bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

Abstract

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

Abstract

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

Abstract
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

Abstract
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

AbstractPDLIM2 (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.