bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ideological Origins of Great Power Politics,
1789–1989
Authors: Redd Steven B.
Published: February 2007

The Ideological Origins of Great Power Politics,
1789–1989. By Mark L. Haas. Ithaca, NY: Cornell University
Press, 2005. 250p. $39.95.

Realists argue that state behavior is predicated on the distribution
of power in the international system. Specifically, states attempt to
acquire, maintain, exercise, and balance power in response to the same
behavior expected of other states in the system. In this book, Mark L.
Haas offers a compelling argument for thinking beyond power variables and
considering the independent effects of ideology on leaders' foreign
policy decisions. The main thrust of his thesis is that the greater the
ideological distance between decision makers of different states, the
greater the likelihood that they will view each other as threats to
domestic power and international security. Conversely, the greater the
ideological affinity between states' leaders, the greater the
likelihood that they will see each other as mutually supportive of one
another's interests and, therefore, as less threatening. Decision
makers' conflictual or accommodative foreign policies, then, are a
function of threat perception caused by ideological distance. The book
begins with the explication of the theoretical argument and then applies
the theory to five different historical case studies. Haas concludes with
policy implications and prescriptions for current and future international
politics generally, and U.S. foreign policy specifically.
Keepers of the Flame: Understanding Amnesty International
Authors: Ron James
Published: February 2007

Keepers of the Flame: Understanding Amnesty International. By
Stephen Hopgood. Ithaca, NY: Cornell University Press, 2006. 249p. $49.95
cloth, $19.95 paper.

As human rights promotion gradually comes to rival development and
democratization in the Western policy pantheon, more human
rights–related books appear each year. Only a minority of these are
empirically and methodologically rigorous, however, and even fewer are
theoretically adventurous. Stephen Hopgood's unique study of Amnesty
International is thus a welcome contribution from a political scientist
with anthropological instincts, and it is likely to become a classic in
the field. Hopgood immersed himself for over a year in Amnesty's
culture, rituals, and politics, and then interpreted this data with
insights from Emile Durkheim and Pierre Bourdieu. He writes clearly and
well, and his interpretations should appeal to students of transnational
organizing, human rights, and international affairs, broadly
conceived.
States, Scarcity, and Civil Strife in the Developing World
Authors: Schlichte Klaus
Published: February 2007

States, Scarcity, and Civil Strife in the Developing World.
By Colin H. Kahl. Princeton: Princeton University Press, 2006. 354p.
$35.00.

Environmental issues have only recently attracted more attention in
social science's reasoning about the causation of war. Even though
many scholars would probably agree with the assertion that environmental
degradation and demographic pressure play a role in the causal nexus of
many civil wars, the question of how this relation could be conceptualized
has remained open for a long time. It is the aim of Colin Kahl's book
to tackle this issue not by a mere theoretical and conceptual discussion
but by using two intensely studied cases as material to construct such a
conceptualization and to render it empirically applicable and
plausible.
The Peace of Illusions: American Grand Strategy from 1940 to the
Present
Authors: Dueck Colin
Published: February 2007

The Peace of Illusions: American Grand Strategy from 1940 to the
Present. By Christopher Layne. Ithaca, NY: Cornell University Press,
2006. 290p. $29.95.

For over a decade, through a series of influential articles,
Christopher Layne has been the leading advocate within the academy of an
entirely new and much more detached foreign policy strategy for the United
States, one based upon what he calls “offshore balancing.” In
The Peace of Illusions, Layne puts his argument in book form,
addressing conceptual as well as historical and policy issues.
Jeffrey C. Isaac
Authors: Isaac Jeffrey C.
Published: February 2007

Dying to Win: The Strategic Logic of Suicide
Terrorism. By Robert Pape. New York: Random House, 2005. 352p. $25.95
cloth, $14.95 paper.

Making Sense of Suicide Missions. Edited by Diego
Gambetta. New York: Oxford University Press, 2005. 392p. $45.00 cloth,
$25.00 paper.

Dying to Kill: The Allure of Suicide Terror. By Mia
Bloom. New York: Columbia University Press, 2005. 280p.
$24.95.
Hayek and Popper on ignorance and intervention
Authors: KERSTENETZKY CELIA LESSA
Published: February 2007

Does limited social knowledgeinhibitgovernment intervention or, conversely,demandit? This article confronts these two positions, as they are respectively advocated by Hayek and Popper, and sets out to substantiate the belief that Popper's view is the more coherent one.
Services and systemic innovation: a cross-sectoral analysis
Authors: CONSOLI DAVIDE
Published: February 2007

This essay presents a cross-sectoral analysis of innovation in some types of services, namely air traffic control, retail banking, and health care. The provision of such services is organized in network structures whose development relies on competences and activities that cut across traditional sectoral and industrial boundaries. The conceptual background provided by the recent synthesis approach explains these features by elaborating a new concept of system of innovation. In so doing, this approach paves the way for new understanding of innovation in services as the endogenous outcome of knowledge growth within and across technologies, organizations, and institutions.
Diagnostik bei funktionellen Darmbeschwerden
Authors: Kruis
Published: February 2007

Funktionelle Darmbeschwerden sind einer der häufigsten Gründe für einen Arztbesuch. Der Begriff umfasst verschiedene Krankheitsbilder. Die häufigsten sind Reizdarmsyndrom, funktionelle Obstipation und funktionelle Diarrhö. In der Diagnostik aller dieser Erkrankungen spielt die gezielte Anamnese eine herausragende Rolle. Sie ist entweder in der Lage, die Diagnose festzulegen oder die Indikation für einige wenige ergänzende Untersuchungen zu stellen. Überflüssige und gefährliche technische Untersuchungsverfahren sollten unbedingt vermieden werden.
Therapie funktioneller Darmbeschwerden
Authors: Layer  , Keller
Published: February 2007

Das Reizdarmsyndrom ist die häufigste und wichtigste funktionelle Erkrankung des Darmes. Es ist charakterisiert durch die Kombination aus abdominalen Schmerzen, Stuhlgangsalterationen (Diarrhoe, Obstipation) und Blähungen. Wahrscheinlich tragen eine viszerale Hypersensitivität, Motilitätsstörungen, Nahrungsmittelunverträglichkeiten, immunologische und mikrobiologische Alterationen sowie psychosomatische Einflüsse zu den Symptomen bei. Bei einer grossen Untergruppe der Patienten wird die Störung durch eine bakterielle Infektion ausgelöst und ist dann meist Diarrhoe-dominiert. Die Diagnosesicherung erfolgt bei typischer Symptomatik durch den Ausschluss wichtiger organischer Differentialdiagnosen mittels gezielter laborchemischer Untersuchungen, Abdomensonographie und ggf. Koloskopie. Diese diagnostische Abklärung ist ein wichtiges Fundament für jede Behandlung und muss ergänzt werden durch die klare Diagnosevermittlung und Aufklärung über den langfristig benignen Verlauf. Die medikamentöse Behandlung konzentriert sich auf die Behandlung der wesentlichen Beschwerden wie Schmerz, Diarrhoe, Obstipation und Meteorismus.
Therapie bei Kolon- und Rektumkarzinom
Authors: Andre  , Schmiegel
Published: February 2007

Der deutlich erkennbare Fortschritt in der Behandlung des kolorektalen Karzinoms beruht in erster Linie auf der erfolgreichen Einführung der neuen Chemotherapeutika Irinotecan und Oxaliplatin. Eine weitere Steigerung der Ansprechraten sowie der Überlebenszeit konnte durch den kombinierten Einsatz biologischer Substanzen erreicht werden. Dabei stehen die Antikörper Bevacizumab und Cetuximab bereits in der klinischen Routine. Und auch der zunehmende Ersatz von infusionalem 5-FU durch Capecitabine bietet eine erhebliche Verbesserung im klinischen Alltag. Welche Therapiestandards aus der Vielzahl der zur Verfügung stehenden Protokolle hervorgehen werden, wird durch entsprechende Studienergebnisse definiert werden. Dabei hat die zügige Zulassung multipler Substanzen zu einer sehr komplexen Studien- und Anwendungssituation geführt. Der Routine-Einsatz von Irinotecan, Oxaliplatin und zunehmend auch Capecitabin in der Erst- und Zweitlinientherapie hat die Komplexität der Therapieplanung deutlich erhöht. Verlängerte Überlebenszeiten eröffnen vermehrt die Frage nach der optimalen Therapiesequenz und Präparateauswahl. Zusätzlich führt der Einsatz der Kombinationstherapien sowie der biologischen Substanzen zu einer Kostensteigerung, deren Auswirkung auf die Finanzierung des Gesundheitswesens noch nicht abzusehen ist. Prädiktive Marker, welche eine sichere Beurteilung des Ansprechens auf eine individuelle Therapie ermöglichen könnten, stehen trotz grosser Anstrengungen in diesem Bereich noch nicht für den klinischen Routineeinsatz zur Verfügung. Umso wichtiger ist es, die Anstrengung der nationalen und internationalen Studiengruppen interdisziplinär zu unterstützen, um die hier skizzierten Herausforderungen anzunehmen.
Geochemical fluxes related to alteration of a subaerially exposed seamount: Nintoku seamount, ODP Leg 197, Site 1205
Authors: Révillon Sidonie , Teagle Damon A. H. , Boulvais Philippe , Shafer John , Neal Clive R.
Published: February 2007

Hole 1205A was drilled on Nintoku Seamount, which lies in the midportion of the Emperor Seamount Chain. This seamount was emergent ∼56 Myr ago but was submerged by 54 Ma, so the lavas have endured weathering in both subaerial and submarine environments. We have studied the petrology, mineralogy, and geochemistry of intercalated altered basalts, breccias, and soil samples recovered at Hole 1205A to quantify the chemical exchanges between the seamount and seawater and/or meteoric fluids. The secondary mineralogy is relatively uniform throughout the section and comprises smectite, Fe‐oxyhydroxides, iddingsite, and Ca‐carbonates. Soils are composed of variably altered basaltic clasts in a matrix of kaolinite, smectite, and vermiculite with minor goethite, hematite, and magnetite. Throughout the basement section, altered basalts, breccias, and soils are depleted in Si, Mg, Ca, Na, Sr, Rb, and Ba and enriched in Fe. Fe3+/FeT (up to ∼1), δ18O (up to ∼+20‰), and 87Sr/86Sr ratios are strongly elevated relative to primary igneous values. Differences in the 87Sr/86Sr ratios define an Upper Alteration Zone with 87Sr/86Sr close to 56 Ma seawater (∼0.7077) from a Lower Alteration Zone where 87Sr/86Sr are less elevated (∼0.704). The Lower Alteration Zone likely reflects interaction with a subaerial oxidizing fluid at low temperature. This zone probably retained most of the original subaerial weathering signature. The Upper Alteration Zone was altered through circulation of large quantities of cold oxidizing seawater that partially overprinted the subaerial weathering chemical characteristics. Altered samples were compared to estimated protolith compositions to calculate chemical gains and losses. Global chemical fluxes are calculated for the entire basement section using different lithological proportions models and different rates of oceanic island emplacement. Although the global construction rate of ocean islands is small compared to igneous accretion at mid‐ocean ridges, the magnitude of the chemical changes indicates that ocean islands and seamounts may be a significant contributor to the chemical budget of the oceans.
Power law burst lifetime distribution of the SYM‐H index
Authors: Wanliss J. A. , Weygand J. M.
Published: February 2007

We have examined the burst lifetime distribution functions of solar wind VBs and ɛ for 1995–2005 and compared them with the same for contemporaneous SYM‐H. The analysis yields clear power‐law exponents of the lifetime probability distributions. When we analyzed three years around solar minimum we found similar scaling behavior for all the variables, including SYM‐H. However, for the three years around solar maximum the difference between solar wind and SYM‐H scaling was very clear. The fact that power laws were consistently observed for different activity thresholds show that these features are robust and repeatable, although scaling can vary depending on solar cycle. During solar maximum it appears that the scaling properties of the low‐latitude magnetosphere, whose output is recorded by SYM‐H, are not purely a direct response to the scale‐free properties of the solar wind but are due to inherent properties of the magnetosphere. Since SYM‐H scaling is remarkably robust, irrespective of solar cycle, it could be that the solar wind never acts as a direct driver for the SYM‐H scaling.
A globally consistent reanalysis of hurricane variability and trends
Authors: Kossin J. P. , Knapp K. R. , Vimont D. J. , Murnane R. J. , Harper B. A.
Published: February 2007

Recently documented trends in the existing records of hurricane intensity and their relationship to increasing sea surface temperatures suggest that hurricane intensity may be increasing due to global warming. However, it is presently being argued that the existing global hurricane records are too inconsistent to accurately measure trends. As a first step in addressing this debate, we constructed a more homogeneous global record of hurricane intensity and found that previously documented trends in some ocean basins are well supported, but in others the existing records contain trends that may be inflated or spurious.
Quantitative classification of northeast Asian dust events
Authors: Song Zhenxin , Wang Jinyan , Wang Shigong
Published: February 2007

In this paper, we introduce a quantitative classification of dust events on the basis of dust, PM10 concentration, and wind speed for northeast Asia. The empirical relationship between visibility and PM10 concentration is established by regression of visibility and PM10 concentration that were taken every 5 min at 11 sites in the spring of 2004 and 2005. The empirical relationship is then applied to establish the spatial and temporal patterns of dust and PM10 concentrations by using the visibility data obtained from 1680 meteorological stations in the spring seasons of 2000–2005. The results showed that the PM10 concentration estimated from visibility is consistent with the observed PM10 concentration. The classification standard of dust events used by different countries did not show consistent results in northeast Asia. It is recommended that dust events in northeast Asia be classified as follows: (1) severe dust storm, ρTSP ≥ 6000 μg m−3, ρPM10 ≥ 5000 μg m−3, and v ≥ 10 m s−1; (2) dust storm, 3000 μg m−3 ≤ ρTSP < 6000 μg m−3, 3000 μg m−3 ≤ ρPM10 < 5000 μg m−3, and 10 m s−1 ≤ v < 15 m s−1; (3) blowing dust, 900 μg m−3 ≤ ρTSP < 1500 μg m−3, 200 μg m−3 ≤ ρPM10 < 600 μg m−3, and 5 m s−1 ≤ v < 10 m s−1; and (4) floating dust, 750 μg m−3 ≤ ρTSP < 1200 μg m−3, 200 μg m−3 ≤ ρPM10 < 400 μg m−3, and 2 m s−1 ≤ v < 5 m s−1.
A density functional study on water‐sulfuric acid‐ammonia clusters and implications for atmospheric cluster formation
Authors: Kurtén Theo , Torpo Leena , Ding Chang‐Geng , Vehkamäki Hanna , Sundberg Markku R. , Laasonen Kari , Kulmala Markku
Published: February 2007

We present results for the electronic and atomic structures of different size molecular clusters containing sulfuric acid, water, and ammonia molecules. The electronic structure calculations are performed using the DMol3 quantum chemical program packages and the PW91 density functional. We report implications of our results for atmospheric cluster size distributions. Our calculations indicate that ammonia is bonded to the cluster structures much more strongly than water. The presence of ammonia also strengthens the binding of sulfuric acid molecules to the clusters, and significantly increases the formation of clusters containing two sulfuric acid molecules and 0–2 water molecules. However, owing to the low overall concentration of two‐acid clusters, the fraction of ammonia‐containing clusters in the calculated atmospheric cluster size distribution was still very low.
Cholera toxin binds to lipid rafts but has a limited specificity for ganglioside GM1
Authors: Blank Norbert , Schiller Martin , Krienke Stefan , Wabnitz Guido , Ho Anthony D , Lorenz Hanns‐Martin
Published: February 2007

Lipid rafts and the formation of an immunological synapse are crucial for T‐cell activation. Binding of cholera toxin B subunit (CTB) to ganglioside GM1 is a marker to identify lipid rafts. Primary human T cells were isolated from healthy donors and were stimulated with superantigen staphylococcus enterotoxin B (SEB) and stained with cholera toxin B‐fluorescein isothiocyanate (CTB‐FITC). An optimized staining procedure is required to stain lipid rafts exclusively on the cell surface. Unstimulated T cells show a few CTB binding spots on the cell surface. The size and number of CTB‐binding lipid rafts are strongly upregulated during T‐cell activation in SEB‐stimulated CD4+ T cells. However, our data show that the specificity of CTB for GM1 ganglioside is limited, because the binding capacity is partly resistant to inhibition of ganglioside synthesis and sensitive to trypsin digestion. Our results indicate that the binding of FITC‐labeled CTB can be divided into at least three different categories: a specific binding of CTB to ganglioside GM1, a nonspecific binding of CTB probably to glycosylated surface proteins and a nonspecific binding of FITC to the cell surface.
Ecologies and Economies of Action—Sustainability, Calculations, and other Things
Authors: Hinchliffe Steve , Kearnes Matthew B , Degen Monica , Whatmore Sarah
Published: February 2007

In ecological, environmental, and urban-regeneration terms, the participatory turn and the turn to action have been written about at length in both academic and official literatures. From neighbourhood renewal to lay ecologies, people are being ‘given’ all kinds of agency in the making of economy and ecology. Yet relatively little has been said regarding the financial organisation of this new populism, which is often achieved through calculation and audit, and the framing of a return. In this paper we look at the uneasy coalition of civic action and its calculability. It focuses on the funding and running of a British Pakistani and Bangladeshi women's gardening initiative in inner city Birmingham, England. We fuse empirical work with gardeners and funding agencies with theoretical understandings of calculation in order to argue for a mode of organisation that not only includes a responsibility to act but also a responsibility to otherness. Rather than arguing for or against calculation, we describe a more diverse ecology of action and in so doing open arguments for reconfiguring the ways in which sustainable activities are funded.
Use of DiazaCon™ as a reproductive inhibitor for monk parakeets (Myiopsitta monachus)
Authors: Yoder Christi A. , Avery Michael L. , Keacher Kandy L. , Tillman Eric A.
Published: February 2007

Feral monk parakeet (Myiopsitta monachus) populations have become established in the United States and other countries around the world, and can cause damage to electrical facilities. Because the monk parakeet is a highly visible species and there is often public opposition to lethal control measures, non-lethal methods, such as contraception, are being developed to help control the spread of feral populations. Two gavage studies and one ad libitum nesting study were conducted to assess the efficacy of DiazaCon™ as a potential contraceptive for the monk parakeet. The first gavage study compared daily dose levels of 0, 50, 75, and 100 mg DiazaCon™ (kg bodyweight)–1 administered for 10 consecutive days. Cholesterol concentrations decreased significantly concomitant with a significant increase in desmosterol concentrations in the treated groups, but did not vary between sexes. Cholesterol and desmosterol concentrations did not differ significantly among DiazaCon™ groups, and cholesterol remained significantly suppressed 12 weeks after treatment. On the basis of these results, the second gavage study compared 5 or 10 consecutive days of DiazaCon™ administration at 50 mg kg–1 bird–1 day–1. Cholesterol concentrations decreased significantly concomitant with a significant increase in desmosterol concentrations in the treated groups, but did not vary between sexes. Cholesterol and desmosterol concentrations did not differ significantly between DiazaCon™ groups, and cholesterol remained significantly suppressed 11 weeks after treatment. Parakeets in the nesting study were fed hulled sunflower seeds treated with a target dose of 50 mg DiazaCon™ kg–1 bird–1 day–1. Birds consumed enough to receive an average dose of 34 mg kg–1 pair–1 day–1, or 17 mg kg–1 bird–1 day–1. Birds in the treated group laid an average of 1.6 ± 0.7 eggs per clutch compared with 3.9 ± 1.1 eggs per clutch in the untreated control group. None of the eggs laid by treated birds hatched compared with 1.1 ± 0.6 eggs per clutch hatching in the control group. Reproductive inhibition was effective for the length of the breeding season, at which time the study was stopped and no more data were collected. DiazaCon™ is a promising avian oral contraceptive that should be further investigated in a field setting with monk parakeets.
Permanent marking in an endangered species: physiological response to hot branding in Steller sea lions (Eumetopias jubatus)
Authors: Mellish Jo-Ann , Hennen Daniel , Thomton Jamie , Petrauskas Lisa , Atkinson Shannon , Calkins Don
Published: February 2007

Identification of individual animals is important in order to evaluate age-specific survival rates, onset of sexual maturity and reproductive rates in wildlife populations. Of the various methods available to researchers, hot branding is the most effective, although somewhat controversial, tool available. The physiological effects of hot-iron branding (n = 7) were assessed using temporarily captive juvenile Steller sea lions (Eumetopias jubatus) (n = 22). Sea lions showed statistically significant increases in white blood cell count, platelet levels, globulin and haptoglobin concentration up to two weeks after branding. No significant differences were found in serum cortisol levels. The changes in health parameters we saw after branding were consistent with minor tissue trauma and indistinguishable from baseline levels after 7–8 weeks.
Comparison of 0.005% and 0.01% diphacinone and chlorophacinone baits for controlling California ground squirrels (Spermophilus beecheyi)
Authors: Salmon Terrell P. , Whisson Desley A. , Berentsen Are R. , Gorenzel W. Paul
Published: February 2007

Abstract.Diphacinone and chlorophacinone, first-generation anticoagulant rodenticides, are frequently used for control of California ground squirrels (Spermophilus beecheyi) in agricultural and rangeland areas in California, USA. Owing to growing concerns over the risks to non-target species associated with the use of these rodenticides, the USA Environmental Protection Agency (EPA) proposed that the concentration of baits for above-ground use should be reduced from 0.01% to 0.005% active ingredient. We conducted field trials to compare the efficacy of 0.005% and 0.01% chlorophacinone and diphacinone baits in broadcast and spot applications for control of California ground squirrels on rangeland. We found no significant difference in efficacy owing to bait type, concentration or application method. Repeat testing is needed in other habitat types (e.g. crop areas) where alternative foods might reduce the effectiveness of a 0.005% bait application.
Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development
Authors: Zhou Xianghua , Tian Fei , Sandzén Johan , Cao Renhai , Flaberg Emilie , Szekely Laszlo , Cao Yihai , Ohlsson Claes , Bergo Martin O. , Borén Jan , Akyürek Levent M.
Published: February 2007

Mutations in
filamin B
(
FLNB
), a gene encoding a cytoplasmic actin-binding protein, have been found in human skeletal disorders, including boomerang dysplasia, spondylocarpotarsal syndrome, Larsen syndrome, and atelosteogenesis phenotypes I and III. To examine the role of FLNB
in vivo
, we generated mice with a targeted disruption of
Flnb
. Fewer than 3% of homozygous embryos reached term, indicating that
Flnb
is important in embryonic development. Heterozygous mutant mice were indistinguishable from their wild-type siblings. Flnb was ubiquitously expressed; strong expression was found in endothelial cells and chondrocytes.
Flnb
-deficient fibroblasts exhibited more disorganized formation of actin filaments and reduced ability to migrate compared with wild-type controls.
Flnb
-deficient embryos exhibited impaired development of the microvasculature and skeletal system. The few
Flnb
-deficient mice that were born were very small and had severe skeletal malformations, including scoliotic and kyphotic spines, lack of intervertebral discs, fusion of vertebral bodies, and reduced hyaline matrix in extremities, thorax, and vertebrae. These mice died or had to be euthanized before 4 weeks of age. Thus, the phenotypes of
Flnb
-deficient mice closely resemble those of human skeletal disorders with mutations in
FLNB
.
Using DNA to track the origin of the largest ivory seizure since the 1989 trade ban
Authors: Wasser Samuel K. , Mailand Celia , Booth Rebecca , Mutayoba Benezeth , Kisamo Emily , Clark Bill , Stephens Matthew
Published: February 2007

The illegal ivory trade recently intensified to the highest levels ever reported. Policing this trafficking has been hampered by the inability to reliably determine geographic origin of contraband ivory. Ivory can be smuggled across multiple international borders and along numerous trade routes, making poaching hotspots and potential trade routes difficult to identify. This fluidity also makes it difficult to refute a country's denial of poaching problems. We extend an innovative DNA assignment method to determine the geographic origin(s) of large elephant ivory seizures. A Voronoi tessellation method is used that utilizes genetic similarities across tusks to simultaneously infer the origin of multiple samples that could have one or more common origin(s). We show that this joint analysis performs better than sample-by-sample methods in assigning sample clusters of known origin. The joint method is then used to infer the geographic origin of the largest ivory seizure since the 1989 ivory trade ban. Wildlife authorities initially suspected that this ivory came from multiple locations across forest and savanna Africa. However, we show that the ivory was entirely from savanna elephants, most probably originating from a narrow east-to-west band of southern Africa, centered on Zambia. These findings enabled law enforcement to focus their investigation to a smaller area and fewer trade routes and led to changes within the Zambian government to improve antipoaching efforts. Such outcomes demonstrate the potential of genetic analyses to help combat the expanding wildlife trade by identifying origin(s) of large seizures of contraband ivory. Broader applications to wildlife trade are discussed.
Structure of the non-redox-active tungsten/[4Fe:4S] enzyme acetylene hydratase
Authors: Seiffert Grazyna B. , Ullmann G. Matthias , Messerschmidt Albrecht , Schink Bernhard , Kroneck Peter M. H. , Einsle Oliver
Published: February 2007

The tungsten–iron–sulfur enzyme acetylene hydratase stands out from its class because it catalyzes a nonredox reaction, the hydration of acetylene to acetaldehyde. Sequence comparisons group the protein into the dimethyl sulfoxide reductase family, and it contains a bis-molybdopterin guanine dinucleotide-ligated tungsten atom and a cubane-type [4Fe:4S] cluster. The crystal structure of acetylene hydratase at 1.26 Å now shows that the tungsten center binds a water molecule that is activated by an adjacent aspartate residue, enabling it to attack acetylene bound in a distinct, hydrophobic pocket. This mechanism requires a strong shift of pKaof the aspartate, caused by a nearby low-potential [4Fe:4S] cluster. To access this previously unrecognized W–Asp active site, the protein evolved a new substrate channel distant from where it is found in other molybdenum and tungsten enzymes.
Attenuated virulence of aFrancisellamutant lacking the lipid A 4′-phosphatase
Authors: Wang Xiaoyuan , Ribeiro Anthony A. , Guan Ziqiang , Abraham Soman N. , Raetz Christian R. H.
Published: February 2007

Francisella tularensiscauses tularemia, a highly contagious disease of animals and humans, but the virulence features ofF. tularensisare poorly defined.F. tularensisand the related mouse pathogenFrancisella novicidasynthesize unusual lipid A molecules lacking the 4′-monophosphate group typically found in the lipid A of Gram-negative bacteria. LpxF, a selective phosphatase located on the periplasmic surface of the inner membrane, removes the 4′-phosphate moiety in the late stages ofF. novicidalipid A assembly. To evaluate the relevance of the 4′-phosphatase to pathogenesis, we constructed a deletion mutant oflpxFand compared its virulence with wild-typeF. novicida. Intradermal injection of 106wild-type but not 108mutantF. novicidacells is lethal to mice. The rapid clearance of thelpxFmutant is associated with a stronger local cytokine response and a greater influx of neutrophils compared with wild-type. TheF. novicidamutant was highly susceptible to the cationic antimicrobial peptide polymyxin. LpxF therefore represents a kind of virulence factor that confers a distinct lipid A phenotype, preventingFrancisellafrom activating the host innate immune response and preventing the bactericidal actions of cationic peptides.Francisella lpxFmutants may be useful for immunization against tularemia.
WNK4 regulates activity of the epithelial Na
+
channel
in vitro
and
in vivo
Authors: Ring Aaron M. , Cheng Sam X. , Leng Qiang , Kahle Kristopher T. , Rinehart Jesse , Lalioti Maria D. , Volkman Heather M. , Wilson Frederick H. , Hebert Steven C. , Lifton Richard P.
Published: February 2007

Homeostasis of intravascular volume, Na
+
, Cl
−
, and K
+
is interdependent and determined by the coordinated activities of structurally diverse mediators in the distal nephron and the distal colon. The behavior of these flux pathways is regulated by the renin–angiotensin–aldosterone system; however, the mechanisms that allow independent modulation of individual elements have been obscure. Previous work has shown that mutations in
WNK4
cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension with hyperkalemia, due to altered activity of specific Na-Cl cotransporters, K
+
channels, and paracellular Cl
−
flux mediators of the distal nephron. By coexpression studies in
Xenopus
oocytes, we now demonstrate that WNK4 also inhibits the epithelial Na
+
channel (ENaC), the major mediator of aldosterone-sensitive Na
+
(re)absorption, via a mechanism that is independent of WNK4's kinase activity. This inhibition requires intact C termini in ENaC β- and γ-subunits, which contain PY motifs used to target ENaC for clearance from the plasma membrane. Importantly, PHAII-causing mutations eliminate WNK4's inhibition of ENaC, thereby paralleling other effects of PHAII to increase sodium balance. The relevance of these findings
in vivo
was studied in mice harboring PHAII-mutant WNK4. The colonic epithelium of these mice demonstrates markedly increased amiloride-sensitive Na
+
flux compared with wild-type littermates. These studies identify ENaC as a previously unrecognized downstream target of WNK4 and demonstrate a functional role for WNK4 in the regulation of colonic Na
+
absorption. These findings support a key role for WNK4 in coordinating the activities of diverse flux pathways to achieve integrated fluid and electrolyte homeostasis.
Functional role and oncogene-regulated expression of the BH3-only factor Bmf in mammary epithelial anoikis and morphogenesis
Authors: Schmelzle Tobias , Mailleux Arnaud A. , Overholtzer Michael , Carroll Jason S. , Solimini Nicole L. , Lightcap Eric S. , Veiby Ole P. , Brugge Joan S.
Published: February 2007

The formation of a lumen in three-dimensional mammary epithelial acinar structures
in vitro
involves selective apoptosis of centrally localized cells that lack matrix attachment. Similarly, apoptosis is induced by forced detachment of mammary epithelial cells from matrix, a process referred to as anoikis. Through microarray analysis, we found that mRNA levels of the proapoptotic BH3-only protein Bmf are up-regulated during both anoikis and acinar morphogenesis. Importantly, down-regulation of Bmf expression by small interfering RNAs is sufficient to prevent anoikis and acinar cell death and promote anchorage-independent growth to a similar extent as down-regulation of another BH3-only protein, Bim, which was previously shown to be required for these processes. Knockdown of the BH3-only proteins Bad or Bid does not suppress anoikis or luminal apoptosis or promote anchorage-independent growth, but protects from other defined apoptotic stimuli, indicating specificity of BH3-only function.
Bmf
mRNA is significantly up-regulated upon loss of matrix attachment or disruption of the actin cytoskeleton, but not in response to several other stresses. Interestingly, constitutive activation of the Mek/Erk or phosphatidylinositol 3-kinase/Akt pathways suppresses the transcriptional up-regulation of
Bmf
during anoikis. Thus, Bmf is a central mediator of anoikis in mammary cells and a target of oncogenes that contribute to the progression of glandular epithelial tumors. Finally,
Bmf
is expressed during involution of the mouse mammary gland, suggesting that Bmf may also critically contribute to developmental processes
in vivo
.
Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells
Authors: Muller-Borer Barbara J. , Cascio Wayne E. , Esch Gwyn L. , Kim Hyung-Suk , Coleman William B. , Grisham Joe W. , Anderson Page A. W. , Malouf Nadia N.
Published: February 2007

The mechanisms underlying stem cell acquisition of a cardiac phenotype are unresolved. We studied early events during the acquisition of a cardiac phenotype by a cloned adult liver stem cell line (WB F344) in a cardiac microenvironment. WB F344 cells express
a priori
the transcription factors GATA4 and SRF, connexin 43 in the cell membrane, and myoinositol 1,4,5-triphosphate receptor in the perinuclear region. Functional cell–cell communication developed between WB F344 cells and adjacent cocultured cardiomyocytes in 24 h.
De novo
cytoplasmic [Ca
2+
]
c
and nuclear [Ca
2+
]
nu
oscillations appeared in WB F344 cells, synchronous with [Ca
2+
]
i
transients in adjacent cardiomyocytes. The [Ca
2+
] oscillations in the WB F344 cells, but not those in the cardiomyocytes, were eliminated by a gap junction uncoupler and reappeared with its removal. By 24 h, WB F344 cells began expressing the cardiac transcription factors Nkx2.5, Tbx5, and cofactor myocardin; cardiac proteins 24 h later; and a sarcomeric pattern 4–6 days later. Myoinositol 1,4,5-triphosphate receptor inhibition suppressed WB F344 cell [Ca
2+
]
nu
oscillations but not [Ca
2+
]
c
oscillations, and L-type calcium channel inhibition eliminated [Ca
2+
] oscillations in cardiomyocytes and WB F344 cells. The use of these inhibitors was associated with a decrease in Nkx2.5, Tbx5, and myocardin expression in the WB F344 cells. Our findings suggest that signals from cardiomyocytes diffuse through shared channels, inducing [Ca
2+
] oscillations in the WB F344 cells. We hypothesize that the WB F344 cell [Ca
2+
]
nu
oscillations activate the expression of a cardiac specifying gene program, ushering in a cardiac phenotype.
αEβ7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis
Authors: Floc'h Audrey Le , Jalil Abdelali , Vergnon Isabelle , Chansac Béatrice Le Maux , Lazar Vladimir , Bismuth Georges , Chouaib Salem , Mami-Chouaib Fathia
Published: February 2007

Various T cell adhesion molecules and their cognate receptors on target cells promote T cell receptor (TCR)–mediated cell killing. In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin αE(CD103)β7, often expressed by tumor-infiltrating lymphocytes (TILs), plays a major role in effective tumor cell lysis. Indeed, we found that although tumor-specific CD103+ TIL-derived cytotoxic T lymphocyte (CTL) clones are able to kill E-cadherin+/intercellular adhesion molecule 1− autologous tumor cells, CD103− peripheral blood lymphocyte (PBL)-derived counterparts are inefficient. This cell killing is abrogated after treatment of the TIL clones with a blocking anti-CD103 monoclonal antibody or after targeting E-cadherin in the tumor using ribonucleic acid interference. Confocal microscopy analysis also demonstrated that αEβ7 is recruited at the immunological synapse and that its interaction with E-cadherin is required for cytolytic granule polarization and subsequent exocytosis. Moreover, we report that the CD103− profile, frequently observed in PBL-derived CTL clones and associated with poor cytotoxicity against the cognate tumor, is up-regulated upon TCR engagement and transforming growth factor β1 treatment, resulting in strong potentiation of antitumor lytic function. Thus, CD8+/CD103+ tumor-reactive T lymphocytes infiltrating epithelial tumors most likely play a major role in antitumor cytotoxic response through αEβ7–E-cadherin interactions.
A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate–mediated egress
Authors: Nombela-Arrieta César , Mempel Thorsten R. , Soriano Silvia F. , Mazo Irina , Wymann Matthias P. , Hirsch Emilio , Martínez-A. Carlos , Fukui Yoshinori , von Andrian Ulrich H. , Stein Jens V.
Published: February 2007

Recent observations using multiphoton intravital microscopy (MP-IVM) have uncovered an unexpectedly high lymphocyte motility within peripheral lymph nodes (PLNs). Lymphocyte-expressed intracellular signaling molecules governing interstitial movement remain largely unknown. Here, we used MP-IVM of murine PLNs to examine interstitial motility of lymphocytes lacking the Rac guanine exchange factor DOCK2 and phosphoinositide-3-kinase (PI3K)γ, signaling molecules that act downstream of G protein–coupled receptors, including chemokine receptors (CKRs). T and B cells lacking DOCK2 alone or DOCK2 and PI3Kγ displayed markedly reduced motility inside T cell area and B cell follicle, respectively. Lack of PI3Kγ alone had no effect on migration velocity but resulted in increased turning angles of T cells. As lymphocyte egress from PLNs requires the sphingosine-1-phosphate (S1P) receptor 1, a Gαi protein–coupled receptor similar to CKR, we further analyzed whether DOCK2 and PI3Kγ contributed to S1P-triggered signaling events. S1P-induced cell migration was significantly reduced in T and B cells lacking DOCK2, whereas T cell–expressed PI3Kγ contributed to F-actin polymerization and protein kinase B phosphorylation but not migration. These findings correlated with delayed lymphocyte egress from PLNs in the absence of DOCK2 but not PI3Kγ, and a markedly reduced cell motility of DOCK2-deficient T cells in close proximity to efferent lymphatic vessels. In summary, our data support a central role for DOCK2, and to a lesser extent T cell–expressed PI3Kγ, for signal transduction during interstitial lymphocyte migration and S1P-mediated egress.
Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock
Authors: Yang Chul-Su , Lee Dong-Seok , Song Chang-Hwa , An Se-Jin , Li Shengjin , Kim Jin-Man , Kim Cuk Seong , Yoo Dae Goon , Jeon Byeong Hwa , Yang Hee-Young , Lee Tae-Hoon , Lee Zee-Won , El-Benna Jamel , Yu Dae-Yeul , Jo Eun-Kyeong
Published: February 2007

Mammalian 2-Cys peroxiredoxin II (Prx II) is a cellular peroxidase that eliminates endogenous H2O2. The involvement of Prx II in the regulation of lipopolysaccharide (LPS) signaling is poorly understood. In this report, we show that LPS induces substantially enhanced inflammatory events, which include the signaling molecules nuclear factor κB and mitogen-activated protein kinase (MAPK), in Prx II–deficient macrophages. This effect of LPS was mediated by the robust up-regulation of the reactive oxygen species (ROS)–generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and the phosphorylation of p47phox. Furthermore, challenge with LPS induced greater sensitivity to LPS-induced lethal shock in Prx II–deficient mice than in wild-type mice. Intravenous injection of Prx II–deficient mice with the adenovirus-encoding Prx II gene significantly rescued mice from LPS-induced lethal shock as compared with the injection of a control virus. The administration of catalase mimicked the reversal effects of Prx II on LPS-induced inflammatory responses in Prx II–deficient cells, which suggests that intracellular H2O2 is attributable, at least in part, to the enhanced sensitivity to LPS. These results indicate that Prx II is an essential negative regulator of LPS-induced inflammatory signaling through modulation of ROS synthesis via NADPH oxidase activities and, therefore, is crucial for the prevention of excessive host responses to microbial products.
Multiple structural alignment and clustering of RNA sequences
Authors: Torarinsson Elfar , Havgaard Jakob H. , Gorodkin Jan
Published: February 2007

Motivation: An apparent paradox in computational RNA structure prediction is that many methods, in advance, require a multiple alignment of a set of related sequences, when searching for a common structure between them. However, such a multiple alignment is hard to obtain even for few sequences with low sequence similarity without simultaneously folding and aligning them. Furthermore, it is of interest to conduct a multiple alignment of RNA sequence candidates found from searching as few as two genomic sequences.

Results: Here, based on the PMcomp program, we present a global multiple alignment program, foldalignM, which performs especially well on few sequences with low sequence similarity, and is comparable in performance with state of the art programs in general. In addition, it can cluster sequences based on sequence and structure similarity and output a multiple alignment for each cluster. Furthermore, preliminary results with local datasets indicate that the program is useful for post processing foldalign pairwise scans.

Availability: The program foldalignM is implemented in JAVA and is, along with some accompanying PERL scripts, available at http://foldalign.ku.dk/

Contact:  gorodkin@genome.ku.dk
Grooming in Barbary macaques: better to give than to receive?
Authors: Shutt Kathryn , MacLarnon Ann , Heistermann Michael , Semple Stuart
Published: February 2007

It is well established that grooming underpins sociality in group-living primates, and a number of studies have documented the stress-reducing effects of being groomed. In this study, we quantified grooming behaviour and physiological stress (assessed by faecal glucocorticoid analysis) in free-ranging Barbary macaques,Macaca sylvanus. Our results indicate that it is the giving rather than the receiving of grooming that is associated with lower stress levels. These findings shed important new light on the benefits of this key behaviour in primate social life.
Nonlinear non-local elliptic equation modelling electrostatic actuation
Authors: Lin Fanghua , Yang Yisong
Published: February 2007

The nonlinear non-local elliptic equation governing the deflection of charged plates in electrostatic actuators is studied under the pinned and the clamped boundary conditions. Results concerning the existence, construction and approximation, and behaviour of classical and singular solutions with respect to the variation of physical parameters of the equation in various situations are presented.
Ultrafast shape recognition for similarity search in molecular databases
Authors: Ballester Pedro J , Richards W. Graham
Published: February 2007

Molecular databases are routinely screened for compounds that most closely resemble a molecule of known biological activity to provide novel drug leads. It is widely believed that three-dimensional molecular shape is the most discriminating pattern for biological activity as it is directly related to the steep repulsive part of the interaction potential between the drug-like molecule and its macromolecular target. However, efficient comparison of molecular shape is currently a challenge. Here, we show that a new approach based on moments of distance distributions is able to recognize molecular shape at least three orders of magnitude faster than current methodologies. Such an ultrafast method permits the identification of similarly shaped compounds within the largest molecular databases. In addition, the problematic requirement of aligning molecules for comparison is circumvented, as the proposed distributions are independent of molecular orientation. Our methodology could be also adapted to tackle similar hard problems in other fields, such as designing content-based Internet search engines for three-dimensional geometrical objects or performing fast similarity comparisons between proteins. From a broader perspective, we anticipate that ultrafast pattern recognition will soon become not only useful, but also essential to address the data explosion currently experienced in most scientific disciplines.
Disease transmission by cannibalism: rare event or common occurrence?
Authors: Rudolf Volker H.W , Antonovics Janis
Published: February 2007

Cannibalism has been documented as a possible disease transmission route in several species, including humans. However, the dynamics resulting from this type of disease transmission are not well understood. Using a theoretical model, we explore how cannibalism (i.e. killing and consumption of dead conspecifics) and intraspecific necrophagy (i.e. consumption of dead conspecifics) affect host–pathogen dynamics. We show that group cannibalism, i.e. shared consumption of victims, is a necessary condition for disease spread by cannibalism in the absence of alternative transmission modes. Thus, endemic diseases transmitted predominantly by cannibalism are likely to be rare, except in social organisms that share conspecific prey. These results are consistent with a review of the literature showing that diseases transmitted by cannibalism are infrequent in animals, even though both cannibalism and trophic transmission are very common.
Sexual reproduction prevails in a world of structured resources in short supply
Authors: Scheu S , Drossel B
Published: February 2007

We present a model for the maintenance of sexual reproduction based on the availability of resources, which is the strongest factor determining the growth of populations. The model compares completely asexual species to species that switch between asexual and sexual reproduction (sexual species). Key features of the model are that sexual reproduction sets in when resources become scarce, and that at a given place only a few genotypes can be present at the same time. We show that under a wide range of conditions the sexual species outcompete the asexual ones. The asexual species win only when survival conditions are harsh and death rates are high, or when resources are so little structured or consumer genotypes are so manifold that all resources are exploited to the same extent. These conditions, largely represent the conditions in which sexuals predominate over asexuals in the field.