bluuebunny/crossref_metadata_2025 huggingface dataset:
IFN-β sensitizes neuroblastoma to the antitumor activity of temozolomide by modulating O6-methylguanine DNA methyltransferase expression
Authors: Rosati Shannon F. , Williams Regan F. , Nunnally Lindsey C. , McGee Mackenzie C. , Sims Thomas L. , Tracey Lorraine , Zhou Junfang , Fan Meiyun , Ng Catherine Y. , Nathwani Amit C. , Stewart Clinton F. , Pfeffer Lawrence M. , Davidoff Andrew M.
Published: December 2008

Although temozolomide has shown clinical activity against neuroblastoma, this activity is likely limited by the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT). We hypothesized that IFN-β could sensitize neuroblastoma cells to the cytotoxic effects of temozolomide through its ability to down-regulate MGMT expression. In vitro proliferation of three neuroblastoma cell lines treated with IFN-β and temozolomide alone or in combination was examined. Antitumor activity was assessed in both localized and disseminated neuroblastoma xenografts using single-agent and combination therapy, with continuous delivery of IFN-β being established by a liver-targeted adeno-associated virus-mediated approach. Two neuroblastoma cell lines (NB-1691 and SK-N-AS) were found to have high baseline levels of MGMT expression, whereas a third cell line (CHLA-255) had low levels. Temozolomide had little effect on in vitro proliferation of the neuroblastoma cell lines with high MGMT expression, but pretreatment with IFN-β significantly decreased MGMT expression and cell counts (NB-1691: 36 ± 3% of control, P = 0.0008; SK-N-AS: 54 ± 7% control, P = 0.003). In vivo, NB-1691 tumors in CB17-SCID mice treated with the combination of IFN-β and temozolomide had lower MGMT expression and a significantly reduced tumor burden, both localized [percent initial tumor volume: 2,516 ± 680% (control) versus 1,272 ± 330% (temozolomide), P = 0.01; 1,348 ± 220%, P = 0.03 (IFN-β); 352 ± 110%, P = 0.0001 (combo)] and disseminated [bioluminescent signal: control (1.32e10 ± 6.5e9) versus IFN-β (2.78e8 ± 3.09e8), P = 0.025, versus temozolomide (2.06e9 ± 1.55e9), P = 0.1, versus combination (2.13e7 ± 7.67e6), P = 0.009]. IFN-β appears to sensitize neuroblastoma cells to the cytotoxic effects of temozolomide through attenuation of MGMT expression. Thus, IFN-β and temozolomide may be a useful combination for treating children with this difficult disease. [Mol Cancer Ther 2008;7(12):3852–8]
Autophagy in Load-Induced Heart Disease
Authors: Rothermel Beverly A. , Hill Joseph A.
Published: December 2008

The heart is a highly plastic organ capable of remodeling in response to changes in physiological or pathological demand. For example, when workload increases, compensatory hypertrophic growth of individual cardiomyocytes occurs to increase cardiac output. Sustained stress, however, such as that occurring with hypertension or following myocardial infarction, triggers changes in energy metabolism and sarcomeric protein composition, loss of cardiomyocytes, ventricular dilation, reduced pump function, and ultimately heart failure. It has been known for some time that autophagy is active in cardiomyocytes, occurring at increased levels in disease. Now, with recent advances in our understanding of molecular mechanisms governing autophagy, the potential contributions of cardiomyocyte autophagy to ventricular remodeling and disease pathogenesis are being explored. As part of this work, several recent studies have focused on autophagy in heart disease elicited by changes in hemodynamic load. Pressure overload stress elicits a robust autophagic response in cardiomyocytes that is maladaptive, contributing to disease progression. In this context, load-induced aggregation of intracellular proteins is a proximal event triggering autophagic clearance mechanisms. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction, where activation of autophagy is beneficial, antagonizing disease progression. Here, we review recent studies of cardiomyocyte autophagy in load-induced disease and address molecular mechanisms and unanswered questions.
Relationship Between Noninvasively Measured Endothelial Function and Peripheral Arterial Disease
Authors: Medina Maldonado Francisco José , de Haro Miralles Joaquín , Martínez Aguilar Esther , Florez Gonzalez Aurora , March García Jose Ramón , Acín García Francisco
Published: December 2008

Objectives: To determine the relationship between endothelial function by means of brachial artery flow-mediated dilation (BAFMD) and the clinical severity of peripheral arterial disease (PAD).

Methods and Results: We examined the brachial artery diameter by ultrasound, before and after ischemia of the arm in 3 groups of participants— group A: healthy individuals under 30 years, without cardiovascular risk factors (n = 30); group B: patients with PAD and ischemic claudication (n = 30); and group C: patients with critical leg ischemia (n = 20). There were no differences between groups B and C, in regard to age, sex, and main cardiovascular risk factor. The BAFMD was 9.9% in group A compared with 5.5% in the pooled patients group (B + C; P < .001). Significant differences were absent between groups B and C (P > .05). Correlation coefficient of ankle-brachial index/BAFMD was r = .1; P = .49.

Conclusions: Patients with PAD present endothelial dysfunction, but this does not seem to determine the severity of the disease.
Self-Improving Motivations and Collectivism
Authors: Heine Steven J. , Raineri Andres
Published: December 2008

Much research reveals pronounced self-improving motivations among East Asians. A question remains whether similar patterns would emerge in non-Asian collectivist cultures. Research that has used self-report measures reveals mixed evidence regarding collectivist self-improvement. The present study assesses self-improving motivations among Chileans using a behavioral measure in a replication of an earlier experiment with Americans and Japanese by Heine and colleagues (2001). The results revealed that Chileans, like Japanese and unlike Americans, were more likely to switch tasks following success feedback than following failure feedback.
Peering into the “Magnum Mysterium” of Culture
Authors: Shteynberg Garriy , Gelfand Michele J. , Kim Kibum
Published: December 2008

The purpose of this research is to test whether descriptive norms, or cognitions about typical beliefs, values, and behaviors of one's group, can explain cultural influence in the domains of blame attribution and harm perception. In Study 1, using participants from the United States and South Korea, the authors find that individuals with lower (vs. higher) collectivistic descriptive norms ascribed more blame after more intentional acts and less blame after less intentional acts. In the second study, using American and South Korean participants, the authors find that individuals with lower (vs. higher) collectivistic descriptive norms perceived more harm after right violations and less harm after duty violations. Collectivistic personal attitudes did not predict the expected differences in attribution of blame or perception of harm. The descriptive norm account of cultural influence provides an alternative to the currently dominant personal attitude paradigm.
Genetic and Environmental Influences on Levels of Self-Control and Delinquent Peer Affiliation
Authors: Beaver Kevin M. , Eagle Schutt J. , Boutwell Brian B. , Ratchford Marie , Roberts Kathleen , Barnes J.C.
Published: December 2008

Despite the fact that low self-control and exposure to delinquent peers are two of the most robust and consistent predictors of crime, delinquency, and antisocial behavior, much remains unknown about what causes self-control to develop and what causes youths to befriend antisocial peers. This study estimated the relative effects of environmental and genetic factors on levels of self-control and contact with delinquent peers in a sample of twins from the National Longitudinal Study of Adolescent Health (Add Health). DeFries-Fulker analysis of the Add Health data revealed that both self-control and contact with drug-using friends were influenced by genetic factors and the nonshared environment, whereas the shared environment exhibited relatively small and inconsistent effects. Implications for self-control theory and social learning theory are discussed.
State of our Unions
Authors: Heath Melanie
Published: December 2008

Marriage promotion is a government strategy aimed at ensuring that children are raised in married, heterosexual families, preferably by their biological parents. This article places critical heterosexuality studies in dialogue with feminist state theory to examine marriage promotion as a reaction of the gendered and sexualized state to crisis tendencies of institutionalized heterosexuality. Drawing on the first in-depth study of marriage promotion politics, the author examines polycentric state practices that seek to stabilize the norm of the white, middle-class, heterosexual family. While explicit policy concerns focus on race and class, state-sponsored marriage workshops teach about gender hierarchy to rehearse an implicit ideology of marital heterosexuality. In contrast to feminist state theories that present a monolithic, top-down model of state control, the author offers a more nuanced examination of the relationship between macro and micro levels of power and their uneven consequences for social change.
An early decrease in Notch activation is required for human TCR-αβ lineage differentiation at the expense of TCR-γδ T cells
Authors: Van de Walle Inge , De Smet Greet , De Smedt Magda , Vandekerckhove Bart , Leclercq Georges , Plum Jean , Taghon Tom
Published: December 2008

Although well characterized in the mouse, the role of Notch signaling in the human T-cell receptor αβ (TCR-αβ) versus TCR-γδ lineage decision is still unclear. Although it is clear in the mouse that TCR-γδ development is less Notch dependent compared with TCR-αβ differentiation, retroviral overexpression studies in human have suggested an opposing role for Notch during human T-cell development. Using the OP9-coculture system, we demonstrate that changes in Notch activation are differentially required during human T-cell development. High Notch activation promotes the generation of T-lineage precursors and γδ T cells but inhibits differentiation toward the αβ lineage. Reducing the amount of Notch activation rescues αβ-lineage differentiation, also at the single-cell level. Gene expression analysis suggests that this is mediated by differential sensitivities of Notch target genes in response to changes in Notch activation. High Notch activity increases DTX1, NRARP, and RUNX3 expression, genes that are down-regulated during αβ-lineage differentiation. Furthermore, increased interleukin-7 levels cannot compensate for the Notch dependent TCR-γδ development. Our results reveal stage-dependent molecular changes in Notch signaling that are critical for normal human T-cell development and reveal fundamental molecular differences between mouse and human.
Evolution of the parasitic wasp subfamily Rogadinae (Braconidae): phylogeny and evolution of lepidopteran host ranges and mummy characteristics
Authors: Zaldívar-Riverón Alejandro , Shaw Mark R , Sáez Alberto G , Mori Miharu , Belokoblylskij Sergey A , Shaw Scott R , Quicke Donald LJ
Published: December 2008

Background

The braconid subfamily Rogadinae is a large, cosmopolitan group of endoparasitoid wasps characterised by 'mummifying' their lepidopteran host larvae, from which the adult subsequently emerges. Rogadines attack a variety of both macro- and microlepidopteran taxa, although the speciose genusAleiodesalmost exclusively attacks macrolepidopterans. Here, we investigate the phylogenetic history of the Rogadinae, revise their higher-level classification and assess the evolution of their host ranges and mummy types. We also assess the divergence times within the subfamily and discuss the reasons for the extraordinary evolutionary diversification ofAleiodes.

Results

Our Bayesian analyses weakly support the monophyly of the subfamily. A clade comprising allAleiodesspecies and some other taxa is not nested within the tribe Rogadini as previously supposed, but instead is recovered as sister to the Yeliconini, with the remaining Rogadini genera being recovered as sister to the Stiropiini. The Rogadinae is estimated to have originated during the mid to late Eocene, 36.1–51.62 MYA. Molecular dating gives a more recent origin for theAleiodesclade (17.98–41.76 MYA) compared to the origins proposed for two of its principal lepidopteran host groups (Noctuidae: 60.7–113.4 MYA; Geometridae 48–62 MYA). The Bayesian ancestral reconstruction of the emergence habits from the mummified hosts weakly recovered an anterior emergence as the ancestral condition for the subfamily. Producing a hard mummy has evolved at various times independently, though most of the species with this biology belong to theAleiodesclade.

Conclusion

Based on our results, we erect the tribe Aleiodininov.to includeAleiodesandHeterogamusstat. rev.Cordylorhogas,PholichoraandHemigyroneuronare synonymised withAleiodes. The molecular dating of clades and the ancestral reconstruction of host ranges support the hypothesis that radiation withinAleiodes s. s.was due to host recruitment leading to host range expansion followed by speciation, and not to parasitoid-host coevolution. Within the Rogadinae, variation in the site of emergence from the mummified host probably evolved as a consequence of the mummy's site and mode of formation, and the extent of mummy tanning/hardness to the degree of protection needed in relation to the cost of providing it.
A globally occurring indel polymorphism in the promoter of the IFNA2 gene is not associated with severity of malaria but with the positivity rate of HCV
Authors: Tena-Tomás Cristina , de Messias-Reason Iara , Song Le H , Tomiuk Jürgen , Kemsner Peter G , Kun Jürgen FJ
Published: December 2008

Background

Type I Interferons (IFNs) are well known cytokines which exert antiviral activity, antitumor activity and immunomodulatory effects. Single-nucleotide polymorphisms (SNP) and deletions in the gene coding for IFNA2 have been shown to influence the level of expression in vitro. The indel polymorphism -305_-300delAACTTT showed the strongest effect in vitro. To analyse the worldwide distribution of this polymorphism we analyzed five different populations (586 Vietnamese, 199 Central Africans, 265 Brazilians, 108 Kaingang and 98 Guarani). To investigate a possible association with susceptibility to infectious diseases we determined the polymorphism in malaria patients suffering either mild or severe malaria and in a cohort of hepatitis C virus infected individuals.

Results

We could detect the indel polymorphism in all populations analysed. There was no association with this polymorphism and the outcome of malaria but we found an increase of this indel polymorphism in hepatitis C virus positive individuals compared to healthy controls (p = 0.014).

Conclusion

Polymorphisms in genes involved in the interferon pathway have been implicated in the resistance or susceptibility against cerebral malaria and HBV. Here we show that an indel polymorphism, which mediates a disadvantageous effect in HBV patients, may also play a disadvantageous role in HCV infections stressing the importance of a fully functional interferon pathway.
SNP discovery in swine by reduced representation and high throughput pyrosequencing
Authors: Wiedmann Ralph T , Smith Timothy PL , Nonneman Dan J
Published: December 2008

Background

Relatively little information is available for sequence variation in the pig. We previously used a combination of short read (25 base pair) high-throughput sequencing and reduced genomic representation to discover > 60,000 single nucleotide polymorphisms (SNP) in cattle, but the current lack of complete genome sequence limits this approach in swine. Longer-read pyrosequencing-based technologies have the potential to overcome this limitation by providing sufficient flanking sequence information for assay design. Swine SNP were discovered in the present study using a reduced representation of 450 base pair (bp) porcine genomic fragments (approximately 4% of the swine genome) prepared from a pool of 26 animals relevant to current pork production, and a GS-FLX instrument producing 240 bp reads.

Results

Approximately 5 million sequence reads were collected and assembled into contigs having an overall observed depth of 7.65-fold coverage. The approximate minor allele frequency was estimated from the number of observations of the alternate alleles. The average coverage at the SNPs was 12.6-fold. This approach identified 115,572 SNPs in 47,830 contigs. Comparison to partial swine genome draft sequence indicated 49,879 SNP (43%) and 22,045 contigs (46%) mapped to a position on a sequenced pig chromosome and the distribution was essentially random. A sample of 176 putative SNPs was examined and 168 (95.5%) were confirmed to have segregating alleles; the correlation of the observed minor allele frequency (MAF) to that predicted from the sequence data was 0.58.

Conclusion

The process was an efficient means to identify a large number of porcine SNP having high validation rate to be used in an ongoing international collaboration to produce a highly parallel genotyping assay for swine. By using a conservative approach, a robust group of SNPs were detected with greater confidence and relatively high MAF that should be suitable for genotyping in a wide variety of commercial populations.
Optimised padlock probe ligation and microarray detection of multiple (non-authorised) GMOs in a single reaction
Authors: Prins Theo W , van Dijk Jeroen P , Beenen Henriek G , Van Hoef AM Angeline , Voorhuijzen Marleen M , Schoen Cor D , Aarts Henk JM , Kok Esther J
Published: December 2008

Background

To maintain EU GMO regulations, producers of new GM crop varieties need to supply an event-specific method for the new variety. As a result methods are nowadays available for EU-authorised genetically modified organisms (GMOs), but only to a limited extent for EU-non-authorised GMOs (NAGs). In the last decade the diversity of genetically modified (GM) ingredients in food and feed has increased significantly. As a result of this increase GMO laboratories currently need to apply many different methods to establish to potential presence of NAGs in raw materials and complex derived products.

Results

In this paper we present an innovative method for detecting (approved) GMOs as well as the potential presence of NAGs in complex DNA samples containing different crop species. An optimised protocol has been developed for padlock probe ligation in combination with microarray detection (PPLMD) that can easily be scaled up. Linear padlock probes targeted against GMO-events, -elements and -species have been developed that can hybridise to their genomic target DNA and are visualised using microarray hybridisation.

In a tenplex PPLMD experiment, different genomic targets in Roundup-Ready soya, MON1445 cotton and Bt176 maize were detected down to at least 1%. In single experiments, the targets were detected down to 0.1%, i.e. comparable to standard qPCR.

Conclusion

Compared to currently available methods this is a significant step forward towards multiplex detection in complex raw materials and derived products. It is shown that the PPLMD approach is suitable for large-scale detection of GMOs in real-life samples and provides the possibility to detect and/or identify NAGs that would otherwise remain undetected.
Therapeutic potential of resveratrol in Alzheimer's disease
Authors: Vingtdeux Valérie , Dreses-Werringloer Ute , Zhao Haitian , Davies Peter , Marambaud Philippe
Published: December 2008

Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent work in cell cultures and animal models has shed light on the molecular mechanisms potentially involved in the beneficial effects of resveratrol intake against the neurodegenerative process in Alzheimer's disease.
Identification of precursor transcripts for 6 novel miRNAs expands the diversity on the genomic organisation and expression of miRNA genes in rice
Authors: Lacombe Séverine , Nagasaki Hiroshi , Santi Carole , Duval David , Piégu Benoît , Bangratz Martine , Breitler Jean-Christophe , Guiderdoni Emmanuel , Brugidou Christophe , Hirsch Judith , Cao Xiaofeng , Brice Claire , Panaud Olivier , Karlowski Wojciech M , Sato Yutaka , Echeverria Manuel
Published: December 2008

Background

The plant miRNAs represent an important class of endogenous small RNAs that guide cleavage of an mRNA target or repress its translation to control development and adaptation to stresses. MiRNAs are nuclear-encoded genes transcribed by RNA polymerase II, producing a primary precursor that is subsequently processed by DCL1 an RNase III Dicer-like protein.

In rice hundreds of miRNAs have been described or predicted, but little is known on their genes and precursors which are important criteria to distinguish them from siRNAs. Here we develop a combination of experimental approaches to detect novel miRNAs in rice, identify their precursor transcripts and genes and predict or validate their mRNA targets.

Results

We produced four cDNA libraries from small RNA fractions extracted from distinct rice tissues. By in silico analysis we selected 6 potential novel miRNAs, and confirmed that their expression requires OsDCL1. We predicted their targets and used 5'RACE to validate cleavage for three of them, targeting a PPR, an SPX domain protein and a GT-like transcription factor respectively.

In addition, we identified precursor transcripts for the 6 miRNAs expressed in rice, showing that these precursors can be efficiently processed using a transient expression assay in transfected Nicotiana benthamiana leaves. Most interestingly, we describe two precursors producing tandem miRNAs, but in distinct arrays. We focus on one of them encoding osa-miR159a.2, a novel miRNA produced from the same stem-loop structure encoding the conserved osa-miR159a.1. We show that this dual osa-miR159a.2-osa-miR159a.1 structure is conserved in distant rice species and maize. Finally we show that the predicted mRNA target of osa-miR159a.2 encoding a GT-like transcription factor is cleaved in vivo at the expected site.

Conclusion

The combination of approaches developed here identified six novel miRNAs expressed in rice which can be clearly distinguished from siRNAs. Importantly, we show that two miRNAs can be produced from a single precursor, either from tandem stem-loops or tandemly arrayed in a single stem-loop. This suggests that processing of these precursors could be an important regulatory step to produce one or more functional miRNAs in plants and perhaps coordinate cleavage of distinct targets in the same plant tissue.
Geographical mapping of a multifocal thyroid tumour using genetic alteration analysis & miRNA profiling
Authors: Aherne Sinéad T , Smyth Paul C , Flavin Richard J , Russell Susan M , Denning Karen M , Li Jing Huan , Guenther Simone M , O'Leary John J , Sheils Orla M
Published: December 2008

Background

Papillary thyroid carcinoma (PTC) frequently presents as multiple tumour-foci within a single thyroid gland or pluriform, with synchronous tumours comprising different histological variants, raising questions regarding its clonality. Among the genetic aberrations described in PTC, the BRAF V600E mutation and ret/PTC activation occur most commonly. Several studies have investigated the genetic alteration status of multifocal thyroid tumours, with discordant results.

To address the question of clonality this study examined disparate geographical and morphological areas from a single PTC (classic PTC, insular and anaplastic foci, and tumour cells adjacent to vascular invasion and lymphocytic infiltrate) for the presence of ret/PTC 1 or BRAF mutations. Moreover, we wanted to investigate the consistency of miRNA signatures within disparate areas of a tumour, and geographical data was further correlated with expression profiles of 330 different miRNAs. Putative miRNA gene targets were predicted for differentially regulated miRNAs and immunohistochemistry was performed on tissue sections in an effort to investigate phenotypic variations in microvascular density (MVD), and cytokeratin and p53 protein expression levels.

Results

All of the morphological areas proved negative for ret/PTC 1 rearrangement. Two distinct foci with classic morphology harboured the BRAF mutation. All other regions, including the insular and anaplastic areas were negative for the mutation.

MiRNA profiles were found to distinguish tumours containing the BRAF mutation from the other tumour types, and to differentiate between the more aggressive insular & anaplastic tumours, and the classic variant. Our data corroborated miRNAs previously discovered in this carcinoma, and additional miRNAs linked to various processes involved in tumour growth and proliferation.

Conclusion

The initial genetic alteration analysis indicated that pluriform PTC did not necessarily evolve from classic PTC progenitor foci. Analysis of miRNA profiles however provided an interesting variation on the clonality question. While hierarchical clustering analysis of miRNA expression supported the hypothesis that discrete areas did not evolve from clonal expansion of tumour cells, it did not exclude the possibility of independent mutational events suggesting both phenomena might occur simultaneously within a tumour to enhance cancer progression in geographical micro-environments within a tumour.
Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis
Authors: Honda Hiroshi , Barrueto Fermin F , Gogusev Jean , Im Dwight D , Morin Patrice J
Published: December 2008

Background

Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer.

Methods

In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues.

Results

We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis.

Conclusion

In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis.
Using the National Health Interview Survey to understand and address the impact of tobacco in the United States: past perspectives and future considerations
Authors: Backinger Cathy L , Lawrence Deirdre , Swan Judith , Winn Deborah M , Breen Nancy , Hartman Anne , Grana Rachel , Tran David , Farrell Samantha
Published: December 2008

Objective

The National Health Interview Survey (NHIS) is a continuous, nationwide, household interview survey of the civilian noninstitutionalized population of the United States. This annual survey is conducted by the National Center for Health Statistics, part of the Centers for Disease Control and Prevention. Since 1965, the survey and its supplements have provided data on issues related to the use of cigarettes and other tobacco products. This paper describes the survey, provides an overview of peer-reviewed and government-issued research that uses tobacco-related data from the NHIS, and suggests additional areas for exploration and directions for future research.

Data sources

We performed literature searches using the PubMed database, selecting articles from 1966 to 2008. Study selection. Inclusion criteria were relevancy to tobacco research and primary use of NHIS data; 117 articles met these criteria. Data extraction and synthesis. Tobacco-related data from the NHIS have been used to analyze smoking prevalence and trends; attitudes, knowledge, and beliefs; initiation; cessation and advice to quit; health care practices; health consequences; secondhand smoke exposure; and use of smokeless tobacco. To date, use of these data has had broad application; however, great potential still exists for additional use.

Conclusion

NHIS data provide information that can be useful to both practitioners and researchers. It is important to explore new and creative ways to best use these data and to address the full range of salient tobacco-related topics. Doing so will better inform future tobacco control research and programs.
A novel method to detect unlabeled inorganic nanoparticles and submicron particles in tissue by sedimentation field-flow fractionation
Authors: Deering Cassandra E , Tadjiki Soheyl , Assemi Shoeleh , Miller Jan D , Yost Garold S , Veranth John M
Published: December 2008

A novel methodology to detect unlabeled inorganic nanoparticles was experimentally demonstrated using a mixture of nano-sized (70 nm) and submicron (250 nm) silicon dioxide particles added to mammalian tissue. The size and concentration of environmentally relevant inorganic particles in a tissue sample can be determined by a procedure consisting of matrix digestion, particle recovery by centrifugation, size separation by sedimentation field-flow fractionation (SdFFF), and detection by light scattering.

Background

Laboratory nanoparticles that have been labeled by fluorescence, radioactivity, or rare elements have provided important information regarding nanoparticle uptake and translocation, but most nanomaterials that are commercially produced for industrial and consumer applications do not contain a specific label.

Methods

Both nitric acid digestion and enzyme digestion were tested with liver and lung tissue as well as with cultured cells. Tissue processing with a mixture of protease enzymes is preferred because it is applicable to a wide range of particle compositions. Samples were visualized via fluorescence microscopy and transmission electron microscopy to validate the SdFFF results. We describe in detail the tissue preparation procedures and discuss method sensitivity compared to reported levels of nanoparticles in vivo.

Conclusion

Tissue digestion and SdFFF complement existing techniques by precisely identifying unlabeled metal oxide nanoparticles and unambiguously distinguishing nanoparticles (diameter<100 nm) from both soluble compounds and from larger particles of the same nominal elemental composition. This is an exciting capability that can facilitate epidemiological and toxicological research on natural and manufactured nanomaterials.
Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats
Authors: Upadhyay Swapna , Stoeger Tobias , Harder Volkar , Thomas Ronald F , Schladweiler Mette C , Semmler-Behnke Manuela , Takenaka Shinji , Karg Erwin , Reitmeir Peter , Bader Michael , Stampfl Andreas , Kodavanti Urmila P , Schulz Holger
Published: December 2008

Background

Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).

Methods

Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).

Results

Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.

Conclusion

Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.
Simultaneous infection of Schistosoma mansoni and S. rodhaini in Biomphalaria glabrata: impact on chronobiology and cercarial behaviour
Authors: Norton Alice , Rollinson David , Richards Louisa , Webster Joanne
Published: December 2008

Background

The chances of a schistosome cercaria encountering a suitable definitive host may be enhanced by emergence from the molluscan intermediate host with maximal glycogen stores and by an appropriate chronobiological rhythm. This study aimed to identify and characterize the effects of potential competitive interactions in the snail host Biomphalaria glabrata, between the closely-related Schistosoma mansoni and S. rodhaini, on phenotypic behavioural traits. It was predicted that inter-specific competition would affect chronobiological emergence rhythms and reduce the activity of schistosome swimming behavioural traits. Biomphalaria glabrata snails (120) were exposed to either S. mansoni or S. rodhaini single infections, or a mixed infection of both species simultaneously and the resulting cercarial phenotypic traits were characterised. Cercariae were identified from co-exposed snails by amplification and sequencing of the mitochondrial cytochrome oxidase subunit 1 (CO1).

Results

S. mansoni and S. rodhaini largely maintained their distinct chronobiological rhythms after mixed exposures and infections. However, inter-specific competition appeared to result in a restriction of the shedding pattern of S. rodhaini and slight shift in the shedding pattern of S. mansoni. Inter-specific competition also significantly lowered hourly cercarial production for both parasite species in comparison to single exposures and infections and reduced cercarial swimming activity.

Conclusion

Inter-specific competition was shown to influence cercarial production, chronobiology and activity and should therefore be investigated further in field situations to determine the effects of these changes on parasite fitness (incorporating both host finding and infectivity) where these two species overlap. Importantly this competition did not result in a large change in chronobiological emergence of cercariae for either species indicating that it would not have a large influence on the species of hosts available for infection at time of emergence. This study has furthermore demonstrated the potential for phenotypic measures to provide markers for species-specific identification even in conditions of co-infection.
Digoxin treatment is associated with an increased incidence of breast cancer: a population-based case-control study
Authors: Ahern Thomas P , Lash Timothy L , Sørensen Henrik T , Pedersen Lars
Published: December 2008

Introduction

Laboratory and epidemiologic studies have suggested a modifying effect of cardiac glycosides (for example, digoxin and digitoxin) on cancer risk. We explored the association between digoxin treatment and invasive breast cancer incidence among postmenopausal Danish women.

Methods

We used Danish registries to identify 5,565 postmenopausal women diagnosed with incident invasive breast carcinoma between 1 January 1991 and 31 December 2007, and 55,650 matched population controls. Cardiac glycoside prescriptions were ascertained from county prescription registries. All subjects had at least 2 years of recorded prescription drug and medical history data. We estimated the odds ratio associating digoxin use with breast cancer in conditional logistic regression models adjusted for age, county of residence, and use of anticoagulants, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, and hormone replacement therapy. We also explored the impact of confounding by indication and detection bias.

Results

Digoxin was the sole cardiac glycoside prescribed to subjects during the study period. There were 324 breast cancer cases (5.8%) and 2,546 controls (4.6%) with a history of digoxin use at least 1 year before their index date (adjusted odds ratio (OR): 1.30; 95% confidence interval: 1.14 to 1.48). The breast cancer OR increased modestly with increasing duration of digoxin exposure (adjusted OR for 7 to 18 years of digoxin use: 1.39; 95% confidence interval: 1.10 to 1.74). The association was robust to adjustment for age, receipt of hormone replacement therapy, coprescribed drugs, and confounding by indication. A comparison of screening mammography rates between cases and controls showed no evidence of detection bias.

Conclusions

Our results suggest that digoxin treatment increases the risk of invasive breast cancer among postmenopausal women.
Anti-oestrogens but not oestrogen deprivation promote cellular invasion in intercellular adhesion-deficient breast cancer cells
Authors: Borley Annabel C , Hiscox Stephen , Gee Julia , Smith Chris , Shaw Victoria , Barrett-Lee Peter , Nicholson Robert I
Published: December 2008

Introduction

Anti-oestrogens have been the mainstay of therapy in patients with oestrogen-receptor (ER) positive breast cancer and have provided significant improvements in survival. However, their benefits are limited by tumour recurrence in a significant proportion of initially drug-responsive breast cancer patients because of acquired anti-oestrogen resistance. Relapse on such therapies clinically presents as local and/or regional recurrences, frequently with distant metastases, and the prognosis for these patients is poor. The selective ER modulator, tamoxifen, classically exerts gene inhibitory effects during the drug-responsive phase in ER-positive breast cancer cells. Paradoxically, this drug is also able to induce the expression of genes, which in the appropriate cell context may contribute to an adverse cell phenotype. Here we have investigated the effects of tamoxifen and fulvestrant treatment on invasive signalling and compared this with the direct effects of oestrogen withdrawal to mimic the action of aromatase inhibitors.

Methods

The effect of oestrogen and 4-hydroxy-tamoxifen on the invasive capacity of endocrine-sensitive MCF-7 cells, in the presence or absence of functional E-cadherin, was determined by Matrigel invasion assays. Studies also monitored the impact of oestrogen withdrawal or treatment with fulvestrant on cell invasion. Western blotting using phospho-specific antibodies was performed to ascertain changes in invasive signalling in response to the two anti-oestrogens versus both oestradiol treatment and withdrawal.

Results

To the best of our knowledge, we report for the first time that tamoxifen can promote an invasive phenotype in ER-positive breast cancer cells under conditions of poor cell-cell contact and suggest a role for Src kinase and associated pro-invasive genes in this process. Our studies revealed that although this adverse effect is also apparent for further classes of anti-oestrogens, exemplified by the steroidal agent fulvestrant, it is absent during oestrogen withdrawal.

Conclusions

These data highlight a previously unreported effect of tamoxifen (and potentially further anti-oestrogens), that such agents appear able to induce breast cancer cell invasion in a specific context (absence of good cell-cell contacts), where these findings may have major clinical implications for those patients with tumours that have inherently poor intercellular adhesion. In such patients oestrogen deprivation with aromatase inhibitors may be more appropriate.
Sequestration of PDLIM2 in the cytoplasm of monocytic/macrophage cells is associated with adhesion and increased nuclear activity of NF-κB
Authors: Healy Nollaig C , O’Connor Rosemary
Published: December 2008

PDLIM2 (Mystique/SLIM) is a postsynaptic density-95/discs large/zonula occludens-1-Lin-11, Isl-1, Mec-3 (PDZ-LIM) domain protein expressed in the nucleus of T lymphocytes, where it promotes degradation of the p65 subunit of NF-κB. It is also expressed at the cytoskeleton in epithelial cells, where it is essential for cell migration. It is not known whether PDLIM2 function at the nucleus and cytoskeleton is linked and whether PDLIM2 subcellular location is regulated in hematopoietic cells. To investigate this, we used the human monocytic leukemia cell line THP-1 that can differentiate into adherent macrophages and the adherent murine macrophage cell line RAW264.7. PMA-induced differentiation of THP-1 cells resulted in increased accumulation of PDLIM2. In differentiated cells, PDLIM2 exhibited retarded mobility indicative of serine phosphorylation, which could be reversed by phosphatases and by inhibition of protein kinase C or ERK kinases. In nondifferentiated THP-1 cells, PDLIM2 was located predominantly in the nucleus, whereas in differentiated cells, PDLIM2 was located predominantly in the cytoplasm. Suppression of PDLIM2 expression in THP-1 and RAW 264.7 cells resulted in decreased adhesion, increased NF-κB transcription reporter activity, and increased LPS-induced TNF-α production. Overexpression of PDLIM2 in THP-1 cells enhanced cell adhesion. Overall, these findings indicate that PDLIM2 sequestration in the cytoplasm is associated with cell adhesion and increased nuclear activity of NF-κB p65. The data suggest that sequestration of PDLIM2 at the cytoskeleton regulates its nuclear function.
Role of leptin receptor-induced STAT3 signaling in modulation of intestinal and hepatic inflammation in mice
Authors: Gove Melissa E , Rhodes Davina H , Pini Maria , van Baal Jantine W , Sennello Joseph A , Fayad Raja , Cabay Robert J , Myers Martin G , Fantuzzi Giamila
Published: December 2008

Leptin-deficient ob/ob mice are resistant to dextran sulfate sodium (DSS)-induced colitis and Concanavalin A (Con A)-induced hepatitis. However, the signal transduction pathways involved have not been identified. The present study investigated the effect of leptin-induced STAT3 signaling in the DSS and Con A models. Mice carrying a leptin receptor (LEPR) gene mutant for Y1138 (s/s mice), with abrogated leptin-induced STAT3 signaling, were compared with wild-type (WT) and LEPR-deficient db/db mice. Administration of DSS to s/s mice resulted in a clinical score and colon shortening of intermediate severity compared with disease induced in WT and db/db mice—the latter group having the lowest disease severity. A comparable degree of inflammatory infiltrate and epithelial damage was observed in the colon of WT and s/s mice, and these parameters were reduced in db/db mice. Levels of IFN-γ, IL-6, IL-10, and TNF-α were comparable in the colon of s/s and db/db mice, and a similar trend was observed for CXCL2. s/s and WT mice developed severe liver disease in response to Con A, whereas db/db mice were protected. However, Con A-induced serum IL-6 and TNF-α levels in s/s mice mimicked levels observed in db/db rather than WT mice. In conclusion, lack of leptin-induced STAT3 signaling is associated with reduced cytokine production following DSS and Con A administration, but it appears to sensitize mice to the effects of proinflammatory mediators.
Cutting forces in wood machining – Basics and applications in industrial processes. A review COST Action E35 2004–2008: Wood machining – micromechanics and fracture
Authors: Marchal Rémy , Mothe Frédéric , Denaud Louis-Etienne , Thibaut Bernard , Bleron Laurent
Published: December 2008

The data available in the literature concerning wood cutting forces permits to build models or to simulate the main wood machining processes (milling, sawing, peeling, etc.). This approach contributes to a better understanding of formation of wood surfaces and chips and the data may be helpful to optimise cutting geometry, reduce tool wear, improve tool material, and to size tool-machines. The models may also be useful for industrial application in two ways: (1) providing data to optimise the settings for a given operation (batch approach), and (2) building predictive models that could be the basis of an online control system for the machining processes (interactive approach). A prerequisite for this is that numerous machining tests on different wood materials are performed based on experiences with different kind of tools and experimental devices. With a focus on potential industrial applications, the emphasis of this review was on the wood peeling process, which is a very demanding special case of wood cutting. Although not so many industrial machines are equipped with expensive force sensors, there is a lot of high quality information available about cutting forces which may be useful to improve the scientific or technological knowledge in wood machining. Alternative parameters, such as vibration or sound measurements, appear to be promising substitutes in the praxis, particularly to feed online control systems of any wood cutting process.