bluuebunny/crossref_metadata_2025 huggingface dataset:
A Single Injection of an Adeno-Associated Virus Vector into Nuclei with Divergent Connections Results in Widespread Vector Distribution in the Brain and Global Correction of a Neurogenetic Disease
Authors: Cearley Cassia N. , Wolfe John H.
Published: September 2007

Neurogenetic disorders typically affect cells throughout the brain. Adeno-associated virus (AAV) vector-mediated transfer of a normal cDNA can correct the metabolic defects at the site of injection, but treatment of the entire brain requires widespread delivery of the normal gene and/or protein. Current methods require multiple injections for widespread distribution. However, some AAV vectors can be transported along neuronal pathways associated with the injected region. Thus, targeting widely dispersed systems in the CNS might be a pathway for gene dispersal from a limited number of sites. We tested this hypothesis in the ventral tegmental area (VTA), a region with numerous efferent and afferent projections. A single 1 μl injection resulted in transport of the vector genome to projection sites in distal parts of the brain. When compared with injections into the striatum, the VTA injection resulted in higher enzyme levels in more regions of the brain. The AAV-9 serotype vector was the most widely disseminated, but AAV-Rh.10 and AAV-1 were also transported after VTA injection. The effect on global lesions of a neurogenetic disease was tested in the mouse model of MPS VII (mucopolysaccharidosis VII), a lysosomal storage disorder. Widespread distribution of the vector genome after AAV-9 VTA injection resulted in even further distribution of the enzyme product, by secretion and uptake by surrounding cells, and complete correction of the storage lesions throughout the entire brain. This unprecedented level of correction from a single injection into the developed brain provides a potential strategy to correct a large volume of brain while minimizing the number of injections.
Coincident Activation of Metabotropic Glutamate Receptors and NMDA Receptors (NMDARs) Downregulates Perisynaptic/Extrasynaptic NMDARs and Enhances High-Fidelity Neurotransmission at the Developing Calyx of Held Synapse
Authors: Joshi Indu , Yang Yi-Mei , Wang Lu-Yang
Published: September 2007

NMDA receptors (NMDARs) are usually downregulated in developing central synapses, but underlying mechanisms and functional consequences are not well established. Using developing calyx of Held synapses in the mouse auditory brainstem, we show here that pairing presynaptic stimulation with postsynaptic depolarization results in a persistent downregulation in the summated amplitude of NMDAR-mediated EPSCs (NMDAR-EPSCs) during a train of stimuli (100/200 Hz, 100 ms) at both 22°C and 35°C. In contrast, the amplitude of single NMDAR-EPSCs or AMPA receptor-mediated EPSCs in the same synapses is not significantly altered, implying a preferential downregulation of perisynaptic/extrasynaptic NMDARs. Induction of this downregulation is blocked by antagonists for NMDARs or group I metabotropic glutamate receptors (mGluRs), suggesting that coincident activation of these two receptors is required. When the postsynaptic neuron is loaded with the fast Ca2+buffer BAPTA or depolarized to +60 mV to reduce the driving force for Ca2+influx, downregulation of the summated NMDAR-EPSCs is abolished, indicating Ca2+plays a critical role in the induction. The expression of this downregulation depends on ongoing synaptic activity, and is attenuated by a dynamin peptide (D15) that blocks clathrin-dependent internalization. We further demonstrated that the same induction paradigm specifically reduces NMDAR-dependent plateau potential and aberrant spike firings during repetitive activity. Together, our results suggest that coincident activation of mGluRs and NMDARs during intense synaptic activity may lead to selective endocytosis of NMDARs in the perisynaptic/extrasynaptic domain, and implicate that mGluRs are potentially important for gating development of high-fidelity neurotransmission at this synapse.
Targeting Cre Recombinase to Specific Neuron Populations with Bacterial Artificial Chromosome Constructs
Authors: Gong Shiaoching , Doughty Martin , Harbaugh Carroll R. , Cummins Alexander , Hatten Mary E. , Heintz Nathaniel , Gerfen Charles R.
Published: September 2007

Transgenic mouse lines are characterized with Cre recombinase driven by promoters of CNS-specific genes using bacterial artificial chromosome (BAC) constructs. BAC-Cre constructs for 10 genes (Chat,Th,Slc6a4,Slc6a2,Etv1,Ntsr1,Drd2,Drd1,Pcp2, andCmtm5) produced 14 lines with Cre expression in specific neuronal and glial populations in the brain. These Cre driver lines add functional utility to the >500 BAC-EGFP (enhanced green fluorescent protein) transgenic mouse lines that are part of the Gene Expression Nervous System Atlas Project.
Vesicle Pool Heterogeneity at Hippocampal Glutamate and GABA Synapses
Authors: Moulder Krista L. , Jiang Xiaoping , Taylor Amanda A. , Shin Wonchul , Gillis Kevin D. , Mennerick Steven
Published: September 2007

Glutamate and GABA are the major fast excitatory and inhibitory neurotransmitters, respectively, in the CNS. Although glutamate and GABA have clearly distinct postsynaptic actions, we are just beginning to appreciate that presynaptic differences between glutamatergic and GABAergic neurons may contribute to distinct functions of these transmitter systems. We therefore probed possible differences between the functional synaptic vesicle populations of glutamatergic and GABAergic neurons. We examined superecliptic synaptopHluorin (SpH) fluorescence during 20 Hz electrical stimulation in transfected hippocampal neurons and identified the phenotype of SpH-fluorescent synapses withpost hocimmunostaining. With 200 stimuli (10 s), individual glutamate synapses displayed considerably more variability in peak SpH fluorescence than GABA synapses, without a strong difference in the mean SpH fluorescence increase. This spatial heterogeneity could not be accounted for by differences in endocytosis, which was nearly constant over these short time periods across glutamate and GABA synapses. Instead, variability in vesicle exocytosis correlated with variability in total vesicle staining and in measures of the total recycling pool size. Differences were also evident using FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide] uptake. These data support the idea that the population of glutamate synapses exhibits more heterogeneity in release properties than the population of GABA synapses, possibly correlated with glutamatergic synaptic malleability.
The Itch-Producing Agents Histamine and Cowhage Activate Separate Populations of Primate Spinothalamic Tract Neurons
Authors: Davidson Steve , Zhang Xijing , Yoon Chul H. , Khasabov Sergey G. , Simone Donald A. , Giesler Glenn J.
Published: September 2007

Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legumeMucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch-producing agent cowhage.
Ethics Committee Experience with Emergency Exception from Informed Consent Protocols
Authors: DeIorio Nicole M. , McClure Katie B. , Nelson Maria , McConnell K. John , Schmidt Terri A.
Published: September 2007

Since 1996, U.S. federal regulations allow research without informed consent to study emergency conditions, if there is currently no satisfactory treatment for the condition, no time to obtain advance consent from the patient or representative, and if there is community involvement through a public disclosure and community consultation process. REB experiences since then are unknown. We surveyed REB chairpersons at the 126 United States medical schools to quantify reviewed protocols and identify attitudes about the rule, to better understand the rule's impact on REBs. Sixty-nine surveys were returned (55%). Fifty-two respondents reviewing human research had heard of the Rule. Forty-eight percent (25/52) had reviewed such a study; 40% of those had rejected at least one. Seventy-eight percent believe the rule protects human subjects, and 88% feel prepared to implement them. REB views differed from public opinion on how best to enact notification and consultation.
Respondent Reactions to Sensitive Questions
Authors: Fendrich Michael , Lippert Adam M. , Johnson Timothy P.
Published: September 2007

We administered debriefing probes to gauge respondent discomfort in reaction to sensitive questions. These probes assessed respondents' own reactions to being asked to report on substance use (subjective discomfort), as well as their beliefs about the reaction of others (projective discomfort). We investigated whether a sample of men from the general population were more uncomfortable with questions about drug use than a sample of men who have sex with men (MSM) surveyed from the same city (Chicago). We also investigated whether those who disclosed drug use on the survey experienced higher levels of discomfort. Contrary to opinions often expressed as research ethics committee (REC) recommendations, questions about drug use do not generate much subjective discomfort. MSM did not differ from the general population with respect to subjective discomfort. General population males did, however, report higher levels of “drug specific” projective discomfort. Respondents disclosing recent drug use reported higher levels of subjective discomfort. Implications for the REC practice, researcher and REC education, and directions for future research are discussed.
The Changing Images of Jihad Leaders: Shamil and Abd al-Qadir in Daghestani and Algerian Historical Writing
Authors: Kemper Michael
Published: September 2007

This article studies the images of two famous jihad leaders of the nineteenth century, the Daghestani Shamil (d. 1871) and the Algerian Abd al-Qadir (d. 1883), in Daghestani/Russian and in Algerian historiography. A combined horizontal and vertical perspective is applied to compare the sequence of new historical interpretations in both countries over time. In particular, the article discusses (1) nineteenth- and early twentieth-century Arabic biographies compiled by persons related to the two jihad leaders; (2) mid-twentieth-century Marxist and nationalist interpretations in Algeria and Daghestan; and (3) late-twentieth-century Islamist and "post-Islamist" interpretations. As is shown, the historiographical discourse went along similar paths in the two countries. At crucial points in time, certain interpretations of the jihad leaders were established and monopolized, while others were repressed (later to be revived), in order to use the historical memory for changing political agendas. The time after 1991 especially saw the publication of several new competing interpretations e.g., of regional and national Islamist and of feminist character. As a result, the term jihad can take on completely different meanings.
Southern Harmony: Catholic-Protestant Relations in the Antebellum South
Authors: Stern Andrew
Published: September 2007

This essay seeks to recover the experiences of Catholics in the antebellum South by focusing on their relations with Protestants. It argues that, despite incidents of animosity, many southern Protestants accepted and supported Catholics, and Catholics integrated themselves into southern society while maintaining their distinct religious identity. Catholic–Protestant cooperation was most clear in the public spaces the two groups shared. Protestants funded Catholic churches, schools, and hospitals, while Catholics also contributed to Protestant causes. Beyond financial support, each group participated in the institutions created by the other. Catholics and Protestants worshipped in each other's churches, studied in each other's schools, and recovered or died in each other's hospitals. This essay explores a series of hypotheses for the cooperation. It argues that Protestants valued Catholic contributions to southern society; it contends that effective Catholic leaders demonstrated the compatibility of Catholicism and American ideals and institutions; and it examines Catholic attitudes towards slavery as a ground for religious harmony. Catholics proved themselves to be useful citizens, true Americans, and loyal Southerners, and their Protestant neighbors approvingly took note. Catholic–Protestant cooperation complicates the dominant historiographical view of interreligious animosity and offers a model of religious pluralism in an unexpected place and time.
Beyond 'reasonable doubt': The criminal standard of proof instruction as communicative act
Authors: Heffer Chris
Published: September 2007

If juries are to bring in just verdicts in criminal trials, they need to understand the criminal standard of proof – beyond reasonable doubt – and apply it to the evidence they have heard in court. Yet courts have been notoriously ineffective in communicating that standard to lay jurors. This paper locates the problem not so much in specific wordings as in the entire paradigm of ‘instruction as legal text’ under which courts have tended to operate. After illustrating the effects of this paradigm on Judge Ito’s instruction in the O. J. Simpson criminal trial, the paper calls for a paradigm shift. It thus reinterprets the criminal standard as a communicative act, beginning with the message to be conveyed, some necessary conditions for conveying that message to the jury, and the role of the judge in delivering the message. The paper concludes with some recommendations for communicating the standard of proof instruction effectively.
Chondrogenic Potential of Human Adult Mesenchymal Stem Cells Is Independent of Age or Osteoarthritis Etiology
Authors: Scharstuhl Alwin , Schewe Bernhard , Benz Karin , Gaissmaier Christoph , Bühring Hans-Jörg , Stoop Reinout
Published: September 2007

Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from the iliac crest, depending on age and overall physical fitness. Here, we analyzed whether the availability and chondrogenic differentiation capacity of MSCs isolated from the femoral shaft as an alternative source is age- or OA etiology-dependent. MSCs were isolated from the bone marrow (BM) of 98 patients, categorized into three OA-etiology groups (age-related, joint trauma, joint dysplasia) at the time of total hip replacement. All BM samples were characterized for cell yield, proliferation capacity, and phenotype. Chondrogenic differentiation was studied using micromass culture and analyzed by histology, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction. Significant volumes of viable BM (up to 25 ml) could be harvested from the femoral shaft without observing donor-site morbidity, typically containing >107 mononuclear cells per milliliter. No correlation of age or OA etiology with the number of mononuclear cells in BM, MSC yield, or cell size was found. Proliferative capacity and cellular spectrum of the harvested cells were independent of age and cause of OA. From all tested donors, MSCs could be differentiated into the chondrogenic lineage. We conclude that, irrespective of age and OA etiology, sufficient numbers of MSCs can be isolated and that these cells possess an adequate chondrogenic differentiation potential. Therefore, a therapeutic application of MSCs for cartilage regeneration of OA lesions seems feasible.

Disclosure of potential conflicts of interest is found at the end of this article.
Ground improvement solutions for motorway widening schemes and new highway embankment construction over soft ground
Authors: Serridge C. J. , Synac O.
Published: September 2007

Over recent years both motorway/highway widening and new highway construction schemes have become increasingly fast track and complex. As such it is not always possible to permit sufficient time within the construction programme to allow settlement to occur for new embankments, particularly over soft ground, without some form of ground improvement. Some important steps in achieving successful ground improvement implementation are: adequate geotechnical site investigation; an appropriate design and review process; consideration of the interfacing of different ground improvement techniques; preliminary trials; monitoring, testing and quality control. Dependent upon the soil profile and geometry, this can be achieved in critical zones using a combination of ground improvement techniques such as vibro concrete columns (VCCs), vibro stone columns (VSCs) and vertical band drains (VBDs), to control settlements and also smooth out the settlement profile on the approach to rigid (piled) bridge abutments to ensure acceptable vehicle ride quality and reduce maintenance. These aspects are discussed, based upon ground improvement experiences on recent motorway widening and new highway construction schemes over soft ground in the UK.

Au cours des dernières années, les projets d'élargissement des grands axes routiers et de construction de nouveaux grands axes sont devenus de plus en plus «urgents» et toujours plus complexes. En conséquence, il n'est pas toujours possible de disposer de délais suffisants, dans le programme de construction, pour permettre le tassement de nouveaux talus, en particulier sur des sols boulants, sans une certaine bonification du sol. Parmi les mesures importantes permettant de réaliser un renforcement réussi du sol, on indiquera les suivantes: recherches géotechniques adéquates sur le site; méthode appropriée d'étude et de révision; examen de l'interface entre différentes techniques de bonification du sol; essais préliminaires; contrôles, essais et contrôle de la qualité. En fonction du profil et de la géométrie du sol, ceci peut être réalisé, dans des zones critiques, avec une combinaison de techniques de bonification du sol, comme les colonnes vibrobéton (VCC), les colonne de vibro-pierre (VSC) et les drains à bande verticale (VBD) pour suivre l'affaissement et réduire les profils d'affaissement à proximité de la culée de ponts rigides (sur piles) afin d'assurer la qualité acceptable de la circulation automobile et la réduction de l'entretien. Ces aspects sont discutés sur la base des expériences de bonification des sols réalisées récemment dans le cadre de l'élargissement d'autoroutes et de projets de construction de nouveaux grands axes routiers sur des terrains boulants, au Royaume-Uni
Acute silver toxicity in the euryhaline copepodAcartia tonsa: Influence of salinity and food
Authors: Pedroso Mariana Saia , Bersano José Guilherme Filho , Bianchini Adalto
Published: September 2007

The euryhaline copepod Acartia tonsa was exposed to silver (AgNO3) in either the absence or the presence of food (diatom Thalassiosira weissflogii; 2 × 104 cells/ml). Standard static-renewal toxicity tests that included a fixed photoperiod of 16: 8 h light:dark and temperature (20°C) were run in three different salinities (5, 15, and 30 ppt) together with measurements of pH, ions (Na+, Cl−, K+, SO2−4, Mg2+, and Ca2+), alkalinity, dissolved organic carbon, and total and dissolved (0.45 μm) silver concentrations in the experimental media. In the absence of food, the 48-h EC50 (concentration causing effect to 50% of the individuals tested) values based on total and dissolved silver concentrations were 11.6, 87.2, and 163.2 μg Ag/L and 7.1, 79.2, and 154.6 μg Ag/L at salinities 5, 15, and 30 ppt, respectively. In the presence of food, they were 62.1, 98.5, and 238.4 μg Ag/L and 48.4, 52.3, and 190.9 μg Ag/L, respectively. In all experimental conditions, most of the toxic silver fraction was in the dissolved phase, regardless of salinity or the presence of food in the water. In either the absence or the presence of food, acute silver toxicity was salinity dependent, decreasing as salinity increased. Data indicate that changes in water chemistry can account for the differences in acute silver toxicity in the absence of food, but not in the presence of food, suggesting that A. tonsa requires extra energy to cope with the stressful conditions imposed by acute silver exposure and ionoregulatory requirements in low salinities. These findings indicate the need for incorporation of both salinity and food (organic carbon) in a future biotic ligand model (BLM) version for estuarine and marine conditions, which could be validated and calibrated using the euryhaline copepod A. tonsa.
Acute and chronic toxicity of glyphosate compounds to glochidia and juveniles of Lampsilis siliquoidea (unionidae)
Authors: Bringolf Robert B. , Cope W. Gregory , Mosher Shad , Barnhart M. Chris , Shea Damian
Published: September 2007

Native freshwater mussels (family Unionidae) are among the most imperiled faunal groups in the world. Factors contributing to the decline of mussel populations likely include pesticides and other aquatic contaminants; however, there is a paucity of data regarding the toxicity of even the most globally distributed pesticides, including glyphosate, to mussels. Therefore, the toxicity of several forms of glyphosate, its formulations, and a surfactant (MON 0818) used in several glyphosate formulations was determined for early life stages of Lampsilis siliquoidea, a native freshwater mussel. Acute and chronic toxicity tests were performed with a newly established American Society of Testing and Materials (ASTM) standard guide for conducting toxicity tests with freshwater mussels. Roundup®, its active ingredient, the technical-grade isopropylamine (IPA) salt of glyphosate, IPA alone, and MON 0818 (the surfactant in Roundup formulations) were each acutely toxic to L. siliquoidea glochidia. MON 0818 was most toxic of the compounds tested and the 48-h median effective concentration (0.5 mg/L) for L. siliquoidea glochidia is the lowest reported for any aquatic organism tested to date. Juvenile L. siliquoidea were also acutely sensitive to MON 0818, Roundup, glyphosate IPA salt, and IPA alone. Technical-grade glyphosate and Aqua Star® were not acutely toxic to glochidia or juveniles. Ranking of relative chronic toxicity of the glyphosate-related compounds to juvenile mussels was similar to the ranking of relative acute toxicity to juveniles. Growth data from chronic tests was largely inconclusive. In summary, these results indicate that L. siliquoidea, a representative of the nearly 300 freshwater mussel taxa in North America, is among the most sensitive aquatic organisms tested to date with glyphosate-based chemicals and the surfactant MON 0818.
Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (unionidae)
Authors: Wang Ning , Ingersoll Christopher G. , Hardesty Douglas K. , Ivey Christopher D. , Kunz James L. , May Thomas W. , Dwyer F. James , Roberts Andy D. , Augspurger Tom , Kane Cynthia M. , Neves Richard J. , Barnhart M. Chris
Published: September 2007

The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 μg Cu/L (except 15 μg Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were <45 μg Cu/L or <12 mg N/L and were often at or below the final acute values (FAVs) used to derive the U.S. Environmental Protection Agency 1996 acute water quality criterion (WQC) for copper and 1999 acute WQC for ammonia. However, the chlorine EC50s for mussels generally were >40 μg/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC.
Are songbirds at risk from lead at small arms ranges? An application of the spatially explicit exposure model
Authors: Johnson Mark S. , Wickwire Ward Theodore , Quinn Michael J. , Ziolkowski David J. , Burmistrov Dima , Menzie Charles A. , Geraghty Ciaran , Minnich Michael , Parsons Patrick J.
Published: September 2007

Use of small arms during training is an important activity associated with the development and proficiency of soldiers. These weapons traditionally have used copper-jacketed lead projectiles; the copper facilitates the oxidation of the metallic lead resulting in more mobile oxides and carbonates. Consequently, many ranges at installations have high soil concentrations of lead. Many of these ranges are no longer used and have become habitat for wildlife. To address the potential for adverse effects from lead exposure in songbirds, we compared the outputs of traditional deterministic exposure models with a spatial model and compared the results of both with blood-lead levels from songbird species at two small arms range complexes. An integrative data collection procedure was used and incorporated into the spatially explicit exposure model (SEEM) for two small arms range sites. Site-specific data were used to refine model input parameters. These data included lead soil concentrations, analysis of lead concentrations in nestling food items, acid-insoluble ash content of feces (to estimate soil ingestion), location and mapping of singing males, and nest site location and characteristics. Territorial males also were spot-mapped to determine likelihood of breeding activity. Modeled estimates of risk were compared with blood and feather lead levels of adults and nestlings. Overall, edge species had higher blood-lead concentrations; however, most had concentrations below subclinical effect levels. Conventional deterministic methods produced risk estimates exceeding 10-fold the highest SEEM estimates. The spatially explicit exposure model provided good agreement with field observations and therefore produced more accurate risk estimates. The present study provides support for the application of spatial methods over conventional deterministic methods.
Effects of dilution on the exposure in sediment toxicity tests—buffering of freely dissolved concentrations and changes in mixture composition
Authors: ter Laak Thomas L. , Mayer Philipp , Klamer Hans J. C. , Hermens Joop L. M.
Published: September 2007

Some sediment toxicity tests, such as the Microtox® test, are conducted by diluting either contaminated sediment or an aqueous phase with clean water. The present study aims to clarify how the dilution procedure affects the exposure of organisms. It is shown that freely dissolved concentrations of hydrophobic compounds are buffered by desorption from the sediment matrix when sediment is diluted with water. The buffering depends on the properties of the sediment matrix and contaminant. Consequently, the composition of a contaminant mixture changes with dilution, and the exposure in a sediment dilution toxicity test is poorly defined. This questions the application and subsequent assessments of such tests. Additionally, the often-observed higher toxicity in sediment dilution tests relative to elutriate dilution tests is not sufficient to claim direct contact exposure, because the enhanced sensitivity in sediment dilution tests also can be explained by buffering from the sediment matrix. In applying these tests, one should be aware of the fundamental differences between the sediment dilution strategy and the dilution of an aqueous phase and of the consequences it has for the outcome of the test.
Effects of subchronic exposure to 2,6-dinitrotoluene in the northern bobwhite (Colinus Virginianus)
Authors: Quinn Michael J. , Bazar Matthew A. , McFarland Craig A. , Perkins Edward J. , Gust Kurt A. , Gogal Robert M. , Johnson Mark S.
Published: September 2007

Explosives and their breakdown products are commonly found in soils at U.S. military installations. Many areas where these compounds are found represent useful habitat for ground-foraging birds. Because these birds likely are exposed to such compounds, we evaluated the oral toxicity of 2,6-dinitrotoluene (DNT) in a representative ground-foraging species of management concern. Adult male and female northern bobwhite (Colinus virginianus) were exposed to either 0, 5, 10, 40, or 60 mg/kg/d via gavage for 60 d (subchronic) following determination of the median acute lethal dose (320 mg/kg). Circulating levels of red blood cells and hemoglobin were significantly decreased in a dose-dependent manner; however, levels remained within normal ranges. Plasma concentrations of total protein, albumin, globulin, aspartate aminotransferase, and potassium, sodium, and chlorine ions were significantly decreased, and circulating levels of uric acid were significantly increased. Decreased body weight, enlarged gallbladders, edematous gastrointestinal tracts, pale kidneys, pale and fibrous livers, and loose stools were consistent observations. The effects found in the clinical chemistries taken together with histopathological abnormalities observed in sections of hepatic and renal tissue suggest that the liver and kidneys are major targets for 2,6-DNT. Oral exposures to 2,6-DNT appear to affect northern bobwhite in a manner similar to that of the other main DNT isomer, 2,4-DNT, but in more subtle ways, adversely affecting the gastrointestinal system and leading to diarrhea and, ultimately, emaciation. The lowest-observed-adverse-effect level is 40 mg/kg/d based on hematological measures, and the no-observed-adverse-effect level is 10 mg/kg/d based on the absence of results indicative of adverse effects.
Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals
Authors: Zounková Radka , Odráška Pavel , Doležalová Lenka , Hilscherová Klára , Maršálek Blahoslav , Bláha Luděk
Published: September 2007

The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5-fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth-inhibition test, algal Pseudokirchneriella subcapitata growth-inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS-chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest-observed-effect concentrations and concentrations causing 50% effects (EC50s) values ranging within μg/L to mg/L. The most toxic compound was 5-fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS-chromotest (minimum genotoxic concentrations [MGC] = 0.07–0.2 mg/L), and 5-fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention.
Effects of a fertilizer, an insecticide, and a pathogenic fungus on hatching and survival of bullfrog (Rana Catesbeiana) tadpoles
Authors: Puglis Holly J. , Boone Michelle D.
Published: September 2007

We assessed the single and interactive effects of ammonium nitrate fertilizer, the insecticide carbaryl, and a widespread waterborne pathogen Saprolegnia ferax on the hatching and survival of bullfrog (Rana catesbeiana) tadpoles in the laboratory. Carbaryl significantly reduced tadpole survival and hatching rate, but no interactive effects were found among stressors.
Governing the Governance of Education: The State Strikes Back?
Authors: Hudson Christine
Published: September 2007

In many countries, there have been changes in the way in which education is governed, with greater fragmentation of responsibility between the state, local government, schools, individuals and the market often accompanied by a move from detailed regulation to framework legislation. Previously, these developments have been seen as part of the move from government to governance whereby the state is forced to step back and allow other interests to play a role. However, in recent years more subtle theories of governance have been developed which argue that, rather than retreating, the state is adapting to changing circumstances and finding new ways of governing. The importance of education not only in terms of creating and maintaining national identity but also for economic development suggests that this is an area from which the state will not willingly abdicate its role. This article suggests that support for the new governance theories can be found in the field of education. It argues that the growth in the attempts to control educational outputs through, for example, demands for quality controls, standardized testing, evaluations and so on and the introduction of national bodies responsible for carrying out these controls can be interpreted as a sign that the state, far from relinquishing its role, is finding other ways of controlling education. A comparative approach is adopted and these ideas are explored in relation to education systems in the Nordic and British countries. The article draws on a qualitative analysis of official policy documents, legislation and official statements concerning education in the respective countries.
Biofunctionalization of Fluorescent Nanoparticles
Authors: Murcia Michael J. , Naumann Christoph A.
Published: September 2007

The sections in this article are

Introduction

Fluorescent Nanoparticle Probes

Dye‐doped Nanoparticles

Quantum Dots (
QDs
)

Metal Nanoparticles

Hybrid Architectures Involving Fluorescent Nanoprobes

Metal–Dye

Dye‐doped Silica Shells

Quantum Dot‐containing Microspheres

Bioconjugation of Fluorescent Nanoparticles

General Considerations

Overview

Common Coupling Reactions

Bioconjugation of Polymeric Nanoparticles

Noncovalent Approaches

Covalent Approaches

Bioconjugation of Quantum Dots

Noncovalent Approaches

Covalent Approaches

Bioconjugation of Metallic Nanoprobes

Noncovalent Approaches

Covalent Approaches

Design of Biocompatible Coatings

General Considerations

Overview

Colloidal Stability

Biocompatible Surfaces

Cytotoxicity

Nanoparticle‐stabilizing Coatings

Low Cytotoxicity Coatings

Applications

Biosensing

Polymeric Sensors

Quantum Dot Sensors

Metallic Sensors

Fluorescent Nanoparticles as Labels in Biological Imaging

Dye‐doped Nanoparticles

Quantum Dots
Biofunctionalization of Carbon Nanotubes
Authors: Bekyarova Elena , Haddon Robert C. , Parpura Vladimir
Published: September 2007

The sections in this article are

Introduction

Carbon Nanotubes – Types, Structures and Properties

Synthesis of Carbon Nanotubes

Approaches to Aqueous Solubilization of Carbon Nanotubes

Chemical Modifications

Use of Water‐compatible Surfactants

Functionalization with Water‐soluble Polymers

Interaction and Functionalization with Biological Molecules

Noncovalent Biofunctionalization

Covalent Biofunctionalization

Applications of Biofunctionalized Carbon Nanotubes

Assembly of Electronic Devices

Biosensing

Substrates for Neuronal Growth

Concluding Remarks

Acknowledgments
Biofunctionalization of Magnetic Nanoparticles
Authors: Gao Yong
Published: September 2007

The sections in this article are

Introduction

Functionalization of Magnetic Nanoparticles forIn VitroProtein/Cell Separation

Functionalization of Magnetic Nanoparticles for Biochemical/Chemical Synthesis of Therapeutic Drugs and Their Intermediates

Functionalization of Magnetic Nanoparticles forIn VivoBio‐imaging, Drug Targeting and Tumor Hyperthermia Treatments

MRImaging

Targeted Drug Delivery

Magnetic Hyperthermia

Conclusions

Acknowledgments
Biofunctionalization of Phospholipid Polymer Nanoparticles
Authors: Watanabe Junji , Park Jongwon , Ito Tomomi , Takai Madoka , Ishihara Kazuhiko
Published: September 2007

The sections in this article are

Introduction

Nanofabrication for Biomedical Applications

Nano‐scaled Processing

Key Materials for Nanofabrication

Design of Bioconjugate Nanoparticles

Bioconjugate Phospholipid Polymer

Solution Properties by Fluorescence Probe

Bioconjugate Nanoparticles

Surface Elemental Analysis by
X
‐ray Photoelectron Spectroscopy

Surface ζ‐Potential on Nanoparticles

Particle Size by Dynamic Light Scattering and Morphology by Scanning Electron Microscope

Determination of Active Ester Groups on Nanoparticles

Biofunction on Nanoparticles

Design of Sequential Enzymatic Reaction

Amplified Signal on Nanoparticles

Application for Molecular Diagnosis

Example of
C
‐reactive Protein Detection Using Nanoparticles

High‐performance Diagnosis in Serum

Conclusions

Acknowledgments
Biofunctionalization of Metallic Nanoparticles and Microarrays for Biomolecular Detection
Authors: Festag Grit , Klenz Uwe , Henkel Thomas , Csáki Andrea , Fritzsche Wolfgang
Published: September 2007

The sections in this article are

Introduction

Applications

Array Fabrication

Detection Methods

Optical Absorbance

SPR
Imaging

R
aman Scattering

Electrical Detection

Electrochemical Detection

Gravimetric

Nanoparticles and their Biofunctionalization

Types of Nanoparticles used for Biomolecular Detection

Metal Nanoparticles

Core/Shell Particles

Magnetic Nanoparticles

Quantum Dots

Synthesis of Gold (Silver) Nanoparticles

Biofunctionalization

Modification of Gold Nanoparticles with Oligonucleotides/
DNA

Modification of Gold Nanoparticles with Proteins

Biofunctionalization of other Metal Nanoparticles

Biological Applications of Gold Nanoparticles

Substrates and their Biofunctionalization

Molecular Thin Films

Self‐assembly Monolayers

Optimization of Gold Nanoparticle‐based Microarrays for
DNA
Detection

Nanoporous Gels

Outlook
Conjugation of Nanomaterials with Proteins
Authors: Meziani Mohammed J. , Lin Yi , Sun Ya‐Ping
Published: September 2007

The sections in this article are

Introduction

Coupling of Inorganic Nanoparticles with Proteins

Chemical Functionalization Methods

Protein‐assisted Assemblies of Inorganic Nanoparticles

Crosslinking Route through Protein Recognition

Template‐directed Approach

Supercritical Fluid Methods

BSA‐conjugated Silver Nanoparticles

BSA‐conjugated Semiconductor Nanoparticles

Assembly and Disassembly of Nanoparticles through Protein Isomeric Conversion

Coupling of Carbon Nanotubes and Proteins

Non‐specific Adsorption

Specific Conjugation and Biorecognition

Conclusions and Perspectives

Acknowledgment
Gelatin Nanoparticles and Their Biofunctionalization
Authors: Kommareddy Sushma , Shenoy Dinesh B. , Amiji Mansoor M.
Published: September 2007

The sections in this article are

Introduction

Gelatin and Gelatin Derivatives

Gelatin

Chemical Modification of Gelatin

PEGylation

Thiolation

Other Conjugates of Gelatin

Nanoparticulate Carriers of Gelatin and Gelatin Derivatives

Desolvation

Desolvation Using Ethanol

Two‐step Desolvation

Coacervation

Nano‐encapsulation by Water‐in‐oil Emulsion Method

Characterization of Gelatin and Modified Gelatin Nanoparticles

Loading and Release of Payload from Gelatin Nanoparticles

Biocompatibility Studies

Applications of Gelatin and Modified Gelatin Nanoparticles

Conclusions
Self‐assembledDNANanotubes
Authors: LaBean Thom , Park Sung Ha
Published: September 2007

The sections in this article are

Introduction

DNANanotubes Self‐assembled fromDXTiles

DAE‐E DXTile Nanotubes

DAE‐O DXTile Nanotubes

TXTile Nanotubes

4 × 4 Tile Nanotubes

6HBTile Nanotubes

Applications

Summary and Perspectives
Nucleic Acid Nanoparticles
Authors: Zuber Guy , Pons Bénédicte , Fraley Andrew W.
Published: September 2007

The sections in this article are

Introduction

The Chemical and Physical Properties of Therapeutic
DNA

Preparation of Nucleic Acid Nanoparticles: Synthesis and Characterization

Rationale

Synthesis, Characterization and Optimization of Surfactants

Organization of the Surfactant–
DNA
Complexes

Quantification of the Stability of Surfactant–
DNA
Complexes

DNA
Functionalization for Cell Recognition and Internalization

Strategies for Functionalization

Intercalation

Triple Helix Formation with Oligodeoxyribonucleotides

Peptide Nucleic Acids (
PNAs
)

Interactions of
DNA
with Fusion Proteins

Agents that Bind to the Minor Groove

DNA
Nanoparticles: Sophistication for Cell Recognition and Internalization

Preparation of
DNA
Nanoparticles Enveloped with a Protective Coat and Cell Internalization Elements

Biomedical Application: Cell Targeting and Internalization Properties of Folate–
PEG
‐coated Nanoparticles

Concluding Remarks
Lipoplexes
Authors: Weisman Sarah
Published: September 2007

The sections in this article are

Introduction

DNA
Lipoplexes

Composition

Nanostructure and Microstructure

Equilibrium Morphology

Nonequilibrium Morphology

Lipoplex Size

Lipofection Efficiency

In Vitro

In Vivo

ODN
Lipoplexes

si
RNA
Lipoplexes

Acknowledgments
DNA
–Chitosan Nanoparticles for Gene Therapy: Current Knowledge and Future Trends
Authors: Fernandes Julio C. , Tiera Marcio José , Winnik Françoise M.
Published: September 2007

The sections in this article are

Introduction

Chitosan as a Carrier for Gene Therapy

Chitosan Chemistry

General Strategies for Chitosan Modification

Chitosan–
DNA
interactions: Transfection Efficacy of Unmodified Chitosan

Modified Chitosans: Strategies to Improve the Transfection Efficacy

The Effects of Charge Density/Solubility and Degree of Acetylation

Improving the Physicochemical Characteristics of the Nanoparticulate Systems: Solubility, Aggregation and
RES
Uptake

Targeting Mediated by Cell Surface Receptors

Hydrophobic Modification: Protecting the
DNA
and Improving the Internalization Process

Methods of Preparation of Chitosan Nanoparticles

Complex Coacervation

Crosslinking Methods

Chemical Crosslinking

Ionic Crosslinking or Ionic Gelation

Emulsion Crosslinking

Spray Drying

Other Methods

DNA
Loading into Nano‐ and Microparticles of Chitosan

DNA
Release and Release Kinetics

Preclinical Evidence of Chitosan–
DNA
Complex Efficacy

Potential Clinical Applications of Chitosan–
DNA
in Gene Therapy

Conclusion

Acknowledgments
Peptide Nanoparticles
Authors: Langer Klaus
Published: September 2007

The sections in this article are

Introduction

Starting Materials for the Preparation of Nanoparticles

Preparation Methods

Nanoparticle Preparation by Emulsion Techniques

Emulsion Technique for the Preparation of Albumin‐based Microspheres and Nanoparticles

Emulsion Technique for the Preparation of Gelatin‐based Microspheres and Nanoparticles

Emulsion Technique for the Preparation of Casein‐based Microspheres and Nanoparticles

Nanoparticle Preparation by Coacervation

Complex Coacervation Techniques for the Preparation of Nanoparticles

Simple Coacervation (Desolvation) Techniques for the Preparation of Nanoparticles

Basic Characterization Techniques for Peptide Nanoparticles

Drug Targeting with Nanoparticles

Passive Drug Targeting with Particle Systems

Active Drug Targeting with Particle Systems

Surface Modifications of Protein‐based Nanoparticles

Surface Modification by Different Hydrophilic Compounds

Surface Modification by Polyethylene Glycol (PEG) Derivatives

Surface Modification by Drug‐targeting Ligands

Different Surface Modification Strategies

Applications as Drug Carriers and for Diagnostic Purposes

Protein‐based Nanoparticles in Gene Therapy

Parenteral Application Route

Preclinical Studies with Protein‐based Particles

Clinical Studies with Protein‐based Particles

Topical Application of Protein‐based Particles

Peroral Application of Protein‐based Particles

Immunological Reactions with Protein‐based Microspheres

Concluding Remarks
Nanoscale Patterning of
S
‐Layer Proteins as a Natural Self‐assembly System
Authors: Sára Margit , Pum D. , Huber C. , Ilk N. , Pleschberger M. , Sleytr U. B.
Published: September 2007

The sections in this article are

Introduction

General Properties of
S
‐Layers

Structure, Isolation, Self‐Assembly and Recrystallization

Chemistry and Molecular Biology

S
‐Layers as Carbohydrate‐binding Proteins

Nanoscale Patterning of
S
‐Layer Proteins

Properties of
S
‐Layer Proteins Relevant for Nanoscale Patterning

Immobilization of Functionalities by Chemical Methods

Patterning by Genetic Approaches

The
S
‐Layer Proteins
Sbs
A
,
Sbs
B
and
Sbs
C

S
‐Layer Fusion Proteins

Spatial Control over
S
‐Layer Reassembly

S
‐Layers as Templates for the Formation of Regularly Arranged Nanoparticles

Binding of Molecules and Nanoparticles to Functional Domains

In Situ
Synthesis of Nanoparticles on
S
‐Layers

Conclusions and Outlook

Acknowledgments