bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of neuroimaging in the diagnosis of mitochondrial disease
Authors: Friedman Seth D. , Shaw Dennis W. W. , Ishak Gisele , Gropman Andrea L. , Saneto Russell P.
Published: September 2010

Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke‐like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:129–135.
Molecular genetics of mitochondrial disorders
Authors: Wong Lee‐Jun C.
Published: September 2010

Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA replication, transcription, and translation, all require nuclear‐encoded genes. In this review, primary molecular defects in the mitochondrial genome and major classes of nuclear genes causing mitochondrial RCDs, including genes underlying mitochondrial DNA (mtDNA) depletion syndrome, as well as genes encoding RC subunits, complex assembly genes, and translation factors, are described. Diagnostic methodologies used to detect common point mutations, large deletions, and unknown point mutations in the mtDNA and to quantify mutation heteroplasmy are also discussed. Finally, the selection of nuclear genes for gold standard sequence analysis, application of novel technologies including oligonucleotide array comparative genomic hybridization, and massive parallel sequencing of target genes are reviewed. © © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:154–162.
Polymerase gamma disease through the ages
Authors: Saneto Russell P. , Naviaux Robert K.
Published: September 2010

The most common group of mitochondrial disease is due to mutations within the mitochondrial DNA polymerase, polymerase gamma 1 (POLG). This gene product is responsible for replication and repair of the small mitochondrial DNA genome. The structure‐function relationship of this gene product produces a wide variety of diseases that at times, seems to defy the common perceptions of genetics. The unique features of mitochondrial physiology are in part responsible, but POLG structure and function add to the conundrum of how one gene product can demonstrate autosomal recessive and autosomal dominant transmission, while also being responsible for pharmacogenetic disease, and exhibiting strong gene‐environment interactions. The wide spectrum of clinical manifestations of POLG disease can arise from infancy to old age. The modulation of clinical findings relate in part to the molecular architecture of the POLG protein. POLG has three distinct molecular domains: exonuclease, linker, and polymerase domains. Most of the mutations leading to dominant forms of POLG disease are located in the Polymerase domain. Mutations leading to recessive inheritance are distributed in all three domains of the gene. Environmental factors like valproic acid and infection can unmask POLG disease, causing it to occur earlier in life than when not exposed to these factors. Other drugs like nucleoside reverse transcriptase inhibitors can produce genotype‐specific POLG pharmacogenetic disease. Our current state of POLG understanding cannot account for many features of POLG disease. There is no answer for why the same mutation can give rise to varying diseases, disease severity, and age of onset. We introduce the term Ecogenetics in the context these features of POLG disease, to emphasize the important interactions between genes and environment in determining the expression of mitochondrial disease. In this article, we identify some of the key features that will help the reader understand POLG pathophysiology. When possible, we also identify genotype‐phenotype relationships, give clues for diagnosis, and summarize the major clinical phenotypes in the spectrum of POLG disease presenting from birth to old age. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:163–174.
Pharmacologic effects on mitochondrial function
Authors: Cohen Bruce H.
Published: September 2010

The vast majority of energy necessary for cellular function is produced in mitochondria. Free‐radical production and apoptosis are other critical mitochondrial functions. The complex structure, electrochemical properties of the inner mitochondrial membrane (IMM), and genetic control from both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) are some of the unique features that explain why the mitochondria are vulnerable to environmental injury. Because of similarity to bacterial translational machinery, mtDNA translation is likewise vulnerable to inhibition by some antibiotics. The mechanism of mtDNA replication, which is required for normal mitochondrial maintenance and duplication, is inhibited by a relatively new class of drugs used to treat AIDS. The electrochemical gradient maintained by the IMM is vulnerable to many drugs that are weak organic acids at physiological pH, resulting in excessive free‐radical generation and uncoupling of oxidative phosphorylation. Many of these drugs can cause clinical injury in otherwise healthy people, but there are also examples where particular gene mutations may predispose to increased drug toxicity. The spectrum of drug‐induced mitochondrial dysfunction extends across many drug classes. It is hoped that preclinical pharmacogenetic and functional studies of mitochondrial toxicity, along with personalized genomic medicine, will improve both our understanding of mitochondrial drug toxicity and patient safety. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:189–199.
The neurologic manifestations of mitochondrial disease
Authors: Parikh Sumit
Published: September 2010

The nervous system contains some of the body's most metabolically demanding cells that are highly dependent on ATP produced via mitochondrial oxidative phosphorylation. Thus, the neurological system is consistently involved in patients with mitochondrial disease. Symptoms differ depending on the part of the nervous system affected. Although almost any neurological symptom can be due to mitochondrial disease, there are select symptoms that are more suggestive of a mitochondrial problem. Certain symptoms that have become sine qua non with underlying mitochondrial cytopathies can serve as diagnostic “red‐flags.” Here, the typical and atypical presentations of mitochondrial disease in the nervous system are reviewed, focusing on “red flag” neurological symptoms as well as associated symptoms that can occur in, but are not specific to, mitochondrial disease. The multitudes of mitochondrial syndromes are not reviewed in‐depth, though a select few are discussed in some detail. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:120–128.
Bacteria, yeast, worms, and flies: Exploiting simple model organisms to investigate human mitochondrial diseases
Authors: Rea Shane L. , Graham Brett H. , Nakamaru‐Ogiso Eiko , Kar Adwitiya , Falk Marni J.
Published: September 2010

The extensive conservation of mitochondrial structure, composition, and function across evolution offers a unique opportunity to expand our understanding of human mitochondrial biology and disease. By investigating the biology of much simpler model organisms, it is often possible to answer questions that are unreachable at the clinical level. Here, we review the relative utility of four different model organisms, namely the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster, in studying the role of mitochondrial proteins relevant to human disease. E. coli are single cell, prokaryotic bacteria that have proven to be a useful model system in which to investigate mitochondrial respiratory chain protein structure and function. S. cerevisiae is a single‐celled eukaryote that can grow equally well by mitochondrial‐dependent respiration or by ethanol fermentation, a property that has proven to be a veritable boon for investigating mitochondrial functionality. C. elegans is a multicellular, microscopic worm that is organized into five major tissues and has proven to be a robust model animal for in vitro and in vivo studies of primary respiratory chain dysfunction and its potential therapies in humans. Studied for over a century, D. melanogaster is a classic metazoan model system offering an abundance of genetic tools and reagents that facilitates investigations of mitochondrial biology using both forward and reverse genetics. The respective strengths and limitations of each species relative to mitochondrial studies are explored. In addition, an overview is provided of major discoveries made in mitochondrial biology in each of these four model systems. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:200–218.
The role of mitochondrial dysfunction in psychiatric disease
Authors: Scaglia Fernando
Published: September 2010

Mitochondrial respiratory chain disorders are a group of genetically and clinically heterogeneous disorders caused by the biochemical complexity of mitochondrial respiration and the fact that two genomes, one mitochondrial and one nuclear, encode the components of the respiratory chain. These disorders can manifest at birth or present later in life. They result, at least in part, in defective production of ATP. Typically, mitochondrial disorders affect tissues with high energetic demands such as skeletal muscle, cardiac muscle, and the central nervous system. Neurological dysfunction is the most frequent clinical presentation of these disorders. The central nervous system is highly dependent on oxidative metabolism, and particular mitochondrial disorders are accompanied by focal brain necrosis (Leigh disease), dementia, or static encephalopathy. Furthermore, many children with mitochondrial encephalomyopathies present with more subtle and indolent signs including focal cognitive deficits of memory, perception, and language. Some subjects with mitochondrial disorders may also exhibit nonverbal cognitive impairment, compromised visuospatial abilities, and short‐term memory deficits associated with working memory that likely reflect defects in synaptic plasticity. Psychiatric features are found within the clinical spectrum of mitochondrial syndromes. It is increasingly recognized that mitochondrial dysfunction may be associated with neuropsychiatric abnormalities such as dementia, major depression, and bipolar disorder. Furthermore, several lines of evidence suggest that there is involvement of mitochondrial dysfunction in schizophrenia, including documented alterations in brain energy metabolism, electron transport chain activity, and expression of genes involved in mitochondrial function. The purpose of this review article is to summarize the psychiatric features observed in mitochondrial cytopathies and discuss possible mechanisms of dysfunctional cellular energy metabolism that underlie the pathophysiology of major subsets of psychiatric disorders. © 2010 Wiley‐Liss, Inc. Dev Disabil Res Rev 2010;16:136–143.
prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon‐Beard sensory neurons
Authors: Olesnicky Eugenia , Hernandez‐Lagunas Laura , Artinger Kristin Bruk
Published: September 2010

The PR domain containing 1a, with ZNF domain factor, gene (prdm1a) plays an integral role in the development of a number of different cell types during vertebrate embryogenesis, including neural crest cells, Rohon‐Beard (RB) sensory neurons and the cranial neural crest‐derived craniofacial skeletal elements. To better understand how Prdm1a regulates the development of various cell types in zebrafish, we performed a microarray analysis comparing wild type and prdm1a mutant embryos and identified a number of genes with altered expression in the absence of prdm1a. Rescue analysis determined that two of these, sox10 and islet1, lie downstream of Prdm1a in the development of neural crest cells and RB neurons, respectively. In addition, we identified a number of other novel downstream targets of Prdm1a that may be important for the development of diverse tissues during zebrafish embryogenesis. genesis 48:656–666, 2010. © 2010 Wiley‐Liss, Inc.
Facile and Green Synthesis of SERS Active and Ferromagnetic Silver Nanorods
Authors: Mohapatra Sudip , Siddhanta Soumik , Kumar D. Ravinder , Narayana Chandrabhas , Maji Tapas Kumar
Published: September 2010

Silver nanorods with increased surface‐enhanced Raman scattering sensitivity and detection have been synthesized in a novel, facile, and eco‐friendly way through a simple chemical reduction method using 2,3‐dihydroxyfumaric acid in aqueous solution under aerobic conditions. The structure and composition of the silver nanorods were characterized by UV/Vis spectroscopy, powder X‐ray diffraction, transmission electron microscopy (TEM), and field emission scanning electron microscopy (FESEM). Simple hard washing agglomerates the nanorods. The agglomerated nanorods consist of several “hot spots”, easily replaceable capping agents and an anisotropic shape, which are all responsible for its high sensitivity and trace detection (picomolar level) of different adsorbate molecules (thiophenol, Rhodamine 6G) in surface‐enhanced Raman scattering. Rarely observed, but theoretically established, unpaired s‐electron‐based ferromagnetism is the other interesting aspect of these nanorods.
Accelerated Syntheses of Porous Isostructural Lanthanide–Benzenetricarboxylates (Ln–BTC) Under Ultrasound at Room Temperature
Authors: Khan Nazmul Abedin , Haque Md. Masuqul , Jhung Sung Hwa
Published: September 2010

Porous isostructural [Ln(BTC)(H2O)·4.3H2O], or Ln–BTC (Ln: Ce, Tb, and Y; BTC stands for 1,3,5‐benzenetricarboxylate), with a tetragonal structure has been synthesized by ultrasonic irradiation at room temperature. Under ultrasound, the syntheses were quickly accelerated to obtain the fully crystallized phase in only minutes. The particle size can be considerably decreased by this method. On the basis of XRD, field‐emission scanning electron microscopy (FE‐SEM), and surface area analyses, it can be understood that the Ln–BTCs are homogeneous in phase, isostructural, and microporous. The synthesis rates are rCe–BTC > rTb–BTC > rY–BTC for both in the nucleation and crystal‐growth stages, thereby illustrating the importance of the lability of the metal ions in the synthesis of the metal‐organic framework (MOF) materials. The Tb–BTC shows luminescence properties, a characteristic property of Tb3+ (green‐light emission), in the range of 470–630 nm at room temperature. It is believed that these lanthanide MOFs with micropores and/or luminescent properties should be proven to be multifunctional materials on further investigations.
A MnII12 Supramolecular Array with Four Independent Spin‐Coupled Subunits
Authors: Shuvaev Konstantin V. , Dawe Louise N. , Thompson Laurence K.
Published: September 2010

The tetratopic pyridazine‐hydrazone ligand L2 is based on a design that successfully produces self‐assembled [4 × 4] MII16 (M = Mn, Cu) grids, but incorporates π‐charge‐rich, strong field bipy end groups. L2 forms an unusual incomplete“super” triangular CuII11 motif, dominated by the bipy ends. We now describe the incomplete MnII12 partial grid [Mn12(L2–2H)6(L–H)2{N(CN)2}2].
Hydrogenation and Dehydrogenation of Pentaphenylcyclopentadienes and Pentaphenylcyclopentenes
Authors: Kanthak Matthias , Muth Enrico , Dyker Gerald
Published: September 2010

Pentaaryl‐substituted cyclopentadienes and cyclopentenes have been employed in catalytic hydrogenation and photochemical cyclodehydrogenation reactions, targeting strained bowl‐shaped structures. Both types of reactions generally stop at the monohydrogenation and monocyclization stage, respectively.
Synthesis and Evaluation of Pseudopeptidic Fluorescence pH Probes for Acidic Cellular Organelles: In Vivo Monitoring of Bacterial Phagocytosis by Multiparametric Flow Cytometry
Authors: Burguete M. Isabel , Galindo Francisco , Izquierdo M. Angeles , O'Connor José‐Enrique , Herrera Guadalupe , Luis Santiago V. , Vigara Laura
Published: September 2010

A new family of fluorescent anthracenic pH probes has been synthesized, chemically characterized, and their photophysical properties have been investigated by steady‐state and time‐resolved fluorescence spectroscopy. The ability of these compounds to monitor pH has been investigated in solution and it was found that molecules 1–12 can act as fluorescent sensors for pH in a range between 4.6 and 6.5. This range corresponds to the pH of acidic organelles in the cell (pH 4.5–6.0) for which a limited number of probes are described. The acid–base behavior of each sensor varies slightly depending on the nature of substituents close to the amines present in the molecules. Thus, the pKa of this family of compounds can be finely tuned by the appropriate selection of the synthetic building blocks at the design stage. To test the potential diagnostic applications of this family of probes, macrocyclic pseudopeptide 2 was used to monitor the phagocytosis of a culture of GFP‐labelled bacteria by human monocytic cells U937 using flow cytometry as the analytical tool. It was found that the occurrence of bacterial killing was concomitant with the production of reactive oxygen species and a drop in pH, the latter monitored indirectly by macrocyclic sensor 2, which suggests its potential use for diagnostic purposes.
Spatial distribution of heavy metals in the coastal zone of “Sfax‐Kerkennah” plateau, Tunisia
Authors: Nedia Ghannem , Chafai Azri , Moncef Serbaji Mohammed , Chokri Yaich
Published: September 2010

The concentrations of selected heavy metals (Cr, Cd, Ni, Zn, Cu, Pb, Mn, and Fe) in surface sediments from the coastal zone of “Sfax‐Kerkennah” plateau (Tunisia) were studied to understand the current degree of metal contamination. The geochemical analyses showed wide spatial variations in metal concentrations. Enrichment factors (EFs) and principal component analysis revealed two distinct groups of metals. The first group corresponded to Mn and Fe that were derived from natural sources, and the second group contained Cr, Cd, Ni, Zn, Cu and to a lesser degree Pb that originated from anthropogenic sources. The localized higher EF values that were in harmony with those of the spatial distribution of element concentrations confirmed the significant impact of anthropogenic activities. On the basis of geoaccumulation index values (Igeo), these activities were shown to be responsible for important sediment contamination, especially close to the coastline. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Effects of microwave pretreatments on the anaerobic digestion of food industrial sewage sludge
Authors: Beszédes Sándor , László Zsuzsanna , Szabó Gábor , Hodúr Cecilia
Published: September 2010

Microwave irradiation is a novel and very promising technology for sludge conditioning. As pretreatment, it has a verified beneficial effect on the microbial degradation and anaerobic digestion of sewage sludge, but in present work we dealt with the applicability of microwave pretreatments for food industrial sludge. However, studies cannot be found that specialize on the effects of the MW treatments with different intensities on the anaerobic digestion of sludge. In our work we focused on the examination of the effect of MW pretreatment for 0.5, 2.5, and 5 W/g on the carbonaceous biochemical oxygen demand (CBOD5), solubilization of organic matters (sCOD/tCOD), and the mesophilic anaerobic digestion of dairy sewage sludge. It can be concluded that the MW pretreatments were appropriate to enhance the efficiency of anaerobic digestion. With MW pretreatments the specific biogas product could be increased from 220 mL g−1 to more than 600 mL g−1 because of the increased solubility (from 9.7% to more than 40%), and the enhanced accessibility of organic compounds for decomposing bacteria. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Life cycle assessment of polylactic acid and polyethylene terephthalate bottles for drinking water
Authors: Gironi Fausto , Piemonte Vincenzo
Published: September 2010

The biodegradable plastics were introduced in the 1980s to detect possible renewable feedstock to produce nonpetroleum‐based plastics as well as to reduce the environmental problems due to the increase of landfill volume. Furthermore, the biodegradable plastics have been used to reduce the environmental impact (in terms of energy requirement from nonrenewable resources and CO2 gas emissions) derived from production, utilization, and disposal of petroleum‐based plastics, like polyethylene terephthalate (PET). To this end, in the last years, different typologies of bioplastics were introduced (both biodegradable plastics and plastics made from renewable resources) like Mater‐Bi (made from starch), poly‐3‐hydroxybuyrate, polycaprolactone, and polylactic acid (PLA).

Nowadays, the most important tool to evaluate the environmental impact of a bioplastic and/or of a petroleum‐based plastic (conventional plastic) is the life cycle assessment (LCA) that determines the overall impact of a plastic on the environment by defining and analyzing several impact indices directly related to production, utilization, and disposal of the considered plastics.

In this work, the LCA (cradle to grave) of PLA bottles for drinking water was developed and compared to the LCA of PET bottles for the same use.

The obtained results highlighted that the true advantage of the PLA bottles with respect to the PET bottles arises from the use of renewable resources, but this benefit is paid in environmental terms due to the higher impact on human health and ecosystem quality (due to the use of pesticides, consumption of land, and consumption of water for the production of raw materials). © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Adaptation of bagasse fly ash, a sugar industry solid waste into zeolitic material for the uptake of phenol
Authors: Shah Bhavna , Tailor Ritesh , Shah and Ajay
Published: September 2010

Bagasse fly ash (BFA), a sugar industry waste was converted into zeolitic material (ZBFA) by alkaline hydrothermal treatment. The virgin BFA and synthesized ZBFA were characterized by various instrumental techniques viz. XRF, FTIR, PXRD. Zeolitazation achieved showed that zeolite‐P was the dominant constituent of ZBFA. The physico‐chemical properties of BFA and ZBFA were compared. Morphology of the sorbents was examined by SEM. The kinetic and thermodynamic data of sorbents were evaluated by Coats and Redfern method using Thermal Analysis (TGA, DTG, and DTA) data. The point of zero charge value of the sorbents determined by mass titration method showed higher value for ZBFA (pH 8.62) as compared with BFA (pH 5.80). The specific surface area of ZBFA increased to 505 m2/g (BFA = 440 m2/g). Sorption capacities of BFA and ZBFA were examined by sorption of phenol at various operational parameters. The equilibrium data were analyzed by various adsorption isotherms viz. Langmuir, Freundlich, Temkin, and D‐R. Langmuir isotherm best fits the experimental data for ZBFA (qm = 35.43 mg/g) and BFA (qm = 16.33 mg/g). The isotherms study indicates that the sorption capacity of synthetic zeolitic (ZBFA) products is significantly increased after alkaline hydrothermal treatment. © 2010 American Institute of Chemical Engineers Environ Prog, 2011
Chronic exposure to fluoxetine (Prozac) causes developmental delays in Rana pipiens larvae
Authors: Foster Hannah R. , Burton G. Allen , Basu Niladri , Werner Earl E.
Published: September 2010

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are among the many pharmaceuticals detected in aquatic ecosystems. Although the acute effects of SSRIs on select organisms have been reported, little is understood about the chronic effects of these drugs on amphibians, which are particularly sensitive to environmental pollutants. Serotonin plays important roles in many physiological functions, including a wide array of developmental processes. Exposure to SSRIs during development may cause developmental complications in a variety of organisms, but little is known about the degree of exposure necessary to cause deleterious effects. Here, we sought to gain a better understanding of the effects of SSRIs on amphibian development by use of a combined laboratory and outdoor mesocosm study. Tadpoles in a laboratory setting were exposed to a low (0.029 µg/L) and a high (0.29 µg/L) concentration of the common SSRI fluoxetine from stages 21 and 22 through completion of metamorphosis. Tadpoles in outdoor mesocosms were exposed to fluoxetine concentrations ranging from 0.1 to 0.3 µg/L. Exposed tadpoles in the laboratory showed delayed development compared with controls when stage was assessed throughout the experiment. Control tadpoles also gained weight faster than treatment tadpoles, which may be explained by reduced food intake. Mesocosm tadpoles exhibited similar trends, but no significant differences were detected. These results indicate that ecologically relevant levels of fluoxetine may cause developmental delays in amphibians. Environ. Toxicol. Chem. 2010;29:2845–2850. © 2010 SETAC
Mixture toxicity from photosystem II inhibitors on microalgal community succession is predictable by concentration addition
Authors: Porsbring Tobias , Backhaus Thomas , Johansson Per , Kuylenstierna Mats , Blanck Hans
Published: September 2010

The typical pollution situation involves chemical mixtures, and assessing the risks of single chemicals one at a time is not sufficient. Concentration addition (CA) has been suggested as a predictive tool in mixture ecotoxicology. The accuracy of CA for mixtures of similarly acting chemicals has been demonstrated under relatively simple biological conditions in single-species tests. To consider the high diversity of interconnected species in ecosystems, one must evaluate CA on a community level of biological organization. We sampled marine periphyton communities from the west coast of Sweden and exposed them to photosystem II (PSII) inhibiting herbicides for 4 d in the SWIFT test, a semistatic, small-scale laboratory test. During this time, the communities went through an ecological succession, influenced by the toxicants in a concentration-dependent manner. Multidimensional scaling was used to assess similarities in the effects of two different sets of PSII inhibitors on pigment profiles, which reflects the taxonomic structure and the physiological status of the microalgal community. One mixture of structurally congeneric phenylureas and one mixture of non-congeneric PSII inhibitors were tested. All PSII inhibitors and their mixtures caused similar changes in the pigment profiles, demonstrating that they not only have a similar biochemical mechanism of action but also are similarly acting on a community level. Concentration addition accurately predicted the effects of both mixtures over the entire effect range. This demonstrates that chemical congenericity is not required for a high predictive power of CA. Instead, in perfect analogy to the situation in single-species tests, a similar mode of action is a sufficient prerequisite for a successful application of CA. Environ. Toxicol. Chem. 2010;29:2806–2813. © 2010 SETAC
Adsorption of tetracycline on single-walled and multi-walled carbon nanotubes as affected by aqueous solution chemistry
Authors: Ji Liangliang , Chen Wei , Bi Jun , Zheng Shourong , Xu Zhaoyi , Zhu Dongqiang , Alvarez Pedro J.
Published: September 2010

Carbon nanotubes have shown great potential as effective adsorbents for hydrophobic organic contaminants in water treatment. The present study investigated the influence of aqueous solution chemistry on the adsorption of tetracycline to carbon nanotubes. Specifically, the effects of ionic strength (NaCl and CaCl2) and presence of Cu2+ ion (7.5 mg/L) or dissolved soil or coal humic acids (50 mg/L) on adsorption of tetracycline to single-walled carbon nanotubes (SWNT), multi-walled carbon nanotubes (MWNT), and nonporous pure graphite as a model of the graphite surface were systematically estimated. The presence of humic acids suppressed tetracycline adsorption on graphite and MWNT prominently, with stronger effects observed on graphite, but only slightly affected tetracycline adsorption on SWNT. The relatively large humic acid components could not readily access the small interstitial spaces of SWNT and thus were less competitive with tetracycline adsorption. The presence of Cu2+ ion increased tetracycline adsorption to both SWNT and MWNT through the mechanism of cation bridging, with much larger effects observed on MWNT. This was probably because when compared with the Cu2+ ions complexed on the surface of SWNT, those on the surface of MWNT having larger mesoporous interstices were more accessible to the relatively bulky tetracycline molecule. Increasing the ionic strength from 10 mM to 100 mM decreased tetracycline adsorption on both SWNT and MWNT, which was attributed to electronic shielding of the negatively charged surface sites. These results show that aqueous solution chemistry is important to tetracycline adsorption on carbon nanotubes. Environ. Toxicol. Chem. 2010;29:2713–2719. © 2010 SETAC
The value of repeating studies and multiple controls: replicated 28-day growth studies of rainbow trout exposed to clofibric acid
Authors: Owen Stewart F. , Huggett Duane B. , Hutchinson Thomas H. , Hetheridge Malcolm J. , McCormack Paul , Kinter Lewis B. , Ericson Jon F. , Constantine Lisa A. , Sumpter John P.
Published: September 2010

Two studies to examine the effect of waterborne clofibric acid (CA) on growth-rate and condition of rainbow trout were conducted using accepted regulatory tests (Organisation for Economic Co-operation and Development [OECD] 215). The first study (in 2005) showed significant reductions after 21 d of exposure (21-d growth lowest-observed-effect concentration [LOEC] = 0.1 µg/L, 21-d condition LOEC = 0.1 µg/L) that continued to 28 d. Growth rate was reduced by approximately 50% (from 5.27 to 2.67% per day), while the condition of the fish reduced in a concentration-dependant manner. Additionally, in a concentration-dependent manner, significant changes in relative liver size were observed, such that increasing concentrations of CA resulted in smaller livers after 28-d exposure. A no-observed-effect concentration (NOEC) was not achieved in the 2005 study. An expanded second study (in 2006) that included a robust bridge to the 2005 study, with four replicate tanks of eight individual fish per concentration, did not repeat the 2005 findings. In the 2006 study, no significant effect on growth rate, condition, or liver biometry was observed after 21 or 28 d (28-d growth NOEC = 10 µg/L, 28-d condition NOEC = 10 µg/L), contrary to the 2005 findings. We do not dismiss either of these findings and suggest both are relevant and stand for comparison. However, the larger 2006 study carries more statistical power and multiple-tank replication, so probably produced the more robust findings. Despite sufficient statistical power in each study, interpretation of these and similar studies should be conducted with caution, because much significance is placed on the role of limited numbers of individual and tank replicates and the influence of control animals. Environ. Toxicol. Chem. 2010;29:2831–2839. © 2010 SETAC
Comparison of field and laboratory exposures ofLumbriculus variegatusto polychlorinated biphenyl-impacted river sediments
Authors: Beckingham Barbara , Ghosh Upal
Published: September 2010

A method is described for conducting 14-d in situ sediment bioaccumulation tests with the freshwater oligochaete Lumbriculus variegatus, at the bottom of a slow-flowing river. The in situ test exposure chambers were constructed from cylindrical plastic tubes with flow-through mesh screens and were attached to a wire basket that was weighted to the river bottom at seven sites in the lower Grasse River in New York State, USA. This design was successful in exposing L. variegatus to native sediment and overlying water under field conditions, with adequate organism mass recovery (87 ± 19%). Results compared well with ex situ laboratory bioaccumulation conducted in parallel, expressed in terms of tissue concentration, biota-sediment accumulation factors (BSAFs), and bioaccumulation factors (BAFs). Bioaccumulation of polychlorinated biphenyls (PCBs) in L. variegatus (µg PCB/g wet wt) in laboratory and field tests was found to be within a factor of 2. The small variation between in situ and ex situ may have been caused by differences in water exchange rate under the two exposure scenarios, or other factors affecting organism behavior. Values of BSAF showed a hyperbolic trend with KOW, peaking at BSAF of 7 for congeners with log KOW of 6. Bioaccumulation factors also peaked at a value of 106.5 for congeners with log KOW value of 6 but remained steady around that value for the higher KOW congeners. These observations may reflect under-equilibration or reduced bioavailability of more hydrophobic PCBs in worm tissues or other analytical artifacts. Environ. Toxicol. Chem. 2010;29:2851–2858. © 2010 SETAC
Assessment of the levels of heavy metal pollution in roadside soils of Eskisehir, Turkey
Authors: Malkoc Semra , Yazıcı Berna , Savas Koparal A.
Published: September 2010

A detailed study was conducted to determine the current status of the heavy metals Cd, Cu, Cr, Fe, Hg, Mn, Ni, Pb, and Zn in Eskisehir, Turkey. The 15 different locations (n = 270) studied were specifically selected to identify the effects of soil pollution on the tramway, which has been in service since December 2004 for public transportation in Eskisehir. The samples were taken from three different lines: tramway-only lines, traffic-only lines, and both traffic and tramway lines. The pollution level was estimated based on the geoaccumulation index (Igeo), the enrichment factor (EF), the pollution index, and the integrated pollution index (IPI). The values for the IPI were in the following order: Pb > Zn > Cu > Fe > Mn > Ni > Cr > Cd, but mercury was not detected at any sample point. These indexes for metals in the soils under consideration correlated with either low or median levels of pollution. In addition, descriptive statistics were provided for the heavy metals under consideration, and box-plots were constructed and interpreted for all measured indices. Environ. Toxicol. Chem. 2010;29:2720–2725. © 2010 SETAC
Use of vegetated agricultural drainage ditches to decrease toxicity of irrigation runoff from tomato and alfalfa fields in California, USA
Authors: Werner Inge , Deanovic Linda A. , Miller Jeff , Denton Debra L. , Crane David , Mekebri Abdou , Moore Matthew T. , Wrysinski Jeanette
Published: September 2010

The current study investigated the potential of vegetated drainage ditches for mitigating the impact of agricultural irrigation runoff on downstream aquatic ecosystems. Water column toxicity to larval fathead minnow (Pimephales promelas),and the amphipod Hyalella azteca was measured for 12 h or less at the ditch inflow and outflow, using custom-built in situ exposure systems. In addition, water and sediment samples were subject to standard toxicity tests with Ceriodaphnia dubia and H. azteca, respectively. No acute toxicity to larval fathead minnow was observed; however, runoff was highly toxic to invertebrates. Passage through a 389- to 402-m section of vegetated ditch had a mitigating effect and reduced toxicity to some degree. However, runoff from an alfalfa field treated with chlorpyrifos remained highly toxic to both invertebrate species, and runoff from a tomato field treated with permethrin remained highly toxic to H. azteca after passage through the ditch. Predicted toxic units calculated from insecticide concentrations in runoff and 96-h median lethal concentration (LC50) values generally agreed with C. dubia toxicity measured in the laboratory but significantly underestimated in situ toxicity to H. azteca. Sediments collected near the ditch outflow were toxic to H. azteca. Results from the current study demonstrate that experimental vegetated ditches were unable to eliminate the risk of irrigation runoff to aquatic ecosystems. In addition, protective measures based on chemical concentrations or laboratory toxicity tests with C. dubia do not ensure adequate protection of aquatic ecosystems from pyrethroid-associated toxicity. Environ. Toxicol. Chem. 2010;29:2859–2868. © 2010 SETAC
Adaptive modelling and forecasting of offshore wind power fluctuations with Markov‐switching autoregressive models
Authors: Pinson Pierre , Madsen Henrik
Published: September 2010

Wind power production data at temporal resolutions of a few minutes exhibit successive periods with fluctuations of various dynamic nature and magnitude, which cannot be explained (so far) by the evolution of some explanatory variable. Our proposal is to capture this regime‐switching behaviour with an approach relying on Markov‐switching autoregressive (MSAR) models. An appropriate parameterization of the model coefficients is introduced, along with an adaptive estimation method allowing accommodation of long‐term variations in the process characteristics. The objective criterion to be recursively optimized is based on penalized maximum likelihood, with exponential forgetting of past observations. MSAR models are then employed for one‐step‐ahead point forecasting of 10 min resolution time series of wind power at two large offshore wind farms. They are favourably compared against persistence and autoregressive models. It is finally shown that the main interest of MSAR models lies in their ability to generate interval/density forecasts of significantly higher skill. Copyright © 2010 John Wiley & Sons, Ltd.
Estimation of P‐value of MAX test with double triangle diagram for 2 × 3 SNP case‐control tables
Authors: Hirosawa Katsura , Kawaguchi Takahisa , Matsuda Fumihiko , Yamada Ryo
Published: September 2010

Single nucle otide polymorphisms (SNPs) are the most popular markers in genetic epidemiology. Multiple tests have been applied to evaluate genetic effect of SNPs, such as Pearson's test with two degrees of freedom, three tests with one degree of freedom (χ2 tests for dominant and recessive modes and Cockran‐Armitage trend test for additive mode) as well as MAX3 test and MAX test, which are combination of four tests mentioned earlier. Because MAX test is a combination of Pearson's test of two degrees of freedom and two tests of one degree of freedom, the probability density function (pdf) of MAX statistics does not match pdf of χ2 distribution of either one or two degrees of freedom. In order to calculate P‐value of MAX test, we introduced a new diagram, Double Triangle Diagram, which was an extension of de Finetti diagram in population genetics which characterized all of the tests for 2 × 3 tables. In the diagram the contour lines of MAX statistics were consisted of elliptic curves and two tangent lines to the ellipses in the space. We normalized the ellipses into regular circles and expressed P‐value of MAX test in an integral form. Although a part of the integral was not analytically solvable, it was calculable with arbitrary accuracy by dividing the area under pdf into finite rectangles. We confirmed that P‐values from our method took uniform distribution from 0 to 1 in three example marginal count sets and concluded that our method was appropriate to give P‐value of MAX test for 2 × 3 tables. Genet. Epidemiol. 34:543–551, 2010. © 2010 Wiley‐Liss, Inc.
A Bayesian approach to genetic association studies with family‐based designs
Authors: Naylor Melissa G. , Weiss Scott T. , Lange Christoph
Published: September 2010

For genome‐wide association studies with family‐based designs, we propose a Bayesian approach. We show that standard transmission disequilibrium test and family‐based association test statistics can naturally be implemented in a Bayesian framework, allowing flexible specification of the likelihood and prior odds. We construct a Bayes factor conditional on the offspring phenotype and parental genotype data and then use the data we conditioned on to inform the prior odds for each marker. In the construction of the prior odds, the evidence for association for each single marker is obtained at the population‐level by estimating its genetic effect size by fitting the conditional mean model. Since such genetic effect size estimates are statistically independent of the effect size estimation within the families, the actual data set can inform the construction of the prior odds without any statistical penalty. In contrast to Bayesian approaches that have recently been proposed for genome‐wide association studies, our approach does not require assumptions about the genetic effect size; this makes the proposed method entirely data‐driven. The power of the approach was assessed through simulation. We then applied the approach to a genome‐wide association scan to search for associations between single nucleotide polymorphisms and body mass index in the Childhood Asthma Management Program data. Genet. Epidemiol. 34:569–574, 2010. © 2010 Wiley‐Liss, Inc.
Hepatitis C Virus Nonstructural Protein 5A Inhibitors: Novel Target—Now for New Trials and New Treatment Strategies†
Authors: Thompson Alex J. , Clark Paul J. , McHutchison John G.
Published: September 2010

Abstract

The worldwide prevalence of chronic hepatitis C virus (HCV) infection is estimated to be approaching 200 million people. Current therapy relies upon a combination of pegylated interferon-alpha and ribavirin, a poorly tolerated regimen typically associated with less than 50% sustained virological response rate in those infected with genotype 1 virus. The development of direct-acting antiviral agents to treat HCV has focused predominantly on inhibitors of the viral enzymes NS3 protease and the RNA-dependent RNA polymerase NS5B. Here we describe the profile of BMS-790052, a small molecule inhibitor of the HCV NS5A protein that exhibits picomolar half-maximum effective concentrations (EC50) towards replicons expressing a broad range of HCV genotypes and the JFH-1 genotype 2a infectious virus in cell culture. In a phase I clinical trial in patients chronically infected with HCV, administration of a single 100-mg dose of BMS-790052 was associated with a 3.3 log10 reduction in mean viral load measured 24 h post-dose that was sustained for an additional 120 h in two patients infected with genotype 1b virus. Genotypic analysis of samples taken at baseline, 24 and 144 h post-dose revealed that the major HCV variants observed had substitutions at amino-acid positions identified using the in vitro replicon system. These results provide the first clinical validation of an inhibitor of HCV NS5A, a protein with no known enzymatic function, as an approach to the suppression of virus replication that offers potential as part of a therapeutic regimen based on combinations of HCV inhibitors.
Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients
Authors: Yu Ming-Lung , Huang Chung-Feng , Huang Jee-Fu , Chang Ning-Chia , Yang Jeng-Fu , Lin Zu-Yau , Chen Shinn-Cherng , Hsieh Ming-Yuh , Wang Liang-Yen , Chang Wen-Yu , Li Yi-Ning , Wu Mei-Shin , Dai Chia-Yen , Juo Suh-Hang Hank , Chuang Wan-Long
Published: September 2010

Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (

r

2
= 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%,

P

= 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87,

P

< 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53,

P

< 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21,

P

= 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00,

P

= 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23,

P

< 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR.

Conclusion:

The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients. (Hepatology 2011)