bluuebunny/crossref_metadata_2025 huggingface dataset:
Extrahelical (CAG)/(CTG) triplet repeat elements support proliferating cell nuclear antigen loading and MutLα endonuclease activation
Authors: Pluciennik Anna , Burdett Vickers , Baitinger Celia , Iyer Ravi R. , Shi Kevin , Modrich Paul
Published: July 2013

MutLα endonuclease can be activated on covalently continuous DNA that contains a MutSα- or MutSβ-recognizable lesion and a helix perturbation that supports proliferating cell nuclear antigen (PCNA) loading by replication factor C, providing a potential mechanism for triggering mismatch repair on nonreplicating DNA. Because mouse models for somatic expansion of disease-associated (CAG)
n
/(CTG)
n
triplet repeat sequences have implicated both MutSβ and MutLα and have suggested that expansions can occur in the absence of replication, we have asked whether an extrahelical (CAG)
n
or (CTG)
n
element is sufficient to trigger MutLα activation. (CAG)
n
and (CTG)
n
extrusions in relaxed closed circular DNA do in fact support MutSβ-, replication factor C-, and PCNA-dependent activation of MutLα endonuclease, which can incise either DNA strand. Extrahelical elements of two or three repeat units are the preferred substrates for MutLα activation, and extrusions of this size also serve as moderately effective sites for loading the PCNA clamp. Relaxed heteroduplex DNA containing a two or three-repeat unit extrusion also triggers MutSβ- and MutLα-endonuclease-dependent mismatch repair in nuclear extracts of human cells. This reaction occurs without obvious strand bias at about 10% the rate of that observed with otherwise identical nicked heteroduplex DNA. These findings provide a mechanism for initiation of triplet repeat processing in nonreplicating DNA that is consistent with several features of the model of Gomes-Pereira et al. [Gomes-Pereira M, Fortune MT, Ingram L, McAbney JP, Monckton DG (2004)
Hum Mol Genet
13(16):1815–1825]. They may also have implications for triplet repeat processing at a replication fork.
Normally hyperbolic invariant manifolds for random dynamical systems: Part I - persistence
Authors: Li Ji , Lu Kening , Bates Peter
Published: July 2013

In this paper, we prove the persistence of smooth normally hyperbolic invariant manifolds for dynamical systems under random perturbations.
BioSmalltalk: a pure object system and library for bioinformatics
Authors: Morales Hernán F. , Giovambattista Guillermo
Published: July 2013

Summary: We have developed BioSmalltalk, a new environment system for pure object-oriented bioinformatics programming. Adaptive end-user programming systems tend to become more important for discovering biological knowledge, as is demonstrated by the emergence of open-source programming toolkits for bioinformatics in the past years. Our software is intended to bridge the gap between bioscientists and rapid software prototyping while preserving the possibility of scaling to whole-system biology applications. BioSmalltalk performs better in terms of execution time and memory usage than Biopython and BioPerl for some classical situations.

Availability: BioSmalltalk is cross-platform and freely available (MIT license) through the Google Project Hosting at http://code.google.com/p/biosmalltalk

Contact:  hernan.morales@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Dabigatran compared with warfarin in patients with atrial fibrillation and symptomatic heart failure: a subgroup analysis of the RE‐LY trial
Authors: Ferreira Jorge , Ezekowitz Michael D. , Connolly Stuart J. , Brueckmann Martina , Fraessdorf Mandy , Reilly Paul A. , Yusuf Salim , Wallentin Lars ,   on behalf of the RE‐LY Investigators
Published: July 2013

Aims

We evaluated the effects of dabigatran compared with warfarin in the subgroup of patients with previous symptomatic heart failure (HF) in the RE‐LY trial.

Methods and results

RE‐LY compared two fixed and blinded doses of dabigatran (110 and 150 mg twice daily) with open‐label warfarin in 18 113 patients with AF at increased risk for stroke. Among 4904 patients with HF, annual rates of stroke or systemic embolism (SE) were 1.92% for patients on warfarin compared with 1.90% for dabigatran 110 mg [hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.69–1.42] and 1.44% for dabigatran 150 mg (HR 0.75, 95% CI 0.51–1.10). Annual rates of major bleeding were 3.90% for the group on warfarin, compared with 3.26% for dabigatran 110 mg (HR 0.83, 95% CI 0.64–1.09) and 3.10% for dabigatran 150 mg (HR 0.79, 95% CI 0.60–1.03). Rates of intracranial bleeding were significantly lower for both dabigatran dosages compared with warfarin in patients with HF (dabigatran 110 mg vs. warfarin, HR 0.34, 95% CI 0.14–0.80; dabigatran 150 mg vs. warfarin, HR 0.39, 95% CI 0.17–0.89). The relative effects of dabigatran vs. warfarin on the occurrence of stroke or SE and major bleeding were consistent among those with and without HF and those with low (≤40%) or preserved (>40%) LVEF (P interaction not significant).

Conclusions

The overall benefits of dabigatran for stroke/SE prevention, and major and intracranial bleeding, relative to warfarin in the RE‐LY trial were consistent in patients with and without HF.
Did massive black holes in globular clusters initially satisfy galactic scaling relations?
Authors: Kruijssen J. M. Diederik , Lützgendorf Nora
Published: July 2013

The masses of supermassive black holes (SMBHs, MBH = 106–1011 M⊙) in the centres of galaxies are related to the host stellar spheroid mass and velocity dispersion. A key question is how these relations originate, and over which range of black hole masses they hold. It has been speculated that intermediate-mass black holes (IMBHs, MBH = 102–105 M⊙) could play a fundamental role in the growth of SMBHs. A handful of IMBHs have recently been detected in Galactic globular clusters (GCs), but their masses are inconsistent with the galactic scaling relations of SMBHs. In this Letter, we derive the initial properties of the GCs using a standard analytical evolutionary model, of which the free parameters are fixed by independent constraints. We find that the observed IMBH masses initially followed the galactic SMBH scaling relations and subsequently moved off these relations due to the dynamical evolution of their host GCs. This work is concluded with a brief discussion of the uncertainties and the implications of our results for the possible universality of massive black hole growth.
How well do we know the halo mass function?
Authors: Murray S. G. , Power C. , Robotham A. S. G.
Published: July 2013

The parameters governing the standard Λ cold dark matter cosmological model have been constrained with unprecedented accuracy by precise measurements of the cosmic microwave background by the Wilkinson Microwave Anisotropy Probe (WMAP) and Planck satellites. Each new data release has refined further our knowledge of quantities – such as the matter density parameter ΩM – that are imprinted on the dark matter halo mass function (HMF), a powerful probe of dark matter and dark energy models. In this Letter, we trace how changes in the cosmological parameters over the last decade have influenced uncertainty in our knowledge of the HMF. We show that this uncertainty has reduced significantly since the third WMAP data release, but the rate of this reduction is slowing. This is limited by uncertainty in the normalization σ8, whose influence is most pronounced at the high-mass end of the mass function. Interestingly, we find that the accuracy with which we can constrain the HMF in terms of the cosmological parameters has now reached the point at which it is comparable to the scatter in HMF fitting functions. This suggests that the power of the HMF as a precision probe of dark matter and dark energy hinges on more accurate determination of the theoretical HMF. Finally, we assess prospects of using the HMF to differentiate between cold and warm dark matter models based on ongoing improvements in measurements of ΩM, and we comment briefly on optimal survey strategies for constraining dark matter and dark energy models using the HMF.
Identification of Resistance to Maize rayado fino virus in Maize Inbred Lines
Authors: Zambrano Jose Luis , Francis David M. , Redinbaugh Margaret G.
Published: July 2013

Maize rayado fino virus (MRFV) causes one of the most important virus diseases of maize in America. Severe yield losses, ranging from 10 to 50% in landraces to nearly 100% in contemporary cultivars, have been reported. Resistance has been reported in maize populations, but few resistant inbred lines have been identified. Maize inbred lines representing the range of diversity in the cultivated types and selected lines known to be resistant to other viruses were evaluated to identify novel sources of resistance to MRFV. The virus was transmitted to maize seedlings using the vector Dalbulus maidis, and disease incidence and severity were evaluated beginning 7 days postinoculation. Most of the 36 lines tested were susceptible to MRFV, with mean disease incidence ranging from 21 to 96%, and severity from 1.0 to 4.3 (using a 0 to 5 severity scale). A few genotypes, including CML333 and Ki11, showed intermediate levels of resistance, with 14 and 10% incidence, respectively. Novel sources of resistance, with incidence of less than 5% and severity ratings of 0.4 or less, included the inbred lines Oh1VI, CML287, and Cuba. In Oh1VI, resistance appeared to be dominant, and segregation of resistance in F2 plants was consistent with one or two resistance genes. The discovery of novel sources of resistance in maize inbred lines will facilitate the identification of virus resistance genes and their incorporation into breeding programs.
Abiotic Stresses Affect Trichoderma harzianum T39-Induced Resistance to Downy Mildew in Grapevine
Authors: Roatti Benedetta , Perazzolli Michele , Gessler Cesare , Pertot Ilaria
Published: July 2013

Enhancement of plant defense through the application of resistance inducers seems a promising alternative to chemical fungicides for controlling crop diseases but the efficacy can be affected by abiotic factors in the field. Plants respond to abiotic stresses with hormonal signals that may interfere with the mechanisms of induced systemic resistance (ISR) to pathogens. In this study, we exposed grapevines to heat, drought, or both to investigate the effects of abiotic stresses on grapevine resistance induced by Trichoderma harzianum T39 (T39) to downy mildew. Whereas the efficacy of T39-induced resistance was not affected by exposure to heat or drought, it was significantly reduced by combined abiotic stresses. Decrease of leaf water potential and upregulation of heat-stress markers confirmed that plants reacted to abiotic stresses. Basal expression of defense-related genes and their upregulation during T39-induced resistance were attenuated by abiotic stresses, in agreement with the reduced efficacy of T39. The evidence reported here suggests that exposure of crops to abiotic stress should be carefully considered to optimize the use of resistance inducers, especially in view of future global climate changes. Expression analysis of ISR marker genes could be helpful to identify when plants are responding to abiotic stresses, in order to optimize treatments with resistance inducers in field.
Expression of taste signal transduction molecules in the caecum of common marmosets
Authors: Gonda Sae , Matsumura Shuichi , Saito Shoichiro , Go Yasuhiro , Imai Hiroo
Published: July 2013

The extraoral presence of taste signal transduction proteins has recently been reported in rodents and humans. Here, we report for the first time the presence of these signal transduction proteins in the caecum of a non-human primate, the common marmoset. Quantitative RT-PCR data on the gene expression of taste signal transduction molecules (gustducin and TRPM5) in common marmosets suggested high expression in the caecum, which was not observed in other non-human primates. Immunohistochemical analysis confirmed the specific presence of gustducin and taste receptors in marmoset caecal cells. These results may relate to the specific feeding behaviour of marmosets, which consume plant exudates, primarily gums.
Collision-based mechanics of bipedal hopping
Authors: Gutmann Anne K. , Lee David V. , McGowan Craig P.
Published: July 2013

The muscle work required to sustain steady-speed locomotion depends largely upon the mechanical energy needed to redirect the centre of mass and the degree to which this energy can be stored and returned elastically. Previous studies have found that large bipedal hoppers can elastically store and return a large fraction of the energy required to hop, whereas small bipedal hoppers can only elastically store and return a relatively small fraction. Here, we consider the extent to which large and small bipedal hoppers (tammar wallabies, approx. 7 kg, and desert kangaroo rats, approx. 0.1 kg) reduce the mechanical energy needed to redirect the centre of mass by reducing collisions. We hypothesize that kangaroo rats will reduce collisions to a greater extent than wallabies since kangaroo rats cannot elastically store and return as high a fraction of the mechanical energy of hopping as wallabies. We find that kangaroo rats use a significantly smaller collision angle than wallabies by employing ground reaction force vectors that are more vertical and center of mass velocity vectors that are more horizontal and thereby reduce their mechanical cost of transport. A collision-based approach paired with tendon morphometry may reveal this effect more generally among bipedal runners and quadrupedal trotters.
Higher rate of tissue regeneration in polyploid asexual versus diploid sexual freshwater snails
Authors: Krois Nicole R. , Cherukuri Anvesh , Puttagunta Nikhil , Neiman Maurine
Published: July 2013

Characterizing phenotypic differences between sexual and asexual organisms is a critical step towards understanding why sexual reproduction is so common. Because asexuals are often polyploid, understanding how ploidy influences phenotype is directly relevant to the study of sex and will provide key insights into the evolution of ploidy-level variation. The well-established association between genome size and cell cycle duration, evidence for a link between genome size and tissue regeneration rate and the growing body of research showing that ploidy influences growth rate and gene expression led us to hypothesize that healing and tissue regeneration might be affected by ploidy-level variation. We evaluated this hypothesis by measuring the rate of regeneration of antenna tissue ofPotamopyrgus antipodarum, a New Zealand snail characterized by frequent coexistence between diploid sexuals and polyploid asexuals. Antennae of triploid and presumptive tetraploid asexuals regenerated more rapidly than the antennae of diploid sexuals, but regeneration rate did not differ between triploids and tetraploids. These results suggest either that ploidy elevation has nonlinear positive effects on tissue regeneration and/or that factors associated directly with reproductive mode affect regeneration rate more than ploidy level. The results of this study also indicate that the lower ploidy of sexualP. antipodarumis unlikely to confer advantages associated with more rapid regeneration.
Stable isotope canopy effects for sympatric monkeys at Taï Forest, Côte d'Ivoire
Authors: Krigbaum John , Berger Michael H. , Daegling David J. , McGraw W. Scott
Published: July 2013

This study tests the hypothesis that vertical habitat preferences of different monkey species inhabiting closed canopy rainforest are reflected in oxygen isotopes. We sampled bone from seven sympatric cercopithecid species in the Taï forest, Côte d'Ivoire, where long-term study has established taxon-specific patterns of habitat use and diet. Modern rib samples (
n
= 34) were examined for oxygen (
δ
18
O
ap
) and carbon (
δ
13
C
ap
) from bone apatite (‘bioapatite’), and carbon (
δ
13
C
co
) and nitrogen (
δ
15
N
co
) from bone collagen. Results are consistent for C
3
feeders in a closed canopy habitat. Low irradiance and evapotranspiration, coupled with high relative humidity and recycled CO
2
in forest understory, contribute to observed isotopic variability. Both
δ
13
C
co
and
δ
13
C
ap
results reflect diet; however,
δ
13
C values are not correlated with species preference for canopy height. By contrast,
δ
18
O
ap
results are correlated with mean observed height and show significant vertical partitioning between taxa feeding at ground, lower and upper canopy levels. This oxygen isotope canopy effect has important palaeobiological implications for reconstructing vertical partitioning among sympatric primates and other species in tropical forests.
Porous convection with local thermal non-equilibrium temperatures and with Cattaneo effects in the solid
Authors: Straughan B.
Published: July 2013

There is increasing interest in convection in local thermal non-equilibrium (LTNE) porous media. This is where the solid skeleton and the fluid may have different temperatures. There is also increasing interest in thermal wave motion, especially at the microscale and nanoscale, and particularly in solids. Much of this work has been based on the famous model proposed by Carlo Cattaneo in 1948. In this paper, we develop a model for thermal convection in a fluid-saturated Darcy porous medium allowing the solid and fluid parts to be at different temperatures. However, we base our thermodynamics for the fluid on Fourier's law of heat conduction, whereas we allow the solid skeleton to transfer heat by means of the Cattaneo heat flux theory. This leads to a novel system of partial differential equations involving Darcy's law, a parabolic fluid temperature equation and effectively a hyperbolic solid skeleton temperature equation. This system leads to novel physics, and oscillatory convection is found, whereas for the standard LTNE Darcy model, this does not exist. We are also able to derive a rigorous nonlinear global stability theory, unlike work in thermal convection in other second sound systems in porous media.
Age-dependent female responses to a male ejaculate signal alter demographic opportunities for selection
Authors: Fricke Claudia , Green Darrell , Mills Walter E. , Chapman Tracey
Published: July 2013

A central tenet of evolutionary explanations for ageing is that the strength of selection wanes with age. However, data on age-specific expression and benefits of sexually selected traits are lacking—particularly for traits subject to sexual conflict. We addressed this by using as a model the responses ofDrosophila melanogasterfemales of different ages to receipt of sex peptide (SP), a seminal fluid protein transferred with sperm during mating. SP can mediate sexual conflict, benefitting males while causing fitness costs in females. Virgin and mated females of all ages showed significantly reduced receptivity in response to SP. However, only young virgin females also showed increased egg laying; hence, there was a narrow demographic window of maximal responses to SP. Males gained significant ‘per mating’ fitness benefits only when mating with young females. The pattern completely reversed in matings with older females, where SP transfer was costly. The overall benefits of SP transfer (hence opportunity for selection) therefore reversed with female age. The data reveal a new example of demographic variation in the strength of selection, with convergence and conflicts of interest between males and ageing females occurring over different facets of responses to a sexually antagonistic trait.
Habitat filtering across tree life stages in tropical forest communities
Authors: Baldeck C. A. , Harms K. E. , Yavitt J. B. , John R. , Turner B. L. , Valencia R. , Navarrete H. , Bunyavejchewin S. , Kiratiprayoon S. , Yaacob A. , Supardi M. N. N. , Davies S. J. , Hubbell S. P. , Chuyong G. B. , Kenfack D. , Thomas D. W. , Dalling J. W.
Published: July 2013

Tropical tree communities are shaped by local-scale habitat heterogeneity in the form of topographic and edaphic variation, but the life-history stage at which habitat associations develop remains poorly understood. This is due, in part, to the fact that previous studies have not accounted for the widely disparate sample sizes (number of stems) that result when trees are divided into size classes. We demonstrate that the observed habitat structuring of a community is directly related to the number of individuals in the community. We then compare the relative importance of habitat heterogeneity to tree community structure for saplings, juveniles and adult trees within seven large (24–50 ha) tropical forest dynamics plots while controlling for sample size. Changes in habitat structuring through tree life stages were small and inconsistent among life stages and study sites. Where found, these differences were an order of magnitude smaller than the findings of previous studies that did not control for sample size. Moreover, community structure and composition were very similar among tree sub-communities of different life stages. We conclude that the structure of these tropical tree communities is established by the time trees are large enough to be included in the census (1 cm diameter at breast height), which indicates that habitat filtering occurs during earlier life stages.
The length–tension curve in muscle depends on lattice spacing
Authors: Williams C. David , Salcedo Mary K. , Irving Thomas C. , Regnier Michael , Daniel Thomas L.
Published: July 2013

Classic interpretations of the striated muscle length–tension curve focus on how force varies with overlap of thin (actin) and thick (myosin) filaments. New models of sarcomere geometry and experiments with skinned synchronous insect flight muscle suggest that changes in the radial distance between the actin and myosin filaments, the filament lattice spacing, are responsible for between 20% and 50% of the change in force seen between sarcomere lengths of 1.4 and 3.4 µm. Thus, lattice spacing is a significant force regulator, increasing the slope of muscle's force–length dependence.
Multiple host transfers, but only one successful lineage in a continent-spanning emergent pathogen
Authors: Hochachka Wesley M. , Dhondt André A. , Dobson Andrew , Hawley Dana M. , Ley David H. , Lovette Irby J.
Published: July 2013

Emergence of a new disease in a novel host is thought to be a rare outcome following frequent pathogen transfers between host species. However, few opportunities exist to examine whether disease emergence stems from a single successful pathogen transfer, and whether this successful lineage represents only one of several pathogen transfers between hosts. We examined the successful host transfer and subsequent evolution of the bacterial pathogen
Mycoplasma gallisepticum
, an emergent pathogen of house finches (
Haemorhous
(formerly
Carpodacus
)
mexicanus
). Our principal goals were to assess whether host transfer has been a repeated event between the original poultry hosts and house finches, whether only a single host transfer was ultimately responsible for the emergence of
M. gallisepticum
in these finches, and whether the spread of the pathogen from east to west across North America has resulted in spatial structuring in the pathogen. Using a phylogeny of
M. gallisepticum
based on 107 isolates from domestic poultry, house finches and other songbirds, we infer that the bacterium has repeatedly jumped between these two groups of hosts but with only a single lineage of
M. gallisepticum
persisting and evolving in house finches; bacterial evolution has produced monophyletic eastern and western North American subclades.
Diversification rates have declined in the Malagasy herpetofauna
Authors: Scantlebury Daniel P.
Published: July 2013

The evolutionary origins of Madagascar's biodiversity remain mysterious despite the fact that relative to land area, there is no other place with consistently high levels of species richness and endemism across a range of taxonomic levels. Most efforts to explain diversification on the island have focused on geographical models of speciation, but recent studies have begun to address the island's accumulation of species through time, although with conflicting results. Prevailing hypotheses for diversification on the island involve either constant diversification rates or scenarios where rates decline through time. Using relative-time-calibrated phylogenies for seven endemic vertebrate clades and a model-fitting framework, I find evidence that diversification rates have declined through time on Madagascar. I show that diversification rates have clearly declined throughout the history of each clade, and models invoking diversity-dependent reductions to diversification rates best explain the diversification histories for each clade. These results are consistent with the ecological theory of adaptive radiation, and, coupled with ancillary observations about ecomorphological and life-history evolution, strongly suggest that adaptive radiation was an important formative process for one of the most species-rich regions on the Earth. These results cast the Malagasy biota in a new light and provide macroevolutionary justification for conservation initiatives.
Bigger mothers are better mothers: disentangling size-related prenatal and postnatal maternal effects
Authors: Steiger Sandra
Published: July 2013

Despite a vast literature on the factors controlling adult size, few studies have investigated how maternal size affects offspring size independent of direct genetic effects, thereby separating prenatal from postnatal influences. I used a novel experimental design that combined a cross-fostering approach with phenotypic manipulation of maternal body size that allowed me to disentangle prenatal and postnatal maternal effects. Using the burying beetleNicrophorus vespilloidesas model organism, I found that a mother's body size affected egg size as well as the quality of postnatal maternal care, with larger mothers producing larger eggs and raising larger offspring than smaller females. However, with respect to the relative importance of prenatal and postnatal maternal effects on offspring growth, only the postnatal effects were important in determining offspring body size. Thus, prenatal effects can be offset by the quality of postnatal maternal care. This finding has implications for the coevolution of prenatal and postnatal maternal effects as they arise as a consequence of maternal body size. In general, my study provides evidence that there can be transgenerational phenotypic plasticity, with maternal size determining offspring size leading to a resemblance between mothers and their offspring above and beyond any direct genetic effects.
Do pathogens become more virulent as they spread? Evidence from the amphibian declines in Central America
Authors: Phillips Ben L. , Puschendorf Robert
Published: July 2013

The virulence of a pathogen can vary strongly through time. While cyclical variation in virulence is regularly observed, directional shifts in virulence are less commonly observed and are typically associated with decreasing virulence of biological control agents through coevolution. It is increasingly appreciated, however, that spatial effects can lead to evolutionary trajectories that differ from standard expectations. One such possibility is that, as a pathogen spreads through a naive host population, its virulence increases on the invasion front. In Central America, there is compelling evidence for the recent spread of pathogenicBatrachochytrium dendrobatidis(Bd) and for its strong impact on amphibian populations. Here, we re-examine data on Bd prevalence and amphibian population decline across 13 sites from southern Mexico through Central America, and show that, in the initial phases of the Bd invasion, amphibian population decline lagged approximately 9 years behind the arrival of the pathogen, but that this lag diminished markedly over time. In total, our analysis suggests an increase in Bd virulence as it spread southwards, a pattern consistent with rapid evolution of increased virulence on Bd's invading front. The impact of Bd on amphibians might therefore be driven by rapid evolution in addition to more proximate environmental drivers.
Indirect genetic effects: an evolutionary mechanism linking feedbacks, genotypic diversity and coadaptation in a climate change context
Authors: Bailey Joseph K. , Genung Mark A. , Ware Ian , Gorman Courtney , Van Nuland Michael E. , Long Hannah , Schweitzer Jennifer A.
Published: July 2013

Predicting the response of communities and ecosystems to range shifts as a consequence of global climate change is a critical challenge confronting modern evolutionary ecologists.

Indirect genetic effects (IGEs) occur when the expression of genes in a conspecific neighbouring species affects the phenotype of a focal species, and the same concept applies for interspecific indirect genetic effects (IIGEs) except that the neighbouring species is then required to be heterospecific.

Theory and empirical data indicate that indirect genetic effects and interspecific indirect genetic effects have fundamental roles in understanding the consequences of genotypic diversity, evolutionary feedbacks, the co‐evolutionary process and coadaptation and are a primary mechanism for the broad ecological and evolutionary dynamics that are likely to be a consequence of climate change.

When indirect genetic effects and interspecific indirect genetic effects occur along environmental gradients, both positive and negative feedbacks can evolve, resulting in regions of strong local adaptation and competition as well as regions of complementarity and facilitation. Such evolutionary dynamics have direct consequences for how individuals interact and evolve in mixture and drive the services ecosystems provide.

Integrating indirect genetic effects and interspecific indirect genetic effects, feedbacks and diversity effects along environmental gradients represents a major conceptual, theoretical and empirical frontier that must be considered to understand the whole‐system consequences of climate change on biodiversity and the services ecosystems provide.
Hot tadpoles from cold environments need more nutrients – life history and stoichiometry reflects latitudinal adaptation
Authors: Liess Antonia , Rowe Owen , Guo Junwen , Thomsson Gustaf , Lind Martin I.
Published: July 2013

High‐latitude species (and populations within species) are adapted to short and cold summers. They often have high growth and development rates to fully use the short growing season and mature before the onset of winter.

Within the context of ecological stoichiometry theory, this study combines ecology with evolution by relating latitudinal life‐history adaptations to their molecular consequences in body nutrient composition in Rana temporaria tadpoles.

Temperature and food quality were manipulated during the development of tadpoles from Arctic and Boreal origins. We determined tadpole growth rate, development rate, body size and nutrient content, to test whether (i) Arctic tadpoles could realize higher growth rates and development rates with the help of higher‐quality food even when food quantity was unchanged, (ii) Arctic and Boreal tadpoles differed in their stoichiometric (and life history) response to temperature changes, (iii) higher growth rates lead to higher tadpole P content (growth rate hypothesis) and (iv) allometric scaling affects tadpole nutrient allocation.

We found that especially Arctic tadpoles grew and developed faster with the help of higher‐quality food and that tadpoles differed in their stoichiometric (and life history) response to temperature changes depending on region of origin (probably due to different temperature optima). There was no evidence that higher growth rates mediated the positive effect of temperature on tadpole P content. On the contrary, the covariate growth rate was negatively connected with tadpole P content (refuting the growth rate hypothesis). Lastly, tadpole P content was not related to body size, but tadpole C content was higher in larger tadpoles, probably due to increased fat storage.

We conclude that temperature had a strong effect on tadpole life history, nutrient demand and stoichiometry and that this effect depended on the evolved life history.
High‐definition magnifying endoscopy with i‐scan in the diagnosis of Helicobacter pylori infection: A pilot study
Authors: Qi Qing Qing , Zuo Xiu Li , Li Chang Qing , Ji Rui , Li Zhen , Zhou Cheng Jun , Li Yan Qing
Published: July 2013

Objective

This study aimed to compare the diagnostic value and image quality of high‐definition magnifying white light endoscopy (M‐WLE) and high‐definition magnifying endoscopy with i‐scan (M‐i‐scan) for Helicobacter pylori (H. pylori) infection.

Methods

Patients complaining of dyspepsia who underwent esophagogastroduodenoscopy at the Endoscopy Unit of Qilu Hospital (Jinan, Shandong Province, China) from January to March, 2011 were prospectively recruited. The greater curvature of the stomach was carefully observed using both M‐WLE and M‐i‐scan. The gastric mucosal classification and image quality scores were recorded. The relationship between gastric mucosal classification and final diagnosis of H. pylori infection was determined.

Results

A total of 84 patients were recruited in this study. The accuracy and specificity of the combination of types 2–3 patterns predicting H. pylori infection were significantly higher for M‐i‐scan than those for M‐WLE (accuracy: 94.0% vs 84.5%, P = 0.046; and specificity: 93.5% vs 80.6%, P = 0.032), while the sensitivity of the two modes was the same. The M‐i‐scan provided a better image quality for H. pylori infection than M‐WLE (P < 0.001).

Conclusion

The M‐i‐scan may be superior to M‐WLE for the prediction of H. pylori infection, but its diagnostic sensitivity needs to be improved.
Revised radiobiological modelling of the contribution of synchronous chemotherapy to the rate of grades 3–4 mucositis in head and neck cancer
Authors: Meade Sara , McConkey Chris , Sanghera Paul , Mehanna Hisham , Hartley Andrew
Published: July 2013

Introduction

Biological effective dose (BED) calculations modelled on reduced accelerated repopulation when synchronous chemotherapy is delivered significantly correlate with observed differences in local control in randomised trials of platinum‐based chemoradiation. The purpose of this study was to examine whether a similar relationship existed in the context of grades 3–4 mucositis.

Methods

Biological effective dose from radiotherapy and synchronous chemotherapy was calculated using three different models: AB using the additional BED attributable to chemotherapy and standard repopulation parameters; zero repopulation (ZRP) using zero correction for repopulation; and variable tp (Vtp) using a variable doubling time for mucosal stem cell repopulation. The correlation between the percentage change in biological effective dose between trial arms, and the observed percentage change in the rate of grades 3–4 mucositis was examined by using the Pearson product–moment correlation.

Results

With the AB model, there were no significant correlations with observed differences in rates of grades 3–4 mucositis. With either the ZRP or Vtp models, significant correlations were observed. A value of 5 days for the doubling time during repopulation (Tp) was associated with the most significant correlation (P = 0.002).

Conclusion

Models where the dose lost due to accelerated repopulation is reduced imply a therapeutic loss from the use of synchronous chemotherapy when only local control and the rate of acute grades 3–4 mucositis are considered.
Safety, Tolerability, and Efficacy of Overnight Switching From Sildenafil to Tadalafil in Patients With Pulmonary Arterial Hypertension
Authors: Shapiro Shelley , Traiger Glenna , Hill Wendy , Zhang Lixia , Doran Aimee K.
Published: July 2013

Aims

Tadalafil, a once‐daily phosphodiesterase type 5 inhibitor (PDE‐5I), offers clinicians an alternative to sildenafil, a 3‐times‐daily (t.i.d.) PDE‐5I for treatment of pulmonary arterial hypertension (PAH). However, there are limited data describing the risks and benefits or recommended methodology of switching patients from sildenafil to tadalafil.

Methods

Chart reviews were conducted on all World Health Organization group 1 patients on sildenafil for ≥3 months who transitioned to tadalafil with documented clinic visits and 6‐min walk tests on both drugs. Most patients were transitioned by discontinuing sildenafil after the evening dose and initiating tadalafil 40 mg/day the next day. Data collected included demographics, PAH etiology, diagnostic hemodynamics, 6‐min walk distance (6MWD), PDE‐5I side effects, and concomitant medications. Data on B‐type natriuretic peptide (BNP) levels were available for most patients also receiving endothelin receptor antagonists (ERAs).

Results

Medical records from 98 patients were evaluated. Most patients (92%) were on sildenafil for >1 year, and 78% were receiving sildenafil 80–100 mg t.i.d. Ninety‐seven percent of patients (95/98) were successfully transitioned and maintained on 40 mg/day. With a mean duration on tadalafil therapy of 243 ± 127 days at the time of analysis, 6MWD was unchanged. Patient‐reported adverse events included headache (4%) and heartburn (2%). There was minimal change in BNP levels in the subset of patients receiving an ERA concomitantly.

Conclusions

Transition from sildenafil to tadalafil 40 mg/day appears feasible without clinical deterioration or intolerable side effects. This study provides guidance to physicians considering transition from sildenafil to tadalafil for selecting patients.
Pyridoxamine Reverts Methylglyoxal‐induced Impairment of Survival Pathways During Heart Ischemia
Authors: Almeida Filipa , Santos‐Silva Daniela , Rodrigues Tiago , Matafome Paulo , Crisóstomo Joana , Sena Cristina , Gonçalves Lino , Seiça Raquel
Published: July 2013

Background and aims

Increased levels of advanced glycation end‐products (AGE) and their precursors, such as methylglyoxal (MG), in patients with diabetes may account for impaired response to heart ischemia. Pyridoxamine is a derivate of vitamin B6, which has been shown to reduce AGE formation. Our goal was to assess the role of pyridoxamine in protecting from MG‐induced impaired heart response to ischemia.

Methods

Wistar rats were subjected to MG administration (WM), MG plus pyridoxamine (WMPyr), or no treatment (W). Half of the hearts from each group were submitted to ischemia and the other half were perfused as control. The levels of CEL, Bcl‐2, Bax, and total and phosphorylated forms of JNK and Akt were determined.

Results

Methylglyoxal led to higher levels of AGE and AGE receptor (RAGE) than in the W group. During ischemia, MG caused an impairment of survival pathways and Bcl‐2/Bax ratio, a marker of apoptosis. Pyridoxamine treatment decreased glycation and restored the activation of JNK and Akt during ischemia. These events were followed by levels of Bcl‐2/Bax ratio similar to W group.

Conclusion

Methylglyoxal‐induced AGE accumulation impairs the activation of cell survival pathways during ischemia. Pyridoxamine‐induced decrease of glycation inhibited the effects of MG accumulation in the heart, suggesting that it can be of added value to usual diabetic therapy.
Ecological prophets: quantifying metapopulation portfolio effects
Authors: Anderson Sean C. , Cooper Andrew B. , Dulvy Nicholas K.
Published: July 2013

A financial portfolio metaphor is often used to describe how population diversity can increase temporal stability of a group of populations. The portfolio effect (PE) refers to the stabilizing effect from a population acting as a group or ‘portfolio’ of diverse subpopulations instead of a single homogeneous population or ‘asset’. A widely used measure of the PE (the average‐CV PE) implicitly assumes that the slope (z) of a log–log plot of mean temporal abundance and variance (Taylor's power law) equals two.

Existing theory suggests an additional unexplored empirical PE that accounts for z, the mean–variance PE. We use a theoretical and empirical approach to explore the strength and drivers of the PE for metapopulations when we account for Taylor's power law compared with when we do not. Our empirical comparison uses data from 51 metapopulations and 1070 subpopulations across salmon, moths and reef fishes.

Ignoring Taylor's power law may overestimate the stabilizing effect of population diversity for metapopulations. The disparity between the metrics is greatest at low z values where the average‐CV PE indicates a strong PE. Compared with the mean–variance method, the average‐CV PE estimated a stronger PE in 84% of metapopulations by up to sevenfold. The divergence between the methods was strongest for reef fishes (1·0 < z < 1·7) followed by moths (1·5 < z < 1·9). The PEs were comparable for salmon where z ≈ 2.

We outline practical recommendations for estimating ecological PEs based on research questions, study systems and available data. Because most PEs were stabilizing and diversity can be slow to restore, our meta‐analysis of metapopulations suggests that the safest management approach is to conserve biological complexity.
Stochastic search item selection for factor analytic models
Authors: Mavridis Dimitris , Ntzoufras Ioannis
Published: July 2013

In this paper we implement a Markov chain Monte Carlo algorithm based on the stochastic search variable selection method of George and McCulloch (1993) for identifying promising subsets of manifest variables (items) for factor analysis models. The suggested algorithm is constructed by embedding in the usual factor analysis model a normal mixture prior for the model loadings with latent indicators used to identify not only which manifest variables should be included in the model but also how each manifest variable is associated with each factor. We further extend the suggested algorithm to allow for factor selection. We also develop a detailed procedure for the specification of the prior parameters values based on the practical significance of factor loadings using ideas from the original work of George and McCulloch (1993). A straightforward Gibbs sampler is used to simulate from the joint posterior distribution of all unknown parameters and the subset of variables with the highest posterior probability is selected. The proposed method is illustrated using real and simulated data sets.
BCL2A1 is a Potential Biomarker for Postoperative Seizure Control in Patients with Low‐grade Gliomas
Authors: You Gan , Feng Lin , Yan Wei , Zhang Wei , Wang Yong‐Zhi , Li Shao‐Wu , Li Shou‐Wei , Li Gui‐Lin , Song Yi‐Jun , Kang Chun‐Sheng , You Yong‐Ping , Jiang Tao
Published: July 2013

Aims

To identify molecular genetic factors that influence preoperative seizure occurrence and postoperative seizure control in patients with low‐grade gliomas (LGGs).

Methods

Fifty‐four WHO grade II astrocytomas were used for microarray analysis under strict inclusion criteria. The primary endpoint was seizure control at 12 months after surgery. Biological processes were investigated by gene ontology (GO) analysis. Quantitative RT‐PCR and immunohistochemistry were used to validate key genes.

Results

Differentially expressed genes correlated with seizure occurrence failed to significantly distinguish patients with and without a history of seizures. With respect to postoperative seizure control, a transcript profile of 92 genes was identified, which successfully separated patients with good and poor seizure prognosis. GO analysis revealed that the most striking overrepresentation of genes was found in a category of anti‐apoptotic genes and their regulation. Increased expression was also observed for genes involved in immune and inflammatory responses. BCL2A1 was proven to be a novel marker associated with seizure prognosis.

Conclusion

Increased anti‐apoptotic activity of tumor cells appears to contribute to seizure recurrence after surgery in patients with LGGs. These findings provide insights that may lead to the development of effective treatment strategies for prolonging the survival of patients with LGG in the future.
Non‐invasive assessment of liver fibrosis using magnetic resonance elastography in liver transplant recipients with hepatitis C
Authors: Crespo Sergio , Bridges Mellena , Nakhleh Raouf , McPhail Andre , Pungpapong Surakit , Keaveny Andrew P.
Published: July 2013

Background

Liver biopsy has been the reference standard when evaluating fibrosis due to recurrent hepatitis after liver transplantation. Magnetic resonance elastography estimates liver stiffness, correlating to fibrosis.

Aim

To investigate the utility of elastography in staging liver fibrosis in transplant recipients with hepatitis C.

Methods

Fifty‐four patients, ≥12 months post‐transplant, underwent elastography within three months of biopsy. Discriminatory capability for METAVIR fibrosis stages F0–2 vs. F3–4 and receiver operating characteristic curve (ROC) analysis were determined.

Results

On biopsy, 27 patients had METAVIR fibrosis score 0–1; 12 had a 3 or 4. There was significant correlation between histologic fibrosis and shear stiffness (R² = 0.588, p < 0.0001). Using a cutoff value of 3.5 kPa, elastography was 91% sensitive and 72% specific in differentiating fibrosis scores of ≥3 from 0 to 1. The AUC of elastography in predicting a fibrosis score of ≥3 was 0.92. Multivariate analysis revealed no correlation between the grade of histologic inflammation and liver stiffness measured by magnetic resonance elastography (R² = 0.265, p = 0.47).

Conclusion

Magnetic resonance elastography is an accurate non‐invasive technique for excluding stage ≥3 graft in recipients with hepatitis C.
Theory of mind in early psychosis
Authors: Langdon Robyn , Still Megan , Connors Michael H. , Ward Philip B. , Catts Stanley V.
Published: July 2013

Aim

A deficit in theory of mind – the ability to infer and reason about the mental states of others – might underpin the poor social functioning of patients with psychosis. Unfortunately, however, there is considerable variation in how such a deficit is assessed. The current study compared three classic tests of theory of mind in terms of their ability to detect impairment in patients in the early stages of psychosis.

Methods

Twenty‐three patients within 2 years of their first psychotic episode and 19 healthy controls received picture‐sequencing, joke‐appreciation and story‐comprehension tests of theory of mind.

Results

Whereas the picture‐sequencing and joke‐appreciation tests successfully detected a selective theory‐of‐mind deficit in patients, the story‐comprehension test did not.

Conclusions

The findings suggest that tests that place minimal demands on language processing and involve indirect, rather than explicit, instructions to assess theory of mind might be best suited to detecting theory‐of‐mind impairment in early stages of psychosis.