bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role for Topoisomerase I in Fusarium graminearum and F. culmorum Pathogenesis and Sporulation
Authors: Baldwin Thomas K. , Urban Martin , Brown Neil , Hammond-Kosack Kim E.
Published: April 2010

Fusarium graminearum and F. culmorum are the causal agents of Fusarium ear blight (FEB) in wheat. A forward genetics approach was taken to discover novel pathogenicity genes in the genome of F. graminearum. A library of transformants created by random plasmid insertional mutagenesis was screened on wheat ears for virulence defects. Plasmid rescue on one of the reduced-virulence mutants revealed a single-copy plasmid insertion in the gene coding for the DNA interacting enzyme, topoisomerase I. Targeted topoisomerase I gene-deletion mutants were created in strains of both F. graminearum and F. culmorum. The top1 mutants of both species exhibited greatly reduced virulence in wheat ear infection assays (GO:0009405 and GO:0044145). Detailed microscopy analyses revealed that top1 hyphal growth was restricted to palea tissue whereas host responses were discernable 1,000 μm further away in the rachis node. Asexual sporulation was reduced in the F. graminearum mutants and was absent from the F. culmorum mutants. The F. graminearum mutant did not develop sexual spores when subjected to an in vitro perithecia production assay. During in vitro growth, the top1 mutants of both species were still able to produce the trichothecene mycotoxin, deoxynivalenol.
Atypical Transcriptional Regulation and Role of a New Toxin-Antitoxin-Like Module and Its Effect on the Lipid Composition of Bradyrhizobium japonicum
Authors: Miclea Paul S. , Péter Mária , Végh Gergely , Cinege Gyöngyi , Kiss Ernö , Váró György , Horváth Ibolya , Dusha Ilona
Published: April 2010

A toxin-antitoxin (TA)-like system (designated as bat/bto genes) was identified in Bradyrhizobium japonicum, based on sequence homology and similarities in organization and size to known TA systems. Deletion of the bat/bto module resulted in pleiotropic alterations in cell morphology and metabolism. The generation time of the mutant was considerably decreased in rich media. Atomic force microscopy revealed the modified shape (shorter and wider) and softness of mutant cells. The synthesis of phosphatidylcholine was completely blocked in the mutant bacteria, and vaccenic acid, the predominant fatty acid of membranes of the wild-type cell, was replaced by palmitic acid in the mutant membranes. The mutant bacteria synthesized incomplete lipopolysaccharide molecules. Remarkable changes in the membrane lipid composition may explain the observed morphological alterations and growth properties of the mutant bacteria. The overlapping promoter region of bat/bto and glpD (coding for the aerobic sn-glycerol-3-phosphate dehydrogenase) genes suggests a complex regulation and the involvement of bat/bto in the control of main metabolic pathways and an important role in the maintenance of a normal physiological state of B. japonicum. These data reveal new aspects of the role of TA systems in bacteria.
Variations in the Mycorrhization Characteristics in Roots of Wild-Type and ABA-Deficient Tomato Are Accompanied by Specific Transcriptomic Alterations
Authors: Garrido José Manuel García , Morcillo Rafael Jorge León , Rodríguez José Ángel Martín , Bote Juan Antonio Ocampo
Published: April 2010

Abscissic acid (ABA) determines mycorrhiza functionality and arbuscule development. In this study, we performed transcriptome analysis in response to different mycorrhization status according to the ABA content in the root to identify genes that may play a role in arbuscule functionality. Affymetrix Tomato GeneChip (approximately 10,000 probes) allowed us to detect and compare the transcriptional root profiling of tomato (Solanum lycopersicum) wild-type and ABA-deficient sitiens plants colonized by Glomus intraradices. A number of identified genes in tomato belong to a category of genes already described as “mycorrhizal core-set” in other host plants. The impairment in arbuscular mycorrhiza (AM) formation in ABA-deficient mutants was associated with upregulation of genes related to defense and cell wall modification, whereas functional mycorrhization in wild-type plants was associated with activation of genes related to isoprenoid metabolism. The oxylipin pathway was activated in tomato mycorrhizal roots at late stages of interaction, and was related to the control of fungal spread in roots, not with the establishment of the symbiosis. Induction of selected genes, representing a range of biological functions and representative of the three sets of genes specifically upregulated in the different plant phenotype, was confirmed by quantitative reverse-transcription polymerase chain reaction, and their response to phythohormone treatment was tested, showing that ethylene and jasmonic acid are key regulators of gene expression during AM development. Comparative analysis of mycorrhiza upregulated functional categories revealed significant changes in gene expression associated with the different mycorrhization status according to the ABA content in the roots.
Positive Regulation of the Hrp Type III Secretion System in Pseudomonas syringae pv. phaseolicola
Authors: Ortiz-Martín Inmaculada , Thwaites Richard , Macho Alberto P. , Mansfield John W. , Beuzón Carmen R.
Published: April 2010

Disease in compatible hosts and induction of the hypersensitive response in resistant plants by most plant-pathogenic bacteria require a functional type III secretion system (T3SS). Expression of T3SS genes responds to host and environmental factors and is induced within the plant. In Pseudomonas syringae, expression of the T3SS requires HrpL, which is transcriptionally upregulated by HrpR and HrpS. In some pathovars, expression of the hrpRS genes is upregulated by the GacA/S two-component system. Additionally, HrpA, the major component of the T3SS pilus, has also been linked to the regulation of the hrpRS gene expression. Previous studies concerning regulation of hypersensitive response and pathogenesis/hypersensitive response conserved (hrp/hrc) gene expression have used mostly in vitro inducing conditions, different pathovars, and methodology. Here, we analyze the roles of HrpL, GacA, and HrpA in the bean pathogen, using single, double, and triple mutants as well as strains ectopically expressing the regulators. We use real-time polymerase chain reaction analysis in vitro and in planta to quantify gene expression and competitive indices and other assays to assess bacterial fitness. Our results indicate that i) HrpL acts as a general virulence regulator that upregulates non-T3SS virulence determinants and downregulates flagellar function; ii) GacA modulates the expression of hrpL, and its contribution to virulence is entirely HrpL dependent; iii) there is a basal HrpL-independent expression of the T3SS genes in rich medium that is important for full activation of the system, maybe by keeping the system primed for rapid activation upon contact with the plant; and iv) HrpA upregulates expression of the T3SS genes and is essential to activate expression of the hrpZ operon upon contact with the plant.
Memory formation: from network structure to neural dynamics
Authors: Feldt Sarah , Wang Jane X. , Hetrick Vaughn L. , Berke Joshua D. , Żochowski Michal
Published: April 2010

Understanding the neural correlates of brain function is an extremely challenging task, since any cognitive process is distributed over a complex and evolving network of neurons that comprise the brain. In order to quantify observed changes in neuronal dynamics during hippocampal memory formation, we present metrics designed to detect directional interactions and the formation of functional neuronal ensembles. We apply these metrics to both experimental and model-derived data in an attempt to link anatomical network changes with observed changes in neuronal dynamics during hippocampal memory formation processes. We show that the developed model provides a consistent explanation of the anatomical network modifications that underlie the activity changes observed in the experimental data.
Vulnerability of networks of interacting Markov chains
Authors: Kocarev L. , Zlatanov N. , Trajanov D.
Published: April 2010

The concept of vulnerability is introduced for a model of random, dynamical interactions on networks. In this model, known as the influence model, the nodes are arranged in an arbitrary network, while the evolution of the status at a node is according to an internal Markov chain, but with transition probabilities that depend not only on the current status of that node but also on the statuses of the neighbouring nodes. Vulnerability is treated analytically and numerically for several networks with different topological structures, as well as for two real networks—the network of infrastructures and the EU power grid—identifying the most vulnerable nodes of these networks.
Phase-resolved analysis of the susceptibility of pinned spiral waves to far-field pacing in a two-dimensional model of excitable media
Authors: Bittihn Philip , Squires Amgad , Luther Gisa , Bodenschatz Eberhard , Krinsky Valentin , Parlitz Ulrich , Luther Stefan
Published: April 2010

Life-threatening cardiac arrhythmias are associated with the existence of stable and unstable spiral waves. Termination of such complex spatio-temporal patterns by local control is substantially limited by anchoring of spiral waves at natural heterogeneities. Far-field pacing (FFP) is a new local control strategy that has been shown to be capable of unpinning waves from obstacles. In this article, we investigate in detail the FFP unpinning mechanism for a single rotating wave pinned to a heterogeneity. We identify qualitatively different phase regimes of the rotating wave showing that the concept of vulnerability is important but not sufficient to explain the failure of unpinning in all cases. Specifically, we find that a reduced excitation threshold can lead to the failure of unpinning, even inside the vulnerable window. The critical value of the excitation threshold (below which no unpinning is possible) decreases for higher electric field strengths and larger obstacles. In contrast, for a high excitation threshold, the success of unpinning is determined solely by vulnerability, allowing for a convenient estimation of the unpinning success rate. In some cases, we also observe phase resetting in discontinuous phase intervals of the spiral wave. This effect is important for the application of multiple stimuli in experiments.
Towards model-based control of Parkinson's disease
Authors: Schiff Steven J.
Published: April 2010

Modern model-based control theory has led to transformative improvements in our ability to track the nonlinear dynamics of systems that we observe, and to engineer control systems of unprecedented efficacy. In parallel with these developments, our ability to build computational models to embody our expanding knowledge of the biophysics of neurons and their networks is maturing at a rapid rate. In the treatment of human dynamical disease, our employment of deep brain stimulators for the treatment of Parkinson’s disease is gaining increasing acceptance. Thus, the confluence of these three developments—control theory, computational neuroscience and deep brain stimulation—offers a unique opportunity to create novel approaches to the treatment of this disease. This paper explores the relevant state of the art of science, medicine and engineering, and proposes a strategy for model-based control of Parkinson’s disease. We present a set of preliminary calculations employing basal ganglia computational models, structured within an unscented Kalman filter for tracking observations and prescribing control. Based upon these findings, we will offer suggestions for future research and development.
Ecosystem biogeochemistry considered as a distributed metabolic network ordered by maximum entropy production
Authors: Vallino Joseph J.
Published: April 2010

We examine the application of the maximum entropy production principle for describing ecosystem biogeochemistry. Since ecosystems can be functionally stable despite changes in species composition, we use a distributed metabolic network for describing biogeochemistry, which synthesizes generic biological structures that catalyse reaction pathways, but is otherwise organism independent. Allocation of biological structure and regulation of biogeochemical reactions is determined via solution of an optimal control problem in which entropy production is maximized. However, because synthesis of biological structures cannot occur if entropy production is maximized instantaneously, we propose that information stored within the metagenome allows biological systems to maximize entropy production when averaged over time. This differs from abiotic systems that maximize entropy production at a point in space–time, which we refer to as the steepest descent pathway. It is the spatio-temporal averaging that allows biological systems to outperform abiotic processes in entropy production, at least in many situations. A simulation of a methanotrophic system is used to demonstrate the approach. We conclude with a brief discussion on the implications of viewing ecosystems as self-organizing molecular machines that function to maximize entropy production at the ecosystem level of organization.
Minimization of a free-energy-like potential for non-equilibrium flow systems at steady state
Authors: Niven Robert K.
Published: April 2010

This study examines a new formulation of non-equilibrium thermodynamics, which gives a conditional derivation of the ‘maximum entropy production’ (MEP) principle for flow and/or chemical reaction systems at steady state. The analysis uses a dimensionless potential function
ϕ
st
for non-equilibrium systems, analogous to the free energy concept of equilibrium thermodynamics. Spontaneous reductions in
ϕ
st
arise from increases in the ‘flux entropy’ of the system—a measure of the variability of the fluxes—or in the local entropy production; conditionally, depending on the behaviour of the flux entropy, the formulation reduces to the MEP principle. The inferred steady state is also shown to exhibit high variability in its instantaneous fluxes and rates, consistent with the observed behaviour of turbulent fluid flow, heat convection and biological systems; one consequence is the coexistence of energy producers and consumers in ecological systems. The different paths for attaining steady state are also classified.
Trends in entropy production during ecosystem development in the Amazon Basin
Authors: Holdaway Robert J. , Sparrow Ashley D. , Coomes David A.
Published: April 2010

Understanding successional trends in energy and matter exchange across the ecosystem–atmosphere boundary layer is an essential focus in ecological research; however, a general theory describing the observed pattern remains elusive. This paper examines whether the principle of maximum entropy production could provide the solution. A general framework is developed for calculating entropy production using data from terrestrial eddy covariance and micrometeorological studies. We apply this framework to data from eight tropical forest and pasture flux sites in the Amazon Basin and show that forest sites had consistently higher entropy production rates than pasture sites (0.461 versus 0.422 W m
−2
K
−1
, respectively). It is suggested that during development, changes in canopy structure minimize surface albedo, and development of deeper root systems optimizes access to soil water and thus potential transpiration, resulting in lower surface temperatures and increased entropy production. We discuss our results in the context of a theoretical model of entropy production versus ecosystem developmental stage. We conclude that, although further work is required, entropy production could potentially provide a much-needed theoretical basis for understanding the effects of deforestation and land-use change on the land-surface energy balance.
The constructal law of design and evolution in nature
Authors: Bejan Adrian , Lorente Sylvie
Published: April 2010

Constructal theory is the view that (i) the generation of images of design (pattern, rhythm) in nature is a phenomenon of physics and (ii) this phenomenon is covered by a principle (the constructal law): ‘for a finite-size flow system to persist in time (to live) it must evolve such that it provides greater and greater access to the currents that flow through it’. This law is about the necessity of design to occur, and about the time direction of the phenomenon: the tape of the design evolution ‘movie’ runs such that existing configurations are replaced by globally easier flowing configurations. The constructal law has two useful sides: the prediction of natural phenomena and the strategic engineering of novel architectures, based on the constructal law, i.e. not by mimicking nature. We show that the emergence of scaling laws in inanimate (geophysical) flow systems is the same phenomenon as the emergence of allometric laws in animate (biological) flow systems. Examples are lung design, animal locomotion, vegetation, river basins, turbulent flow structure, self-lubrication and natural multi-scale porous media. This article outlines the place of the constructal law as a self-standing law in physics, which covers all the ad hoc (and contradictory) statements of optimality such as minimum entropy generation, maximum entropy generation, minimum flow resistance, maximum flow resistance, minimum time, minimum weight, uniform maximum stresses and characteristic organ sizes. Nature is configured to flow and move as a conglomerate of ‘engine and brake’ designs.
The principle of ‘maximum energy dissipation’: a novel thermodynamic perspective on rapid water flow in connected soil structures
Authors: Zehe Erwin , Blume Theresa , Blöschl Günter
Published: April 2010

Preferential flow in biological soil structures is of key importance for infiltration and soil water flow at a range of scales. In the present study, we treat soil water flow as a dissipative process in an open non-equilibrium thermodynamic system, to better understand this key process. We define the chemical potential and Helmholtz free energy based on soil physical quantities, parametrize a physically based hydrological model based on field data and simulate the evolution of Helmholtz free energy in a cohesive soil with different populations of worm burrows for a range of rainfall scenarios. The simulations suggest that flow in connected worm burrows allows a more efficient redistribution of water within the soil, which implies a more efficient dissipation of free energy/higher production of entropy. There is additional evidence that the spatial pattern of worm burrow density at the hillslope scale is a major control of energy dissipation. The pattern typically found in the study is more efficient in dissipating energy/producing entropy than other patterns. This is because upslope run-off accumulates and infiltrates via the worm burrows into the dry soil in the lower part of the hillslope, which results in an overall more efficient dissipation of free energy.
Maximum entropy production allows a simple representation of heterogeneity in semiarid ecosystems
Authors: Schymanski Stanislaus J. , Kleidon Axel , Stieglitz Marc , Narula Jatin
Published: April 2010

Feedbacks between water use, biomass and infiltration capacity in semiarid ecosystems have been shown to lead to the spontaneous formation of vegetation patterns in a simple model. The formation of patterns permits the maintenance of larger overall biomass at low rainfall rates compared with homogeneous vegetation. This results in a bias of models run at larger scales neglecting subgrid-scale variability. In the present study, we investigate the question whether subgrid-scale heterogeneity can be parameterized as the outcome of optimal partitioning between bare soil and vegetated area. We find that a two-box model reproduces the time-averaged biomass of the patterns emerging in a 100 × 100 grid model if the vegetated fraction is optimized for maximum entropy production (MEP). This suggests that the proposed optimality-based representation of subgrid-scale heterogeneity may be generally applicable to different systems and at different scales. The implications for our understanding of self-organized behaviour and its modelling are discussed.
A basic introduction to the thermodynamics of the Earth system far from equilibrium and maximum entropy production
Authors: Kleidon A.
Published: April 2010

The Earth system is remarkably different from its planetary neighbours in that it shows pronounced, strong global cycling of matter. These global cycles result in the maintenance of a unique thermodynamic state of the Earth's atmosphere which is far from thermodynamic equilibrium (TE). Here, I provide a simple introduction of the thermodynamic basis to understand why Earth system processes operate so far away from TE. I use a simple toy model to illustrate the application of non-equilibrium thermodynamics and to classify applications of the proposed principle of maximum entropy production (MEP) to such processes into three different cases of contrasting flexibility in the boundary conditions. I then provide a brief overview of the different processes within the Earth system that produce entropy, review actual examples of MEP in environmental and ecological systems, and discuss the role of interactions among dissipative processes in making boundary conditions more flexible. I close with a brief summary and conclusion.
Maximum entropy production in environmental and ecological systems
Authors: Kleidon Axel , Malhi Yadvinder , Cox Peter M.
Published: April 2010

The coupled biosphere–atmosphere system entails a vast range of processes at different scales, from ecosystem exchange fluxes of energy, water and carbon to the processes that drive global biogeochemical cycles, atmospheric composition and, ultimately, the planetary energy balance. These processes are generally complex with numerous interactions and feedbacks, and they are irreversible in their nature, thereby producing entropy. The proposed principle of maximum entropy production (MEP), based on statistical mechanics and information theory, states that thermodynamic processes far from thermodynamic equilibrium will adapt to steady states at which they dissipate energy and produce entropy at the maximum possible rate. This issue focuses on the latest development of applications of MEP to the biosphere–atmosphere system including aspects of the atmospheric circulation, the role of clouds, hydrology, vegetation effects, ecosystem exchange of energy and mass, biogeochemical interactions and the Gaia hypothesis. The examples shown in this special issue demonstrate the potential of MEP to contribute to improved understanding and modelling of the biosphere and the wider Earth system, and also explore limitations and constraints to the application of the MEP principle.
It is not the entropy you produce, rather, how you produce it
Authors: Volk Tyler , Pauluis Olivier
Published: April 2010

The principle of maximum entropy production (MEP) seeks to better understand a large variety of the Earth's environmental and ecological systems by postulating that processes far from thermodynamic equilibrium will ‘adapt to steady states at which they dissipate energy and produce entropy at the maximum possible rate’. Our aim in this ‘outside view’, invited by Axel Kleidon, is to focus on what we think is an outstanding challenge for MEP and for irreversible thermodynamics in general: making specific predictions about the relative contribution of individual processes to entropy production. Using studies that compared entropy production in the atmosphere of a dry versus humid Earth, we show that two systems might have the same entropy production rate but very different internal dynamics of dissipation. Using the results of several of the papers in this special issue and a thought experiment, we show that components of life-containing systems can evolve to either lower or raise the entropy production rate. Our analysis makes explicit fundamental questions for MEP that should be brought into focus: can MEP predict not just the overall state of entropy production of a system but also the details of the sub-systems of dissipaters within the system? Which fluxes of the system are those that are most likely to be maximized? How it is possible for MEP theory to be so domain-neutral that it can claim to apply equally to both purely physical–chemical systems and also systems governed by the ‘laws’ of biological evolution? We conclude that the principle of MEP needs to take on the issue of exactly how entropy is produced.
Identification of Specific DNA Binding Residues in the TCP Family of Transcription Factors in Arabidopsis
Authors: Aggarwal Pooja , Das Gupta Mainak , Joseph Agnel Praveen , Chatterjee Nirmalya , Srinivasan N. , Nath Utpal
Published: April 2010

The TCP transcription factors control multiple developmental traits in diverse plant species. Members of this family share an ∼60-residue-long TCP domain that binds to DNA. The TCP domain is predicted to form a basic helix-loop-helix (bHLH) structure but shares little sequence similarity with canonical bHLH domain. This classifies the TCP domain as a novel class of DNA binding domain specific to the plant kingdom. Little is known about how the TCP domain interacts with its target DNA. We report biochemical characterization and DNA binding properties of a TCP member in Arabidopsis thaliana, TCP4. We have shown that the 58-residue domain of TCP4 is essential and sufficient for binding to DNA and possesses DNA binding parameters comparable to canonical bHLH proteins. Using a yeast-based random mutagenesis screen and site-directed mutants, we identified the residues important for DNA binding and dimer formation. Mutants defective in binding and dimerization failed to rescue the phenotype of an Arabidopsis line lacking the endogenous TCP4 activity. By combining structure prediction, functional characterization of the mutants, and molecular modeling, we suggest a possible DNA binding mechanism for this class of transcription factors.
miR390,Arabidopsis TAS3tasiRNAs, and TheirAUXIN RESPONSE FACTORTargets Define an Autoregulatory Network Quantitatively Regulating Lateral Root Growth
Authors: Marin Elena , Jouannet Virginie , Herz Aurélie , Lokerse Annemarie S. , Weijers Dolf , Vaucheret Herve , Nussaume Laurent , Crespi Martin D. , Maizel Alexis
Published: April 2010

Plants adapt to different environmental conditions by constantly forming new organs in response to morphogenetic signals. Lateral roots branch from the main root in response to local auxin maxima. How a local auxin maximum translates into a robust pattern of gene activation ensuring the proper growth of the newly formed lateral root is largely unknown. Here, we demonstrate that miR390, TAS3-derived trans-acting short-interfering RNAs (tasiRNAs), and AUXIN RESPONSE FACTORS (ARFs) form an auxin-responsive regulatory network controlling lateral root growth. Spatial expression analysis using reporter gene fusions, tasi/miRNA sensors, and mutant analysis showed that miR390 is specifically expressed at the sites of lateral root initiation where it triggers the biogenesis of tasiRNAs. These tasiRNAs inhibit ARF2, ARF3, and ARF4, thus releasing repression of lateral root growth. In addition, ARF2, ARF3, and ARF4 affect auxin-induced miR390 accumulation. Positive and negative feedback regulation of miR390 by ARF2, ARF3, and ARF4 thus ensures the proper definition of the miR390 expression pattern. This regulatory network maintains ARF expression in a concentration range optimal for specifying the timing of lateral root growth, a function similar to its activity during leaf development. These results also show how small regulatory RNAs integrate with auxin signaling to quantitatively regulate organ growth during development.
Malaria: looking for selection signatures in the human PKLR gene region
Authors: Machado Patrícia , Pereira Rui , Rocha Ana Mafalda , Manco Licínio , Fernandes Natércia , Miranda Juliana , Ribeiro Letícia , Do Rosário Virgílio E. , Amorim António , Gusmão Leonor , Arez Ana Paula
Published: April 2010

The genetic component of susceptibility to malaria is both complex and multigenic and the better‐known protective polymorphisms are those involving erythrocyte‐specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase‐encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub‐Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase‐deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.
Epidemiology of paediatric immune thrombocytopenia in the General Practice Research Database
Authors: Yong Mellissa , Schoonen Wilma Marieke , Li Lin , Kanas Gena , Coalson Jenna , Mowat Fionna , Fryzek Jon , Kaye James A.
Published: April 2010

This study assessed the incidence of immune thrombocytopenia (ITP) and characteristics associated with ITP in the paediatric population using the General Practice Research Database (GPRD). Two hundred and fifty‐seven paediatric ITP patients were identified out of 1145 incident patients with ITP recorded between 1990 and 2005. The age‐specific incidence for ITP in paediatric patients was 4·2 per 100 000 person‐years (PY) [95% confidence interval (CI): 3·7–4·8 per 100 000 PY], with a statistically significantly higher incidence in boys compared to girls aged 2–5 years [9·7 (95% CI: 7·5–12·2) per 100 000 PY vs. 4·7 (95% CI: 3·2–6·6) per 100 000 PY, respectively]. By contrast, among teenagers aged 13–17 years, the overall incidence was lower [2·4 (95% CI: 1·7–3·3) per 100 000 PY] with a similar incidence in girls and boys. There was a relationship between age and sex with ITP incidence, suggesting that patterns of disease burden differ among children and teenagers. Evidence of an infection or immunization shortly before ITP diagnosis was apparent in 52 (20·2%) and 22 (8·6%) of the 257 paediatric ITP patients, respectively. Two deaths were observed during the study period. ITP is an important although rarely fatal disease in paediatric patients and its aetiology remains unexplained in the majority of cases.
The effects of autumn closing date on sward leaf area index and herbage mass during the winter period
Authors: Ryan W. , Hennessy D. , Murphy J. J. , Boland T. M.
Published: April 2010

The provision of grass for early spring grazing in Ireland is critical for spring calving grass‐based milk production systems. This experiment investigated the effect of a range of autumn closing dates (CD), on herbage mass (kg DM ha−1), leaf area index (LAI) and tiller density (m−2) during winter and early spring. Thirty‐six grazing paddocks, closed from 23 September to 1 December 2007, were grouped to create five mean CD treatments – 29 September, 13 October, 27 October, 10 November, 24 November. Herbage mass, tiller density and LAI were measured every 3 weeks from 28 November 2007 to 20 February 2008; additionally, herbage mass was measured prior to initial spring grazing and tiller density was measured intermittently until September 2008. Delaying CD until November significantly (P < 0·05) reduced herbage mass (by approximately 500 kg DM ha−1) and LAI (by approximately 0·86 units) in mid‐February. On average, 35% of herbage mass present on swards on 20 February was grown between 28 November and 30 January. LAI was positively correlated with herbage mass (R2 = 0·78). Herbage mass increased by approximately 1000 kg DM ha−1 as spring grazing was delayed from February to April. Tiller density increased from November to February, although it did fluctuate, and it was greatest in April (9930 m−2). This experiment concludes that in the south of Ireland adequate herbage mass for grazing in early spring can be achieved by delaying closing to early mid‐October; swards required for grazing after mid‐March can be closed during November.
Extraction time of kidneys during organ procurement impacts function
Authors: Osband Adena J. , Zaki Radi F.
Published: April 2010

Osband AJ, Zaki RF. Extraction time of kidneys during organ procurement impacts function.  Clin Transplant 2011: 25: 235–238. © 2010 John Wiley & Sons A/S.

Abstract:  It is well established that ischemic times affect rates of delayed graft function (DGF) and allograft survival following deceased donor kidney transplant. There is, however, a paucity of data regarding what we term extraction time, the time between aortic cross‐clamp and perfusion/cooling, and removal of the kidneys from the body and placement on ice on the back table. We posit that this time is an additional insult, and may significantly contribute to transplant kidney function. Data pooled from May 2003 to December 2004 from the local OPO (Gift of Life) and UNOS included 316 transplanted kidneys (28 en bloc and 52 donation after cardiac death excluded). Retrospective review and statistical analysis of donor, recipient, and transplant characteristics were performed. When divided into 30‐minute intervals, extraction time was found to directly correlate with early graft failure, (rates 0%, 8.1%, and 14.5%, Spearman’s rank correlation p < 0.05). DGF rates were not tied to extraction time, but shorter extraction time was strongly associated with recovery from DGF and eventual kidney function. Further studies are needed to better assess this factor and its impact.
Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis
Authors: Damodar Amar , Mustafa Reem , Bhatnagar Jyotsna , Panesar Mandip , Gundroo Aijaz , Zachariah Mareena , Blessios George , Tornatore Kathleen , Weber‐Shrikant Edit , Venuto Rocco
Published: April 2010

Damodar A, Mustafa R, Bhatnagar J, Panesar M, Gundroo A, Zachariah M, Blessios G, Tornatore K, Weber‐Shrikant E, Venuto R. Use of anti‐CD20 antibody in the treatment of post‐transplant glomerulonephritis. Clin Transplant 2011: 25: 375–379. © 2010 John Wiley & Sons A/S.

Abstract:  Post‐transplant glomerulonephritis (PTGN) accounts for 4–10% of late graft loss. Six consecutive patients who developed PTGN 3–72 months post‐transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steriods and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5 g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.
KEL*02alleles with alterations in and around exon 8 in individuals with apparent KEL:1,−2 phenotypes
Authors: Wester E. S. , Steffensen R. , Ligthart P. C. , Vad J. , De Haas M. , Storry J. R. , Olsson M. L.
Published: April 2010

Background and Objectives Antibodies to antigens in the Kell blood group system, especially anti‐KEL1, are involved in both haemolytic disease of the newborn and foetus and haemolytic transfusion reactions. Correct typing results are important and discrepancies between serologic and genetic typing must be resolved. Here, we describe the investigation of three healthy individuals who were initially phenotyped as KEL:1,−2.

Materials and Methods Antigen typing was performed by standard serological techniques and by flow cytometric analysis. TheKEL*01/02polymorphism was tested by an allele‐discrimination TaqMan assay as well as by PCR with allele‐specific primers and PCR–RFLP. DNA sequencing of theKELcoding region was also performed.

Results TwoKEL*02Nalleles with mutated splice sites around exon 8 were identified: intron 7 −1g>c (novel) and intron 8 +1g>t (previously reported in one case of K0). In the third sample, a missense mutation in exon 8, 787G>A (novel) predicting Gly263Arg, was detected on aKEL*02allele and associated with dramatically weakened KEL2 antigen expression.

Conclusion Resolution of discrepant phenotype/genotype results identified silencing mutations in or around exon 8. A combination of molecular and serologic methods has the potential to improve the quality of test results and was required to ensure both the accurate KEL2 antigen status andKEL*01zygosity of these individuals.
Singing the Popular Songs? Nightingales Share More Song Types with Their Breeding Population in Their Second Season than in Their First
Authors: Kiefer Sarah , Sommer Christina , Scharff Constance , Kipper Silke
Published: April 2010

Signals used in communication often change throughout an individual’s life course. For example, in many song bird species, males modify their song especially between their first and second breeding season. To address one possible reason of such modification, we investigated whether common nightingalesLuscinia megarhynchosadjust their song type repertoires to sing the song types commonly occurring in their breeding population. We analysed nocturnal singing of six nightingales in their first and second breeding season and compared their repertoire composition and usage to the ‘typical’ repertoire and usage on the breeding ground (represented by seven reference birds). Songs that were maintained between the first and second season by the six focal birds occurred in most of the repertoires of the seven reference birds and were sung often. In contrast, song types that were dropped from the repertoires occurred less often in the reference birds’ repertoires and were sung less often. Furthermore, in the first year, each focal nightingale’s repertoire was less similar to the reference birds’ repertoires than in the second year. Thus, nightingales adjusted their singing towards the songs popular in the breeding grounds by keeping song types that were common and frequently sung by other individuals in their breeding area and by disposing of infrequently performed ones. This resulted in increased similarity with the population’s repertoire from the first to the second year. We discuss possible ontogenetic processes that may lead to such an adjustment and suggest an improved ability to match song types as possible adaptive value.
Molecular cloning, function prediction and phylogenetic analysis of LMW glutenin subunit genes in Triticum timopheevii (Zhuk.)
Authors: Zhang M. Y. , Wang K. , Wang S. L. , Li X. H. , Zeller F. J. , Hsam S. L. K. , Yan Y. M.
Published: April 2010

With 4 figures and 3 tables

Two new low‐molecular‐weight glutenin subunits (LMW‐GS) genes from Triticum timopheevii (Zhuk.) were cloned by reverse‐transcription PCR (RT‐PCR). The complete open reading frames of 897 and 894 bp, corresponding to the size of LMW‐GS genes were designated as TTLMW‐m1 and TTLMW‐m2, respectively. Multiple sequence alignment analysis indicated that these two genes showed high similarity with known LMW‐m type genes, albeit possessing distinct sequence variations. A total of 10 single‐nucleotide polymorphisms in the TTLMW‐m1 and TTLMW‐m2 genes were identified, including five non‐synonymous mutations. The predicted secondary structure of the deduced mature glutenin subunits of TTLMW‐m1 and TTLMW‐m2 genes showed that both subunits possessed more α‐helixes and β‐strands than the control subunit AY263369, suggesting a more viscoelastic dough structure and a positive effect on quality. The homology tree and phylogenetic analysis showed that the two LMW‐m type genes were most likely located at the Glu‐G3 locus and that they diverged from the LMW‐i type genes about 13 million years ago (MYA). The G genome in T. timopheevii appears to be closely related to the D and B genomes of Triticum aestivum.
Does the current stepwise approach to asthma pharmacotherapy encourage over‐treatment?
Authors: O'BYRNE Paul M. , REDDEL Helen K. , COLICE Gene L.
Published: April 2010

For the past 20 years, asthma pharmacotherapy has been described in clinical practice guidelines in terms of a stepwise approach, with medications and/or doses increased if asthma is not well‐controlled, and reduced once good control is achieved and maintained. Although many patients with asthma are untreated, there are also significant problems with over‐treatment once regular controller therapy is commenced. This increases the cost of treatment and exposes patients to unnecessary risks of side‐effects. The present pro‐con debate addresses the question of whether the stepwise approach itself leads to over‐treatment. Two asthma experts discuss factors for and against this proposition, identify issues on which more research is needed, and suggest areas in which guidelines can be changed in order to facilitate more appropriate prescribing of asthma medications. These strategies include better validation of the concepts underlying asthma treatment recommendations, stronger recommendations that every treatment change should be followed up with a scheduled review using evidence‐based assessment tools and incorporation of phenotype‐specific considerations into treatment recommendations. In addition, the process for development and dissemination of clinical practice guidelines should ensure that recommendations are easily understood, feasible to implement, and relevant to everyday asthma care and the needs and concerns of patients and clinicians.
TWO STALEMATES IN THE PHILOSOPHICAL DEBATE ABOUT ABORTION AND WHY THEY CANNOT BE RESOLVED USING ANALOGICAL ARGUMENTS
Authors: KAPOSY CHRIS
Published: April 2010

Philosophical debate about the ethics of abortion has reached stalemate on two key issues. First, the claim that foetuses have moral standing that entitles them to protections for their lives has been neither convincingly established nor refuted. Second, the question of a pregnant woman's obligation to allow the gestating foetus the use of her body has not been resolved. Both issues are deadlocked because philosophers addressing them invariably rely on intuitions and analogies, and such arguments have weaknesses that make them unfit for resolving the abortion issue. Analogical arguments work by building a kind of consensus, and such a consensus is virtually unimaginable because (1) intuitions are revisable, and in the abortion debate there is great motive to revise them, (2) one's position on abortion influences judgments about other issues, making it difficult to leverage intuitions about other ethical questions into changing peoples' minds about abortion, and (3) the extent of shared values in the abortion debate is overstated. Arguments by analogy rely on an assumption of the commensurability of moral worldviews. But the abortion debate is currently unfolding in a context of genuinely incommensurable moral worldviews. The article ends by arguing that the default position must be to permit abortion as a consequence of the freedom of conscience protected in liberal societies.
Perception and the Categories: A Conceptualist Reading of Kant's Critique of Pure Reason
Authors: Griffith Aaron M.
Published: April 2010

Abstract: Philosophers interested in Kant's relevance to contemporary debates over the nature of mental content—notably Robert Hanna and Lucy Allais—have argued that Kant ought to be credited with being the original proponent of the existence of ‘nonconceptual content’. However, I think the ‘nonconceptualist’ interpretations that Hanna and Allais give do not show that Kant allowed for nonconceptual content as they construe it. I argue, on the basis of an analysis of certain sections of the A and B editions of the Transcendental Deduction, for a ‘conceptualist’ reading of Kant's Critique of Pure Reason. My contention is that since Kant's notion of empirical intuition makes essential reference to the categories, it must be true for him that no empirical intuition can be given in sensibility independently of the understanding and its categories.
Dermoscopy‐guided surgery in basal cell carcinoma
Authors: Caresana G , Giardini R.
Published: April 2010

Background  In basal cell carcinoma (BCC), excision margins between 3 and 10 mm, according to site, size, borders, previous treatment and histology, can allow for radical excision in at least 95% of cases.

Objective  The objective was to ascertain whether dermoscopy can detect more accurately the lateral borders in BCCs than clinical examination alone, and allow us to obtain radical excision in more than 95% of cases with only 2‐mm excision margins.

Methods  A prospective study was performed of 200 consecutive BCCs of the head and neck removed with 2‐mm dermoscopically detected excision margins. Morpheaform BCC, deeply recurrent BCC, BCC in Gorlin‐Goltz syndrome, BCC located in sites not accessible through dermoscopy and superficial multifocal BCC were excluded. All cases of excised BCC were submitted to a uniform method of histological examination of the whole specimen with serial parallel sections at 2‐mm intervals.

Results  In only three cases did surgical excision with 2‐mm margins prove to be inadequate; in the remaining 197 cases, the excision margins were tumour‐free. The comparison of clinical and dermoscopic extension measurement showed concordance in 131 cases (65.5%). In 69 cases (34.5%), dermoscopic evaluation showed a larger peripheral extension.

Conclusions  These results indicate that 2‐mm dermoscopically detected excision margins can achieve histologically confirmed complete excisions in 98.5% of cases.
Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis
Authors: Akhyani M , Chams‐Davatchi C , Hemami MR , Fateh S
Published: April 2010

Background  Methotrexate (MTX) is a well‐known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis.

Objective  To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis.

Methods  Thirty‐eight consecutive patients with Psoriasis Area and Severity Index (PASI) >10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow‐up comparing with baseline values.

Results  After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P > 0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P > 0.05). PASI ‐75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI‐75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side‐effects were minor and transient.

Conclusions  No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.