bluuebunny/crossref_metadata_2025 huggingface dataset:
The Law: Bush, Cheney, and the Separation of Powers: A Lasting Legal Legacy?
Authors: SILVERSTEIN GORDON
Published: October 2009

The George W. Bush administration will long be remembered for its constitutional and legal arguments on behalf of exclusive and inherent executive power. In its extreme form, this uncompromising effort appears to have failed, and may even have pushed the judicial branch to limit executive authority and return to a more traditional insistence on interbranch cooperation in foreign affairs. Ironically, the Bush‐Cheney legal legacy ultimately will depend on the Barack Obama administration's public commitments and legal arguments, but early evidence suggests that President Obama's assertions of executive power will rest less on assertions of constitutional prerogative, and more heavily on statutory delegation as well as long‐standing judicial precedent.
The Rhetorical Presidency Today: How Does It Stand Up?
Authors: LARACEY MEL
Published: October 2009

Jeffrey Tulis based his book “The Rhetorical Presidency” on the empirical assertion that pre‐twentieth‐century presidents avoided communicating with the public on policy matters and instead directed their policy‐oriented communications to Congress, in writing. Subsequent scholarship, however, has demonstrated that many of these presidents actually did communicate extensively with the American people on policy matters, rather than going through Congress. Some gave speeches or wrote public letters, while others utilized the façade of a presidential newspaper that featured commentaries widely understood to reflect the president's views. Presidential communications behavior during this era was much more variable, and far less influenced by one constitutional norm, than Tulis portrays in “The Rhetorical Presidency.” The variability is due to presidents attempting to accommodate conflicting views of their appropriate role in the constitutional order.
The Rhetorical Presidency: Still Standing Tall
Authors: CROCKETT DAVID A.
Published: October 2009

Mel Laracey has done a singular service to presidency studies by highlighting how early premodern presidents were engaged in public discourse. His attempt to consign Jeffrey Tulis's scholarship in The Rhetorical Presidency to the dustbin of history, however, is premature. On a small scale, some of Laracey's evidence countering Tulis's thesis is unconvincing. On a larger scale, much of Laracey's analysis appears to be a case of disputes over definitions, a dispute that does not address the enduring insights of Tulis's work concerning the consequences of constitutional reinterpretation. Finally, the attempt to construct a Kuhnian paradigm shift fails, as much of Tulis's diagnosis of the problem of presidential power in republican government remains valid.
The Eagleton Affair: Thomas Eagleton, George McGovern, and the 1972 Vice Presidential Nomination
Authors: GIGLIO JAMES N.
Published: October 2009

The frequent mention of the Eagleton affair during discussions over vice presidential selections in the past election cycle has further enhanced the relevancy of the controversy surrounding Senator George McGovern's choice of Senator Tom Eagleton as his running mate in 1972. That soon led to Eagleton's forced resignation because of past treatment for depression—the only nominee who has ever had to depart from the ticket. This is the first scholarly study of that controversy. It is grounded in extensive interviews and archival research in the McGovern and the untapped Eagleton Papers. This Greek tragedy has much to say about the two protagonists and the casual way in which political parties sometimes selected vice presidential candidates. As a result, the Eagleton affair has also contributed to a more thoughtful approach to the selection of vice presidential nominees.
Checking Presidential Detention Power in the War on Terror: What Should We Expect from the Judiciary?
Authors: WHEELER DARREN A.
Published: October 2009

When the U.S. Supreme Court issued its first detainee decisions in 2004, many cheered the Court for serving as a check on the George W. Bush administration's unilateral detainee policies. A closer examination, however, reveals that the Bush administration was adept at retaining significant power over detainee matters in spite of the seemingly negative judicial decisions. This article explores four institutional and political factors that, individually and collectively, work to limit the Supreme Court's ability to serve as a significant check on presidential power in the area of detainee affairs in the war on terror. The article concludes that, even if the judiciary is inclined to be active in this area, these factors are likely to constrain any judicial attempts to significantly check presidential detention power in the war on terror.
Melatonin and Vitamin C Attenuates Alcohol‐Induced Oxidative Stress in Aorta
Authors: Sönmez Mehmet Fatih , Narin Figen , Balcioğlu Esra
Published: October 2009

Abstract: Epidemiological studies have shown that low to moderate doses of alcohol consumption are beneficial to cardiac health. However, chronic high doses of alcohol ingestion cause cardiovascular complications. The aim of this study was to investigate both the effects of melatonin and vitamin C and expression of endothelial nitric oxide synthase in aorta of chronic alcoholic rats. Twenty‐four adult male Wistar rats weighing 200–250 g were used in the study. Rats were divided into four equal groups. Group I (control): rats were not fed on alcohol; Group II: rats were fed on alcohol; Group III: rats were fed on alcohol and 40 mg/kg vitamin C were injected intraperitoneally and Group IV: rats were fed on alcohol and 4 mg/kg melatonin were injected intraperitoneally. At the end of the experiment, rats were killed and aorta tissues were removed. Some parts of the aorta tissues were used for biochemical analyses and the other parts were used at histological procedures. In the control group, endothelial nitric oxide synthase immunoreactivity was (++) in smooth muscle cells and endothelial cells. Expression of endothelial nitric oxide synthase in the alcohol group was stronger than control group. Chronic ethanol ingestion significantly increased (p < 0.05); and melatonin significantly decreased both the plasma and tissue malondialdehyde levels. The superoxide dismutase levels and catalase activity did not change significantly in the Vitamin C and melatonin groups (p > 0.05) compared to the control and alcohol groups. The present results indicate that chronic alcohol consumption increase lipid peroxidation and cause endothelial nitric oxide synthase expression in the aorta. However, melatonin and vitamin C administration provide partial protection against alcohol‐induced damage.
Land Market Interactions between Heterogeneous Agents in a Heterogeneous Landscape—Tracing the Macro‐Scale Effects of Individual Trade‐Offs between Environmental Amenities and Disamenities
Authors: Filatova Tatiana , Van Der Veen Anne , Parker Dawn C.
Published: October 2009

Heterogeneity in both the spatial environment and economic agents is a crucial driver of land market dynamics. We present an agent‐based land market model where land from agriculture use is transferred into urban. The model combines the microeconomic demand, supply, and bidding foundations of spatial economics models with the spatial heterogeneity of spatial econometric models in a single methodological platform. Heterogeneous agents exchange heterogeneous spatial goods via simulated bilateral market interactions. We model a coastal city where both coastal amenities and flooding or erosion disamenities drive land market outcomes, facilitating separate analysis of the effects of each driver on land rents and land development patterns. We also analyze the implications of homogeneous versus heterogeneous but unbiased flood risk perceptions. Since buyers with low risk perceptions drive market outcomes, spatial development under heterogeneous risk perceptions differs qualitatively, with more expansion into risky areas. Our results highlight the shortcomings of policy models based on representative agent assumptions and the importance of including agent‐level data in empirical modeling.

L'hétérogénéité de l'environnement spatial et des agents économiques constitue un élément moteur crucial de la dynamique du marché foncier. Nous présentons un modèle multi‐agent du marché foncier dans lequel des terres agricoles ont été transférées pour des fins urbaines. Le modèle combine les fondements microéconomiques de la demande, de l'offre et des enchères de modèles de l'économie spatiale avec l'hétérogénéité spatiale des modèles de l'économétrie spatiale dans une plateforme méthodologique unique. Les agents hétérogènes échangent des biens hétérogènes par le biais du jeu des forces du marché bilatéral simulé. Nous avons modélisé une ville côtière où les agréments côtiers et les désagréments causés par les inondations ou l'érosion influent sur le marché foncier, facilitant l'analyse individuelle des effets de chaque élément moteur sur les loyers fonciers et les modèles d'aménagement de terrain. Nous avons également analysé les répercussions des perceptions homogènes et hétérogènes mais non biaisées à l'égard du risque d'inondation. Étant donné que les acquéreurs qui ont de faibles perceptions du risque motivent les effets du marché, le développement spatial selon des perceptions hétérogènes à l'égard du risque varie qualitativement, avec plus d'expansion dans les zones à risque. Nos résultats ont mis en lumière les lacunes des modèles de politiques fondés sur les hypothèses d'un agent représentatif et l'importance d'inclure des données sur l'hétérogénéité des agents dans la modélisation empirique.
The Diffusion of Greenhouse Agriculture in Northern Thailand: Combining Econometrics and Agent‐Based Modeling
Authors: Schreinemachers Pepijn , Berger Thomas , Sirijinda Aer , Praneetvatakul Suwanna
Published: October 2009

This paper studies the diffusion of greenhouse agriculture in a watershed in the northern uplands of Thailand by applying econometrics and agent‐based modeling in combination. Adoption has been rapid by farmers in the central valley of the watershed, while farmers at higher altitudes, lacking transferable land titles that could serve as mortgage collateral, have been unable to obtain loans for greenhouse investment. The objectives of the paper are both methodological and empirical. On the methodological side, it shows that econometrically estimated models of farm household behavior are useful to design and to parameterize an agent‐based model. On the empirical side, simulation results show that if mortgage collateral would not be required, then adoption in the upper part of the watershed could reach nearly 77% of farm households by 2020, as compared to about 36% under current conditions. Furthermore results suggest a significant increase in incomes related to the innovation and a substantially greater irrigation water use, especially in the central part. As bell pepper under greenhouses has replaced pesticide‐intensive chrysanthemum, it has declined average levels of pesticide use. Nevertheless, pesticide use is high and farmers are struggling to control pests, which raises questions about the long‐term sustainability of the innovation.

Dans le présent article, nous avons analysé, à l'aide d'un modèle économétrique et d'un modèle multi‐agent, l'expansion de la culture en serre dans un bassin versant des hautes terres du Nord de la Thaïlande. Les agriculteurs de la vallée centrale du bassin versant ont adopté rapidement cette forme d'agriculture, tandis que les agriculteurs installés dans les hautes altitudes n’ont pu, faute de titres fonciers transférables pouvant servir de garantie, obtenir de prêts pour construire des serres. Les objectifs du présent article étaient à la fois méthodologiques et empiriques. Sur le plan méthodologique, notre étude a montré que les modèles de comportement des ménages agricoles estimés économétriquement sont utiles pour concevoir et paramétrer un modèle multi‐agent. Sur le plan empirique, les résultats de simulation ont montré que, si des garanties de prêt n’étaient pas exigées, 77 p. 100 des ménages agricoles adopteraient la culture en serre dans les hautes terres du bassin versant d'ici 2020, comparativement à environ 36 p. 100 dans les conditions actuelles. De nouveaux résultats ont indiqué que cette innovation ainsi qu’un usage accru de l'eau pour l'irrigation, particulièrement dans la partie centrale, pourraient générer une hausse substantielle des revenus. Depuis que la culture en serre du poivron vert a remplacé la culture du chrysanthème exigeante en pesticides, l'usage des pesticides a beaucoup diminué, mais demeure tout de même élevé. Les agriculteurs ont de la difficultéà lutter contre les ravageurs, ce qui soulève des questions sur la viabilitéà long terme de l'innovation.
An Agent‐Based Simulation Model of Structural Change in Canadian Prairie Agriculture, 1960–2000
Authors: Freeman Tyler , Nolan James , Schoney Richard
Published: October 2009

Agent‐based simulation modeling (or ABM) is used to examine the evolution of farm size and financial structure in Canadian prairie agriculture over the period 1960–2000. Individual farm agent interaction and dynamics in this model occur through land ownership and leasing markets. A base scenario is developed and the model is validated against actual data from a typical Saskatchewan farm region. Subsequently, we simulate counterfactual policy scenarios applicable to farms in this region. Overall, we view the contribution of this paper as twofold—first, it represents a “proof of concept” of ABM's ability to simulate farming on a medium to large scale. Second, the model allows us to examine the contributions of entrepreneurship, factor endowment, and historical government agricultural support payments on the evolution of Canadian prairie farm structure.

Dans le présent article, nous avons utilisé un modèle multi‐agent pour analyser l'évolution de la taille et de la structure financière de fermes dans les Prairies canadiennes, de 1960 à 2000. Dans ce modèle, les agents interagissent dans le temps par le biais des marchés de la propriété foncière et du bail foncier. Nous avons élaboré un scénario de référence et nous avons validé le modèle à partir de données réelles tirées d'une région agricole typique de la Saskatchewan. Ensuite, nous avons simulé des scénarios contrefactuels de politiques applicables à des fermes de cette région. Le présent article poursuivait un double objectif. Le présent article est à double volet. Premièrement, il comprend une démonstration de faisabilité de la capacité du modèle multiagent à simuler l'agriculture de moyenne à grande échelle. Deuxièmement, le modèle a permis d'examiner l'apport de l'entrepreneuriat, de la dotation en facteurs de production et des paiements de soutien agricole sur l'évolution de la structure des fermes dans les Prairies canadiennes.
Orbital eccentricity as a probe of thick disc formation scenarios
Authors: Sales Laura V. , Helmi Amina , Abadi Mario G. , Brook Chris B. , Gómez Facundo A. , Roškar Rok , Debattista Victor P. , House Elisa , Steinmetz Matthias , Villalobos Álvaro
Published: October 2009

We study the orbital properties of stars in four (published) simulations of thick discs formed by (i) accretion from disrupted satellites, (ii) heating of a pre-existing thin disc by a minor merger, (iii) radial migration and (iv) gas-rich mergers. We find that the distribution of orbital eccentricities is predicted to be different for each model: a prominent peak at low eccentricity is expected for the heating, migration and gas-rich merging scenarios, while the eccentricity distribution is broader and shifted towards higher values for the accretion model. These differences can be traced back to whether the bulk of the stars in each case is formed in situ or is accreted, and is robust to the peculiarities of each model. A simple test based on the eccentricity distribution of nearby thick-disc stars may thus help elucidate the dominant formation mechanism of the Galactic thick disc.
A Practical Approach to the Design, Monitoring, and Optimization of In Situ MTBE Aerobic Biobarriers
Authors: Johnson Paul C. , Bruce Cristin L. , Miller Karen D.
Published: October 2009

A paradigm for the design, monitoring, and optimization of in situ methyl tert‐butyl ether (MTBE) aerobic biobarriers is presented. In this technology, an oxygen‐rich biologically reactive treatment zone (the “biobarrier”) is established in situ and downgradient of the source of dissolved MTBE contamination in groundwater, typically gasoline‐impacted soils resulting from leaks and spills at service station sites or other fuel storage and distribution facilities. The system is designed so that groundwater containing dissolved MTBE flows to, and through, the biobarrier treatment zone, ideally under natural gradient conditions so that no pumping is necessary. As the groundwater passes through the biobarrier, the MTBE is converted by microorganisms to innocuous by‐products. The system also reduces concentrations of other aerobically degradable chemicals dissolved in the groundwater, such as benzene, toluene, xylenes, and tert‐butyl alcohol. This design paradigm is based on experience gained while designing, monitoring, and optimizing pilot‐scale and full‐scale MTBE biobarrier systems. It is largely empirically based, although the design approach does rely on simple engineering calculations. The paradigm emphasizes gas injection–based oxygen delivery schemes, although many of the steps would be common to other methods of delivering oxygen to aquifers.
Speciation and Kinetics of Trihalomethane Formation in Drinking Water in Mexico
Authors: Garrido Sofía E. , Fonseca M. Guadalupe
Published: October 2009

Water chlorination continues to be one of the most common water disinfection processes, especially in developing countries. When natural organic matter (NOM) is present, the process produces disinfection by‐products (DBPs), some of them being trihalomethanes (THMs). This study determined the presence, speciation, and kinetics of THMs formation in the water supply for the northern area of the city of Toluca, Mexico. The results show that the concentrations of THMs are below the maximum allowable limits of 200 μg/L in accordance with NOM‐127‐SSA1‐1994. Regarding THMs speciation, the presence of chloroform was more frequently observed in domestic water; furthermore, in one sample in which bromoform was present, it dominated over the chlorine species. Regarding the kinetics of THMs formation, a maximum concentration of THMs (THMsMax) of 13.02 μg/L was obtained, and the time required to reach 50% THMsMax (t50) was 39.45 min.
Noncoding RNAs: Persistent Viral Agents as Modular Tools for Cellular Needs
Authors: Witzany Günther
Published: October 2009

It appears that all the detailed steps of evolution stored in DNA that are read, transcribed, and translated in every developmental and growth process of each individual cell depend on RNA‐mediated processes, in most cases interconnected with other RNAs and their associated protein complexes and functions in a strict hierarchy of temporal and spatial steps. Life could not function without the key agents of DNA replication, namely mRNA, tRNA, and rRNA. Not only rRNA, but also tRNA and the processing of the primary transcript into the pre‐mRNA and the mature mRNA are clearly descended from retro‐“elements” with obvious retroviral ancestry. They seem to be remnants of viral infection events that did not kill their host but transferred phenotypic competences to their host and changed both the genetic identity of the host organism and the identity of the former infectious viral swarms. In this respect, noncoding RNAs may represent a great variety of modular tools for cellular needs that are derived from persistent nonlytic viral settlers.
Deconstructing the Dogma
Authors: Mattick John S.
Published: October 2009

Since the birth of molecular biology it has been generally assumed that most genetic information is transacted by proteins, and that RNA plays an intermediary role. This led to the subsidiary assumption that the vast tracts of noncoding sequences in the genomes of higher organisms are largely nonfunctional, despite the fact that they are transcribed. These assumptions have since become articles of faith, but they are not necessarily correct. I propose an alternative evolutionary history whereby developmental and cognitive complexity has arisen by constructing sophisticated RNA‐based regulatory networks that interact with generic effector complexes to control gene expression patterns and the epigenetic trajectories of differentiation and development. Environmental information can also be conveyed into this regulatory system via RNA editing, especially in the brain. Moreover, the observations that RNA‐directed epigenetic changes can be inherited raises the intriguing question: has evolution learnt how to learn?
On the Origin of Cells and Viruses
Authors: Koonin Eugene V.
Published: October 2009

It is proposed that the precellular stage of biological evolution unraveled within networks of inorganic compartments that harbored a diverse mix of virus‐like genetic elements. This stage of evolution might makes up the Last Universal Cellular Ancestor (LUCA) that more appropriately could be denoted Last Universal Cellular Ancestral State (LUCAS). Such a scenario recapitulates the ideas of J. B. S. Haldane sketched in his classic 1928 essay. However, unlike in Haldane's day, considerable support for this scenario exits today: lack of homology between core DNA replication system components in archaea and bacteria, distinct membrane chemistries and enzymes of lipid biosynthesis in archaea and bacteria, spread of several viral hallmark genes among diverse groups of viruses, and the extant archaeal and bacterial chromosomes appear to be shaped by accretion of diverse, smaller replicons. Under the viral model of precellular evolution, the key components of cells originated as components of virus‐like entities. The two surviving types of cellular life forms, archaea and bacteria, might have emerged from the LUCAS independently, along with, probably, numerous forms now extinct.
The Viral Eukaryogenesis Hypothesis
Authors: Bell Philip John Livingstone
Published: October 2009

Understanding how the gulf between prokaryotic and eukaryotic cellular design arose is a major challenge. The viral eukaryogenesis (VE) hypothesis addresses the challenge of eukaryotic origins by suggesting the first eukaryotic cell was a multimember consortium consisting of a viral ancestor of the nucleus, an archaeal ancestor of the eukaryotic cytoplasm, and a bacterial ancestor of the mitochondria. Using only prokaryotes and their viruses, and invoking selective pressures observed in modern organisms, the VE hypothesis can explain the origins of the eukaryotic cell, sex, and meiosis. In the VE hypothesis, a cell wall‐less archaeon and an alpha‐proteobacterium established a syntrophic relationship, and then a complex DNA virus permanently lysogenized the archaeal syntroph to produce a consortium of three organisms that evolved into the eukaryotic cell. The mechanisms by which the virus replicated, controlled its copy number, and segregated to daughter cells led to the evolution of the asexual mitotic replication cycle and the sexual meiotic replication cycle. The VE hypothesis conceptually unifies prokaryotic and eukaryotic sex into variants of a single process.
Friendly Viruses
Authors: Varela Mariana , Spencer Thomas E. , Palmarini Massimo , Arnaud Frederick
Published: October 2009

Endogenous retroviruses (ERVs) are present in the genome of all vertebrates and have coevolved with their hosts for millions of years. Some ERVs play a critical role in placental development, contribute to genome plasticity, and protect the host against infection of related pathogenic and exogenous retroviruses, thus some ERVs have been positively selected and maintained in the host genome. The sheep genome contains 27 endogenous retroviruses (enJSRVs) related to the pathogenic Jaagsiekte sheep retrovirus (JSRV), the causative agent of a transmissible lung cancer in sheep. enJSRVs are able to protect their host against JSRV infection by blocking different steps of the viral replication cycle. In addition, enJSRVs are absolutely required for sheep placental development. Thus, enJSRVs‐JSRV provides a unique and interesting model to study the symbiotic relationship and interplay between host ERVs and evolution. This review will provide some examples of the biological functions of ERVs. In particular, the role of ERVs in reproductive biology and in protecting the host against pathogenic retrovirus infections will be emphasized using enJSRVs/JSRV and the sheep as a model.
The Fragmented Gene
Authors: Brosius Jürgen
Published: October 2009

While once almost synonymous, there is an increasing gap between the expanding definition of what constitutes a gene and the conservative and narrowly defined terms code or coding, which for a long time, almost exclusively constituted the open reading frame. Much confusion results from this disparity, especially in light of the plethora of noncoding RNAs (more correctly termed “non‐protein‐coding RNAs”) that usually are encoded and transcribed by their own genes. A simple solution would be to adopt Ed Trifonov's less constrained definition of a code as any sequence pattern that can have a biological function. Such consideration favors not only a more complex view of the gene as an entity composed of many more or less conserved subgenic modules, but also a concept of modular evolution of genes and entire genomes.
APOBEC3 Proteins Inhibit LINE‐1 Retrotransposition in the Absence of ORF1p Binding
Authors: Lovšin Nika , Peterlin B. Matija
Published: October 2009

Members of the apolipoprotein B mRNA editing complex polypeptide 1‐like (APOBEC) family of enzymes exhibit inhibitory activity against a variety of exogenous and endogenous retroviruses including retrotransposons, such as long interspersed element 1 (LINE‐1). Indeed, human APOBEC3A, APOBEC3B, and APOBEC3F inhibit retrotransposition of human LINE‐1, mouse IAP and MusD retrotransposons. In our study, we examined whether the inhibitory effect of APOBEC3 proteins correlates with APOBEC3 ability to bind the LINE‐1 ORF1 protein. We examined the interactions between the LINE‐1 ORF1 protein and the most potent LINE‐1 retrotransposon inhibitors, human APOBEC3A and APOBEC3B, by immunofluorescence and immunoprecipitation. Although human APOBEC3A shows the highest inhibitory potency against LINE‐1 retrotransposon, no direct interactions were identified either by immunofluorescence or by co‐immunoprecipitation. APOBEC3B binds to LINE‐1 ORF1 protein, yet no co‐localization was detected. We concluded that APOBEC3 proteins interfere indirectly with the LINE‐1 retrotransposition pathway, probably through interference with RNA targeting.
Epigenetic Regulation of Mammalian Genomes by Transposable Elements
Authors: Huda Ahsan , Jordan I. King
Published: October 2009

Transposable element (TE) sequences make up a substantial fraction of mammalian genomes and exert a variety of regulatory influences on mammalian genes. We explore the contributions of TEs to the epigenetic mechanisms that regulate mammalian genomes, emphasizing nucleosome positioning and epigenetic histone modifications. A link between TEs and epigenetics rests on the fact that underlying genetic sequences partially mediate the nature and identity of epigenetic modifications. Here, we review the studies that have uncovered histone modifications that are targeted to mammalian TE sequences and propose a series of hypotheses regarding the potential epigenetic regulatory effects of mammalian TEs. We propose that mammalian TE sequences have specific nucleosome binding properties with regulatory implications for nearby genes, are involved in the phasing of nucleosomes, and recruit epigenetic modifications to function as enhancers; that epigenetic modifications at TE sequences affect the regulation of nearby genes; and that TEs serve as epigenetic boundary elements. It is hoped that these proposed scenarios may help to serve as a roadmap for future investigations into the epigenetic regulatory effects of mammalian TEs.
Are There Epigenetic Controls in Trypanosoma cruzi?
Authors: Elias Maria Carolina , Faria Marcella
Published: October 2009

RNA interference (RNAi) is defined as the mechanism through which double‐stranded RNA (dsRNA) triggers degradation of homologous transcripts. Besides providing an invaluable tool to downregulate gene expression in a variety of organisms, it is now evident that RNAi acts beyond the cytoplasm and is involved in a variety of gene‐silencing phenomena in the nucleus. In the present work we review the current status of the knowledge about RNAi in protozoan parasites that belong to the Trypanosoma genus and have medical relevance. While RNAi was first discovered in Trypanosoma brucei, it became evident that other members of the same genus of organisms, namely Trypanosoma cruzi, does not possess RNAi, probably due to the lack of Ago protein analogs in their genomes. We will discuss the genome organization of Trypanosoma cruzi and propose that the absence of both RNAi and gene promoters is symptomatic of alternative epigenetic controls in this parasite orchestrated by parasite‐host interactions. Whereas in Trypanosoma brucei, RNAi and other epigenetic controls dictate alternative transcriptional programs critical for virulence.
Learning from Bacteria about Natural Information Processing
Authors: Ben‐Jacob Eshel
Published: October 2009

Under natural growth conditions, bacteria live in complex hierarchical communities. To conduct complex cooperative behaviors, bacteria utilize sophisticated communication to the extent that their chemical language includes semantic and even pragmatic aspects. I describe how complex colony forms (patterns) emerge through the communication‐based interplay between individual bacteria and the colony. Individual cells assume newly co‐generated traits and abilities that are not prestored in the genetic information of the cells, that is, not all the information required for efficient responses to all environmental conditions is stored. To solve newly encountered problems, they assess the problem via collective sensing, recall stored information of past experience, and then execute distributed information processing of the 109–1012 bacteria in the colony—transforming the colony into a “super‐brain.” I show illuminating examples of swarming intelligence of live bacteria in which they solve optimization problems that are beyond what human beings can solve. This will lead to a discussion about the special nature of bacterial computational principles compared to Turing algorithm computational principles, in particular about the role of distributed information processing.
Molecular Imaging
Authors: Konietzny Rebecca , König Anna , Wotzlaw Christoph , Bernadini André , Berchner‐Pfannschmidt Utta , Fandrey Joachim
Published: October 2009

Fluorescence resonance energy transfer (FRET) combined with confocal laser microscopy is a powerful tool to analyze protein−protein interaction in vivo. We have applied this combination to study the assembly of the hypoxia‐inducible factor (HIF) complex in living cells under hypoxic conditions. In hypoxia, the basic helix‐loop‐helix/Period/ARNT/Single‐minded (PAS) proteins HIF‐1α and HIF‐2α accumulate and are translocated into the nucleus. Here, HIF‐1α and HIF‐2α dimerize with HIF‐1β, also known as aryl hydrocarbon receptor nuclear translocator (ARNT), to form HIF‐1/HIF‐2 complexes, which control the expression of specific target genes. Therefore, a new Java‐based analyzing program was developed at our institute to calculate the nanometer distance between α and β subunits of the transcriptionally active HIF‐1/‐2 complex bound to DNA. Fusion proteins of HIF subunits and variants of green fluorescent proteins (cyan and yellow fluorescent proteins) were expressed in living cells and protein−protein interactions were imaged in vivo by means of FRET.
Pathophysiological Consequences of HIF Activation
Authors: Haase Volker H.
Published: October 2009

Tissue fibrosis is associated with structural and functional changes that limit blood flow and oxygen availability. In the kidney, tubulointerstitial fibrosis, which leads to progressive destruction of renal tissue and irreversible loss of kidney function, is associated with reduced tissue oxygen levels and activation of hypoxia‐inducible factor (HIF) signaling. Although cytoprotective in acute injury models, HIF‐1 was found to promote fibrosis in an experimental model of chronic renal injury following unilateral ureteral obstruction. Pharmacological inhibition of lysyl oxidases phenocopied the effects of genetic HIF‐1 ablation on cell motility in vitro and on fibrogenesis in vivo, suggesting that lysyl oxidases are important mediators of profibrotic HIF signaling. These findings support the notion that HIF‐mediated cellular responses differ under conditions of acute and chronic oxygen deprivation. Under certain conditions, these responses may lead to further tissue destruction by promoting fibrogenesis.
Regulation of Vascularization by Hypoxia‐Inducible Factor 1
Authors: Semenza Gregg L.
Published: October 2009

Vascularization and vascular remodeling represent critical adaptive responses to tissue hypoxia that are mediated by hypoxia‐inducible factor 1 (HIF‐1). In patients with peripheral arterial disease, these responses are impaired by aging and diabetes, leading to critical limb ischemia and amputation. Intramuscular injection of an adenovirus encoding a constitutively active form of the HIF‐1α subunit (CA5) increases the recovery of blood flow following femoral artery ligation in a mouse model of age‐dependent critical limb ischemia. Intradermal injection of a plasmid encoding CA5 promotes healing of cutaneous wounds in a mouse model of diabetes. In cancer, vascularization is required for tumors to grow beyond microscopic size, a process that involves HIF‐1‐dependent production of angiogenic growth factors. Daily treatment of prostate cancer xenograft‐bearing mice with low‐dose anthracycline (doxorubicin or daunorubicin) chemotherapy inhibits HIF‐1 DNA‐binding activity, HIF‐1‐dependent expression of angiogenic growth factors, mobilization of circulating angiogenic cells, and tumor vascularization, thereby arresting tumor growth.
Oxygen Sensing in the Carotid Body
Authors: López‐Barneo José , Ortega‐Sáenz Patricia , Pardal Ricardo , Pascual Alberto , Piruat José I. , Durán Rocío , Gómez‐Díaz Raquel
Published: October 2009

The carotid body (CB) is a neural crest‐derived organ whose function is to elicit hyperventilation in response to hypoxemia. The CB contains clusters of neuron‐like glomus cells enveloped by glia‐like sustentacular cells. CB responsiveness to acute hypoxia relies on the inhibition of O2‐sensitive K+ channels in glomus cells, which leads to depolarization, Ca2+ entry and release of transmitters that activate afferent nerve fibers. The molecular mechanisms underlying K+ channel modulation by O2 tension are unknown. Putative hypoxia‐sensing mechanisms can be studied in detail using genetically modified mice in conjunction with a thin carotid body slice preparation. We discuss here the role in CB oxygen sensing of the hypoxia‐inducible factor 1α, the mitochondrial complex II subunit D, and heme oxygenase 2. In chronic hypoxia the CB grows with increase in glomus cell number. We identified CB stem cells of glial lineage, which can differentiate into functionally normal glomus cells.
From Polyps to People
Authors: Hampton‐Smith R.J. , Peet D.J.
Published: October 2009

Obligate aerobes, by definition, require oxygen in order to sustain life. Therefore, changes in environment or physiology that cause metabolic demand for oxygen to exceed supply (hypoxia) can be highly detrimental. Despite considerable variation in physiology and habitat between species, a majority of metazoa employ homologues of the hypoxia‐inducible factor (HIF) transcription factors to adapt to oxygen deprivation. Studies in mammals, Drosophila and C. elegans have shown that regulation of HIF‐α by prolyl hydroxylase (PHD)‐mediated proteasomal degradation is conserved, as are a number of HIF target genes. More recently, analysis of coral and beetle HIFs has revealed that, unlike flies and worms, the C‐terminal transactivation domain of HIF‐α and its regulatory hydroxylase FIH‐1 are also preserved. The reasons for variable conservation of this system are unknown. However, discovery of the “intermediary” properties of the beetle HIF pathway may prove a useful tool to better define HIF signaling in both mammals and invertebrates.
Oxidative DNA Modifications in Hypoxic Signaling
Authors: Gillespie Mark N. , Pastukh Viktor , Ruchko Mykhaylo V.
Published: October 2009

Hypoxia, a fundamental biological stimulus, uses reactive oxygen species (ROS) as second messengers.  Surprising molecular targets of hypoxia‐generated ROS are the specific bases within hypoxic response elements (HREs) of the vascular endothelial growth factor (VEGF) and other hypoxia‐inducible genes. Oxidative modifications coincide with the onset of mRNA accumulation and are localized to transcriptionally active mononucleosomes. The oxidative base modifications are removed, and the base excision DNA repair pathway is likely involved since Ref‐1/Ape1, a transcriptional co‐activator and DNA repair enzyme, is critical for transcription complex assembly. Mimicking the effect of hypoxia by introducing an abasic site in an oligonucleotide‐based model of ROS‐enhanced VEGF HRE sequence flexibility resulted in altered transcription factor binding and engendered more robust reporter gene expression. These observations suggest that controlled DNA “damage” and repair, mediated by ROS used as second messengers and by the base excision pathway of DNA repair, respectively, are important for hypoxia‐induced transcriptional activation.
Oxygen‐Sensitive Potassium Channels in Chemoreceptor Cell Physiology
Authors: Gonzalez Constancio , Vaquero Luis M. , López‐López José Ramón , Pérez‐García M. Teresa
Published: October 2009

The characterization of the molecular mechanisms involved in low‐oxygen chemotransduction has been an active field of research since the first description of an oxygen‐sensitive K+ channel in rabbit carotid body (CB) chemoreceptor cells. As a result, a large number of components of the transduction cascade, from O2 sensors to O2‐sensitive ion channels, have been found. Although the endpoints of the process are analogous, the heterogeneity of the elements involved in the different chemoreceptor tissues precludes a unifying theory of hypoxic signaling, and it has been a source of controversy. However, when these molecular constituents of the hypoxic cascade are brought back to their physiological context, it becomes clear that the diversity of mechanisms is necessary to build up an integrated cellular response that demands the concerted action of several O2 sensors and several effectors.
Maintaining Mammalian Iron and Oxygen Homeostasis
Authors: Salahudeen Ameen A. , Bruick Richard K.
Published: October 2009

Though iron and oxygen are required to sustain essential biological processes, an excess of either can result in oxidative stress. Therefore, mammals tightly regulate cellular and systemic iron and oxygen homeostasis. At the cellular level, the hypoxia‐inducible transcription factors (HIFs) are key mediators of oxygen homeostasis through their regulation of genes involved in anaerobic metabolism and oxygen delivery, among others. Iron regulatory proteins (IRPs) largely govern cellular iron homeostasis through their effects on the translation and stability of mRNAs involved in iron uptake, utilization, export, and storage. Here, we describe regulatory factors for each pathway that sense both iron and oxygen availability and coordinate the maintenance of mammalian iron and oxygen homeostasis at both the cellular and systemic levels.
Mitochondria and Hypoxic Signaling
Authors: Poyton Robert O. , Castello Pablo R. , Ball Kerri A. , Woo Dong Kyun , Pan Ning
Published: October 2009

Eukaryotic cells respond to low oxygen concentrations by upregulating hypoxic and downregulating aerobic nuclear genes (hypoxic signaling). Most of the oxygen‐regulated genes in yeast require the mitochondrial respiratory chain for their up‐ or downregulation when cells experience hypoxia. Although it was shown previously that the mitochondrial respiratory chain is required for the upregulation of some hypoxic genes in both yeast and mammalian cells, its underlying role in this process has been unclear. Recently, we have reported that mitochondria produce nitric oxide (NO•) when oxygen becomes limiting. This NO• production is nitrite (NO2−)‐dependent, requires an electron donor, and is carried out by cytochrome c oxidase in a pH‐dependent fashion. We call this activity Cco/NO• and incorporate it into a new model for hypoxic signaling. In addition, we have found that some of the NO• produced by Cco/NO• is released from cells, raising the possibility that mitochondrially generated NO• also functions in extracellular hypoxic signaling pathways.
Ribose utilization by the human commensal Bifidobacterium breve UCC2003
Authors: Pokusaeva Karina , Neves Ana Rute , Zomer Aldert , O'Connell‐Motherway Mary , MacSharry John , Curley Peter , Fitzgerald Gerald F. , Van Sinderen Douwe
Published: October 2009

Growth of Bifidobacterium breve UCC2003 on ribose leads to the transcriptional induction of the rbsACBDK gene cluster. Generation and phenotypic analysis of an rbsA insertion mutant established that the rbs gene cluster is essential for ribose utilization, and that its transcription is likely regulated by a LacI‐type regulator encoded by rbsR, located immediately upstream of rbsA. Gel mobility shift assays using purified RbsRHis indicate that the promoter upstream of rbsABCDK is negatively controlled by RbsRHis binding to an 18 bp inverted repeat and that RbsRHis binding activity is modulated by d‐ribose. The rbsK gene of the rbs operon of B. breve UCC2003 was shown to specify a ribokinase (EC 2.7.1.15), which specifically directs its phosphorylating activity towards d‐ribose, converting this pentose sugar to ribose‐5‐phosphate.
Cost‐effectiveness of clean air administered to the breathing zone in allergic asthma
Authors: Brodtkorb Thor‐Henrik , Zetterström Olle , Tinghög Gustav
Published: October 2009

Introduction: Airsonett Airshower (AA) is a novel non‐pharmaceutical treatment for patients with perennial allergic asthma that uses a laminar airflow directed to the breathing zone of patients during sleep. It has been shown that AA treatment in addition to optimized standard therapy significantly increases asthma‐related quality of life among adolescent asthmatics. However, the cost‐effectiveness of AA treatment has not yet been assessed. As reimbursement decisions are increasingly guided by results from the cost‐effectiveness analysis, such information is valuable for health‐care policy‐makers.

Objective: The objective of this study was to estimate the cost‐effectiveness of adding AA treatment with allergen‐free air during night sleep to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo.

Materials and Methods: A probabilistic Markov model was developed to estimate costs and health outcomes over a 5‐year period. Costs and effects are presented from a Swedish health‐care perspective (QALYs). The main outcome of interest was cost per QALY gained.

Results: The Airshower strategy resulted in a mean gain of 0.25 QALYs per patient, thus yielding a cost per QALY gained of under €35 000 as long as the cost of Airshower is below €8200.

Conclusions: Adding AA treatment to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo is generating additional QALYs at a reasonable cost. However, further studies taking more detailed resource use and events such as exacerbations into account would be needed to fully evaluate the cost‐effectiveness of AA treatment.

Please cite this paper as: Brodtkorb T‐H, Zetterström O and Tinghög G. Cost‐effectiveness of clean air administered to the breathing zone in allergic asthma.The Clinical Respiratory Journal2010; 4: 104–110.
Unique distribution of deep groundwater bacteria constrained by geological setting
Authors: Kato Kenji , Nagaosa Kazuyo , Kimura Hiroyuki , Katsuyama Chie , Hama Katsuhiro , Kunimaru Takanori , Tsunogai Urumu , Aoki Kazuhiro
Published: October 2009

We collected groundwater samples at depths of up to 482 m from three boreholes drilled into sedimentary rock within two formations in Hokkaido, Japan. The prokaryotic community in each subsurface groundwater sample was analysed by microscopic counts and cloning–sequencing the 16S rRNA genes. On total direct counts, there were between 4.61 × 104 and 5.06 × 106 prokaryote cells ml−1 in the samples, which is similar to the numbers observed at the marine subsurface. However, the vertical distribution of the prokaryotes did not show a simple decrease in abundance with increasing depth. A high abundance of cells with significant amounts of RNA was identified in the domain Bacteria using fluorescence in situ hybridization, with a high frequency of dividing cells at the transition zone between the two sedimentary rock formations. Cloning–sequencing analysis showed the predominance of γ‐Proteobacteria at this transition zone at 281–312 m. The horizontal heterogeneity of the microbial distribution in the subsurface environment was also demonstrated by a relatively high density of members of the domain Archaea in borehole HDB‐4, drilled only 1.5 km northeast of HDB‐6 and in the same formation.
Fine‐scale spatial and temporal genetic differentiation of water bloom‐forming cyanobacterium Microcystis aeruginosa: revealed by multilocus sequence typing
Authors: Tanabe Yuuhiko , Kasai Fumie , Watanabe Makoto M.
Published: October 2009

Accumulating evidence suggests that physical isolation can potentially make a significant contribution to microbial population structure and incipient speciation. However, the effect of geographic factors on population structure has not been explicitly studied for ubiquitous cyanobacteria such as a water bloom‐forming Microcystis aeruginosa. To investigate whether a fine‐scale geographic structure is developed within M. aeruginosa, 96 isolates from five Japanese lakes separated by < 55 km were analysed using multilocus sequence typing. The results of multilocus sequence typing analyses indicated that M. aeruginosa was not phylogeographically structured, although a high level of genetic differentiation was observed among locations (FST = 0.372). Most surprisingly, the highest levels of genetic differentiation were observed between populations at the same location at different times of the same year, and between those separated by only 3 km on the same day. The isolation‐by‐distance pattern was not supported, but not completely ruled out. Taken together, our results suggest that geographic factors, if present, have far less impact on the fine‐scale spatial genetic diversity of M. aeruginosa than local genetic drift or, possibly, selection.