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Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3
- Seth Frietze†1,
- Rui Wang†2, 3,
- Lijing Yao1,
- Yu Gyoung Tak1,
- Zhenqing Ye3,
- Malaina Gaddis1,
- Heather Witt1,
- Peggy J Farnham1Email author and
- Victor X Jin3Email author
DOI: 10.1186/gb-2012-13-9-r52
© Frietze et al.; licensee BioMed Central Ltd. 2012
Received: 9 March 2012
Accepted: 25 May 2012
Published: 5 September 2012
The TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in six human cell lines.
We identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to the six cell lines. Using ChIP-seq, we showed that many genomic regions that are marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer activity. Bioinformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells. Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the genome via GATA3.
Our studies demonstrate a novel relationship between GATA3 and TCF7L2, and reveal important insights into TCF7L2-mediated gene regulation.
The TCF7L2 (transcription factor 7-like 2) gene encodes a high mobility group box-containing transcription factor that is highly up-regulated in several types of human cancer, such as colon, liver, breast, and pancreatic cancer [1–4]. Although TCF7L2 is sometimes called TCF4, there is a helix-loop-helix transcription factor that has been given the official gene name of TCF4 and it is important, therefore, to be aware of possible confusion in the literature. Numerous studies have shown that TCF7L2 is an important component of the WNT pathway [3, 5, 6]. TCF7L2 mediates the downstream effects of WNT signaling via its interaction with CTNNB1 (beta-catenin) and it can function as an activator or a repressor, depending on the availability of CTNNB1 in the nucleus. For example, TCF7L2 can associate with the members of the Groucho repressor family in the absence of CTNNB1. The WNT pathway is often constitutively activated in cancers, leading to increased levels of nuclear CTNNB1 and up-regulation of TCF7L2 target genes [3]. In addition to being linked to neoplastic transformation, variants in TCF7L2 are thought to be the most critical risk factors for type 2 diabetes [7–10]. However, the functional role of TCF7L2 in these diseases remains unclear. One hypothesis is that TCF7L2 regulates its downstream target genes in a tissue-specific manner, with a different cohort of target genes being turned on or off by TCF7L2 in each cell type. One way to test this hypothesis is to identify TCF7L2 target genes in a diverse set of cell types.
Previous studies have used genome-wide approaches to identify TCF7L2 target genes in human colon cancer cells [11, 12] and, more recently, chromatin immunoprecipitation sequencing (ChIP-seq) analysis of TCF7L2 was reported in hematopoietic cells [13]. In addition, TCF7L2 binding has been studied in rat islets and rat hepatocytes [14, 15]. However, to date no one study has performed comparative analyses of genome-wide binding patterns of TCF7L2 in diverse human cell types. We have now conducted ChIP-seq experiments and comprehensively mapped TCF7L2 binding loci in six human cell lines. We identified datasets of common and cell-specific TCF7L2 binding loci and a set of predicted TCF7L2-regulated enhancers (by comparing the TCF7L2 peak locations with ChIP-seq data for the active enhancer marks H3K4me1 (histone H3 monomethylated on lysine 4) and H3K27Ac (histone H3 acetylated on lysine 27)). We also predicted bioinformatically and confirmed experimentally that TCF7L2 co-localizes with cell type-specific factors. Finally, we showed that GATA3 (GATA binding protein 3), which co-localizes with TCF7L2 in MCF7 breast cancer cells, is required for recruitment of TCF7L2 to a subset of binding sites. Our studies reveal new insights into TCF7L2-mediated gene regulation and suggest that cooperation with other factors dictates different roles for TCF7L2 in different tissues.
Defining TCF7L2 genomic binding patterns
TCF7L2 binding sites and target genes
Total peaks
Nearest genes
Peaks per gene
Total unique
To determine the potential set of genes regulated by TCF7L2 in each cell type, we identified the closest annotated gene to each TCF7L2 binding site in the six different cell types and the closest annotated gene to the set of 1,864 common TCF7L2 binding sites. The number of target genes (as defined by the nearest gene to a TCF7L2 binding site) ranged from approximately 6,000 to 11,000 in the different cell lines (Table 1). In addition, we also observed that the number of target genes in each cell line was considerably less than the number of TCF7L2 binding sites, demonstrating that TC7L2 binds to multiple locations near each target gene (Table 1). Although less than 2% (1,864 of 116,270 peaks) of the total number of peaks were commonly bound by TCF7L2 in all 6 cell lines, 9% of target genes were common to all 6 cell lines (1,287 of 14,193 genes). This indicates that TCF7L2 regulates certain genes in different cell types using different binding sites. For example, there are 12 TCF7L2 binding sites near the SH3BP4 gene, but these sites are different in MCF7, HCT116, and PANC1 cells (Figure 2c).
TCF7L2 binds to enhancer regions
TCF7L2 binds to enhancer regions
Cell line
Percentage of TCF7L2 peaks at H3K4me1 sites
Percentage of TCF7L2 peaks at H3K27Ac sites
Percentage of TCF7L2 peaks at active enhancers (H3K4me1 and H3K27Ac)
To further investigate the role of TCF7L2 in cell type-specific enhancers, we determined the percentage of active enhancers in each of the six cell types (that is, genomic regions bound by both H3K4me1 and H3K27Ac) that are also bound by TCF7L2. We found that more than 40% of all enhancers in the different cell lines are occupied by TCF7L2 (Figure 3b). These results indicate that TCF7L2 ChIP-seq data identify many of the active enhancers in a given cell type and suggest that TCF7L2 may play a critical role in specifying the transcriptome in a variety of cancer cells. An example of TCF7L2 binding to sites marked by H3K4me1 and H3K27Ac in HepG2 cells is shown in Additional file 12; TCF7L2 does not bind to this same site in HeLa cells and these sites are also not marked by the modified histones in HeLa cells.
Motif analysis of genomic regions bound by TCF7L2
To investigate the predominant motifs enriched in TCF7L2 binding sites, we applied a de novo motif discovery program, ChIPMotifs [28, 29], to the sets of TCF7L2 peaks in each cell type. We retrieved 300 bp for each loci from the top 1,000 binding sites in each set of TCF7L2 peaks and identified the top represented 6-mer and 8-mer (Additional file 13). For all cell lines, the same 6-mer (CTTTGA) and 8-mer (CTTTGATC) motif was identified (except for HCT116 cells, for which the 8-mer was CCTTTGAT). These sites are almost identical to the Transfac binding motifs for TCF7L2 (TCF4-Q5:SCTTTGAW) and for the highly related family member LEF1 (LEF1-Q2:CTTTGA) and to experimentally discovered motifs in previous TCF7L2 ChIP-chip and ChIP-seq data [11, 30]. These motifs are present in a large percentage of the TCF7L2 binding sites. For example, more than 80% of the top 1,000 peaks in each dataset from each cell type contain the core TCF7L2 6-mer W1 motif, with the percentage gradually dropping to approximately 50% of all peaks (Additional file 14).
TCF7L2 cell type-specific modules
Cell line
Top four co-localized motifs
HNF4α, FOXA2, ERRα, PPARγ
TCF7L2 co-localizes with HNF4α and FOXA2 in HepG2 cells
GATA3 is required for TCF7L2 recruitment to a subset of sites in MCF7 cells
TCF7L2 functions as a repressor when tethered to the genome by GATA3
Genes repressed by TCF7L2 via a GATA motif
Cooperative repression by TCF7L2 and GATA3
TCF7L2 antagonizes GATA3-mediated activation
The TCF7L2 transcription factor has been linked to a variety of human diseases such as type 2 diabetes and cancer [3, 7–9, 35]. To investigate the mechanisms by which this site-specific DNA binding transcriptional regulator can impact on such diverse diseases, we performed ChIP-seq analysis for TCF7L2 in 6 different human cell lines, identifying more than 116,000 non-redundant binding sites, with only 1,864 sites being common to all 6 cell types. Several striking discoveries that came from our ChIP-seq analysis of the 6 different cell lines are: i) TCF7L2 has multiple binding sites near each target gene; ii) TCF7L2 has developed cell type-specific mechanisms for regulating a set of approximately 14,000 genes; iii) TCF7L2 binds to more than 40% of the active enhancers in each of the 6 cancer cell lines; and iv) TCF7L2 functions as repressor when recruited to the genome via tethering by the master regulator GATA3.
By analysis of the TCF7L2 ChIP-seq datasets from 6 different human cancer cell lines, we identified 116,270 TCF7L2 binding sites, with each cell type having approximately 25,000 to 50,000 TCF7L2 peaks. We note that another group has examined TCF7L2 binding in human HCT116 cells [12], identifying only 1,095 binding sites. It is not clear why Zhao and colleagues [12] identified such smaller numbers of TCF7L2 binding sites in HCT116 cells, but it is not likely due to the antibody specificity (the antibodies used in both studies give similar patterns on western blots). It is more likely that the 30-fold difference in peak number is due to the ChIP protocol. Zhao et al. [12] used protein A agarose beads, whereas we used magnetic protein A/G beads; we have found that protein A agarose beads produce low signals in many ChIP assays (unpublished data). Interestingly, the 116,270 TCF7L2 binding sites that we identified correspond to only 14,193 genes, with each target gene having an average of 8.2 TCF7L2 binding sites. Many of these binding sites are cell type-specific, as exemplified by the fact that there are only three to four TCF7L2 binding sites per target gene in any one cell type (Figure 2c).
Cell type-specific binding patterns suggest that TCF7L2 binds cooperatively to the genome along with cell type-specific factors. For example, the AP1 (activator protein 1) motif is enriched in the sets of HCT116-specific and MCF7-specific TCF7L2 binding sites. Interestingly, TCF7L2 has previously been shown to physically interact with JUN (which is one of the heterodimeric components of AP1) and it has been suggested that the JUN and TCF7L2 interaction is a molecular mechanism that integrates the activation of the TCF and CTNNB1 pathway by the JNK (Jun N-terminal kinase) pathway [36]. Although ChIP-seq data for AP1 components is not available for HCT116 or MCF7 cells, there are 7,400 genomic locations that are bound by TCF7L2 in HCT116 cells that are also bound by JUN in HeLa cells [11]; it is likely that a much larger number of co-localizing regions would be identified if the datasets were from the same cell type. Our detailed bioinformatic analysis of the HepG2-specific TCF7L2 peaks suggested that HNF4α and FOXA2 might be binding partners of TCF7L2 in this cell type. A previous study had shown that FOXA2 and HNF4α colocalize at a subset of sites in mouse liver [37], but that study did not examine the relationship of these sites with TCF7L2 binding. Therefore, we experimentally validated our bioinformatic prediction by comparing ChIP-seq data for all three factors. We found that greater than 50% of the TCF7L2 HepG2-specific binding sites are also bound by the liver transcription factors HNF4α and FOXA2, suggesting that this trio of factors cooperate in gene regulation. Based on the identification of motifs for all three factors in the TCF7L2 peaks, we suggest that TCF7L2, HNF4α, and FOXA2 all bind directly to the DNA, perhaps with the liver-specific factors helping to stabilize TCF7L2 genomic binding to particular enhancer regions in HepG2 cells. HNF4α and FOXA2 have been shown to be critical determinants of hepatocyte identity; Hnf4α plus Foxa1, Foxa2, or Foxa3 can convert mouse embryonic and adult fibroblasts into cells that closely resemble hepatocytes in vitro [38]. The induced hepatocyte-like cells had multiple hepatocyte-specific features and reconstituted damaged hepatic tissues after transplantation. Future studies should address a potential role of TCF7L2 in hepatocyte identity.
Specification of cell phenotypes is achieved by sets of master transcriptional regulators that activate the genes specific for one cell fate while repressing genes that specify other cell fates. The GATA factors, which include six site-specific DNA binding proteins that bind to the sequence (A/T)GATA(A/G), are master regulators that govern cell differentiation [39–44]. For example, GATA1-3 have been linked to the specification of different hematopoietic cell fates and GATA4-6 are involved in differentiation of cardiac and lung tissues. Also, GATA3 is the most highly enriched transcription factor in the mammary epithelium, has been shown to be necessary for mammary cell differentiation, and is specifically required to maintain the luminal cell fate [43, 44]. Studies of human breast cancers have shown that GATA3 is expressed in early stage, well-differentiated tumors but not in advanced invasive cancers. In addition, GATA3 expression is correlated with longer disease-free survival and evidence suggests that it can prevent or reverse the epithelial to mesenchymal transition that is characteristic of cancer metastasis [45]. Our studies show that TCF7L2 cooperates with the master regulator GATA3 to repress transcription in the well-differentiated MCF7 breast cancer cell line and suggest that a TCF7L2-GATA3 complex may be a critical regulator of breast cell differentiation.
Our finding that TCF7L2 co-localizes and cooperates in gene regulation with a GATA factor in MCF7 breast cancer cells is similar to a recent study of TCF7L2 in hematopoietic cells. Trompouki et al. [13] showed that in hematopoietic cells, TCF7L2 co-occupies sites with GATA1 and GATA2, which are master regulators of blood cell differentiation. Both the TCF7L2 motif and the GATA motif were found at the co-bound sites (suggesting adjacent binding of the two factors, not tethering) and TCF7L2 functioned as a transcriptional activator at those sites. In contrast, our studies indicate that co-localization of TCF7L2 with GATA3 in MCF7 cells is not due to adjacent binding but rather TCF7L2 is tethered to the genome by interaction with GATA3 binding to a GATA motif and that this tethering results in transcriptional repression. A study of Drosophila TCF binding to the Ugt36Bc upstream region indicated that TCF represses transcription of the Ugt36Bc gene by binding to non-traditional TCF motifs [46]. Interestingly, the three Ugt36Bc TCF sites (AGAAAT, AGATAA, AGATAA) are almost identical to the GATA3 motif. Blauwkamp et al. [46] suggest that the sequence to which TCF binds has an important function in determining whether a gene will be activated or repressed. Their studies did not address whether TCF bound directly to the GATA-like motifs. However, based on our studies, it would be worthwhile to investigate a possible genomic tethering mechanism of TCF by GATA factors in Drosophila.
Our studies reveal numerous new insights into TCF7L2-mediated gene regulation and suggest that TCF7L2 cooperates with other site-specific DNA binding factors to regulate transcription in a cell type-specific manner. Specifically, we show that TCF7L2 has highly cell type-specific binding patterns, co-localizes with different factors in different cell types, and can be tethered to the DNA by GATA3 in breast cancer cells. Our work, in combination with other studies [13, 47], suggests that TCF7L2 may play a critical role in creating and maintaining differentiated phenotypes by cooperating with cell type-specific master regulators such as HNF4α and FOXA2 in liver cells and GATA3 in breast cells. Both FOXA and GATA family members have been classified as pioneer factors, that is, transcription factors that can access their binding sites when other factors cannot, helping to create open chromatin to enable subsequent binding of other factors [48]. It is possible that FOXA2 and GATA3 serve as pioneer factors that enhance the ability of TCF7L2 to access its sites in liver and breast cells. In addition to having cell type-specific partners, there are many different isoforms of TCF7L2. Although the major isoforms of TCF7L2 are similar in most cell types, it is possible that minor isoforms contribute to the cell type-specificity of TCF7L2 binding via interaction of co-localizing proteins with alternatively encoded exons of TCF7L2. We anticipate that future studies employing isoform-specific antibodies to identify TCF7L2 binding sites in normal and diseased tissues will provide additional insight into the transcriptional networks that are altered in diseases such as type 2 diabetes, pancreatic cancer, and coronary artery disease.
Materials and methods
Cell culture
The human cell lines HCT116 (ATCC #CCL-247), HepG2 (ATCC # HB-8065), HEK293 (ATCC #CRL-1573), MCF7 (ATCC #HTB-22), HeLa (ATCC #CCL-2.) and PANC1 (ATCC #CRL-1469) were obtained from the American Type Culture Collection. HCT116 cells were grown in McCoy's 5A Medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin until 80% confluent, whereas HepG2, HEK293, MCF7, HeLa and PANC1 cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mM L-glutamine and 1% penicillin/streptomycin) until 75 to 90% confluent.
siRNA-mediated knockdown
All siRNAs were purchased from Dharmacon (Thermo Fisher Scientific-Dharmacon Products, Lafayette, CO, USA; ON-TARGET plus SMART pool - Human GATA3, TCF7L2 and Non-Targeting siRNA) and transfected using Lipofectamine™ 2000 Transfection Reagent according to the manufacturer's instructions (Life Technologies, Grand Island, NY, USA). Then, 48 to 56 h following transfection, cells were either crosslinked for ChIP assays or collected for RNA and protein extraction.
ChIP-seq assays
The antibodies used for ChIP-seq were: TCF7L2 (Cell Signaling Technology, Danvers, MA, USA; C48H11 #2569), GATA3 (Santa Cruz Biotechnology, Santa Cruz, CA, USA; #sc-268), H3K4me1 (Cell Signaling Technology, Danvers, MA, USA; 9723S lot1), and H3K27Ac (Abcam, Cambridge, MA, USA; Ab4729 lot #GR16377-1). The TCF7L2 antibody will detect both major isoforms of TCF7L2. See Additional file 2 for details of all ChIP-seq experiments. For all factor or histone modification and cell type combination, we performed duplicate ChIP-seq experiments using chromatin from two different cell culture dates. For the TCF7L2 ChIP-seq assays, 500 μg chromatin was incubated with 25 μg of antibody; for the GATA3 experiments, 600 μg chromatin was incubated with 50 μg of antibody; and for the histone ChIP-seq experiments, 10 to 12 μg chromatin and 8 to 10 μg of antibody were used. TCF7L2 and histone ChIP assays were performed as described previously [49] using protein A/G magnetic beads to collect the immunoprecipitates. GATA3 ChIP-seq experiments were performed using StaphA (Sigma-Aldrich, St. Louis, MO, USA) to collect the immunoprecipitates [50]. After qPCR confirmed enrichment of target sequences in ChIP versus input samples, libraries were created as previously described with minor modifications [49]. Gel size selection of the 200 to 500 bp fraction (TCF7L2 and histones) or the 300 to 600 bp fraction (GATA3) was conducted after the adapter ligation step, followed by 15 amplification cycles. qPCR (see Additional file 17 for a list of primers used in this study) was performed to confirm enrichment of targets in the libraries and then the libraries were analyzed using an Illumina GAIIx. Sequence reads were aligned to the UCSC human genome assembly HG19 using the Eland pipeline (Illumina).
ChIP-seq data processing
The BELT program [24] and Sole-search [11, 51] were used to identify peaks for TCF7L2 and for modified histones. We used the ENCODE overlap rules to evaluate the reproducibility of the two biological replicates for each factor or histone modification and cell-type combination. For this, we first truncated the peak lists of the two replicates for a given factor/cell-type combination so that both the A and B replicate peak list were the same length. Then, we overlapped the top 40% of the replicate A peak list with the entire replicate B peak list (and vice versa). ENCODE standards state that approximately 80% of the top 40% set should be contained in the larger set. After determining that replicate datasets met this standard (Additional file 4), we merged the two replicates and called peaks on the merged dataset. To determine if we had identified the majority of the TCF7L2 peaks in each cell type, we performed a saturation analysis. We randomly selected different percentages of the reads (10%, 20%, 30%,...,100%) from the merged datasets from the TCF7L2 ChIP-seq experiments for each cell line and called peaks using the BELT program; each merged dataset was analyzed three times. The number of peaks identified in each subset of the total reads was plotted to demonstrate that we had enough reads for each dataset to identify the majority of peaks (Additional file 7).
RNA was extracted using Trizol Reagent (Life Technologies) following the suggested protocol; 2 μg of each RNA sample was used with the Illumina TruSeq RNA Sample Prep Kit (catalogue number RS-122-2001) to make RNA libraries following the Illumina TruSeq RNA Sample preparation Low-Throughput protocol. Briefly, RNA was fragmented, then first-strand cDNA was prepared using the kit-supplied 1st Strand Master Mix and user-supplied Superscript III (Life Technologies, catalogue number 18080-051) followed by second strand cDNA synthesis. The Illumina protocol and reagents were used to complete the library preparation, with 12 cycles of PCR amplification. Libraries were sequenced using an Illumina GAIIx and analyzed as described in Additional file 3.
ChIP-qPCR assays
ChIP assays were performed as described in the ChIP-seq section, except that 30 μg equivalents of DNA was used for each ChIP reaction. The ChIP eluates were analyzed by qPCR using the Bio-Rad SsoFast™ EvaGreen® Supermix (catalogue number 172-5202) according to the manufacturer's instructions (Bio-Rad, Hercules, CA, USA).
Generation of TCF7L2 expression constructs and co-immunoprecipitation assays
TCF7L2 expression constructs were generated by PCR amplification of cDNA prepared from RNA isolated from MCF7 cell cultures and used for GATEWAY cloning into the pTRED-N-FLAG expression vector, which contains an amino-terminal FLAG tag. Control empty vector or an expression construct was transfected into MCF7 cells using Lipofectamine™ 2000 according to the manufacturer's instructions (Life Technologies); 36 h following transfection, cells were harvested and lysed in ice-cold NP-40 lysis buffer (phosphate-buffered saline, 0.25% NP-40, 0.1% sodium-deoxycholate, 2 mM phenylmethylsulfonyl fluoride (PMSF) and 10 μg/ml leupeptin and aprotinin) for co-immunoprecipitation assays. Following extraction on ice for 30 minutes and clarification by centrifugation, soluble protein extracts were diluted 1:10 with lysis buffer and incubated with either an anti-FLAG M2 agarose conjugated antibody (Sigma catalogue number A2220), an anti-GATA3 conjugated antibody (Santa Cruz HG3-31-AC), or a control rabbit IgG agarose conjugated antibody (Sigma catalogue number A2909) for 4 hours at 4°C. The beads were then washed four times and eluted with SDS-PAGE sample buffer prior to SDS-PAGE and western blot analysis using antibodies specific for GATA3 (Santa Cruz HG3-31) or FLAG (Sigma catalogue number A8592).
Data access
All data are publicly available via the UCSC Genome Preview Browser and/or has been submitted to the Gene Expression Omnibus (information concerning how to access the data is provided in Additional file 2).
activator protein 1
- bp:
base pair
- ChIP:
chromatin immunoprecipitation
catenin beta 1
forkhead box
GATA binding protein
- H3K27Ac:
histone H3 acetylated on lysine 27
- H3K4me1:
histone H3 monomethylated on lysine 4
hepatocyte nuclear factor
polymerase chain reaction
- qPCR:
quantitative PCR
- siRNA:
small interfering RNA
transcription factor 7-like 2.
The work was supported in part by 1U54HG004558 as a component of the ENCODE Project and by P30CA014089 from the National Cancer Institute. The HepG2 and HeLa H3K4me1 and H3K27Ac ChIP-seq data were generated at the Broad Institute and in the Brad Bernstein lab at the Massachusetts General Hospital/Harvard Medical School; the HNF4α and FOXA2 ChIP-seq data were produced in the lab of Rick Myers at the HudsonAlpha Institute for Biotechnology; the MCF7 H3K4me3 and RNA polymerase II ChIP-seq data were generated by the Iyer lab at UT-Austin. For these ChIP-seq datasets, data generation and analysis was supported, in part, by funds from the NHGRI as part of the ENCODE project. We thank Drs Bernstein, Myers, and Iyer and the Data Coordination Center at UCSC for providing access to these data. All other ChIP-seq data and the RNA-seq data from control and siRNA-treated MCF7 cells were generated by the Farnham lab at the University of Southern California; libraries were sequenced at the USC Epigenome Data Production Facility and at Stanford University.
Authors' Affiliations
- Poy F, Lepourcelet M, Shivdasani RA, Eck MJ: Structure of a human Tcf4-beta-catenin complex. Nat Struct Biol. 2001, 8: 1053-1057. 10.1038/nsb720.PubMedView ArticleGoogle Scholar
- Prokunina-Olsson L, Welch C, Hansson O, Adhikari N, Scott LJ, Usher N, Tong M, Sprau A, Swift A, Bonnycastle LL, Erdos MR, He Z, Saxena R, Harmon B, Kotova O, Hoffman EP, Altshuler D, Groop L, Boehnke M, Collins FS, Hall JL: Tissue-specific alternative splicing of TCF7L2. Hum Mol Genet. 2009, 18: 3795-3804. 10.1093/hmg/ddp321.PubMedPubMed CentralView ArticleGoogle Scholar
- Ravindranath A, O'Connell A, Johnston PG, El-Tanani MK: The role of LEF/TCF factors in neoplastic transformation. Curr Mol Med. 2008, 8: 38-50. 10.2174/156652408783565559.PubMedView ArticleGoogle Scholar
- Roose J, Clevers H: TCF transcription factors: molecular switches in carcinogenesis. Biochem Biophys Acta. 1999, 87456: M23-M37.Google Scholar
- Shitashige M, Hirohashi S, Yamada T: Wnt signaling inside the nucleus. Cancer Sci. 2008, 99: 631-637. 10.1111/j.1349-7006.2007.00716.x.PubMedView ArticleGoogle Scholar
- Grove EA: Wnt signaling meets internal dissent. Genes Dev. 2011, 25: 1759-1762. 10.1101/gad.17594311.PubMedPubMed CentralView ArticleGoogle Scholar
- Gambino R, Bo S, Gentile L, Musso G, Pagano G, Cavallo-Perin P, Cassader M: Transcription factor 7-like 2 (TCF7L2) polymorphism and hyperglycemia in an adult Italian population-based cohort. Diabetes Care. 2010, 33: 1233-1235. 10.2337/dc09-1690.PubMedPubMed CentralView ArticleGoogle Scholar
- Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, Helgason A, Stefansson H, Emilsson V, Helgadottir A, Styrkarsdottir U, Magnusson KP, Walters GB, Palsdottir E, Jonsdottir T, Gudmundsdottir T, Gylfason A, Saemundsdottir J, Wilensky RL, Reilly MP, Rader DJ, Bagger Y, Christiansen C, Gudnason V, Sigurdsson G, Thorsteinsdottir U, Gulcher JR, Kong A, Stefansson K: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet. 2006, 38: 320-323. 10.1038/ng1732.PubMedView ArticleGoogle Scholar
- Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, Segre AV, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, et al: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet. 2010, 42: 579-589. 10.1038/ng.609.PubMedPubMed CentralView ArticleGoogle Scholar
- Weedon MN: The importance of TCF7L2. Diabet Med. 2007, 24: 1062-1066. 10.1111/j.1464-5491.2007.02258.x.PubMedView ArticleGoogle Scholar
- Blahnik KR, Dou L, O'Geen H, McPhillips T, Xu X, Cao AR, Iyengar S, Nicolet CM, Ludaescher B, Korf I, Farnham PJ: Sole-search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data. Nucleic Acids Res. 2010, 38: e13-10.1093/nar/gkp1012.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhao J, Schug J, Li M, Kaestner KH, Grant SF: Disease-associated loci are significantly over-represented among genes bound by transcription factor 7-like 2 (TCF7L2) in vivo. Diabetologia. 2010, 53: 2340-2346. 10.1007/s00125-010-1852-3.PubMedView ArticleGoogle Scholar
- Trompouki E, Bowman TV, Lawton LN, Fan ZP, Wu DC, DiBiase A, Martin CS, Cech JN, Sessa AK, Leblanc JL, Li P, Durand EM, Mosimann C, Heffner GC, Daley GQ, Paulson RF, Young RA, Zon LI: Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration. Cell. 2011, 147: 577-589. 10.1016/j.cell.2011.09.044.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhou Y, Zhang E, Berggreen C, Jing X, Osmark P, Lang S, Cilio CM, Goransson O, Groop L, Renstrom E, Hansson O: Survival of pancreatic beta cells is partly controlled by a TCF7L2-p53-p53INP1-dependent pathway. Hum Mol Genet. 2012, 21: 196-207. 10.1093/hmg/ddr454.PubMedView ArticleGoogle Scholar
- Norton L, Fourcaudot M, Abdul-Ghani MA, Winnier D, Mehta FF, Jenkinson CP, Defronzo RA: Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism. Diabetologia. 2011, 54: 3132-3142. 10.1007/s00125-011-2289-z.PubMedView ArticleGoogle Scholar
- Osmark P, Hansson O, Jonsson A, Ronn T, Groop L, Renstrom E: Unique splicing pattern of the TCF7L2 gene in human pancreatic islets. Diabetologia. 2009, 52: 850-854. 10.1007/s00125-009-1293-z.PubMedView ArticleGoogle Scholar
- Weise A, Bruser K, Elfert S, Wallmen B, Wittel Y, Wohrle S, Hecht A: Alternative splicing of Tcf7l2 transcripts generates protein variants with differential promoter-binding and transcriptional activation properties at Wnt/beta-catenin targets. Nucleic Acids Res. 2010, 38: 1964-1981. 10.1093/nar/gkp1197.PubMedPubMed CentralView ArticleGoogle Scholar
- Hansson O, Zhou Y, Renstrom E, Osmark P: Molecular function of TCF7L2: Consequences of TCF7L2 splicing for molecular function and risk for type 2 diabetes. Curr Diab Rep. 2010, 10: 444-451. 10.1007/s11892-010-0149-8.PubMedView ArticleGoogle Scholar
- Le Bacquer O, Shu L, Marchand M, Neve B, Paroni F, Kerr Conte J, Pattou F, Froguel P, Maedler K: TCF7L2 splice variants have distinct effects on beta-cell turnover and function. Hum Mol Genet. 2011, 20: 1906-1915. 10.1093/hmg/ddr072.PubMedView ArticleGoogle Scholar
- Locke JM, Da Silva Xavier G, Rutter GA, Harries LW: An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes. Diabetologia. 2011, 54: 3078-3082. 10.1007/s00125-011-2290-6.PubMedPubMed CentralView ArticleGoogle Scholar
- Cuilliere-Dartigues P, El-Bchiri J, Krimi A, Buhard O, Fontanges P, Flejou JF, Hamelin R, Duval A: TCF-4 isoforms absent in TCF-4 mutated MSI-H colorectal cancer cells colocalize with nuclear CtBP and repress TCF-4-mediated transcription. Oncogene. 2006, 25: 4441-4448. 10.1038/sj.onc.1209471.PubMedView ArticleGoogle Scholar
- Duval A, Rolland S, Tubacher E, Bui H, Thomas G, Hamelin R: The human T-cell transcription factor-4 gene: structure, extensive characterization of alternative splicings, and mutational analysis in colorectal cancer cell lines. Cancer Res. 2000, 60: 3872-3879.PubMedGoogle Scholar
- Frietze S, Lan X, Jin VX, Farnham PJ: Genomic targets of the KRAB and SCAN domain-containing zinc finger protein 263. J Biol Chem. 2010, 285: 1393-1403. 10.1074/jbc.M109.063032.PubMedPubMed CentralView ArticleGoogle Scholar
- Lan X, Bonneville R, Apostolos J, Wu W, Jin VX: W-ChIPeaks: a comprehensive web application tool for processing ChIP-chip and ChIP-seq data. Bioinformatics. 2011, 27: 428-430. 10.1093/bioinformatics/btq669.PubMedPubMed CentralView ArticleGoogle Scholar
- Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K: High-resolution profiling of histone methylations in the human genome. Cell. 2007, 129: 823-837. 10.1016/j.cell.2007.05.009.PubMedView ArticleGoogle Scholar
- Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alverez P, Brockman W, Kim T-K, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE: Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature. 2007, 448: 553-560. 10.1038/nature06008.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh T-Y, Peng W, Zhang MQ, Zhao K: Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008, 40: 897-903. 10.1038/ng.154.PubMedPubMed CentralView ArticleGoogle Scholar
- Jin V, Apostolos J, Nagisetty NS, Farnham PJ: W-ChIPMotifs: a web application tool for de novo motif discovery from ChIP-based high throughput data. Bioinformatics. 2009, 25: 3191-3193. 10.1093/bioinformatics/btp570.PubMedPubMed CentralView ArticleGoogle Scholar
- Jin VX, O'Geen H, Iyengar S, Green R, Farnham PJ: Identification of an OCT4 and SRY regulatory module using integrated computational and experimental genomics approaches. Genome Res. 2007, 17: 807-817. 10.1101/gr.6006107.PubMedPubMed CentralView ArticleGoogle Scholar
- Hatzis P, van der Flier LG, van Driel MA, Guryev V, Nielsen F, Denissov S, Nijman IJ, Koster J, Santo EE, Welboren W, Versteeg R, Cuppen E, van de Wetering M, Clevers H, Stunnenberg HG: Genome-wide pattern of TCF7L2/TCF4 chromatin occupancy in colorectal cancer cells. Mol Cell Biol. 2008, 28: 2732-2744. 10.1128/MCB.02175-07.PubMedPubMed CentralView ArticleGoogle Scholar
- Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK: Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010, 38: 576-589. 10.1016/j.molcel.2010.05.004.PubMedPubMed CentralView ArticleGoogle Scholar
- Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W: Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996, 382: 638-642. 10.1038/382638a0.PubMedView ArticleGoogle Scholar
- Fasolini M, Wu X, Flocco M, Trosset JY, Oppermann U, Knapp S: Hot spots in Tcf4 for the interaction with beta-catenin. J Biol Chem. 2003, 278: 21092-21098. 10.1074/jbc.M301781200.PubMedView ArticleGoogle Scholar
- Hecht A, Stemmler MP: Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4. J Biol Chem. 2003, 278: 3776-3785. 10.1074/jbc.M210081200.PubMedView ArticleGoogle Scholar
- Hansen T, Ingason A, Djurovic S, Melle I, Fenger M, Gustafsson O, Jakobsen KD, Rasmussen HB, Tosato S, Rietschel M, Frank J, Owen M, Bonetto C, Suvisaari J, Thygesen JH, Petursson H, Lonnqvist J, Sigurdsson E, Giegling I, Craddock N, O'Donovan MC, Ruggeri M, Cichon S, Ophoff RA, Pietilainen O, Peltonen L, Nothen MM, Rujescu D, St Clair D, Collier DA, et al: At-risk variant in TCF7L2 for type II diabetes increases risk of schizophrenia. Biol Psychiatry. 2011, 70: 59-63. 10.1016/j.biopsych.2011.01.031.PubMedView ArticleGoogle Scholar
- Nateri A, Spencer-Dene B, Behrens A: Interaction of phosphorylated c-Jun with TCF4 regulates intestinal cancer development. Nature. 2005, 437: 281-285. 10.1038/nature03914.PubMedView ArticleGoogle Scholar
- Hoffman BG, Robertson G, Zavaglia B, Beach M, Cullum R, Lee S, Soukhatcheva G, Li L, Wederell ED, Thiessen N, Bilenky M, Cezard T, Tam A, Kamoh B, Birol I, Dai D, Zhao Y, Hirst M, Verchere CB, Helgason CD, Marra MA, Jones SJ, Hoodless PA: Locus co-occupancy, nucleosome positioning, and H3K4me1 regulate the functionality of FOXA2-, HNF4A-, and PDX1-bound loci in islets and liver. Genome Res. 2010, 20: 1037-1051. 10.1101/gr.104356.109.PubMedPubMed CentralView ArticleGoogle Scholar
- Sekiya S, Suzuki A: Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature. 2011, 475: 390-393. 10.1038/nature10263.PubMedView ArticleGoogle Scholar
- Bresnick EH, Lee HY, Fujiwara T, Johnson KD, Keles S: GATA switches as developmental drivers. J Biol Chem. 2010, 285: 31087-31093. 10.1074/jbc.R110.159079.PubMedPubMed CentralView ArticleGoogle Scholar
- Brewer A, Pizzey J: GATA factors in vertebrate heart development and disease. Expert Rev Mol Med. 2006, 8: 1-20.PubMedView ArticleGoogle Scholar
- Chou J, Provot S, Werb Z: GATA3 in development and cancer differentiation: cells GATA have it!. J Cell Physiol. 2010, 222: 42-49. 10.1002/jcp.21943.PubMedPubMed CentralView ArticleGoogle Scholar
- Patient RK, McGhee JD: The GATA family (vertebrates and invertebrates). Curr Opin Genet Dev. 2002, 12: 416-422. 10.1016/S0959-437X(02)00319-2.PubMedView ArticleGoogle Scholar
- Kouros-Mehr H, Bechis SK, Slorach EM, Littlepage LE, Egeblad M, Ewald AJ, Pai SY, Ho IC, Werb Z: GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell. 2008, 13: 141-152. 10.1016/j.ccr.2008.01.011.PubMedPubMed CentralView ArticleGoogle Scholar
- Kouros-Mehr H, Kim JW, Bechis SK, Werb Z: GATA-3 and the regulation of the mammary luminal cell fate. Curr Opin Cell Biol. 2008, 20: 164-170. 10.1016/j.ceb.2008.02.003.PubMedPubMed CentralView ArticleGoogle Scholar
- Yan W, Cao QJ, Arenas RB, Bentley B, Shao R: GATA3 inhibits breast cancer metastasis through the reversal of epithelial-mesenchymal transition. J Biol Chem. 2010, 285: 14042-14051. 10.1074/jbc.M110.105262.PubMedPubMed CentralView ArticleGoogle Scholar
- Blauwkamp TA, Chang MV, Cadigan KM: Novel TCF-binding sites specify transcriptional repression by Wnt signalling. EMBO J. 2008, 27: 1436-1446.PubMedPubMed CentralGoogle Scholar
- Verzi MP, Hatzis P, Sulahian R, Philips J, Schuijers J, Shin H, Freed E, Lynch JP, Dang DT, Brown M, Clevers H, Liu XS, Shivdasani RA: TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci USA. 2010, 107: 15157-15162. 10.1073/pnas.1003822107.PubMedPubMed CentralView ArticleGoogle Scholar
- Zaret KS, Carroll JS: Pioneer transcription factors: establishing competence for gene expression. Genes Dev. 2011, 25: 2227-2241. 10.1101/gad.176826.111.PubMedPubMed CentralView ArticleGoogle Scholar
- O'Geen H, Echipare L, Farnham PJ: Using ChIP-Seq technology to generate high-resolution profiles of histone modifications. Methods Mol Biol. 2011, 791: 265-286. 10.1007/978-1-61779-316-5_20.PubMedPubMed CentralView ArticleGoogle Scholar
- O'Geen H, Frietze S, Farnham PJ: Using ChIP-seq technology to identify targets of zinc finger transcription factors. Methods Mol Biol. 2010, 649: 437-455. 10.1007/978-1-60761-753-2_27.PubMedPubMed CentralView ArticleGoogle Scholar
- Blahnik KR, Dou L, Echipare L, Iyengar S, O'Geen H, Sanchez E, Zhao Y, Marra MA, Hirst M, Costello JF, Korf I, Farnham PJ: Characterization of the contradictory chromatin signatures at the 3' exons of zinc finger genes. PLOS One. 2011, 6: e17121-10.1371/journal.pone.0017121.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
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subset: commoncrawl


text: Seriously, I did not make that comparison, and when I heard it, I stated it was inappropriate, as did many on the news as well. Both sides will have their fringe elements that get all the media attention. I try not to judge by what a few wackos do on the news. One thing that really annoys me is when I see someone from my camp acting like a fool, giving all of us a blackeye. Thats why I started the thread on the moron toting an AR15 to a rally.


text:
As a child, Annie Dean's grandmother would encourage her granddaughter to practice handshakes and such polite phrases as "How do you do?" So it was inevitable, perhaps, that this month the 27-year-old Manhattan-ite launched The Elements of Style, a blog celebrating "etiquette, entertaining and everyday glamour."
There, purveyors of all things proper will find everything from classic cocktail recipes to cleaning tricks. Here, you'll find more interesting tidbits about Annie, such as why she favors unlocked doors and why there isn't an etiquette rule she wouldn't break.
When did your interest in the epistolary world begin?
My mother required me to send thank you notes since before I could sign my name. In the beginning, I would dictate. I also loved receiving letters from my grandmother even as a very little girl, but I could never read her cursive! The funny thing is my handwriting looks just like hers now.
Why do you enjoy writing correspondence?
I love to write. And I love the good things in life. Stationery and letter writing add loveliness to life for all types of people in all types of situations. When you take the time to write a letter you take the time to share something genuine of yourself, which isn't that common.
What is your favorite step in the process of written correspondence?
Dropping it in the mailbox!
If you could be pen pals with anyone in history, to whom would you write and what would you say?
Probably Mozart. I'd ask what it sounds like in his head. Does he hear the instruments one at a time? Or is it a symphony right from the start? Is it loud? Does he hear it in spurts? I'd like to talk to a lot of people, though. I have a lot of questions.
To whom do you most often write?
Well now, to my readers on The Elements of Style. But in terms of handwritten notes, I send thank you notes to all sorts of people all the time. Many notes of thanks for dinners or little gifts (we entertain a lot so we receive many). I probably send two per week.
Describe the most memorable letter you have ever received.
My husband and I met because we were both tenants in the same building (our doorman set us up!). At that time I was in law school and always in and out, and had a tendency to leave my apartment door unlocked. In the first month that we started dating, Peter rushed out to buy Crane stationery (he thought it was the most classic!) and a calligrapher's pen and practiced writing script. I found the scrap paper with a cursive alphabet! He would write me little notes and leave them in my apartment, sometimes with flowers or little presents. I know I should have locked my door, but after that I just couldn't bring myself to make it a habit!
What makes a particular letter stand out from a stack of cards?
Oh you can tell right away when it's a 'real' letter, can't you! A 'real' letter on true stationery is a heavy enough weight that you can't see through to the contents inside. The paper is much nicer than the rest of the envelopes and junk mail stuffed into your mailbox. It isn't loud or trying to grab your attention. And so you notice it in an instant.
Do you have a favorite stamp or stamp series?
I'm a sucker for anything that features a President or a First Lady. There is a Miles Davis/Edith Piaf series out right now that I adore.
What makes your correspondence distinct?
I'm not a "Dear David, Thank you! Love, Annie" kinda gal. I really like to spend the time to write a real letter each time I send out something in the mail. I also have a very specific way of signing the return address on the back of each envelope, using a signature of my husband's last name and our address printed in capital letters.
What do you think classic correspondence will look like in a decade or two?
I think that as we move into a more overtly digital world, tangible luxuries will come into greater favor. I couldn't live without the Internet, but there is something so special about buying stationery, thinking about a note, writing a letter, signing it. I think more and more people will connect with writing things in ink as time goes on. We'll be desperate for permanency.
What is the one etiquette rule you will never break?
Rules are made to be broken. The purpose of etiquette is to learn how to break them with grace.
Have a question for Annie? Email our Crane Concierge at email@example.com.


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Olga Bakawa
MADISON - Olga Bakawa, age 96, left this world peacefully on February 26, 2013 at her last home, Rest Haven Care Center, Verona, Wis. Her daughter Lois and son-in-law Charles were with her.
She was preceded in death by her beloved husband, Michael, parents, siblings, and other relatives. She is survived by her children Lois Evenson (Charles), Robert Bakawa (Fanny), grandchildren Sandra Beyer (Howard), Andrew Evenson (Paula), Amber Evenson (Andrew Dean) and great grandchildren Haley, Delaney, Libbey, and Charles. She is survived by her dear friend Hildegard Fischer whose strength and faith sustained her daughter through this final journey. The family is deeply indebted to the wonderful care she received at Rest Haven, where the staff and residents had each become her loving extended family.
A Mass of Christian Burial will be held at ST. THOMAS AQUINAS CATHOLIC CHURCH, 602 Everglade Dr., Madison on Saturday, March 2, 2013, at 11:00 a.m. Burial will follow at Resurrection Cemetery. A visitation will be held at the church on Saturday from 10:00 a.m. until the time of mass.


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Matrimony is a civil and indissoluble contract between a consenting man and woman of competent capacity.
These marriages are prohibited:—A widower with his deceased wife's sister; a widow with the brother of her deceased husband; a widower with his deceased wife's sister's daughter, for she is by affinity in the same degree as a niece to her uncle by consanguinity; a widower with a daughter of his deceased wife by a former husband; and a widower with his deceased wife's mother's sister. Consanguinity or affinity, where the children are illegitimate, is equally an impediment.
A lunatic or idiot cannot lawfully contract a marriage, but insanity after marriage does not make the marriage null and void.
A lunatic may contract a marriage during a lucid interval. Deaf and dumb people may marry by signs.page: 5
The consent of the father or guardians is necessary to the marriage of an infant ( i.e. id est , a person under twenty‐one), unless the marriage takes place by banns. The consent of the mother is not necessary if there be a father or a guardian appointed by him.
A second marriage while a husband or wife is living is felony, and punishable by transportation.
An agreement to marry made by a man and woman who do not come under any of these disabilities is a contract of betrothment, and either party can bring an action upon a refusal to complete the contract in a superior court of Common Law.
Marriages may be celebrated as a religious ceremony after the requisite public proclamations or banns, or as a secular form.
The object of the Act* for authorizing civil marriages was to relieve Dissenters and those who could not conscientiously join in the formulary of the Church. Due provision is made for necessary publicity, and the marriage can be legally contracted in a Register Office.
Marriages in the Church of England (without banns or licence), marriages of Quakers, Jews, Dissenters, and Roman Catholics, and marriages according to the civil or secular form, must be preceded by a given notice from of the parties to the Superintendent‐Registrar of the district.
The marriage law of Scotland is founded upon the Canon Law ( i.e. id est , rules drawn from Scriptures and the writings of the Church). In Scotland there are regular and irregular marriages. Irregular marriages are legal without any ceremony, and are of three sorts.
1. By a promise of marriage given in writing or proved by a reference to the oath of the party, followed by consummation.
2. By the solemn mutual declaration of a man and woman, either verbally or in writing, expressing that the parties consent to take each other for husband and wife.
3. By notorious cohabitation as man and wife.
Persons living in England and having illegitimate
6th and 7th of Wm. IV. chap. 85.
page: 6 children, cannot by going to Scotland, there marrying, and then returning, legitimatize their children in England. A domicile (or abiding home) in Scotland, and a marriage of the father and mother, legitimatizes the children in Scotland whenever born.
Lawful marriages in foreign countries are valid in England unless they are directly contrary to our laws.
Marriage with a deceased wife's sister is valid in England, if it has been celebrated in a country where such marriage is legal, provided the parties were at the time of the marriage domiciled in such country.
Married women no legal existence.
A man and wife are one person in law; the wife loses all her rights as a single woman, and her existence is entirely absorbed in that of her husband. He is civilly responsible for her acts; she lives under his protection or cover, and her condition is called coverture.
A husband has a right to the person of his wife.
A woman's body belongs to her husband; she is in his custody, and he can enforce his right by a writ of habeas corpus.
Her personal property becomes his.
What was her personal property before marriage, such as money in hand, money at the bank, jewels, household goods, clothes, &c., becomes absolutely her husband's, and he may assign or dispose of them at his pleasure whether he and his wife live together or not.
A wife's chattels real ( i.e. id est , estates held during a term of years, or the next presentation to a church living, &c.) become her husband's by his doing some act to appropriate them; but, if the wife survives, she resumes her property.
Equity is defined to be a correction or qualification of the law, generally made in the part wherein it faileth, or is too severe. In other words, the correction of that wherein the law, by reason of its universality, is deficient. While the Common Law gives the whole of a wife's personal property to her husband, the Courts of Equity, when he proceeds therein to recover property in right of his wife, oblige him to make a settlement of some portion of it upon her, if she be unprovided for and virtuous.
If her property be under 200 l. pound , or 10 l. pound a‐year, a Court of Equity will not interpose.
Neither the Courts of Common Law nor Equity have any page: 7 direct power to oblige a man to support his wife,—the Ecclesiastical Courts ( i.e. id est Courts held by the Queen's authority as governor of the Church, for matters which chiefly concern religion) and a Magistrate's court at the instance of her parish alone can do this.
His power over her real property.
A husband has a freehold estate in his wife's lands during the joint existence of himself and his wife, that is to say, he has absolute possession of them as long as they both live. If the wife dies without children, the property goes to his heir, but if she has borne a child, her husband holds possession until his death.
A married woman's earnings not her own but her husband's.
Money earned by a married woman belongs absolutely to her husband; that and all sources of income, excepting those mentioned above, are included in the term personal property.
By the particular permission of her husband she can make a will of her personal property, for by such a permission he gives up his right. But he may revoke his permission at any time before probate ( i.e. id est the exhibiting and proving a will before the Ecclesiastical Judge having jurisdiction over the place where the party died).
A mother's rights over children.
The legal custody of children belongs to the father. During the life‐time of a sane father, the mother has no rights over her children, except a limited power over infants, and the father may take them from her and dispose of them as he thinks fit.
If there be a legal separation of the parents, and there be neither agreement nor order of the Court, giving the custody of the children to either parent, then the right to the custody of the children (except for the nutriment of infants) belongs legally to the father.
A married woman cannot sue or be sued for contracts—nor can she enter into contracts except as the agent of her husband; that is to say, her word alone is not binding in law, and persons giving a wife credit have no remedy against her. There are some exceptions, as where she contracts debts upon estates settled to her separate use, or where a wife carries on trade separately, according to the custom of London, &c.
A husband is liable for his wife's debts contracted before page: 8
band for his wife's debts prior to marriagemarriage, and also for her breaches of trust committed before marriage.
Neither a husband nor a wife can be witnesses against one another in criminal cases, not even after the death or divorce of either.
A wife cannot bring actions unless the husband's name is joined.
A wife acts under coercion of her husband.
As the wife acts under the command and control of her husband, she is excused from punishment for certain offences, such as theft, burglary, housebreaking, &c., if committed in his presence and under his influence. A wife cannot be found guilty of concealing her felon husband or of concealing a felon jointly with her husband. She cannot be found guilty of stealing from her husband or of setting his house on fire, as they are one person in law. A husband and wife cannot be found guilty of conspiracy, as that offence cannot be committed unless there are two persons.


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I just received our Christmas cards from Paper Culture ... and I'm in LOVE! I don't know about you, but I haven't ordered Holiday Greeting cards in years because I'm a bit lazy and have been a bit intimidated by going online to find a layout I liked, decide which photos I want to use, and the wording to go along with it. But, I'm so glad I found Paper Culture! It was so easy to go in and choose, plunk my photos in, and write a little note. Some layouts don't require any writing at all, but I wanted this layout that had space for a personal message. I am so impressed with their delivery and packaging. Our holiday greeting cards came in this cute little box... They even included a … [Read more...]
Ordering Holiday Greeting Cards – Paper Culture is So Easy to Order From!!
November 17, 2012 by 2 Comments


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By JB Clark/NEMS Daily Journal
TUPELO – Joni Johnson volunteers to help women in violent relationships because two years ago she was a victim of dating violence.
In September of 2011, 33-year-old Johnson of Baldwyn packed her children and pets into a friend's car and left Dallas for a new life in Mississippi, free of her abusive boyfriend.
"I was in a violent situation that I didn't see coming and by the time I realized it, (my boyfriend) had cut me off from all of my friends and family," Johnson said. "We got along great and moved in together and then all of a sudden he starting controlling everything I did – who I talked to and what I was wearing."
Johnson said because she had separated herself from her friends and family at her boyfriend's behest, and because he convinced her she was worthless, she didn't know where to go.
Luckily, she kept in touch with one friend and that person came to the rescue.
"My friend and her mother got some money together and drove over to pick me up," she said. "I've got kids. I had dogs. It's like a whole family they had to take on when they took me."
The friend's mother volunteered at S.A.F.E. in Tupelo, and now Johnson does too.
S.A.F.E. is a shelter and resource center for victims of domestic violence and sexual assault.
"They told me about it and I wanted to be as much a part as I can because they do help people," she said. "They've helped me to get my feet on the ground."
More than two years later, Johnson is finishing her associate's degree at Itawamba Community College and enrolled to start her bachelor's in social work at the University of Mississippi.
"He told me I wasn't worth anything – that I'm stupid," she recalled of the abusive boyfriend. "And he had me believing it for a little bit, but I graduate in May and made the president's list with five As. I'm anything but stupid."
Johnson said dating violence and domestic violence are hard to talk about because victims often feel foolish for letting themselves be victims.
The abuse started slowly and happened over time until she felt trapped, Johnson said.
"It's easy to see all the signs when you look back on it but not when it's happening," she said.
Now, she's helping to organize the Silence Hides Violence 5k race to raise money for S.A.F.E. and promote dating abuse awareness.
What is dating violence?
Almost 1.5 million high school students in America experience physical abuse from the person they are dating each year, according to LoveIsRespect.org. In adolescents, 1 in 3 is a victim of physical, sexual, emotional or verbal abuse from the person they're dating.
Of all teens in a violent relationship, only 33 percent will report it.
Amelia Parkes, community educator for S.A.F.E., said 10 of the most common sign of abuse from a dating partner are:
• Checking your cellphone or email without permission.
• Constantly putting you down.
• Extreme jealousy or insecurity.
• Explosive temper.
• Isolating you from family or friends.
• Making false accusations.
• Mood swings.
• Physically hurting you in any way.
• Possessiveness.
• Telling you what to do.
Anyone who needs help leaving an abuser can call S.A.F.E.'s 24-hour hotline at (800)527-7233.


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|Classic Atlantic Salmon No pursuit rivals salmon rivers, flies & legacy
|Topic Review (Newest First)
|Gary W
I know, it's a slow process buying anything on Ebay unless you want to put in crazy bids.
Unfortunately, to buy JC from a shop also means paying too much in my opinion. I've tried countless searches on the internet and drawn a bit of a blank on quality capes for a reasonable price.
You could try emailing the Glasgow Angling Centre to see if they could email you a photograph of the different quality capes they sell. I think the price ranges from around £25 to £50. However, I always like to select tying materials by hand to make sure I get what I am looking for.
I'm sure you've already tried it, but if you do a search for - "jungle cock" cape - on google and select the UK only box, you will find a few suppliers. However, they are not cheap and there is no guarantee of quality.
Like Juro said, Fishermans Feathers have a supply and I think they can be trusted on quality.
Personally, I wouldn't opt for the best capes for anything other than display flies.
|You should look up "fishermens feathers" - we used to do bulk purchases with our own CITIES certificate but it's expired now.
|Gary I have been looking on Ebay and there are some good capes on there but it is a slow process of getting one unless I want to pay well over the odds. I have been putting good bids on in the last few seconds only to get outbid. May try and contact some of the sellers and try to buy direct ??
|Gary W
Glasgow Angling Centre sell JC Capes. However, capes vary greatly in number, colour, size, of feather, and I would suggest that mail order is not the way to go if you are particular about the colour and shape of feather you want.
I too have struggled to get capes at decent prices and quality over the last two or three years. The last cape I bought was very good quality and at a reasonable price; I got it from a seller on Ebay. The advantage of this was the seller provided a picture of the actual cape before I bought it.
Jungle Cock in the UK
Can anyone in the Uk give me details of anywhere that I can get a good quality jungle cock cape from. Most places I have found either sell small packets of feathers or the substitute which look cr*p. None of my local shops can get hold of it so it looks like it will have to be mail order.
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Room 309 in the Frist Campus Center served as the "crisis room" for a session of the Princeton Interactive Crisis Simulation, a high-tech version of a Model United Nations conference run by Princeton students. From the crisis room, Princeton student liaisons communicated with delegates from other institutions situated in 11 rooms around Frist.
At left: Senior Sashank Rishyasringa, one of the founders of the Princeton conference, served as this year's "mastermind," leading the efforts to devise various crisis scenarios around the Middle East.
Photos: John Jameson
Featured Story
Students manage Middle East crises at high-tech Model United Nations
Posted March 6, 2006; 03:10 p.m.
Each time the door to room 309 opened, the late-afternoon quiet of the Frist Campus Center was shattered by the din of 30 Princeton students engulfed by crises in the Middle East.
The Princeton Interactive Crisis Simulation (PICSim), a high-tech, student-run version of a Model United Nations conference, was in mid-session on Friday, March 3. Frist 309 was the "crisis room," where the Princeton students huddled around laptop computers to communicate with committees of delegates situated in 11 rooms around the building, representing various Middle Eastern nations and the United States.
The numerous crises at play included the bombing of a cruise ship in the Suez Canal, an assassination attempt on Pakistan's president, a threat by Iran to move its nuclear facilities and negotiations over oil transport routes through Afghanistan. Like traders on the floor of a stock exchange, the student "masterminds" concocting the various scenarios barked out additional details to be communicated to the delegates:
"I want Iranian operatives caught!"
"Syria has begun mobilizing!"
"Hezbollah is bombing Jordan!"
In total, more than 240 students -- including roughly 80 from Princeton -- participated in the March 2-5 conference, which was organized by the student-run International Relations Council. Other participants came from 14 colleges and universities in the United States, Canada and Germany.
According to conference organizers, the Princeton event is unique among Model U.N. programs because of the student-designed software that enables the far-flung groups of participants to communicate with each other in real-time to analyze and solve problems.
Taking a quick break from the action, sophomore Kayvon Tehranian, the conference's chief of staff, pointed to sophomore Emily Norris, liaison to the Iranian delegation, working on her laptop. "She's communicating with our Iranian chair," he said. "In that committee, they have the defense minister, foreign minister, interior minister, oil minister -- all the cabinet members. They deliberate on the issues, communicate with the Princeton student running that committee, and it's relayed to us. It's a very elaborate communication channel."
Now in its third year, the interactive simulation was developed by students who had participated in Model U.N. conferences and felt "constrained" by their more traditional format, according to chair Luke Goodwin, a sophomore.
"The options available to committees at PICSim include the whole spectrum of economic, social, political, diplomatic and military policy choices," Goodwin said. "Also addressed is the influence of non-state actors such as rebel groups, NGOs [nongovernmental organizations], terrorists, private economic interests and the news media in international politics."
Personifying many of the characters involved in the scenarios was sophomore Michael van Landingham, who shuttled in and out of Frist 309 in a variety of costumes. He and junior Will Wachter, the conference's media director, produced numerous videos and other communications to provide delegates with updates on hostage situations and other escalating incidents around the Middle East.
"We have done news reports and terrorist intelligence meetings," he said. "I also have done voice clips and live chats with some of the committees as characters who have intelligence information."
Following news of terrorists seizing a cruise ship in the Suez Canal, freshman Jessica Frey tried to sort out the details in her role as crisis communications liaison for Egypt.
"The Americans were trying to help Egypt get it out of the canal. They tried to send in the Marines to take over the ship and get the hostages out, but unfortunately the whole ship was wired with explosives and blown up," she said. Reviewing messages from her committee members, Frey noted, "There was some discrepancy in what the news said, and now they're trying to figure out what the U.S. said."
As the "Global News Report" team to her left rushed to post another breaking news update, Frey said of the conference, "It's really fun, but it can be kind of frustrating at times. I guess this gives you an idea of how crazy making decisions in a split second can be."
Tehranian, the chief of staff, and senior Sashank Rishyasringa, a conference co-founder and this year's lead "mastermind," noted in a summary written for conference participants that "several delegates felt overwhelmed at the pace of events in the Middle East, and especially, the ability for situations to escalate and spin out of control."
"They did, however, with confidence and clarity articulate clear policy directives at each of these junctures; most importantly, they demonstrated a knowledge of existing Middle Eastern geopolitics and political relations that both enabled to them to achieve a very precise level of decision-making [and] set up head-on collisions between several of the countries in the simulation," the organizers wrote.


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Vail's gondola opens up this weekend (June 3-5) and with a bit of snow still up on the top of Vail Mountain, they are opening up the tubing hill and the kids snowmobiling area. Don't worry, down in town it is all green and the flowers are out, but YES, us locals are a bit sick of the snow up on our mountains. The climbing wall and bungee trampoline are also open. The gondola will run from 10am – 6pm and then the tubing and snowmobiling are available 11am – 5pm. If you signed up for an Epic Pass for next year, your current pass will get you up.
Tubing $25
Tubing + Lift $39
Tubing + Lift +Lunch $44


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The General Assembly is IDF's general guiding body. It normally meets every two years at the same time as the World Diabetes Congress, unless a special meeting is convened by the IDF President or the General Assembly itself.
The General Assembly determines the policies and activities of IDF and has the power to:
- admit and terminate the Members of IDF;
- elect (from the potential candidates put forward by the Nominating Committee) and terminate the Board of Directors members ;
- approve the election of Regional Chairs and Regional Chairs-Elect;
- elect the Nominating Committee;
- approve the changes to the Articles of Association and to the Standard Operating Procedures;
- approve the budget and annual audited accounts;
- appoint and terminate the auditors;
- decide upon dissolution and liquidation of IDF.
The General Assembly is composed of the following persons, who are referred to as "Members of the General Assembly":
- the members of the Board of Directors (President, President-Elect, Vice-Presidents and Regional Chairs)
- Delegates of each Member
Observers, who have no voting rights, are invited to attend the General Assembly (for example, Honorary Presidents, Provisional Members or Committee Chairs).


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There's a reason bare-knuckle boxing was banned in the earliest years of the 20th century.
It was a savage "sport" that exacted a grim toll among its practitioners.
The NHL is the only team sport that allows fighting. To the delight of Don Cherry and his minions, "character players" (translation: big hearts, limited skills) drop their gloves and try to beat other's brains in.
How much longer?
(In a Reuters photo, Brian McGrattan lands a haymaker on Wade Belak)
• Red Fisher weighs in on Wade Belak
• Pat Hickey on the hard life of NHL enforcers
• Comments on Belak tragedy from from Stu Hackel, Bruce Arthur, Bob McKenzie, J.T., Cathal Kelly
• Canucks get proactive on mental health
• Fantasy Focus on Mathieu Darche
• Guess they like the Caps: THN picks Penguins as runners-up
•Byfuglien busted for drunk boating


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St. Croix Legend Salt Conventional Rod
- This item can only be shipped to U.S. addresses.
- Additional discounts do not apply.
Lightweight, ultra-sensitive, and super-strong
Alps marine-grade aluminum reel seat and gimbal
Fuji HB saltwater guides with SiC rings
High-density nylon slick butt and EVA foregrip
The Legend Salt Conventional Rod from St. Croix is an incredibly lightweight offshore saltwater rod packed with the most advanced technology for unbeatable performance. A premium-quality SCII graphite blank with NSi resin provides for an ultra-lightweight feel and extreme sensitivity. St. Croix's exclusive Integrated Poly Curve (IPC) tooling technology for continuous-curve tapers provide unparalleled casting smoothness. Advanced Reinforcing Technology (ART) adds hoop strength where needed without adding weight for jaw-breaking hooksets and fighting oversized fish.
• Fuji HB saltwater guides with SiC rings and gunsmoke frames.
• Alps Triangular marine-grade aluminum reel seat with hard-anodized finish.
• Alps marine-grade aluminum gimbal with hard-anodized finish.
• High-density nylon slick butt and premium EVA foregrip.
• Two coats of Flex Coat slow-cure finish.
• Lifetime limited warranty backed by St. Croix Superstar Service.


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Web Stories
Massey to deliver President's Lecture on immigration
Posted November 5, 2009; 04:34 p.m.
Douglas Massey, Princeton's Henry G. Bryant Professor of Sociology and Public Affairs, will deliver the second talk in this year's President's Lecture Series, titled "America's War on Immigrants: Causes, Consequences and Solutions" at 4:30 p.m. Thursday, Dec. 10, in 101 Friend Center.
Massey studies international migration, race and housing, discrimination, education, urban poverty and Latin America. In his lecture, Massey will address U.S. border enforcement efforts from the 1980s to the present. He will argue for a new course based on a philosophy of immigration management rather than immigrant repression, following the successful model of economic integration under the European Union.
Massey earned his Ph.D. in sociology from Princeton in 1978 and joined the faculty of the Department of Sociology and the Woodrow Wilson School of Public and International Affairs in 2003. His books include "Return of the L-Word: A Liberal Vision for the New Century" and "Strangers in a Strange Land: Humans in an Urbanizing World."
The President's Lecture Series, inaugurated in 2001, brings together faculty members from different disciplines to learn about the work others are doing in a variety of fields. Michael Oppenheimer, the Albert G. Milbank Professor of Geosciences and International Affairs, will deliver this year's final talk at 4:30 p.m. Thursday, March 4, in 101 Friend Center. The talks will be webcast; viewing information will be available online.


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5.11 Tactical Products in Canada
We only ship to Canadian & U.S. addresses. U.S. Orders by PayPal only.
Click to skip to: Pants, Shorts, Shirts, T-Shirts, Vests, Jackets & Outerwear, Women's, Footwear, Hats, Gloves, Socks, Belts, Sunglasses & Watches, Morale Patches, Bags & Packs, Pouches & Accessories, Flashlights, Knives
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Campus History
Columbia College-Patrick Air Force Base was established in 1999 to be an integral part of Patrick Air Force Base 45th Mission Support Group's educational plan. Today it continues to serve civilian and military adult learners in the area.
Columbia College-Patrick Air Force Base is part of Columbia College's network of nationwide campuses. The first extended campus was founded in St. Louis in 1973 after an Army education services officer was interested in providing courses to Army recruiters in the area.
Today, the Division of Adult Higher Education at Columbia College includes 30 campuses, including one in Guantanamo Bay, Cuba. About half of Columbia College's nationwide campuses are on military bases. The Online Campus at Columbia College also serves students in the Patrick Air Force Base area.
Columbia College-Patrick Air Force Base is part of the college's extended network of more than 35 Nationwide Campuses across the country, including 18 on military bases.
Degree programs at the extended campuses vary. However, no matter which degree you pursue or which campus you attend, degree programs meet the same accreditation standards as degree programs from the main campus in Columbia, MO, as well as meet requirements set by the respective state education departments.Columbia College was founded in 1851 in Columbia, MO, as Christian Female College, the first women's college west of the Mississippi River to be chartered by state legislature. In 1970, the college was renamed Columbia College when it opened its doors to men and women. In 1973, the college began educating adult learners. Today, the college serves nearly 25,000 students nationwide each year.
Read more about Columbia College history.


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kygobbler wrote:This story also reminds me something that has always confussed me. On fish you have two limits, you have the creel limit and possession limit. The possession limit is always double of the creel. Does the possession limit mean that is all you can have in your freezer? Or lets say there are 3 guys in a boat and the creel limit is 30 and the possession limit is 60 does that mean that the guys can not catch over 60 fish instead of 90?
This has always confused me and no one has ever gave me the explantion because Ive heard it both ways. Maybe one of you guys can explain this to me.
I don't think anyone answered your question.
FWIW a lot of small game has possession limits too.
In most states that I know of possession limit means the total number you can have at one time anywhere. With you while on a hunt, in your cabin, or in your freezer at home. I have heard of one state, Idaho, that a guy said possession limit did not apply once you got back home and had the game or fish in your freezer. I have not confirmed that and I have my doubts.
In your example of the 3 guys in the boat with a daily limit of 30 and possession limit of 60...Each man can catch 30 fish in one day and then he must stop keeping fish. They can each keep a total of 60 fish if they fish more than 1 day, so 3 guys could have 180 fish total for their combined possession limit as long as they fish multiple days. However in most states each guy has to catch his own fish.
As for small game lets take pheasant. In Colo the daily limit is 3 and possession limit is 3 tines the daily limit so thats 9 pheasants you can keep on hand. In Kansas the daily limit on pheasants is 4 and the possession limit is 4 times the daily so you can have 16 pheasants in your freezer.
Now lets just throw a wrench in all this just for fun...eh? :D For some reason gallinules (rails and coots) have the possession limit the same as the daily limit in many states. In Colo you can shoot 25 rails a day but only have 25 in possession. They are a migratory bird and are federally regulated so maybe that has something to do with it.


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photo: farmers market radishes by hannah queen
since we've been traveling this week (and i haven't been in the kitchen), i thought i might share with you a few tips on how we make traveling vegan easy. at first it takes a little thought and planning ahead, but it soon becomes like second nature (i promise!).
1) plan ahead. take some time before your trip to pack some snacks that are both easy to grab and really healthy. if you're flying, you can take any of your own food on the plane, as long as it's not liquid. you can either purchase these snacks or make them yourself, but here are some of my favorites: granola, ginger snaps, blueberries, trail mix, whole fruit and dried fruit (mango is my favorite!).
2) ask. the number one thing you can do while traveling or visiting a new restaurant is just ask what they have or what what they can make vegan. just this week i discovered two restaurants that actually had separate vegan menus, just by asking! even if there's nothing vegan on an entire menu, they can usually always make something for you pretty easily. pasta dishes, vegetable plates, hearty salads, and baked potatoes loaded with veggies are almost always an option!
3) do your research. sometimes during travel you just have to eat on the go (especially on layovers) at places you wouldn't ordinarily eat. just by doing a little research, you can find several restaurants that offer vegan eats (even though they may not know it!). auntie anne's salted pretzels are vegan if you just ask for one without the butter. starbucks has really good hot oatmeal and bagels that fit the bill. brixx pizza and mellow mushroom both have great options (and veg cheese) and jamba juice is possibly one of the easiest/healthiest places to stop.
4) eat at a health food store. this is a 'bonnie and dave' classic. lots of times we'll just swing by whole foods (or another local health food store) and eat at their hot bar. it's always totally amazing! plus, while we're there we can stock up on goodies for the next day.
5) travel with a plan. this is especially fun when you're road tripping. by doing a little research on restaurants, you can literately plan your stops around which cities have the best veg fare! (call us nerds, but this is one of our favorite things to do.) we love to use the happy cow app and the google maps app to find the best veg restaurants from city to city.
do you have any tips on traveling veg? share with us in the comments section!


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Hi, my blog is www.princessandtherock.com. It is only about 2 weeks old, so I'll appreciate some followers. :) Thank you.
Hi Felicia and welcome! I just subscribed to your blog posts and am looking forward to reading more! My blog can be found at http://simplyathomemom.com/
FB https://www.facebook.com/SimplyAtHomeMom
Twitter @SimplyAtHomeMom
Pinterest http://pinterest.com/brazil820/
Welcome! I'd love to know the story about the title of your blog. I love how we bloggers come up with our names. I'll be sure to check you out! Hop on over to my blog if you'd like.
twitter: @PursuitOfNormal
I followed your blog! Would love if you can reciprocate.
Hi Melissa, welcome! Your babies are soo adorable. I am now following your blog. Please stop by and follow me at http://simplyathomemom.com/
FB https://www.facebook.com/SimplyAtHomeMom
Twitter @SimplyAtHomeMom
Pinterest http://pinterest.com/brazil820/
Welcome Sara! I'm following your blog and look forward to your posts! You can follow me at http://simplyathomemom.com/
A mom who blogs about her artwork...
Looks beautiful Sara! Looking forward to checking you out!
twitter: @PursuitOfNormal
Oh this sounds different and exciting! I can't wait to check it out! As someone wth no artistic skill whatsoever, I love to see when others create beautiful things!
twitter: @PursuitOfNormal
I am excited to visit! We Bloggers can really use some great writing sites and blogs to follow. Personally, I know I have a lot to learn and so much room for improvement when it comes to my writing, so I am eager to learn as much as I can. Thank you for sharing your site!
twitter: @PursuitOfNormal


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Your spreadsheet is getting closer but you still have some players who's contracts are expiring after this season as being on the roster for next season and being active players. You have 43 active players and the number is much lower than that.
Jason Trusnik - signed a 2 year/$2 million contract in 2011...there should be no 2013 cap hit for him since he will be an UFA at season's end.
Jeron Mustrud - signed a 1 year/$540,000 contract in 2012...he will be a RFA in 2013. He should have no salary for 2013 although I think he still gives us a cap hit unless he signs somewhere else or we don't give him an offer.
Austin Spitler - Same as Mustrud
Legedu Naanee - signed a 1 year/$540,000 contract in 2012...should not be counted in 2013 as a cap hit or on the roster...obviously.
RJ Stanford - signed a 1 year/$540,000 in 2012...he will be a RFA in 2013...same story as Mustrud, RFA shouldn't be counted as on the roster.
Marlon Moore - signed a 3 year/$1,215,000 contract in 2010...will be a RFA in 2013...shouldn't be counted on the roster.
Jonathan Amaya - same as RJ Stanford and Mustrud...RFA in 2013 shouldn't be counted on the roster.
Jonathan Freeny - signed a 1 year/$390,000 in 2012 as an undrafted free agent...RFA in 2013...shouldn't be counted on the roster.
Marcus Thigpen - same as Freeny.
Pat Devlin - same as Freeny and Thigpen.
Will Barker - Same as RJ Stanford and Mustrud.
So that's 11 guys you're counting as being Active Players in 2013 that shouldn't be. We should have 32 players signed for 2013. We'll probably tender a few of the RFA's but not all of them and you can't count them as active players until those qualifying offers are made. If RFA are not offered qualifying tenders then they become unrestricted.


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La Quinta Inn & Suites Alamo is located just east of the airport, La Plaza Mall and the Rio Grande Premium Outlets, and the closest hotel to the Santa
La Quinta Inn Harlingen is located in the heart of the Rio Grande Valley offering free deluxe continental breakfast, free high speed internet service
Value Place offers affordable weekly stays for fully furnished studios with a full kitchen.
Victoria Palms Inn and Suites offers resort-style living with the comforts and convenience of home in our well-appointed suites. The property is located
With easy access to McAllen Convention Center, this motel is conveniently located at entrance of the McAllen Foreign Trade Zone, and two miles from the
The European-style Holiday Inn Express Suites Airport is located one mile from the airport and seven miles from the International Bridge.
The beautiful new Holiday Inn Express Hotel and Suites Pharr is within minutes of the McAllen and Harlingen airports, and close to the border of Mexico.
The Holiday Inn Express Hotel and Suites is located four miles from RGV Premium Outlet mall. Guests will enjoy a complimentary breakfast buffet, free high
This Super 8 is located approximately two miles from downtown Weslaco and 15 miles from McAllen/Miller International Airport.
This Country Inn & Suites is located just minutes from Rio Grande Valley International Airport and 35 miles from South Padre Island.
Find great deals on quality hotels & resorts in Alamo Texas, or indulge at one of our luxury resorts. Take advantage of the many amenities that can be included with your stay such as in-room internet access, wifi, room service, fitness center, pool, hot tub, steam room, and shuttle services to and from the airport. Browse our hotels and resorts in Alamo Texas and plan your Alamo Texas vacation today!


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Radio One announced that it will consolidate its Syndication One Urban programming line-up with Reach Media, Inc. in 2013. Reach Media will use its affiliate lineup and relationships with leading Urban stations to also launch a new network, as well as expand its dedicated sales and marketing staff to sell radio network advertising inventory along with web and event sponsorships. In making the announcement, Radio One CEO/President Alfred Liggins and Reach Media CEO David Kantor also disclosed that Radio One would increase its ownership stake in Reach Media from 53 percent to 80 percent.
The combination will consolidate several of the largest Urban formatted shows into the same company, including: Tom Joyner, Rickey Smiley, Russ Parr, Yolanda Adams, Reverend Al Sharpton, Warren Ballentine and CoCo Brother.
Liggins stated, "Radio One has a commitment to be the leader in radio and online programming with compelling entertainment and information for the African-American audience. Combining our assets under Reach Media offers an incredibly broad platform for affiliate stations and advertisers to connect with our loyal audience."
Kantor added, "In bringing together the most compelling Urban programming in radio, we've created a platform that can focus on outstanding talent for our affiliates and the delivery of an incredibly responsive consumer base. We look forward to expanding our offerings and becoming the primary radio network for advertisers to reach African- Americans."
Reach Media will also represent sponsorship and integrated marketing opportunities created by its talent including online content, events and community initiatives.
Nikki Nite, VP of Prog. & Ops, Entercom/Austin
Copyright © 2017 Friday Morning Quarterback Album Report, Inc. and Mediaspan Online Services - All Rights Reserved
Contact: Mediaspan Online Services
FMQB, 1930 East Marlton Pike, Executive Mews, Suite F-36, Cherry Hill, NJ 08003. (856) 424-9114.


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5 Ways to Reduce Waste and Save Money at the Same Time
June 4th, 2013 | by Guest Author
You may be surprised to learn that you can produce less waste and actually save money at the same time. It may require a bit of research and a change in habits, but the rewards are worthwhile. If you want to leave the world a better place for your kids and simultaneously cash in, check out these tips


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madhatter: Thank you for the pointer -- I shall check it out.
fxn: Please do use the personalized recentlog idea. I'll likely code up an Advogato diary browser in ObjC (with Cocoa) as a way to get familiar with NSDistantObject. Your implementation will be much more useful, though.
Code and the likes
Checked out the Aegis SCM system. It looks fabulous for group work, so I'm playing with it a bit. I still like PRCS for my own projects, though. I'm considering writing a wrapper for PRCS to add support for automatic builds and unit testing -- something Aegis excels at.
Other stuff
Puppies are fine, but being severe brats. I can't blame them too much, though. There are a lot of changes going on right now. Hopefully they'll adapt quickly.


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A quick walk around the house can uncover a multitude of items we've spent too much on. From pricey shampoos and body washes, to household cleaners and medications, there's a veritable fortune being spent unnecessarily. But once you can identify the culprits and tweak your shopping habits, it's like finding change in the sofa cushions.
Chances are you've got way too many household cleaners under the kitchen sink: one for the windows, one for the dishwasher, one for the countertops — the list could go on forever. Bear in mind that items with name brands don't necessarily clean better than the generic alternatives. Better yet, even bigger savings can be found by mixing a few inexpensive basics like vinegar and baking soda. The all-purpose powder is a natural deodorizer, and when mixed with water makes a great scouring agent. For window treatments, there's really nothing more effective than vinegar and water for cleaning glass surfaces. Go a step further and use old newspapers instead of paper towels for a streak-free, guilt-free, cost-free shine.
Toiletries, like pricey shampoos, body washes and moisturizer are also dollar swallowers. Beauty experts say the basic ingredients of soap and detergents are universal. While the cleaning agent is important, everything else (including fragrance) literally washes down the drain. In the case of shampoo — we only need a gentle cleanser at most — there's even a growing "no-poo" movement that advocates forgoing shampoo altogether. Face cleaners, pricey moisturizers and dental care products all also command more for the label and marketing than for performance.
Forbes.com slideshow: Household items you're spending too much money on
Electronic or more tech-laden versions of old standbys are even bigger wastes of money. "If it's a battery operated toothbrush which will need replacement heads, buy them at the same time you purchase the toothbrush," says Christine Frietchen, editor of ConsumerSearch. "Let's face it, when you need new heads, you're not going to find them." After time, the company might not sell the item anymore, or you won't remember the model you need and will wind up purchasing an entirely new toothbrush. Battery-fueled face cleaners, razors with special blades, or electronic toothbrushes have more moving parts, making them more likely to break.
Perhaps the most surprising budget black holes are room fragrances and candles, now a multi-billion dollar category. That's money spent to mask odors a good cleaning or open window can take care of, and don't forget that spending anywhere from $10 to $75 for a pricey, celebrity-endorsed candle is forking over money for something you'll set on fire, literally.
Forbes.com: 10 treasures hiding in your attic or garage
Forbes.com: How to retire early
Forbes.com: Surprising home-energy hogs
Forbes.com: 10 steps to cut your real estate taxes
Forbes.com: How to complain to customer service and win
© 2012 Forbes.com


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My friend's fiance found TWO Evil-Lyns and a Roboto down in Georgia last week while she was on a business trip. So that's the end of the line for me. No Zodak, no Fisto (c'mon people, that's who it is...) and no Roboto for me.
I've come to think of the Batman and MOTU lines as synonomous since Mattel is shmucking both of them up with the same incompetence. It's Marvel Legends and Muppets for me now. If Toybiz or Palisades were given the DC license, I would be a happy happy hunter.


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