bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-21 targets peroxisome proliferators-activated receptor-α in an autoregulatory loop to modulate flow-induced endothelial inflammation
Authors: Zhou Jing , Wang Kuei-Chun , Wu Wei , Subramaniam Shankar , Shyy John Y.-J. , Chiu Jeng-Jiann , Li Julie Y.-S. , Chien Shu
Published: June 2011

Adhesion of circulating monocytes to vascular endothelial cells (ECs) is a critical event leading to vascular inflammation and, hence, development of atherosclerosis. MicroRNAs (miRs) are a class of endogenous, highly conserved, noncoding small RNAs that play important roles in regulating gene expression and cellular function, as well as pathogenesis of atherosclerosis. Here, we showed that oscillatory shear stress (OSS) induces the expression of miR-21 at the transcriptional level in cultured human umbilical vein ECs via an increased binding of c-Jun, which is a component of transcription factor activator protein-1 (AP-1), to the promoter region of miR-21. OSS induction of miR-21 inhibited the translation, but not transcription, of peroxisome proliferators-activated receptor-α (PPARα) by 3′-UTR targeting. Overexpression of miR-21 up-regulated AP-1 activation, which was attenuated by exogenous expression of PPARα. OSS and overexpression of miR-21 enhanced the expression of adhesion molecules vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and the consequential adhesion of monocytes to ECs. Overexpression of PPARα significantly attenuated the AP-1–mediated miR-21 expression. These results demonstrate a unique mechanism by which OSS induces AP-1–dependent miR-21 expression, which directly targets PPARα to inhibit its expression, thereby allowing activation of AP-1 and the promotion of monocyte adhesion. Our findings suggest the presence of a positive feedback loop that enables the sustained induction of miR-21, thus contributing to the proinflammatory responses of vascular endothelium under OSS.
Measured 3D turbulent mixing in a small-scale circuit breaker model
Authors: Basse Nils T , Kissing Christopher , Bini Riccardo
Published: June 2011

Turbulence plays a key role in several physical processes related to the interruption of current in a gas circuit breaker (GCB). In this paper we study one aspect, namely turbulent gas mixing in the heating volume of a small-scale 3D GCB model. Mixing is observed using a shadowgraphy setup; postprocessing extracts information on the time-varying velocity field. Discharges with two different current amplitudes were studied and their repeatability investigated. A measure of mixing completeness, the largest vortex area, was investigated. The experiments reported upon in this paper were done in air at atmospheric pressure.
Pre-plasma effects on core heating and enhancing heating efficiency by extended double cone for FIREX
Authors: Johzaki T. , Nagatomo H. , Sunahara A. , Cai H.-B. , Sakagami H. , Nakao Y. , Mima K.
Published: June 2011

The effect of pre-plasma on core heating in cone-guiding fast ignition is evaluated by two-dimensional particle-in-cell (PIC) and Fokker–Planck (FP) simulations. If the long-scale pre-plasma exists in the cone, the generated fast electron energy becomes too high for effective core heating. As a result, the energy coupling from laser to core ηL→core is reduced by 80% compared with the case without a pre-plasma. Even for the case without a pre-plasma, ηL→core obtained in the simulation is smaller than that required for 5 keV heating in FIREX-I. In order to enhance ηL→core, we propose a new target design ‘extended double cone with short inner cone wall’ for fast electron guiding to imploded core and show sufficient improvement of heating efficiency using this new cone on the basis of PIC and FP hydro-simulations.
Corrigendum to “Existence of solutions for semilinear elliptic problems without (𝑃𝑆) condition”
Authors: Yang Jianfu
Published: June 2011

In this corrigendum we give a correct proof for equation (3.17), as well as the assertion on line 15, page 1364, of “Existence of solutions for semilinear elliptic problems without

(
P
S
)

(PS)

condition”, Proc. Amer. Math. Soc. 132(5) (2004), 1355-1366.
Topological arrangement of the intracellular membrane fusion machinery
Authors: Rathore Shailendra S. , Ghosh Nilanjan , Ouyang Yan , Shen Jingshi
Published: June 2011

Soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) form a four-helix coiled-coil bundle that juxtaposes two bilayers and drives a basal level of membrane fusion. The Sec1/Munc18 (SM) protein binds to its cognate SNARE bundle and accelerates the basal fusion reaction. The question of how the topological arrangement of the SNARE helices affects the reactivity of the fusion proteins remains unanswered. Here we address the problem for the first time in a reconstituted system containing both SNAREs and SM proteins. We find that to be fusogenic a SNARE topology must support both basal fusion and SM stimulation. Certain topological combinations of exocytic SNAREs result in basal fusion but cannot support SM stimulation, whereas other topologies support SM stimulation without inducing basal fusion. It is striking that of all the possible topological combinations of exocytic SNARE helices, only one induces efficient fusion. Our results suggest that the intracellular membrane fusion complex is designed to fuse bilayers according to one genetically programmed topology.
Agricultural Distortions, Structural Change, and Economic Growth: A Cross‐Country Analysis
Authors: Dennis Benjamin N. , İşcan Talan B.
Published: June 2011

Taxing agriculture to mobilize resources for industrialization has been a widely used development strategy. Using novel cross‐country time‐series data sets with direct measures of agricultural taxation, we examine how a policy bias against agriculture affects the speed of convergence in income per capita, structural change, and economic growth. We find that distortionary agricultural policies in poor economies can account for the emergence of convergence clubs in our sample by significantly retarding their structural transformation and economic growth. Overall, we find no evidence suggesting that policies that discriminate against agriculture have been beneficial for long‐term economic growth.
Comparative studies of de novo assembly tools for next-generation sequencing technologies
Authors: Lin Yong , Li Jian , Shen Hui , Zhang Lei , Papasian Christopher J. , Deng Hong−Wen
Published: June 2011

Motivation: Several new de novo assembly tools have been developed recently to assemble short sequencing reads generated by next-generation sequencing platforms. However, the performance of these tools under various conditions has not been fully investigated, and sufficient information is not currently available for informed decisions to be made regarding the tool that would be most likely to produce the best performance under a specific set of conditions.

Results: We studied and compared the performance of commonly used de novo assembly tools specifically designed for next-generation sequencing data, including SSAKE, VCAKE, Euler-sr, Edena, Velvet, ABySS and SOAPdenovo. Tools were compared using several performance criteria, including N50 length, sequence coverage and assembly accuracy. Various properties of read data, including single-end/paired-end, sequence GC content, depth of coverage and base calling error rates, were investigated for their effects on the performance of different assembly tools. We also compared the computation time and memory usage of these seven tools. Based on the results of our comparison, the relative performance of individual tools are summarized and tentative guidelines for optimal selection of different assembly tools, under different conditions, are provided.

Contact:  hdeng2@tulane.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Robust biclustering by sparse singular value decomposition incorporating stability selection
Authors: Sill Martin , Kaiser Sebastian , Benner Axel , Kopp-Schneider Annette
Published: June 2011

Motivation: Over the past decade, several biclustering approaches have been published in the field of gene expression data analysis. Despite of huge diversity regarding the mathematical concepts of the different biclustering methods, many of them can be related to the singular value decomposition (SVD). Recently, a sparse SVD approach (SSVD) has been proposed to reveal biclusters in gene expression data. In this article, we propose to incorporate stability selection to improve this method. Stability selection is a subsampling-based variable selection that allows to control Type I error rates. The here proposed S4VD algorithm incorporates this subsampling approach to find stable biclusters, and to estimate the selection probabilities of genes and samples to belong to the biclusters.

Results: So far, the S4VD method is the first biclustering approach that takes the cluster stability regarding perturbations of the data into account. Application of the S4VD algorithm to a lung cancer microarray dataset revealed biclusters that correspond to coregulated genes associated with cancer subtypes. Marker genes for different lung cancer subtypes showed high selection probabilities to belong to the corresponding biclusters. Moreover, the genes associated with the biclusters belong to significantly enriched cancer-related Gene Ontology categories. In a simulation study, the S4VD algorithm outperformed the SSVD algorithm and two other SVD-related biclustering methods in recovering artificial biclusters and in being robust to noisy data.

Availability: R-Code of the S4VD algorithm as well as a documentation can be found at http://s4vd.r-forge.r-project.org/.

Contact:  m.sill@dkfz.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
The Botrytis cinerea Reg1 Protein, a Putative Transcriptional Regulator, Is Required for Pathogenicity, Conidiogenesis, and the Production of Secondary Metabolites
Authors: Michielse Caroline B. , Becker Matthias , Heller Jens , Moraga Javier , Collado Isidro G. , Tudzynski Paul
Published: June 2011

Botrytis cinerea, which causes gray-mold rot, attacks a wide range of plant species. To understand the infection process, the role of a putative transcriptional regulator, BcReg1 (regulator 1), in pathogenicity was studied. This transcriptional regulator shows similarity to the morphological switch regulators Candida albicans Wor1 and Histoplasma capsulatum Ryp1. Gene knock-out and complementation studies revealed that bcreg1 is required for pathogenicity. The bcreg1 mutant is able to penetrate plant tissue but is not able to cause necrotic lesions. In addition, the mutant is blocked in conidia formation and does not produce detectable levels of the sesquiterpene botrydial and the polyketide botcinic acid. Based on transcript expression levels, it can be concluded that bcreg1 is a downstream target of two mitogen-activated protein kinases, BcSak1 and Bmp3.
The Fusarium virguliforme Toxin FvTox1 Causes Foliar Sudden Death Syndrome-Like Symptoms in Soybean
Authors: Brar Hargeet K. , Swaminathan Sivakumar , Bhattacharyya Madan K.
Published: June 2011

Fusarium virguliforme causes sudden death syndrome (SDS) in soybean. The pathogen has never been isolated from diseased foliar tissues; therefore, one or more toxins have been considered to cause foliar SDS development. Cell-free F. virguliforme culture filtrates containing a toxin causes foliar SDS in soybean. A low-molecular-weight protein of approximately 13.5 kDa (FvTox1), purified from F. virguliforme culture filtrates, produces foliar SDS-like symptoms in cut soybean seedlings. Anti-FvTox1 monoclonal antibodies raised against the purified FvTox1 were used in isolating the FvTox1 gene. In the presence of light, recombinant FvTox1 protein expressed in an insect cell line resulted in chlorosis and necrosis in soybean leaf disks that are typical foliar SDS symptoms. SDS-susceptible but not the SDS-resistant soybean lines were sensitive to the baculovirus-expressed toxin. The requirement of light for foliar SDS-like symptom development indicates that FvTox1 induces foliar SDS in soybean, most likely through production of free radicals by interrupting photosynthesis.
Temporal Genetic Structure ofPhytophthora capsiciPopulations from a Creek Used for Irrigation in Michigan
Authors: Quesada-Ocampo L. M. , Granke L. L. , Hausbeck M. K.
Published: June 2011

Irrigation water may harbor Phytophthora capsici, and irrigating susceptible vegetable crops with infested water can initiate epidemics. In this study, we evaluated the genetic structure of 106 P. capsici isolates collected from a creek used for irrigation (2002, 2003, and 2006) and from a field adjacent to the creek (2001) using six polymorphic nuclear loci. Bayesian clustering analysis detected four clusters in the sample, and some clusters occurred more or less frequently in certain years. In 2006, isolates belonging to cluster four predominated in the sampling. Mean pairwise FSTvalues (0.008 to 0.065) indicated low differentiation between categories, but the most differentiation was observed when 2006 was compared to 2001 and 2002. Differences in isolate phenotypic traits were observed year-to-year. Isolates insensitive to mefenoxam were more common in 2006 and 2003 than in 2002 and 2001. The mating type ratio was approximately 1:1 in 2002 and 2003, but was skewed toward A1 in 2001 and toward A2 in 2006. Since irrigation water can remain infested or become reinfested annually with P. capsici for years after the adjacent fields are transitioned to nonsusceptible crops, growers are advised to avoid potentially infested irrigation water even after rotating to nonhost crops for several years.
First Report of Chrysanthemum chlorotic mottle viroid in Chrysanthemum in China
Authors: Zhang Z. Z. , Pan S. , Li S. F.
Published: June 2011

During the spring of 2008, a chrysanthemum plant showing mild mottle on young leaves was observed in a garden in Beijing, China. After the plant was moved into a greenhouse, symptoms became severe with obvious yellowing and complete chlorosis on new leaves. In addition, when a survey was conducted for chrysanthemum diseases in 2010, plants with mild chlorotic spots on leaves were also found occasionally in a commercial field in Hainan, China. These symptoms resembled symptoms induced by Chrysanthemum chlorotic mottle viroid (CChMVd). Therefore, total RNA of 13 samples collected from Beijing (cultivar unknown) and Hainan (cv. Golden) was extracted according to Li et al. (2) and tested for CChMVd by northern blot hybridization using DIG-labeled CChMVd cRNA probe (1). All samples were CChMVd positive, and the healthy control was negative. The viroid was further confirmed by reverse transcription (RT)-PCR using CChMVd specific primers (forward: 5′-AGGTCGTA(T)AAACTTCCCCTCTAAA(G)CG-3′, homologous to nucleotides 134 to 159; and reverse: 5′-TCCAGTCGAGACCTGAAGTGGGTTTC-3′, complementary to nucleotides 133 to 108) (1). Two amplified products of approximately 400 bp were cloned into the pGEM-T vector (Promega, Madison, WI) and transformed into E. coli DH5α competent cells. Two positive clones were obtained from each isolate and sequenced. Four sequences obtained have been submitted to GenBank (Accession Nos. HQ891014 to HQ891017). Sequence analysis revealed that the obtained sequences shared 96.49 to 96.99% similarity with the reference sequence CChMVd (GenBank Accession No. NC003540). All the clones are 399 nucleotides long and are thought to be the symptomatic type based on their UUUC sequence at positions 82 to 85 in the CChMVd tetraloop (1). In addition, both isolates were mechanically inoculated to three healthy chrysanthemum plants of the unknown cultivar from Beijing. All inoculated plants developed chlorosis after 5 weeks and CChMVd infections were confirmed by northern blot hybridization and RT-PCR. CChMVd is an important pathogen that may potentially cause losses to the chrysanthemum industry. It is necessary to survey for CChMVd infection in various chrysanthemums cultivated in China. To our knowledge, this is the first report of CChMVd in chrysanthemum in China.

References: (1) P. M. De la Pena et al. Proc. Natl. Acad. Sci. USA. 96:9960, 1999. (2) S. F. Li et al. Ann. Phytopathol. Soc. Jpn. 61:381, 1995.
Susceptibility of Onion Relatives (Allium spp.) to Iris yellow spot virus
Authors: Cramer C. S. , Bag S. , Schwartz H. F. , Pappu H. R.
Published: June 2011

Iris yellow spot virus (IYSV; family Bunyaviridae, genus Tospovirus) is becoming an increasingly important constraint to the production of bulb and seed onions (Allium cepa L.) in many onion-growing regions of the continental United States and the world (4). During an evaluation of onion germplasm for susceptibility to IYSV, six other Allium species (A. altaicum, A. galanthum, A. roylei, A. schoenoprasum, A. tuberosum, and A. vavilovii) were also evaluated under natural field conditions. In July 2010, symptoms suggestive of IYSV infection (straw-colored necrotic lesions) were observed on leaves of these Allium spp. in experimental plots in Las Cruces, NM. IYSV was detected in symptomatic leaves of A. altaicum, A. vavilovii, A. tuberosum, A. schoenoprasum and A. roylei with a commercially available ELISA kit (Agdia Inc., Elkhart, IN). IYSV infection was confirmed by reverse transcription (RT)-PCR with forward and complementary primers 5′-CTCTTAAACACATTTAACAAGCAC-3′ and 5′-TAAAACAAACATTCAAACAA-3′ flanking the nucleocapsid (N) gene encoded by the small RNA of IYSV as previously described (1,3). Amplicons, approximately 1.1 kb long, were obtained from all symptomatic Allium spp. samples but not from healthy samples or water controls. Sequencing of selected amplicons confirmed IYSV infection. The highest nucleotide identity of 98% was shared with IYSV isolates from Japan (GenBank Accession No. AB180921). A. altaicum, A. vavilovii, and A. pskemense were previously reported from Washington to be susceptible to IYSV (2). Current findings expand the list of Allium spp. that are susceptible to IYSV and underscores the need for continued screening of other members of the genus to find sources of resistance to IYSV.

References: (1) H. R. Pappu et al. Arch. Virol. 151:1015, 2006. (2) H. R. Pappu et al. Plant Dis. 90:378, 2006. (3) H. R. Pappu et al. Plant Dis. 92:588, 2008. (4) H. R. Pappu et al. Virus Res. 141:219, 2009.
Quantitative Trait Loci for Adult-Plant Resistance to Mycosphaerella graminicola in Two Winter Wheat Populations
Authors: Risser P. , Ebmeyer E. , Korzun V. , Hartl L. , Miedaner T.
Published: June 2011

Septoria tritici blotch (STB) is one of the most important leaf spot diseases in wheat worldwide. The goal of this study was to detect chromosomal regions for adult-plant resistance in large winter wheat populations to STB. Inoculation by two isolates with virulence to Stb6 and Stb15, both present in the parents, was performed and STB severity was visually scored plotwise as percent coverage of flag leaves with pycnidia-bearing lesions. ‘Florett’/‘Biscay’ and ‘Tuareg’/‘Biscay’, each comprising a cross of a resistant and a susceptible cultivar, with population sizes of 316 and 269 F7:8 recombinant inbred lines, respectively, were phenotyped across four and five environments and mapped with amplified fragment length polymorphism, diversity array technology, and simple sequence repeat markers covering polymorphic regions of ≈1,340 centimorgans. Phenotypic data revealed significant (P < 0.01) genotypic differentiation for STB, heading date, and plant height. Entry-mean heritabilities (h2) for STB were 0.73 for ‘Florett’/‘Biscay’ and 0.38 for ‘Tuareg’/‘Biscay’. All correlations between STB and heading date as well as between STB and plant height were low (r = –0.13 to –0.20). In quantitative trait loci (QTL) analysis, nine and six QTL were found for STB ratings explaining, together, 55 and 51% of phenotypic variation in ‘Florett’/‘Biscay’ and ‘Tuareg’/‘Biscay’, respectively. Genotype–environment and QTL–environment interactions had a large impact. Two major QTL were detected consistently across environments on chromosomes 3B and 6D from ‘Florett’ and chromosomes 4B and 6B from ‘Tuareg’, each explaining 12 to 17% of normalized adjusted phenotypic variance. These results indicate that adult-plant resistance to STB in both mapping populations was of a quantitative nature.
Efficacy of an MFGM‐enriched Complementary Food in Diarrhea, Anemia, and Micronutrient Status in Infants
Authors: Zavaleta Nelly , Kvistgaard Anne Staudt , Graverholt Gitte , Respicio Graciela , Guija Henry , Valencia Norma , Lönnerdal Bo
Published: June 2011

Objective:

The aim of the present study was to evaluate the efficacy of a milkfat globule membrane (MFGM)–enriched protein fraction in a complementary food, on diarrhea, anemia, and micronutrient status.

Subjects and Methods:

A randomized, double‐blind controlled design to study 550 infants, 6 to 11 months old, who received daily for 6 months a complementary food (40 g/day) with the protein source being either the MFGM protein fraction or skim milk proteins (control). Health and nutritional status of infants were examined monthly in the outpatient clinic; product intake, food patterns, and diarrhea morbidity were assessed by home visits twice per week. Hemoglobin and micronutrient status were measured at 0 and 6 months of intervention. Results are presented as the entire group and as 6 to 8 and 9 to 11 months subgroups.

Results:

A total of 499 infants completed the study. Global prevalence of diarrhea was 3.84% and 4.37% in the MFGM group and control group, respectively (P < 0.05). Consumption of the MFGM protein fraction reduced episodes of bloody diarrhea (odds ratio 0.54; 95% confidence interval 0.31–0.93, P = 0.025) adjusting for anemia and potable water facilities as covariates. There were no differences between groups in anemia, serum ferritin, zinc, or folate.

Conclusions:

Addition of an MFGM‐enriched protein fraction to complementary food had beneficial effects on diarrhea in infants and may thus help to improve the health of vulnerable populations.
Shame and honour drive cooperation
Authors: Jacquet Jennifer , Hauert Christoph , Traulsen Arne , Milinski Manfred
Published: June 2011

Can the threat of being shamed or the prospect of being honoured lead to greater cooperation? We test this hypothesis with anonymous six-player public goods experiments, an experimental paradigm used to investigate problems related to overusing common resources. We instructed the players that the two individuals who were least generous after 10 rounds would be exposed to the group. As the natural antithesis, we also test the effects of honour by revealing the identities of the two players who were most generous. The non-monetary, reputational effects induced by shame and honour each led to approximately 50 per cent higher donations to the public good when compared with the control, demonstrating that both shame and honour can drive cooperation and can help alleviate the tragedy of the commons.
Differential effect of acute and persistent Junín virus infections on the nucleo-cytoplasmic trafficking and expression of heterogeneous nuclear ribonucleoproteins type A and B
Authors: Maeto Cynthia A. , Knott María E. , Linero Florencia N. , Ellenberg Paula C. , Scolaro Luis A. , Castilla Viviana
Published: June 2011

Heterogeneous nuclear ribonucleoproteins A and B (hnRNPs A/B), cellular RNA-binding proteins that participate in splicing, trafficking, translation and turnover of mRNAs, have been implicated in the life cycles of several cytoplasmic RNA viruses. Here, we demonstrate that silencing of hnRNPs A1 and A2 significantly reduces the replication of the arenavirus Junín virus (JUNV), the aetiological agent of Argentine haemorrhagic fever. While acute JUNV infection did not modify total levels of expression of hnRNPs A/B in comparison with uninfected cells, non-cytopathic persistent infection exhibited low levels of these cell proteins. Furthermore, acutely infected cells showed a cytoplasmic relocalization of overexpressed hnRNP A1, probably related to the involvement of this protein in virus replicative cycle. This cytoplasmic accumulation was also observed in cells expressing viral nucleoprotein (N), and co-immunoprecipitation studies revealed the interaction between hnRNP A1 and N protein. By contrast, a predominantly nuclear distribution of overexpressed hnRNP A1 was found during persistent infection, even in the presence of endogenous or overexpressed N protein, indicating a differential modulation of nucleo–cytoplasmic trafficking in acute and persistent JUNV infections.
Molecular diversity and evolutionary history of rabies virus strains circulating in the Balkans
Authors: McElhinney L. M. , Marston D. A. , Freuling C. M. , Cragg W. , Stankov S. , Lalosević D. , Lalosević V. , Müller T. , Fooks A. R.
Published: June 2011

Molecular studies of European classical rabies viruses (RABV) have revealed a number of geographically clustered lineages. To study the diversity of Balkan RABV, partial nucleoprotein (N) gene sequences were analysed from a unique panel of isolates (n = 210), collected from various hosts between 1972 and 2006. All of the Balkan isolates grouped within the European/Middle East Lineage, with the majority most closely related to East European strains. A number of RABV from Bosnia & Herzegovina and Montenegro, collected between 1986 and 2006, grouped with the West European strains, believed to be responsible for the rabies epizootic that spread throughout Europe in the latter half of the 20th Century. In contrast, no Serbian RABV belonged to this sublineage. However, a distinct group of Serbian fox RABV provided further evidence for the southwards wildlife-mediated movement of rabies from Hungary, Romania and Serbia into Bulgaria. To determine the optimal region for evolutionary analysis, partial, full and concatenated N-gene and glycoprotein (G) gene sequences were compared. Whilst both the divergence times and evolutionary rates were similar irrespective of genomic region, the 95 % highest probability density (HPD) limits were significantly reduced for full N-gene and concatenated NG-gene sequences compared with partial gene sequences. Bayesian coalescent analysis estimated the date of the most common recent ancestor of the Balkan RABV to be 1885 (95 % HPD, 1852–1913), and skyline plots suggested an expansion of the local viral population in 1980–1990, which coincides with the observed emergence of fox rabies in the region.
Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus
Authors: Scott Paul D. , Meng Bo , Marriott Anthony C. , Easton Andrew J. , Dimmock Nigel J.
Published: June 2011

Influenza A and B viruses are major human respiratory pathogens that contribute to the burden of seasonal influenza. They are both members of the family Orthomyxoviridae but do not interact genetically and are classified in different genera. Defective interfering (DI) influenza viruses have a major deletion of one or more of their eight genome segments, which renders them both non-infectious and able to interfere in cell culture with the production of infectious progeny by a genetically compatible, homologous virus. It has been shown previously that intranasal administration of a cloned DI influenza A virus, 244/PR8, protects mice from various homologous influenza A virus subtypes and that it also protects mice from respiratory disease caused by a heterologous virus belonging to the family Paramyxoviridae. The mechanisms of action in vivo differ, with homologous and heterologous protection being mediated by probable genome competition and type I interferon (IFN), respectively. In the current study, it was shown that 244/PR8 also protects against disease caused by a heterologous influenza B virus (B/Lee/40). Protection from B/Lee/40 challenge was partially eliminated in mice that did not express a functional type I IFN receptor, suggesting that innate immunity, and type I IFN in particular, are important in mediating protection against this virus. It was concluded that 244/PR8 has the ability to protect in vivo against heterologous IFN-sensitive respiratory viruses, in addition to homologous influenza A viruses, and that it acts by fundamentally different mechanisms.
Tissue-Specific Differences in Cytosine Methylation and Their Association with Differential Gene Expression in Sorghum
Authors: Zhang Meishan , Xu Chunming , von Wettstein Diter , Liu Bao
Published: June 2011

It has been well established that DNA cytosine methylation plays essential regulatory roles in imprinting gene expression in endosperm, and hence normal embryonic development, in the model plant Arabidopsis (Arabidopsis thaliana). Nonetheless, the developmental role of this epigenetic marker in cereal crops remains largely unexplored. Here, we report for sorghum (Sorghum bicolor) differences in relative cytosine methylation levels and patterns at 5′-CCGG sites in seven tissues (endosperm, embryo, leaf, root, young inflorescence, anther, and ovary), and characterize a set of tissue-specific differentially methylated regions (TDMRs). We found that the most enriched TDMRs in sorghum are specific for the endosperm and are generated concomitantly but imbalanced by decrease versus increase in cytosine methylation at multiple 5′-CCGG sites across the genome. This leads to more extensive demethylation in the endosperm than in other tissues, where TDMRs are mainly tissue nonspecific rather than specific to a particular tissue. Accordingly, relative to endosperm, the other six tissues showed grossly similar levels though distinct patterns of cytosine methylation, presumably as a result of a similar extent of concomitant decrease versus increase in cytosine methylation that occurred at variable genomic loci. All four tested TDMRs were validated by bisulfite genomic sequencing. Diverse sequences were found to underlie the TDMRs, including those encoding various known-function or predicted proteins, transposable elements, and those bearing homology to putative imprinted genes in maize (Zea mays). We further found that the expression pattern of at least some genic TDMRs was correlated with its tissue-specific methylation state, implicating a developmental role of DNA methylation in regulating tissue-specific or -preferential gene expression in sorghum.
BBX32, an Arabidopsis B-Box Protein, Functions in Light Signaling by Suppressing HY5-Regulated Gene Expression and Interacting with STH2/BBX21
Authors: Holtan Hans E. , Bandong Simona , Marion Colleen M. , Adam Luc , Tiwari Shiv , Shen Yu , Maloof Julin N. , Maszle Don R. , Ohto Masa-aki , Preuss Sasha , Meister Rob , Petracek Marie , Repetti Peter P. , Reuber T. Lynne , Ratcliffe Oliver J. , Khanna Rajnish
Published: June 2011

A B-box zinc finger protein, B-BOX32 (BBX32), was identified as playing a role in determining hypocotyl length during a large-scale functional genomics study in Arabidopsis (Arabidopsis thaliana). Further analysis revealed that seedlings overexpressing BBX32 display elongated hypocotyls in red, far-red, and blue light, along with reduced cotyledon expansion in red light. Through comparative analysis of mutant and overexpression line phenotypes, including global expression profiling and growth curve studies, we demonstrate that BBX32 acts antagonistically to ELONGATED HYPOCOTYL5 (HY5). We further show that BBX32 interacts with SALT TOLERANCE HOMOLOG2/BBX21, another B-box protein previously shown to interact with HY5. Based on these data, we propose that BBX32 functions downstream of multiple photoreceptors as a modulator of light responses. As such, BBX32 potentially has a native role in mediating gene repression to maintain dark adaptation.
Dual cut‐off transient elastography to assess liver fibrosis in chronic hepatitis B: a cohort study with internal validation
Authors: Viganò M. , Paggi S. , Lampertico P. , Fraquelli M. , Massironi S. , Ronchi G. , Rigamonti C. , Conte D. , Colombo M.
Published: June 2011

Aliment Pharmacol Ther 2011; 34: 353–362

Background  Transient elastography has gained popularity to stage liver fibrosis in chronic viral hepatitis, however, diagnostic cut‐offs for severe fibrosis in chronic hepatitis B are poorly defined.

Aim  To evaluate an algorithm with two distinct cut‐offs for positive and negative prediction of significant fibrosis and cirrhosis in chronic hepatitis B patients.

Methods  Two cohorts of treatment‐naïve patients with chronic hepatitis B (125 training and 92 validations) were consecutively and concurrently examined by percutaneous liver biopsy and transient elastography. Fibrosis was staged by Metavir (significant fibrosis = F ≥ 2; cirrhosis = F4) in ≥2 cm long liver tissue cores.

Results  A >13.1 kPa positive and a ≤9.4 kPa negative cut‐off for cirrhosis had a >90% sensitivity and specificity, with an accuracy of 94%. The corresponding cut‐offs for F ≥ 2 were >9.4 and ≤6.2 kPa, thus classifying 56% of patients with an overall accuracy of 90%. In the validation cohort, F4 and F ≥ 2 were predicted by the above transient elastography cut‐offs with an overall accuracy >90%. In 165 patients with higher than upper limit of normal transaminase activity the dual cut‐off algorithm of transient elastography was as accurate as in the 52 patients with normal alanine aminotransferase values in the prediction and exclusion of cirrhosis, only.

Conclusions  A dual cut‐off algorithm allowed for correctly classifying both significant fibrosis and cirrhosis in the majority of the patients with chronic hepatitis B, independent of alanine aminotransferase values, thus reducing the need for liver biopsy investigations.
Association between the presence of brown adipose tissue and non‐alcoholic fatty liver disease in adult humans
Authors: Yilmaz Y. , Ones T. , Purnak T. , Ozguven S. , Kurt R. , Atug O. , Turoglu H. T. , Imeryuz N.
Published: June 2011

Aliment Pharmacol Ther 2011; 34: 318–323

Background  The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans.

Aim  To examine whether the presence and activity of BAT in patients undergoing PET‐CT examinations is related to the presence of fatty liver.

Method  We retrospectively analysed 3666 consecutive PET‐CT whole‐body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT‐positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET‐CT scans. In areas where uptake of [18F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD.

Results  Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT− subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT− subjects (3.12, 95% confidence interval = 1.03–9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05).

Conclusion  The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.
Very low birth weight survivors have reduced peak bone mass and reduced insulin sensitivity
Authors: Smith C. M. , Wright N. P. , Wales J. K. H. , Mackenzie C. , Primhak R. A. , Eastell R. , Walsh J. S.
Published: June 2011

Context  Increasing numbers of very low birth weight (VLBW) infants are surviving into adulthood because of improvements in neonatal intensive care. Adverse events in early life can have long‐term effects through reprogramming of metabolic systems.

Objective  To determine whether young adult VLBW survivors have abnormalities of skeletal development or endocrine function.

Design  Cross‐sectional, observational, case‐control study.

Participants  Thirty‐seven VLBW subjects and 27 healthy controls at peak bone mass (mean age 23).

Measurements  Differences between cases and controls in body size, body composition, bone mass and bone geometry [assessed by dual‐energy X‐ray absorptiometry (DXA), hip structure analysis and peripheral quantitative computed tomography (pQCT)], bone turnover [urine N‐terminal telopeptide of type I collagen (NTX), serum C‐terminal telopeptide of type I collagen (CTX)], aminoterminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase), hormones (sex steroids, IGF‐1, PTH and 25‐OH vitamin D) and insulin sensitivity (HOMA‐IR and oral glucose tolerance testing).

Results  VLBW subjects had lower bone density at the lumbar spine (5.7%) and femoral neck (8.6%), which persisted after correction for bone size by the estimation of volumetric density (bone mineral apparent density). Urine NTX was higher in VLBW subjects than in controls, but there were no significant differences in other bone turnover markers. VLBW survivors had lower insulin sensitivity (mean INS‐30 controls = 57.0, VLBW subjects = 94.3, P < 0.01), but there were no differences in whole body fat mass or truncal fat mass between VLBW subjects and controls.

Conclusions  Young adult VLBW survivors have reduced bone density for their bone size and reduced insulin sensitivity, which may have significant implications for their risk of fracture and diabetes in later life.
Inflamed gut mucosa: downstream of interleukin‐10
Authors: Paul Gregor , Khare Vineeta , Gasche Christoph
Published: June 2011

Eur J Clin Invest 2012; 42 (1): 95–109

Background  Interleukin‐10 is a pleiotropic cytokine, whose main function is limitation and ultimately termination of immune responses. This is especially true for environmental interfaces such as the gastrointestinal tract. IL‐10 acts as a key mediator for maintaining gut homeostasis. IL‐10 knockout mice are well established as a genetic model for inflammatory bowel disease (IBD), and sequence variants in the IL‐10 locus contribute to ulcerative colitis (UC).

Design  This review covers the significance of IL‐10 signalling in the intestinal immune response both in health and disease. It explains the biological role of IL‐10, its deregulation in IBD and its contribution to intestinal inflammation via endoplasmic reticulum stress response.

Results  Many IBD susceptibility genes have been discovered in the past years, linking fundamental biological systems, like innate and adaptive immunity, stress responses, autophagy and mucosal barrier to the pathogenesis of Crohn’s disease (CD) and UC. IL‐10 has long been known for its substantial role in regulating gut immunity, but its contribution to IBD was somewhat elusive. A recent study identified mutations in either IL‐10 receptor subunits that are associated with early‐onset enterocolitis, a severe phenotype of IBD. Other than genetic variants of IL‐10 receptors, IL‐10 and STAT3 genes are also associated with IBD, emphasizing the involvement of the IL‐10 signalling cascade in the pathogenesis of CD and UC.

Conclusions  The discovery of inherited deregulations in the IL‐10 signalling cascade is not only considered the missing link between IL‐10 and intestinal homeostasis, but also demonstrates how findings made in animal models help explaining human disease.
Small artery dilation and endothelial markers in cardiovascular risk patients
Authors: Aragonès Gemma , Ferré Raimon , Girona Josefa , Plana Núria , Merino Jordi , Heras Mercedes , Masana Lluís
Published: June 2011

Eur J Clin Invest 2012; 42 (1): 34–41

Background  The use of methods based on reactive hyperaemia of small distal arteries to assess endothelial function (EF) is increasing; however, the mechanisms regulating vascular function in large and small arteries are probably different. We studied the correlations between the hyperaemia reactivity of small peripheral arteries determined by peripheral artery tonometry (PAT) and the levels of serum biomarkers of EF, inflammation and oxidation in patients with cardiovascular (CV) risk factors.

Methods  Four hundred and seven patients with intermediate CV risk were recruited into a cross‐sectional study to examine whether soluble endothelial, inflammatory and lipid oxidative biomarkers correlate with small artery reactive hyperaemia index (saRHI) values, which were measured by PAT.

Results  A significant correlation was found between saRHI values and the concentrations of soluble E‐selectin (sE‐selectin) and soluble vascular cell adhesion molecule 1 (sVCAM‐1). These correlations were stronger when only non‐metabolic syndrome patients (46%) were analysed (r = −0·310, P < 0·0001; r = −0·264, P < 0·0001, respectively). In this subgroup, the oxidised low‐density lipoprotein/LDL (oxLDL/LDL) was also correlated with saRHI (r = −0·193, P = 0·009). A stepwise regression study showed that sE‐selectin was the only biomarker significantly correlated with saRHI values (P < 0·0001). In multivariate linear regression analysis, this relationship was still strong when the main confounding covariates were taken into consideration.

Conclusions  Elevated levels of sE‐selectin and, to a smaller degree, sVCAM‐1 and oxLDL/LDL are associated with lower postischemic reactivity in the small distal arteries. sE‐selectin is the main determinant biomarker of saRHI as assessed by regression analysis. The presence of multiple risk factors weakens this association.
Comparison of different bile acid–phospholipid conjugates in acute hepatitis
Authors: Pathil Anita , Warth Arne , Chamulitrat Walee , Stremmel Wolfgang
Published: June 2011

Eur J Clin Invest 2011

Introduction  The bile acid–phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA‐LPE) is a promising novel compound with profound hepatoprotective functions in vitro and in vivo. Because of high costs of LPE synthesis from hydrolysis of phosphatidylethanolamide (PE), costs for UDCA‐LPE synthesis for in vivo and human use can become quite high. In this study, we evaluated whether ursodeoxycholyl phosphatidylethanolamide (UDCA‐PE), which is more cost‐effective, could replace UDCA‐LPE in terms of protection from hepatocellular injury.

Materials and methods  Anti‐apoptotic and anti‐inflammatory properties of UDCA‐PE and UDCA‐LPE were compared in TNFα/cyclohexamide (CHX)‐treated HepG2 cells as well as in a mouse model of d‐galactosamine/lipopolysaccharide (Gal/LPS)‐induced acute liver injury.

Results  Ursodeoxycholyl lysophosphatidylethanolamide inhibited TNFα/CHX‐induced apoptosis in HepG2 cells in a dose‐dependent manner and markedly ameliorated Gal/LPS‐mediated fulminant hepatitis in mice. In contrast, UDCA‐PE showed weaker hepatoprotective functions at low concentrations, and protection was lost at higher dosage. Analysis of hepatic gene expression showed that both conjugates significantly reduced Gal/LPS‐mediated expression of chemoattractants, such as monocyte chemotactic protein 1 (MCP1) and RANTES. These inhibitory effects by UDCA‐PE were transient while those by UDCA‐LPE were sustained in attenuating expression of inflammatory MCP1 and RANTES expression.

Conclusions  Our data underline the superiority of UDCA‐LPE compared to UDCA‐PE in ameliorating acute liver inflammation. This indicates the significance of the lyso‐functional group of bile acid conjugate for optimal hepatoprotection and reduction in inflammation in vivo.
Active tissue factor and activated factor XI in patients with acute ischemic cerebrovascular events
Authors: Undas Anetta , Slowik Agnieszka , Gissel Matthew , Mann Kenneth G. , Butenas Saulius
Published: June 2011

Eur J Clin Invest 2011

Background  Elevated factor (F)XI and tissue factor (TF) have been reported to occur in patients with acute ischemic stroke (AIS). We sought to investigate whether circulating activated FXI (FXIa) and TF on admission can predict clinical outcomes in patients with acute cerebrovascular events.

Materials and methods  In the observational study, we evaluated 205 consecutive patients aged 70 years or less within the first 72 h of acute event, including 140 with AIS and 65 with transient ischemic attack (TIA). Plasma TF and FXIa activity were determined on admission in clotting assays by measuring the response to inhibitory monoclonal antibodies.

Results  Active TF and FXIa activity were detected in 58 (28·9%) and 132 (64·4%) patients on admission, respectively. Active TF was detected in 45 of the 136 AIS patients with available TF levels (33·1%) and 13 of the 65 patients with acute TIA (20%; P = 0·05). Corresponding values for FXIa were 99 of the 140 (70·7%) and 33 of the 65 (50·8%; P = 0·006), respectively. Patients with detectable TF were more frequently women and hypertensive, while subjects with detectable FXIa had more often diabetes and higher levels of fibrinogen, C‐reactive protein and interleukin‐6 (all P < 0·05). Patients with detectable FXIa but not TF had higher National Institutes of Health Stroke Scale score, higher modified Rankin scale score and lower Barthel Index at discharge (all P < 0·05).

Conclusions  Circulating active TF and FXIa occur frequently in acute cerebrovascular ischemic events. Active FXIa in plasma might be useful as a novel risk marker of worse functional outcomes in patients with acute cerebrovascular events.
Group integrative reminiscence therapy on self‐esteem, life satisfaction and depressive symptoms in institutionalised older veterans
Authors: Wu Li‐Fen
Published: June 2011

Aims and objectives.  The purpose of this study was to use group integrative reminiscence as a nursing intervention to evaluate the immediate effects on self‐esteem, life satisfaction and depressive symptoms for a special group named ‘institutionalised older veterans’ after a 12‐week intervention.

Background.  The study group comprised institutionalised older veterans with combat experience, including being wounded in war and who were twice forced to relocate. The group participants had lower life satisfaction, and greater use for mental health services and greater non‐specific health complaints were reported from this group. Reminiscence therapy has been considered an effective nursing intervention, but the effects on institutionalised older veterans have not been studied.

Design.  A quasi‐experimental design and purposive sampling were conducted.

Methods.  A total of 74 participants were studied with pre‐ and post‐tests to measure the effect of group integrative reminiscence therapy. The activity was held once weekly for 12 weeks. The Life Satisfaction Index A, self‐esteem scale and Geriatric Depression Scale Short Form were used as research tools, and the t‐test, Fisher’s exact test and generalised estimating equation were used for data analysis.

Results.  All participants were male, with an average age of 81·34 years old, 91·9% unmarried and were in bad health. After 12 weeks of intervention, the reminiscence groups significantly improved their self‐esteem and life satisfaction and decreased depressive symptoms compared with control groups.

Conclusion.  Group integrative reminiscence revealed immediate effects on improving the self‐esteem and life satisfaction of institutionalised older veterans, and depressive symptoms were also decreased. Moreover, a sense of positive self‐value and belonging to the institution was produced.

Relevance to clinical practice.  Group integrative reminiscence is an applicable nursing intervention for vulnerable persons such as institutionalised older veterans. A structured protocol based on the characteristics of the residents and the aim of the intervention can lead nurses to provide appropriate reminiscent activities.