bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Tropospheric Jet Latitude on Coupling between the Stratospheric Polar Vortex and the Troposphere
Authors: Garfinkel Chaim I. , Waugh Darryn W. , Gerber Edwin P. 
Published: September 2012

AbstractA dry general circulation model is used to investigate how coupling between the stratospheric polar vortex and the extratropical tropospheric circulation depends on the latitude of the tropospheric jet. The tropospheric response to an identical stratospheric vortex configuration is shown to be strongest for a jet centered near 40° and weaker for jets near either 30° or 50° by more than a factor of 3. Stratosphere-focused mechanisms based on stratospheric potential vorticity inversion, eddy phase speed, and planetary wave reflection, as well as arguments based on tropospheric eddy heat flux and zonal length scale, appear to be incapable of explaining the differences in the magnitude of the jet shift. In contrast, arguments based purely on tropospheric variability involving the strength of eddy–zonal mean flow feedbacks and jet persistence, and related changes in the synoptic eddy momentum flux, appear to explain this effect. The dependence of coupling between the stratospheric polar vortex and the troposphere on tropospheric jet latitude found here is consistent with 1) the observed variability in the North Atlantic and the North Pacific and 2) the trend in the Southern Hemisphere as projected by comprehensive models.
Long-Term Functional Outcome of Bilateral Spontaneous and Simultaneous Achilles Tendon Ruptures
Authors: Ellanti Prasad , Davarinos Nikos , Burke Thomas E. , D’Souza Lester G. 
Published: September 2012

Bilateral simultaneous ruptures are rare comprising less than 1% of all Achilles tendon ruptures. Risk factors for bilateral ruptures include chronic diseases and medications such as corticosteroids and fluoroquinolones. There is little in the literature on the long-term functional outcome of bilateral Achilles tendon ruptures. This article present a series of 3 cases of simultaneous and spontaneous bilateral Achilles tendon ruptures with a minimum of 5-year follow up suggesting a good functional outcome. Level of Evidence: Therapeutic Level IV
Regulatory network operations in the Pathway Tools software
Authors: Paley Suzanne M , Latendresse Mario , Karp Peter D 
Published: September 2012

Abstract

Background
Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data.

Results
The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene.

Conclusions
Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism’s genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.
ncRNAclassifier: a tool for detection and classification of transposable element sequences in RNA hairpins
Authors: Tempel Sébastien , Pollet Nicolas , Tahi Fariza 
Published: September 2012

Abstract

Background
Inverted repeat genes encode precursor RNAs characterized by hairpin structures. These RNA hairpins are then metabolized by biosynthetic pathways to produce functional small RNAs. In eukaryotic genomes, short non-autonomous transposable elements can have similar size and hairpin structures as non-coding precursor RNAs. This resemblance leads to problems annotating small RNAs.

Results
We mapped all microRNA precursors from miRBASE to several genomes and studied the repetition and dispersion of the corresponding loci. We then searched for repetitive elements overlapping these loci. We developed an automatic method called ncRNAclassifier to classify pre-ncRNAs according to their relationship with transposable elements (TEs). We showed that there is a correlation between the number of scattered occurrences of ncRNA precursor candidates and the presence of TEs. We applied ncRNAclassifier on six chordate genomes and report our findings. Among the 1,426 human and 721 mouse pre-miRNAs of miRBase, we identified 235 and 68 mis-annotated pre-miRNAs respectively corresponding completely to TEs.

Conclusions
We provide a tool enabling the identification of repetitive elements in precursor ncRNA sequences. ncRNAclassifier is available athttp://EvryRNA.ibisc.univ-evry.fr.
Comparative exome sequencing of metastatic lesions provides insights into the mutational progression of melanoma
Authors: Gartner Jared J , Davis Sean , Wei Xiaomu , Lin Jimmy C , Trivedi Niraj S , Teer Jamie K ,   NISC Comparative Sequencing Program, Meltzer Paul S , Rosenberg Steven A , Samuels Yardena 
Published: September 2012

AbstractBackgroundMetastasis is characterized by spreading of neoplastic cells to an organ other than where they originated and is the predominant cause of death among cancer patients. This holds true for melanoma, whose incidence is increasing more rapidly than any other cancer and once disseminated has few therapeutic options. Here we performed whole exome sequencing of two sets of matched normal and metastatic tumor DNAs.ResultsUsing stringent criteria, we evaluated the similarities and differences between the lesions. We find that in both cases, 96% of the single nucleotide variants are shared between the two metastases indicating that clonal populations gave rise to the distant metastases. Analysis of copy number variation patterns of both metastatic sets revealed a trend similar to that seen with our single nucleotide variants. Analysis of pathway enrichment on tumor sets shows commonly mutated pathways enriched between individual sets of metastases and all metastases combined.ConclusionsThese data provide a proof-of-concept suggesting that individual metastases may have sufficient similarity for successful targeting of driver mutations.
Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23
Authors: Zhao Jianhua , Deliard Sandra , Aziz Ali Rahim , Grant Struan FA 
Published: September 2012

Abstract

Background
There is evidence that one of the key type 2 diabetes (T2D) loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and kinesin family member 11 (KIF11), respectively.

Methods
We analyzed the impact of adipogeneis on the mRNA and protein expression levels of these genes in the human adipocyte Simpson-Golabi-Behmel syndrome (SGBS) cell line in order to investigate which could be the culprit gene(s) in this region of linkage disequilibrium.

Results
Following activation of differentiation with a PPARγ ligand, we observed ~20% decrease in IDE, ~40% decrease in HHEX and in excess of 80% decrease in KIF11 mRNA levels when comparing the adipocyte and pre-adipocyte states. We also observed decreases in KIF11 and IDE protein levels, but conversely we observed a dramatic increase in HHEX protein levels. Subsequent time course experiments revealed some marked changes in expression as early as three hours after activation of differentiation.

Conclusion
Our data suggest that the expression of all three genes at this locus are impacted during SGBS adipogenesis and provides insights in to the possible mechanisms of how the genes at this 10q23 locus could influence both adipocyte differentiation and susceptibility to T2D through insulin resistance.
MHC2TA mRNA levels and human herpesvirus 6 in multiple sclerosis patients treated with interferon beta along two-year follow-up
Authors: Dominguez-Mozo Maria Inmaculada , Garcia-Montojo Marta , De Las Heras Virginia , Garcia-Martinez Angel , Arias-Leal Ana Maria , Casanova Ignacio , Arroyo Rafael , Alvarez-Lafuente Roberto 
Published: September 2012

Abstract

Background
In previous studies we found that MHC2TA +1614 genotype frequency was very different when MS patients with and without human herpesvirus 6 (HHV-6) in serum samples were compared; a different clinical behavior was also described. The purpose of the study was: 1. To evaluate if MHC2TA expression in MS patients was influenced by interferon beta (IFN-beta) treatment. 2. To study MHC2TA expression in MS patients with and without minor allele C. 3. To analyze the relation between MHC2TA mRNA levels and HHV-6 active infection in MS patients.

Methods
Blood and serum samples of 154 MS patients were collected in five programmed visits: basal (prior to beginning IFN-beta treatment), six, twelve, eighteen and twenty-four months later. HHV-6 in serum and MHC2TA mRNA levels were evaluated by PCR and RT-PCR, respectively. Neutralizing antibodies (NAbs) against IFN-beta were analyzed by the cytopathic effect assay.

Results
We found that MHC2TA mRNA levels were significantly lower among MS patients with HHV-6 active infection at the basal visit (without treatment) than in those MS patients without HHV-6 active infection at the basal visit (p = 0.012); in all the positive samples we only found variant A. Furthermore, 58/99 (58.6%) MS patients without HHV-6 along the five programmed visits and an increase of MHC2TA expression after two-years of IFN-beta treatment were clinical responders vs. 5/21 (23.8%) among those MS patients with HHV-6 and a decrease of MHC2TA mRNA levels along the two-years with IFN-beta treatment (p = 0.004); no differences were found between patients with and without NAbs.

Conclusions
MHC2TA mRNA levels could be decreased by the active replication of HHV-6; the absence of HHV-6 in serum and the increase of MHC2TA expression could be further studied as markers of good clinical response to IFN-beta treatment.
Hypoxic enhancement of exosome release by breast cancer cells
Authors: King Hamish W , Michael Michael Z , Gleadle Jonathan M 
Published: September 2012

Abstract

Background
Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling.

Methods
Breast cancer cell lines were cultured under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant.

Results
Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions.

Conclusions
These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more exosomes into their microenvironment to promote their own survival and invasion.
Obstructive sleep apnea and multimorbidity
Authors: Robichaud-Hallé Laurence , Beaudry Michel , Fortin Martin 
Published: September 2012

Abstract

Background
Obstructive sleep apnea (OSA) is becoming increasingly prevalent in North America and has been described in association with specific chronic diseases, particularly cardiovascular diseases. In primary care, where the prevalence of co-occurring chronic conditions is very high, the potential association with OSA is unknown. The purpose of this study was to explore the association between OSA and 1) the presence and severity of multimorbidity (multiple co-occurring chronic conditions), and 2) subcategories of multimorbidity.

Methods
A cluster sampling technique was used to recruit 120 patients presenting with OSA of various severities from the records of a sleep laboratory in 2008. Severity of OSA was based on the results of the polysomnography. Patients invited to participate received a mail questionnaire including questions on sociodemographic characteristics and the Disease Burden Morbidity Assessment (DBMA). They also consented to give access to their medical records. The DBMA was used to provide an overall multimorbidity score and sub-score of diseases affecting various systems.

Results
Bivariate analysis did not demonstrate an association between OSA and multimorbidity (r = 0.117; p = 0.205). However, severe OSA was associated with multimorbidity (adjusted odds ratio = 7.33 [1.67-32.23], p = 0.05). OSA was moderately correlated with vascular (r = 0.26, p = 0.01) and metabolic syndrome (r = 0.26, p = 0.01) multimorbidity sub-scores.

Conclusions
This study showed that severe OSA is associated with severe multimorbidity and sub-scores of multimorbidity. These results do not allow any causal inference. More research is required to confirm these associations. However, primary care providers should be aware of these potential associations and investigate OSA when deemed appropriate.
Triple-negative breast cancer is associated with EGFR, CK5/6 and c-KIT expression in Malaysian women
Authors: Kanapathy Pillai Shant Kishen , Tay Annie , Nair Suseela , Leong Chee-Onn 
Published: September 2012

Abstract

Background
Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) expressions. This subgroup of refractory disease tends to have aggressive clinical behavior, high frequency of metastasis and lack of response to current hormonal or targeted therapies. Despite numerous studies reporting the clinicopathological features of TNBC and its association with the basal-like phenotype in the Western population, only limited data are available in the Asian population. Therefore, the aim of this study was to investigate the clinicopathological characteristics of TNBC and its association with epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6) and mast/stem cell growth factor receptor (c-KIT or CD117) expression in Malaysian women.

Methods
A total of 340 patients diagnosed with primary breast cancer between 2002 and 2006 in Malaysia were reviewed and analyzed.

Results
The incidence of TNBC was 12.4% (42/340). Bivariate analysis revealed that TNBC was strongly associated with a younger age, higher grade tumor and p53 expression. Further immunohistochemical analysis suggested that TNBC in Malaysian women was strongly associated with EGFR, CK5/6 and c-KIT expression with high a Ki-67 proliferation index.

Conclusion
In conclusion, our study confirms the association of TNBC with basal-like marker expression (EGFR, CK5/6 and c-KIT) in Malaysian women, consistent with studies in other populations.
Chromosomal structural analysis in carcinoma of the gallbladder
Authors: Dixit Ruhi , Kumar Prabhat , Tripathi Ratnakar , Basu Somprakash , Mishra Rajnikanth , Shukla VK 
Published: September 2012

Abstract

Background
The etiopathogenesis of gallbladder cancer is still unknown. Both environmental and patient factors have been incriminated in its cause. That it is found in pockets of epidemiological distribution raises an issue of genetic changes associated with it. The aim of this study was to find out the chromosomal changes in gallbladder cancer.

Methods
Lymphocyte cell culture was carried out on blood of gallbladder cancer patients to determine chromosomal banding abnormalities. Native PAGE was also evaluated to analyze lactate dehydrogenase (LDH), superoxide dismutase (SOD) and catalase enzyme activity from the same blood of gallbladder cancer patients.

Results
Out of 30 gallbladder cancer patients, 4 male showed breakage on the long arm of chromosome 1 while only one male patient showed the translocation from the long arm of chromosome 4 to the long arm of chromosome 6 in a male patient.

Conclusion
The aberrations found in our study may suggest underlying genetic predisposition for the development of gallbladder cancer. They can act as a marker for gallbladder cancer, which needs further study.
Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis
Authors: Khan Meraj A , Sengupta Jayasree , Mittal Suneeta , Ghosh Debabrata 
Published: September 2012

Abstract

Background
In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n = 18) suffering from moderate (stage 3; n = 8) or severe (stage 4; n = 10) ovarian endometriosis during proliferative (n = 13) and secretory (n = 5) phases of menstrual cycle was performed.

Methods
Individual pure RNA samples were subjected to Agilent’s Whole Human Genome 44K microarray experiments. Microarray data were validated (P < 0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n = 4/each) during proliferative and secretory (n = 4/each) phases.

Results
Higher clustering effect of pairing (cluster distance, cd = 0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd = 0.5) and phases of menstrual cycle (cd = 0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered.

Conclusions
Dysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue.
Overexpression of FoxM1 is associated with tumor progression in patients with clear cell renal cell carcinoma
Authors: Xue Yi-Jun , Xiao Ri-Hai , Long Da-Zhi , Zou Xiao-Feng , Wang Xiao-Ning , Zhang Guo-Xi , Yuan Yuan-Hu , Wu Geng-Qing , Yang Jun , Wu Yu-Ting , Xu Hui , Liu Fo-Lin , Liu Min 
Published: September 2012

Abstract

Background
Fork head box M1 (FoxM1) is a proliferation-associated transcription factor essential for cell cycle progression. Numerous studies have documented that FoxM1 has multiple functions in tumorigenesis and its elevated levels are frequently associated with cancer progression. The present study was conducted to investigate the expression of FoxM1 and its prognostic significance in clear cell renal cell carcinoma (ccRCC). Meanwhile, the function of FoxM1 in human ccRCC was further investigated in cell culture models.

Methods
Real-time quantitative PCR, western blot and immunohistochemistry were used to explore FoxM1 expression in ccRCC cell lines and primary ccRCC clinical specimens. FoxM1 expression was knocked down by small interfering RNA (siRNA) in Caki-1 and 786-O cells; proliferation, colony formation, cell cycle, migration, invasion, and angiogenesis were assayed.

Results
FoxM1 expression was up-regulated in the majority of the ccRCC clinical tissue specimens at both mRNA and protein levels. Clinic pathological analysis showed that FoxM1 expression was significantly correlated with primary tumor stage (P <0.001), lymph node metastasis (P = 0.01), distant metastasis (P = 0.01), TNM stage (P < 0.001) and histological grade (P = 0.003). The Kaplan–Meier survival curves revealed that high FoxM1 expression was associated with poor prognosis in ccRCC patients (P < 0.001). FoxM1 expression was an independent prognostic marker of overall ccRCC patient survival in a multivariate analysis (P = 0.008). Experimentally, we found that down-regulation of FoxM1 inhibited cell proliferation and induced cell cycle arrest with reduced expression of cyclin B1, cyclin D1, and Cdk2, and increased expression of p21 and p27. Also, down-regulation of FoxM1 reduced expression and activity of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of migration, invasion, and angiogenesis.

Conclusions
These results suggest that FoxM1 expression is likely to play important roles in ccRCC development and progression, and that FoxM1 is a prognostic biomarker and a promising therapeutic target for ccRCC.