bluuebunny/crossref_metadata_2025 huggingface dataset:
Etoposide Induces the Dispersal of DNA Ligase I from Replication Factories
Authors: Montecucco Alessandra , Rossi Rossella , Ferrari Giovanni , Scovassi A. Ivana , Prosperi Ennio , Biamonti Giuseppe
Published: July 2013

In eukaryotic cells DNA replication occurs in specific nuclear compartments, called replication factories, that undergo complex rearrangements during S-phase. The molecular mechanisms underlying the dynamics of replication factories are still poorly defined. Here we show that etoposide, an anticancer drug that induces double-strand breaks, triggers the redistribution of DNA ligase I and proliferating cell nuclear antigen from replicative patterns and the ensuing dephosphorylation of DNA ligase I. Moreover, etoposide triggers the formation of RPA foci, distinct from replication factories. The effect of etoposide on DNA ligase I localization is prevented by aphidicolin, an inhibitor of DNA replication, and by staurosporine, a protein kinase inhibitor and checkpoints' abrogator. We suggest that dispersal of DNA ligase I is triggered by an intra-S-phase checkpoint activated when replicative forks meet topoisomerase II-DNA–cleavable complexes. However, etoposide treatment of ataxia telangiectasia cells demonstrated that ataxia-telangiectasia-mutated activity is not required for the disassembly of replication factories and the formation of replication protein A foci.
Activation of RhoA and ROCK Are Essential for Detachment of Migrating Leukocytes
Authors: Alblas Jacqueline , Ulfman Laurien , Hordijk Peter , Koenderman Leo
Published: July 2013

Detachment of the rear of the cell from its substratum is an important aspect of locomotion. The signaling routes involved in this adhesive release are largely unknown. One of the few candidate proteins to play a role is RhoA, because activation of RhoA in many cell types leads to contraction, a mechanism probably involved in detachment. To study the role of RhoA in detachment regulation, we analyzed several subsets of expert migratory leukocytes by video microscopy. In contrast to fast-migrating neutrophils, eosinophils do not detach the rear of the cell unless stimulated with serum. When measuring the amount of active RhoA, with the use of a GST-Rhotekin pulldown assay, we found that serum is an excellent activator of RhoA in granulocytes. Inhibition of RhoA or one of Rho's target proteins, the kinase ROCK, in neutrophils leads to the phenotype seen in eosinophils: the rear of the cell is firmly attached to the substratum, whereas the cell body is highly motile. ROCK-inhibition leads to impaired migration of granulocytes in filters, on glass, and through endothelial monolayers. Also, the ROCK signaling pathway is involved in changes of integrin-mediated adhesion. Eosinophil transduction by a tat-fusion construct containing active RhoA resulted in detachment stimulation in the presence of chemoattractant. From these results we conclude that activation of the RhoA-ROCK pathway is essential for detachment of migratory leukocytes.
Werner's Syndrome Protein Is Required for Correct Recovery after Replication Arrest and DNA Damage Induced in S-Phase of Cell Cycle
Authors: Pichierri Pietro , Franchitto Annapaola , Mosesso Pasquale , Palitti Fabrizio
Published: July 2013

Werner's syndrome (WS) is a rare autosomal recessive disorder that arises as a consequence of mutations in a gene coding for a protein that is a member of RecQ family of DNA helicases, WRN. The cellular function of WRN is still unclear, but on the basis of the cellular phenotypes of WS and of RecQ yeast mutants, its possible role in controlling recombination and/or in maintenance of genomic integrity during S-phase has been envisaged. With the use of two drugs, camptothecin and hydroxyurea, which produce replication-associated DNA damage and/or inhibit replication fork progression, we find that WS cells have a slower rate of repair associated with DNA damage induced in the S-phase and a reduced induction of RAD51 foci. As a consequence, WS cells undergo apoptotic cell death more than normal cells, even if they arrest and resume DNA synthesis at an apparently normal rate. Furthermore, we report that WS cells show a higher background level of DNA strand breaks and an elevated spontaneous induction of RAD51 foci. Our findings support the hypothesis that WRN could be involved in the correct resolution of recombinational intermediates that arise from replication arrest due to either DNA damage or replication fork collapse.
Conditional Mutations in γ-Tubulin Reveal Its Involvement in Chromosome Segregation and Cytokinesis
Authors: Hendrickson Triscia W. , Yao Joyce , Bhadury Saswata , Corbett Anita H. , Joshi Harish C.
Published: July 2013

γ-Tubulin is a conserved essential protein required for assembly and function of the mitotic spindle in humans and yeast. For example, human γ-tubulin can replace the γ-tubulin gene inSchizosaccharomyces pombe. To understand the structural/functional domains of γ-tubulin, we performed a systematic alanine-scanning mutagenesis of human γ-tubulin (TUBG1) and studied phenotypes of each mutant allele inS. pombe. Our screen, both in the presence and absence of the endogenous S. pombe γ-tubulin, resulted in 11 lethal mutations and 12 cold-sensitive mutations. Based on structural mapping onto a homology model of human γ-tubulin generated by free energy minimization, all deleterious mutations are found in residues predicted to be located on the surface, some in positions to interact with α- and/or β-tubulins in the microtubule lattice. As expected, one class of tubg1 mutations has either an abnormal assembly or loss of the mitotic spindle. Surprisingly, a subset of mutants with abnormal spindles does not arrest in M phase but proceeds through anaphase followed by abnormal cytokinesis. These studies reveal that in addition to its previously appreciated role in spindle microtubule nucleation, γ-tubulin is involved in the coordination of postmetaphase events, anaphase, and cytokinesis.
Polyubiquitination Is Required for US11-dependent Movement of MHC Class I Heavy Chain from Endoplasmic Reticulum into Cytosol
Authors: Shamu Caroline E. , Flierman Dennis , Ploegh Hidde L. , Rapoport Tom A. , Chau Vincent
Published: July 2013

The human cytomegalovirus protein US11 induces the dislocation of MHC class I heavy chains from the endoplasmic reticulum (ER) into the cytosol for degradation by the proteasome. With the use of a fractionated, permeabilized cell system, we find that US11 activity is needed only in the cell membranes and that additional cytosolic factors are required for heavy chain dislocation. We identify ubiquitin as one of the required cytosolic factors. Cytosol depleted of ubiquitin does not support heavy chain dislocation from the ER, and activity can be restored by adding back purified ubiquitin. Methylated-ubiquitin or a ubiquitin mutant lacking all lysine residues does not substitute for wild-type ubiquitin, suggesting that polyubiquitination is required for US11-dependent dislocation. We propose a new function for ubiquitin in which polyubiquitination prevents the lumenal domain of the MHC class I heavy chain from moving back into the ER lumen. A similar mechanism may be operating in the dislocation of misfolded proteins from the ER in the cellular quality control pathway.
Cyclin B/cdc2 Induces c-Mos Stability by Direct Phosphorylation inXenopusOocytes
Authors: Castro Anna , Peter Marion , Magnaghi-Jaulin Laura , Vigneron Suzanne , Galas Simon , Lorca Thierry , Labbé Jean-Claude
Published: July 2013

The c-Mos proto-oncogene product plays an essential role during meiotic divisions in vertebrate eggs. In Xenopus, it is required for progression of oocyte maturation and meiotic arrest of unfertilized eggs. Its degradation after fertilization is essential to early embryogenesis. In this study we investigated the mechanisms involved in c-Mos degradation. We present in vivo evidence for ubiquitin-dependent degradation of c-Mos in activated eggs. We found that c-Mos degradation is not directly dependent on the anaphase-promoting factor activator Fizzy/cdc20 but requires cyclin degradation. We demonstrate that cyclin B/cdc2 controls in vivo c-Mos phosphorylation and stabilization. Moreover, we show that cyclin B/cdc2 is capable of directly phosphorylating c-Mos in vitro, inducing a similar mobility shift to the one observed in vivo. Tryptic phosphopeptide analysis revealed a practically identical in vivo and in vitro phosphopeptide map and allowed identification of serine-3 as the largely preferential phosphorylation site as previously described ( Freeman et al., 1992 ). Altogether, these results demonstrate that, in vivo, stability of c-Mos is directly regulated by cyclin B/cdc2 kinase activity.
The Domain Structure of Centromeres Is Conserved from Fission Yeast to Humans
Authors: Kniola Barbara , O'Toole Eileen , McIntosh J. Richard , Mellone Barbara , Allshire Robin , Mengarelli Silwa , Hultenby Kjell , Ekwall Karl
Published: July 2013

The centromeric DNA of fission yeast is arranged with a central core flanked by repeated sequences. The centromere-associated proteins, Mis6p and Cnp1p (SpCENP-A), associate exclusively with central core DNA, whereas the Swi6 protein binds the surrounding repeats. Here, electron microscopy and immunofluorescence light microscopy reveal that the central core and flanking regions occupy distinct positions within a heterochromatic domain. An “anchor” structure containing the Ndc80 protein resides between this heterochromatic domain and the spindle pole body. The organization of centromere-associated proteins in fission yeast is reminiscent of the multilayered structures of human kinetochores, indicating that such domain structure is conserved in eukaryotes.
Mediation of Elicitin Activity on Tobacco Is Assumed by Elicitin-Sterol Complexes
Authors: Osman Hanan , Vauthrin Sébastien , Mikes Vladimir , Milat Marie-Louise , Panabières Franck , Marais Antoine , Brunie Simone , Maume Bernard , Ponchet Michel , Blein Jean-Pierre
Published: July 2013

Elicitins secreted by phytopathogenic Phytophthoraspp. are proteinaceous elicitors of plant defense mechanisms and were demonstrated to load, carry, and transfer sterols between membranes. The link between elicitor and sterol-loading properties was assessed with the use of site-directed mutagenesis of the 47 and 87 cryptogein tyrosine residues, postulated to be involved in sterol binding. Mutated cryptogeins were tested for their ability to load sterols, bind to plasma membrane putative receptors, and trigger biological responses. For each mutated elicitin, the chemical characterization of the corresponding complexes with stigmasterol (1:1 stoichiometry) demonstrated their full functionality. However, these proteins were strongly altered in their sterol-loading efficiency, specific binding to high-affinity sites, and activities on tobacco cells. Ligand replacement experiments strongly suggest that the formation of a sterol-elicitin complex is a requisite step before elicitins fasten to specific binding sites. This was confirmed with the use of two sterol-preloaded elicitins. Both more rapidly displaced labeled cryptogein from its specific binding sites than the unloaded proteins. Moreover, the binding kinetics of elicitins are related to their biological effects, which constitutes the first evidence that binding sites could be the biological receptors. The first event involved in elicitin-mediated cell responses is proposed to be the protein loading with a sterol molecule.
Lnetwork: an efficient and effective method for constructing phylogenetic networks
Authors: Wang Juan , Guo Maozu , Liu Xiaoyan , Liu Yang , Wang Chunyu , Xing Linlin , Che Kai
Published: June 2013

Motivation: The evolutionary history of species is traditionally represented with a rooted phylogenetic tree. Each tree comprises a set of clusters, i.e. subsets of the species that are descended from a common ancestor. When rooted phylogenetic trees are built from several different datasets (e.g. from different genes), the clusters are often conflicting. These conflicting clusters cannot be expressed as a simple phylogenetic tree; however, they can be expressed in a phylogenetic network. Phylogenetic networks are a generalization of phylogenetic trees that can account for processes such as hybridization, horizontal gene transfer and recombination, which are difficult to represent in standard tree-like models of evolutionary histories. There is currently a large body of research aimed at developing appropriate methods for constructing phylogenetic networks from cluster sets. The Cass algorithm can construct a much simpler network than other available methods, but is extremely slow for large datasets or for datasets that need lots of reticulate nodes. The networks constructed by Cass are also greatly dependent on the order of input data, i.e. it generally derives different phylogenetic networks for the same dataset when different input orders are used.

Results: In this study, we introduce an improved Cass algorithm, Lnetwork, which can construct a phylogenetic network for a given set of clusters. We show that Lnetwork is significantly faster than Cass and effectively weakens the influence of input data order. Moreover, we show that Lnetwork can construct a much simpler network than most of the other available methods.

Availability: Lnetwork has been built as a Java software package and is freely available at http://nclab.hit.edu.cn/∼wangjuan/Lnetwork/.

Contact:  maozuguo@hit.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
The signal within the noise: efficient inference of stochastic gene regulation models using fluorescence histograms and stochastic simulations
Authors: Lillacci Gabriele , Khammash Mustafa
Published: July 2013

Motivation: In the noisy cellular environment, stochastic fluctuations at the molecular level manifest as cell–cell variability at the population level that is quantifiable using high-throughput single-cell measurements. Such variability is rich with information about the cell’s underlying gene regulatory networks, their architecture and the parameters of the biochemical reactions at their core.

Results: We report a novel method, called Inference for Networks of Stochastic Interactions among Genes using High-Throughput data (INSIGHT), for systematically combining high-throughput time-course flow cytometry measurements with computer-generated stochastic simulations of candidate gene network models to infer the network’s stochastic model and all its parameters. By exploiting the mathematical relationships between experimental and simulated population histograms, INSIGHT achieves scalability, efficiency and accuracy while entirely avoiding approximate stochastic methods. We demonstrate our method on a synthetic gene network in bacteria and show that a detailed mechanistic model of this network can be estimated with high accuracy and high efficiency. Our method is completely general and can be used to infer models of signal-activated gene networks in any organism based solely on flow cytometry data and stochastic simulations.

Availability: A free C source code implementing the INSIGHT algorithm, together with test data is available from the authors.

Contact: mustafa.khammash@bsse.ethz.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
Hawkmoths produce anti-bat ultrasound
Authors: Barber Jesse R. , Kawahara Akito Y.
Published: July 2013

Bats and moths have been engaged in aerial warfare for nearly 65 Myr. This arms race has produced a suite of counter-adaptations in moths, including bat-detecting ears. One set of defensive strategies involves the active production of sound; tiger moths' ultrasonic replies to bat attack have been shown to startle bats, warn the predators of bad taste and jam their biosonar. Here, we report that hawkmoths in the Choerocampina produce entirely ultrasonic sounds in response to tactile stimulation and the playback of biosonar attack sequences. Males do so by grating modified scraper scales on the outer surface of the genital valves against the inner margin of the last abdominal tergum. Preliminary data indicate that females also produce ultrasound to touch and playback of echolocation attack, but they do so with an entirely different mechanism. The anti-bat function of these sounds is unknown but might include startling, cross-family acoustic mimicry, warning of unprofitability or physical defence and/or jamming of echolocation. Hawkmoths present a novel and tractable system to study both the function and evolution of anti-bat defences.
Constraints on muscle performance provide a novel explanation for the scaling of posture in terrestrial animals
Authors: Usherwood James R.
Published: July 2013

Larger terrestrial animals tend to support their weight with more upright limbs. This makes structural sense, reducing the loading on muscles and bones, which is disproportionately challenging in larger animals. However, it does not account for why smaller animals are more crouched; instead, they could enjoy relatively more slender supporting structures or higher safety factors. Here, an alternative account for the scaling of posture is proposed, with close parallels to the scaling of jump performance. If the costs of locomotion are related to the volume of active muscle, and the active muscle volume required depends on both the work and the power demanded during the push-off phase of each step (not just the net positive work), then the disproportional scaling of requirements for work and push-off power are revealing. Larger animals require relatively greater active muscle volumes for dynamically similar gaits (e.g. top walking speed)—which may present an ultimate constraint to the size of running animals. Further, just as for jumping, animals with shorter legs and briefer push-off periods are challenged to provide the power (not the work) required for push-off. This can be ameliorated by having relatively long push-off periods, potentially accounting for the crouched stance of small animals.
Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza andStreptococcus pneumoniae
Authors: Shrestha Sourya , Foxman Betsy , Dawid Suzanne , Aiello Allison E. , Davis Brian M. , Berus Joshua , Rohani Pejman
Published: July 2013

A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with bothStreptococcus pneumoniaeandStaphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus andS. pneumoniaein the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness.
Rogue waves: analytical predictions
Authors: Grimshaw R. H. J. , Tovbis A.
Published: July 2013

Rogue waves observed in the ocean and elsewhere are often modelled by certain solutions of the nonlinear Schrodinger equation, describing the modulational instability of a plane wave and the subsequent development of multi-phase nonlinear wavetrains. In this paper, we describe how integrability and application of the inverse scattering transform can be used to construct a class of explicit asymptotic solutions that describe this process. We discuss the universal mechanism of the onset of multi-phase nonlinear waves (rogue waves) through the sequence of successive multi-breather wavetrains. Some applications to ocean waves and laboratory experiments are presented.
The Oxford Questions on the foundations of quantum physics
Authors: Briggs G. A. D. , Butterfield J. N. , Zeilinger A.
Published: July 2013

The twentieth century saw two fundamental revolutions in physics—relativity and quantum. Daily use of these theories can numb the sense of wonder at their immense empirical success. Does their instrumental effectiveness stand on the rock of secure concepts or the sand of unresolved fundamentals? Does measuring a quantum system probe, or even create, reality or merely change belief? Must relativity and quantum theory just coexist or might we find a new theory which unifies the two? To bring such questions into sharper focus, we convened a conference on Quantum Physics and the Nature of Reality. Some issues remain as controversial as ever, but some are being nudged by theory's secret weapon of experiment.
Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value
Authors: Bloch Guy , Barnes Brian M. , Gerkema Menno P. , Helm Barbara
Published: July 2013

Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles.
Parallel changes in genital morphology delineate cryptic diversification of planktonic nudibranchs
Authors: Churchill Celia K. C. , Alejandrino Alvin , Valdés Ángel , Ó Foighil Diarmaid
Published: July 2013

The relative roles of geographical and non-geographical barriers in the genesis of genetic isolation are highly debated in evolutionary biology, yet knowing how speciation occurs is essential to our understanding of biodiversity. In the open ocean, differentiating between the two is particularly difficult, because of the high levels of gene flow found in pelagic communities. Here, we use molecular phylogenetics to test the hypothesis that geography is the primary isolating mechanism in a clade of pelagic nudibranchs, Glaucinae. Our results contradict allopatric expectations: the cosmopolitanGlaucus atlanticusis panmictic, whereas the Indo-PacificGlaucus marginatuscontains two pairs of cryptic species with overlapping distributions. Within theG. marginatusspecies complex, a parallel reproductive change has occurred in each cryptic species pair: the loss of a bursa copulatrix. AvailableG. marginatusdata are most consistent with non-geographical speciation events, but we cannot rule out the possibility of allopatric speciation, followed by iterative range extension and secondary overlap. Irrespective of ancestral range distributions, our results implicate a central role for reproductive character differentiation in glaucinin speciation—a novel result in a planktonic system.
ATR acts stage specifically to regulate multiple aspects of mammalian meiotic silencing
Authors: Royo Hélène , Prosser Haydn , Ruzankina Yaroslava , Mahadevaiah Shantha K. , Cloutier Jeffrey M. , Baumann Marek , Fukuda Tomoyuki , Höög Christer , Tóth Attila , de Rooij Dirk G. , Bradley Allan , Brown Eric J. , Turner James M.A.
Published: July 2013

In mammals, homologs that fail to synapse during meiosis are transcriptionally inactivated. This process, meiotic silencing, drives inactivation of the heterologous XY bivalent in male germ cells (meiotic sex chromosome inactivation [MSCI]) and is thought to act as a meiotic surveillance mechanism. The checkpoint protein ATM and Rad3-related (ATR) localizes to unsynapsed chromosomes, but its role in the initiation and maintenance of meiotic silencing is unknown. Here we show that ATR has multiple roles in silencing. ATR first regulates HORMA (Hop1, Rev7, and Mad2) domain protein HORMAD1/2 phosphorylation and localization of breast cancer I (BRCA1) and ATR cofactors ATR-interacting peptide (ATRIP)/topoisomerase 2-binding protein 1 (TOPBP1) at unsynapsed axes. Later, it acts as an adaptor, transducing signaling at unsynapsed axes into surrounding chromatin in a manner that requires interdependence with mediator of DNA damage checkpoint 1 (MDC1) and H2AFX. Finally, ATR catalyzes histone H2AFX phosphorylation, the epigenetic event leading to gene inactivation. Using a novel genetic strategy in which MSCI is used to silence a chosen gene in pachytene, we show that ATR depletion does not disrupt the maintenance of silencing and that silencing comprises two phases: The first is dynamic and reversible, and the second is stable and irreversible. Our work identifies a role for ATR in the epigenetic regulation of gene expression and presents a new technique for ablating gene function in the germline.
Autophagy suppresses progression of K-ras-induced lung tumors to oncocytomas and maintains lipid homeostasis
Authors: Guo Jessie Yanxiang , Karsli-Uzunbas Gizem , Mathew Robin , Aisner Seena C. , Kamphorst Jurre J. , Strohecker Anne M. , Chen Guanghua , Price Sandy , Lu Wenyun , Teng Xin , Snyder Eric , Santanam Urmila , DiPaola Robert S. , Jacks Tyler , Rabinowitz Joshua D. , White Eileen
Published: July 2013

Macroautophagy (autophagy hereafter) degrades and recycles proteins and organelles to support metabolism and survival in starvation. Oncogenic Ras up-regulates autophagy, and Ras-transformed cell lines require autophagy for mitochondrial function, stress survival, and engrafted tumor growth. Here, the essential autophagy gene autophagy-related-7 (atg7) was deleted concurrently with K-rasG12D activation in mouse models for non-small-cell lung cancer (NSCLC). atg7-deficient tumors accumulated dysfunctional mitochondria and prematurely induced p53 and proliferative arrest, which reduced tumor burden that was partly relieved by p53 deletion. atg7 loss altered tumor fate from adenomas and carcinomas to oncocytomas—rare, predominantly benign tumors characterized by the accumulation of defective mitochondria. Surprisingly, lipid accumulation occurred in atg7-deficient tumors only when p53 was deleted. atg7- and p53-deficient tumor-derived cell lines (TDCLs) had compromised starvation survival and formed lipidic cysts instead of tumors, suggesting defective utilization of lipid stores. atg7 deficiency reduced fatty acid oxidation (FAO) and increased sensitivity to FAO inhibition, indicating that with p53 loss, Ras-driven tumors require autophagy for mitochondrial function and lipid catabolism. Thus, autophagy is required for carcinoma fate, and autophagy defects may be a molecular basis for the occurrence of oncocytomas. Moreover, cancers require autophagy for distinct roles in metabolism that are oncogene- and tumor suppressor gene-specific.
Hippocampal neuron soma size is associated with population differences in winter climate severity in food‐caching chickadees
Authors: Freas Cody A. , Roth Timothy C. , LaDage Lara D. , Pravosudov Vladimir V.
Published: July 2013

Differential demands on cognitive ability may be expected to result in the evolution of cognition and associated changes in underlying neural mechanisms. While most comparative studies of cognition have focused on volumetric brain measurements, it remains unclear whether neuron morphology, which appears to be directly linked to cognitive functions, may be responsive to differential selection on cognitive ability.

Food‐caching birds rely on caches to survive winter and use spatial memory to recover previously stored food. Birds in more harsh winter climates have been hypothesized to be more dependent on cached food, and therefore, their winter survival may be expected to be more memory‐dependent relative to their conspecifics from the milder winter climates. Here, we show that neuron soma size in the hippocampus, a brain region involved in memory function, exhibits significant population variation associated with different environmental pressures on spatial memory related to differences in winter climate harshness in two species of food‐caching chickadees. Comparing ten populations of black‐capped chickadees and three populations of mountain chickadees along a gradient of winter climate harshness, we found that birds from harsher environments had significantly larger hippocampal neuron soma sizes.

Using chickadees from the two most divergent populations reared in a laboratory environment, we showed that these differences appear to be at least partly heritable as significant differences between these populations remained in birds sharing the same laboratory environment. At the same time, laboratory‐reared birds had significantly smaller neuron soma size compared with the wild‐sampled birds, suggesting that at least some variation in neuron soma size may be due to environment‐related plasticity.

Our data suggest that environment‐related selection on memory may generate differences in neuron morphology, which appear to be controlled by some heritable mechanisms and likely underlie population differences in spatial memory.
Rapid assessment of rat eradication after aerial baiting
Authors: Samaniego‐Herrera Araceli , Anderson Dean P. , Parkes John P. , Aguirre‐Muñoz Alfonso
Published: July 2013

Eradication of introduced rodents on islands is increasingly implemented as a conservation tool. Aerial baiting, currently the main eradication technique, provides no information on whether eradication has been achieved. Success is usually evaluated after a standard period of 2 years with no sign of rodents.

We describe a novel approach to assess the success of eradication efforts based on a project to eradicate ship rats Rattus rattus from Isabel Island (82 ha), Mexico. We used detection and home‐range parameters obtained from a capture–recapture study completed prior to aerial baiting to build a spatial‐survey model that predicts probability of eradication after the treatment.

The spatial‐survey model estimated a >99% probability of success after two surveys with no rats detected. This approach can be used to make eradication projects more cost‐effective. Survivors, if any, could be located and dispatched by localized control methods. This avoids repeat aerial baiting of the whole island if failure becomes apparent.

This model is a useful tool for (a) assessing the probability of eradication within weeks, rather than years of an operation, and (b) predicting the required survey effort to achieve a probability of success consistent with the costs and risks of falsely declaring eradication success.

Synthesis and applications: Rapid assessment of success after rodent eradication efforts on islands results in financial savings by potentially reducing the duration of the projects. Improvements in biosecurity guidelines might also accrue as delays in detecting rats after an operation may confound their identification as offspring of survivors or re‐invaders. Advanced techniques and predictive modelling will increase confidence among partners and donors and allow more efficient achievement of regional programmes.
Contemporary food policy challenges and opportunities
Authors: Pinstrup‐Andersen Per
Published: July 2013

The global food system and related government policies are in disarray. In response to expected increasing food prices and greater food price volatility, national governments are pursuing a variety of policies. Some policies amplify price fluctuations while others attempt to prohibit price signals from reaching domestic markets. Extreme weather events, irrational expectations by speculators, sensationalism by the news media, oil price fluctuations and the pursuit of self‐interests by international organisations, NGOs and the private sector, have created a sense of uncertainty and heightened political risks among many governments, pushing governments towards crisis management, short‐term political interventions and bandaid solutions. This paper discusses these interventions, the associated policy challenges and related policies. The paper will argue that food price volatility will continue to be with us, but that real food prices need not increase. It will further show that the main bottlenecks in expanding food production in most low‐income developing countries are found outside the farm and that government intervention in the food system should focus on improvements in rural infrastructure, domestic markets and policies to facilitate efficiency and effectiveness in postharvest value chains and input sectors. Full costing of environmental damage is suggested to be pursued to help assure sustainability.
How well can pelvic floor muscles with major defects contract? A cross‐sectional comparative study 6 weeks after delivery using transperineal 3D/4D ultrasound and manometer
Authors: Hilde G , Stær‐Jensen J , Siafarikas F , Gjestland K , Ellström Engh M , Bø K
Published: July 2013

Objective

To investigate ability to contract, vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength and PFM endurance 6 weeks after vaginal delivery in primiparous women, with and without major defects of the levator ani (LA) muscle.

Design

Cross‐sectional comparative study.

Setting

Akershus University Hospital, Norway.

Sample

A cohort of 175 singleton primiparous women delivering vaginally after more than 32 weeks of gestation.

Methods

Major LA defects were assessed by 3D/4D transperineal ultrasound at maximal PFM contraction, using tomographic imaging. VRP, PFM strength and PFM endurance were measured vaginally by manometer. Data were analysed by independent‐samples Student's t test, chi‐square test, and standard multiple and simple linear regression.

Main outcome measures

VRP, PFM strength and PFM endurance.

Results

Of the women included in the study, 4% were not able to contract their PFM 6 weeks after delivery. Women with major LA defects (n = 55) had 47% lower PFM strength and 47% lower endurance when compared with women without major LA defects (n = 120). Mean differences were 7.5 cmH2O (95% CI 5.1–9.9, P < 0.001) and 51.2 cmH2O seconds (95% CI 32.8–69.6, P < 0.001), respectively. These estimates were unchanged by adjustment in multivariable linear regression for potentially confounding demographic and obstetric factors. No difference was found regarding VRP (P = 0.670).

Conclusions

Women with major LA defects after vaginal delivery had pronounced lower PFM strength and endurance than women without such defects; however, most women with major LA defects were able to contract the PFM. This indicates a potential capacity by non‐injured muscle fibres to compensate for loss in muscle strength, even at an early stage after delivery.
Third‐ and fourth‐degree perineal tears among primiparous women in England between 2000 and 2012: time trends and risk factors
Authors: Gurol‐Urganci I , Cromwell DA , Edozien LC , Mahmood TA , Adams EJ , Richmond DH , Templeton A , van der Meulen JH
Published: July 2013

Objective

To describe the trends of severe perineal tears in England and to investigate to what extent the changes in related risk factors could explain the observed trends.

Design

A retrospective cohort study of singleton deliveries from a national administrative database.

Setting

The English National Health Service between 1 April 2000 and 31 March 2012.

Population

A cohort of 1 035 253 primiparous women who had a singleton, term, cephalic, vaginal birth.

Methods

Multivariable logistic regression was used to estimate the impact of financial year of birth (labelled by starting year), adjusting for major risk factors.

Main outcome measure

The rate of third‐degree (anal sphincter is torn) or fourth‐degree (anal sphincter as well as rectal mucosa are torn) perineal tears.

Results

The rate of reported third‐ or fourth‐degree perineal tears tripled from 1.8 to 5.9% during the study period. The rate of episiotomy varied between 30 and 36%. An increasing proportion of ventouse deliveries (from 67.8 to 78.6%) and non‐instrumental deliveries (from 15.1 to 19.1%) were assisted by an episiotomy. A higher risk of third‐ or fourth‐degree perineal tears was associated with a maternal age above 25 years, instrumental delivery (forceps and ventouse), especially without episiotomy, Asian ethnicity, a more affluent socio‐economic status, higher birthweight, and shoulder dystocia.

Conclusions

Changes in major risk factors are unlikely explanations for the observed increase in the rate of third‐ or fourth‐degree tears. The improved recognition of tears following the implementation of a standardised classification of perineal tears is the most likely explanation.
The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta‐analysis
Authors: Harb HM , Gallos ID , Chu J , Harb M , Coomarasamy A
Published: July 2013

Background

Endometriosis is found in 0.5–5% of fertile women and 25–40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment.

Objectives

To explore the association between endometriosis and IVF outcome.

Search strategy

Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers.

Selection criteria

Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle‐Ottawa Quality Assessment Scale was used for quality assessment.

Data collection and analysis

Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta‐analysed.

Main results

Twenty‐seven observational studies were included, comprising 8984 women. Meta‐analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87–0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67–0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69–0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment.

Conclusion

The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment.
Retarded head growth and neurocognitive development in infants of mothers with a history of eating disorders: longitudinal cohort study
Authors: Koubaa S , Hällström T , Hagenäs L , Hirschberg AL
Published: July 2013

Objective

To characterise early growth and neurocognitive development in children of mothers with a history of eating disorders (ED).

Design

A longitudinal cohort study.

Setting

Child‐care centres in Stockholm, Sweden.

Population

Children born to mothers with previous ED (n = 47) (24 anorexia nervosa, 20 bulimia nervosa, 3 unspecified ED), and controls (n = 65).

Methods

Mean values and standard deviation scores of weight and height from birth to 5 years of age and head circumference up to 18 months of age were compared between groups. Neurocognitive development was studied at the age of 5 years by the validated parent questionnaire Five to Fifteen.

Main outcome measures

Head growth and neurocognitive development.

Results

We previously reported that mothers with a history of ED conceived infants with lower birthweight and head circumference than controls. At 3 months of age, body mass index (BMI) was no longer reduced but mean head circumferences of the children born to mothers with ED were smaller throughout the observation period. Similarly, the longitudinal results of the standard deviation scores of head circumference showed a significant overall group effect with lower levels in both subgroups of ED (anorexia nervosa and bulimia nervosa). The children of the ED mothers also had significantly higher Five to Fifteen scores than controls, reflecting difficulties in language skills. Head circumference at birth correlated with language skills in the children of mothers with ED.

Conclusion

Children of mothers with previous ED demonstrated an early catch‐up in BMI, but the average head circumference continued to be delayed until at least 18 months of age. The reduced head growth was related to delayed neurocognitive development.
Rate of Ankle‐Brachial Index Decline Predicts Cardiovascular Mortality in Hemodialysis Patients
Authors: Kuwahara Michio , Hasumi Syoko , Mandai Shintaro , Tanaka Tomomi , Shikuma Satomi , Akita Wataru , Mori Yoshihiro , Sasaki Sei
Published: July 2013

Chronic kidney disease is a risk factor for cardiovascular mortality and morbidity of cardiovascular events (CVEs). We obtained baseline data regarding blood biochemistry, ankle‐brachial index (ABI), brachial‐ankle pulse wave velocity (baPWV) and echocardiographic parameters from 300 patients on hemodialysis in 2005. We also measured ABI and baPWV annually from June 2005 until June 2012 and calculated rates of changes in ABI and baPWV to identify factors associated with CVEs. Seventy‐three patients died of cardiovascular disease and 199 CVEs occurred in 164 patients during the study period. Cardiac, cerebrovascular and peripheral artery disease (PAD) events occurred in 124, 43 and 32 patients, respectively, and 30 patients had more than two types of CVEs. Analysis using the Cox proportional hazards model showed that a higher rate of decline in ABI (hazard ratio [HR], 4.034; P < 0.001) was the most significant risk factor for decreased patient survival. Multivariate Cox analysis revealed that a higher rate of ABI decline (HR, 2.342; P < 0.001) was a significant risk factor for cardiac events, and that a lower baseline ABI was a risk factor for cerebrovascular (HR, 0.793; P = 0.03) and PAD (HR, 0.595; P < 0.0001) events. Our findings suggested that the rate of a decline in ABI and the baseline ABI value are potent correlation factors for survival and CVE morbidity among patients on hemodialysis in Japan.
Geometric Optimization of a Step Bearing for a Hydrodynamically Levitated Centrifugal Blood Pump for the Reduction of Hemolysis
Authors: Kosaka Ryo , Yada Toru , Nishida Masahiro , Maruyama Osamu , Yamane Takashi
Published: July 2013

A hydrodynamically levitated centrifugal blood pump with a semi‐open impeller has been developed for mechanical circulatory assistance. However, a narrow bearing gap has the potential to cause hemolysis. The purpose of the present study is to optimize the geometric configuration of the hydrodynamic step bearing in order to reduce hemolysis by expansion of the bearing gap. First, a numerical analysis of the step bearing, based on lubrication theory, was performed to determine the optimal design. Second, in order to assess the accuracy of the numerical analysis, the hydrodynamic forces calculated in the numerical analysis were compared with those obtained in an actual measurement test using impellers having step lengths of 0%, 33%, and 67% of the vane length. Finally, a bearing gap measurement test and a hemolysis test were performed. As a result, the numerical analysis revealed that the hydrodynamic force was the largest when the step length was approximately 70%. The hydrodynamic force calculated in the numerical analysis was approximately equivalent to that obtained in the measurement test. In the measurement test and the hemolysis test, the blood pump having a step length of 67% achieved the maximum bearing gap and reduced hemolysis, as compared with the pumps having step lengths of 0% and 33%. It was confirmed that the numerical analysis of the step bearing was effective, and the developed blood pump having a step length of approximately 70% was found to be a suitable configuration for the reduction of hemolysis.
An online adaptive learning environment for critical‐thinking‐infused English literacy instruction
Authors: Yang Ya‐Ting Carolyn , Gamble Jeffrey Hugh , Hung Yu‐Wan , Lin Tzu‐Yun
Published: July 2013

Critical thinking (CT) and English literacy are two essential 21st century competencies that are a priority for teaching and learning in an increasingly digital learning environment. Taking advantage of innovations in educational technology, this study empirically investigates the effectiveness of CT‐infused adaptive English literacy instruction using a Moodle system. A one‐group pretest–posttest design was employed to evaluate the effect of the treatment on students' acquisition of CT skills (CTS) and English literacy. A total of 83 students enrolled in two sections of a general studies course at a large university in Taiwan participated in the semester‐long experiment. Adaptive learning was achieved through the use of an online Moodle system for (1) online grouping (based on pretest English literacy scores), (2) delivery of specifically designed adaptive learning materials for each group and (3) provision of individualised feedback. CT‐infused language activities based on social constructivist principles were designed for each level of adaptive instruction, whereas direct instruction for fostering CTS was provided in class and practiced or reflected upon in groups. Empirical results demonstrate that CT‐enhanced adaptive English literacy instruction simultaneously improved students' CTS and English literacy and that students' online discussions developed towards higher levels of interaction. This paper illustrates an effective blended learning model for adaptive instruction and offers recommendations for designing CT‐infused language learning activities that can successfully foster both CT and English literacy outcomes.