bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Vouchers to Increase Continuing Care Participation in Veterans: Does Magnitude Matter?
Authors: Businelle Michael S. , Rash Carla J. , Burke Randy S. , Parker Jefferson D.
Published: March 2009

The present study examined the comparative effects of adding contingency management (CM) schedules to an existing substance abuse continuing care program, with the goal of increasing attendance. We retrospectively examined the attendance of 135 veterans enrolled in one of three CM programs and a quasi‐control condition of 55 veterans. Results indicated that participants enrolled in the two higher magnitude CM voucher programs increased both continuing care attendance and length of participation. Findings support the use of CM to increase continuing care attendance among veterans with substance use disorders, and suggest that voucher magnitude and bonuses both had a positive impact.
Early Outcomes Following Low Dose Naltrexone Enhancement of Opioid Detoxification
Authors: Mannelli Paolo , Patkar Ashwin A , Peindl Kathleen , Gottheil Edward , Wu Li‐Tzy , Gorelick David A
Published: March 2009

Although withdrawal severity and treatment completion are the initial focus of opioid detoxification, post‐detoxification outcome better defines effective interventions. Very low dose naltrexone (VLNTX) in addition to methadone taper was recently associated with attenuated withdrawal intensity during detoxification. We describe the results of a seven‐day follow‐up evaluation of 96 subjects who completed inpatient detoxification consisting of the addition of VLNTX (0.125 or 0.250 mg per day) or placebo to methadone taper in a double blind, randomized investigation. Individuals receiving VLNTX during detoxification reported reduced withdrawal and drug use during the first 24 hours after discharge. VLNTX addition was also associated with higher rates of negative drug tests for opioids and cannabis and increased engagement in outpatient treatment after one week. Further studies are needed to test the utility of this approach in easing the transition from detoxification to various follow‐up treatment modalities designed to address opioid dependence.
Affirmative action, gender equity and university admissions – Kenya, Uganda and Tanzania
Authors: Onsongo Jane
Published: March 2009

The article examines the outcomes of affirmative action policies aimed at improving access for women students to university education in Kenya, Uganda and Tanzania. Different interpretations of affirmative action are found in the three countries. These include lower entry scores, remedial
pre-university programmes and financial assistance. There are limitations and weaknesses inherent in the piecemeal strategies that focus only on the point of admission to university. Thus affirmative action as currently applied does not enhance access and gender equity in university education.
A multifaceted approach to developing gender equality in universities would require various strategies to support one another in order to enhance access and gender equity in university education in the three countries.
Adult age differences in memory for distinctive information: Evidence from the bizarreness effect
Authors: Nicolas Serge , Worthen James B.
Published: March 2009

Two experiments examined age-related differences in memory for bizarre and common pictures. In Experiment 1, a facilitative effect of bizarreness was obtained for young adults and one of the older groups, but not for the oldest group (over age 70). However, the bizarreness effect was found for even the oldest group when predominantly common lists were used in Experiment 2. It is concluded that older adults suffer from deficits in distinctive processing, but those deficits can be reduced by providing a more uniformly common context in which differences can be processed.
Short article: Implicit motor sequence learning is not represented purely in response locations
Authors: Richard Marc V. , Clegg Benjamin A. , Seger Carol A.
Published: March 2009

This study employed a novel variant of the serial reaction time task, focused on sequencing one element of movement—direction. During the task a repeated pattern of alternating directions (right–left–right, etc.) was embedded in the stimuli, and there was no series of response locations. Responses were made via two effector systems: single-finger responding (necessitates lateral arm movements between response keys), and four-fingered responding (4 individual fingers on 4 individual keys; requires no lateral arm movement). The sequence of directions was only learned by participants who performed lateral movements during training, indicating that learning was contingent on the particular motor effector used. Participants with low levels of sequence awareness displayed the same pattern of results.
Memory Consolidation, Multiple Realizations, and Modest Reductions
Authors: Sullivan Jacqueline Anne
Published: March 2009

This article investigates several consequences of a recent trend in philosophy of mind to shift the relata of realization from mental state–physical state to function-mechanism. It is shown, by applying both frameworks to the neuroscientific case study of memory consolidation, that, although this shift can be used to avoid the immediate antireductionist consequences of the traditional argument from multiple realizability, what is gained is a far more modest form of reductionism than recent philosophical accounts have intimated and neuroscientists themselves have claimed.
Causal Processes, Fitness, and the Differential Persistence of Lineages
Authors: Bouchard Frédéric
Published: March 2009

Ecological fitness has been suggested to provide a unifying definition of fitness. However, a metric for this notion of fitness was in most cases unavailable except by proxy with differential reproductive success. In this article, I show how differential persistence of lineages can be used as a way to assess ecological fitness. This view is inspired by a better understanding of the evolution of some clonal plants, colonial organisms, and ecosystems. Differential persistence shows the limitation of an ensemblist noncausal understanding of evolution. Causal explanations are necessary to understand the evolution by natural selection of these biological systems.
Stable Models and Causal Explanation in Evolutionary Biology
Authors: Glymour Bruce
Published: March 2009

Models that fail to satisfy the Markov condition are unstable because changes in state variable values may cause changes in the values of background variables, and these changes in background lead to predictive error. Such error arises because non-Markovian models fail to track the causal relations generating the values of response variables. This has implications for discussions of the level of selection: under certain plausible conditoins most standard models of group selection will not satisfy the Markov condition when fit to data from real populations. These models neither correctly represent the causal structure generating nor correctly explain the phenomena of interest.
Chance in Boltzmannian Statistical Mechanics
Authors: Frigg Roman
Published: March 2009

In two recent papers Barry Loewer (2001, 2004) has suggested to interpret probabilities in statistical mechanics as chances in David Lewis's (1994) sense. I first give a precise formulation of this proposal, then raise two fundamental objections, and finally conclude that these can be overcome only at the price of interpreting these probabilities epistemically.
How Practical Know-How Contextualizes Theoretical Knowledge: Exporting Causal Knowledge from Laboratory to Nature
Authors: Waters C. Kenneth
Published: March 2009

Leading philosophical accounts presume that Thomas H. Morgan's transmission theory can be understood independently of experimental practices. Experimentation is taken to be relevant to confirming, rather than interpreting, the transmission theory. But the construction of Morgan's theory went hand in hand with the reconstruction of the chief experimental object, the model organismDrosophila melanogaster. This raises an important question: when a theory is constructed to account for phenomena in carefully controlled laboratory settings, what knowledge, if any, indicates the theory's relevance to phenomena outside highly controlled settings? The answer, I argue, is found within the procedural knowledge embedded within laboratory practice.
How Determinism Can Fail in Classical Physics and How Quantum Physics Can (Sometimes) Provide a Cure
Authors: Earman John
Published: March 2009

Various fault modes of determinism in classical physics are outlined. It is shown how quantum mechanics can cure some forms of classical indeterminism.
Norms and Games
Authors: Hardin Russell
Published: March 2009

There are three centrally important ways in which norms have been elaborated and explained: in terms of religious or natural law strictures on behavior, in terms of constraints imposed by rationality, and, recently, in terms of agents' behavior in well-defined games. The principal difficulty of a gaming account of norms is to show how the account explains motivations of individuals to follow the norms. This issue is examined in the context of small-number norms and large-number norms.
Fairness and Social Norms
Authors: Hausman Daniel M.
Published: March 2009

This essay comments on the theory of social norms developed by Cristina Bicchieri in The Grammar of Society (2006). It applauds her theory of norms but argues that it cannot account for the experimental results concerning ultimatum games. A theory of fairness is also needed. It develops a number of specific criticisms of her way of incorporating the influence of norms into preferences.
Evolutionary Innovations and Developmental Resources: From Stability to Variation and Back Again
Authors: Kaplan Jonathan
Published: March 2009

Will a synthesis of developmental and evolutionary biology require a focus on the role of nongenetic resources in evolution? Nongenetic variation may exist but be hidden because the phenotypes are stable (developmentally canalized) under certain background conditions. In this case, those differences may come to play important roles in evolution when background conditions change. If this is so, then a focus on the way that developmental resources are made reliable, and the ways in which reliability fails, may prove to be of crucial importance to linking developmental and evolutionary biology.
Explaining Evolutionary Innovations and Novelties: Criteria of Explanatory Adequacy and Epistemological Prerequisites
Authors: Love Alan C.
Published: March 2009

It is a common complaint that antireductionist arguments are primarily negative. Here I describe an alternative nonreductionist epistemology based on considerations taken from multidisciplinary research in biology. The core of this framework consists in seeing investigation as coordinated around sets of problems (problem agendas) that have associated criteria of explanatory adequacy. These ideas are developed in a case study, the explanation of evolutionary innovations and novelties, which demonstrates the applicability and fruitfulness of this nonreductionist epistemological perspective. This account also bears on questions of conceptual change and theory structure in philosophy of science.
Toward a Modern Revival of Darwin's Theory of Evolutionary Novelty
Authors: West-Eberhard Mary Jane
Published: March 2009

Darwin proposed that evolutionary novelties are environmentally induced in organisms “constitutionally” sensitive to environmental change, with selection effective owing to the inheritance of constitutional responses. A molecular theory of inheritance, pangenesis, explained the cross-generational transmission of environmentally induced traits, as required for evolution by natural selection. The twentieth-century evolutionary synthesis featured mutation as the source of novelty, neglecting the role of environmental induction. But current knowledge of environmentally sensitive gene expression, combined with the idea of genetic accommodation of mutationally and environmentally induced change, supports a revival of Darwin's original theory that is consistent with modern molecular and population genetics.
Molecules with Very Weak Bonds: The Edge of Covalency
Authors: Berson Jerome A.
Published: March 2009

Because most chemical reactions, by definition, cannot avoid breaking of bonds, weakly bonded species exist fleetingly in almost every chemical change. Historically, chemical quantum mechanics was aimed at explaining the nature of strong bonds. The theory involved a number of approximations to the full solution of the Schrödinger equation. The study of non-Kekulé molecules provides an opportunity to test whether modern quantum chemical computations are competent to deal with the nature of molecules with very weak bonds.
Thinking Again about Biological Mechanisms
Authors: Darden Lindley
Published: March 2009

The new research program to understand mechanisms in biology has developed rapidly in the last 10 years. Reconsideration of the characterization of mechanisms in biology in the light of this recent work is now in order. This article discusses the perspectival aspect of the characterization of mechanisms (and ways of mitigating rampant perspectivalism), refinements in claims about working entities and kinds of activities, challenges and responses to claims about regularity, productive continuity, and the organizational aspects of a mechanism, and issues about representations of mechanisms in schemas and sketches.
Causes without Mechanisms: Experimental Regularities, Physical Laws, and Neuroscientific Explanation
Authors: Weber Marcel
Published: March 2009

This article examines the role of experimental generalizations and physical laws in neuroscientific explanations, using Hodgkin and Huxley's electrophysiological model from 1952 as a test case. I show that the fact that the model was partly fitted to experimental data did not affect its explanatory status, nor did the false mechanistic assumptions made by Hodgkin and Huxley. The model satisfies two important criteria of explanatory status: it contains invariant generalizations and it is modular (both in James Woodward's sense). Further, I argue that there is a sense in which the explanatory heteronomy thesis holds true for this case.
The Hodgkin-Huxley Equations and the Concrete Model: Comments on Craver, Schaffner, and Weber
Authors: Bogen Jim
Published: March 2009

I claim that the Hodgkin-Huxley (HH) current equations owe a great deal of their importance to their role in bringing results from experiments on squid giant action preparations to bear on the study of the action potential in other neurons in other in vitro and in vivo environments. I consider ideas from Weber and Craver about the role of Coulomb's and other fundamental equations in explaining the action potential and in HH's development of their equations. Also, I offer an embellishment to Schaffner's emergent unifier conception of the HH model.
A Computational Modeling Strategy for Levels
Authors: Symons John
Published: March 2009

Rather than taking the ontological fundamentality of an ideal microphysics as a starting point, this article sketches an approach to the problem of levels that swaps assumptions about ontology for assumptions about inquiry. These assumptions can be implemented formally via computational modeling techniques that will be described below. It is argued that these models offer a way to save some of our prominent commonsense intuitions concerning levels. This strategy offers a way of exploring the individuation of higher level properties in a systematic and formally constrained manner.
Computational and Conceptual Emergence
Authors: Humphreys Paul
Published: March 2009

A twofold taxonomy for emergence is presented into which a variety of contemporary accounts of emergence fit. The first taxonomy consists of inferential, conceptual, and ontological emergence; the second of diachronic and synchronic emergence. The adequacy of weak emergence, a computational form of inferential emergence, is then examined and its relationship to conceptual emergence and ontological emergence is detailed.
Emergence Made Ontological? Computational versus Combinatorial Approaches
Authors: Huneman Philippe
Published: March 2009

I challenge the usual approach of defining emergence in terms of properties of wholes “emerging” upon properties of parts. This approach indeed fails to meet the requirement of nontriviality, since it renders a bunch of ordinary properties emergent; however, by defining emergence as the incompressibility of a simulation process, we have an objective meaning of emergence because the difference between the processes satisfying the incompressibility criterion and the other processes does not depend on our cognitive abilities. Finally, this definition fulfills the nontriviality and the scientific-adequacy requirements better than the combinatorial approach, emergence here being a predicate of processes rather than of properties.
Seasonal Influenza in Adults and Children—Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management: Clinical Practice Guidelines of the Infectious Diseases Society of America
Authors: Harper Scott A. , Bradley John S. , Englund Janet A. , File Thomas M. , Gravenstein Stefan , Hayden Frederick G. , McGeer Allison J. , Neuzil Kathleen M. , Pavia Andrew T. , Tapper Michael L. , Uyeki Timothy M. , Zimmerman Richard K.
Published: March 2009

Guidelines for the treatment of persons with influenza virus infection were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic issues, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal (interpandemic) influenza. They are intended for use by physicians in all medical specialties with direct patient care, because influenza virus infection is common in communities during influenza season and may be encountered by practitioners caring for a wide variety of patients.
Negative Corona Discharge Ion Source Under Ambient Conditions with Mini Line-cylinder Electrodes
Authors: Liu Kun , Tang Fei , Wang Xiao-hao , Zhang Liang , Wei Xue-ye
Published: March 2009

A novel ambient negative corona discharge ion source with mini line-cylinder electrodes is designed. The diameters of inner and outer electrode are 0.16 and 4 mm respectively. With a special assembly method, a perfect coaxiality of the two electrodes is obtained. An injection system utilizing a temperature control technique, achieves a constant and stable concentration of the sample, which is critical to the experiment. The formulas of the corona onset voltage of line-cylinder electrodes are also introduced. The experiment results show that negative substances such as formic acid and acetic acid can be ionized under ambient conditions. When combined with micro electrical mechanical system fabrication process, the volume of the ion source can be reduced dramatically, but there is an undesirable surface discharge. To solve the surface discharge problem, an improved structure was designed and tested. The simplicity of the interface of the ion source makes it suitable for mass spectrometer, micro mass spectrometer, ion mobility spectrometer, and high-field asymmetric waveform ion mobility spectrometer applications.
-related Quantum Interference of 2 [Case(a)] Diatom on Rotational Energy Transfer
Authors: Li Jian , Ni Yan-qing , Li Yong-qing , Wang Wei-li , Ma Feng-cai
Published: March 2009

To study theoretically the relationship between the integral interference angle and the scattering angle in collisional quantum interference, the integral interference angle of atom-2[case(a)] diatomic molecules system is described. To simulate the experiment theoretically, the theoretical model on collision-induced rotational energy transfer in an atom-2[case(a)]diatom system is presented based on the first order Born approximation taking into account of the long-range interaction potential. For the 2 electronic state in the Hund's case(a) diatom, the degree of the interference is discussed. The interference angles of collision-induced rotational energy transfer of CN(A2) in Hund's case(a) with He, Ne, and Ar are calculated quantitatively. The key parameters in the determination of integral interference angles are obtained.
Neural Network Based on Quantum Chemistry for Predicting Melting Point of Organic Compounds
Authors: A. Lazzus Juan
Published: March 2009

The melting points of organic compounds were estimated using a combined method that includes a backpropagation neural network and quantitative structure property relationship (QSPR) parameters in quantum chemistry. Eleven descriptors that reflect the intermolecular forces and molecular symmetry were used as input variables. QSPR parameters were calculated using molecular modeling and PM3 semi-empirical molecular orbital theories. A total of 260 compounds were used to train the network, which was developed using MatLab. Then, the melting points of 73 other compounds were predicted and results were compared to experimental data from the literature. The study shows that the chosen artificial neural network and the quantitative structure property relationships method present an excellent alternative for the estimation of the melting point of an organic compound, with average absolute deviation of 5%.
Genome-wide Mapping of the Coactivator Ada2p Yields Insight into the Functional Roles of SAGA/ADA Complex inCandida albicans
Authors: Sellam Adnane , Askew Christopher , Epp Elias , Lavoie Hugo , Whiteway Malcolm , Nantel André
Published: March 2009

The SAGA/ADA coactivator complex, which regulates numerous cellular processes by coordinating histone acetylation, is widely conserved throughout eukaryotes, and analysis of the Candida albicans genome identifies the components of this complex in the fungal pathogen. We investigated the multiple functions of SAGA/ADA in C. albicans by determining the genome-wide occupancy of Ada2p using chromatin immunoprecipitation (ChIP). Ada2p is recruited to 200 promoters upstream of genes involved in different stress-response functions and metabolic processes. Phenotypic and transcriptomic analysis of ada2 mutant showed that Ada2p is required for the responses to oxidative stress, as well as to treatments with tunicamycin and fluconazole. Ada2p recruitment to the promoters of oxidative resistance genes is mediated by the transcription factor Cap1p, and coactivator function were also established for Gal4p, which recruits Ada2p to the promoters of glycolysis and pyruvate metabolism genes. Cooccupancy of Ada2p and the drug resistance regulator Mrr1p on the promoters of core resistance genes characterizing drug resistance in clinical strains was also demonstrated. Ada2p recruitment to the promoters of these genes were shown to be completely dependent on Mrr1p. Furthermore, ADA2 deletion causes a decrease in H3K9 acetylation levels of target genes, thus illustrating its importance for histone acetyl transferase activity.
CodonExplorer: an online tool for analyzing codon usage and sequence composition, scaling from genes to genomes
Authors: Hamady Micah , Wilson Stephanie A. , Zaneveld Jesse , Sueoka Noboru , Knight Rob
Published: March 2009

DNA composition in general, and codon usage in particular, is crucial for understanding gene function and evolution. CodonExplorer, available online at http://bmf.colorado.edu/codonexplorer/, is an online tool and interactive database that contains millions of genes, allowing rapid exploration of the factors governing gene and genome compositional evolution and exploiting GC content and codon usage frequency to identify genes with composition suggesting high levels of expression or horizontal transfer.

Contact:  rob@spot.colorado.edu
The influence of the environment on the variability of monthly tuna biomass around a moored, fish-aggregating device
Authors: Doray Mathieu , Petitgas Pierre , Nelson Laetitia , Mahévas Stéphanie , Josse Erwan , Reynal Lionel
Published: March 2009

Doray, M., Petitgas, P., Nelson, L., Mahévas, S., Josse, E., and Reynal, L. 2009. The influence of the environment on the variability of monthly tuna biomass around a moored, fish-aggregating device. – ICES Journal of Marine Science, 66: 1410–1416. Fish-aggregating devices (FADs) are increasingly used worldwide to enhance tuna catches. Meanwhile, ecosystem-based management of this fishery is constrained by a paucity of information regarding the interaction of FAD-associated tuna aggregations with their local environment. This paper reports the results of a nine-month study around a FAD moored near Martinique Island, aimed at assessing the effects of the local environment on the variability of monthly estimates of proximate tuna biomass. Dual-frequency, active acoustics provided high-resolution quantitative data on the pelagic community around the FAD, from fish to micronekton forage. Geostatistics were used to compute biomass estimates of the tuna aggregation comprising most of the FAD-associated fish biomass, with a sampling error of 27%. Environmental variability was summarized by a small set of principal components (PCs) derived from profiles of temperature, salinity, and dissolved oxygen vs. depth; and maps of chlorophyll a derived from remotely sensed, sea surface colour. A generalized linear model was used to relate tuna biomass to environmental PCs and revealed a positive correlation between tuna abundance and: (i) a micronekton layer sensed at 38 kHz and potentially consisting of preferred prey at ∼180-m depth; and (ii) low subsurface salinity (60–80 m). These favourable environmental conditions may be related to the presence of North Brazilian Current eddies that migrating tuna follow when not temporally associated with the FADs.
Autophagy mediates the mitotic senescence transition
Authors: Young Andrew R.J. , Narita Masako , Ferreira Manuela , Kirschner Kristina , Sadaie Mahito , Darot Jeremy F.J. , Tavaré Simon , Arakawa Satoko , Shimizu Shigeomi , Watt Fiona M. , Narita Masashi
Published: March 2009

As a stress response, senescence is a dynamic process involving multiple effector mechanisms whose combination determines the phenotypic quality. Here we identify autophagy as a new effector mechanism of senescence. Autophagy is activated during senescence and its activation is correlated with negative feedback in the PI3K–mammalian target of rapamycin (mTOR) pathway. A subset of autophagy-related genes are up-regulated during senescence: Overexpression of one of those genes, ULK3, induces autophagy and senescence. Furthermore, inhibition of autophagy delays the senescence phenotype, including senescence-associated secretion. Our data suggest that autophagy, and its consequent protein turnover, mediate the acquisition of the senescence phenotype.
Enhanced Tolerance to Chilling Stress in OsMYB3R-2 Transgenic Rice Is Mediated by Alteration in Cell Cycle and Ectopic Expression of Stress Genes
Authors: Ma Qibin , Dai Xiaoyan , Xu Yunyuan , Guo Jing , Liu Yaju , Chen Na , Xiao Jun , Zhang Dajian , Xu Zhihong , Zhang Xiansheng , Chong Kang
Published: March 2009

MYB transcription factors play central roles in plant responses to abiotic stresses. How stress affects development is poorly understood. Here, we show that OsMYB3R-2 functions in both stress and developmental processes in rice (Oryza sativa). Transgenic plants overexpressing OsMYB3R-2 exhibited enhanced cold tolerance. Cold treatment greatly induced the expression of OsMYB3R-2, which encodes an active transcription factor. We show that OsMYB3R-2 specifically bound to a mitosis-specific activator cis-element, (T/C)C(T/C)AACGG(T/C)(T/C)A, a conserved sequence that was found in promoters of cyclin genes such as OsCycB1;1 and OsKNOLLE2. In addition, overexpression of OsMYB3R-2 in rice led to higher transcript levels of several G2/M phase-specific genes, including OsCycB1;1, OsCycB2;1, OsCycB2;2, and OsCDC20.1, than those in OsMYB3R-2 antisense lines or wild-type plants in response to cold treatment. Flow cytometry analysis revealed an increased cell mitotic index in overexpressed transgenic lines of OsMYB3R-2 after cold treatment. Furthermore, resistance to cold stress in the transgenic plants overexpressing OsCycB1;1 was also enhanced. The level of cellular free proline was increased in the overexpressed rice lines of OsMYB3R-2 and OsCycB1;1 transgenic plants compared with wild-type plants under the cold treatment. These results suggest that OsMYB3R-2 targets OsCycB1;1 and regulates the progress of the cell cycle during chilling stress. OsCPT1, which may be involved in the dehydration-responsive element-binding factor 1A pathway, showed the same transcription pattern in response to cold as did OsCycB1;1 in transgenic rice. Therefore, a cold resistance mechanism in rice could be mediated by regulating the cell cycle, which is controlled by key genes including OsMYB3R-2.
Physiological Roles of GlutathioneS-Transferases in Soybean Root Nodules
Authors: Dalton David A. , Boniface Chris , Turner Zachary , Lindahl Amy , Kim Hyeon Jeong , Jelinek Laura , Govindarajulu Manjula , Finger Richard E. , Taylor Christopher G.
Published: March 2009

Glutathione S-transferases (GSTs) are ubiquitous enzymes that catalyze the conjugation of toxic xenobiotics and oxidatively produced compounds to reduced glutathione, which facilitates their metabolism, sequestration, or removal. We report here that soybean (Glycine max) root nodules contain at least 14 forms of GST, with GST9 being most prevalent, as measured by both real-time reverse transcription-polymerase chain reaction and identification of peptides in glutathione-affinity purified extracts. GST8 was prevalent in stems and uninfected roots, whereas GST2/10 prevailed in leaves. Purified, recombinant GSTs were shown to have wide-ranging kinetic properties, suggesting that the suite of GSTs could provide physiological flexibility to deal with numerous stresses. Levels of GST9 increased with aging, suggesting a role related to senescence. RNA interference studies of nodules on composite plants showed that a down-regulation of GST9 led to a decrease in nitrogenase (acetylene reduction) activity and an increase in oxidatively damaged proteins. These findings indicate that GSTs are abundant in nodules and likely function to provide antioxidant defenses that are critical to support nitrogen fixation.
Biochemical composition of a dominant detritivorous fish Prochilodus lineatus along pollution gradients in the Paraná‐Río de la Plata Basin
Authors: Speranza E. D. , Colombo J. C.
Published: March 2009

The biochemical composition of muscle, liver and stomach contents of a detritivorous fish Prochilodus lineatus was analysed and compared to settling particles and sediments along pollution gradients over 1500 km of the Río de la Plata Basin to evaluate the effects of anthropogenic discharges in a detritus food chain. The stomach contents of P. lineatus collected in the polluted Metropolitan Buenos Aires coast were enriched in proteins, carbohydrates and lipids, similar to settling particulates collected in the sewer area, and two to five times higher than underlying sediments, supporting the interpretation that P. lineatus feeds on unconsolidated organic flocs freshly decanted from mixed industrial and sewage outfalls. Fish from Buenos Aires had consistently higher standard length (LS) and mass (MT) slopes (b = 3·5), condition indexes (K = 3·01 ± 0·47, mean ±s.d.) and muscle fat content (fat = 23·8 ± 13·8% wet mass, mean ±s.d.) relative to northern fish (b = 2·7, K = 2·22 ± 0·39, fat = 3·4 ± 3·2% wet mass, respectively), suggesting that sewage‐derived organic matter was an enriched diet, which allowed an enhanced body mass gain and fat accumulation compared to organic‐poor vegetal detritus in the north Paraná area. Buenos Aires fish also showed higher hepato‐somatic indices (mean ±s.d. IH 1·41 ± 0·49 v. 0·70 ± 0·32, respectively), which correlated with their two to three orders of magnitude higher hydrocarbon and polychlorinated biphenyl (PCB) loads, suggesting an enhanced detoxifying metabolism. The northward migration of fatty P. lineatus was evidenced by the presence of clear outliers in the LS and MT relationship, K and fat content along the Paraná River.
Occurrence of the African subgroup (Ia) of BK polyomavirus in younger Japanese children
Authors: Tanaka Kaori , Hori Tsukasa , Hatakeyama Naoki , Yamamoto Masaki , Takayama Rumiko , Yoto Yuko , Suzuki Nobuhiro , Hayashi Toshiaki , Ikeda Yukiho , Ikeda Hiroshi , Ishida Tadao , Tsutsumi Hiroyuki
Published: March 2009

BK polyomavirus (BKV) is ubiquitous among humans, usually infecting them asymptomatically during childhood. BKV persists in renal tissue of individuals and their progeny are excreted in urine, particularly in immunocompromised patients. JC virus, another human polyomavirus, has been considered to be transmitted from parents to children during prolonged cohabitation. However, BKV has been supposed to be transmitted not only within but also outside the family. In the present study, to clarify this possibility, we analyzed phylogenetically 35 BKV which were excreted in the urine by Japanese children and adults undergoing stem cell transplantation. Subtypes I, III and IV were detected in 15, two and one children and in 15, one and one adults, respectively. Among 15 subtype I isolates from children, three, four and eight belonged to subgroups Ia, Ib‐1 and Ic, respectively. All the three children from whom Ia was detected were less than 9 years old. In contrast in the adults, three subtype I belonged to Ib‐1 and the other 12 to Ic. These findings may reflect the recent transmission of BKV Ia strains to Japanese children.
Chemotherapeutic agents potentiate adenoviral gene therapy for pancreatic cancer
Authors: Egami Takuya , Ohuchida Kenoki , Miyoshi Kei , Mizumoto Kazuhiro , Onimaru Manabu , Toma Hiroki , Sato Norihiro , Matsumoto Kunio , Tanaka Masao
Published: March 2009

Adenovirus‐mediated gene therapy combined with chemotherapeutic agents is expected to represent a new approach for treating pancreatic cancer. However, there have been no reports of definitive effects of chemotherapeutic agents on adenovirus‐mediated gene therapies. In the present study, we investigated the effects of chemotherapeutic agents on the transduction efficiency of an adenovirus‐based gene therapy. Adenovirus (Ad‐NK4) expressing NK4, which acts as a hepatocyte growth factor antagonist, was used as a representative gene therapy. Pancreatic cancer cells infected with Ad‐NK4 were treated with chemotherapeutic agents (5‐fluorouracil [5FU], cisplatin or etoposide), and the NK4 levels in their culture media were measured. To examine the effects of chemotherapeutic agents in vivo, Ad‐NK4 was administered to subcutaneous tumors in mice after treatment with the agents, and the tumor NK4 levels were measured. The NK4 levels in culture media from cells treated with 5FU, cisplatin and etoposide were 5.2‐fold (P = 0.026), 6‐fold (P < 0.001) and 4.3‐fold (P < 0.001) higher than those of untreated cells, respectively. The chemotherapeutic agents also increased Ad‐NK4 uptake. The NK4 levels in tumors treated with 5FU, cisplatin and etoposide were 5.4‐fold (P = 0.006), 11.8‐fold (P < 0.001) and 4.9‐fold (P = 0.017) higher than those in untreated tumors, respectively. The present findings suggest that chemotherapeutic agents significantly improve the efficiency of adenovirus‐mediated gene transfer in pancreatic cancer. Furthermore, they will contribute to decreases in the adenovirus doses required for gene transfer, thereby controlling the side‐effects of adenovirus infection in normal tissues. (Cancer Sci 2009; 100: 722–729)
Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity
Authors: Zheng Sheng , Shen Jian , Jiao Yang , Liu Yan , Zhang Chunmei , Wei Min , Hao Shui , Zeng Xianlu
Published: March 2009

The functions of platelets and fibrinogen in protecting tumor cells from natural killer cytotoxicity have been discussed for more than 20 years. However, their exact roles and relationships in the process are still not clear. In this study, we show that tumor cells prefer to adhere to fibrinogen than to platelets, and fibrinogen can enhance the adhesion of tumor cells to platelets. β3 integrin plays an important role in the adhesion of B16F10 to platelets enhanced by fibrinogen. In the presence of thrombin, fibrinogen forms dense fibrin(ogen) layers around tumor cells. Tumor cells can induce platelets to aggregate and form thrombin. Platelets, as well as thrombin, can help fibrinogen protect tumor cells from lethal contact with natural killer cells and natural killer cytotoxicity. Hirudin, a specific inhibitor of thrombin, can reverse the effect of platelets on fibrinogen in blocking natural killer cytotoxicity. Our results suggest that fibrinogen helps platelets to adhere to tumor cells, and platelets in turn promote more fibrinogen to aggregate around tumor cells by forming thrombin. They facilitate each other in protecting tumor cells from natural killer cytotoxicity. (Cancer Sci 2009; 100: 859–865)
Activity of triptolide against human mast cells harboring the kinase domain mutant KIT
Authors: Jin Yanli , Chen Qi , Shi Xianping , Lu Zhongzheng , Cheng Chao , Lai Yingrong , Zheng Qin , Pan Jingxuan
Published: March 2009

Gain‐of‐function mutations of the receptor tyrosine kinase KIT can cause systemic mastocytosis (SM) and gastrointestinal stromal tumors. Most of the constitutively active KIT can be inhibited by imatinib; D816V KIT cannot. In this study, we investigated the activity of triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook. f., in cells expressing mutant KIT, including D816V KIT. Imatinib‐sensitive HMC‐1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib‐resistant HMC‐1.2 cells harboring both V560G and D816V mutations, and murine P815 cells, were treated with triptolide, and analyzed in terms of growth, apoptosis, and signal transduction. The in vivo antitumor activity was evaluated by using the nude mouse xenograft model. Our results demonstrated that triptolide potently inhibits the growth of both human and murine mast cells harboring not only imatinib‐sensitive KIT mutation but also imatinib‐resistant D816V KIT. Triptolide markedly inhibited KIT mRNA levels and strikingly reduced the levels of phosphorylated and total Stat3, Akt, and Erk1/2, downstream targets of KIT. Triptolide triggered apoptosis by inducing depolarization of mitochondrial potential and release of cytochrome c, downregulation of Mcl‐1 and XIAP. Furthermore, triptolide significantly abrogated the growth of imatinib‐resistant HMC‐1.2 cell xenografts in nude mice and decreased KIT expression in xenografts. Our data demonstrate that triptolide inhibits imatinib‐resistant mast cells harboring D816V KIT. Further investigation of triptolide for treatment of human neoplasms driven by gain‐of‐function KIT mutations is warranted. (Cancer Sci 2009; 100: 1335–1343)
Does a rise in the BCR‐ABL1 transcript level identify chronic phase CML patients responding to imatinib who have a high risk of cytogenetic relapse?
Authors: Marin David , Khorashad Jamshid S. , Foroni Letizia , Milojkovic Dragana , Szydlo Richard , Reid Alistair G. , Rezvani Katayoun , Bua Marco , Goldman John M. , Apperley Jane F.
Published: March 2009

BCR‐ABL1 transcript numbers were monitored in 161 patients who started treatment with imatinib early after diagnosis of chronic myeloid leukaemia in chronic phase and achieved complete cytogenetic responses (CCyR). A confirmed doubling in BCR‐ABL1/ABL1 transcript levels was found to be a significant factor for predicting loss of CCyR [relative risk (RR) 8·3, P < 0·0001] and progression to advanced phase (RR 0·07, P = 0·03) provided that the eventual BCR‐ABL1/ABL1 transcript level exceeded 0·05%; increases that never exceeded 0·05% had no predictive value. The finding of a kinase domain mutation in a patient in CCyR, though rare, also predicted for loss of CCyR.
Sex ratio, reproductive mode and genetic diversity in Triops cancriformis
Authors: ZIEROLD THORID , MONTERO‐PAU JAVIER , HÄNFLING BERND , GÓMEZ AFRICA
Published: March 2009

1. Aquatic invertebrates display a wide array of alternative reproductive modes from apomixis to hermaphroditism and cyclical parthenogenesis. These have important effects on genetic diversity and population structure. Populations of the ‘living fossil’Triops cancriformis display a range of sex ratios, and various reproductive modes are thought to underlie this variation. Using sex ratio information and histological analyses European populations have been inferred to be gonochoric (with separate males and females), selfing hermaphroditic and androdioecious, a rare reproductive mode in which selfing hermaphrodites coexist with variable proportions of males. In addition, some populations have been described as meiotic parthenogens.

2. Here we use population genetic analysis using microsatellite loci in populations with a range of sex ratios including a gonochoric population, and marker segregation patterns in heterozygote individuals reared in isolation, to clarify the reproductive mode in this species.

3. Our data show that populations in general have very low levels of genetic diversity. Non‐gonochoric populations show lower genetic diversity, more heterozygote deficiencies, higher inbreeding coefficients and stronger linkage disequilibria than the gonochoric population. The maintenance of some heterozygosity in populations is consistent with some male influence in T. cancriformis populations, as would be expected from an androdioecious reproductive system. Results of marker segregation in eggs produced in isolation from non‐gonochoric populations indicate that meiosis occurs and are consistent with two reproductive modes: selfing hermaphroditism and a type of ameiotic parthenogenesis.

4. Overall, our data indicate that androdioecy and selfing hermaphroditism are the most likely reproductive modes of non‐gonochoric European Triops populations. Triops populations are strongly structured, suggesting high genetic drift and low levels of gene flow.
Trade‐off between root nitrogen acquisition and shoot nitrogen utilization across 13 co‐occurring pasture grass species
Authors: Maire Vincent , Gross Nicolas , Da Silveira Pontes Laise , Picon‐Cochard Catherine , Soussana Jean‐François
Published: March 2009

Although plant nitrogen (N) strategies may play an important role for community structure and ecosystem functioning, there is not a clear understanding of the link between N acquisition by roots and N utilization by shoots. Particularly, it is unclear how the co‐variations between size‐ and physiology‐related traits determine N acquisition and N utilization at the plant scale.

We used 13 co‐occurring temperate pasture grasses to study inter‐specific variations in above‐ground N yield and in root N acquisition and shoot N utilization traits. N acquisition traits concerned root influx capacities for and , root mass and specific root area in ingrowth cores. N utilization traits concerned leaf life span, leaf N content, leaf N resorption, mean residence time of N and leaf N use efficiency.

We found evidence for three trade‐offs across species concerning root N acquisition: (i) root mass increased when specific root area declined; (ii) an increase in root area was observed when total N influx capacity decreased; and (iii) root influx capacity increased when capacity declined.

High total root uptake capacity gave rise to high leaf N content and was associated across species to low leaf N use efficiency. Tall grasses were characterized by high shoot N yield, high root biomass and high leaf N use efficiency. Physiology‐related traits and size‐related traits were generally found independent.

Our study demonstrates how size and N uptake related root traits are associated to major axes of plant specialization ((i) plant size and (ii) conservation vs. exploitation of N) which were previously identified based on shoot traits. Contrasted N strategies were segregated across species according to four combinations along these two axes.
Seed availability and gap size influence seedling emergence of dandelion (Taraxacum officinale) in grasslands
Authors: Martinkova Z. , Honek A. , Pekar S.
Published: March 2009

Dandelion (Taraxacum officinale agg.) seedlings colonize gaps in agricultural grassland and give rise to weedy pastures. It was investigated how this colonization is affected by seed availability and gap size. Flowering, seed production and spontaneous seedling emergence in artificial gaps were recorded at seven grassland sites. Fifteen to 126 flowers m−2 (2·2–18·6 thousands of seeds m−2) were produced at particular sites in May 2005. Seed availability explained 0·91 of the between‐site variation in seedling abundance. Seedling populations represented c. 0·03 of the seed produced at these sites. Shading, pH, soil nutrients and soil texture did not affect seedling emergence. In 2006, seed was sown at one site in small (33 cm2) and large (400 cm2) gaps on eight occassions during the growing season. Time to germination was on average 10 d shorter and 0·20 more of the seed germinated in small than large gaps, and both varied significantly with date of sowing. Germination was not limited by low temperature. Predation of seeds may have decreased the density of established seedlings. Patches of dandelions in sparse or weakly disturbed grassland are unlikely to disappear spontaneously and repeated cutting during spring flowering is recommended as an effective means of management.
Gene therapy for haemophilia…yes, but…with non‐viral vectors?
Authors: LIRAS A. , OLMEDILLAS S.
Published: March 2009

Summary.  High‐purity plasma‐derived and recombinant factors are currently safe and efficient treatment for haemophilia. The mid‐term future of haemophilia treatment will involve the use of modified recombinant factors to achieve advantages such as decreased immunogenicity in inhibitor formation and enhanced efficacy as a result of their longer half‐life. In the long‐term, gene therapy and cell therapy strategies will have to be considered. Achievements in cell therapy to date have been using embryonic stem cells and hepatic sinusoidal endothelial cells. Current gene therapy strategies for haemophilia are based on gene transfer using adeno‐associated viruses and non‐viral vectors. Gene therapy for haemophilia is justified because it is a chronic disease and because a very regular factor infusion is required that may involve fatal risks and because it is very expensive. Haemophilia is a very good candidate for use of gene therapy protocols because it is a monogenic disease, and even low expression is able to achieve reversion from a severe to a moderate phenotype. The current trends in haemophilia using adeno‐associated viral vectors are safe but also involve immunogenicity problems. The other alternatives are non‐viral vectors. There have been in recent years relevant advances in non‐viral transfection that raise hope for considering this possibility. Several research groups are opting for this experimental alternative. An expression over 5%, representing a moderate phenotype, for a few months with a high safety, regarding vector, transfected cells, and implantation procedure, would already be a great success. This may represent an intermediate protocol in which the expression levels and times obtained are lower and shorter respectively as compared to viral vectors, but which provide a potential greater patient safety. This may more readily win acceptance among both patients and haematologists because fatal events in the past due to HIV/HCV infection may constrain the implementation of viruses as vectors.