bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for liquid-like and nonideal behavior of a mixture of organic aerosol components
Authors: Cappa Christopher D. , Lovejoy Edward R. , Ravishankara A. R.
Published: November 2008

The condensation, evaporation, and repartitioning of semivolatile organic compounds (SVOCs) in the atmosphere depends both on the phase of condensed material and the effective condensed phase vapor pressures of the SVOCs. Although direct measurements of vapor pressures of individual SVOCs exist, there are limited measurements of how the properties of a given compound changes in mixtures of multiple components that exist in the atmosphere. Here, the evaporation behavior of mixtures of dicarboxylic acids, which are common atmospheric aerosol constituents, is investigated. These measurements demonstrate that complex mixtures of the individually solid organic compounds take on liquid-like properties. Additionally, the vapor pressures of individual components show strong, identity-dependent deviations from ideality (i.e., Raoult's Law), with the vapor pressures of the smaller, more volatile compounds decreased significantly in the mixtures. The addition of an inorganic compound (NaNO
3
) further influences the nonideal behavior, again in a compound-specific manner. These results suggest that nonideal behavior of particle-phase compounds influences the abundances of organic aerosol observed in the atmosphere and in the laboratory.
Impaired bone development and increased mesenchymal progenitor cells in calvaria of
RB1
−/−
mice
Authors: Gutierrez Gabriel M. , Kong Elizabeth , Sabbagh Yves , Brown Nelson E. , Lee Jong-Seo , Demay Marie B. , Thomas David M. , Hinds Philip W.
Published: November 2008

We have previously shown that the retinoblastoma protein (pRb) can activate expression of Runx2-dependent, bone-specific genes in cultured cells. We now show that pRb also plays a role early in osteogenesis, and that in primary
RB1
−/−
calvarial cells there is an increased osteoprogenitor pool. To understand pRb's function in vivo, we generated a conditional
RB1
-KO mouse in which pRb expression is efficiently extinguished in osteoblasts. These animals display an apparent developmental defect in bones, most strikingly in the calvaria. Cultured
RB1
−/−
calvarial osteoblasts fail to cease proliferation upon reaching confluence or following differentiation. Re-plating assays of primary
RB1
−/−
calvarial cells after differentiation showed a clear adipogenic ability with increased multipotency.
RB1
−/−
osteoblasts display a severe reduction in levels of mRNAs expressed late in differentiation. In this study, we present strong evidence that pRb has multiple regulatory roles in osteogenesis. Furthermore, in the absence of
RB1
−/−
there is a larger pool of multipotent cells compared with the WT counterpart. This increased pool of osteoprogenitor cells may be susceptible to additional transforming events leading to osteosarcoma, and is therefore key to understanding
RB1
as a target in malignancy.
Measuring internal friction of an ultrafast-folding protein
Authors: Cellmer Troy , Henry Eric R. , Hofrichter James , Eaton William A.
Published: November 2008

Nanosecond laser T-jump was used to measure the viscosity dependence of the folding kinetics of the villin subdomain under conditions where the viscogen has no effect on its equilibrium properties. The dependence of the unfolding/refolding relaxation time on solvent viscosity indicates a major contribution to the dynamics from internal friction. The internal friction increases with increasing temperature, suggesting a shift in the transition state along the reaction coordinate toward the native state with more compact structures, and therefore, a smaller diffusion coefficient due to increased landscape roughness. Fitting the data with an Ising-like model yields a relatively small position dependence for the diffusion coefficient. This finding is consistent with the excellent correlation found between experimental and calculated folding rates based on free energy barrier heights using the same diffusion coefficient for every protein.
Evolutionary and functional divergence between the cystic fibrosis transmembrane conductance regulator and related ATP-binding cassette transporters
Authors: King Jordan I. , Kota Karthik C. , Cui Guiying , Thompson Christopher H. , McCarty Nael A.
Published: November 2008

The cystic fibrosis transmembrane conductance regulator (CFTR) is a member of the ATP-binding cassette (ABC) transporter superfamily, an ancient family of proteins found in all phyla. In nearly all cases, ABC proteins are transporters that couple the hydrolysis of ATP to the transmembrane movement of substrate via an alternating access mechanism. In contrast, CFTR is best known for its activity as an ATP-dependent chloride channel. We asked why CFTR, which shares the domain architecture of ABC proteins that function as transporters, exhibits functional divergence. We compared CFTR protein sequences to those of other ABC transporters, which identified the ABCC4 proteins as the closest mammalian paralogs, and used statistical analysis of the CFTR-ABCC4 multiple sequence alignment to identify the specific domains and residues most likely to be involved in the evolutionary transition from transporter to channel activity. Among the residues identified as being involved in CFTR functional divergence, by virtue of being both CFTR-specific and conserved among all CFTR orthologs, was R352 in the sixth transmembrane helix (TM6). Patch-clamp experiments show that R352 interacts with D993 in TM9 to stabilize the open-channel state; D993 is absolutely conserved between CFTRs and ABCC4s. These data suggest that CFTR channel activity evolved, at least in part, by converting the conformational changes associated with binding and hydrolysis of ATP, as are found in true ABC Transporters, into an open permeation pathway by means of intraprotein interactions that stabilize the open state. This analysis sets the stage for understanding the evolutionary and functional relationships that make CFTR a unique ABC transporter protein.
8-Oxoguanine-mediated transcriptional mutagenesis causes Ras activation in mammalian cells
Authors: Saxowsky Tina T. , Meadows Kellen L. , Klungland Arne , Doetsch Paul W.
Published: November 2008

8-Oxoguanine (8OG) is efficiently bypassed by RNA polymerases
in vitro
and in bacterial cells
in vivo
, leading to mutant transcripts by directing incorporation of an incorrect nucleotide during transcription. Such transcriptional mutagenesis (TM) may produce a pool of mutant proteins. In contrast, transcription-coupled repair safeguards against DNA damage, contingent upon the ability of lesions to arrest elongating RNA polymerase. In mammalian cells, the Cockayne syndrome B protein (Csb) mediates transcription-coupled repair, and its involvement in the repair of 8OG is controversial. The DNA glycosylase Ogg1 initiates base excision repair of 8OG, but its influence on TM is unknown. We have developed a mammalian system for TM in congenic mouse embryonic fibroblasts (MEFs), either WT or deficient in Ogg1 (ogg
−/−
), Csb (csb
−/−
), or both. This system uses expression of the Ras oncogene in which an 8OG replaces guanine in codon 61. Repair of 8OG restores the WT sequence; however, bypass and misinsertion opposite this lesion during transcription leads to a constitutively active mutant Ras protein and activation of downstream signaling events, including increased phosphorylation of ERK kinase. Upon transfection of MEFs with replication-incompetent 8OG constructs, we observed a marked increase in phospho-ERK in ogg
−/−
and csb
−/−
ogg
−/−
cells at 6 h, indicating persistence of the lesion and the occurrence of TM. This effect is absent in WT and csb
−/−
cells, suggesting rapid repair. These studies provide evidence that 8OG causes TM in mammalian cells, leading to a phenotypic change with important implications for the role of TM in tumorigenesis.
Eight genes are required for functional reconstitution of the
Caenorhabditis elegans
levamisole-sensitive acetylcholine receptor
Authors: Boulin Thomas , Gielen Marc , Richmond Janet E. , Williams Daniel C. , Paoletti Pierre , Bessereau Jean-Louis
Published: November 2008

Levamisole-sensitive acetylcholine receptors (L-AChRs) are ligand-gated ion channels that mediate excitatory neurotransmission at the neuromuscular junctions of nematodes. They constitute a major drug target for anthelminthic treatments because they can be activated by nematode-specific cholinergic agonists such as levamisole. Genetic screens conducted in
Caenorhabditis elegans
for resistance to levamisole toxicity identified genes that are indispensable for the biosynthesis of L-AChRs. These include 5 genes encoding distinct AChR subunits and 3 genes coding for ancillary proteins involved in assembly and trafficking of the receptors. Despite extensive analysis of L-AChRs in vivo, pharmacological and biophysical characterization of these receptors has been greatly hampered by the absence of a heterologous expression system. Using
Xenopus laevis
oocytes, we were able to reconstitute functional L-AChRs by coexpressing the 5 distinct receptor subunits and the 3 ancillary proteins. Strikingly, this system recapitulates the genetic requirements for receptor expression in vivo because omission of any of these 8 genes dramatically impairs L-AChR expression. We demonstrate that 3 α- and 2 non-α-subunits assemble into the same receptor. Pharmacological analysis reveals that the prototypical cholinergic agonist nicotine is unable to activate L-AChRs but rather acts as a potent allosteric inhibitor. These results emphasize the role of ancillary proteins for efficient expression of recombinant neurotransmitter receptors and open the way for in vitro screening of novel anthelminthic agents.
NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide
Authors: Oberhauser Vitus , Voolstra Olaf , Bangert Annette , von Lintig Johannes , Vogt Klaus
Published: November 2008

In animals, successful production of the visual chromophore (11-
cis
-retinal or derivatives thereof such as 11-
cis
-3-hydroxy-retinal) is essential for photoreceptor cell function and survival. These carotenoid-derived compounds must combine with a protein moiety (the opsin) to establish functional visual pigments. Evidence from cell culture systems has implicated that the retinal pigment epithelium protein of 65 kDa (RPE65) is the long-sought all-
trans
to 11-
cis
retinoid isomerase. RPE65 is structurally related to nonheme iron oxygenases that catalyze the conversion of carotenoids into retinoids. In vertebrate genomes, two carotenoid oxygenases and RPE65 are encoded, whereas in insect genomes only a single representative of this protein family, named NinaB (denoting neither inactivation nor afterpotential mutant B), is encoded. We here cloned and functionally characterized the
ninaB
gene from the great wax moth
Galleria mellonella
. We show that the recombinant purified enzyme combines isomerase and oxygenase (isomerooxygenase) activity in a single polypeptide. From kinetics and isomeric composition of cleavage products of asymmetrical carotenoid substrates, we propose a model for the spatial arrangement between substrate and enzyme. In
Drosophila
, we show that carotenoid-isomerooxygenase activity of NinaB is more generally found in insects, and we provide physiological evidence that carotenoids such as 11-
cis
-retinal can promote visual pigment biogenesis in the dark. Our study demonstrates that
trans/cis
isomerase activity can be intrinsic to this class of proteins and establishes these enzymes as key components for both invertebrate and vertebrate vision.
Multiple genome sequences reveal adaptations of a phototrophic bacterium to sediment microenvironments
Authors: Oda Yasuhiro , Larimer Frank W. , Chain Patrick S. G. , Malfatti Stephanie , Shin Maria V. , Vergez Lisa M. , Hauser Loren , Land Miriam L. , Braatsch Stephan , Beatty J. Thomas , Pelletier Dale A. , Schaefer Amy L. , Harwood Caroline S.
Published: November 2008

The bacterial genus
Rhodopseudomonas
is comprised of photosynthetic bacteria found widely distributed in aquatic sediments. Members of the genus catalyze hydrogen gas production, carbon dioxide sequestration, and biomass turnover. The genome sequence of
Rhodopseudomonas palustris
CGA009 revealed a surprising richness of metabolic versatility that would seem to explain its ability to live in a heterogeneous environment like sediment. However, there is considerable genotypic diversity among
Rhodopseudomonas
isolates. Here we report the complete genome sequences of four additional members of the genus isolated from a restricted geographical area. The sequences confirm that the isolates belong to a coherent taxonomic unit, but they also have significant differences. Whole genome alignments show that the circular chromosomes of the isolates consist of a collinear backbone with a moderate number of genomic rearrangements that impact local gene order and orientation. There are 3,319 genes, 70% of the genes in each genome, shared by four or more strains. Between 10% and 18% of the genes in each genome are strain specific. Some of these genes suggest specialized physiological traits, which we verified experimentally, that include expanded light harvesting, oxygen respiration, and nitrogen fixation capabilities, as well as anaerobic fermentation. Strain-specific adaptations include traits that may be useful in bioenergy applications. This work suggests that against a backdrop of metabolic versatility that is a defining characteristic of
Rhodopseudomonas
, different ecotypes have evolved to take advantage of physical and chemical conditions in sediment microenvironments that are too small for human observation.
Digoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth
Authors: Zhang Huafeng , Qian David Z. , Tan Yee Sun , Lee KangAe , Gao Ping , Ren Yunzhao R. , Rey Sergio , Hammers Hans , Chang Daniel , Pili Roberto , Dang Chi V. , Liu Jun O. , Semenza Gregg L.
Published: November 2008

A library of drugs that are in clinical trials or use was screened for inhibitors of hypoxia-inducible factor 1 (HIF-1). Twenty drugs inhibited HIF-1-dependent gene transcription by >88% at a concentration of 0.4 μM. Eleven of these drugs were cardiac glycosides, including digoxin, ouabain, and proscillaridin A, which inhibited HIF-1α protein synthesis and expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency and decreased growth of tumor xenografts, whereas treatment of established tumors resulted in growth arrest within one week. Enforced expression of HIF-1α by transfection was not inhibited by digoxin, and xenografts derived from these cells were resistant to the anti-tumor effects of digoxin, demonstrating that HIF-1 is a critical target of digoxin for cancer therapy.
The Danish anal sphincter rupture questionnaire: Validity and reliability
Authors: DUE ULLA , OTTESEN MARIANNE
Published: November 2008

Objective. To revise, validate and test for reliability an anal sphincter rupture questionnaire in relation to construct, content and face validity. Setting and background. Since 1996 women with anal sphincter rupture (ASR) at one of the public university hospitals in Copenhagen, Denmark have been offered pelvic floor muscle examination and instruction by a specialist physiotherapist. In relation to that, a non‐validated questionnaire about anal and urinary incontinence was to be answered six months after childbirth. Method. The original questionnaire was revised and a pilot test was performed among health care personnel, followed by an expert panel discussion. Ten women were interviewed about their understanding and attitude toward answering the questionnaire and it was pre‐tested on 52 women with ASR. The questionnaire was revised five times during the validation process. The final version was test‐retested among 20 women with ASR. Results. The questionnaire revealed typical problems after ASR. The length, use of language, and the way the questionnaire was constructed, was deemed appropriate. The reliability test showed good to very good correlation (Kappa values from 0.733 to 0.923) in all main questions but one. Two questions needed further explanation. Seven women made minor errors. Conclusion. The validated Danish questionnaire has a good construct, content and face validity. It is a well accepted, reliable, simple and clinically relevant screening tool. It reveals physical problems including sexual problems, impact on quality of life and need for treatment among women 6–8 months after ASR.
Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology
Authors: PETRI ANETTE LYKKE , SIMONSEN ANJA HVIID , YIP TAI‐TUNG , HOGDALL ESTRID , FUNG ERIC T. , LUNDVALL LENE , HOGDALL CLAUS
Published: November 2008

Objective. To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass. Methods. A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at −80° until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry. Results. Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann–Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z = 2570.21), collagen alpha 1 (III) fragment (m/z = 2707.32) and fibrinogen beta NT fragment (m/z = 4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96. Conclusion. This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.
Heart rate variability changes in pregnant and non‐pregnant women during standardized psychosocial stress1
Authors: KLINKENBERG ARIADNE V. , NATER URS M. , NIEROP ADA , BRATSIKAS ALIKI , ZIMMERMANN ROLAND , EHLERT ULRIKE
Published: November 2008

Objectives. To test the reactivity of the autonomic nervous system (ANS) of women in different stages of pregnancy to a psychosocial stressor. Design. Psychosocial stress was induced by a standardized test, the Trier Social Stress Test. Setting. University of Zurich, Switzerland. Population. Fifty‐five healthy pregnant women (28 in the second and 27 in or close to the third trimester) and 24 non‐pregnant women in the follicular phase of the menstrual cycle. Methods. Heart rate variability (HRV) was recorded before, during and after the test. Subjective stress perception was measured by a visual analog scale. Main outcome measures. Heart rate, HRV components (high frequency, HF; low frequency, LF, and LF/HF ratio), subjective stress ratings. Results. HF significantly decreased and LF/HF ratio increased during psychosocial stress in all three groups. LF values indicated no significant reaction to psychosocial stress, but a trend towards significance with group interaction was seen. There were no significant differences in subjective stress ratings between the groups. Conclusions. ANS activity during psychosocial stress seems to be decreased in proceeding pregnancy, whereas subjective stress perception does not show significant changes. The decline of HF due to stress compared to non‐pregnant women is not attenuated, just on a lower level.
Event‐Tracking Model of Adhesion Identifies Load‐Bearing Bonds in Rolling Leukocytes
Authors: POSPIESZALSKA MARIA K. , ZARBOCK ALEXANDER , PICKARD JOHN E. , LEY KLAUS
Published: November 2008

Objectives: P‐selectin binding to P‐selectin glycoprotein ligand‐1 (PSGL)‐1 mediates leukocyte rolling under conditions of inflammation and injury. The aims of this study were to develop an efficient, high temporal resolution model for direct simulation of leukocyte rolling and conduct a study of load‐bearing bonds using the model.

Materials and Methods: A stochastic π‐calculus‐driven event‐tracking model of adhesion (ETMA) was developed and compared with experimental data. Multiple simulations for each case were conducted to obtain high‐confidence numerical characteristics of leukocyte rolling.

Results: Leukocyte rolling and the underlying P‐selectin—PSGL‐1 bonds were studied under low wall shear rate (25–50 s−1) conditions from measured parameters of leukocyte rolling and bond properties. For the first time, the location, number, lifetime, history, and kinetics of load‐bearing bonds and their influence on cell rolling were identified and instantaneous cell displacements, translational and rotational velocities, and cell‐substrate distances derived. The model explains the commonly observed “stop‐start” type rolling behavior and reveals that a few load‐bearing bonds are sufficient to support rolling, while a large number of bonds dissociate before becoming load bearing.

Conclusions: ETMA provides a method for more precise, direct simulation of leukocyte rolling at low wall shear rates and sets a foundation upon which further refinements can be introduced.
The Three Fungal Transmembrane Nuclear Pore Complex Proteins ofAspergillus nidulansAre Dispensable in the Presence of an Intact An-Nup84-120 Complex
Authors: Liu Hui-Lin , De Souza Colin P.C. , Osmani Aysha H. , Osmani Stephen A.
Published: November 2008

In Aspergillus nidulans nuclear pore complexes (NPCs) undergo partial mitotic disassembly such that 12 NPC proteins (Nups) form a core structure anchored across the nuclear envelope (NE). To investigate how the NPC core is maintained, we affinity purified the major core An-Nup84-120 complex and identified two new fungal Nups, An-Nup37 and An-ELYS, previously thought to be vertebrate specific. During mitosis the An-Nup84-120 complex locates to the NE and spindle pole bodies but, unlike vertebrate cells, does not concentrate at kinetochores. We find that mutants lacking individual An-Nup84-120 components are sensitive to the membrane destabilizer benzyl alcohol (BA) and high temperature. Although such mutants display no defects in mitotic spindle formation, they undergo mitotic specific disassembly of the NPC core and transient aggregation of the mitotic NE, suggesting the An-Nup84-120 complex might function with membrane. Supporting this, we show cells devoid of all known fungal transmembrane Nups (An-Ndc1, An-Pom152, and An-Pom34) are viable but that An-ndc1 deletion combined with deletion of individual An-Nup84-120 components is either lethal or causes sensitivity to treatments expected to destabilize membrane. Therefore, the An-Nup84-120 complex performs roles, perhaps at the NPC membrane as proposed previously, that become essential without the An-Ndc1 transmembrane Nup.
Mutations in theArabidopsisPeroxisomal ABC Transporter COMATOSE Allow Differentiation between Multiple Functions In Planta: Insights from an Allelic Series
Authors: Dietrich Daniela , Schmuths Heike , Lousa Carine De Marcos , Baldwin Jocelyn M. , Baldwin Stephen A. , Baker Alison , Theodoulou Frederica L. , Holdsworth Michael J.
Published: November 2008

COMATOSE (CTS), the Arabidopsis homologue of human Adrenoleukodystrophy protein (ALDP), is required for import of substrates for peroxisomal β-oxidation. A new allelic series and a homology model based on the bacterial ABC transporter, Sav1866, provide novel insights into structure-function relations of ABC subfamily D proteins. In contrast to ALDP, where the majority of mutations result in protein absence from the peroxisomal membrane, all CTS mutants produced stable protein. Mutation of conserved residues in the Walker A and B motifs in CTS nucleotide-binding domain (NBD) 1 resulted in a null phenotype but had little effect in NBD2, indicating that the NBDs are functionally distinct in vivo. Two alleles containing mutations in NBD1 outside the Walker motifs (E617K and C631Y) exhibited resistance to auxin precursors 2,4-dichlorophenoxybutyric acid (2,4-DB) and indole butyric acid (IBA) but were wild type in all other tests. The homology model predicted that the transmission interfaces are domain-swapped in CTS, and the differential effects of mutations in the conserved “EAA motif” of coupling helix 2 supported this prediction, consistent with distinct roles for each NBD. Our findings demonstrate that CTS functions can be separated by mutagenesis and the structural model provides a framework for interpretation of phenotypic data.
Sequence-specific Retention and Regulated Integration of a Nascent Membrane Protein by the Endoplasmic Reticulum Sec61 Translocon
Authors: Pitonzo David , Yang Zhongying , Matsumura Yoshihiro , Johnson Arthur E. , Skach William R.
Published: November 2008

A defining feature of eukaryotic polytopic protein biogenesis involves integration, folding, and packing of hydrophobic transmembrane (TM) segments into the apolar environment of the lipid bilayer. In the endoplasmic reticulum, this process is facilitated by the Sec61 translocon. Here, we use a photocross-linking approach to examine integration intermediates derived from the ATP-binding cassette transporter cystic fibrosis transmembrane conductance regulator (CFTR) and show that the timing of translocon-mediated integration can be regulated at specific stages of synthesis. During CFTR biogenesis, the eighth TM segment exits the ribosome and enters the translocon in proximity to Sec61α. This interaction is initially weak, and TM8 spontaneously dissociates from the translocon when the nascent chain is released from the ribosome. Polypeptide extension by only a few residues, however, results in stable TM8-Sec61α photocross-links that persist after peptidyl-tRNA bond cleavage. Retention of these untethered polypeptides within the translocon requires ribosome binding and is mediated by an acidic residue, Asp924, near the center of the putative TM8 helix. Remarkably, at this stage of synthesis, nascent chain release from the translocon is also strongly inhibited by ATP depletion. These findings contrast with passive partitioning models and indicate that Sec61α can retain TMs and actively inhibit membrane integration in a sequence-specific and ATP-dependent manner.
The role of predator selection on polymorphic aposematic poison frogs
Authors: Noonan Brice P , Comeault Aaron A
Published: November 2008

Demonstrations of interactions between diverse selective forces on bright coloration in defended species are rare. Recent work has suggested that not only do the bright colours of Neotropical poison frogs serve to deter predators, but they also play a role in sexual selection, with females preferring males similar to themselves. These studies report an interaction between the selective forces of mate choice and predation. However, evidence demonstrating phenotypic discrimination by potential predators on these polymorphic species is lacking. The possibility remains that visual (avian) predators possess an inherent avoidance of brightly coloured diurnal anurans and purifying selection against novel phenotypes within populations is due solely to non-random mating. Here, we examine the influence of predation on phenotypic variation in a polymorphic species of poison frog,Dendrobates tinctorius. Using clay models, we demonstrate a purifying role for predator selection, as brightly coloured novel forms are more likely to suffer an attack than both local aposematic and cryptic forms. Additionally, local aposematic forms are attacked, though infrequently, indicating ongoing testing/learning and a lack of innate avoidance. These results demonstrate predator-driven phenotypic purification within populations and suggest colour patterns of poison frogs may truly represent a ‘magic trait’.
Effect of the initial dose of foot-and-mouth disease virus on the early viral dynamics within pigs
Authors: Howey Richard , Quan Melvyn , Savill Nicholas J. , Matthews Louise , Alexandersen Søren , Woolhouse Mark
Published: November 2008

This paper investigates the early viral dynamics of foot-and-mouth disease (FMD) within infected pigs. Using an existing within-host model, we investigate whether individual variation can be explained by the effect of the initial dose of FMD virus. To do this, we consider the experimental data on the concentration of FMD virus genomes in the blood (viral load). In this experiment, 12 pigs were inoculated with one of three different doses of FMD virus: low; medium; or high. Measurements of the viral load were recorded over a time course of approximately 11 days for every 8 hours. The model is a set of deterministic differential equations with the following variables: viral load; virus in the interstitial space; and the proportion of epithelial cells available for infection, infected and uninfected. The model was fitted to the data for each animal individually and also simultaneously over all animals varying only the initial dose. We show that the general trend in the data can be explained by varying only the initial dose. The higher the initial dose the earlier the development of a detectable viral load.
Overcoming the order barrier in the numerical approximation of stochastic partial differential equations with additive space–time noise
Authors: Jentzen Arnulf , Kloeden Peter E
Published: November 2008

We consider the numerical approximation of parabolic stochastic partial differential equations driven by additive space–time white noise. We introduce a new numerical scheme for the time discretization of the finite-dimensional Galerkin stochastic differential equations, which we call the exponential Euler scheme, and show that it converges (in the strong sense) faster than the classical numerical schemes, such as the linear-implicit Euler scheme or the Crank–Nicholson scheme, for this equation with the general noise. In particular, we prove that our scheme applied to a semilinear stochastic heat equation converges with an overall computational order 1/3 which exceeds the barrier order 1/6 for numerical schemes using only basic increments of the noise process reported previously. By contrast, our scheme takes advantage of the smoothening effect of the Laplace operator and of a linear functional of the noise and, therefore overcomes this order barrier.
Energy of tsunami waves generated by bottom motion
Authors: Dutykh Denys , Dias Frédéric
Published: November 2008

In the vast literature on tsunami research, few articles have been devoted to energy issues. A theoretical investigation on the energy of waves generated by bottom motion is performed here. We start with the full incompressible Euler equations in the presence of a free surface and derive both dispersive and non-dispersive shallow-water equations with an energy equation. It is shown that dispersive effects appear only at higher order in the energy budget. Then we solve the Cauchy–Poisson problem of tsunami generation for the linearized water-wave equations. Exchanges between potential and kinetic energies are clearly revealed.
The strength of a female mate preference increases with predation risk
Authors: Kim Tae Won , Christy John H , Dennenmoser Stefan , Choe Jae C
Published: November 2008

When females search for mates and their perceived risk of predation increases, they less often express preferences for males that use conspicuous courtship signals, relaxing sexual selection on production of these signals. Here, we report an apparent exception to this general pattern. Courting male fiddler crabs
Uca beebei
sometimes build pillars of mud at the openings to their burrows in which crabs mate. Females visit several males before they choose a mate by staying and breeding in their burrows, and they preferentially visit males with pillars. Previous studies suggested that this preference is based on a visual orientation behaviour that may reduce females' risk of predation while searching for a mate. We tested this idea by determining whether the female preference for males with pillars increases with perceived predation risk. We attracted avian predators to where crabs were courting and measured the rates that sexually receptive females visited courting males with and without mud pillars. Under elevated risk, females continued to search for mates and they showed a stronger relative preference for males with pillars. Thus, when predation risk is high, females may continue to express preferences that are under natural selection because they help females avoid predation, strengthening sexual selection for use of the preferred signal.
Relict or colonizer? Extinction and range expansion of penguins in southern New Zealand
Authors: Boessenkool Sanne , Austin Jeremy J , Worthy Trevor H , Scofield Paul , Cooper Alan , Seddon Philip J , Waters Jonathan M
Published: November 2008

Recent human expansion into the Pacific initiated a dramatic avian extinction crisis, and surviving taxa are typically interpreted as declining remnants of previously abundant populations. As a case in point, New Zealand's endangered yellow-eyed penguin (
Megadyptes antipodes
) is widely considered to have been more abundant and widespread in the past. By contrast, our genetic and morphological analyses of prehistoric, historic and modern penguin samples reveal that this species expanded its range to the New Zealand mainland only in the last few hundred years. This range expansion was apparently facilitated by the extinction of
M. antipodes
' previously unrecognized sister species following Polynesian settlement in New Zealand. Based on combined genetic and morphological data, we describe this new penguin species, the first known to have suffered human-mediated extinction. The range expansion of
M. antipodes
so soon after the extinction of its sister species supports a historic paradigmatic shift in New Zealand Polynesian culture. Additionally, such a dynamic biological response to human predation reveals a surprising and less recognized potential for species to have benefited from the extinction of their ecologically similar sister taxa and highlights the complexity of large-scale extinction events.
Warning displays may function as honest signals of toxicity
Authors: Blount Jonathan D , Speed Michael P , Ruxton Graeme D , Stephens Philip A
Published: November 2008

Many prey species use colourful ‘aposematic’ signalling to advertise the fact that they are toxic. Some recent studies have shown that the brightness of aposematic displays correlates positively with the strength of toxicity, suggesting that aposematic displays are a form of handicap signal, the conspicuousness of which reliably indicates the level of toxicity. The theoretical consensus in the literature is, however, at odds with this finding. It is commonly assumed that the most toxic prey should have less bright advertisements because they have better chances of surviving attacks and can therefore reduce the costs incurred by signalling. Using a novel theoretical model, we show that aposematic signals can indeed function as handicaps. To generate this prediction, we make a key assumption that the expression of bright displays and the storage of anti-predator toxins compete for resources within prey individuals. One shared currency is energy. However, competition for antioxidant molecules, which serve dual roles as pigments and in protecting prey against oxidative stress when they accumulate toxins, provides a specific candidate resource that could explain signal honesty. Thus, contrary to the prevailing theoretical orthodoxy, warning displays may in fact be honest signals of the level of (rather than simply the existence of) toxicity.
Outline and surface disruption in animal camouflage
Authors: Stevens Martin , Winney Isabel S , Cantor Abi , Graham Julia
Published: November 2008

Camouflage is an important strategy in animals to prevent predation. This includes disruptive coloration, where high-contrast markings placed at an animal's edge break up the true body shape. Successful disruption may also involve non-marginal markings found away from the body outline that create ‘false edges’ more salient than the true body form (‘surface disruption’). However, previous work has focused on breaking up the true body outline, not on surface disruption. Furthermore, while high contrast may enhance disruption, it is untested where on the body different contrasts should be placed for maximum effect. We used artificial prey presented to wild avian predators in the field, to determine the effectiveness of surface disruption, and of different luminance contrast placed in different prey locations. Disruptive coloration was no more effective when comprising high luminance contrastper se, but its effectiveness was dramatically increased with high-contrast markings placed away from the body outline, creating effective surface disruption. A model of avian visual edge processing showed that surface disruption does not make object detection more difficult simply by creating false edges away from the true body outline, but its effect may also be based on a different visual mechanism. Our study has implications for whether animals can combine disruptive coloration with other ‘conspicuous’ signalling strategies.
Marine mammals through time: when less is more in studying palaeodiversity
Authors: Marx Felix G
Published: November 2008

The validity of biological explanations of patterns of palaeodiversity has been called into question owing to an apparent correlation of diversity with the amount of sedimentary rock preserved. However, this claim has largely been based on comprehensive estimates of global marine Phanerozoic diversity, thus raising the question of whether a similar bias applies to the records of smaller, well-defined taxonomic groups. Here, new data on European Caenozoic marine sedimentary rock outcrop area are presented and compared with European occurrences of three groups of marine mammals (cetaceans, pinnipedimorphs and sirenians). Limited evidence was found for a correlation of outcrop area with marine mammal palaeodiversity. In addition, similar patterns were identified in the cetacean and pinnipedimorph diversity data. This may point to the preservation of a genuine biological signal not overwhelmed by geological biases in the marine mammal diversity data, and opens the door to further analyses of both marine mammal evolution and geological bias in other small and well-defined groups of taxa.
On the relationship between farmland biodiversity and land-use intensity in Europe
Authors: Kleijn D , Kohler F , Báldi A , Batáry P , Concepción E.D , Clough Y , Díaz M , Gabriel D , Holzschuh A , Knop E , Kovács A , Marshall E.J.P , Tscharntke T , Verhulst J
Published: November 2008

Worldwide agriculture is one of the main drivers of biodiversity decline. Effective conservation strategies depend on the type of relationship between biodiversity and land-use intensity, but to date the shape of this relationship is unknown. We linked plant species richness with nitrogen (N) input as an indicator of land-use intensity on 130 grasslands and 141 arable fields in six European countries. Using Poisson regression, we found that plant species richness was significantly negatively related to N input on both field types after the effects of confounding environmental factors had been accounted for. Subsequent analyses showed that exponentially declining relationships provided a better fit than linear or unimodal relationships and that this was largely the result of the response of rare species (relative cover less than 1%). Our results indicate that conservation benefits are disproportionally more costly on high-intensity than on low-intensity farmland. For example, reducing N inputs from 75 to 0 and 400 to 60 kg ha
−1
 yr
−1
resulted in about the same estimated species gain for arable plants. Conservation initiatives are most (cost-)effective if they are preferentially implemented in extensively farmed areas that still support high levels of biodiversity.
Composition and chemistry of Titan's stratosphere
Authors: Bézard Bruno
Published: November 2008

Our present knowledge of the composition and chemistry of Titan's stratosphere is reviewed. Thermal measurements by the Cassini spacecraft show that the mixing ratios of all photochemical species, except ethylene, increase with altitude at equatorial and southern latitudes, reflecting transport from a high-altitude source to a condensation sink in the lower stratosphere. Most compounds are enriched at latitudes northward of 45° N, a consequence of subsidence in the winter polar vortex. This enrichment is much stronger for nitriles and complex hydrocarbons than for ethane and acetylene. Titan's chemistry originates from breakdown of methane due to photodissociation in the upper atmosphere and catalytical reactions in the stratosphere, and from destruction of nitrogen both by UV photons and electrons. Photochemistry also produces haze particles made of complex refractory material, albeit at a lower rate than ethane, the most abundant gas product. Haze characteristics (vertical distribution, physical and spectral properties) inferred by several instruments aboard Cassini/Huygens are discussed here.
The origin of Titan's atmosphere: some recent advances
Authors: Owen Tobias , Niemann H.B
Published: November 2008

It is possible to make a consistent story for the origin of Titan's atmosphere starting with the birth of Titan in the Saturn subnebula. If we use comet nuclei as a model, Titan's nitrogen and methane could have easily been delivered by the ice that makes up approximately 50 per cent of its mass. If Titan's atmospheric hydrogen is derived from that ice, it is possible that Titan and comet nuclei are in fact made of the same protosolar ice. The noble gas abundances are consistent with relative abundances found in the atmospheres of Mars and Earth, the Sun, and the meteorites.
Angiopoietin‐1 alters tumor growth by stabilizing blood vessels or by promoting angiogenesis
Authors: Satoh Naoyuki , Yamada Yoshihiro , Kinugasa Yumi , Takakura Nobuyuki
Published: November 2008

The maturation of blood vessels requires mural cell adhesion to endothelial cells. Angiopoietin‐1 (Ang1), a ligand for Tie2 receptor expressed on endothelial cells, plays a critical role in cell adhesion between mural cells and endothelial cells and in endothelial cell sprouting from preexisting vessels in the absence of mural cells. Much information has been amassed on the Tie2–Ang1 system in physiological blood vessel formation during embryogenesis; however, the role of Ang1 in the tumor environment and its interaction with mural cells has not been well documented. Here we studied how Ang1 regulates maturation of blood vessels using the human colon cancer cell line HT29 and the human prostate cancer cell line PC3, and studied how Ang1 affects tumor growth. In a xenograft tumor model using female nude mice, we found that Ang1 enhanced angiogenesis and resulted in tumor growth in the case of PC3 tumors but suppressed tumor growth in the case of HT29 tumors. In PC3 tumors, the number of mural cells adhering to endothelial cells was less than that in HT29 tumors. Ang1 induced sprouting angiogenesis in PC3 tumors although there was little maturation of blood vessels. On the other hand, there was abundant mural cell adhesion to endothelial cells in HT29 tumors and Ang1 did not induce angiogenesis. These results suggest that Ang1 alters tumor growth in a manner that is dependent on the adhesion of mural cells and their localization in the tumor environment. (Cancer Sci 2008; 99: 2373–2379)
Differential effector mechanisms induced by vaccination with MUC1 DNA in the rejection of colon carcinoma growth at orthotopic sites and metastases
Authors: Sugiura Daisuke , Aida Satoshi , Denda‐Nagai Kaori , Takeda Kazuyoshi , Kamata‐Sakurai Mika , Yagita Hideo , Irimura Tatsuro
Published: November 2008

The effects of MUC1 DNA vaccination on the orthotopic growth and liver metastasis of colon carcinoma cells were investigated in mice. Vaccination with MUC1 DNA resulted in immune responses that were effective in suppressing mouse colon carcinoma cells transfected with MUC1 cDNA. CD4+ T cells but not CD8+ T cells mediated this antitumor response as shown by the in vivo depletion of lymphocyte subpopulations with the use of anti‐CD4 or anti‐CD8 antibody. The effects of neutralizing antibodies in vivo revealed that the predominant effector molecule in preventing orthotopic tumor growth was FasL, whereas the effector molecule effective in preventing liver metastasis was tumor necrosis factor‐α. Colon carcinoma cells isolated from tumors growing in the ceca, spleens, and livers were shown to be equally sensitive to FasL and tumor necrosis factor‐α. The results strongly suggest that elimination of tumor cells initiated by DNA vaccination in the present protocol is mediated by antigen‐specific CD4+ T cells and the effector mechanisms in the cecum and in the liver are distinct due to a unique organ microenvironment. (Cancer Sci 2008; 99: 2477–2484)
Interferon‐α enhances CD317 expression and the antitumor activity of anti‐CD317 monoclonal antibody in renal cell carcinoma xenograft models
Authors: Kawai Shigeto , Azuma Yumiko , Fujii Etsuko , Furugaki Kou , Ozaki Shuji , Matsumoto Toshio , Kosaka Masaaki , Yamada‐Okabe Hisafumi
Published: November 2008

A murine (mAHM) and a humanized (AHM) monoclonal antibody against CD317 (also called tetherin, BST2, or HM1.24 antigen), expressed preferentially in neoplastic B cells such as multiple myeloma, exhibited antitumor effects as a result of antibody‐dependent cellular cytotoxicity (ADCC). The putative interferon (IFN) response elements IRF‐1/2 and ISGF3 are present in the promoter of the CD317 gene, and IFN has been used for the treatment of not only myeloproliferative diseases but also solid tumors such as renal cell carcinoma (RCC) and melanoma. Therefore, we examined the effects of IFN on the expression of CD317 and on the antitumor activity of AHM and mAHM in RCC and melanoma. Flow cytometry and in vitro ADCC assays with human or mouse effector cells demonstrated that IFN‐α markedly increased the amount of cell surface CD317 and augmented the ADCC activity of mAHM and AHM in RCC cells and to a lesser extent in melanoma cells. Administration of IFN‐α to mice bearing RCC xenografts also increased the expression of CD317 in tumor cells. When coadministered with IFN‐α, mAHM exhibited more profound antitumor activity in both IFN‐α‐sensitive and ‐insensitive RCC xenograft models. Thus, AHM in combination with IFN‐α may be an effective therapy for the treatment of RCC. (Cancer Sci 2008; 99: 2461–2466)