bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of acidic and neutral drugs in surface waters near sewage treatment plants in the lower Great Lakes, Canada
Authors: Metcalfe Chris D. , Miao Xiu-Sheng , Koenig Brenda G. , Struger John
Published: March 2005

Prescription and nonprescription drugs have been detected in rivers and streams in Europe and the United States. Sewage treatment plants (STPs) are an important source of these contaminants, but few data exist on the spatial distribution of drugs in surface waters near STPs. Samples of surface water were collected in the summer and fall of 2000 at open-water sites in the lower Great Lakes (Lake Ontario and Lake Erie), at sites near the two STPs for the city of Windsor (ON, Canada), and at sites in Hamilton Harbour (ON, Canada), an embayment of western Lake Ontario that receives discharges from several STPs. In a follow-up study in the summer of 2002, samples of surface water and final effluent from adjacent STPs were collected from sites in Hamilton Harbour and Windsor. In addition, surface water and STP effluent samples were collected in Peterborough (ON, Canada). All samples of surface water and STP effluents were analyzed for selected acidic and neutral drugs. In the survey of Hamilton Harbour and Windsor conducted in 2000, acidic drugs and the antiepileptic drug carbamazepine were detected at ng/L concentrations at sites that were up to 500 m away from the STP, but the hydrological conditions of the receiving waters strongly influenced the spatial distribution of these compounds. Drugs were not detected at open-water locations in western Lake Erie or in the Niagara River near the municipality of Niagara-on-the-Lake (ON, Canada). However, clofibric acid, ketoprofen, fenoprofen, and carba-mazepine were detected in samples collected in the summer of 2000 at sites in Lake Ontario and at a site in the Niagara River (Fort Erie, ON, Canada) that were relatively remote from STP discharges. Follow-up studies in the summer of 2002 indicated that concentrations of acidic and neutral drugs in surface waters near the point of sewage discharge into the Little River (ON, Canada) STP were approximately equal to the concentrations in the final effluent from the STP. Caffeine and cotinine, a metabolite of nicotine, were generally present in STP effluents and surface waters contaminated by drugs. The antidepressant fluoxetine and the antibiotic trimethoprom were also detected in most STP effluents and some surface water samples. For the first time, the lipid regulating drug atorvastatin was detected in samples of STP effluent and surface water.
Insecticidal activity of synthetic pyrethroids, organophosphates, insect growth regulators, and other livestock parasiticides: An Australian perspective
Authors: Wardhaugh Keith G.
Published: March 2005

The present review is restricted to the collation and evaluation of information describing the excretion profile and ecotoxicity of veterinary medicines developed specifically for the control of either internal or external parasites of livestock. It identifies numerous gaps in our knowledge and highlights our poor understanding of the environmental fate of many of these chemicals, especially those developed for the control of ticks, lice, and/or biting flies. Residues of most anthelmintics are largely harmless to dung-feeding arthropods, but those of many ectoparasiticides, especially the synthetic pyrethroids, are highly toxic to fly larvae and adult dung beetles. Organophosphates, because they are metabolized extensively and eliminated mostly in urine, are considered to be unlikely to have a major impact on the development or survival of dung-dwelling organisms. The present review stresses the need for better information regarding spatial and temporal usage patterns of veterinary parasiticides, and it examines the role of ecotoxicological models for evaluating their impact on populations of dung-dependent arthropods.
Factors influencing the sorption of oxytetracycline to soils
Authors: Jones Aaryn D. , Bruland Gregory L. , Agrawal Sheela G. , Vasudevan Dharni
Published: March 2005

Veterinary antibiotics such as oxytetracycline (OTC) increasingly are found in the environment and often come into direct contact with soils via the release of animal wastes. Oxytetracycline is known to sorb strongly to soils by interaction with soil organic matter, clay minerals, and metal oxides. However, current knowledge of the influence of soil properties on OTC sorption is limited, as is our ability to predict OTC sorption to soils. This work was aimed at identifying properties that most influence the extent of OTC sorption in a suite of soils from the eastern United States representing a wide range in soil properties. Thirty soils were well characterized, an OTC soil-water distribution coefficient (Kd) was determined for each soil, and statistical analyses were employed to determine appropriate soil descriptors of OTC sorption. Soil texture, cation exchange capacity, and iron oxide content seemed to most influence the extent of OTC sorption in soils with organic carbon (OC) content between 0 and 4%. Thus, the knowledge of these three soil properties would be key to anticipating the extent of OTC sorption and gaining insight into OTC fate within a given soil system. Notably, OC content appeared to influence OTC sorption only in a soil with 9% OC.
Fate of mercury accumulated by blowflies feeding on fish carcasses
Authors: Sarica José , Amyot Marc , Bey Julien , Hare Landis
Published: March 2005

Because fish represent the principal methylmercury (MeHg) pool in the water column of freshwater systems, MeHg released from their carcasses could represent an important flux to the environment. Necrophagous invertebrates such as fly larvae can play an important role in this Hg recycling. We studied Hg accumulation by blowflies (Diptera, Calliphoridae) feeding on beached fish carcasses in the field. We found that the MeHg these flies accumulated as larvae is retained in their pupal stage but is eliminated by the adult following emergence. We conclude that calliphorids possess an efficient mechanism for excreting the MeHg that they accumulate from carcasses.
Biofilm formation by algae as a mechanism for surviving on mine tailings
Authors: García-Meza J. Viridiana , Barrangue Christiane , Admiraal Wim
Published: March 2005

Photosynthetic biofilms successfully colonize the sediments of a mine tailings reservoir (Guanajuato, Mexico) despite the high metal concentrations that are present. To elucidate the mechanisms of biofilm survival despite metal ores, experiments were performed to evaluate the response of seminatural biofilms to Cu, Zn, and a combination of both metals at concentrations observed in the field. The biofilms were composed mostly of the chlorophyte Chlorococcum sp. and the cyanobacterium Phormidium sp., and their response to the two added metals was described by measurements of extracellular polymeric substances (EPS) and in vivo fluorescence. The photosynthetic efficiency and the minimal chlorophyll fluorescence of dark-adapted cells were measured by multiwavelength pulse amplitude–modulated fluorometry. The photosynthetic efficiency of light-adapted cells (ϕPSII) also was measured. Metal exposure increased the EPS production of biofilms, as visualized with confocal laser-scanning microscopy. Extracellular polymeric substances enhanced the extracellular metal accumulation from the first day of metal exposure. Metals provoked changes in the relative abundance of the dominant taxa because of a species-specific response to the metals when added individually. Metals affected the ϕpsii less than the total biomass, suggesting ongoing activity of the surviving biofilms. Survival of individual biofilm photosynthetic cells was found to resume from the embedding in the mucilaginous structure, which immobilizes the metals extracellularly. The survival of biofilms under mixed-metal exposure has practical applications in the remediation of mine tailings.
Screening test battery for pharmaceuticals in urine and wastewater
Authors: Escher Beate I. , Bramaz Nadine , Maurer Max , Richter Manuela , Sutter Daniel , von Känel Christoph , Zschokke Mischa
Published: March 2005

A test battery for identifying ecotoxicological hazards was applied to six pharmaceuticals (carbamazepine, diclofenac, ethinylestradiol, ibuprofen, propranolol, and sulfamethoxazole), to their mixtures, and to urine spiked with pharmaceuticals to test the suitability of biotests for screening urine and wastewater and for monitoring the efficiency of wastewater treatment. The test battery comprised the bioluminescence inhibition test with Vibrio fischeri, the yeast estrogen screen, and a photosynthesis inhibition assay in algae based on chlorophyll fluorescence measurements. Mixture and additional experiments with a cocktail of pharmaceuticals added to urine confirmed the applicability of the test systems as an integrated measure of the overall micropollutant burden. Because the concentration of pharmaceuticals in wastewater is low and the nutrients and salts may have a negative impact on the bioassays, urine and wastewater samples were cleaned and concentrated by solid-phase extraction (SPE). The compounds of interest ranged from polar to nonpolar and from positively charged to neutral and negatively charged. Consequently, the SPE method was optimized for universality rather than for specificity. Results of preliminary experiments with raw and treated urine and wastewater indicate the suitability of the proposed test battery for screening urine and wastewater.
Bioavailability of polybrominated diphenyl ether flame retardants in biosolids and spiked sediment to the aquatic oligochaete, Lumbriculus variegatus
Authors: Ciparis Serena , Hale Robert C.
Published: March 2005

Polybrominated diphenyl ether (PBDE) flame retardants have become distributed ubiquitously in the environment. High concentrations have been reported in U.S. sewage sludge (biosolids). The burgeoning practice of land-applying biosolids as fertilizer creates an avenue for reintroduction of PBDEs to surface waters and aquatic sediments. Bioavailability of biosolids- and sediment-associated PBDEs was assessed using the freshwater oligochaete, Lumbriculus variegatus. Oligochaetes were exposed to composted biosolids (1,600 ng/g total PBDEs) and artificial sediment spiked with penta- and deca-brominated diphenyl ether (BDE) formulations (1,300 ng/g total PBDEs). Uptake (28-d exposure) and depuration (21 d) of eight congeners were studied. Polybrominated diphenyl ethers in both substrates were bioavailable, but bioaccumulation was 5 to 10 times greater from spiked artificial sediment. The congeners BDE 47 and BDE 99 were the most prevalent congeners in oligochaetes after exposure. Congener BDE 47 was more bioaccumulative, possibly due to the threefold greater depuration rate of BDE 99. Bioaccumulation of penta- and hexa-brominated congeners appeared to be affected more strongly by substitution pattern than degree of bromination. Uptake of BDE 209, the dominant congener in deca-BDE, was minimal. Accumulation of certain PBDE congeners from biosolids and sediments by benthos provides a pathway for transfer to higher trophic levels, and congener discrimination may increase with each trophic transfer.
Projected population-level effects of thiobencarb exposure on the mysid, Americamysis bahia, and extinction probability in a concentration-decay exposure system
Authors: Raimondo Sandy , McKenney Charles L.
Published: March 2005

Population-level effects of the mysid, Americamysis bahia, exposed to varying thiobencarb concentrations were estimated using stage-structured matrix models. A deterministic density-independent matrix model estimated the decrease in population growth rate (λ) with increasing thiobencarb concentration. An elasticity analysis determined that survival of middle stages provided the largest contribution to λ. Decomposing the effects of λ in terms of changes in the matrix components determined that reduced reproduction had a large influence on population dynamics at lower thiobencarb concentrations, whereas reduced survivorship had the largest impact on populations at higher concentrations. A simulation model of a concentration-decay system was developed to demonstrate the importance of integrating chemical half-life and management practices in determining population viability. In this model, mysids were originally exposed to a high thiobencarb concentration (300 μg/L) that decayed an order of magnitude in the number of mysid generations corresponding to thiobencarb half-life values under three different exposure regimes. Environmental stochasticity was added to the model to estimate the cumulative extinction probability of mysids exposed to fluctuating concentrations of thiobencarb in random environments. The cumulative extinction probability increased with thiobencarb half-life, stochasticity, and concentration present at the time of a new exposure. The model demonstrated the expansion of population projection models in determining the ecological impact of a population exposed to pesticides.
Description and initial evaluation of a Xenopus metamorphosis assay for detection of thyroid system-disrupting activities of environmental compounds
Authors: Opitz Robert , Braunbeck Thomas , Bogi Christian , Pickford Daniel B. , Nentwig Gerrit , Oehlmann Jorg , Tooi Osamu , Lutz Ilka , Kloas Werner
Published: March 2005

A eedi recognizedforthedevelopmentandevaluationofbioassaysfordetectionofthyroid s stem–disrupting compounds. The issue of testing for thyroid disruption can be addressed by exploiting amphibian metamorphosis as a biological model. In the present study, a test protocol for a Xenopus metamorphosis assay (XEMA) was developed and its interlaboratory transferability was evaluated in an informal ring test with six laboratories participating. In the XEMA test, exposure of Xenopus laevis tadpoles was initiated at stages 48 to 50 and continued for 28 d. Development and growth of tadpoles were assessed by means of developmental stage and whole body length determinations, respectively. For initial test protocol evaluation, thyroxine (T4), and propylthiouracil (PTU) were used as positive controls for thyroid system–modulating activity, and ethylenethiourea (ETU) was used as a test compound. Exposure of tadpoles to 1 μg/L T4 produced a significant acceleration of metamorphosis whereas PTU concentrations of 75 and 100 mg/L completely inhibited metamorphosis. Five different ETU concentrations (5, 10, 25, 50, and 100 mg/L) were tested and a concentration-dependent inhibition of metamorphosis was observed. None of the compounds affected tadpole survival, and only PTU caused a slight retardation in tadpole growth. This study demonstrates that the XEMA test provides a sensitive, robust, and practical testing approach for detection of compounds with both agonistic and antagonistic effects on the thyroid system in Xenopus tadpoles.
Organochlorine pesticides and mercury in cottonmouths (Agkistrodon piscivorus) from northeastern Texas, USA
Authors: Rainwater Thomas R. , Reynolds Kevin D. , Cañas Jaclyn E. , Cobb Georgev P. , Andersonv Todd A. , McMurry Scott T. , Smith Philip N.
Published: March 2005

Dspite their ecological importance andglobal decline, snakes remain poorly studied in ecotoxicology. In this study, we examined organochlorine (OC) pesticide and mercury accumulation in cottonmouths (Agkistrodon piscivorus) living on a contaminated site in northeastern Texas (USA). Mercury and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) were detected in all snakes examined. Other OCs, including p,p′-dichlorodiphenyltrichloroethane (p,p′-DDT), methoxychlor, aldrin, and heptachlor, also were detected, but less frequently. Concentrations of p,p′-DDE were higher in fat than in liver, while mercury concentrations were highest in liver, followed by kidney and tail clips. One animal contained the highest mercury concentration yet reported for a snake (8,610 ng/g). Mercury concentrations in liver and kidney were higher in males than females, while no intersex differences in p,p′-DDE concentrations were observed. Concentrations of p,p′-DDE in fat were correlated positively with body size in male cottonmouths but not females, suggesting a slower rate of accumulation in females. Body size strongly predicted mercury concentrations in liver, kidney, and tail clips of both sexes. Tail clips were strong predictors of mercury in liver and kidney in males but not females, suggesting possible sex-dependent differences in mercury toxicokinetics. Both long-term field studies and controlled laboratory investigations are needed to adequately assess the response of cottonmouths to chronic contaminant exposure.
Evaluation of Recombinant Human Bone Morphogenetic Protein‐2 on the Repair of Alveolar Ridge Defects in Baboons
Authors: Miranda Dario A.O. , Blumenthal Neil M. , Sorensen Rachel G. , Wozney John M. , Wikesjö Ulf M.E.
Published: March 2005

Background: The objective of this study was to evaluate alveolar ridge augmentation following surgical implantation of recombinant human bone morphogenetic protein‐2 (rhBMP‐2) using two novel space‐providing carrier technologies in the baboon (Papio anubis) model.

Methods: Standardized alveolar ridge defects (∼15 × 8 × 5 mm) were surgically produced in maxillary and mandibular edentulous areas in four baboons. The defect sites were implanted with rhBMP‐2 (0.4 mg/mL) in a tricalcium phosphate/hydroxyapatite/ absorbable collagen sponge composite (TCP/HA/ACS) or calcium phosphate cement (α‐BSM). Control treatments were TCP/HA/ACS and α‐BSM without rhBMP‐2 and sham surgery. Stainless steel pins were placed at the mid‐apical and coronal level of the defect sites to provide landmarks for clinical measurements pre‐ and post‐implantation. Impressions were obtained pre‐ and postimplantation to determine changes in alveolar ridge volume. Radiographic registrations were obtained pre‐ and post‐implantation. Block sections of the defect sites were harvested at week 16 postimplantation and processed for histometric analysis including new bone area and bone density. Statistical comparisons between treatments were made using a mixed effect generalized linear model using least squares estimation.

Results: The carrier systems without rhBMP‐2 provided a modest ridge augmentation. The addition of rhBMP‐2 resulted in an almost 2‐fold increase in alveolar ridge width, including a greater percentage of trabecular bone and a higher bone density compared to controls (P ≤0.05) without significant differences between the two rhBMP‐2 protocols.

Conclusions: TCP/HA/ACS and αBSM appear to be suitable carrier technologies for rhBMP‐2. Alveolar augmentation procedures using either technology combined with rhBMP‐2, rather than stand‐alone therapies, may provide clinically relevant augmentation of alveolar ridge defects for placement of endosseous dental implants. J Periodontol 2005;76:210‐220.
Experimental Arthritis in Rats Induces Biomarkers of Periodontitis Which Are Ameliorated by Gene Therapy With Tissue Inhibitor of Matrix Metalloproteinases
Authors: Ramamurthy Nungavaram S. , Greenwald Robert A. , Celiker Mohamed Y. , Shi Eric Y.
Published: March 2005

Background: Periodontal disease (PD) and rheumatoid arthritis (RA) share many common pathophysiologic features, but a clinical relationship between the two conditions remains controversial, in part because of the confounding effects of anti‐inflammatory drug therapy universally used in the latter disease. To further explore this issue, inflammatory arthritis was induced in rats to determine the effect on gingival biomarkers of inflammation and tissue destruction and to investigate the effect of a therapeutic intervention devoid of conventional anti‐inflammatory properties.

Methods: Adjuvant arthritis (AA) was induced in Lewis male rats by injecting mycobacterium cell wall in complete Freund's adjuvant using standard techniques. One group of animals was treated by induction of systemic tissue inhibitor of matrix metalloproteinases (TIMP‐4). At 3 weeks, arthritis severity was recorded and both paw and gingival tissues were collected for matrix metalloproteinase activity (MMP) and cytokine analysis. In addition, the maxillary jaws were removed for assessment of periodontal bone loss.

Results: The development of arthritis was associated with elevated joint tissue MMPs, tumor necrosis factor (TNF)‐α, and interleukin (IL)‐1β levels compared to control rats. In the gingival tissue of the untreated arthritic rats, gelatinase, collagenase, TNF‐α, and IL‐1β were also elevated compared to control rats. Periodontal bone loss and tooth mobility were also increased significantly (P <0.05) in untreated arthritic rats. All parameters improved after TIMP‐4 gene therapy.

Conclusions: To our knowledge, this is the first study to report an association between experimental systemic arthritis in rats and elevated gingival tissue MMPs, cytokine levels, and periodontal disease. Reversal of these changes with TIMP‐4 gene therapy strengthens the pathophysiologic correlation between systemic and local disease. J Periodontol 2005;76:229‐233.
A Pilot Study Applying Digital Radiography for Estimating Ratio of Supported Single‐Root Surface Area
Authors: Chen Ssu‐Kuang , Pan Ju‐Hung , Lin Chi‐Hao , Leu Liang‐Jenq , Chen Chung‐Ming , Jeng Jeng‐Ywan
Published: March 2005

Background: The prognosis of a tooth with periodontitis is affected by the amount of supporting bone. A key factor in retaining a tooth is the ratio of supported root surface. Currently, root surfaces cannot be accurately measured using conventional dental radiographs, which only measure the length of bone support on proximal surfaces.

Methods: Eight extracted, single‐rooted teeth were 3‐dimensionally digitized using a contact technique for true surface area measurements. Root length, projection area, and pixel values were then measured on digital radiographs. The accuracy of the ratio estimation of supported surface area from linear, area, and pixel values was calculated and compared.

Results: The mean error from linear estimation was 7.9%; the mean error from area estimation was 1.0%; and the mean error from pixel value estimation was 1.3%. One‐way analysis of variance (ANOVA) showed significant differences in all estimations while Scheffé's analysis further revealed significant differences only in the linear estimation.

Conclusions: A three‐dimensional digitizing device could be used as a non‐destructive method of measuring root surface area. The ratio of supported single‐root surface area could be estimated with high accuracy from the projected area data acquired on the digital dental radiographs. The thickness data as reflected from the pixel values in the digital images did not improve the estimation accuracy. Estimations using only length data yielded significantly less accuracy. Digital dental x‐ray images provide the potential for estimating the ratio of supported root surface efficiently. J Periodontol 2005;76:268‐271.
Heritability of age at menarche in girls from the Fels Longitudinal Study
Authors: Towne Bradford , Czerwinski Stefan A. , Demerath Ellen W. , Blangero John , Roche Alex F. , Siervogel Roger M.
Published: March 2005

Menarche is the hallmark maturational event of female childhood. Many studies indicated a significant genetic contribution to the timing of the onset of menstruation, but most of these studies were limited by the use of retrospective data and by the use of data from only certain types of relatives (i.e., mothers and daughters, sisters, or twin sisters). The primary goal of this study was to use a modern maximum likelihood quantitative genetic method to estimate the heritability (h2) of age at menarche, using familial data collected over the course of the 74‐year‐old Fels Longitudinal Study. The secondary goal was to review earlier studies of the heritability of age at menarche. The study of the heritability of age at menarche presented here is unique for two reasons. First, because of the Fels Longitudinal Study's serial design, age‐at‐menarche data were collected prospectively from most participants. Second, because the Fels Longitudinal Study is a family study that has been conducted for decades, age‐at‐menarche data are available from many types of female relatives spanning multiple households and generations. The best‐fitting and most parsimonious quantitative genetic model included provision for a secular decrease in age at menarche, and estimated the h2 of age at menarche to be 0.49 ± 0.13 (95% confidence interval of h2, = 0.24–0.73). The results of this study are in general agreement with the findings of most previous studies of genetic influences on age at menarche, and suggest that it is reasonable to consider it well‐established that approximately half the phenotypic variation among girls from developed nations in the timing of menarche is due to genetic factors. Am J Phys Anthropol 128:210‐219, 2005. © 2005 Wiley‐Liss, Inc.
Importance of cooperation and affiliation in the evolution of primate sociality
Authors: Sussman R.W. , Garber Paul A. , Cheverud Jim M.
Published: March 2005

The idea that competition and aggression are central to an understanding of the origins of group‐living and sociality among human and nonhuman primates is the dominant theory in primatology today. Using this paradigm, researchers have focused their attention on competitive and aggressive behaviors, and have tended to overlook the importance of cooperative and affiliative behaviors. However, cooperative and affiliative behaviors are considerably more common than agonistic behaviors in all primate species. The current paradigm often fails to explain the context, function, and social tactics underlying affiliative and agonistic behavior. Here, we present data on a basic question of primate sociality: how much time do diurnal, group‐living primates spend in social behavior, and how much of this time is affiliative and agonistic? These data are derived from a survey of 81 studies, including 28 genera and 60 species. We find that group‐living prosimians, New World monkeys, Old World monkeys, and apes usually devote less than 10% of their activity budget to active social interactions. Further, rates of agonistic behaviors are extremely low, normally less than 1% of the activity budget. If the cost to the actors of affiliative behavior is low even if the rewards are low or extremely variable, we should expect affiliation and cooperation to be frequent. This is especially true under conditions in which individuals benefit from the collective environment of living in stable social groups. Am J Phys Anthropol 128:84–97, 2005. © 2005 Wiley‐Liss, Inc.
Effective invariant features for shape‐based image retrieval
Authors: Li Shan , Lee Moon‐Chuen , Adjeroh Donald
Published: March 2005

The success of content‐based image retrieval (CBIR) relies critically on the ability to find effective image features to represent the database images. The shape of an object is a fundamental image feature and belongs to one of the most important image features used in CBIR. In this article we propose a robust and effective shape feature known as the compound image descriptor (CID), which combines the Fourier transform (FT) magnitude and phase coefficients with the global features. The underlying FT coefficients have been shown analytically to be invariant to rotation, translation, and scaling. We also present details of the underlying innovative shape feature extraction method. The global features, besides being incorporated with the FT coefficients to form the CID, are also used to filter out the highly dissimilar images during the image retrieval process. Thus, they serve a dual purpose of improving the accuracy and hence the robustness of the shape descriptor, and of speeding up the retrieval process, leading to a reduced query response time. Experiment results show that the proposed shape descriptor is, in general, robust to changes caused by image shape rotation, translation, and/or scaling. It also outperforms other recently published proposals, such as the generic Fourier descriptor (Zhang & Lu, 2002).
Cell proliferation in the developing lateral line system of zebrafish embryos
Authors: Laguerre Laurent , Soubiran Fabien , Ghysen Alain , König Norbert , Dambly‐Chaudière Christine
Published: March 2005

The sensory organs of the embryonic lateral line system are deposited by migrating primordia that originate in the otic region. Here, we examine the pattern of cell proliferation in the posterior lateral line system. We conclude that three phases of cell proliferation are involved in the generation of this system, separated by two phases of mitotic quiescence. The first phase corresponds to generalized proliferation during gastrulation, followed by a first period of quiescence that may be related to the determination of the lateral line precursor cells. A second phase of proliferation takes place in the placode and migrating primordium. This region is organized in annuli that correspond to the expression of proneural/neurogenic genes. A second period of quiescence follows, corresponding to deposition and differentiation of the sensory organs. The third period of proliferation corresponds to continued renewal of hair cells by division of support cells within each sensory organ. Developmental Dynamics 233:466–472, 2005. © 2005 Wiley‐Liss, Inc.
Endogenously expressed estrogen receptors mediate neuroprotection in hippocampal cells (HT22)
Authors: Deecher Darlene C. , Daoud Pamela , Bhat Ramesh A. , O'Connor Lawrence T.
Published: March 2005

Discovery of estrogen receptors (ER) in the central nervous system and the ability of estrogens to modulate neural circuitry and act as neurotrophic factors, suggest a therapeutic role of this steroid. To gain better understanding of the specificity and cellular mechanisms involved in estrogen‐mediated neuroprotection, a mouse hippocampal neuronal cell line (HT22) was evaluated. Earlier reports indicated this cell line was devoid of ERs. Contrary to these findings, characterization of HT22 cells using RT‐PCR, immunoblot, immunocytochemical, and radioligand binding techniques revealed endogenous expression of ER. The predominant subtype appeared to be ERα with functional activity confirmed using an ERE‐tk‐luciferase assay. The ability of an ER antagonist, ICI‐182780, to block the neuroprotective effects of estrogens confirmed ER was involved mechanistically in neuroprotection. In conclusion, HT22 cells express functional ERα or a closely related ER enabling this cell line to be used to profile estrogens for neuroprotective properties acting via an ER‐dependent mechanism. © 2005 Wiley‐Liss, Inc.
Molecular profile of catabolic versus anabolic treatment regimens of parathyroid hormone (PTH) in rat bone: An analysis by DNA microarray
Authors: Onyia Jude E. , Helvering Leah M. , Gelbert Lawrence , Wei Tao , Huang Shuguang , Chen Peining , Dow Ernst R. , Maran Avudaiappan , Zhang Minzhi , Lotinun Sutada , Lin Xi , Halladay David L. , Miles Rebecca R. , Kulkarni Nalini H. , Ambrose Emily M. , Ma Yanfei L. , Frolik Charles A. , Sato Masahiko , Bryant Henry U. , Turner Russell T.
Published: March 2005

Teriparatide, human PTH (1‐34), a new therapy for osteoporosis, elicits markedly different skeletal responses depending on the treatment regimen. In order to understand potential mechanisms for this dichotomy, the present investigation utilized microarrays to delineate the genes and pathways that are regulated by intermittent (subcutaneous injection of 80 μg/kg/day) and continuous (subcutaneous infusion of 40 μg/kg/day by osmotic mini pump) PTH (1–34) for 1 week in 6‐month‐old female rats. The effect of each PTH regimen was confirmed by histomorphometric analysis of the proximal tibial metaphysis, and mRNA from the distal femoral metaphysis was analyzed using an Affymetrix microarray. Both PTH paradigms co‐regulated 22 genes including known bone formation genes (i.e., collagens, osteocalcin, decorin, and osteonectin) and also uniquely modulated additional genes. Intermittent PTH regulated 19 additional genes while continuous treatment regulated 173 additional genes. This investigation details for the first time the broad profiling of the gene and pathway changes that occur in vivo following treatment of intermittent versus continuous PTH (1–34). These results extend previous observations of gene expression changes and reveal the in vivo regulation of BMP3 and multiple neuronal genes by PTH treatment. © 2005 Wiley‐Liss, Inc.
Overexpression of GSTA2 protects against cell cycle arrest and apoptosis induced by the DNA inter‐strand crosslinking nitrogen mustard, mechlorethamine
Authors: Xie Jingping , Shults Keith , Flye Leanne , Jiang Fen , Head David R. , Briggs Robert C.
Published: March 2005

The effectiveness of bifunctional alkylating nitrogen mustard compounds in chemotherapy is related to their ability to form DNA inter‐strand crosslinks. Patients exposed to DNA inter‐strand crosslinking (ICL) agents subsequently experience an elevated incidence of myelodysplastic syndromes (MDS) and MDS related acute myeloid leukemia. Fanconi's anemia (FA) patients are deficient in the repair of crosslink DNA damage and they experience a high incidence of MDS. These observations indicate that hematopoietic cells are specific target for the transforming effects of DNA crosslinking damage. Changes in transcript levels were characterized in human hematopoietic cells occurring in response to the nitrogen mustard, mechlorethamine (HN2), but not in response to monofunctional analogs. Only modest changes in a few gene transcripts were detected in HL60 cells exposed to levels of HN2 tittered to maximal dose that caused growth suppression with minimal cell death and allowed eventual resumption of normal cell growth. Under conditions of transient growth suppression, a subset of glutathione‐S‐transferase (GST) isoenzyme genes was consistently upregulated three to fourfold by HN2, but not by monofunctional analogs. Subsequent efforts to confirm the changes detected by microarray analyses revealed an unexpected dependence on treatment conditions. The GST alpha class A2 subfamily member transcripts were upregulated 24 h after a 1 h exposure to HN2 that caused an extensive, but transient block in late S/G2 cell cycle phase, but were minimally altered with continuous exposure. The 1‐h exposure to HN2 caused a transient late S/G2 cell cycle arrest in both the HL‐60 cell line and the Colo 320HSR human colon cancer cell line. Overexpression of GSTA2 by transient transfection protected Colo 320HSR cells against both cycle arrest and apoptosis following exposure to HN2. Overexpression of GSTA2 in Colo 320HSR cells induced after exposure to HN2 did not alter cycle arrest or apoptosis. The results indicate that human GSTA2 facilitates the protection of cells from HN2 damage and not repair. Our results are consistent with the possibility that GSTA2 polymorphisms, variable isoenzyme expression, and variable induced expression may be factors in the pathogenesis of MDS. © 2005 Wiley‐Liss, Inc.
Two sufficient conditions for dominating cycles
Authors: Lu Mei , Liu Huiqing , Tian Feng
Published: March 2005

A cycle C of a graph G is dominating if each component of $G\backslash C$ is edgeless. In the paper, we will give two sufficient conditions for each longest cycle of a 3‐connected graph to be a dominating cycle. © 2005 Wiley Periodicals, Inc. J Graph Theory
Magnetic resonance voiding cystography in the diagnosis of vesicoureteral reflux: Comparative study with voiding cystourethrography
Authors: Lee Sang Kwon , Chang Yongmin , Park Noh Hyuck , Kim Young Hwan , Woo Seongku
Published: March 2005

Purpose

To evaluate the feasibility of magnetic resonance voiding cystography (MRVC) compared with voiding cystourethrography (VCUG) for detecting and grading vesicoureteral reflux (VUR).

Materials and Methods

MRVC was performed upon 20 children referred for investigation of reflux. Either coronal T1‐weighted spin‐echo (SE) or gradient‐echo (GE) (fast multiplanar spoiled gradient‐echo (FMPSPGR) or turbo fast low‐angle‐shot (FLASH)) images were obtained before and after transurethral administration of gadolinium solution, and immediately after voiding. The findings of MRVC were compared with those of VCUG and technetium‐99m (99mTc) dimercaptosuccinic acid (DMSA) single‐photon emission computed tomography (SPECT) performed within 6 months of MRVC.

Results

VUR was detected in 23 ureterorenal units (16 VURs by both methods, 5 VURs by VCUG, and 2 VURs by MRVC). With VCUG as the standard of reference, the sensitivity of MRVC was 76.2%; the specificity, 90.0%; the positive predictive value, 88.9%; and the negative predictive value, 78.3%. There was concordance between two methods regarding the grade of reflux in all 16 ureterorenal units with VUR detected by both methods. Of 40 kidneys, MRVC detected findings of renal damage or reflux nephropathy in 13 kidneys, and 99mTc DMSA renal SPECT detected findings of reflux nephropathy in 17 kidneys.

Conclusion

Although MRVC is shown to have less sensitivity for VUR than VCUG, MRVC may represent a method of choice offering a safer nonradiation test that can additionally evaluate the kidneys for changes related to reflux nephropathy. J. Magn. Reson. Imaging 2005;21:406–414. © 2005 Wiley‐Liss, Inc.
Magnetic resonance angiography of the carotid arteries using three different techniques: Accuracy compared with intraarterial x‐ray angiography and endarterectomy specimens
Authors: Fellner Claudia , Lang Werner , Janka Rolf , Wutke Ralf , Bautz Werner , Fellner Franz A.
Published: March 2005

Purpose

To compare three different magnetic resonance angiography (MRA) techniques with x‐ray angiography and endarterectomy specimens.

Materials and Methods

Twenty‐one patients underwent x‐ray angiography, three‐dimensional time‐of‐flight (TOF) focusing on the carotid bifurcation, high‐resolution (HR) contrast‐enhanced (CE) MRA, and time‐resolved CE MRA. Stenoses of internal carotid arteries were evaluated by three independent observers on identical projection of x‐ray angiography and MRA. Maximum stenosis grades on MRA were assessed additionally and correlated with endarterectomy specimens in 12 cases.

Results

Sensitivity for the detection of severe stenoses was excellent (100%) for all MRA techniques, and specificity was superior for three‐dimensional TOF (96.7%) compared with HR CE MRA (80.6%) and time‐resolved CE MRA (83.9%). The correlation between x‐ray angiography and MRA for all stenoses was slightly superior for three‐dimensional TOF and HR CE MRA compared with the time‐resolved technique (κ = 0.87 and 0.86 vs. 0.84). The same trend was seen for the interobserver agreement and for the correlation with endarterectomy specimens. Eleven up to 17 stenoses (depending on the MRA technique) were graded higher using additional projections.

Conclusion

Three‐dimensional TOF MRA yielded even more accurate results than HR CE MRA in grading of stenoses near the carotid bifurcation. Therefore, a combination of both methods seems to be advantageous. J. Magn. Reson. Imaging 2005;21:424–431. © 2005 Wiley‐Liss, Inc.
Small bowel motility assessment with magnetic resonance imaging
Authors: Froehlich Johannes M. , Patak Michael A. , von Weymarn Constantin , Juli Christoph F. , Zollikofer Christoph L. , Wentz Klaus‐Ulrich
Published: March 2005

Purpose

To assess primarily the feasibility of magnetic resonance imaging (MRI) as a tool to monitor small bowel peristaltic motion and secondarily to validate this technique by demonstrating drug‐induced motility changes.

Materials and Methods

After a standardized oral preparation of Ispaghula husk (Metamucil®) and meglumine gadoterate (Gd‐DOTA; Dotarem®), 10 volunteers underwent dynamic MRI using a two‐dimensional turbofast field echo (TFE) sequence with a slice repetition time of 500 msec. Intraluminal cross‐sectional caliber changes over time were assessed allowing quantification of the peristaltic frequencies and amplitudes of the small gut on various regions of interest. Pharmacologically induced alterations of the peristaltic motion after spasmolytics and gastrokinetic motion enhancers were investigated.

Results

Small bowel diameter measurement resulted in a peristalsis of 10.96 (SD = ±2.51) waves per minute, oscillating regularly with mean amplitudes of 6.65 mm (SD = ±1.15 mm). Peristaltic frequency in normal individuals is consistent with that observed with other techniques. Intravenous administration of scopolamine butylbromide (= hyoscine butylbromide/Buscopan®) resulted in small bowel paralysis within 21.3 seconds (SD = ±2.8 seconds). Prokinetic effect of intravenous metoclopramide (Paspertin®) after Buscopan paralysis was tested in one volunteer, characterized by a slow recovery of peristalsis, which propagated from the proximal to the distal segments and enhanced contraction amplitudes.

Conclusion

Dynamic MRI allows observing and quantifying small bowel peristalsis, characterizing motion patterns, and monitoring the effects of interfering factors such as drugs. J. Magn. Reson. Imaging 2005;21:370–375. © 2005 Wiley‐Liss, Inc.
In vivo measurements of T1 relaxation times in mouse brain associated with different modes of systemic administration of manganese chloride
Authors: Kuo Yu‐Ting , Herlihy Amy H. , So Po‐Wah , Bhakoo Kishore K. , Bell Jimmy D.
Published: March 2005

Purpose

To measure regional T1 and T2 values for normal C57Bl/6 mouse brain and changes in T1 after systemic administration of manganese chloride (MnCl2) at 9.4 T.

Materials and Methods

C57Bl/6 mice were anesthetized and baseline T1 and T2 measurements obtained prior to measurement of T1 after administration of MnCl2 at 9.4 T. MnCl2 was administered systemically either by the intravenous (IV), intraperitoneal (IP), or subcutaneous (SC) routes. T1 and T2 maps for each MRI transverse slice were generated using commercial software, and T1 and T2 values of white matter (WM), gray matter (GM), pituitary gland, and lateral ventricle were obtained.

Results

When compared with baseline values at low‐field, significant lengthening of the T1 values was shown at 9.4 T, while no significant change was seen for T2 values. Significant T1 shortening of the normal mouse brain was observed following IV, IP, and SC administration of MnCl2, with IV and IP showing similar acute effects. Significant decreases in T1 values were seen for the pituitary gland and the ventricles 15 minutes after either IV or IP injection. GM showed greater uptake of the contrast agent than WM at 15 and 45 minutes after either IV or IP injections. Although both structures are within the blood‐brain barrier (BBB), GM and WM revealed a steady decrease in T1 values at 24 and 72 hours after MnCl2 injection regardless of the route of administration.

Conclusion

Systemic administration of MnCl2 by IV and IP routes induced similar time‐course of T1 changes in different regions of the mouse brain. Acute effects of MnCl2 administration were mainly influenced by either the presence or absence of BBB. SC injection also provided significant T1 change at subacute stage after MnCl2 administration. J. Magn. Reson. Imaging 2005;21:334–339. © 2005 Wiley‐Liss, Inc.
Reproducibility and dependence on diffusion weighting of line scan diffusion in the lumbar intervertebral discs
Authors: Newitt David C. , Majumdar Sharmila
Published: March 2005

Purpose

To investigate the dependence of line scan diffusion imaging (LSDI) in the lumbar vertebral discs on diffusion weighting, fat suppression (FS), and postprocessing noise correction.

Materials and Methods

Eleven normal volunteers were scanned using 4 b‐value and 12 b‐value LSDI protocols, with and without FS. Three repeated four b‐value scans were performed for evaluation of the reproducibility of apparent diffusion coefficient (ADC) values calculated with mono‐ and biexponential decay models. Two‐point ADC analysis for 12 b‐value scans was performed with and without noise correction to evaluate the ADC dependence on diffusion weighting. Correlations between different ADC calculation and acquisition methods were evaluated.

Results

Monoexponential ADC measures had a coefficient of variation (CV) under 3%, while use of a constrained biexponential increased the CV to 6% to 9%. Strong dependence on b‐value was seen from chemically shifted marrow fat signal and noise. These systematic variations in ADC were eliminated using noise correction and FS. ADC values from 4 and 12 b‐value FS scans correlated strongly (R2 = 0.91), while biexponentially derived ADC values correlated moderately well with the FS ADC (R2 = 0.51).

Conclusion

LSDI gives reproducible ADC measurements in the lumbar discs, largely independent of b‐value and signal‐to‐noise ratio (SNR) when used with noise correction and FS. J. Magn. Reson. Imaging 2005;21:482–488. © 2005 Wiley‐Liss, Inc.
Voluntary muscle activation, contractile properties, and fatigability in children with and without cerebral palsy
Authors: Stackhouse Scott K. , Binder‐Macleod Stuart A. , Lee Samuel C. K.
Published: March 2005

Cerebral palsy (CP) may lead to profound weakness in affected portions of the extremities and trunk. Knowing the mechanisms underlying muscle weakness will help to better design interventions for increasing force production in children with CP. This study quantified voluntary muscle activation, contractile properties, and fatigability of the quadriceps femoris and triceps surae in children with and without CP. Twelve children with CP (7–13 years) and 10 unaffected children (controls, 8–12 years) were assessed for (1) voluntary muscle activation during maximum voluntary isometric contractions (MVICs); (2) antagonist coactivation during agonist MVICs; (3) contractile properties, and (4) fatigability using electrically elicited tests. Children with CP were significantly weaker, had lower agonist voluntary muscle activation, and greater antagonist coactivation. In children with CP, the quadriceps normalized force–frequency relationship (FFR) was shifted upward at low frequencies and was less fatigable than controls. No differences were seen between groups in the normalized FFR and fatigability of the triceps surae. In addition, no differences were seen in the sum of the time to peak tension and half‐relaxation times between groups for either muscle. Because children with CP demonstrated large deficits in voluntary muscle activation, using voluntary contractions for strength training may not produce forces sufficient to induce muscle hypertrophy. Techniques such as enhanced feedback and neuromuscular electrical stimulation may be helpful for strengthening muscles that cannot be sufficiently recruited with voluntary effort. Muscle Nerve, 2005
Induced refolding of a temperature denatured llama heavy‐chain antibody fragment by its antigen
Authors: Dolk Edward , van Vliet Cees , Perez Janice M.J. , Vriend Gert , Darbon Hervé , Ferrat Gilles , Cambillau Christian , Frenken Leon G.J. , Verrips Theo
Published: March 2005

In a previous study we have shown that llama VHH antibody fragments are able to bind their antigen after a heat shock of 90°C, in contrast to the murine monoclonal antibodies. However, the molecular mechanism by which antibody:antigen interaction occurs under these extreme conditions remains unclear. To examine in more detail the structural and thermodynamic aspects of the binding mechanism, an extensive CD, ITC, and NMR study was initiated. In this study the interaction between the llama VHH ‐R2 fragment and its antigen, the dye Reactive Red‐6 (RR6) has been explored. The data show clearly that most of the VHH‐R2 population at 80°C is in an unfolded conformation. In contrast, CD spectra representing the complex between VHH‐R2 and the dye remained the same up to 80°C. Interestingly, addition of the dye to the denatured VHH‐R2 at 80°C yielded the spectrum of the native complex. These results suggest an induced refolding of denatured VHH‐R2 by its antigen under these extreme conditions. This induced refolding showed some similarities with the well established “induced fit” mechanism of antibody–antigen interactions at ambient temperature. However, the main difference with the “induced fit” mechanism is that at the start of the addition of the antigen most of the VHH molecules are in an unfolded conformation. The refolding capability under these extreme conditions and the stable complex formation make VHHs useful in a wide variety of applications. Proteins 2005. © 2005 Wiley‐Liss, Inc.