bluuebunny/crossref_metadata_2025 huggingface dataset:
TheCaenorhabditis eleganspaxillin orthologue, PXL-1, is required for pharyngeal muscle contraction and for viability
Authors: Warner Adam , Qadota Hiroshi , Benian Guy M. , Vogl A. Wayne , Moerman Donald G.
Published: June 2011

We have identified the gene C28H8.6 (pxl-1) as the Caenorhabditis elegans orthologue of vertebrate paxillin. PXL-1 contains the four C-terminal LIM domains conserved in paxillin across all species and three of the five LD motifs found in the N-terminal half of most paxillins. In body wall muscle, PXL-1 antibodies and a full-length green fluorescent protein translational fusion localize to adhesion sites in the sarcomere, the functional repeat unit in muscle responsible for contraction. PXL-1 also localizes to ring-shaped structures near the sarcolemma in pharyngeal muscle corresponding to podosome-like sites of actin attachment. Our analysis of a loss-of-function allele of pxl-1, ok1483, shows that loss of paxillin leads to early larval arrested animals with paralyzed pharyngeal muscles and eventual lethality, presumably due to an inability to feed. We rescued the mutant phenotype by expressing paxillin solely in the pharynx and found that these animals survived and are essentially wild type in movement and body wall muscle structure. This indicates a differential requirement for paxillin in these two types of muscle. In pharyngeal muscle it is essential for contraction, whereas in body wall muscle it is dispensable for filament assembly, sarcomere stability, and ultimately movement.
Measurement of Dynamic Efficiency: A Directional Distance Function Parametric Approach
Authors: Serra Teresa , Lansink Alfons Oude , Stefanou Spiro E.
Published: June 2011

This research proposes a parametric estimation of the structural dynamic efficiency measures proposed in 2009 by Silva and Oude Lansink. Overall, technical and allocative efficiency measurements are derived based on a directional distance function and the duality between this function and the optimal value function. The applicability of the parametric proposal is illustrated by assessing dynamic efficiency ratings for a sample of Dutch dairy farms observed from 1995 to 2005. Dynamic efficiency ratings indicate the possibility to achieve long‐run cost savings on the order of 12% that are mainly to be accomplished through a reduction in input use.
Coverage tradeoffs and power estimation in the design of whole-genome sequencing experiments for detecting association
Authors: Shen Yufeng , Song Ruijie , Pe'er Itsik
Published: June 2011

Motivation: Whole-genome sequencing (WGS) allows direct interrogation of previously undetected uncommon or rare variants, which potentially contribute to the missing heritability of human disease. However, cost of sequencing large numbers of samples limits its application in case–control association studies. Here, we describe theoretical and empirical design considerations for such sequencing studies, aimed at maximizing the power of detecting association under the constraint of study-wide cost.

Results: We consider two cost regimes. First, assuming cost is proportional to the total amount of base pairs to be sequenced across all samples, which is a practical model for whole-genome sequencing, we explored the tradeoff in terms of study power between increasing the number of subjects and increasing depth coverage. We demonstrate that the optimal power of detecting association is achieved at medium depth coverage under a wide range of realistic conditions for case-only sequencing designs. Second, if cost is fixed per sample, which is approximately the case in exome sequencing, we show that in a simple case+control sequencing study, the optimal design should include cases totaling 1/e of all subjects.

Availability: A web tool implementing the methods is available at http://www.cs.columbia.edu/~itsik/OPERA/.

Contact:  yshen@c2b2.columbia.edu; itsik@cs.columbia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
PathVisio-MIM: PathVisio plugin for creating and editing Molecular Interaction Maps (MIMs)
Authors: Luna Augustin , Sunshine Margot L. , van Iersel Martijn P. , Aladjem Mirit I. , Kohn Kurt W.
Published: June 2011

Motivation: A plugin for the Java-based PathVisio pathway editor has been developed to help users draw diagrams of bioregulatory networks according to the Molecular Interaction Map (MIM) notation. Together with the core PathVisio application, this plugin presents a simple to use and cross-platform application for the construction of complex MIM diagrams with the ability to annotate diagram elements with comments, literature references and links to external databases. This tool extends the capabilities of the PathVisio pathway editor by providing both MIM-specific glyphs and support for a MIM-specific markup language file format for exchange with other MIM-compatible tools and diagram validation.

Availability: The PathVisio-MIM plugin is freely available and works with versions of PathVisio 2.0.11 and later on Windows, Mac OS X and Linux. Information about MIM notation and the MIMML format is available at http://discover.nci.nih.gov/mim. The plugin, along with diagram examples, instructions and Java source code, may be downloaded at http://discover.nci.nih.gov/mim/mim_pathvisio.html.

Contact:  margot@discover.nci.nih.gov; augustin@mail.nih.gov

Supplementary information:  Supplementary data are available at Bioinformatics online.
Glaucoma—In the GP's Blind Spot?
Authors: Simpson David
Published: June 2011

Glaucoma is a group of common sight-threatening disorders affecting the optic nerve and visual fields. It afflicts 2% of the population over the age of 40 years with an incidence of 2.5 per 1000 people per year and is the second most common cause of blindness in the UK. Incidence and consequent morbidity are increasing as a result of increased life expectancy. This article aims to provide an overview for GPs of the common types of glaucoma, their presentation and management.
Oxford Handbook of Diabetes Nursing
Authors: Sumner Janet
Published: June 2011

The Oxford Handbook of Diabetes Nursing provides a comprehensive overview of diabetes care. It compiles evidence, information and guidance on the area making it an essential tool for practice nurses with a special interest in diabetes, as well as a useful resource for those working in community and acute settings.
First Report of Buckeye Rot Caused by Phytophthora nicotianae in Tomato in New Mexico
Authors: French J. M. , Stamler R. A. , Randall J. J. , Goldberg N. P.
Published: June 2011

Phytophthora nicotianae Breda de Haan was isolated from turning tomato fruit (Solanum lycopersicum L.) in August 2010 from a garden in central New Mexico. Symptoms typical of buckeye rot including brown, water-soaked, necrotic lesions with concentric rings were observed on three tomato fruit. Tissue from each fruit was surface sterilized and plated onto water agar and incubated at room temperature. After 72 h, colonies of Phytophthora (identified by the presence of coenocytic hyphae and papillate sporangia) were found and subcultured by hyphal tips to V8 agar amended with ampicillin (250 mg/liter), rifampicin (10 mg/liter), and pimaricin (0.2% wt/vol). The isolates of Phytophthora were identified as P. nicotianae based on morphological characteristics and DNA analysis. Sporangia were sharply papillate, noncaducous, and ovoid to spherical. The average sporangium size was 44.5 × 35.5 μm with a length-to-width ratio of 1.26. Chlamydospores, both terminal and intercalary, were spherical to ovoid and averaged 38.9 × 37.5 μm. PCR amplification and sequence analysis on three isolates from the infected tomato tissue was performed using primers ITS4 and ITS6 that amplify the 5.8S rDNA and ITSI and ITSII internal transcribed spacers (1,2). A band of approximately 890 bp was amplified and directly sequenced (GenBank Accession No. HQ711620). A BLAST search of the NCBI total nucleotide collection revealed a 100% similarity to multiple P. nicotianae isolates previously sequenced. Pathogenicity tests with sequenced P. nicotianae isolates were performed to confirm virulence on tomato fruit. Tomatoes were surface sterilized with 95% ethanol and 0.1 ml of a P. nicotianae zoospore suspension (10,000 zoospores/ml) or sterile water was pipetted onto the surface of the tomato fruit. After 5 days in a humidity chamber, all three inoculated tomatoes had expanding water-soaked, circular lesions and the negative control showed no disease symptoms. P. nicotianae was successfully reisolated from the inoculated tomato tissue and the ITS region was sequenced to confirm its identity. Although the disease has been reported in many other states since the early 1900s, to our knowledge, this is the first report of P. nicotianae causing disease on tomato in New Mexico.

References: (1) D. E. L. Cooke and J. M. Duncan. Mycol. Res. 101:667, 1997. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.
Effects of Hydrolyzable Tannins on In Vitro Growth of Armillaria calvescens and A. gallica
Authors: Brazee Nicholas J. , Wick Robert L. , Wargo Phillip M.
Published: June 2011

We hypothesized that Armillaria gallica, which is abundant in oak-dominated forests, is more successful at oxidizing and metabolizing polyphenols than A. calvescens, which is mostly restricted to maple-dominated forests. Isolates were challenged with up to seven concentrations of tannic acid (TA), gallic acid (GA), and black oak root bark extracts (RBE). Six concentrations of glucose and ethanol were also tested to determine the influence of available carbon on growth. Colony area and biomass values were analyzed using a GLM and Tukey's HSD test. When challenged with 0.12% concentrations of TA, GA, and RBE, A. gallica produced a significantly larger biomass in all treatments and larger colony areas in four of the five treatments compared to control values. A. gallica also produced a significantly larger number of rhizomorphs than A. calvescens on RBE medium. In contrast, A. calvescens generated significantly larger biomass over control treatments only when RBE was added, and values were substantially less compared to A. gallica. Growth of both species was significantly greater when ethanol was added, especially on GA medium, while glucose had little effect. Results from this study suggest that A. gallica is better at oxidizing and metabolizing polyphenols than A. calvescens.
First Report of a Root Rot Caused by Phytophthora palmivora on Lavandula angustifolia in Turkey
Authors: Dervis S. , Arslan M. , Serce C. U. , Soylu S. , Uremis I.
Published: June 2011

English Lavender (Lavandula angustifolia Mill.) has been considered an alternative crop to tobacco in Hatay Province of Turkey because of its great production potential. As a new, nonnative crop, diseases and pests of lavender are not well known in the region. In summer 2010, root rot symptoms were observed with an average incidence of 45% in a 2-year-old lavender nursery in Hatay. Initial symptoms of chlorosis and wilting were followed by progressive death of the plants starting at the shoot tips. An oomycetous species was isolated consistently from the stems and roots of diseased plants on potato dextrose agar (PDA) amended with several fungicides and antibiotics. The culture of the single-zoospore isolate produced arachnoid growth on PDA. Chlamydospores of the isolate were approximately 35.0 μm in diameter. The isolate produced papillate, caduceus, hyaline sporangia in different shapes ranging from spherical to ellipsoidal. Sporangia with short pedicels (5 μm) were 35.0 to 57.5 × 27.5 to 42.5 μm with a length/width ratio of 1.2 to 1.8. On the basis of symptoms and morphology of the organism, the pathogen was identified as Phytophthora palmivora (E.J. Butler) E.J. Butler (3). Identification of the isolate was also confirmed by comparison of the sequence of the nuclear ribosomal internal transcribed spacer (ITS) region with reference isolates. The ITS region of rDNA was amplified by PCR with primers ITS1/ITS4 and sequenced (GenBank Accession No. JF777117). BLAST analysis of the sequence obtained showed a 99 to 100% homology with P. palmivora. Pathogenicity tests were performed on 12 greenhouse-grown 2-year-old lavender plants in 2-liter pots containing a steamed sand/peat/soil mixture. After rooting, the plants were inoculated by placing mycelial plugs from a 1-week-old culture of the isolate into an incision made at the base of each plant. Control plants were treated with plugs of sterile PDA. Inoculated plants were kept at 27°C for 5 weeks. Similar symptoms developed on the inoculated plants within 4 weeks after inoculation. P. palmivora was consistently reisolated from symptomatic plants. No symptoms developed on control plants. P. palmivora attacks a wide range of crop species including lavenders (1,2,4). To our knowledge, this is the first report of a root rot caused by P. palmivora, a new pathogen of lavender in Turkey.

References: (1) S. Davino et al. Plant Dis. 86:561, 2002. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St Paul, MN, 1996. (3) D. J. Stamps. C.M.I. Descr. Fungi Bact. 831:1, 1985. (4) G. A. Torres et al. Plant Dis. 94:1163, 2010.
Interaction Among Ethnicity, Socioeconomic Status, and Helicobacter pylori Seroprevalence in Israeli Children and Adolescents
Authors: Muhsen Khitam , Nir Avishag , Spungin‐Bialik Anya , Bassal Ravit , Goren Sophy , Cohen Dani
Published: June 2011

Objectives:

The aim of the study was to examine the prevalence of Helicobacter pylori infection among Israeli children from different backgrounds and to assess potential interactions between ethnicity, socioeconomic status (SES), and H pylori seroprevalence.

Patients and Methods:

The present sero‐epidemiologic study was conducted among 0‐ to 20‐year‐old children seeking medical attention, not specifically gastrointestinal symptoms, using sera collected between 2000 and 2001 from 575 Israeli Arab children, 584 Jewish children from the general population, and sera that were obtained between 1997 and 2007 from 464 children of an ultraorthodox Jewish community. An enzyme‐linked immunosorbent assay was used to measure H pylori serum immunoglobulin G antibodies and seropositivity to H pylori CagA strains.

Results:

H pylori seropositivity was 22.9% (95% confidence interval [CI] 19.7–26.5) among Jewish children from the general population, 25.2% (95% CI 21.5–29.4) among ultraorthodox Jewish children, and 45.6% (95% CI 41.5–49.7) among Arab children. H pylori seroprevalence increased significantly with age in the 3 study groups, but it was consistently higher in Arab children. Compared with Jewish participants from high SES and controlling for age and sex, the odds ratio for H pylori seropositivity was 2.03 (95% CI 1.31–3.12) in Jewish children from intermediate SES, 2.42 (95% CI 1.29–4.53) in Arab children from intermediate SES, 2.26 (95% CI 1.52–3.36) in Jewish children from low SES, and 5.72 (95% CI 3.89–8.42) in Arab children from low SES. CagA seropositivity was 40.8% and 45.0% among Jewish and Arab children, respectively (P = 0.59), and it was highest among subjects of lower SES.

Conclusions:

Socioeconomic factors may not totally explain the ethnic differences in H pylori prevalence.
Nutritional geometry: gorillas prioritize non-protein energy while consuming surplus protein
Authors: Rothman Jessica M. , Raubenheimer David , Chapman Colin A.
Published: June 2011

It is widely assumed that terrestrial food webs are built on a nitrogen-limited base and consequently herbivores must compensate through selection of high-protein foods and efficient nitrogen retention. Like many folivorous primates, gorillas' diet selection supports this assumption, as they apparently prefer protein-rich foods. Our study of mountain gorillas (
Gorilla beringei
) in Uganda revealed that, in some periods, carbohydrate-rich fruits displace a large portion of protein-rich leaves in their diet. We show that non-protein energy (NPE) intake was invariant throughout the year, whereas protein intake was substantially higher when leaves were the major portion of the diet. This pattern of macronutrient intake suggests that gorillas prioritize NPE and, to achieve this when leaves are the major dietary item, they over-eat protein. The concentrations of protein consumed in relation to energy when leaves were the major portion of the diet were close to the maximum recommended for humans and similar to high-protein human weight-loss diets. By contrast, the concentrations of protein in relation to energy when gorillas ate fruit-dominated diets were similar to those recommended for humans. Our results question the generality of nitrogen limitation in terrestrial herbivores and provide a fascinating contrast with human macronutrient intake.
Agricultural intensification, priming for persistence and the emergence of Nipah virus: a lethal bat-borne zoonosis
Authors: Pulliam Juliet R. C. , Epstein Jonathan H. , Dushoff Jonathan , Rahman Sohayati A. , Bunning Michel , Jamaluddin Aziz A. , Hyatt Alex D. , Field Hume E. , Dobson Andrew P. , Daszak Peter
Published: June 2011

Emerging zoonoses threaten global health, yet the processes by which they emerge are complex and poorly understood. Nipah virus (NiV) is an important threat owing to its broad host and geographical range, high case fatality, potential for human-to-human transmission and lack of effective prevention or therapies. Here, we investigate the origin of the first identified outbreak of NiV encephalitis in Malaysia and Singapore. We analyse data on livestock production from the index site (a commercial pig farm in Malaysia) prior to and during the outbreak, on Malaysian agricultural production, and from surveys of NiV's wildlife reservoir (flying foxes). Our analyses suggest that repeated introduction of NiV from wildlife changed infection dynamics in pigs. Initial viral introduction produced an explosive epizootic that drove itself to extinction but primed the population for enzootic persistence upon reintroduction of the virus. The resultant within-farm persistence permitted regional spread and increased the number of human infections. This study refutes an earlier hypothesis that anomalous El Niño Southern Oscillation-related climatic conditions drove emergence and suggests that priming for persistence drove the emergence of a novel zoonotic pathogen. Thus, we provide empirical evidence for a causative mechanism previously proposed as a precursor to widespread infection with H5N1 avian influenza and other emerging pathogens.
Fishing destabilizes the biomass flow in the marine size spectrum
Authors: Rochet M.-J. , Benoît E.
Published: June 2011

Fishing impacts on marine food webs are predicted by simulations of a size spectrum community model. In this model, predation is determined by predator and prey size and abundance, and drives predator growth and prey mortality. Fishing amplifies temporal oscillations in the biomass flow. Oscillations appear at lower fishing intensity and have wider amplitude when fishing is selective (removes a narrow size range) and/or when large fish are targeted, than when fishing is more balanced (catching a larger size range) or when small fish are targeted. A novel index of size diversity is developed, and is shown to be sensitive to both fishing intensity and selectivity. To avoid unstable food web dynamics with potential harmful consequences for fisheries, limiting both fishing intensity and selectivity might be an appropriate exploitation strategy.
A conserved residue, PomB-F22, in the transmembrane segment of the flagellar stator complex, has a critical role in conducting ions and generating torque
Authors: Terauchi Takashi , Terashima Hiroyuki , Kojima Seiji , Homma Michio
Published: June 2011

Bacterial flagellar motors exploit the electrochemical potential gradient of a coupling ion (H+ or Na+) as their energy source, and are composed of stator and rotor proteins. Sodium-driven and proton-driven motors have the stator proteins PomA and PomB or MotA and MotB, respectively, which interact with each other in their transmembrane (TM) regions to form an ion channel. The single TM region of PomB or MotB, which forms the ion-conduction pathway together with TM3 and TM4 of PomA or MotA, respectively, has a highly conserved aspartate residue that is the ion binding site and is essential for rotation. To investigate the ion conductivity and selectivity of the Na+-driven PomA/PomB stator complex, we replaced conserved residues predicted to be near the conserved aspartate with H+-type residues, PomA-N194Y, PomB-F22Y and/or PomB-S27T. Motility analysis revealed that the ion specificity was not changed by either of the PomB mutations. PomB-F22Y required a higher concentration of Na+ to exhibit swimming, but this effect was suppressed by additional mutations, PomA-N194Y or PomB-S27T. Moreover, the motility of the PomB-F22Y mutant was resistant to phenamil, a specific inhibitor for the Na+ channel. When PomB-F22 was changed to other amino acids and the effects on swimming ability were investigated, replacement with a hydrophilic residue decreased the maximum swimming speed and conferred strong resistance to phenamil. From these results, we speculate that the Na+ flux is reduced by the PomB-F22Y mutation, and that PomB-F22 is important for the effective release of Na+ from PomB-D24.
Diversity and distribution of transcription factors: their partner domains play an important role in regulatory plasticity in bacteria
Authors: Rivera-Gómez Nancy , Segovia Lorenzo , Pérez-Rueda Ernesto
Published: June 2011

The ability of bacteria to deal with diverse environmental changes depends on their repertoire of genes and their ability to regulate their expression. In this process, DNA-binding transcription factors (TFs) have a fundamental role because they affect gene expression positively and/or negatively depending on operator context and ligand-binding status. Here, we show an exhaustive analysis of winged helix–turn–helix domains (wHTHs), a class of DNA-binding TFs. These proteins were identified in high proportions and widely distributed in bacteria, representing around half of the total TFs identified so far. In addition, we evaluated the repertoire of wHTHs in terms of their partner domains (PaDos), identifying a similar trend, as with TFs, i.e. they are abundant and widely distributed in bacteria. Based on the PaDos, we defined three main groups of families: (i) monolithic, those families with little PaDo diversity, such as LysR; (ii) promiscuous, those families with a high PaDo diversity; and (iii) monodomain, with families of small sizes, such as MarR. These findings suggest that PaDos have a very important role in the diversification of regulatory responses in bacteria, probably contributing to their regulatory complexity. Thus, the TFs discriminate over longer regions on the DNA through their diverse DNA-binding domains. On the other hand, the PaDos would allow a great flexibility for transcriptional regulation due to their ability to sense diverse stimuli through a variety of ligand-binding compounds.
Herpes simplex virus type 2 virion host shutoff protein suppresses innate dsRNA antiviral pathways in human vaginal epithelial cells
Authors: Yao Xiao-Dan , Rosenthal Kenneth Lee
Published: June 2011

Viruses that establish persistent infections have evolved numerous strategies to evade host innate antiviral responses. We functionally assessed the role of herpes simplex virus type 2 (HSV-2) virion host shutoff (vhs) protein on innate immune sensing pathways in human vaginal epithelial cells (VK2 ECs). Infection of cells with wild-type (WT) HSV-2 significantly decreased expression of innate immune sensors of viral infection, Toll-like receptor (TLR)2, TLR3, retinoic acid inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda-5), relative to cells infected with a mutant that lacks vhs (vhsB) or mock-infected cells. Transfection with HSV-2 vhs similarly decreased expression of TLR2, TLR3, RIG-I and Mda-5, which was also confirmed in human embryonic kidney (HEK) 293 cells. vhsB infection of VK2 cells caused robust increases in the active form of interferon regulatory factor (IRF)3 and its translocation to the nucleus compared with the WT. Additionally, IRF3 activation by Sendai virus and polyinosinic : polycytidylic acid-induced stimulation of beta interferon (IFN-β) was significantly inhibited in vhs-transfected cells. Overall, our findings provide the first evidence that HSV-2 vhs plays roles in selectively inhibiting TLR3 and RIG-I/Mda-5, as well as TLR2-mediated antiviral pathways for sensing dsRNA and effectively suppresses IFN-β antiviral responses in human vaginal ECs.
Lack of type-specific concordance between human papillomavirus (HPV) serology and HPV DNA detection in the uterine cervix and oral mucosa
Authors: Paaso A. E. , Louvanto K. , Syrjänen K. J. , Waterboer T. , Grénman S. E. , Pawlita M. , Syrjänen S. M.
Published: June 2011

There is limited knowledge about longitudinal genotype-specific concordance between human papillomavirus (HPV) serology and co-existent presence of HPV DNA in the uterine cervix. The role of oral HPV infections in inducing serological response is unclear, as is the effect of HPV antibodies on the outcome of oral HPV infections. The present study is part of the Finnish Family HPV Study designed to evaluate dynamics of HPV infections within families. Here, we correlated the point prevalence of HPV6, 11, 16, 18 and 45 antibodies and concomitant genotype-specific HPV DNA detection in cervical and oral samples of 323 mothers during their 3 year (mean 37.5 months) follow-up. The mean age of these pregnant mothers at enrolment (third trimester) was 25.5 years. HPV antibodies were analysed with multiplex HPV serology and HPV genotyping was performed using a Multimetrix kit (Progen Biotechnik). There was no concordance between cervical DNA detection and co-existent seropositivity, and the same was true even in samples taken 12 months apart. Women who cleared their cervical HPV16 infection had the highest HPV16 antibody levels, whereas those who acquired incident HPV16 infections had the lowest antibody levels. Neither the presence nor the dynamics of oral HPV DNA had any correlation with HPV serology.
Co-existence of multiple strains of two novel porcine bocaviruses in the same pig, a previously undescribed phenomenon in members of the family Parvoviridae, and evidence for inter- and intra-host genetic diversity and recombination
Authors: Lau Susanna K. P. , Woo Patrick C. Y. , Yip Cyril C. Y. , Li Kenneth S. M. , Fu Clara T. Y. , Huang Yi , Chan Kwok-Hung , Yuen Kwok-Yung
Published: June 2011

Despite the recent discovery of novel bocaviruses from porcine samples, their genetic evolution and diversity are poorly understood. This study reports the identification and complete genome characterization of two novel parvoviruses, porcine bocavirus 3 (PBoV3) and porcine bocavirus 4 (PBoV4), from various porcine tissues/samples, displaying marked intra- and inter-host genetic diversity, with recombination events. Bocaviruses were detected by PCR among 16.5 % (55/333) of porcine samples (lymph nodes, serum, nasopharyngeal and faecal samples) from healthy, sick or deceased pigs from farms and a slaughterhouse in Hong Kong. As marked nucleotide polymorphisms were observed in the partial VP1 sequences, complete VP1 genes from one nasopharyngeal and three faecal specimens were cloned and sequenced, which suggested the presence of two different bocaviruses and demonstrated significant intra- and inter-host genetic diversity. Complete genome sequences revealed the presence of two bocaviruses, PBoV3 and PBoV4, in a faecal and nasopharyngeal specimen, respectively, with two genotypes, PBoV4-1 and PBoV4-2, in the latter. Their genomes encoded three ORFs, characteristic of bocaviruses. Phylogenetic analysis showed that they were distantly related to other bocaviruses, forming a distinct cluster within the genus. Recombination analysis showed possible recombination events among VP1 sequences of PBoV4 strains from a faecal specimen, with two breakpoints identified (with a 68 and 71 bp region), suggesting that different strains/variants within the same host could have arisen from recombination. This is the first report describing marked sequence diversity and the co-existence of two viruses of the family Parvoviridae within the same host, which may have originated from and, in turn, facilitated recombination.
A Shift toward Smaller Cell Size via Manipulation of Cell Cycle Gene Expression Acts to Smoothen Arabidopsis Leaf Shape
Authors: Kuwabara Asuka , Backhaus Andreas , Malinowski Robert , Bauch Marion , Hunt Lee , Nagata Toshiyuki , Monk Nick , Sanguinetti Guido , Fleming Andrew
Published: June 2011

Understanding the relationship of the size and shape of an organism to the size, shape, and number of its constituent cells is a basic problem in biology; however, numerous studies indicate that the relationship is complex and often nonintuitive. To investigate this problem, we used a system for the inducible expression of genes involved in the G1/S transition of the plant cell cycle and analyzed the outcome on leaf shape. By combining a careful developmental staging with a quantitative analysis of the temporal and spatial response of cell division pattern and leaf shape to these manipulations, we found that changes in cell division frequency occurred much later than the observed changes in leaf shape. These data indicate that altered cell division frequency cannot be causally involved in the observed change of shape. Rather, a shift to a smaller cell size as a result of the genetic manipulations performed correlated with the formation of a smoother leaf perimeter, i.e. appeared to be the primary cellular driver influencing form. These data are discussed in the context of the relationship of cell division, growth, and leaf size and shape.
Arabidopsis SUMO E3 Ligase SIZ1 Is Involved in Excess Copper Tolerance
Authors: Chen Chyi-Chuann , Chen Yong-Yi , Tang I-Chien , Liang Hong-Ming , Lai Chong-Cheong , Chiou Jeng-Min , Yeh Kuo-Chen
Published: June 2011

The reversible conjugation of the small ubiquitin-like modifier (SUMO) to protein substrates occurs as a posttranslational regulatory process in eukaryotic organisms. In Arabidopsis (Arabidopsis thaliana), several stress-responsive SUMO conjugations are mediated mainly by the SUMO E3 ligase SIZ1. In this study, we observed a phenotype of hypersensitivity to excess copper in the siz1-2 and siz1-3 mutants. Excess copper can stimulate the accumulation of SUMO1 conjugates in wild-type plants but not in the siz1 mutant. Copper accumulated to a higher level in the aerial parts of soil-grown plants in the siz1 mutant than in the wild type. A dramatic difference in copper distribution was also observed between siz1 and wild-type Arabidopsis treated with excess copper. As a result, the shoot-to-root ratio of copper concentration in siz1 is nearly twice as high as that in the wild type. We have found that copper-induced Sumoylation is involved in the gene regulation of metal transporters YELLOW STRIPE-LIKE 1 (YSL1) and YSL3, as the siz1 mutant is unable to down-regulate the expression of YSL1 and YSL3 under excess copper stress. The hypersensitivity to excess copper and anomalous distribution of copper observed in the siz1 mutant are greatly diminished in the siz1ysl3 double mutant and slightly in the siz1ysl1 double mutant. These data suggest that SIZ1-mediated sumoylation is involved specifically in copper homeostasis and tolerance in planta.
Polycyclic aromatic hydrocarbons induce migration in human hepatocellular carcinoma cells (HepG2) through reactive oxygen species‐mediated p38 MAPK signal transduction
Authors: Song Mi‐Kyung , Kim Youn‐Jung , Song Mee , Choi Han‐Seam , Park Yong‐Keun , Ryu Jae‐Chun
Published: June 2011

Although polycyclic aromatic hydrocarbons (PAHs) are carcinogenic and have been extensively studied with regard to tumor formation, few studies have investigated the involvement of these environmental chemicals in tumor migration and invasion. Polycyclic aromatic hydrocarbons induce reactive oxygen species (ROS) and activate MAPK signal transduction. The p38 signaling transduction pathway, one of the most typical MAPK pathways, plays an essential role in regulating cell migration. Therefore, we investigated whether three PAHs, benzo[a]anthracene (B[a]A), benzo[k]fluoranthene (B[k]F), and indeno[1,2,3‐c,d]pyrene (IND), induce migration in human hepatocellular carcinoma cell line HepG2 through ROS‐mediated p38 MAPK signal transduction. Reactive oxygen species generation and p38 MAPK activity both increased in a dose‐dependent manner and were prevented by SB203580, an inhibitor of p38 MAPK, and N‐acetylcysteine (NAC), a ROS scavenger. Expression of migration‐related genes was also increased by B[a]A, B[k]F, and IND in a dose‐dependent manner and was inhibited by SB203580 and NAC. The migration of HepG2 cells, observed using the Transwell migration assay, also increased in a dose‐dependent manner and was prevented by SB203580 and NAC. Our results indicate that the ROS‐mediated p38 MAPK signaling pathway plays an essential role in the PAH‐induced migration of HepG2 cells. (Cancer Sci 2011; 102: 1636–1644)
454‐pyrosequencing of Coffea arabica leaves infected by the rust fungus Hemileia vastatrix reveals in planta‐expressed pathogen‐secreted proteins and plant functions in a late compatible plant–rust interaction
Authors: FERNANDEZ DIANA , TISSERANT EMILIE , TALHINHAS PEDRO , AZINHEIRA HELENA , VIEIRA ANA , PETITOT ANNE‐SOPHIE , LOUREIRO ANDREIA , POULAIN JULIE , DA SILVA CORINNE , SILVA MARIA DO CÉU , DUPLESSIS SÉBASTIEN
Published: June 2011

Coffee (Coffea arabica L.), one of the key export and cash crops in tropical and subtropical countries, suffers severe losses from the rust fungus Hemileia vastatrix. The transcriptome of H. vastatrix was analysed during a compatible interaction with coffee to obtain an exhaustive repertoire of the genes expressed during infection and to identify potential effector genes. Large‐scale sequencing (454‐GS‐FLEX Titanium) of mixed coffee and rust cDNAs obtained from 21‐day rust‐infected leaves generated 352 146 sequences which assembled into 22 774 contigs. In the absence of any reference genomic sequences for Coffea or Hemileia, specific trinucleotide frequencies within expressed sequence tags (ESTs) and blast homology against a set of dicots and basidiomycete genomes were used to distinguish pathogen from plant sequences. About 30% (6763) of the contigs were assigned to H. vastatrix and 61% (13 951) to C. arabica. The majority (60%) of the rust sequences did not show homology to any genomic database, indicating that they were potential novel fungal genes. In silico analyses of the 6763 H. vastatrix contigs predicted 382 secreted proteins and identified homologues of the flax rust haustorially expressed secreted proteins (HESPs) and bean rust transferred protein 1 (RTP1). These rust candidate effectors showed conserved amino‐acid domains and conserved patterns of cysteine positions suggestive of conserved functions during infection of host plants. Quantitative reverse transcription‐polymerase chain reaction profiling of selected rust genes revealed dynamic expression patterns during the time course of infection of coffee leaves. This study provides the first valuable genomic resource for the agriculturally important plant pathogen H. vastatrix and the first comprehensive C. arabica EST dataset.
High frequencies of CD62L+ naive regulatory T cells in allografts are associated with a low risk of acute graft-versus-host disease following unmanipulated allogeneic haematopoietic stem cell transplantation
Authors: Lu S-Y , Liu K-Y , Liu D-H , Xu L-P , Huang X-J
Published: June 2011

Regulatory T cells (Tregs) play a key role in the prevention of acute graft-versus-host disease (aGVHD). To investigate the association between Treg subsets and aGVHD, we prospectively analysed T cell subsets in the allografts of 35 patients undergoing myeloablative unmanipulated haematopoietic stem cell transplantation. Multivariate analysis found that patients infused with less than 0·29 × 106/kg of CD4+CD25highCD45RA+CD62L+ T cells during transplantation exhibited an increased incidence of II−IV aGVHD [hazard ratio (HR) = 0·000, 95% CI = 0·000–0·106, P = 0·013]. Next, we compared the reconstitution characteristics of T cell subsets between haploidentical haematopoietic stem cell transplantation (HSCT) and sibling HSCT by collecting peripheral blood samples at regular intervals (days 30, 60 and 90) after transplantation. No significant differences were observed in the reconstitution of conventional T cells between haploidentical HSCT and sibling identical HSCT. However, total counts of recovered naiveTregs and CD62L+ naive Tregs from haploidentical HSCT were significantly lower compared to sibling identical HSCT; P-values were 0·045 and 0·021, respectively. Although total counts of conventional T cells in aGVHD patients reached similar levels compared to non-aGVHD patients before day 60 post-HSCT, total counts of naive Tregs and CD62L+ naive Tregs in aGVHD patients did not reach similar levels to non-aGVHD patients until 90 days post-HSCT. Taken together, our findings demonstrate that a large population of CD62L+ naive Tregs in allografts reduces the incidence of aGVHD. Further, development of aGVHD is related closely to the delayed reconstitution of the naive Treg population.
Interleukin-10 receptor expression and signalling were down-regulated in CD4+ T cells of lupus nephritis patients
Authors: Cui H D , Qi Z M , Yang L L , Qi L , Zhang N , Zhang X L , Du S Y , Jiang Y
Published: June 2011

Studies have indicated that interleukin (IL)-10 has a pathogenic role in systemic lupus erythematosus (SLE); however, a protective effect of IL-10 in SLE was also observed. Because the exact mechanism of IL-10 signalling in the pathogenesis of SLE is unclear, this study sought to assess the expression and signalling of interleukin-10 receptor (IL-10R) in peripheral leucocytes from patients with SLE. We used flow cytometry to examine the expression of IL-10R1 on different peripheral leucocytes from 28 SLE patients, of whom 14 had lupus nephritis (LN) and 14 were healthy controls. We also examined the effects of IL-10 on phosphorylation of signal transducer and activator of transcription (STAT)-3 and STAT-1 in peripheral blood mononuclear cells (PBMCs) obtained from 13 SLE patients and seven healthy controls. Plasma cytokines were detected by flow cytometric bead array (CBA) techniques. Although IL-10R1 expression levels on each peripheral leucocyte subset from 28 SLE patients and 14 healthy controls were similar, the expression levels on CD4+ T cells from LN patients were significantly lower than on CD4+ T cells from controls and SLE patients without nephritis (P < 0·01). IL-10R1 expression levels on CD4+ and CD8+ T cells were correlated negatively with the SLE disease activity index (P < 0·01). Additionally, the phosphorylation of STAT-3 was delayed and reduced in PBMCs from LN patients and active SLE patients. Plasma IL-10 levels were significantly higher in LN patients than controls. IL-10R1 expression on CD4+ T cells and signalling in PBMCs were down-regulated in LN patients, indicating that IL-10 and its receptor may have a special role in LN pathogenesis.
Airway and interstitial lung disease are distinct entities in paediatric common variable immunodeficiency
Authors: van de Ven A A J M , de Jong P A , van Konijnenburg D P Hoytema , Kessels O A M , Boes M , Sanders E A M , Terheggen-Lagro S W J , van Montfrans J M
Published: June 2011

Common variable immunodeficiency (CVID) is a common primary immune deficiency, caused by undefined defects in lymphocyte function, and is treated routinely by immunoglobulin substitution. CVID complications include airway disease (AD) and interstitial lung disease (ILD). It was not known if AD and ILD in CVID have a common immunological aetiology and should be considered separate features of the same disease, or as distinct syndromes that require specialized monitoring and treatment. We used high-resolution computed tomography (CT) to diagnose AD or ILD in paediatric CVID patients. Spirometry and body plethysmography did not differentiate between ILD and AD. Patients with AD (n = 11, 20%) developed more pneumonias while children with ILD (n = 8, 15%) showed immune dysregulation characterized by autoimmune complications, more severe memory B cell reduction and expansion of non-naive cytotoxic T cells. In conclusion, ILD and AD in CVID have dissimilar clinical and immunological characteristics, suggesting distinct aetiology requiring tailored monitoring and treatment of these patient subgroups.
Sustainable, low‐input, warm‐season, grass–legume grassland mixtures: mission (nearly) impossible?
Authors: Muir J. P. , Pitman W. D. , Foster J. L.
Published: June 2011

Grazing lands in warm‐temperate and subtropical North America have become less diverse. Pastures are typically grass monocultures, while rangelands are generally managed for the grass components. Overstocking, selective herbicides, fire exclusion and heavy rates of nitrogen fertilizer have contributed to near exclusion of native, warm‐season legumes. The simplicity of managing grass monocultures, pasture production responses to nitrogen fertilizer and profitability of grass‐only systems have limited interest in legume‐based approaches. Changing economics and ecological concerns with ecosystem accumulation of industrial inputs contribute to an increasing interest in legumes. Unlike the development of temperate pasture legumes and recent research in the tropics, legumes tolerant of both freezing temperatures and hot weather have received less attention. Poor establishment, limited persistence and potential invasiveness limit currently available introduced species. Native, herbaceous, warm‐season legume species occur throughout warm‐temperate North America, but little attention has been directed to these plants as potential forage species. Some success with a few native legume species, primarily in the genus Desmanthus, suggests potential for expanded assessment of forage value of the many species available. Current assessments of native legumes, primarily for conservation purposes, provide an opportunity to expand evaluations of these species for pasture and rangeland potential while economics of livestock production and public interest in ecosystem health are supportive. Experiences with legumes of warm‐temperate origin in North America, along with results with temperate and tropical pasture legumes globally, provide a starting point for future efforts at incorporating greater legume diversity in pastures and rangelands of subtropical and warm‐temperate regions around the world.
Expression and interdependencies of pluripotency factors LIN28, OCT3/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis
Authors: Gillis A. J. M. , Stoop H. , Biermann K. , van Gurp R. J. H. L. M. , Swartzman E. , Cribbes S. , Ferlinz A. , Shannon M. , Oosterhuis J.W. , Looijenga L. H. J.
Published: June 2011

OCT3/4, NANOG, SOX2 and, most recently, LIN28 have been identified as key regulators of pluripotency in mammalian embryonic and induced stem cells, and are proven to be crucial for generation of the mouse germ‐cell lineage. These factors are a hallmark of certain histological types of germ‐cell tumours (GCTs). Here, we report novel information on the temporal and spatial expression pattern of LIN28 during normal human male germ‐cell development as well as various types of GCTs. To investigate LIN28 expression, immunohistochemical analyses and quantitative proximity ligation assay‐based TaqMan protein assays were applied on snap‐frozen and formalin‐fixed, paraffin‐embedded samples as well as representative cell lines. LIN28 was found in primordial germ cells, gonocytes and pre‐spermatogonia, in contrast to OCT3/4 and NANOG, which were found only in the first two stages. LIN28 was also found in all precursor lesions (carcinoma in situ and gonadoblastoma) of type II GCTs, as well as the invasive components seminoma and the non‐seminomatous elements embryonal carcinoma and yolk sac tumour. Choriocarcinoma showed a heterogeneous pattern, while teratomas and spermatocytic seminomas (type III GCTs) were negative. This expression pattern suggests that LIN28 is associated with malignant behaviour of type II GCTs. Cell line experiments involving siRNA knockdown of LIN28, OCT3/4 and SOX2 showed that LIN28 plays a role in the maintenance of the undifferentiated state of both seminoma and embryonal carcinoma, closely linked to, and likely upstream of OCT3/4 and NANOG. In conclusion, LIN28 regulates the differentiation status of seminoma and embryonal carcinoma and is likely to play a related role in normal human germ‐cell development.
Combat stressors and post‐traumatic stress in deployed military healthcare professionals: an integrative review
Authors: Gibbons Susanne W. , Hickling Edward J. , Watts Dorraine D.
Published: June 2011

gibbons s.w., hickling e.j. & watts d.d. (2012) Combat stressors and post‐traumatic stress in deployed military healthcare professionals: an integrative review. Journal of Advanced Nursing68(1), 3–21.

Background.  While there has been a growing body of literature on the impact of combat stressors and post‐traumatic stress on military service members involved in current conflicts, there has been little available information that directly examines the impact of these on healthcare providers.

Aims.  Aims for this integrative review included: (1) identifying exposures, experiences and other factors influencing stress responses in military healthcare providers previously engaged in a war effort and (2) describing the incidence of post‐traumatic stress and related mental health problems in this population.

Review Methods.  Using Cooper’s integrative review method, relevant documents were collected and analysed using content categories and a coding scheme to assist with identifying and recording data for units of analysis.

Data Sources.  Literature searches (including all years to present) were conducted using keywords for stress reaction, for healthcare provider and for military war effort involvement. Literature was obtained using the Cumulative Index to Nursing and Allied Health Literature, the National Library of Medicine and the American Psychological Association databases.

Results.  Evidence suggests that similar to military combatants, military healthcare provider exposure to life‐threatening situations will increase the probability of adverse psychological disorders following these traumatic experiences. The presence of a strong sense of meaning and purpose, within a supportive environment appear to help mediate the impact of these dangerous and stressful events.

Conclusion.  Results of this review and other supporting literature indicate the need for a systematic approach to studying combat stress and post‐traumatic stress in deployed healthcare providers.