bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Dyads Really Groups?
Authors: Moreland Richard L.
Published: February 2010

Social scientists who study groups disagree about whether (and to what extent) dyads ought to be included in their work. In this article, I argue that dyads are not really groups because (a) dyads are more ephemeral than groups, forming and dissolving more quickly; (b) people feel stronger (and often different) emotions in dyads than in groups; (c) dyads are simpler than groups—some group phenomena cannot occur in dyads, and those that do may operate differently there; and (d) research on dyads is carried out almost independently (by different people, applying different theories and methods, and publishing their work in different outlets) from research on groups. I also review some of the conceptual and methodological problems that can arise when dyads are mistakenly viewed as groups.
Best Practice Mistake Management
Authors: Nelson Julie A.
Published: February 2010

Mistake management is rapidly emerging as an important, and often overlooked, component of risk management programs in health care. Nationwide legislative efforts and recent regulatory requirements support the movement away from a “deny and defend” mistake management culture and toward a more patient friendly method of mistake mediation. These “best practice” methods of mistake management have been proven effective in decreasing legal claims and settlement expenses and offer the bonus of increasing patient satisfaction and trust.
Don’t Rush to Flush: Safer Pharmaceutical Practices for Hospice Home Care and Home Health Nurses
Authors: Becker Julie A. , Ortner Pamela M. , Tullai-McGuinness Susan
Published: February 2010

Hospice home care and home health nurses are essential providers in efforts to improve the care and quality of life with families who have someone living with advanced or life-limiting conditions. Because these nursing professionals are part of end-of-life care, their duties include education about and disposal of unused medications. But drug disposal has broader implications, especially for the environment, aquatic life, and ultimately for human health. The purpose of this article is to (a) introduce the topic of drug disposal within an environmental and health context, (b) identify current recommendations for drug disposal, and (c) provide suggestions for hospice home care and home health care nurses for safer drug disposal.
The Perils of Being a Nice Guy: Contextual Variation in Five Young Women’s Constructions of Acceptable Hegemonic and Alternative Masculinities
Authors: Talbot Kirsten , Quayle Michael
Published: February 2010

Masculinity is often studied as produced and enacted by men, unintentionally positioning women as mere consumers of masculinity, rather than active agents in its construction. This study explored five young South African women’s constructions of masculinity in the contexts of work, friendships, family, and romantic relationships and the contextual variation of acceptable masculinity across contexts. While they advocated nonhegemonic ‘‘nice guy’’ masculinities in social and work contexts, they appealed strongly to ‘‘hegemonic’’ or traditional masculine ideals in romantic and family contexts. It seems that these women were particularly willing to accept subjugation to engage in ideals of romantic partnership congruent with emphasized femininity. This study demonstrates that (1) contextual variation is a very important feature in the production of hegemonic masculinity and (2) analyzing masculinity from women’s perspectives may provide valuable insight into the contribution that women make to the construction and maintenance of counterfeminist masculine ideals and identity frameworks.
Young Men’s Vulnerability in Relation to Women’s Resistance to Emphasized Femininity
Authors: Korobov Neill
Published: February 2010

This study uses a critical discursive approach to examine young men’s vulnerabilities in relation to emphasized femininity. Since masculinity is inextricably defined in relation to femininity, men’s achievement of masculinity is intimately dependent on, and vulnerable to, women’s complicity with traditional or emphasized femininity. Analysis centers on men’s negotiations of women’s resistance to one of three forms of emphasized femininity: (1) compliance or receptivity to men’s sexual advances and desires, (2) emotional caretaking, and (3) passivity. Rather than ratcheting up traditionally heroic and macho masculine responses, the young men managed vulnerability through self-deprecation, nonchalance, and scripting to construct an antiheroic and ordinary masculinity. Insights into the nature of men’s vulnerability in relation to women’s experience of emphasized femininity are discussed with the aim of expanding theoretical models of ‘‘men’s pain,’’ models that continue to pivot predominantly around hegemonic masculinity.
Transformation of Fundamental Parameters for Energy Demand and Indoor Temperature from Room Level to Building Level
Authors: Korjenic Azra , Bednar Thomas
Published: February 2010

Because the thermal optimization of a new building must be done in the planning phase, possible thermal optimizations are sought for the building by varying several parameters. This research article is based on the research of ‘climate surfaces’ by Prof. Keller and Dr Burmeister at the Federal Institute of Technology in Zurich (Burmeister and Keller, 1998). The question should be resolved whether this simplified method using climate surfaces is applicable to the entire building. The most important parameters of the building have been systematically changed and their impact on energy performance during different outdoor climate changes was observed. As a result, the impacts on the following are presented and discussed: Heat energy demands, Cooling energy demands, and Summer indoor temperatures.

The results of these investigations showed that the ‘multizone climate surface’ method is a very practical and clear strategy for estimating the thermal behavior of a building by the correct selection of three determining parameters. Already in an early planning stage, it is possible to establish the optimal building data, at a sufficient level of detail, where energy consumption has been concerned. The study is carried out using the monthly energy balance method and dynamic simulation using ‘BuildOpt’ software. The objective was to establish if the much simpler monthly balance method will give sufficiently precise results for this optimization, or if a simulation must be performed. The results of the analysis indicate that the monthly balance method is inaccurate, especially for buildings with low energy demands. Subsequent studies deal with the optimization of the most important construction assembly parameters of a building for specific climates. The results of the optimization studies are presented in this article.
A Naturalist’s View of Pride
Authors: Tracy Jessica L. , Shariff Azim F. , Cheng Joey T.
Published: February 2010

Although pride has been central to philosophical and religious discussions of emotion for thousands of years, it has largely been neglected by psychologists. However, in the past decade a growing body of psychological research on pride has emerged; new theory and findings suggest that pride is a psychologically important and evolutionarily adaptive emotion. In this article we review this accumulated body of research and argue for a naturalist account of pride, which presumes that pride emerged by way of natural selection. In this view, pride is prevalent in human life because of the functional and adaptive role it has played in the attainment, maintenance, and communication of social status throughout our evolutionary history.
A new plasminogen receptor
Authors: Strickland Dudley K.
Published: February 2010

Efficient activation of the fibrinolytic pathway occurs when plasminogen and its activators are sequestered on the cell surface. Identification of receptors responsible for localizing plasminogen to the cell surface has been elusive. Using a proteomics approach, Andronicos and colleagues have identified a novel 17-kDa transmembrane receptor, termed Plg-RKT, that binds plasminogen with high affinity and promotes its activation.1
Targeting telomerase: T-cell friendly fire
Authors: Calado Rodrigo T.
Published: February 2010

In this issue of Blood, Ugel and colleagues provide evidence that, in murine models, telomerase is an efficient target for adoptive cell therapy against a variety of cancer cells, but also can elicit an autoimmune response against B cells.1
General and species-specific transcriptional responses to downy mildew infection in a susceptible (Vitis vinifera) and a resistant (V. riparia) grapevine species
Authors: Polesani Marianna , Bortesi Luisa , Ferrarini Alberto , Zamboni Anita , Fasoli Marianna , Zadra Claudia , Lovato Arianna , Pezzotti Mario , Delledonne Massimo , Polverari Annalisa
Published: February 2010

Background

Downy mildew is a destructive grapevine disease caused byPlasmopara viticola(Berk. and Curt.) Berl. and de Toni, which can only be controlled by intensive fungicide treatments. Natural sources of resistance from wild grapevine (Vitis) species are used in conventional breeding approaches, but the signals and effectors involved in resistance in this important crop species are not well understood.

Results

Early transcriptional changes associated withP. viticolainfection in susceptibleV. viniferaand resistantV. ripariaplants were analyzed using the Combimatrix microarray platform. Transcript levels were measured 12 and 24 h post-inoculation, reflecting the time points immediately preceding the onset of resistance inV. riparia, as determined by microscopic analysis. Our data indicate that resistance inV. ripariais induced after infection, and is not based on differences in basal gene expression between the two species. The strong and rapid transcriptional reprogramming involves the induction of pathogenesis-related proteins and enzymes required for the synthesis of phenylpropanoid-derived compounds, many of which are also induced, albeit to a lesser extent, inV. vinifera. More interestingly, resistance inV. ripariaalso involves the specific modulation of numerous transcripts encoding components of signal transduction cascades, hypersensitive reaction markers and genes involved in jasmonate biosynthesis. The limited transcriptional modulation inV. viniferarepresents a weak attempted defense response rather than the activation of compatibility-specific pathways.

Conclusions

Several candidate resistance genes were identified that could be exploited in future biotechnological approaches to increase disease resistance in susceptible grapevine species. Measurements of jasmonic acid and methyl jasmonate in infected leaves suggest that this hormone may also be involved inV. ripariaresistance toP. viticola.
Toxicity of unsaturated fatty acids to the biohydrogenating ruminal bacterium, Butyrivibrio fibrisolvens
Authors: Maia Margarida RG , Chaudhary Lal C , Bestwick Charles S , Richardson Anthony J , McKain Nest , Larson Tony R , Graham Ian A , Wallace Robert J
Published: February 2010

Background

Health-promoting polyunsaturated fatty acids (PUFA) are abundant in forages grazed by ruminants and in vegetable and fish oils used as dietary supplements, but only a small proportion of PUFA finds its way into meat and milk, because of biohydrogenation in the rumen. Butyrivibrio fibrisolvens plays a major role in this activity. The aim of this study was to investigate the mechanisms by which PUFA affect the growth of B. fibrisolvens, how PUFA are metabolized and the metabolic response to growth in the presence of PUFA.

Results

Linoleic acid (LA; cis-9, cis-12-18:2) and α-linolenic acid (LNA; cis-9, cis-12, cis-15-18:3) increased the lag phase of B. fibrisolvens JW11, LNA having the greater effect. Growth was initiated only when the PUFA had been converted to vaccenic acid (VA; trans- 11-18:1). The major fish oil fatty acids, eicosapentaenoic acid (EPA; 20:5(n- 3)) and docosahexaenoic acid (DHA; 22:6(n- 3)), were not metabolized and prevented growth. Cellular integrity, as determined fluorimetrically by propidium iodide (PI) ingression, was affected as much by 18:1 fatty acids, including VA, as 18:2 fatty acids. The methyl esters of LNA, LA, EPA and DHA had no effect on growth or other measurements. The ATP pool decreased by 2/3 when LA was added to growing bacteria, whereas most acyl CoA pools decreased by >96%.

Conclusions

It was concluded that biohydrogenation occurs to enable B. fibrisolvens to survive the bacteriostatic effects of PUFA, and that the toxicity of PUFA is probably mediated via a metabolic effect rather than disruption of membrane integrity.
Multiple controls affect arsenite oxidase gene expression in Herminiimonas arsenicoxydans
Authors: Koechler Sandrine , Cleiss-Arnold Jessica , Proux Caroline , Sismeiro Odile , Dillies Marie-Agnès , Goulhen-Chollet Florence , Hommais Florence , Lièvremont Didier , Arsène-Ploetze Florence , Coppée Jean-Yves , Bertin Philippe N
Published: February 2010

Background

Both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. These transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. Herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of As(III) to As(V) as a detoxification mechanism.

Results

In the present study, a differential transcriptome analysis was used to identify genes, including arsenite oxidase encoding genes, involved in the response of H. arsenicoxydans to As(III). To get insight into the molecular mechanisms of this enzyme activity, a Tn5 transposon mutagenesis was performed. Transposon insertions resulting in a lack of arsenite oxidase activity disrupted aoxR and aoxS genes, showing that the aox operon transcription is regulated by the AoxRS two-component system. Remarkably, transposon insertions were also identified in rpoN coding for the alternative N sigma factor (σ54) of RNA polymerase and in dnaJ coding for the Hsp70 co-chaperone. Western blotting with anti-AoxB antibodies and quantitative RT-PCR experiments allowed us to demonstrate that the rpoN and dnaJ gene products are involved in the control of arsenite oxidase gene expression. Finally, the transcriptional start site of the aoxAB operon was determined using rapid amplification of cDNA ends (RACE) and a putative -12/-24 σ54-dependent promoter motif was identified upstream of aoxAB coding sequences.

Conclusion

These results reveal the existence of novel molecular regulatory processes governing arsenite oxidase expression in H. arsenicoxydans. These data are summarized in a model that functionally integrates arsenite oxidation in the adaptive response to As(III) in this microorganism.
Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome/X-linked mental retardation
Authors: Jentarra Garilyn M , Olfers Shannon L , Rice Stephen G , Srivastava Nishit , Homanics Gregg E , Blue Mary , Naidu SakkuBai , Narayanan Vinodh
Published: February 2010

Background

Rett syndrome (RTT), a common cause of mental retardation in girls, is associated with mutations in the MECP2 gene. Most human cases of MECP2 mutation in girls result in classical or variant forms of RTT. When these same mutations occur in males, they often present as severe neonatal encephalopathy. However, some MECP2 mutations can also lead to diseases characterized as mental retardation syndromes, particularly in boys. One of these mutations, A140V, is a common, recurring missense mutation accounting for about 0.6% of all MeCP2 mutations and ranking 21st by frequency. It has been described in familial X-linked mental retardation (XLMR), PPM- X syndrome (Parkinsonism, Pyramidal signs, Macroorchidism, X-linked mental retardation) and in other neuropsychiatric syndromes. Interestingly, this mutation has been reported to preserve the methyl-CpG binding function of the MeCP2 protein while compromising its ability to bind to the mental retardation associated protein ATRX.

Results

We report the construction and initial characterization of a mouse model expressing the A140V MeCP2 mutation. These initial descriptive studies in male hemizygous mice have revealed brain abnormalities seen in both RTT and mental retardation. The abnormalities found include increases in cell packing density in the brain and a significant reduction in the complexity of neuronal dendritic branching. In contrast to some MeCP2 mutation mouse models, the A140V mouse has an apparently normal lifespan and normal weight gain patterns with no obvious seizures, tremors, breathing difficulties or kyphosis.

Conclusion

We have identified various neurological abnormalities in this mouse model of Rett syndrome/X-linked mental retardation which may help to elucidate the manner in which MECP2 mutations cause neuronal changes resulting in mental retardation without the confounding effects of seizures, chronic hypoventilation, or other Rett syndrome associated symptoms.
Cellular toxicity following application of adeno-associated viral vector-mediated RNA interference in the nervous system
Authors: Ehlert Erich M , Eggers Ruben , Niclou Simone P , Verhaagen Joost
Published: February 2010

Background

After a spinal cord lesion, axon regeneration is inhibited by the presence of a diversity of inhibitory molecules in the lesion environment. At and around the lesion site myelin-associated inhibitors, chondroitin sulfate proteoglycans (CSPGs) and several axon guidance molecules, including all members of the secreted (class 3) Semaphorins, are expressed. Interfering with multiple inhibitory signals could potentially enhance the previously reported beneficial effects of blocking single molecules. RNA interference (RNAi) is a tool that can be used to simultaneously silence expression of multiple genes. In this study we aimed to employ adeno-associated virus (AAV) mediated expression of short hairpin RNAs (shRNAs) to target all Semaphorin class 3 signaling by knocking down its receptors, Neuropilin 1 (Npn-1) and Neuropilin 2 (Npn-2).

Results

We have successfully generated shRNAs that knock down Npn-1 and Npn-2 in a neuronal cell line. We detected substantial knockdown of Npn-2 mRNA when AAV5 viral vector particles expressing Npn-2 specific shRNAs were injected in dorsal root ganglia (DRG) of the rat. Unexpectedly however, AAV1-mediated expression of Npn-2 shRNAs and a control shRNA in the red nucleus resulted in an adverse tissue response and neuronal degeneration. The observed toxicity was dose dependent and was not seen with control GFP expressing AAV vectors, implicating the shRNAs as the causative toxic agents.

Conclusions

RNAi is a powerful tool to knock down Semaphorin receptor expression in neuronal cells in vitro and in vivo. However, when shRNAs are expressed at high levels in CNS neurons, they trigger an adverse tissue response leading to neuronal degradation.
Exposure of beta-tubulin regions defined by antibodies on an Arabidopsis thalianamicrotubule protofilament model and in the cells
Authors: Blume Yaroslav , Yemets Alla , Sheremet Yarina , Nyporko Alexey , Sulimenko Vadym , Sulimenko Tetyana , Dráber Pavel
Published: February 2010

Background

The function of the cortical microtubules, composed of αβ-tubulin heterodimers, is linked to their organizational state which is subject to spatial and temporal modulation by environmental cues. The role of tubulin posttranslational modifications in these processes is largely unknown. Although antibodies against small tubulin regions represent useful tool for studying molecular configuration of microtubules, data on the exposure of tubulin epitopes on plant microtubules are still limited.

Results

Using homology modeling we have generated anArabidopsis thalianamicrotubule protofilament model that served for the prediction of surface exposure of five β-tubulin epitopes as well as tyrosine residues. Peptide scans newly disclosed the position of epitopes detected by antibodies 18D6 (β1-10), TUB2.1 (β426-435) and TU-14 (β436-445). Experimental verification of the results by immunofluorescence microscopy revealed that the exposure of epitopes depended on the mode of fixation. Moreover, homology modeling showed that only tyrosines in the C-terminal region of β-tubulins (behind β425) were exposed on the microtubule external side. Immunofluorescence microscopy revealed tyrosine phosphorylation of microtubules in plant cells, implying that β-tubulins could be one of the targets for tyrosine kinases.

Conclusions

We predicted surface exposure of five β-tubulin epitopes, as well as tyrosine residues, on the surface ofA. thalianamicrotubule protofilament model, and validated the obtained results by immunofluorescence microscopy on cortical microtubules in cells.

The results suggest that prediction of epitope exposure on microtubules by means of homology modeling combined with site-directed antibodies can contribute to a better understanding of the interactions of plant microtubules with associated proteins.
Functional characterization of Arabidopsis thaliana transthyretin-like protein
Authors: Pessoa João , Sárkány Zsuzsa , Ferreira-da-Silva Frederico , Martins Sónia , Almeida Maria R , Li Jianming , Damas Ana M
Published: February 2010

Background

Arabidopsis thalianatransthyretin-like (TTL) protein is a potential substrate in the brassinosteroid signalling cascade, having a role that moderates plant growth. Moreover, sequence homology revealed two sequence domains similar to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) decarboxylase (N-terminal domain) and 5-hydroxyisourate (5-HIU) hydrolase (C-terminal domain). TTL is a member of the transthyretin-related protein family (TRP), which comprises a number of proteins with sequence homology to transthyretin (TTR) and the characteristic C-terminal sequence motif Tyr-Arg-Gly-Ser. TRPs are single domain proteins that form tetrameric structures with 5-HIU hydrolase activity. Experimental evidence is fundamental for knowing if TTL is a tetrameric protein, formed by the association of the 5-HIU hydrolase domains and, in this case, if the structural arrangement allows for OHCU decarboxylase activity. This work reports about the biochemical and functional characterization of TTL.

Results

The TTL gene was cloned and the protein expressed and purified for biochemical and functional characterization. The results show that TTL is composed of four subunits, with a moderately elongated shape. We also found evidence for 5-HIU hydrolase and OHCU decarboxylase activitiesin vitro, in the full-length protein.

Conclusions

TheArabidopsis thalianatransthyretin-like (TTL) protein is a tetrameric bifunctional enzyme, since it has 5-HIU hydrolase and OHCU decarboxylase activities, which were simultaneously observedin vitro.
Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas
Authors: Xiang Shengyan , Liu Zhaojun , Zhang Baozhen , Zhou Jing , Zhu Bu-Dong , Ji Jiafu , Deng Dajun
Published: February 2010

Background

Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation.

Methods

Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0.

Results

From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%).

Conclusions

Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively.
4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest
Authors: Yen Ching-Yu , Chiu Chien-Chih , Chang Fang-Rong , Chen Jeff Yi-Fu , Hwang Chi-Ching , Hseu You-Cheng , Yang Hsin-Ling , Lee Alan Yueh-Luen , Tsai Ming-Tz , Guo Zong-Lun , Cheng Yu-Shan , Liu Yin-Chang , Lan Yu-Hsuan , Chang Yu-Ching , Ko Ying-Chin , Chang Hsueh-Wei , Wu Yang-Chang
Published: February 2010

Background

The crude extract of the fruit bearing plant, Physalis peruviana (golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.

Methods

Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.

Results

It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (p < 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (p < 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC50) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G1 accumulation and slight arrest at the G2/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G2/M arrest for H1299 cells treated with 5 μg/mL for 24 h.

Conclusions

In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.
Novel genetic variants in miR-191 gene and familial ovarian cancer
Authors: Shen Jie , DiCioccio Richard , Odunsi Kunle , Lele Shashikant B , Zhao Hua
Published: February 2010

Background

Half of the familial aggregation of ovarian cancer can't be explained by any known risk genes, suggesting the existence of other genetic risk factors. Some of these unknown factors may not be traditional protein encoding genes. MicroRNA (miRNA) plays a critical role in tumorigenesis, but it is still unknown if variants in miRNA genes lead to predisposition to cancer. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk.

Methods and Results

To test this hypothesis in familial ovarian cancer, we screened for genetic variants in thirty selected miRNA genes, which are predicted to regulate key ovarian cancer genes and are reported to be misexpressed in ovarian tumor tissues, in eighty-three patients with familial ovarian cancer. All of the patients are non-carriers of any known BRCA1/2 or mismatch repair (MMR) gene mutations. Seven novel genetic variants were observed in four primary or precursor miRNA genes. Among them, three rare variants were found in the precursor or primary precursor of the miR-191 gene. In functional assays, the one variant located in the precursor of miR-191 resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR-191. In further analysis, we found that this particular variant exists in five family members who had ovarian cancer.

Conclusions

Our findings suggest that there are novel genetic variants in miRNA genes, and those certain genetic variants in miRNA genes can affect the expression of mature miRNAs and, consequently, might alter the regulation of TSGs or oncogenes. Additionally, the variant might be potentially associated with the development of familial ovarian cancer.
Determinants of smoking initiation among women in five European countries: a cross-sectional survey
Authors: Oh Debora L , Heck Julia E , Dresler Carolyn , Allwright Shane , Haglund Margaretha , Del Mazo Sara S , Kralikova Eva , Stucker Isabelle , Tamang Elizabeth , Gritz Ellen R , Hashibe Mia
Published: February 2010

Background

The rate of smoking and lung cancer among women is rising in Europe. The primary aim of this study was to determine why women begin smoking in five different European countries at different stages of the tobacco epidemic and to determine if smoking is associated with certain characteristics and/or beliefs about smoking.

Methods

A cross-sectional telephone survey on knowledge and beliefs about tobacco was conducted as part of the Women in Europe Against Lung Cancer and Smoking (WELAS) Project. A total of 5 000 adult women from France, Ireland, Italy, Czech Republic, and Sweden were interviewed, with 1 000 from each participating country. All participants were asked questions about demographics, knowledge and beliefs about smoking, and their tobacco use background. Current and former smokers also were asked questions about smoking initiation. Basic statistics on the cross-sectional data was reported with chi-squared and ANOVA p-values. Logistic regression was used to analyze ever versus never smokers. Linear regression analyses were used to analyze age of smoking initiation.

Results

Being older, being divorced, having friends/family who smoke, and having parents who smoke were all significantly associated with ever smoking, though the strength of the associations varied by country. The most frequently reported reason for initiation smoking was friend smoking, with 62.3% of ever smokers reporting friends as one of the reasons why they began smoking. Mean age of smoking initiation was 18.2 years and over 80% of participants started smoking by the age of 20. The highest levels of young initiators were in Sweden with 29.3% of women initiating smoking at age 14-15 and 12.0% initiating smoking younger than age 14. The lowest level of young initiators was in the Czech Republic with 13.7% of women initiating smoking at age 14-15 and 1.4% of women initiating smoking younger than age 14. Women who started smoking because their friends smoked or to look 'cool' were more likely to start smoking at a younger age. Women who started smoking to manage stress or to feel less depressed were more likely to start smoking at an older age.

Conclusions

In all five participating countries, friends were the primary factor influencing ever smoking, especially among younger women. The majority of participants began smoking in adolescence and the average reported age of smoking initiation was youngest in Sweden and oldest in the Czech Republic.
The role of social support and social networks in smoking behavior among middle and older aged people in rural areas of South Korea: A cross-sectional study
Authors: Yun E Hwa , Kang Yoon Hwa , Lim Min Kyung , Oh Jin-Kyoung , Son Jung Min
Published: February 2010

Background

Although the number of studies on anti-smoking interventions has increased, studies focused on identifying social contextual factors in rural areas are scarce. The purpose of this study was to explore the role of social support and social networks in smoking behavior among middle and older aged people living in rural areas of South Korea.

Methods

The study employed a cross-sectional design. Participants included 1,057 adults, with a mean age of 60.7 years, residing in rural areas. Information on participants' tobacco use, stress, social support, and social networks was collected using structured questionnaires. The chi-square test, the t-test, ANOVA, and logistic regression were used for data analysis.

Results

The overall smoking prevalence in the study was 17.4% (men, 38.8%; women, 5.1%). Overall, stress was high among women, and social support was high among men. Smokers had high levels of social support (t = -2.90, p = .0038) and social networks (t = -2.22, p = .0271), as compared to non- and former smokers. Those in the high social support group were likely to be smokers (AOR = 2.21, 95% CI 1.15-4.26). Women with moderate social ties were less likely to smoke (AOR = 0.18, 95% CI 0.05-0.61).

Conclusion

There was a protective role of a moderate social network level among women, and a high level of social support was associated with smoking behaviors in rural areas. Findings suggest the need for a comprehensive understanding of the functions and characteristics of social contextual factors including social support and social networks in order to conduct more effective anti-smoking interventions in rural areas.
Characterization of a molecular switch system that regulates gene expression in mammalian cells through a small molecule
Authors: Taylor Jennifer L , Rohatgi Priyanka , Spencer H Trent , Doyle Donald F , Azizi Bahareh
Published: February 2010

Background

Molecular switch systems that activate gene expression by a small molecule are effective technologies that are widely used in applied biological research. Nuclear receptors are valuable candidates for these regulation systems due to their functional role as ligand activated transcription factors. Previously, our group engineered a variant of the retinoid × receptor to be responsive to the synthetic compound, LG335, but not responsive to its natural ligand, 9-cis-retinoic acid.

Results

This work focuses on characterizing a molecular switch system that quantitatively controls transgene expression. This system is composed of an orthogonal ligand/nuclear receptor pair, LG335 and GRQCIMFI, along with an artificial promoter controlling expression of a target transgene. GRQCIMFI is composed of the fusion of the DNA binding domain of the yeast transcription factor, Gal4, and a retinoid × receptor variant. The variant consists of the following mutations: Q275C, I310M, and F313I in the ligand binding domain. When introduced into mammalian cell culture, the switch shows luciferase activity at concentrations as low as 100 nM of LG335 with a 6.3 ± 1.7-fold induction ratio. The developed one-component system activates transgene expression when introduced transiently or virally.

Conclusions

We have successfully shown that this system can induce tightly controlled transgene expression and can be used for transient transfections or retroviral transductions in mammalian cell culture. Further characterization is needed for gene therapy applications.
Keratin 19 marks poor differentiation and a more aggressive behaviour in canine and human hepatocellular tumours
Authors: van Sprundel Renee GHM , van den Ingh Ted SGAM , Desmet Valeer J , Katoonizadeh Azeam , Penning Louis C , Rothuizen Jan , Roskams Tania , Spee Bart
Published: February 2010

Background

The expression of Keratin 19 (K19) was reported in a subset of hepatocellular carcinomas (HCCs). K19 positive HCCs are associated with an increased malignancy compared to K19 negative HCCs. No suitable mouse models exist for this subtype of HCC, nor is the incidence of K19 expression in hepatocellular neoplasia in model animals known. Therefore, we compared the occurrence and tumour behaviour of K19 positive hepatocellular neoplasias in dog and man.

Results

The expression of hepatocellular differentiation (HepPar-1), biliary/progenitor cell (K7, K19), and malignancy (glypican-3) markers was semi-quantitatively assessed by immunohistochemistry. The histological grade of tumour differentiation was determined according to a modified classification of Edmondson and Steiner; the staging included intrahepatic, lymph node or distant metastases. Four of the 34 canine hepatocellular neoplasias showed K19 positivity (12%), of which two co-expressed K7. K19 positive tumours did not express HepPar-1, despite the histological evidence of a hepatocellular origin. Like in human HCC, all K19 positive hepatocellular neoplasias were glypican-3 positive and histologically poorly differentiated and revealed intra- or extrahepatic metastases whereas K19 negative hepatocellular neoplasias did not.

Conclusions

K19 positive hepatocellular neoplasias are highly comparable to man and occur in 12% of canine hepatocellular tumours and are associated with a poorly differentiated histology and aggressive tumour behaviour.
Role of PPAR-δ in the development of zymosan-induced multiple organ failure: an experiment mice study
Authors: Galuppo Maria , Di Paola Rosanna , Mazzon Emanuela , Genovese Tiziana , Crisafulli Concetta , Paterniti Irene , Cuzzocrea Elisabetta , Bramanti Placido , Kapoor Amar , Thiemermann Christoph , Cuzzocrea Salvatore
Published: February 2010

Background

Peroxisome proliferator-activated receptor (PPAR)-beta/delta is a nuclear receptor transcription factor that regulates gene expression in many important biological processes. It is expressed ubiquitously, especially white adipose tissue, heart, muscle, intestine, placenta and macrophages but many of its functions are unknown. Saturated and polyunsaturated fatty acids activate PPAR-beta/delta, but physiological ligands have not yet been identified. In the present study, we investigated the anti-inflammatory effects of PPAR-beta/delta activation, through the use of GW0742 (0,3 mg/kg 10% Dimethyl sulfoxide (DMSO) i.p), a synthetic high affinity ligand, on the development of zymosan-induced multiple organ failure (MOF).

Methods

Multiple organ failure (MOF) was induced in mice by administration of zymosan (given at 500 mg/kg, i.p. as a suspension in saline). The control groups were treated with vehicle (0.25 ml/mouse saline), while the pharmacological treatment was the administration of GW0742 (0,3 mg/kg 10% DMSO i.p. 1 h and 6 h after zymosan administration). MOF and systemic inflammation in mice was assessed 18 hours after administration of zymosan.

Results

Treatment with GW0742 caused a significant reduction of the peritoneal exudate formation and of the neutrophil infiltration caused by zymosan resulting in a reduction in myeloperoxidase activity. The PPAR-beta/delta agonist, GW0742, at the dose of 0,3 mg/kg in 10% DMSO, also attenuated the multiple organ dysfunction syndrome caused by zymosan. In pancreas, lung and gut, immunohistochemical analysis of some end points of the inflammatory response, such as inducible nitric oxide synthase (iNOS), nitrotyrosine, poly (ADP-ribose) (PAR), TNF- and IL-1as well as FasL, Bax, Bcl-2 and apoptosis, revealed positive staining in sections of tissue obtained from zymosan-injected mice. On the contrary, these parameters were markedly reduced in samples obtained from mice treated with GW0742

Conclusions

In this study, we have shown that GW0742 attenuates the degree of zymosan-induced non-septic shock in mice.
miR-17-92 expression in differentiated T cells - implications for cancer immunotherapy
Authors: Sasaki Kotaro , Kohanbash Gary , Hoji Aki , Ueda Ryo , McDonald Heather A , Reinhart Todd A , Martinson Jeremy , Lotze Michael T , Marincola Francesco M , Wang Ena , Fujita Mitsugu , Okada Hideho
Published: February 2010

Background

Type-1 T cells are critical for effective anti-tumor immune responses. The recently discovered microRNAs (miRs) are a large family of small regulatory RNAs that control diverse aspects of cell function, including immune regulation. We identified miRs differentially regulated between type-1 and type-2 T cells, and determined how the expression of such miRs is regulated.

Methods

We performed miR microarray analyses on in vitro differentiated murine T helper type-1 (Th1) and T helper type-2 (Th2) cells to identify differentially expressed miRs. We used quantitative RT-PCR to confirm the differential expression levels. We also used WST-1, ELISA, and flow cytometry to evaluate the survival, function and phenotype of cells, respectively. We employed mice transgenic for the identified miRs to determine the biological impact of miR-17-92 expression in T cells.

Results

Our initial miR microarray analyses revealed that the miR-17-92 cluster is one of the most significantly over-expressed miR in murine Th1 cells when compared with Th2 cells. RT-PCR confirmed that the miR-17-92 cluster expression was consistently higher in Th1 cells than Th2 cells. Disruption of the IL-4 signaling through either IL-4 neutralizing antibody or knockout of signal transducer and activator of transcription (STAT)6 reversed the miR-17-92 cluster suppression in Th2 cells. Furthermore, T cells from tumor bearing mice and glioma patients had decreased levels of miR-17-92 when compared with cells from non-tumor bearing counterparts. CD4+ T cells derived from miR-17-92 transgenic mice demonstrated superior type-1 phenotype with increased IFN-γ production and very late antigen (VLA)-4 expression when compared with counterparts derived from wild type mice. Human Jurkat T cells ectopically expressing increased levels of miR-17-92 cluster members demonstrated increased IL-2 production and resistance to activation-induced cell death (AICD).

Conclusion

The type-2-skewing tumor microenvironment induces the down-regulation of miR-17-92 expression in T cells, thereby diminishing the persistence of tumor-specific T cells and tumor control. Genetic engineering of T cells to express miR-17-92 may represent a promising approach for cancer immunotherapy.
Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study
Authors: Casanova Nathalie , Mazouni Zohra , Bieri Sabine , Combescure Christophe , Pica Alessia , Weber Damien C
Published: February 2010

Background

To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT).

Methods

A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5 - 54). Median follow-up was 12.0 months.

Results

During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (≤ 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA ≥ 2.5 (p = 0.01), KPS ≥ 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance.

Conclusions

The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.
Bilateral rectus femoris intramuscular haematoma following simultaneous quadriceps strain in an athlete: a case report
Authors: Natsis Konstantinos , Lyrtzis Christos , Noussios Georgios , Papathanasiou Efthymia , Anastasopoulos Nikolaos , Totlis Trifon
Published: February 2010

Introduction

Bilateral rectus femoris haematoma following a simultaneous strain of the quadriceps muscles is a very rare condition.

Case presentation

We report the case of a 21-year-old Greek Caucasian female rowing athlete who was injured on both thighs. She complained of pain and inability to walk. Physical examination revealed tenderness over the thighs and restriction of knee movement. The result of a roentgenogram was normal, and there was no evidence of fracture or patella displacement. Magnetic resonance imaging revealed haematoma formation in both the rectus femoris muscles. The diameters of the left and right haematomas within the muscles were 6 cm and 5 cm, respectively. Therapeutic approaches included compression bandages, ice application, rest, elevation, and administration of muscle relaxant drugs. Active stretching and isometric exercises were performed after three days. The patient was able to walk using crutches two days after the initiation of treatment. On the seventh day, she had regained her full ability to walk without crutches. Non-steroidal anti-inflammatory drugs were administered on the fifth day and continued for one week. Six weeks later, she had pain-free function and the result of magnetic resonance imaging was normal. She was able to resume her training programme and two weeks later, she returned to her previous sport activities and competitions.

Conclusion

There are references in the literature regarding the occurrence of unilateral quadriceps haematomas following strain and bilateral quadriceps tendon rupture in athletes. Simultaneous bilateral rectus femoris haematomas after a muscle strain is a rare condition. It must be diagnosed early. The three phases of treatment are rest, knee mobilization, and restoration of quadriceps function.
Ophthalmic complications of endoscopic ethmoidectomy: a case report
Authors: Niedzielska Iwona , Cieslik Tadeusz , Janic Tomasz
Published: February 2010

Damage to ethmoid structures following removal of nasal polyps can cause severe complications. A patient aged 48 years with damage to right orbital structures sustained in the course of transnasal endoscopic surgery for ethmoid polyps was operated. After operation were complications.