bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Yiddish Book Printed in Amsterdam: Śefer Mismor Lethode
Authors: Neuberg Simon
Published: September 2010

This is a first approach to the text of Mismor-lethode a strophic retelling of parts of the Bible, first printed in Amsterdam 1644 (which has so far only been the object of short bibliographical notices), highlighting some of its specific typographical, literary and linguistic aspects:

• It is a very nice piece of work and inaugurates the renowned tradition of Amsterdam Yiddish typographical works; it is also presented within the output of Amsterdam typesetters whose career is reflected in many later books.

• It is remarkable as a late specimen of biblical strophic poetry that makes no use of midrashic elements (perhaps in keeping with the Sephardic influence prevalent in Amsterdam).

• Linguistically it is an important document—among other idiosyncrasies— for its use of the all-purpose relative pronoun s2o and for the free usage of final unstressed vowels for reasons of euphony, rhythm and rhyme.
Ale Brider: Yiddish Culture in Montreal and New York City
Authors: Margolis Rebecca
Published: September 2010

As a minor centre in transnational pre-Holocaust Yiddish culture, Montreal aligned itself with major centres, in particular the nearby metropolis of New York City. This study examines the relationship between Yiddish Montreal and Yiddish New York City from the very beginnings of eastern European Jewish immigration in the 1880s through the Second World War, with a particular focus on publishing and literary life. It compares the two cities and presents theatre as an area of Montreal’s ongoing dependence on New York City. It discusses the interconnected spheres of publishing and literary life as presenting a more complex and evolving relationship between the minor and major city. Here Montreal’s literary culture evolved from a dependent of New York City towards a position of maturity and active exchange. Montreal’s emergence as a primary centre of Yiddish culture after the Holocaust forms part of a process of maturation vis-à-vis the wider Yiddish world, notably New York City. The study also posits that during this ongoing evolution of the Montreal-New York City relationship, the bonds between the cities remained much stronger than the ties between Yiddish and non-Yiddish Canadian culture.
Correlations Among Variables in Message and Messenger Credibility Scales
Authors: Roberts Chris
Published: September 2010

Although credibility is a complicated construct involving interrelationships among messenger, message, communication channels, and recipients, the most widely used credibility indexes seek to measure only one of those attributes at a time. This study used two widely used credibility scales to simultaneously measure message and messenger credibility. An analysis showed high correlations between the two scales and among their individual variables but still distinguished differences between messenger and message.
Still Cruising and Believing? An Analysis of Online Credibility Across Three Presidential Campaigns
Authors: Johnson Thomas J. , Kaye Barbara K.
Published: September 2010

This study relies on online surveys of politically interested web users during the 1996, 2000, and 2004 presidential elections to examine the degree to which people judge online information as credible and to compare how credibility has shifted in the past decade. Whereas credibility scores jumped in 2000, they declined in 2004. Online issue sources were judged the most credible and online broadcast TV news sources the least credible. Whereas respondents perceived few differences between online and traditionally delivered sources in the 2000 campaign, greater differences emerged in the 2004 campaign.
Advice-implicative Interrogatives
Authors: Butler Carly W. , Potter Jonathan , Danby Susan , Emmison Michael , Hepburn Alexa
Published: September 2010

Interactional research on advice giving has described advice as normative and asymmetric. In this paper we examine how these dimensions of advice are softened by counselors on a helpline for children and young people through the use of questions. Through what we term “advice-implicative interrogatives,” counselors ask clients about the relevance or applicability of a possible future course of action. The allusion to this possible action by the counselor identifies it as normatively relevant, and displays the counselor’s epistemic authority in relation to dealing with a client’s problems. However, the interrogative format mitigates the normative and asymmetric dimensions typical of advice sequences by orienting to the client’s epistemic authority in relation to their own lives, and delivering advice in a way that is contingent upon the client’s accounts of their experiences, capacities, and understandings. The demonstration of the use of questions in advice sequences offers an interactional specification of the “client-centered” support that is characteristic of prevailing counseling practice. More specifically, it shows how the values of empowerment and child-centered practice, which underpin services such as Kids Helpline, are embodied in specific interactional devices. Detailed descriptions of this interactional practice offer fresh insights into the use of interrogatives in counseling contexts, and provide practitioners with new ways of thinking about, and discussing, their current practices.
Tipifarnib sensitizes cells to proteasome inhibition by blocking degradation of bortezomib-induced aggresomes
Authors: David Ebenezer , Kaufman Jonathan L. , Flowers Christopher R. , Schafer-Hales Katherine , Torre Claire , Chen Jing , Marcus Adam I. , Sun Shi-Yong , Boise Lawrence H. , Lonial Sagar
Published: September 2010

In this report, we investigated the mechanism responsible for synergistic induction of myeloma cell apoptosis induced by the combination of tipifarnib and bortezomib. Immunofluorescence studies revealed that bortezomib alone resulted in an accumulation of puncta of ubiquitinated proteins that was further enhanced by the addition of tipifarnib. These data suggest inhibition of the degradation of bortezomib-induced aggresomes; and consistent with this possibility, we also observed an increase in p62SQSTM1 in cells treated with the combination. However, autophagy in these cells appears to be normal as LC3BII is present, and autophagic flux appears to be unaffected as demonstrated by the addition of bafilomycin A1. Together, these data demonstrate that tipifarnib synergizes with bortezomib by inducing protein accumulation as a result of the uncoupling of the aggresome and autophagy pathways.
HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway
Authors: Jiang Xiaoyu , Lu Xiaoqing , McNamara George , Liu Xiaofei , Cubedo Elena , Sarosiek Kristopher A. , Sánchez-García Isidro , Helfman David M. , Lossos Izidore S.
Published: September 2010

HGAL is a germinal center (GC)–specific gene that negatively regulates lymphocyte motility and whose expression predicts improved survival of patients with diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). We demonstrate that HGAL serves as a regulator of the RhoA signaling pathway. HGAL enhances activation of RhoA and its down-stream effectors by a novel mechanism – direct binding to the catalytic DH-domain of the RhoA-specific guanine nucleotide exchange factors (RhoGEFs) PDZ-RhoGEF and LARG that stimulate the GDP-GTP exchange rate of RhoA. We delineate the structural domain of HGAL that mediates its interaction with the PDZ-RhoGEF protein. These observations reveal a novel molecular mechanism underlying the inhibitory effects of GC-specific HGAL protein on the motility of GC-derived lymphoma cells. This mechanism may underlie the limited dissemination and better outcome of patients with HGAL-expressing DLBCL and cHL.
Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation
Authors: Millot Sarah , Andrieu Valérie , Letteron Philippe , Lyoumi Saïd , Hurtado-Nedelec Margarita , Karim Zoubida , Thibaudeau Olivier , Bennada Samira , Charrier Jean-Luc , Lasocki Sigismond , Beaumont Carole
Published: September 2010

Mouse bone marrow erythropoiesis is homeostatic, whereas after acute anemia, bone morphogenetic protein 4 (BMP4)–dependent stress erythropoiesis develops in the spleen. The aim of this work was to compare spleen stress erythropoiesis and bone marrow erythropoiesis in a mouse model of zymosan-induced generalized inflammation, which induces long-lasting anemia and to evaluate the ability of erythropoietin (Epo) injections to correct anemia in this setting. The effects of zymosan and/or Epo injections on erythroid precursor maturation and apoptosis, serum interferon-γ levels, hematologic parameters, and spleen BMP4 expression were analyzed, as well as the effect of zymosan on red blood cell half-life. We found that bone marrow erythropoiesis is suppressed by inflammation and does not respond to Epo administration, despite repression of erythroblast apoptosis. On the contrary, a robust erythropoietic response takes place in the spleen after Epo injections in both control and zymosan-induced generalized inflammation mice. This specific response implies Epo-mediated induction of BMP4 expression by F4/80+ spleen macrophages, proliferation of stress burst-forming units-erythroid, and increased number of spleen erythroblasts. It allows only partial recovery of anemia, probably because of peripheral destruction of mature red cells. It is not clear whether similar BMP4-dependent stress erythropoiesis can occur in human bone marrow after Epo injections.
Mapping Quantitative Trait Loci (QTL) in sheep. III. QTL for carcass composition traits derived from CT scans and aligned with a meta-assembly for sheep and cattle carcass QTL
Authors: Cavanagh Colin R , Jonas Elisabeth , Hobbs Matthew , Thomson Peter C , Tammen Imke , Raadsma Herman W
Published: September 2010

An (Awassi × Merino) × Merino single-sire backcross family with 165 male offspring was used to map quantitative trait loci (QTL) for body composition traits on a framework map of 189 microsatellite loci across all autosomes. Two cohorts were created from the experimental progeny to represent alternative maturity classes for body composition assessment. Animals were raised under paddock conditions prior to entering the feedlot for a 90-day fattening phase. Body composition traits were derived in vivo at the end of the experiment prior to slaughter at 2 (cohort 1) and 3.5 (cohort 2) years of age, using computed tomography. Image analysis was used to gain accurate predictions for 13 traits describing major fat depots, lean muscle, bone, body proportions and body weight which were used for single- and two-QTL mapping analysis. Using a maximum-likelihood approach, three highly significant (LOD ≥ 3), 15 significant (LOD ≥ 2), and 11 suggestive QTL (1.7 ≤ LOD < 2) were detected on eleven chromosomes. Regression analysis confirmed 28 of these QTL and an additional 17 suggestive (P < 0.1) and two significant (P < 0.05) QTL were identified using this method. QTL with pleiotropic effects for two or more tissues were identified on chromosomes 1, 6, 10, 14, 16 and 23. No tissue-specific QTL were identified.

A meta-assembly of ovine QTL for carcass traits from this study and public domain sources was performed and compared with a corresponding bovine meta-assembly. The assembly demonstrated QTL with effects on carcass composition in homologous regions on OAR1, 2, 6 and 21.
Pan-genome sequence analysis using Panseq: an online tool for the rapid analysis of core and accessory genomic regions
Authors: Laing Chad , Buchanan Cody , Taboada Eduardo N , Zhang Yongxiang , Kropinski Andrew , Villegas Andre , Thomas James E , Gannon Victor PJ
Published: September 2010

Background

The pan-genome of a bacterial species consists of a core and an accessory gene pool. The accessory genome is thought to be an important source of genetic variability in bacterial populations and is gained through lateral gene transfer, allowing subpopulations of bacteria to better adapt to specific niches. Low-cost and high-throughput sequencing platforms have created an exponential increase in genome sequence data and an opportunity to study the pan-genomes of many bacterial species. In this study, we describe a new online pan-genome sequence analysis program, Panseq.

Results

Panseq was used to identifyEscherichia coliO157:H7 andE. coliK-12 genomic islands. Within a population of 60E. coliO157:H7 strains, the existence of 65 accessory genomic regions identified by Panseq analysis was confirmed by PCR. The accessory genome and binary presence/absence data, and core genome and single nucleotide polymorphisms (SNPs) of sixL. monocytogenesstrains were extracted with Panseq and hierarchically clustered and visualized. The nucleotide core and binary accessory data were also used to construct maximum parsimony (MP) trees, which were compared to the MP tree generated by multi-locus sequence typing (MLST). The topology of the accessory and core trees was identical but differed from the tree produced using seven MLST loci. The Loci Selector module found the most variable and discriminatory combinations of four loci within a 100 loci set among 10 strains in 1 s, compared to the 449 s required to exhaustively search for all possible combinations; it also found the most discriminatory 20 loci from a 96 lociE. coliO157:H7 SNP dataset.

Conclusion

Panseq determines the core and accessory regions among a collection of genomic sequences based on user-defined parameters. It readily extracts regions unique to a genome or group of genomes, identifies SNPs within shared core genomic regions, constructs files for use in phylogeny programs based on both the presence/absence of accessory regions and SNPs within core regions and produces a graphical overview of the output. Panseq also includes a loci selector that calculates the most variable and discriminatory loci among sets of accessory loci or core gene SNPs.

Availability

Panseq is freely available online athttp://76.70.11.198/panseq. Panseq is written in Perl.
Context dependent substitution biases vary within the human genome
Authors: Nevarez P Andrew , DeBoever Christopher M , Freeland Benjamin J , Quitt Marissa A , Bush Eliot C
Published: September 2010

Background

Models of sequence evolution typically assume that different nucleotide positions evolve independently. This assumption is widely appreciated to be an over-simplification. The best known violations involve biases due to adjacent nucleotides. There have also been suggestions that biases exist at larger scales, however this possibility has not been systematically explored.

Results

To address this we have developed a method which identifies over- and under-represented substitution patterns and assesses their overall impact on the evolution of genome composition. Our method is designed to account for biases at smaller pattern sizes, removing their effects. We used this method to investigate context bias in the human lineage after the divergence from chimpanzee. We examined bias effects in substitution patterns between 2 and 5 bp long and found significant effects at all sizes. This included some individual three and four base pair patterns with relatively large biases. We also found that bias effects vary across the genome, differing between transposons and non-transposons, between different classes of transposons, and also near and far from genes.

Conclusions

We found that nucleotides beyond the immediately adjacent one are responsible for substantial context effects, and that these biases vary across the genome.
Intracellular localization and interaction of mRNA binding proteins as detected by FRET
Authors: David Gerecht Pamela S , Taylor Molly A , Port J David
Published: September 2010

Background

A number of RNA binding proteins (BPs) bind to A+U rich elements (AREs), commonly present within 3'UTRs of highly regulated RNAs. Individual RNA-BPs proteins can modulate RNA stability, RNA localization, and/or translational efficiency. Although biochemical studies have demonstrated selectivity of ARE-BPs for individual RNAs, less certain is thein vivocomposition of RNA-BP multiprotein complexes and how their composition is affected by signaling events and intracellular localization. Using FRET, we previously demonstrated that two ARE-BPs, HuR and AUF1, form stable homomeric and heteromeric associations in the nucleus and cytoplasm. In the current study, we use immuno-FRET of endogenous proteins to examine the intracellular localization and interactions of HuR and AUF1 as well as KSRP, TIA-1, and Hedls. These results were compared to those obtained with their exogenously expressed, fluorescently labeled counterparts.

Results

All ARE-BPs examined were found to colocalize and to form stable associations with selected other RNA-BPs in one or more cellular locations variably including the nucleus, cytoplasm (in general), or in stress granules or P bodies. Interestingly, FRET based interaction of the translational suppressor, TIA-1, and the decapping protein, Hedls, was found to occur at the interface of stress granules and P bodies, dynamic sites of intracellular RNA storage and/or turnover. To explore the physical interactions of RNA-BPs with ARE containing RNAs,in vitrotranscribed Cy3-labeled RNA was transfected into cells. Interestingly, Cy3-RNA was found to coalesce in P body like punctate structures and, by FRET, was found to interact with the RNA decapping proteins, Hedls and Dcp1.

Conclusions

Biochemical methodologies, such as co-immunoprecipitation, and cell biological approaches such as standard confocal microscopy are useful in demonstrating the possibility of proteins and/or proteins and RNAs interacting. However, as demonstrated herein, colocalization of proteins and proteins and RNA is not always indicative of interaction. To this point, using FRET and immuno-FRET, we have demonstrated that RNA-BPs can visually colocalize without producing a FRET signal. In contrast, proteins that appear to be delimited to one or another intracellular compartment can be shown to interact when those compartments are juxtaposed.
Extracellular Paracoccidioides brasiliensis phospholipase B involvement in alveolar macrophage interaction
Authors: Soares Deyze Alencar , de Andrade Rosângela Vieira , Silva Simoneide Sousa , Bocca Anamélia Lorenzetti , Soares Felipe Sueli Maria , Petrofeza Silvana
Published: September 2010

Background

Phospholipase B (PLB) has been reported to be one of the virulence factors for human pathogenic fungi and has also been described as necessary for the early events in infection. Based on these data, we investigated the role of PLB in virulence and modulation of the alveolar pulmonary immune response during infection using an in-vitro model of host-pathogen interaction, i.e. Paracoccidioides brasiliensis yeast cells infecting alveolar macrophage (MH-S) cells.

Results

The effect of PLB was analyzed using the specific inhibitor alexidine dihydrochloride (0.25 μM), and pulmonary surfactant (100 μg mL-1), during 6 hours of co-cultivation of P. brasiliensis and MH-S cells. Alexidine dihydrochloride inhibited PLB activity by 66% and significantly decreased the adhesion and internalization of yeast cells by MH-S cells. Genes involved in phagocytosis (trl2, cd14) and the inflammatory response (nfkb, tnf-α, il-1β) were down-regulated in the presence of this PLB inhibitor. In contrast, PLB activity and internalization of yeast cells significantly increased in the presence of pulmonary surfactant; under this condition, genes such as clec 2 and the pro-inflammatory inhibitor (nkrf) were up-regulated. Also, the pulmonary surfactant did not alter cytokine production, while alexidine dihydrochloride decreased the levels of interleukin-10 (IL-10) and increased the levels of IL-12 and tumor necrosis factor-α (TNF-α). In addition, gene expression analysis of plb1, sod3 and icl1 suggests that P. brasiliensis gene re-programming is effective in facilitating adaptation to this inhospitable environment, which mimics the lung-environment interaction.

Conclusion

P. brasiliensis PLB activity is involved in the process of adhesion and internalization of yeast cells at the MH-S cell surface and may enhance virulence and subsequent down-regulation of macrophage activation.
Molecular cloning and tissue expression of the fatty acid-binding protein (Es-FABP) gene in female Chinese mitten crab (Eriocheir sinensis)
Authors: Gong Ya-Nan , Li Wei-Wei , Sun Jiang-Ling , Ren Fei , He Lin , Jiang Hui , Wang Qun
Published: September 2010

Background

Fatty acid-binding proteins (FABPs), small cytosolic proteins that function in the uptake and utilization of fatty acids, have been extensively studied in higher vertebrates while invertebrates have received little attention despite similar nutritional requirements during periods of reproductive activity.

Results

Therefore, a cDNA encoding Eriocheir sinensis FABP (Es-FABP) was cloned based upon EST analysis of a hepatopancreas cDNA library. The full length cDNA was 750 bp and encoded a 131 aa polypeptide that was highly homologous to related genes reported in shrimp. The 9108 bp Es-FABP gene contained four exons that were interrupted by three introns, a genomic organization common among FABP multigene family members in vertebrates. Gene expression analysis, as determined by RT-PCR, revealed the presence of Es-FABP transcripts in hepatopancreas, hemocytes, ovary, gills, muscle, thoracic ganglia, heart, and intestine, but not stomach or eyestalk. Real-time quantitative RT-PCR analysis revealed that Es-FABP expression in ovary, hemocytes, and hepatopancreas was dependent on the status of ovarian development, with peak expression observed in January.

Conclusions

Evidence provided in the present report supports a role of Es-FABP in lipid transport during the period of rapid ovarian growth in E. sinensis, and indirectly confirms the participation of the hepatopancreas, ovary, and hemocytes in lipid nutrient absorption and utilization processes.
DNA barcoding of the Lemnaceae, a family of aquatic monocots
Authors: Wang Wenqin , Wu Yongrui , Yan Yiheng , Ermakova Marina , Kerstetter Randall , Messing Joachim
Published: September 2010

Background

Members of the aquatic monocot family Lemnaceae (commonly called duckweeds) represent the smallest and fastest growing flowering plants. Their highly reduced morphology and infrequent flowering result in a dearth of characters for distinguishing between the nearly 38 species that exhibit these tiny, closely-related and often morphologically similar features within the same family of plants.

Results

We developed a simple and rapid DNA-based molecular identification system for the Lemnaceae based on sequence polymorphisms. We compared the barcoding potential of the seven plastid-markers proposed by the CBOL (Consortium for the Barcode of Life) plant-working group to discriminate species within the land plants in 97 accessions representing 31 species from the family of Lemnaceae. A Lemnaceae-specific set of PCR and sequencing primers were designed for four plastid coding genes (rpoB, rpoC1, rbcL and matK) and three noncoding spacers (atpF-atpH, psbK-psbI and trnH-psbA) based on the Lemna minor chloroplast genome sequence. We assessed the ease of amplification and sequencing for these markers, examined the extent of the barcoding gap between intra- and inter-specific variation by pairwise distances, evaluated successful identifications based on direct sequence comparison of the "best close match" and the construction of a phylogenetic tree.

Conclusions

Based on its reliable amplification, straightforward sequence alignment, and rates of DNA variation between species and within species, we propose that the atpF-atpH noncoding spacer could serve as a universal DNA barcoding marker for species-level identification of duckweeds.
Epidemiological study of phylogenetic transmission clusters in a local HIV-1 epidemic reveals distinct differences between subtype B and non-B infections
Authors: Chalmet Kristen , Staelens Delfien , Blot Stijn , Dinakis Sylvie , Pelgrom Jolanda , Plum Jean , Vogelaers Dirk , Vandekerckhove Linos , Verhofstede Chris
Published: September 2010

Background

The number of HIV-1 infected individuals in the Western world continues to rise. More in-depth understanding of regional HIV-1 epidemics is necessary for the optimal design and adequate use of future prevention strategies. The use of a combination of phylogenetic analysis of HIV sequences, with data on patients' demographics, infection route, clinical information and laboratory results, will allow a better characterization of individuals responsible for local transmission.

Methods

Baseline HIV-1polsequences, obtained through routine drug-resistance testing, from 506 patients, newly diagnosed between 2001 and 2009, were used to construct phylogenetic trees and identify transmission-clusters. Patients' demographics, laboratory and clinical data, were retrieved anonymously. Statistical analysis was performed to identify subtype-specific and transmission-cluster-specific characteristics.

Results

Multivariate analysis showed significant differences between the 59.7% of individuals with subtype B infection and the 40.3% non-B infected individuals, with regard to route of transmission, origin, infection withChlamydia(p = 0.01) and infection with Hepatitis C virus (p = 0.017). More and larger transmission-clusters were identified among the subtype B infections (p < 0.001). Overall, in multivariate analysis, clustering was significantly associated with Caucasian origin, infection through homosexual contact and younger age (all p < 0.001). Bivariate analysis additionally showed a correlation between clustering and syphilis (p < 0.001), higher CD4 counts (p = 0.002),Chlamydiainfection (p = 0.013) and primary HIV (p = 0.017).

Conclusions

Combination of phylogenetics with demographic information, laboratory and clinical data, revealed that HIV-1 subtype B infected Caucasian men-who-have-sex-with-men with high prevalence of sexually transmitted diseases, account for the majority of local HIV-transmissions. This finding elucidates observed epidemiological trends through molecular analysis, and justifies sustained focus in prevention on this high risk group.
Selenium hyperaccumulation offers protection from cell disruptor herbivores
Authors: Quinn Colin F , Freeman John L , Reynolds Ray JB , Cappa Jennifer J , Fakra Sirine C , Marcus Matthew A , Lindblom Stormy D , Quinn Erin K , Bennett Lindsay E , Pilon-Smits Elizabeth AH
Published: September 2010

Background

Hyperaccumulation, the rare capacity of certain plant species to accumulate toxic trace elements to levels several orders of magnitude higher than other species growing on the same site, is thought to be an elemental defense mechanism against herbivores and pathogens. Previous research has shown that selenium (Se) hyperaccumulation protects plants from a variety of herbivores and pathogens. Selenium hyperaccumulating plants sequester Se in discrete locations in the leaf periphery, making them potentially more susceptible to some herbivore feeding modes than others. In this study we investigate the protective function of Se in the Se hyperaccumulators Stanleya pinnata and Astragalus bisulcatus against two cell disrupting herbivores, the western flower thrips (Frankliniella occidentalis) and the two-spotted spider mite (Tetranychus urticae).

Results

Astragalus bisulcatus and S. pinnata with high Se concentrations (greater than 650 mg Se kg-1) were less subject to thrips herbivory than plants with low Se levels (less than 150 mg Se kg-1). Furthermore, in plants containing elevated Se levels, leaves with higher concentrations of Se suffered less herbivory than leaves with less Se. Spider mites also preferred to feed on low-Se A. bisulcatus and S. pinnata plants rather than high-Se plants. Spider mite populations on A. bisulcatus decreased after plants were given a higher concentration of Se. Interestingly, spider mites could colonize A. bisulcatus plants containing up to 200 mg Se kg-1 dry weight, concentrations which are toxic to many other herbivores. Selenium distribution and speciation studies using micro-focused X-ray fluorescence (μXRF) mapping and Se K-edge X-ray absorption spectroscopy revealed that the spider mites accumulated primarily methylselenocysteine, the relatively non-toxic form of Se that is also the predominant form of Se in hyperaccumulators.

Conclusions

This is the first reported study investigating the protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.
Attitudes towards transfers of human tissue samples across borders: An international survey of researchers and policy makers in five countries
Authors: Zhang Xinqing , Matsui Kenji , Krohmal Benjamin , Zeid Alaa Abou , Muthuswamy Vasantha , Koo Young Mo , Kita Yoshikuni , Lie Reidar K
Published: September 2010

Background

Sharing of tissue samples for research and disease surveillance purposes has become increasingly important. While it is clear that this is an area of intense, international controversy, there is an absence of data about what researchers themselves and those involved in the transfer of samples think about these issues, particularly in developing countries.

Methods

A survey was carried out in a number of Asian countries and in Egypt to explore what researchers and others involved in research, storage and transfer of human tissue samples thought about some of the issues related to sharing of such samples.

Results

The results demonstrated broad agreement with the positions taken by developing countries in the current debate, favoring quite severe restrictions on the use of samples by developed countries.

Conclusions

It is recommended that an international agreement is developed on what conditions should be attached to any sharing of human tissue samples across borders.
A regret theory approach to decision curve analysis: A novel method for eliciting decision makers' preferences and decision-making
Authors: Tsalatsanis Athanasios , Hozo Iztok , Vickers Andrew , Djulbegovic Benjamin
Published: September 2010

Background

Decision curve analysis (DCA) has been proposed as an alternative method for evaluation of diagnostic tests, prediction models, and molecular markers. However, DCA is based on expected utility theory, which has been routinely violated by decision makers. Decision-making is governed by intuition (system 1), and analytical, deliberative process (system 2), thus, rational decision-making should reflect both formal principles of rationality and intuition about good decisions. We use the cognitive emotion of regret to serve as a link between systems 1 and 2 and to reformulate DCA.

Methods

First, we analysed a classic decision tree describing three decision alternatives: treat, do not treat, and treat or no treat based on a predictive model. We then computed the expected regret for each of these alternatives as the difference between the utility of the action taken and the utility of the action that, in retrospect, should have been taken. For any pair of strategies, we measure the difference in net expected regret. Finally, we employ the concept of acceptable regret to identify the circumstances under which a potentially wrong strategy is tolerable to a decision-maker.

Results

We developed a novel dual visual analog scale to describe the relationship between regret associated with "omissions" (e.g. failure to treat) vs. "commissions" (e.g. treating unnecessary) and decision maker's preferences as expressed in terms of threshold probability. We then proved that the Net Expected Regret Difference, first presented in this paper, is equivalent to net benefits as described in the original DCA. Based on the concept of acceptable regret we identified the circumstances under which a decision maker tolerates a potentially wrong decision and expressed it in terms of probability of disease.

Conclusions

We present a novel method for eliciting decision maker's preferences and an alternative derivation of DCA based on regret theory. Our approach may be intuitively more appealing to a decision-maker, particularly in those clinical situations when the best management option is the one associated with the least amount of regret (e.g. diagnosis and treatment of advanced cancer, etc).
Production of functionalized polyhydroxyalkanoates by genetically modified Methylobacterium extorquens strains
Authors: Höfer Philipp , Choi Young J , Osborne Michael J , Miguez Carlos B , Vermette Patrick , Groleau Denis
Published: September 2010

Background

Methylotrophic (methanol-utilizing) bacteria offer great potential as cell factories in the production of numerous products from biomass-derived methanol. Bio-methanol is essentially a non-food substrate, an advantage over sugar-utilizing cell factories. Low-value products as well as fine chemicals and advanced materials are envisageable from methanol. For example, several methylotrophic bacteria, including Methylobacterium extorquens, can produce large quantities of the biodegradable polyester polyhydroxybutyric acid (PHB), the best known polyhydroxyalkanoate (PHA). With the purpose of producing second-generation PHAs with increased value, we have explored the feasibility of using M. extorquens for producing functionalized PHAs containing C-C double bonds, thus, making them amenable to future chemical/biochemical modifications for high value applications.

Results

Our proprietary M. extorquens ATCC 55366 was found unable to yield functionalized PHAs when fed methanol and selected unsaturated carboxylic acids as secondary substrates. However, cloning of either the phaC1 or the phaC2 gene from P. fluorescens GK13, using an inducible and regulated expression system based on cumate as inducer (the cumate switch), yielded recombinant M. extorquens strains capable of incorporating modest quantities of C-C double bonds into PHA, starting from either C6= and/or C8=. The two recombinant strains gave poor results with C11=. The strain containing the phaC2 gene was better at using C8= and at incorporating C-C double bonds into PHA. Solvent fractioning indicated that the produced polymers were PHA blends that consequently originated from independent actions of the native and the recombinant PHA synthases.

Conclusions

This work constitutes an example of metabolic engineering applied to the construction of a methanol-utilizing bacterium capable of producing functionalized PHAs containing C-C double bonds. In this regard, the PhaC2 synthase appeared superior to the PhaC1 synthase at utilizing C8= as source of C-C double bonds and at incorporating C-C double bonds into PHA from either C6= or C8=. The M. ex-phaC2 strain is, therefore, a promising biocatalyst for generating advanced (functionalized) PHAs for future high value applications in various fields.
Data-guide for brain deformation in surgery: comparison of linear and nonlinear models
Authors: Hamidian Hajar , Soltanian-Zadeh Hamid , Faraji-Dana Reza , Gity Masoumeh
Published: September 2010

Background

Pre-operative imaging devices generate high-resolution images but intra-operative imaging devices generate low-resolution images. To use high-resolution pre-operative images during surgery, they must be deformed to reflect intra-operative geometry of brain.

Methods

We employ biomechanical models, guided by low resolution intra-operative images, to determine location of normal and abnormal regions of brain after craniotomy. We also employ finite element methods to discretize and solve the related differential equations. In the process, pre- and intra-operative images are utilized and corresponding points are determined and used to optimize parameters of the models. This paper develops a nonlinear model and compares it with linear models while our previous work developed and compared linear models (mechanical and elastic).

Results

Nonlinear model is evaluated and compared with linear models using simulated and real data. Partial validation using intra-operative images indicates that the proposed models reduce the localization error caused by brain deformation after craniotomy.

Conclusions

The proposed nonlinear model generates more accurate results than the linear models. When guided by limited intra-operative surface data, it predicts deformation of entire brain. Its execution time is however considerably more than those of linear models.
Anti-angiogenic effects of differentiation-inducing factor-1 involving VEGFR-2 expression inhibition independent of the Wnt/β-catenin signaling pathway
Authors: Yoshihara Tatsuya , Takahashi-Yanaga Fumi , Shiraishi Fumie , Morimoto Sachio , Watanabe Yutaka , Hirata Masato , Hoka Sumio , Sasaguri Toshiyuki
Published: September 2010

Background

Differentiation-inducing factor-1 (DIF-1) is a putative morphogen that induces cell differentiation in Dictyostelium discoideum. DIF-1 inhibits proliferation of various mammalian tumor cells by suppressing the canonical Wnt/β-catenin signaling pathway. To assess the potential of a novel cancer chemotherapy based on the pharmacological effect of DIF-1, we investigated whether DIF-1 exhibits anti-angiogenic effects in vitro and in vivo.

Results

DIF-1 not only inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) by restricting cell cycle in the G0/G1 phase and degrading cyclin D1, but also inhibited the ability of HUVECs to form capillaries and migrate. Moreover, DIF-1 suppressed VEGF- and cancer cell-induced neovascularization in Matrigel plugs injected subcutaneously to murine flank. Subsequently, we attempted to identify the mechanism behind the anti-angiogenic effects of DIF-1. We showed that DIF-1 strongly decreased vascular endothelial growth factor receptor-2 (VEGFR-2) expression in HUVECs by inhibiting the promoter activity of human VEGFR-2 gene, though it was not caused by inhibition of the Wnt/β-catenin signaling pathway.

Conclusion

These results suggested that DIF-1 inhibits angiogenesis both in vitro and in vivo, and reduction of VEGFR-2 expression is involved in the mechanism. A novel anti-cancer drug that inhibits neovascularization and tumor growth may be developed by successful elucidation of the target molecules for DIF-1 in the future.
Predictive performances of lipid accumulation product vs. adiposity measures for cardiovascular diseases and all-cause mortality, 8.6-year follow-up: Tehran lipid and glucose study
Authors: Bozorgmanesh Mohammadreza , Hadaegh Farzad , Azizi Fereidoun
Published: September 2010

Background

The body mass index (BMI) is the most commonly used marker for evaluating obesity related risks, however, central obesity measures have been proposed to be more informative. Lipid accumulation product (LAP) is an alternative continuous index of lipid accumulation. We sought in this study to assess if LAP can outperform BMI, waist-to-height-ratio (WHtR), or waist-to-hip-ratio (WHpR) in predicting incident cardiovascular disease (CVD) or all-cause mortality.

Results

Among participants of Tehran Lipid and Glucose Study, 6,751 participants (2,964 men), aged ≥ 30 years, were followed for a median of 8.6 years. We observed 274 deaths (men: 168) and 447 CVD events (men: 257). Levels of common CVD risk factors significantly increased across LAP quartiles. Mortality rates did not differ by LAP quartiles. Among participants free of CVD at baseline [6331 (2,741 men)], CVD incident rates per 1000 person increased in a stepwise fashion with increasing LAP quartile values in both men (from 6.9 to 17.0) and women (from 1.3 to 13.0), (Ps < 0.001).

Among women, a 1-SD increment in log-LAP conferred a 41% increased risk for CVD (HR 1.41, 95% CIs 1.02-1.96). Among men, however, LAP was not observed to be independently associated with increased risk of CVD; except in a sub-group of men assigned to the lifestyle modification interventions, where, LAP predicted CVD risk.

After adjustment with CVD risk factors LAP turned to be inversely associated with risk of all-cause mortality (HR, men 0.74, 95% CIs 0.61-0.90; women, 0.94 95% CIs 0.74-1.20).

Among women, magnitude of increased risk of CVD due to LAP was not different from those of anthropometric measures. Among men, however, WHpR was observed to be more strongly associated with increased risk of CVD than was LAP.

Among neither men nor women were the predictive performances (discrimination, calibration, goodness-of-fit) of the LAP better than those of different anthropometric measures were.

Conclusions

If LAP is to be used for predicting CVD, it might not be superior to WHtR or WHpR.
Peroxisome proliferator-activated receptors (PPARs)-independent functions of fish oil on glucose and lipid metabolism in diet-induced obese mice
Authors: Wakutsu Masaki , Tsunoda Nobuyo , Shiba Sachiko , Muraki Etsuko , Kasono Keizo
Published: September 2010

Background

Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway.

Methods

Mice were fed a diet containing 30 en% beef tallow (B diet) for twelve weeks to induce obesity. The mice were then divided into two groups which were fed either a B diet or a diet containing 30 en% fish oil (F diet). Each group was further divided into two groups which were administered PPARα and γ antagonists or vehicle once a day for three weeks.

Results

The F diet groups showed lower triglyceride levels in plasma and liver than the B diet groups, but PPARs antagonists did not affect the triglyceride levels in either diet groups. The F diet groups also showed improvement of glucose tolerance compared with the B diet groups. However, PPARs antagonists made glucose tolerance worse in the F diet group but improved it in the B diet group. Therefore, by the administration of antagonists, glucose tolerance was inversely regulated between the B and F diets, and hypolipidemic action in the plasma and liver of the F diet group was not affected.

Conclusion

These results suggest that fish oil decreases lipid levels in plasma and liver via PPARs pathway-independent mechanism, and that glucose tolerance is inversely regulated by PPARs antagonists under diets containing different oils.
Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine
Authors: Liu Lianxing , Wan Yanmin , Wu Lan , Sun Jianping , Li Huiguang , Li Haishan , Ma Liying , Shao Yiming
Published: September 2010

Background

In order to induce a potent and cross-reactive neutralizing antibody (nAb), an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV). The Chinese equine infectious anemia virus (EIAV) attenuated vaccine has controlled the epidemic of this virus after its vaccination in over 70 million equine animals during the last 3 decades in China. Data from our past studies demonstrate that the Env protein of this vaccine plays a pivotal role in protecting horses from both homologous and heterogeneous EIAV challenges. Therefore, the amino acid sequence information from the Chinese EIAV attenuated vaccine, in comparison with the parental wild-type EIAV strains, was applied to modify the corresponding region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations was made towards the amino acids conserved in the two EIAV vaccine strains, distinguishing them from the two wild-type strains. The purpose of the modification was to enhance the immunogenicity of the HIV Env.

Results

The induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the highest titer of 1:270. Further studies showed that a single amino acid change in the C1 region accounts for the substantial enhancement in induction of anti-HIV-1 neutralizing antibodies.

Conclusions

This study shows that an HIV envelope modified by the information of another lentivirus vaccine induces effective broadly neutralizing antibodies. A single amino acid mutation was found to increase the immunogenicity of the HIV Env.
Molecular characterization of hepatitis A virus isolates from environmental and clinical samples in Greece
Authors: Kokkinos Petros , Ziros Panos , Filippidou Sevasti , Mpampounakis Ioannis , Vantarakis Apostolos
Published: September 2010

Background

Hepatitis A virus (HAV) strains detected in environmental and clinical samples were analysed to characterize the genotypes of HAV circulating in Greece. Fifty (50) sewage samples were collected from Patras (South-Western Greece) and Alexandroupolis (North-Eastern Greece) from 2007 until 2009, accordingly. The clinical samples derived from an HAV outbreak involved populations from three neighbouring prefectures of North-Eastern Greece (Xanthi, Rodopi, and Evros). HAV particles were detected by nested RT-PCR, using a previously validated set of primers to amplify a 290-bp fragment encompassing the 5'-NTR. Positive HAV samples were confirmed by sequencing of the PCR product. To determine the relatedness between the different isolated sequences, a phylogenetic tree was constructed.

Results

Results showed a 100% prevalence of genotype I, and particularly subgenotype IA. The analyzed HAV strains were closely related between them with the percentage of nucleotide identity ranging between 96% and 100%.

Conclusions

The study revealed the major prevalence of circulating strains of IA genotype in Greece and underlined the usefulness of molecular methods for the detection and typing of viruses in both environmental and clinical samples. The present study is, to our knowledge, the first in Greece to depict the simultaneous molecular characterization of HAV strains isolated from both clinical and environmental samples.
Echoviruses are a major cause of aseptic meningitis in infants and young children in Kuwait
Authors: Dalwai Ajmal , Ahmad Suhail , Al-Nakib Widad
Published: September 2010

Background

The etiologic agents of aseptic meningitis (AM) often include human enteroviruses. The role of enteroviruses causing AM in young children was investigated during a 3-year period in Kuwait.

Results

Enteroviral RNA was detected in cerebrospinal fluid (CSF) by reverse transcription-PCR and specific genotypes of enteroviruses were identified by direct DNA sequencing of VP4-VP2 region. Enteroviral RNA was detected in 92 of 387 (24%) suspected AM cases and the results were confirmed by hybridization of amplicons with an internal, enterovirus-specific probe. The CSF samples from 75 of 281 (27%) children < 2 years old but only from 3 of 38 (8%) 4-12 year-old children were positive for enteroviral RNA (p= 0.011). Majority of infections in children < 2 years old (49 of 75, 65%) were due to three echoviruses; echovirus type 9 (E9), E11 and E30. Only three other enteroviruses, namely coxsackievirus type B4, coxsackievirus type B5 and enterovirus 71 were detected among AM cases in Kuwait.

Conclusions

Our data show that three types of echoviruses (E9, E11 and E30) are associated with the majority of AM cases in Kuwait. To the best of our knowledge, this is the first report to characterize different enterovirus genotypes associated with AM in the Arabian Gulf region.