bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetic architecture of economic and political preferences
Authors: Benjamin Daniel J. , Cesarini David , van der Loos Matthijs J. H. M. , Dawes Christopher T. , Koellinger Philipp D. , Magnusson Patrik K. E. , Chabris Christopher F. , Conley Dalton , Laibson David , Johannesson Magnus , Visscher Peter M.
Published: May 2012

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic–based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs.
A short adaptive path from DNA to RNA polymerases
Authors: Cozens Christopher , Pinheiro Vitor B. , Vaisman Alexandra , Woodgate Roger , Holliger Philipp
Published: May 2012

DNA polymerase substrate specificity is fundamental to genome integrity and to polymerase applications in biotechnology. In the current paradigm, active site geometry is the main site of specificity control. Here, we describe the discovery of a distinct specificity checkpoint located over 25 Å from the active site in the polymerase thumb subdomain. In Tgo, the replicative DNA polymerase from
Thermococcus gorgonarius
, we identify a single mutation (E664K) within this region that enables translesion synthesis across a template abasic site or a cyclobutane thymidine dimer. In conjunction with a classic “steric-gate” mutation (Y409G) in the active site, E664K transforms Tgo DNA polymerase into an RNA polymerase capable of synthesizing RNAs up to 1.7 kb long as well as fully pseudouridine-, 5-methyl-C–, 2′-fluoro–, or 2′-azido–modified RNAs primed from a wide range of primer chemistries comprising DNA, RNA, locked nucleic acid (LNA), or 2′O-methyl–DNA. We find that E664K enables RNA synthesis by selectively increasing polymerase affinity for the noncognate RNA/DNA duplex as well as lowering the
K
m
for ribonucleotide triphosphate incorporation. This gatekeeper mutation therefore identifies a key missing step in the adaptive path from DNA to RNA polymerases and defines a previously unknown postsynthetic determinant of polymerase substrate specificity with implications for the synthesis and replication of noncognate nucleic acid polymers.
Spatial-temporal dynamics of collective chemosensing
Authors: Sun Bo , Lembong Josephine , Normand Valery , Rogers Matthew , Stone Howard A.
Published: May 2012

Although the process of chemosensing by individual cells is intrisically stochastic, multicellular organisms exhibit highly regulated responses to external stimulations. Two key elements to understand the deterministic features of chemosensing are intercellular communications and the role of pacemaker cells. To characterize the collective behavior induced by these two factors, we study the spatial-temporal calcium dynamics of fibroblast cells in response to ATP stimulation. We find that closely packed cell colonies exhibit faster, more synchronized, and highly correlated responses compared to isolated cells. In addition, we demonstrate for chemosensing the existence of pacemaker cells and how the presence of gap junctions impact the first step of the collective response. By further comparing these results with the calcium dynamics of cells embedded in thin hydrogel films, where intercellular communication is only possible via diffusing molecules, we conclude that gap junctions are required for synchronized and highly correlated responses among cells in high density colonies. In addition, in high density cell colonies, both communication channels lead to calcium oscillations following the stimulation by external ATP. While the calcium oscillations associated with cells directly exposed to external flows were transient, the oscillations of hydrogel trapped cells can persist with a fundamental frequency and higher harmonics. Our observations and measurements highlight the crucial role of intercellular signaling for generating regulated spatial and temporal dynamics in cell colonies and tissues.
RIP1, a member of an
Arabidopsis
protein family, interacts with the protein RARE1 and broadly affects RNA editing
Authors: Bentolila Stephane , Heller Wade P. , Sun Tao , Babina Arianne M. , Friso Giulia , van Wijk Klaas J. , Hanson Maureen R.
Published: May 2012

Transcripts of plant organelle genes are modified by cytidine-to-uridine (C-to-U) RNA editing, often changing the encoded amino acid predicted from the DNA sequence. Members of the PLS subclass of the pentatricopeptide repeat (PPR) motif-containing family are site-specific recognition factors for either chloroplast or mitochondrial C targets of editing. However, other than PPR proteins and the
cis
-elements on the organelle transcripts, no other components of the editing machinery in either organelle have previously been identified. The
Arabidopsis
chloroplast PPR protein Required for AccD RNA Editing 1 (RARE1) specifies editing of a C in the
accD
transcript. RARE1 was detected in a complex of >200 kDa. We immunoprecipitated epitope-tagged RARE1, and tandem MS/MS analysis identified a protein of unknown function lacking PPR motifs; we named it RNA-editing factor interacting protein 1 (RIP1). Yeast two-hybrid analysis confirmed RIP1 interaction with RARE1, and RIP1-GFP fusions were found in both chloroplasts and mitochondria. Editing assays for all 34 known
Arabidopsis
chloroplast targets in a
rip1
mutant revealed altered efficiency of 14 editing events. In mitochondria, 266 editing events were found to have reduced efficiency, with major loss of editing at 108 C targets. Virus-induced gene silencing of
RIP1
confirmed the altered editing efficiency. Transient introduction of a WT
RIP1
allele into
rip1
improved the defective RNA editing. The presence of RIP1 in a protein complex along with chloroplast editing factor RARE1 indicates that RIP1 is an important component of the RNA editing apparatus that acts on many chloroplast and mitochondrial C targets.
Moment-based inference predicts bimodality in transient gene expression
Authors: Zechner Christoph , Ruess Jakob , Krenn Peter , Pelet Serge , Peter Matthias , Lygeros John , Koeppl Heinz
Published: May 2012

Recent computational studies indicate that the molecular noise of a cellular process may be a rich source of information about process dynamics and parameters. However, accessing this source requires stochastic models that are usually difficult to analyze. Therefore, parameter estimation for stochastic systems using distribution measurements, as provided for instance by flow cytometry, currently remains limited to very small and simple systems. Here we propose a new method that makes use of low-order moments of the measured distribution and thereby keeps the essential parts of the provided information, while still staying applicable to systems of realistic size. We demonstrate how cell-to-cell variability can be incorporated into the analysis obviating the need for the ubiquitous assumption that the measurements stem from a homogeneous cell population. We demonstrate the method for a simple example of gene expression using synthetic data generated by stochastic simulation. Subsequently, we use time-lapsed flow cytometry data for the osmo-stress induced transcriptional response in budding yeast to calibrate a stochastic model, which is then used as a basis for predictions. Our results show that measurements of the mean and the variance can be enough to determine the model parameters, even if the measured distributions are not well-characterized by low-order moments only—e.g., if they are bimodal.
Memory B cells are a more reliable archive for historical antimalarial responses than plasma antibodies in no-longer exposed children
Authors: Ndungu Francis Maina , Olotu Ally , Mwacharo Jedidah , Nyonda Mary , Apfeld Jordan , Mramba Lazarus K. , Fegan Gregory W. , Bejon Philip , Marsh Kevin
Published: May 2012

Humans respond to foreign antigen by generating plasma Abs and memory B cells (MBCs). The Ab response then declines, sometimes to below the limit of detection. In contrast, MBCs are generally thought to be long-lived. We tested and comparedPlasmodium falciparum(Pf)-specific Ab and MBC responses in two populations of children: (i) previously exposed children who had documentedPfinfections several years ago, but minimal exposure since then; and (ii) persistently exposed children living in a separate but nearby endemic area. We found that althoughPf-specific plasma Abs were lower in previously exposed children compared with persistently exposed children, their cognate MBCs were maintained at similar frequencies. We conclude that serological analysis by itself would greatly underestimate the true memory ofPf-specific Ab responses in previously exposed children living in areas wherePftransmission has been reduced or eliminated.
Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro
Authors: Hayes John A. , Wang Xueying , Del Negro Christopher A.
Published: May 2012

How brain functions degenerate in the face of progressive cell loss is an important issue that pertains to neurodegenerative diseases and basic properties of neural networks. We developed an automated system that uses two-photon microscopy to detect rhythmic neurons from calcium activity, and then individually laser ablates the targets while monitoring network function in real time. We applied this system to the mammalian respiratory oscillator located in the pre-Bötzinger Complex (preBötC) of the ventral medulla, which spontaneously generates breathing-related motor activity in vitro. Here, we show that cumulatively deleting preBötC neurons progressively decreases respiratory frequency and the amplitude of motor output. On average, the deletion of 120 ± 45 neurons stopped spontaneous respiratory rhythm, and our data suggest ≈82% of the rhythm-generating neurons remain unlesioned. Cumulative ablations in other medullary respiratory regions did not affect frequency but diminished the amplitude of motor output to a lesser degree. These results suggest that the preBötC can sustain insults that destroy no more than ≈18% of its constituent interneurons, which may have implications for the onset of respiratory pathologies in disease states.
First wave of cultivators spread to Cyprus at least 10,600 y ago
Authors: Vigne Jean-Denis , Briois François , Zazzo Antoine , Willcox George , Cucchi Thomas , Thiébault Stéphanie , Carrère Isabelle , Franel Yodrik , Touquet Régis , Martin Chloé , Moreau Christophe , Comby Clothilde , Guilaine Jean
Published: May 2012

Early Neolithic sedentary villagers started cultivating wild cereals in the Near East 11,500 y ago [Pre-Pottery Neolithic A (PPNA)]. Recent discoveries indicated that Cyprus was frequented by Late PPNA people, but the earliest evidence until now for both the use of cereals and Neolithic villages on the island dates to 10,400 y ago. Here we present the recent archaeological excavation at Klimonas, which demonstrates that established villagers were living on Cyprus between 11,100 and 10,600 y ago. Villagers had stone artifacts and buildings (including a remarkable 10-m diameter communal building) that were similar to those found on Late PPNA sites on the mainland. Cereals were introduced from the Levant, and meat was obtained by hunting the only ungulate living on the island, a small indigenous Cypriot wild boar. Cats and small domestic dogs were brought from the mainland. This colonization suggests well-developed maritime capabilities by the PPNA period, but also that migration from the mainland may have occurred shortly after the beginning of agriculture.
Disclosing information about the self is intrinsically rewarding
Authors: Tamir Diana I. , Mitchell Jason P.
Published: May 2012

Humans devote 30–40% of speech output solely to informing others of their own subjective experiences. What drives this propensity for disclosure? Here, we test recent theories that individuals place high subjective value on opportunities to communicate their thoughts and feelings to others and that doing so engages neural and cognitive mechanisms associated with reward. Five studies provided support for this hypothesis. Self-disclosure was strongly associated with increased activation in brain regions that form the mesolimbic dopamine system, including the nucleus accumbens and ventral tegmental area. Moreover, individuals were willing to forgo money to disclose about the self. Two additional studies demonstrated that these effects stemmed from the independent value that individuals placed on self-referential thought and on simply sharing information with others. Together, these findings suggest that the human tendency to convey information about personal experience may arise from the intrinsic value associated with self-disclosure.
Dynamics of the O(
3
P) + CHD
3
(
v
CH
= 0,1) reactions on an accurate ab initio potential energy surface
Authors: Czakó Gábor , Bowman Joel M.
Published: May 2012

Recent experimental and theoretical studies on the dynamics of the reactions of methane with F and Cl atoms have modified our understanding of mode-selective chemical reactivity. The O + methane reaction is also an important candidate to extend our knowledge on the rules of reactivity. Here, we report a unique full-dimensional ab initio potential energy surface for the O(
3
P) + methane reaction, which opens the door for accurate dynamics calculations using this surface. Quasiclassical trajectory calculations of the angular and vibrational distributions for the ground state and CH stretching excited O + CHD
3
(
v
1
 = 0,1) → OH + CD
3
reactions are in excellent agreement with the experiment. Our theory confirms what was proposed experimentally: The mechanistic origin of the vibrational enhancement is that the CH-stretching excitation enlarges the reactive cone of acceptance.
Human spermatozoa migration in microchannels reveals boundary-following navigation
Authors: Denissenko Petr , Kantsler Vasily , Smith David J. , Kirkman-Brown Jackson
Published: May 2012

The migratory abilities of motile human spermatozoa in vivo are essential for natural fertility, but it remains a mystery what properties distinguish the tens of cells which find an egg from the millions of cells ejaculated. To reach the site of fertilization, sperm must traverse narrow and convoluted channels, filled with viscous fluids. To elucidate individual and group behaviors that may occur in the complex three-dimensional female tract environment, we examine the behavior of migrating sperm in assorted microchannel geometries. Cells rarely swim in the central part of the channel cross-section, instead traveling along the intersection of the channel walls (“channel corners”). When the channel turns sharply, cells leave the corner, continuing ahead until hitting the opposite wall of the channel, with a distribution of departure angles, the latter being modulated by fluid viscosity. If the channel bend is smooth, cells depart from the inner wall when the curvature radius is less than a threshold value close to 150 μm. Specific wall shapes are able to preferentially direct motile cells. As a consequence of swimming along the corners, the domain occupied by cells becomes essentially one-dimensional, leading to frequent collisions, and needs to be accounted for when modeling the behavior of populations of migratory cells and considering how sperm populate and navigate the female tract. The combined effect of viscosity and three-dimensional architecture should be accounted for in future in vitro studies of sperm chemoattraction.
Depolymerization dynamics of individual filaments of bacterial cytoskeletal protein FtsZ
Authors: Mateos-Gil Pablo , Paez Alfonso , Hörger Ines , Rivas Germán , Vicente Miguel , Tarazona Pedro , Vélez Marisela
Published: May 2012

We report observation and analysis of the depolymerization filaments of the bacterial cytoskeletal protein FtsZ (filament temperature-sensitive Z) formed on a mica surface. At low concentration, proteins adsorbed on the surface polymerize forming curved filaments that close into rings that remain stable for some time before opening irreversibly and fully depolymerizing. The distribution of ring lifetimes (
T
) as a function of length (
N
), shows that the rate of ring aperture correlates with filament length. If this ring lifetime is expressed as a bond survival time, (
T

b

 ≡ 
NT
), this correlation is abolished, indicating that these rupture events occur randomly and independently at each monomer interface. After rings open irreversibly, depolymerization of the remaining filaments is fast, but can be slowed down and followed using a nonhydrolyzing GTP analogue. The histogram of depolymerization velocities of individual filaments has an asymmetric distribution that can be fit with a computer model that assumes two rupture rates, a slow one similar to the one observed for ring aperture, affecting monomers in the central part of the filaments, and a faster one affecting monomers closer to the open ends. From the quantitative analysis, we conclude that the depolymerization rate is affected both by nucleotide hydrolysis rate and by its exchange along the filament, that all monomer interfaces are equally competent for hydrolysis, although depolymerization is faster at the open ends than in central filament regions, and that all monomer–monomer interactions, regardless of the nucleotide present, can adopt a curved configuration.
Generation of quinolone antimalarials targeting the
Plasmodium falciparum
mitochondrial respiratory chain for the treatment and prophylaxis of malaria
Authors: Biagini Giancarlo A. , Fisher Nicholas , Shone Alison E. , Mubaraki Murad A. , Srivastava Abhishek , Hill Alisdair , Antoine Thomas , Warman Ashley J. , Davies Jill , Pidathala Chandrakala , Amewu Richard K. , Leung Suet C. , Sharma Raman , Gibbons Peter , Hong David W. , Pacorel Bénédicte , Lawrenson Alexandre S. , Charoensutthivarakul Sitthivut , Taylor Lee , Berger Olivier , Mbekeani Alison , Stocks Paul A. , Nixon Gemma L. , Chadwick James , Hemingway Janet , Delves Michael J. , Sinden Robert E. , Zeeman Anne-Marie , Kocken Clemens H. M. , Berry Neil G. , O’Neill Paul M. , Ward Stephen A.
Published: May 2012

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (
Plasmodium falciparum
NDH2) and cytochrome
bc
1
. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant
P. falciparum
parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (
Plasmodium cynomolgi
) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the
Plasmodium berghei
mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria.
Connexin 43 controls the multipolar phase of neuronal migration to the cerebral cortex
Authors: Liu Xiuxin , Sun Lin , Torii Masaaki , Rakic Pasko
Published: May 2012

The prospective pyramidal neurons, migrating from the proliferative ventricular zone to the overlaying cortical plate, assume multipolar morphology while passing through the transient subventricular zone. Here, we show that this morphogenetic transformation, from the bipolar to the mutipolar and then back to bipolar again, is associated with expression of connexin 43 (Cx43) and, that knockdown of Cx43 retards, whereas its overexpression enhances, this morphogenetic process. In addition, we have observed that knockdown of Cx43 reduces expression of p27, whereas overexpression of p27 rescues the effect of Cx43 knockdown in the multipolar neurons. Furthermore, functional gap junction/hemichannel domain, and the C-terminal domain of Cx43, independently enhance the expression of p27 and promote the morphological transformation and migration of the multipolar neurons in the SVZ/IZ. Collectively, these results indicate that Cx43 regulates the passage of migrating neurons through their multipolar stage via p27 signaling and that interference with this process, by either genetic and/or environmental factors, may cause cortical malformations.
Gene 5.5 protein of bacteriophage T7 in complex with
Escherichia coli
nucleoid protein H-NS and transfer RNA masks transfer RNA priming in T7 DNA replication
Authors: Zhu Bin , Lee Seung-Joo , Tan Min , Wang En-Duo , Richardson Charles C.
Published: May 2012

DNA primases provide oligoribonucleotides for DNA polymerase to initiate lagging strand synthesis. A deficiency in the primase of bacteriophage T7 to synthesize primers can be overcome by genetic alterations that decrease the expression of T7 gene 5.5, suggesting an alternative mechanism to prime DNA synthesis. The product of gene 5.5 (gp5.5) forms a stable complex with the
Escherichia coli
histone-like protein H-NS and transfer RNAs (tRNAs). The 3′-terminal sequence (5′-ACCA-3′) of tRNAs is identical to that of a functional primer synthesized by T7 primase. Mutations in T7 that suppress the inability of primase reduce the amount of gp5.5 and thus increase the pool of tRNA to serve as primers. Alterations in T7 gene 3 facilitate tRNA priming by reducing its endonuclease activity that cleaves at the tRNA–DNA junction. The tRNA bound to gp5.5 recruits H-NS. H-NS alone inhibits reactions involved in DNA replication, but the binding to gp5.5–tRNA complex abolishes this inhibition.
A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions
Authors: Xue Wen , Kitzing Thomas , Roessler Stephanie , Zuber Johannes , Krasnitz Alexander , Schultz Nikolaus , Revill Kate , Weissmueller Susann , Rappaport Amy R. , Simon Janelle , Zhang Jack , Luo Weijun , Hicks James , Zender Lars , Wang Xin Wei , Powers Scott , Wigler Michael , Lowe Scott W.
Published: May 2012

The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a “two-hit” mechanism in the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events.
Headteachers’ readings of and responses to disadvantaged contexts: evidence from English primary schools
Authors: Lupton Ruth , Thrupp Martin
Published: May 2012

Existing research demonstrates the impact of context on school organisation and management, curriculum and pedagogy and on student peer relations. New developments in English education policy will devolve more responsibility for dealing with these issues to headteachers. Headteachers' readings of their contexts and the responses that they make are thus of increasing interest. This paper draws on interviews with eight headteachers of less advantaged English primary schools to explore how they understand and articulate the contexts in which their schools operate and how this knowledge is translated into strategies for organising curriculum, pedagogy and other school processes. These headteachers observed context through the lens of the behaviour of parents and children in relation to school, contrasting it with an assumed middle‐class normality. More critical perspectives on families' social and economic position or on the contribution of school practice to educational exclusion were largely absent. School responses were many and varied but, given the constraints of budgets, market and performative pressures, were unlikely to substantially transform the educational experiences and outcomes of disadvantaged students. We point to the continuing need for more contextualised funding mechanisms and policies to improve schools in disadvantaged areas and also, in the light of devolution to schools, to the need to develop mechanisms of support to headteachers to help them to develop critical understandings of context and to reflect on school process and practices in the light of these understandings.
miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2
Authors: Wei Jianwen , Shi Yu , Zheng Lihua , Zhou Bin , Inose Hiroyuki , Wang Ji , Guo X. Edward , Grosschedl Rudolf , Karsenty Gerard
Published: May 2012

A screen of microRNAs preferentially expressed in osteoblasts identified members of the miR-34 family as regulators of osteoblast proliferation and/or differentiation. Osteoblast-specific gain- and loss-of-function experiments performed in vivo revealed that miR-34b and -c affected skeletogenesis during embryonic development, as well as bone mass accrual after birth, through two complementary cellular and molecular mechanisms. First, they inhibited osteoblast proliferation by suppressing Cyclin D1, CDK4, and CDK6 accumulation. Second, they inhibited terminal differentiation of osteoblasts, at least in part through the inhibition of SATB2, a nuclear matrix protein that is a critical determinant of osteoblast differentiation. Genetic evidence obtained in the mouse confirmed the importance of SATB2 regulation by miR-34b/c. These results are the first to identify a family of microRNAs involved in bone formation in vivo and to identify a specific genetic pathway by which these microRNAs regulate osteoblast differentiation.
Teichmüller space for iterated function systems
Authors: Hille Martial , Snigireva Nina
Published: May 2012

In this paper we investigate families of iterated function systems (IFS) and conformal iterated function systems (CIFS) from a deformation point of view. Namely, we introduce the notion of Teichmüller space for finitely and infinitely generated (C)IFS and study its topological and metric properties. Firstly, we completely classify its boundary. In particular, we prove that this boundary essentially consists of inhomogeneous systems. Secondly, we equip Teichmüller space for (C)IFS with different metrics, an Euclidean, a hyperbolic, and aλ\lambda-metric. We then study continuity of the Hausdorff dimension function and the pressure function with respect to these metrics. We also show that the hyperbolic metric and theλ\lambda-metric induce topologies stronger than the non-metrizableλ\lambda-topology introduced by Roy and Urbanski and, therefore, provide an alternative to theλ\lambda-topology in the study of continuity of the Hausdorff dimension function and the pressure function. Finally, we investigate continuity properties of various limit sets associated with infinitely generated (C)IFS with respect to our metrics.
Structural Changes in the Time Series of Food Prices and Volatility Measurement
Authors: Jin Hyun Joung , Kim Taeho
Published: May 2012

Volatility in product prices is of considerable interest in the food and agricultural policy arena. Standard deviation (SD) type of measures, including variance and the coefficient of variation, have been commonly used for estimating realized volatility. These methods are relatively simple to calculate and focus on the width of the data. Despite these merits, they have a shortcoming in that the statistics can be amplified when the time series is nonstationary. This study suggests a new way to measure price variation. The structural breaks in the unconditional mean of a time series are determined, and then the conventional SD type of measures for each regime are calculated. This method addresses the weak point of the SD type of measure and is a competitive alternative to the conditional variance type or the trend deviation type of measures when the time series at comparison have notably different data‐generating processes or have nonstationarity.
First Report of Botryosphaeria obtusa as Causal Agent of Olive Tree Branch Dieback in Tunisia
Authors: Chattaoui M. , Rhouma A. , Msallem M. , Pérez M. , Moral J. , Trapero A.
Published: May 2012

A branch dieback of olive trees (Olea europaea L. cv. Manzanilla de Sevilla) was observed in 2010 in an orchard (50 ha), located in the Testour region of northern Tunisia. More than 50% of trees were severely damaged by the disease. Symptomatic trees presented dead branches and wilted leaves, which remained attached to the shoots, and the affected tissues appeared abnormally dark compared with the inner bark of healthy branches. Numerous pycnidia were observed on the surface of the infected branches. For diagnosis, symptomatic stems were collected and small pieces of discolored tissues were excised from lesion margins, surface sterilized in 0.5% sodium hypochlorite for 1 min, rinsed and dried on sterilized filter paper, then placed on acidified Difco potato dextrose agar plates (APDA; 2.5 ml of 25% lactic acid per liter). Plates were incubated at 25°C for 4 to 5 days, and hyphal tips from developing fungal colonies were transferred to PDA and placed under fluorescent light (12 h/day). A fastgrowing, pycnidia-producing fungus was consistently isolated, with conidia exuding onto the agar surface of 10-day-old cultures. On the basis of colony characteristics, isolates were identified as Botryosphaeria obtusa (3). Conidia were large, dark brown, aseptate, rounded at both ends or truncate at base, and 25 to 26.8 × 10.5 to 12.03 μm. Pathogenicity tests were performed on detached stems of cv. Manzanilla by 7-mm diameter mycelial plugs cut from actively growing cultures of the fungus. Stems (30 cm length) were cleaned, surface sterilized with sodium hypochlorite (0.25% for 2 min), and wounded with a sterilized scalpel. Mycelial disks were placed over wounds and wrapped with Parafilm to prevent desiccation. Control stems were mock inoculated with sterile agar plugs. Inoculated and control stems were placed in polyethylene boxes and incubated at 25°C. After 45 days, inoculated stems developed brown discoloration, and small dark pycnidia appeared on stem surfaces. Controls remained healthy. Koch's postulates were verified by isolating the fungus from symptomatic stems. To confirm the identification, DNA of one isolate was extracted and the fungal primers ITS1 and ITS4 (4) were used to amplify the internal transcribed spacer region of rDNA. Purified amplicons were sequenced and a BLAST search of the GenBank database revealed 99% homology with B. obtusa isolate HO166525.1. The anamorph of the fungus, Diplodia seriata, has been recognized as the cause of fruit rot of olive (1) and branch canker or dieback (2). To our knowledge, this is the first report of a canker disease of olive trees caused by B. obtusa in Tunisia.

References: (1) J. Moral et al. Plant Dis. 92:311, 2008. (2) J. Moral et al. Phytopathology 100:1340, 2010. (3) A. Taylor et al. Australas. Plant Pathol. 34:187, 2005. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA, 1990.
First Report of Fruit Rot in Pear Caused by Botryosphaeria dothidea in Italy
Authors: Garibaldi A. , Bertetti D. , Poli A. , Gullino M. L.
Published: May 2012

Pear (Pyrus communis L.) is widely grown in Italy, the leading producer in Europe. In summer 2011, a previously unknown rot was observed on fruit of an old cultivar, Spadoncina, in a garden in Torino Province (northern Italy). The decayed area of the fruit was soft, dark brown, slightly sunken, circular, and surrounded by an irregular margin. The internal decayed area appeared rotten and brown and rotted fruit eventually fell. To isolate the causal agent, fruits were soaked in 1% NaOCl for 30 s and fragments (approximately 2 mm) were taken from the margin of the internal diseased tissues, cultured on potato dextrose agar (PDA), and incubated at temperatures between 20 and 28°C under alternating light and darkness. Colonies of the fungus initially appeared whitish, then turned dark gray. After about 30 days of growth, unicellular elliptical hyaline conidia were produced in pycnidia. Conidia measured 16 to 24 × 5 to 7 (average 20.1 × 5.7) μm (n = 50). The morphological characteristics are similar to those of the fungus Botryosphaeria dothidea (Moug.: Fr.) Ces. & De Not. (4). The internal transcribed spacer (ITS) region of rDNA was amplified with the primers ITS1/ITS4 and sequenced. BLAST analysis (1) of the 473-bp segment showed a 100% similarity with the sequence of the epitype of B. dothidea AY236949. The nucleotide sequence has been assigned the GenBank Accession No. JQ418493. Pathogenicity tests were performed by inoculating six pear fruits of the same cultivar (Spadoncina) after surface disinfesting in 1% sodium hypochlorite and wounding. Mycelial disks (8 mm diameter), obtained from 10-day-old PDA cultures of one strain, were placed on wounds. Six control fruits were inoculated with plain PDA. Fruits were incubated at 25 ± 1°C in plastic boxes. The first symptoms developed 3 days after inoculation. After 5 days, the rot was very evident and B. dothidea was consistently reisolated. Noninoculated fruits remained healthy. The pathogenicity test was performed twice. B. dothidea was identified on decayed pears in the United States (2), South Africa, New Zealand, Japan, and Taiwan (3). To our knowledge, this is the first report of the presence of B. dothidea on pear in Italy, as well as in Europe. In Italy, the economic importance of the disease on pear fruit is at present limited, although the pathogen could represent a risk for this crop.

References: (1) S. F. Altschul et al. Nucleic Acids Res., 25:3389, 1997. (2) L. F. Grand. Agr. Res. Serv. Techn. Bull. 240:1, 1985. (3) Y. Ko et al. Plant Prot. Bull. (Taiwan) 35:211, 1993. (4) B. Slippers et al. Mycologia 96:83, 2004.
A Graft-Based Chemotherapy Method for Screening Effective Molecules and Rescuing Huanglongbing-Affected Citrus Plants
Authors: Zhang Muqing , Powell Charles A. , Guo Ying , Doud Melissa S. , Duan Yongping
Published: May 2012

Huanglongbing (HLB) is the most devastating disease of citrus. The global citrus industry is in urgent need of effective chemical treatments for HLB control because of its rapid spreading worldwide. Due to the fastidious nature of the pathogens, and the poor permissibility of citrus leaf surfaces, effective screening of chemicals for the HLB control can be challenging. In this study, we developed a graft-based chemotherapy method to rapidly screen potential HLB-controlling chemical compounds. In addition, we improved transmission efficiency by using the best HLB-affected scion–rootstock combination, and demonstrated the HLB bacterial titer was the critical factor in transmission. The HLB-affected lemon scions had a high titer of HLB bacterium, survival rate (83.3%), and pathogen transmission rate (59.9%). Trifoliate, a widely used commercial rootstock, had the highest survival rate (>70.0%) compared with grapefruit (52.6%) and sour orange (50.4%). Using this method, we confirmed a mixture of penicillin and streptomycin was the most effective compounds in eliminating the HLB bacterium from the HLB-affected scions, and in successfully rescuing severely HLB-affected citrus germplasms. These findings are useful not only for chemical treatments but also for graft-based transmission studies in HLB and other Liberibacter diseases.
High Intraoperative Inspired Oxygen Does Not Increase Postoperative Supplemental Oxygen Requirements
Authors: Mackintosh Natalie , Gertsch Matthew C. , Hopf Harriet W. , Pace Nathan L. , White Julia , Morris Rebecca , Morrissey Candice , Wilding Victoria , Herway Seth
Published: May 2012

Background

Although a high fraction of inspired oxygen (FIO2) could reduce surgical site infection, there is concern it could increase postoperative pulmonary complications, including hypoxemia. Intraoperative positive end-expiratory pressure can improve postoperative pulmonary function. A practical measure of postoperative pulmonary function and the degree of hypoxemia is supplemental oxygen requirement. We performed a double-blind randomized 2 × 2 factorial study on the effects of intraoperative FIO2 0.3 versus more than 0.9 with and without positive end-expiratory pressure on the primary outcome of postoperative supplemental oxygen requirements in patients undergoing lower risk surgery.

Methods

After Institutional Review Board approval and consent, 100 subjects were randomized using computer-generated lists into four treatment groups (intraoperative FIO2 0.3 vs. more than 0.9, with and without 3-5 cm H2O positive end-expiratory pressure). Thirty minutes and 24 h after extubation, supplemental oxygen was discontinued. Arterial oxygen saturation by pulse oximetry was recorded 15 min later. If oxygen saturation decreased to less than 90%, supplemental oxygen was added incrementally to maintain saturation more than 90%.

Results

Nearly all subjects required supplemental oxygen in the postanesthesia care unit. Nonparametric Wilcoxon rank sum test demonstrated no statistically significant difference between groups in supplemental oxygen requirements at 45 min and 24 h after tracheal extubation (P = 0.56 and 0.98, respectively).

Conclusions

Use of intraoperative FIO2 more than 0.9 was not associated with increased oxygen requirement, suggesting it does not induce postoperative hypoxemia beyond anesthetic induction and surgery. Therefore, it may be reasonable to use high inspired oxygen in surgical patients with relatively normal pulmonary function.
Identification of Serum Protein Biomarkers in Biliary Atresia by Mass Spectrometry and Enzyme‐linked Immunosorbent Assay
Authors: Song Zai , Dong Rui , Fan Yuxia , Zheng Shan
Published: May 2012

Objective:

There is an urgent need to identify noninvasive and convenient biomarkers for early diagnosis of biliary atresia (BA). The aim of the present study was to identify potential protein biomarkers for BA.

Methods:

Serum samples from 42 infants with BA, 38 infants with non‐BA neonatal cholestasis (NC), and 36 healthy controls (HC) were randomly divided into a training set and a test set. Serum proteomic profiles were measured using surface‐enhanced desorption/ionization time‐of‐flight mass spectrometry. Candidate biomarkers were purified using high‐performance liquid chromatography, identified using liquid chromatography tandem mass spectrometry, and validated using enzyme‐linked immunosorbent assay.

Results:

A total of 2 protein peaks (m/z with 8697 and 9098 Da) with differential expression levels were found using surface‐enhanced desorption/ionization time‐of‐flight mass spectrometry. These peaks were then analyzed by a support vector machine to construct a classification model in the training set. The sensitivity and specificity of the model were 94.1% and 91.8%, respectively, in the test set. One candidate biomarker (9098 Da) was identified as Apo C‐II, and was found to be downregulated in BA samples compared with HC samples, and upregulated in BA samples compared with NC samples. The other candidate biomarker (8697 Da) was identified as Apo C‐III, and was found to be upregulated in BA compared with NC and HC.

Conclusions:

Apo C‐II and Apo C‐III may be potential protein biomarkers of BA and may be useful in distinguishing infants with BA from healthy and NC infants. Further studies with additional populations or using prediagnostic serum are needed to confirm the importance of these findings as diagnostic markers of infants with BA.
Investigative MR Cholangiopancreatography for Primary Sclerosing Cholangitis–type Lesions in Children With IBD
Authors: Alexopoulou Efthymia , Xenophontos Polis E. , Economopoulos Nikos , Spyridopoulos Themistoklis N. , Papakonstantinou Olympia , Panayotou Ioanna , Dimakou Konstantina , Roma Eleftheria , Kelekis Nikolaos L.
Published: May 2012

Objectives:

The aim of the study was to estimate the frequency of primary sclerosing cholangitis (PSC)–type lesions in children with inflammatory bowel disease (IBD) by means of magnetic resonance cholangiopancreatography (MRCP), and to investigate the association between a series of easily applicable data on the one hand and the presentation of such lesions at MRCP on the other hand.

Methods:

Collected demographic, laboratory, and magnetic resonance enterography data from the records of 73 children with IBD were cross‐sectionally related to the MRCP‐based diagnosis.

Results:

Around the time of MRCP, the distribution of IBD subtypes was 64.4%, 24.7%, and 11% for Crohn disease, indeterminate colitis, and ulcerative colitis, respectively. A total of 11 patients (15.1%) were identified with PSC‐type lesions. Demographic and magnetic resonance enterography data were unrelated to the MRCP outcome. Biochemical abnormalities were of low prevalence (<50%) among patients with PSC. The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ‐glutamyl transferase were significantly higher in the PSC group, both at initial diagnosis of IBD and at the time of MRCP. Less‐consistent results were documented for bilirubin and alkaline phosphatase, especially at initial diagnosis of IBD.

Conclusions:

The abnormality prevalences of aspartate transaminase, alanine transaminase, and γ‐glutamyl transferase were significantly higher in the PSC group. Nevertheless, PSC‐type lesions frequently occur in pediatric IBD, even if the biochemical profile is hardly indicative of this probability.
Diagnostic Approach and Management of Cow's‐Milk Protein Allergy in Infants and Children
Authors: Koletzko S. , Niggemann B. , Arato A. , Dias J.A. , Heuschkel R. , Husby S. , Mearin M.L. , Papadopoulou A. , Ruemmele F.M. , Staiano A. , Schäppi M.G. , Vandenplas Y.
Published: May 2012

Objectives:

This guideline provides recommendations for the diagnosis and management of suspected cow's‐milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence‐based guidelines on CMPA.

Diagnosis:

If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life‐threatening reaction with a positive test for CMP–specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA.

Treatment:

In breast‐fed infants, the mother should start a strict CMP‐free diet. Non–breast‐fed infants with confirmed CMPA should receive an extensively hydrolyzed protein‐based formula with proven efficacy in appropriate clinical trials; amino acids–based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion.

Reevaluation:

Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.
Posttranscriptional Control of Photosynthetic mRNA Decay under Stress Conditions Requires 3′ and 5′ Untranslated Regions and Correlates with Differential Polysome Association in Rice
Authors: Park Su-Hyun , Chung Pil Joong , Juntawong Piyada , Bailey-Serres Julia , Kim Youn Shic , Jung Harin , Bang Seung Woon , Kim Yeon-Ki , Do Choi Yang , Kim Ju-Kon
Published: May 2012

Abiotic stress, including drought, salinity, and temperature extremes, regulates gene expression at the transcriptional and posttranscriptional levels. Expression profiling of total messenger RNAs (mRNAs) from rice (Oryza sativa) leaves grown under stress conditions revealed that the transcript levels of photosynthetic genes are reduced more rapidly than others, a phenomenon referred to as stress-induced mRNA decay (SMD). By comparing RNA polymerase II engagement with the steady-state mRNA level, we show here that SMD is a posttranscriptional event. The SMD of photosynthetic genes was further verified by measuring the half-lives of the small subunit of Rubisco (RbcS1) and Chlorophyll a/b-Binding Protein1 (Cab1) mRNAs during stress conditions in the presence of the transcription inhibitor cordycepin. To discern any correlation between SMD and the process of translation, changes in total and polysome-associated mRNA levels after stress were measured. Total and polysome-associated mRNA levels of two photosynthetic (RbcS1 and Cab1) and two stress-inducible (Dehydration Stress-Inducible Protein1 and Salt-Induced Protein) genes were found to be markedly similar. This demonstrated the importance of polysome association for transcript stability under stress conditions. Microarray experiments performed on total and polysomal mRNAs indicate that approximately half of all mRNAs that undergo SMD remain polysome associated during stress treatments. To delineate the functional determinant(s) of mRNAs responsible for SMD, the RbcS1 and Cab1 transcripts were dissected into several components. The expressions of different combinations of the mRNA components were analyzed under stress conditions, revealing that both 3′ and 5′ untranslated regions are necessary for SMD. Our results, therefore, suggest that the posttranscriptional control of photosynthetic mRNA decay under stress conditions requires both 3′ and 5′ untranslated regions and correlates with differential polysome association.