentrations in ancient alluvium will be most successful in situations where post‐depositional nuclide accumulation is minimized, for example in lakes or marine basins. Copyright © 2005 John Wiley & Sons, Ltd.