bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Nonmarket Institution under Imperfect Markets: Labor Sharing for Tropical Forest Clearing
Authors: Takasaki Yoshito , Coomes Oliver T. , Abizaid Christian , Brisson Stéphanie
Published: January 2014

This article examines the substitutability, productivity, efficiency, and evolution of an important agrarian nonmarket institution—labor sharing. Analysis of field‐level data on forest clearing through time among Amazonian shifting cultivators reveals that (a) family, hired, and cooperative labor are perfect substitutes, and hired and cooperative labor are equally productive, and both are more productive than family labor; (b) the combination of labor market and labor sharing makes productivity‐adjusted total labor use unconstrained by household and network endowments (i.e., efficient labor allocation); and (c) as labor composition is constrained by network endowments and liquidity, credit policies alter both labor composition and labor network formation.
Subclonal variant calling with multiple samples and prior knowledge
Authors: Gerstung Moritz , Papaemmanuil Elli , Campbell Peter J.
Published: January 2014

Motivation: Targeted resequencing of cancer genes in large cohorts of patients is important to understand the biological and clinical consequences of mutations. Cancers are often clonally heterogeneous, and the detection of subclonal mutations is important from a diagnostic point of view, but presents strong statistical challenges.

Results: Here we present a novel statistical approach for calling mutations from large cohorts of deeply resequenced cancer genes. These data allow for precisely estimating local error profiles and enable detecting mutations with high sensitivity and specificity. Our probabilistic method incorporates knowledge about the distribution of variants in terms of a prior probability. We show that our algorithm has a high accuracy of calling cancer mutations and demonstrate that the detected clonal and subclonal variants have important prognostic consequences.

Availability: Code is available as part of the Bioconductor package deepSNV.

Contact:  mg14@sanger.ac.uk; pc8@sanger.ac.uk
Preventing overfishing: evolving approaches and emerging challenges
Authors: Sissenwine Michael M. , Mace Pamela M. , Lassen Hans J.
Published: January 2014

Sissenwine, M. M., Mace P. M., and Lassen, H. J. 2014. Preventing Overfishing: Evolving Approaches and Emerging Challenges. – ICES Journal of Marine Science, 71: 153–156. The evolution of fishery management frameworks to prevent overfishing is the theme of the eight papers that follow in this issue of the ICES Journal of Marine Science. The current paper describes common elements of the frameworks. All the frameworks are based on the maximum sustainable yield concept. Frameworks to prevent overfishing have evolved to be increasingly prescriptive. This evolution probably reflects past abuse of flexibility which led to overfishing. The outcome has been a decline in the proportion of stocks suffering from overfishing. However, loss of flexibility may result in large foregone yields from multispecies fisheries, create a mis-match between the expectations for scientific information and the realities of scientific uncertainty, and fail to recognize ecosystem dynamics.
Simulation testing the robustness of stock assessment models to error: some results from the ICES strategic initiative on stock assessment methods
Authors: Deroba J.J. , Butterworth D.S. , Methot R.D. , De Oliveira J.A.A. , Fernandez C. , Nielsen A. , Cadrin S.X. , Dickey-Collas M. , Legault C.M. , Ianelli J. , Valero J.L. , Needle C.L. , O'Malley J.M. , Chang Y-J. , Thompson G.G. , Canales C. , Swain D.P. , Miller D.C.M. , Hintzen N.T. , Bertignac M. , Ibaibarriaga L. , Silva A. , Murta A. , Kell L.T. , de Moor C.L. , Parma A.M. , Dichmont C.M. , Restrepo V.R. , Ye Y. , Jardim E. , Spencer P.D. , Hanselman D.H. , Blaylock J. , Mood M. , Hulson P.-J. F.
Published: January 2014

The World Conference on Stock Assessment Methods (July 2013) included a workshop on testing assessment methods through simulations. The exercise was made up of two steps applied to datasets from 14 representative fish stocks from around the world. Step 1 involved applying stock assessments to datasets with varying degrees of effort dedicated to optimizing fit. Step 2 was applied to a subset of the stocks and involved characteristics of given model fits being used to generate pseudo-data with error. These pseudo-data were then provided to assessment modellers and fits to the pseudo-data provided consistency checks within (self-tests) and among (cross-tests) assessment models. Although trends in biomass were often similar across models, the scaling of absolute biomass was not consistent across models. Similar types of models tended to perform similarly (e.g. age based or production models). Self-testing and cross-testing of models are a useful diagnostic approach, and suggested that estimates in the most recent years of time-series were the least robust. Results from the simulation exercise provide a basis for guidance on future large-scale simulation experiments and demonstrate the need for strategic investments in the evaluation and development of stock assessment methods.
Predicting DNA methylation level across human tissues
Authors: Ma Baoshan , Wilker Elissa H. , Willis-Owen Saffron A. G. , Byun Hyang-Min , Wong Kenny C. C. , Motta Valeria , Baccarelli Andrea A. , Schwartz Joel , Cookson William O. C. M. , Khabbaz Kamal , Mittleman Murray A. , Moffatt Miriam F. , Liang Liming
Published: January 2014

Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles.
Complexity and Loan Performance: Evidence from the Securitization of Commercial Mortgages
Authors: Furfine Craig H.
Published: January 2014

Between 2001 and 2007, the complexity of commercial mortgage-backed securities (CMBS) increased substantially. The median size of commercial mortgage loan pools tripled and the median number of AAA-rated tranches doubled. I examine whether deal complexity is related to loan performance by analyzing a sample of approximately 40,000 commercial mortgage loans from 334 CMBS deals. I find that loan performance is worse for loans in more complex securitizations. However, neither the price of a deal’s securities nor a deal’s risk retention reflected that complexity correlates with lower loan quality. These findings present a challenge for theories of optimal security design.
Time-based reward maximization
Authors: Çavdaroğlu Bilgehan , Zeki Mustafa , Balcı Fuat
Published: January 2014

Humans and animals time intervals from seconds to minutes with high accuracy but limited precision. Consequently, time-based decisions are inevitably subjected to our endogenous timing uncertainty, and thus require temporal risk assessment. In this study, we tested temporal risk assessment ability of humans when participants had to withhold each subsequent response for a minimum duration to earn reward and each response reset the trial time. Premature responses were not penalized in Experiment 1 but were penalized in Experiment 2. Participants tried to maximize reward within a fixed session time (over eight sessions) by pressing a key. No instructions were provided regarding the task rules/parameters. We evaluated empirical performance within the framework of optimality that was based on the level of endogenous timing uncertainty and the payoff structure. Participants nearly tracked the optimal target inter-response times (IRTs) that changed as a function of the level of timing uncertainty and maximized the reward rate in both experiments. Acquisition of optimal target IRT was rapid and abrupt without any further improvement or worsening. These results constitute an example of optimal temporal risk assessment performance in a task that required finding the optimal trade-off between the ‘speed’ (timing) and ‘accuracy’ (reward probability) of timed responses for reward maximization.
Cognitive assessment of mice strains heterozygous for cell-adhesion genes reveals strain-specific alterations in timing
Authors: Gallistel C. R. , Tucci Valter , Nolan Patrick M. , Schachner Melitta , Jakovcevski Igor , Kheifets Aaron , Barboza Luendro
Published: January 2014

We used a fully automated system for the behavioural measurement of physiologically meaningful properties of basic mechanisms of cognition to test two strains of heterozygous mutant mice,Bfc(batface) andL1, and their wild-type littermate controls. Both of the target genes are involved in the establishment and maintenance of synapses. We find that theBfcheterozygotes show reduced precision in their representation of interval duration, whereas theL1heterozygotes show increased precision. These effects are functionally specific, because many other measures made on the same mice are unaffected, namely: the accuracy of matching temporal investment ratios to income ratios in a matching protocol, the rate of instrumental and classical conditioning, the latency to initiate a cued instrumental response, the trials on task and the impulsivity in a switch paradigm, the accuracy with which mice adjust timed switches to changes in the temporal constraints, the days to acquisition, and mean onset time and onset variability in the circadian anticipation of food availability.
OmpR phosphorylation regulates ompS1 expression by differentially controlling the use of promoters
Authors: Flores-Valdez Mario Alberto , Fernández-Mora Marcos , Ares Miguel Ángel , Girón Jorge A. , Calva Edmundo , De la Cruz Miguel Ángel
Published: January 2014

TheSalmonella enterica ompS1gene encodes a quiescent porin that belongs to the OmpC/OmpF family. In the present work we analysed the regulatory effects of OmpR phosphorylation onompS1expression. We found thatin vivo, OmpR in its phosphorylated form (OmpR-P) was important in the regulation of the twoompS1promoters: OmpR-P activated the P1 promoter and repressed the P2 promoter in an EnvZ-dependent manner; expression occurs from the P2 promoter in anompRmutant.In vitro, OmpR-P had a higher DNA-binding-affinity to theompS1promoter region than OmpR and OmpRD55A, showing an affinity even higher than that of equivalent DNA regions in the 5′-upstream regulatory sequence of the major porin-encoding genesompCandompF. By analysing different environmental conditions, we found that glucose and glycerol enhancedompS1expression in the wild-type strain. Interestingly the stimulation by glycerol was OmpR-dependent while the effect of glucose was still observed in the absence of OmpR. Acetyl phosphate produced by the AckA-Pta pathway did not influenceompS1regulation. These data indicate the important role of the phosphorylation in the activity of OmpR on the differential regulation of bothompS1promoters and its impact on the pathogenesis.
A 2,4-dichlorophenoxyacetic acid degradation plasmid pM7012 discloses distribution of an unclassified megaplasmid group across bacterial species
Authors: Sakai Yoriko , Ogawa Naoto , Shimomura Yumi , Fujii Takeshi
Published: January 2014

Analysis of the complete nucleotide sequence of plasmid pM7012 from 2,4-dichlorophenoxyacetic-acid (2,4-D)-degrading bacterium Burkholderia sp. M701 revealed that the plasmid had 582 142 bp, with 541 putative protein-coding sequences and 39 putative tRNA genes for the transport of the standard 20 aa. pM7012 contains sequences homologous to the regions involved in conjugal transfer and plasmid maintenance found in plasmids byi_2p from Burkholderia sp. YI23 and pBVIE01 from Burkholderia sp. G4. No relaxase gene was found in any of these plasmids, although genes for a type IV secretion system and type IV coupling proteins were identified. Plasmids with no relaxase gene have been classified as non-mobile plasmids. However, nucleotide sequences with a high level of similarity to the genes for plasmid transfer, plasmid maintenance, 2,4-D degradation and arsenic resistance contained on pM7012 were also detected in eight other megaplasmids (~600 or 900 kb) found in seven Burkholderia strains and a strain of Cupriavidus, which were isolated as 2,4-D-degrading bacteria in Japan and the United States. These results suggested that the 2,4-D degradation megaplasmids related to pM7012 are mobile and distributed across various bacterial species worldwide, and that the plasmid group could be distinguished from known mobile plasmid groups.
Proteomic analyses of baculovirus Anticarsia gemmatalis multiple nucleopolyhedrovirus budded and occluded virus
Authors: Braconi Carla Torres , Ardisson-Araújo Daniel Mendes Pereira , Leme Adriana Franco Paes , Oliveira Juliana Velasco de Castro , Pauletti Bianca Alves , Garcia-Maruniak Alejandra , Ribeiro Bergmann Morais , Maruniak James E. , Zanotto Paolo Marinho de Andrade
Published: January 2014

Baculoviruses infect insects, producing two distinct phenotypes during the viral life cycle: the budded virus (BV) and the occlusion-derived virus (ODV) for intra- and inter-host spread, respectively. Since the 1980s, several countries have been using Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) as a biological control agent against the velvet bean caterpillar, A. gemmatalis. The genome of AgMNPV isolate 2D (AgMNPV-2D) carries at least 152 potential genes, with 24 that possibly code for structural proteins. Proteomic studies have been carried out on a few baculoviruses, with six ODV and two BV proteomes completed so far. Moreover, there are limited data on virion proteins carried by AgMNPV-2D. Therefore, structural proteins of AgMNPV-2D were analysed by MALDI- quadrupole-TOF and liquid chromatography MS/MS. A total of 44 proteins were associated with the ODV and 33 with the BV of AgMNPV-2D. Although 38 structural proteins were already known, we found six new proteins in the ODV and seven new proteins carried by the AgMNPV-2D BV. Eleven cellular proteins that were found on several other enveloped viruses were also identified, which are possibly carried with the virion. These findings may provide novel insights into baculovirus biology and their host interaction. Moreover, our data may be helpful in subsequent applied studies aiming to improve AgMNPV use as a biopesticide and a biotechnology tool for gene expression or delivery.
The ORF4b-encoded accessory proteins of Middle East respiratory syndrome coronavirus and two related bat coronaviruses localize to the nucleus and inhibit innate immune signalling
Authors: Matthews Krystal L. , Coleman Christopher M. , van der Meer Yvonne , Snijder Eric J. , Frieman Matthew B.
Published: January 2014

The recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV), a betacoronavirus, is associated with severe pneumonia and renal failure. The environmental origin of MERS-CoV is as yet unknown; however, its genome sequence is closely related to those of two bat coronaviruses, named BtCoV-HKU4 and BtCoV-HKU5, which were derived from Chinese bat samples. A hallmark of highly pathogenic respiratory viruses is their ability to evade the innate immune response of the host. CoV accessory proteins, for example those from severe acute respiratory syndrome CoV (SARS-CoV), have been shown to block innate antiviral signalling pathways. MERS-CoV, similar to SARS-CoV, has been shown to inhibit type I IFN induction in a variety of cell types in vitro. We therefore hypothesized that MERS-CoV and the phylogenetically related BtCoV-HKU4 and BtCoV-HKU5 may encode proteins with similar capabilities. In this study, we have demonstrated that the ORF4b-encoded accessory protein (p4b) of MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 may indeed facilitate innate immune evasion by inhibiting the type I IFN and NF-κB signalling pathways. We also analysed the subcellular localization of p4b from MERS-CoV, BtCoV-HKU4 and BtCoV-HKU5 and demonstrated that all are localized to the nucleus.
Cimodo virus belongs to a novel lineage of reoviruses isolated from African mosquitoes
Authors: Hermanns Kyra , Zirkel Florian , Kurth Andreas , Drosten Christian , Junglen Sandra
Published: January 2014

A novel reovirus, designated Cimodo virus (CMDV), was isolated from mosquitoes collected in a rainforest region in Côte d’Ivoire. The entire genome comprised 24 835 bp divided into 12 segments ranging from 585 to 4080 bp. The icosahedral non-enveloped virions were 80 nm in diameter. Eight major viral proteins of about 150, 135, 120, 80, 66, 59, 42 and 30 kDa were identified and seven proteins were mapped to the corresponding genome segments by liquid chromatography mass spectrometry. Predicted protein genes diverged by >77 % encoded amino acids from their closest reovirus relatives. The deep phylogenetic branching suggests that CMDV defines an as-yet-unidentified genus within the subfamily Spinareovirinae.
Estimating seed bank accumulation and dynamics in three obligate-seeder Proteaceae species
Authors: Jenkins Meaghan E. , Morrison David A. , Auld Tony D.
Published: January 2014

The seed bank dynamics of the three co-occurring obligate-seeder (i.e. fire-sensitive) Proteaceae species,Banksia ericifolia,Banksia marginataandPetrophile pulchella, were examined at sites of varying time since the most recent fire (i.e. plant age) in the Sydney region. Significant variation among species was found in the number of cones produced, the position of the cones within the canopy, the percentage of barren cones produced (Banksiaspecies only), the number of follicles/bracts produced per cone, and the number of seeds lost/released due to spontaneous fruit rupture. Thus, three different regeneration strategies were observed, highlighting the variation in reproductive strategies of co-occurring Proteaceae species. Ultimately,B. marginatapotentially accumulated a seed bank of ∼3000 seeds per plant after 20 years, with ∼1500 seeds per plant forP. pulchellaand ∼500 forB. ericifolia. Based on these data,B. marginataandB. ericifoliarequire a minimum fire-free period of 8–10 years, with 7–8 years forP. pulchella, to allow for an adequate seed bank to accumulate and thus ensure local persistence of these species in fire-prone habitats.
Tracking global changes induced in the CD4 T cell receptor repertoire by immunisation with a complex antigen using local sequence features of CDR3 protein sequence
Authors: Thomas Niclas , Best Katharine , Cinelli Mattia , Reich-Zeliger Shlomit , Gal Hilah , Shifrut Eric , Madi Asaf , Friedman Nir , Shawe-Taylor John , Chain Benny
Published: January 2014

The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different TcRs in CD4+ T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis, using high throughput parallel sequencing of the TcR beta chain. In order to track the changes induced by immunisation within this very heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the CDR3 repertoire of different mice. Both unsupervised (hierarchical clustering) and supervised (support vector machine) analysis of these different distributions of sequence clusters differentiated between immunised and unimmunised mice with 100% efficiency. The CD4+ T cell receptor repertoires of mice 5 and 14 days post immunisation were clearly different from that of unimmunised mice, but were not distinguishable from each other. However, the repertoires of mice 60 days post immunisation were distinct both from unimmunised mice, and the day 5/14 animals. Our results reinforce the remarkable diversity of the T cell receptor repertoire, resulting in many diverse private TcRs contributing to the T cell response even in genetically identical mice responding to the same antigen. Finally, specific motifs defined by short sequences of amino acids within the CDR3 region may have a major effect on TcR specificity. The results of this study provide new insights into the properties of the CD4+ adaptive T cell response.
Population genomics ofSaccharomyces cerevisiaehuman isolates: passengers, colonizers, invaders
Authors: De Filippo Carlotta , Di Paola Monica , Stefanini Irene , Rizzetto Lisa , Berná Luisa , Ramazzotti Matteo , Dapporto Leonardo , Rivero Damariz , Gut Ivo G. , Gut Marta , Bayés Mónica , Legras Jean-Luc , Viola Roberto , Massi-Benedetti Cristina , De Luca Antonella , Romani Luigina , Lionetti Paolo , Cavalieri Duccio
Published: January 2014

The quest for the ecological niches ofSaccharomyces cerevisiaeranged from wineries to oaks and more recently to the gut ofCrabroWasps. Here we propose the role of the human gut in shapingS. cerevisiaeevolution, presenting the genetic structure of a previously unknown population of yeasts, associated with Crohn’s disease, providing evidence for clonal expansion within human’s gut. To understand the role of immune function in the human-yeast interaction we classified strains according to their immunomodulatory properties, discovering a set of genetically homogeneous isolates, capable of inducing anti-inflammatory signalsviaregulatory T cells proliferation, and on the contrary, a positive association between strain mosaicism and ability to elicit inflammatory, IL-17 driven, immune responses. The approach integrating genomics with immune phenotyping showed selection on genes involved in sporulation and cell wall remodeling as central for the evolution ofS. cerevisiaeCrohn’s strains from passengers to commensals to potential pathogens.
A hierarchical model for assembly of eukaryotic 60S ribosomal subunit domains
Authors: Gamalinda Michael , Ohmayer Uli , Jakovljevic Jelena , Kumcuoglu Beril , Woolford Joshua , Mbom Bertrade , Lin Lawrence , Woolford John L.
Published: January 2014

Despite having high-resolution structures for eukaryotic large ribosomal subunits, it remained unclear how these ribonucleoprotein complexes are constructed in living cells. Nevertheless, knowing where ribosomal proteins interact with ribosomal RNA (rRNA) provides a strategic platform to investigate the connection between spatial and temporal aspects of 60S subunit biogenesis. We previously found that the function of individual yeast large subunit ribosomal proteins (RPLs) in precursor rRNA (pre-rRNA) processing correlates with their location in the structure of mature 60S subunits. This observation suggested that there is an order by which 60S subunits are formed. To test this model, we used proteomic approaches to assay changes in the levels of ribosomal proteins and assembly factors in preribosomes when RPLs functioning in early, middle, and late steps of pre-60S assembly are depleted. Our results demonstrate that structural domains of eukaryotic 60S ribosomal subunits are formed in a hierarchical fashion. Assembly begins at the convex solvent side, followed by the polypeptide exit tunnel, the intersubunit side, and finally the central protuberance. This model provides an initial paradigm for the sequential assembly of eukaryotic 60S subunits. Our results reveal striking differences and similarities between assembly of bacterial and eukaryotic large ribosomal subunits, providing insights into how these RNA–protein particles evolved.
Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition
Authors: Webster Dan E. , Barajas Brook , Bussat Rose T. , Yan Karen J. , Neela Poornima H. , Flockhart Ross J. , Kovalski Joanna , Zehnder Ashley , Khavari Paul A.
Published: January 2014

Thousands of putative enhancers are characterized in the human genome, yet few have been shown to have a functional role in cancer progression. Inhibiting oncokinases, such as EGFR, ALK, ERBB2, and BRAF, is a mainstay of current cancer therapy but is hindered by innate drug resistance mediated by up-regulation of the HGF receptor, MET. The mechanisms mediating such genomic responses to targeted therapy are unknown. Here, we identify lineage-specific enhancers at the MET locus for multiple common tumor types, including a melanoma lineage-specific enhancer 63 kb downstream from the MET TSS. This enhancer displays inducible chromatin looping with the MET promoter to up-regulate MET expression upon BRAF inhibition. Epigenomic analysis demonstrated that the melanocyte-specific transcription factor, MITF, mediates this enhancer function. Targeted genomic deletion (<7 bp) of the MITF motif within the MET enhancer suppressed inducible chromatin looping and innate drug resistance, while maintaining MITF-dependent, inhibitor-induced melanoma cell differentiation. Epigenomic analysis can thus guide functional disruption of regulatory DNA to decouple pro- and anti-oncogenic functions of a dominant transcription factor and block innate resistance to oncokinase therapy.
Learning to ignore: A modeling study of a decremental cholinergic pathway and its influence on attention and learning
Authors: Oros Nicolas , Chiba Andrea A. , Nitz Douglas A. , Krichmar Jeffrey L.
Published: January 2014

Learning to ignore irrelevant stimuli is essential to achieving efficient and fluid attention, and serves as the complement to increasing attention to relevant stimuli. The different cholinergic (ACh) subsystems within the basal forebrain regulate attention in distinct but complementary ways. ACh projections from the substantia innominata/nucleus basalis region (SI/nBM) to the neocortex are necessary to increase attention to relevant stimuli and have been well studied. Lesser known are ACh projections from the medial septum/vertical limb of the diagonal band (MS/VDB) to the hippocampus and the cingulate that are necessary to reduce attention to irrelevant stimuli. We developed a neural simulation to provide insight into how ACh can decrement attention using this distinct pathway from the MS/VDB. We tested the model in behavioral paradigms that require decremental attention. The model exhibits behavioral effects such as associative learning, latent inhibition, and persisting behavior. Lesioning the MS/VDB disrupts latent inhibition, and drastically increases perseverative behavior. Taken together, the model demonstrates that the ACh decremental pathway is necessary for appropriate learning and attention under dynamic circumstances and suggests a canonical neural architecture for decrementing attention.
ANGUSTIFOLIA3 Binds to SWI/SNF Chromatin Remodeling Complexes to Regulate Transcription during Arabidopsis Leaf Development
Authors: Vercruyssen Liesbeth , Verkest Aurine , Gonzalez Nathalie , Heyndrickx Ken S. , Eeckhout Dominique , Han Soon-Ki , Jégu Teddy , Archacki Rafal , Van Leene Jelle , Andriankaja Megan , De Bodt Stefanie , Abeel Thomas , Coppens Frederik , Dhondt Stijn , De Milde Liesbeth , Vermeersch Mattias , Maleux Katrien , Gevaert Kris , Jerzmanowski Andrzej , Benhamed Moussa , Wagner Doris , Vandepoele Klaas , De Jaeger Geert , Inzé Dirk
Published: January 2014

The transcriptional coactivator ANGUSTIFOLIA3 (AN3) stimulates cell proliferation during Arabidopsis thaliana leaf development, but the molecular mechanism is largely unknown. Here, we show that inducible nuclear localization of AN3 during initial leaf growth results in differential expression of important transcriptional regulators, including GROWTH REGULATING FACTORs (GRFs). Chromatin purification further revealed the presence of AN3 at the loci of GRF5, GRF6, CYTOKININ RESPONSE FACTOR2, CONSTANS-LIKE5 (COL5), HECATE1 (HEC1), and ARABIDOPSIS RESPONSE REGULATOR4 (ARR4). Tandem affinity purification of protein complexes using AN3 as bait identified plant SWITCH/SUCROSE NONFERMENTING (SWI/SNF) chromatin remodeling complexes formed around the ATPases BRAHMA (BRM) or SPLAYED. Moreover, SWI/SNF ASSOCIATED PROTEIN 73B (SWP73B) is recruited by AN3 to the promoters of GRF5, GRF3, COL5, and ARR4, and both SWP73B and BRM occupy the HEC1 promoter. Furthermore, we show that AN3 and BRM genetically interact. The data indicate that AN3 associates with chromatin remodelers to regulate transcription. In addition, modification of SWI3C expression levels increases leaf size, underlining the importance of chromatin dynamics for growth regulation. Our results place the SWI/SNF-AN3 module as a major player at the transition from cell proliferation to cell differentiation in a developing leaf.
A Wheat SIMILAR TO RCD-ONE Gene Enhances Seedling Growth and Abiotic Stress Resistance by Modulating Redox Homeostasis and Maintaining Genomic Integrity
Authors: Liu Shuantao , Liu Shuwei , Wang Mei , Wei Tiandi , Meng Chen , Wang Meng , Xia Guangmin
Published: January 2014

Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability.
DNA Replicons for Plant Genome Engineering
Authors: Baltes Nicholas J. , Gil-Humanes Javier , Cermak Tomas , Atkins Paul A. , Voytas Daniel F.
Published: January 2014

Sequence-specific nucleases enable facile editing of higher eukaryotic genomic DNA; however, targeted modification of plant genomes remains challenging due to ineffective methods for delivering reagents for genome engineering to plant cells. Here, we use geminivirus-based replicons for transient expression of sequence-specific nucleases (zinc-finger nucleases, transcription activator–like effector nucleases, and the clustered, regularly interspaced, short palindromic repeat/Cas system) and delivery of DNA repair templates. In tobacco (Nicotiana tabacum), replicons based on the bean yellow dwarf virus enhanced gene targeting frequencies one to two orders of magnitude over conventional Agrobacterium tumefaciens T-DNA. In addition to the nuclease-mediated DNA double-strand breaks, gene targeting was promoted by replication of the repair template and pleiotropic activity of the geminivirus replication initiator proteins. We demonstrate the feasibility of using geminivirus replicons to generate plants with a desired DNA sequence modification. By adopting a general plant transformation method, plantlets with a desired DNA change were regenerated in <6 weeks. These results, in addition to the large host range of geminiviruses, advocate the use of replicons for plant genome engineering.
Cardiolipin-Mediated Mitochondrial Dynamics and Stress Response inArabidopsis
Authors: Pan Ronghui , Jones A. Daniel , Hu Jianping
Published: January 2014

Mitochondria are essential and dynamic organelles in eukaryotes. Cardiolipin (CL) is a key phospholipid in mitochondrial membranes, playing important roles in maintaining the functional integrity and dynamics of mitochondria in animals and yeasts. However, CL's role in plants is just beginning to be elucidated. In this study, we used Arabidopsis thaliana to examine the subcellular distribution of CL and CARDIOLIPIN SYNTHASE (CLS) and analyzed loss-of-function cls mutants for defects in mitochondrial morphogenesis and stress response. We show that CL localizes to mitochondria and is enriched at specific domains, and CLS targets to the inner membrane of mitochondria with its C terminus in the intermembrane space. Furthermore, cls mutants exhibit significantly impaired growth as well as altered structural integrity and morphogenesis of mitochondria. In contrast to animals and yeasts, in which CL's effect on mitochondrial fusion is more profound, Arabidopsis  CL plays a dominant role in mitochondrial fission and exerts this function, at least in part, through stabilizing the protein complex of the major mitochondrial fission factor, DYNAMIN-RELATED PROTEIN3. CL also plays a role in plant responses to heat and extended darkness, stresses that induce programmed cell death. Our study has uncovered conserved and plant-specific aspects of CL biology in mitochondrial dynamics and the organism response to environmental stresses.
Expression, purification, crystallization and preliminary X-ray analysis of the PaaI-like thioesterase SAV0944 from Staphylococcus aureus
Authors: Khandokar Yogesh B. , Roman Noelia , Smith Kate M. , Srivastava Parul , Forwood Jade K.
Published: January 2014

Staphylococcus aureus is the causative agent of many diseases, including meningitis, bacteraemia, pneumonia, food poisoning and toxic shock syndrome. Structural characterization of the PaaI-like thioesterase SAV0944 (SaPaaI) from S. aureus subsp. aureus Mu50 will aid in understanding its potential as a new therapeutic target by knowledge of its molecular details and cellular functions. Here, the recombinant expression, purification and crystallization of SaPaaI thioesterase from S. aureus are reported. This protein initially crystallized with the ligand coenzyme A using the hanging-drop vapour-diffusion technique with condition No. 40 of Crystal Screen from Hampton Research at 296 K. Optimal final conditions consisting of 24% PEG 4000, 100 mM sodium citrate pH 6.5, 12% 2-propanol gave single diffraction-quality crystals. These crystals diffracted to beyond 2 Å resolution at the Australian Synchrotron and belonged to space group P1211, with unit-cell parameters a = 44.05, b = 89.05, c = 60.74 Å, β = 100.5°. Initial structure determination and refinement gave an R factor and R
free of 17.3 and 22.0%, respectively, confirming a positive solution in obtaining phases using molecular replacement.
Competitive effects of co‐operation with suppliers and buyers in the sawmill industry
Authors: Gueimonde‐Canto Ana , González‐Benito Javier , Manuel García‐Vázquez José
Published: January 2014

Purpose

The present paper proposes simultaneous research into the effects of co‐operation with buyers and suppliers on company performance, and how both types of co‐operation interact in one specific industry.

Design/methodology/approach

The paper conducts an analysis of a sample of 80 sawmills in the Spanish regions of Galicia and the Basque Country, comprising most of the wood production in Spain.

Findings

Contrary to prior research, the results suggest that contextual factors, inherent to each supply chain, affect the relationship between supplier‐customer co‐operation and performance.

Research limitations/implications

The findings lead one to argue that some traditional arguments in favour of co‐operation with buyers and suppliers might not be applicable to specific industries, positions in the value chain or exchanged products, and that industry‐specific variables should be included in future research.

Practical implications

Sawmills appear to benefit only from co‐operation with buyers, but not from co‐operation with suppliers. Furthermore, the two types of co‐operation do not appear to generate synergy.

Originality/value

The study adopts a systemic view of the supply chain and argues that industry‐specific factors, and position in the value chain, should be included as control variables in empirical work researching the competitive consequences of co‐operation in the value chain.
Harlequin color change in two preterm newborns
Authors: Dang Dan , Zhou Wenli , Liu Ying , Wu Hui
Published: January 2014

Harlequin color change is a benign transient skin change usually seen in the neonatal period with unknown etiology. It has been rarely reported in preterm infants. Herein, we report two cases of harlequin color change developed in premature infants without any adverse consequences. During the event, one infant was receiving antibiotic treatment for an Escherichia coli bacteremia in addition to routine supportive care and the other one was in a very stable condition. Both preterm infants were also diagnosed to have a patent ductus arteriosus. As a benign transient skin change, harlequin color change should be recognized properly to avoid unnecessary treatment.
Mycosis fungoides palmaris et plantaris successfully treated with radiotherapy: Case report and mini‐review of the published work
Authors: Nakai Noriaki , Hagura Asami , Yamazato Shiho , Katoh Norito
Published: January 2014

Mycosis fungoides palmaris et plantaris (MFPP) is a rare variant of cutaneous T‐cell lymphoma limited to the palms and soles that is not widely recognized because of its uncommon occurrence. We report a 73‐year‐old Japanese man who presented with an erosion on the left dorsal hand, a reddish tumor on the right palm, and hyperkeratotic erythematous plaques on the right sole. Skin biopsy showed histological features of mycosis fungoides (MF) with invasion into the deeper layers of skin. There was no visceral or lymph node invasion. We diagnosed this case as MFPP. External beam radiotherapy (EBRT) was performed to treat the hand lesions. Combination treatment with topical steroids and topical psoralen plus ultraviolet light therapy was performed to treat the right sole lesion, but was ineffective. Therefore, sequential EBRT was performed. Complete remission of all lesions was obtained. This is the first report of MFPP with a locally advanced tumor for which the efficacy of radiotherapy is described in detail. MFPP lesions occur on the dorsal aspect of hand or foot, and here we propose a classification of MFPP as hand and foot MF. The pathogenesis of MFPP is still unclear and further accumulation of data is required.
Epstein–Barr virus‐associated T/natural killer‐cell lymphoproliferative disorders
Authors: Park Sanghui , Ko Young H.
Published: January 2014

Primary infection with Epstein–Barr virus (EBV) is usually asymptomatic and, in a normal host, EBV remains latent in B cells after primary infection for the remainder of life. Uncommonly, EBV can infect T or natural killer (NK) cells in a person with a defect in innate immunity, and EBV infection can cause unique systemic lymphoproliferative diseases (LPD) of childhood. Primary infection in young children can be complicated by hemophagocytic lymphohistiocytosis or fulminant systemic T‐cell LPD of childhood. Uncommonly, patients can develop chronic active EBV (CAEBV) disease‐type T/NK LPD, which includes CAEBV infection of the systemic form, hydroa vacciniforme‐like T‐cell LPD, and mosquito‐bite hypersensitivity. The clinical course of CAEBV disease‐type T/NK LPD can be smoldering, persistent or progressive, depending on the balance between viral factors and host immunity. Aggressive NK‐cell leukemia, hydroa vacciniforme‐like T‐cell lymphoma, or uncommonly extranodal NK/T‐cell lymphoma can develop in children and young adults with CAEBV disease‐type T/NK‐cell LPD. Extranodal T/NK‐cell lymphoma is a disease of adults, and its incidence begins to increase in the third decade and comprises the major subtype of T/NK LPD throughout life. Aggressive NK‐cell leukemia and nodal T/NK‐cell lymphoma of the elderly are fulminant diseases, and immune senescence may be an important pathogenetic factor. This review describes the current progress in identifying different types of EBV‐associated T/NK‐cell LPD and includes a brief presentation of data from Korea.
Skin manifestations of adult T‐cell leukemia/lymphoma: Clinical, cytological and immunological features
Authors: Tokura Yoshiki , Sawada Yu , Shimauchi Takatoshi
Published: January 2014

Adult T‐cell leukemia/lymphoma (ATLL) is a malignancy of mature T cells caused by human T‐cell leukemia virus type I. The endemic areas include Japan, especially in Kyushu, the Caribbean, Papua New Guinea, South America and Africa. Approximately 50% of ATLL patients exhibit skin manifestations. Cytologically, ATLL tumor cells are characterized by CD4+CD25+ regulatory T‐cell phenotype, high expressions of CCR4, and programmed cell death (PD)‐1 and PD‐ligand 1. The skin eruptions are categorized into six types: patch, plaque, multipapular, nodulotumoral, erythrodermic and purpuric. The overall survival of the eruption‐bearing patients was poorer than that of the non‐eruption‐bearing patients in acute, chronic and smoldering types, but the survival levels of both groups were comparable in lymphoma type. The prognosis was poor in the order of: erythrodermic, nodulotumoral, multipapular/purpuric, plaque, then patch. Multivariate analysis revealed that the eruption type is an independent prognostic factor for ATLL. Patients may have other skin manifestations, secondary and infective lesions.
Current therapy of choice for cutaneous lymphomas: Complementary to the Japanese Dermatological Association/Japanese Skin Cancer Society guidelines
Authors: Iwatsuki Keiji , Hamada Toshihisa ,   Japanese Skin Cancer Society – Lymphoma Study Group
Published: January 2014

The first Japanese edition of guidelines for management of cutaneous lymphoma was published jointly in 2009 by the Japanese Dermatological Association (JDA) and the Japanese Skin Cancer Society (JSCS) – Lymphoma Study Group; the guidelines were revised in 2011, and published in English in 2013. The JDA/JSCS guidelines are unique because they describe information and management practices for lymphomas specific to Asia, such as adult T‐cell leukemia/lymphoma and extranodal natural killer/T‐cell lymphoma, nasal type. In the present article, we have highlighted the essential points of management for cutaneous lymphomas in Asia. In order to complement the guidelines, we have added further information and our clinical experience of some currently available agents for cutaneous lymphomas in Japan.
Antiviral activity of extracts from Morinda citrifolia leaves and chlorophyll catabolites, pheophorbide a and pyropheophorbide a, against hepatitis C virus
Authors: Ratnoglik Suratno Lulut , Aoki Chie , Sudarmono Pratiwi , Komoto Mari , Deng Lin , Shoji Ikuo , Fuchino Hiroyuki , Kawahara Nobuo , Hotta Hak
Published: January 2014

The development of complementary and/or alternative drugs for treatment of hepatitis C virus (HCV) infection is still needed. Antiviral compounds in medicinal plants are potentially good targets to study. Morinda citrifolia is a common plant distributed widely in Indo‐Pacific region; its fruits and leaves are food sources and are also used as a treatment in traditional medicine. In this study, using a HCV cell culture system, it was demonstrated that a methanol extract, its n‐hexane, and ethyl acetate fractions from M. citrifolia leaves possess anti‐HCV activities with 50%‐inhibitory concentrations (IC50) of 20.6, 6.1, and 6.6 μg/mL, respectively. Bioactivity‐guided purification and structural analysis led to isolation and identification of pheophorbide a, the major catabolite of chlorophyll a, as an anti‐HCV compound present in the extracts (IC50  = 0.3 μg/mL). It was also found that pyropheophorbide a possesses anti‐HCV activity (IC50 = 0.2 μg/mL). The 50%‐cytotoxic concentrations (CC50) of pheophorbide a and pyropheophorbide a were 10.0 and 7.2 μg/mL, respectively, their selectivity indexes being 33 and 36, respectively. On the other hand, chlorophyll a, sodium copper chlorophyllin, and pheophytin a barely, or only marginally, exhibited anti‐HCV activities. Time‐of‐addition analysis revealed that pheophorbide a and pyropheophorbide a act at both entry and the post‐entry steps. The present results suggest that pheophorbide a and its related compounds would be good candidates for seed compounds for developing antivirals against HCV.
Pneumocystis jirovecii colonization is associated with enhanced Th1 inflammatory gene expression in lungs of humans with chronic obstructive pulmonary disease
Authors: Fitzpatrick Meghan E. , Tedrow John R. , Hillenbrand Maria E. , Lucht Lorrie , Richards Thomas , Norris Karen A. , Zhang Yingze , Sciurba Frank C. , Kaminski Naftali , Morris Alison
Published: January 2014

Chronic obstructive pulmonary disease (COPD) is a complex disease, the pathogenesis of which remains incompletely understood. Colonization with Pneumocystis jirovecii may play a role in COPD pathogenesis; however, the mechanisms by which such colonization contributes to COPD are unknown. The objective of this study was to determine lung gene expression profiles associated with Pneumocystis colonization in patients with COPD to identify potential key pathways involved in disease pathogenesis. Using COPD lung tissue samples made available through the Lung Tissue Research Consortium (LTRC), Pneumocystis colonization status was determined by nested PCR. Microarray gene expression profiles were performed for each sample and the profiles of colonized and non‐colonized samples compared. Overall, 18 participants (8.5%) were Pneumocystis‐colonized. Pneumocystis colonization was associated with fold increase in expression of four closely related genes: INF‐γ and the three chemokine ligands CXCL9, CXCL10, and CXCL11. These ligands are chemoattractants for the common cognate receptor CXCR3, which is predominantly expressed on activated Th1 T‐lymphocytes. Although these ligand–receptor pairs have previously been implicated in COPD pathogenesis, few initiators of ligand expression and subsequent lymphocyte trafficking have been identified: our findings implicate Pneumocystis as a potential trigger. The finding of upregulation of these inflammatory genes in the setting of Pneumocystis colonization sheds light on infectious‐immune relationships in COPD.
‘A City upon a Hill’: The Wire and Its Distillation of the United States Polity
Authors: Wheeler Mark
Published: January 2014

The Home Box Office's series The Wire (2002–2008) provides an informed critique of the decline of the democratic American ideal of the ‘city upon a hill’. From its inception as a police procedural, it expanded its interests across the dystopian city of Baltimore to consider the linkage between drug crimes, policing, the collapse of blue-collar life, social deprivation, institutional compromise, the public school system, media compliance and political self-interest. Therefore, this article will situate The Wire into the debates that have defined the US polity and will discuss how it employs the narrative conventions of a contemporary thriller to offer an alternative view of American democracy.