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Alternative selection of splice sites in tandem donors and acceptors is a major mode of alternative splicing. Here, we analyzed whether in-frame tandem sites leading to subtle mRNA insertions/deletions of 3, 6, or 9 nucleotides are under natural selection.
We found multiple lines of evidence that the human protein coding sequences are under selection against such in-frame tandem splice events, indicating that these events are often deleterious. The strength of selection is not homogeneous within the coding sequence as protein regions that fold into a fixed 3D structure (intrinsically ordered) are under stronger selection, especially against sites with a strong minor splice site. Investigating structures of functional protein domains, we found that tandem acceptors are preferentially located at the domain surface and outside structural elements such as helices and sheets. Using three-species comparisons, we estimate that more than half of all mutations that create NAGNAG acceptors in the coding region have been eliminated by selection.
We estimate that ~2,400 introns are under selection against possessing a tandem site.
Many genes in animal and plant genomes express more than one transcript by alternative splicing. These transcripts can encode proteins with different, sometimes even antagonistic functions. For example, many members of the human caspase gene family express alternative splice variants that encode pro- and anti-apoptotic proteins [1]. In mammals, most alternative splice events skip complete exons or utilize either alternative donor or acceptor splice site pairs. Most of the latter (called tandem splice sites in the following) are in close proximity [2-6], thus leading to the insertion/deletion (indel) of only a few nucleotides. Alternative splice events at NAGNAG acceptors are the most frequent of these events. Previous studies suggest that the splicing mechanism of short-distance tandem sites involves stochastic selection of either site [7]. A subset of these events is under purifying selection, thus contributing to the repertoire of biologically relevant alternative splice events [8].
In humans, a substantial number of alternative splice events either shift the protein reading frame or directly introduce a premature termination codon by skipping of exons or alternative usage of tandem splice sites [3,9-11]. Most of these events render the transcript a target for nonsense-mediated mRNA decay (NMD) [11]. Conservation of such events implies functionality, maybe by regulating the protein level [8,12-14]. On the other hand, many of these events likely have no functional relevance or may be due to splicing errors [15]. Here, NMD is an important surveillance mechanism reducing the amount of transcripts that would be translated to truncated proteins [16].
Apart from NMD, cells can use the complex splicing regulatory mechanisms to silence deleterious splice events. For example, pseudo exons (silent intronic regions that resemble real exons) are enriched in binding sites for silencing splicing factors, which prevent their inclusion into the mature transcript [17]. Likewise, silencer motifs located between two alternative splice sites inhibit the use of one splice site [18]. Thus, auxiliary splicing enhancer and silencer signals enable a high splicing fidelity, despite the occurrence of numerous pseudo splice sites. Consequently, there seems to have been no need to get rid of all these pseudo splice sites in the course of evolution.
This situation is different for deleterious short-distance tandem splice sites that preserve the reading frame. Firstly, they do not elicit NMD and secondly, mechanisms to inhibit the use of the alternative splice site seem to be limited. The latter reason is due to spatial restrictions that do not allow the placement of splicing silencer motifs between two splice sites separated by as few as 3 nucleotides (nt).
Furthermore, core components of the spliceosome are likely to be the major factors that enable such alternative splice events, whereas other splice events often depend on additional enhancing and/or silencing splicing factors. This makes tandem splice events rather independent of tissue-specific fluctuations in splicing factor concentrations. Consistently, many tandem sites produce constant splice variant ratios [19-21], although variation in the ratio was observed in several cases [4,20,22-24]. Assuming that splicing regulatory mechanisms in general cannot completely inhibit alternative splicing at these sites, the ultimate option to get rid of a deleterious tandem splice event is to destroy the tandem site, for example by a mutation that destroys one GT/GC donor or one AG acceptor dinucleotide. Under this assumption, we would expect to find traces of natural selection, evident as an underrepresentation of tandem splice sites at places where they are deleterious.
To test this hypothesis, we analyzed frame-preserving tandem splice sites with a distance of 3, 6, and 9 nt (Δ3, Δ6, and Δ9 nt, respectively). We focused on short-distance sites because a stochastic splicing mechanism is likely to be the basis for such alternative splice events [7]. We present multiple lines of evidence that such tandem sites are underrepresented in protein-coding sequences (CDS), and in particular in regions that form ordered 3D protein structures. We estimate that ~2,400 introns are under selection against possessing a tandem site.
Underrepresentation of tandem splice sites in coding regions
We used human RefSeq transcript exon-intron structures and a series of stringent filtering steps (see Methods) to create a data set of 15,511 protein coding genes. Each gene is represented by a single transcript. These genes contain 140,975 introns that reside within the CDS and 9,077 introns in the 5' or 3' untranslated region (UTR). In the following, we analyze Δ3, Δ6, and Δ9 tandem donor and acceptor sites, where the occurrence of alternative splicing could be inferred from mRNA/EST data.
We found that 0.26% of the CDS introns have a tandem donor (100, 142, 127 for Δ3, Δ6, Δ9, respectively) and 1.25% a tandem acceptor (1,396, 238, 132). In contrast, UTR introns, where such subtle events are expected to be neutral or only slightly deleterious, have a more than 2-fold higher fraction of tandem donors and acceptors (0.64% and 2.54%, respectively, Fisher's exact test: P < 0.0001, Figure 1). This suggests a general underrepresentation of tandem splice events in coding regions and is consistent with a report for NAGNAG sites [7].
Figure 1. Frequency of tandem splice sites in the CDS and UTR. Each bar is the percentage of human introns having a tandem donor (A) or acceptor (B). Introns are divided into a location in the CDS (blue) and the UTR (green). CDS introns are further divided into a location in ordered and disordered protein regions (light blue). Absolute numbers are given above the bars.
Inhomogeneous distribution of tandem sites in ordered and disordered protein regions
Next, we analyzed if this underrepresentation is homogeneous within the CDS. We divided the proteins into regions that are predicted to have an intrinsically ordered or disordered 3D structure [25]. As shown in Figure 1B, tandem acceptors are substantially underrepresented in ordered regions. Tandem donors exhibit the same trend but the underrepresentation in ordered regions is moderate (Figure 1A). This moderate underrepresentation might be due to differences in the frequency of polar and hydrophobic protein indels. The toleration of tandem donors in ordered regions might be higher, since they often insert hydrophobic residues (in particular Val [19]), which are preferred in ordered regions [25]. We also analyzed how frequently tandem sites affect other characteristic protein features such as Pfam domains, transmembrane (TM) helices, signal peptides, low complexity regions, coiled coil regions, and nuclear localization signals (NLS), which is described in detail in the Additional File 1 (see also Additional File 2). We found that low complexity regions are rather tolerant for tandem splice events (Additional File 3), which is consistent with observations for amino acid indels [26]. We also found evidence that tandem sites affecting TM helices, signal peptides, and NLS are selected against the insertion of particular amino acids (Additional File 1, 4, 5). Tandem sites are also significantly associated with specific DNA and RNA binding Pfam domains (Additional File 1, 6), consistent with reports for NAGNAG acceptors [4,27].
Additional file 1. Supplementary Text.
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Additional file 2. Overlap between the protein features.
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Additional file 3. Frequency of tandem splice sites in different protein features.
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Additional file 4. Selection against insertion of particular amino acids.
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Additional file 5. Distribution of the insertion sequences of tandem sites in the protein features.
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Additional file 6. Association of tandem sites with specific Pfam domains or clans.
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Selection against a strong minor splice site in ordered regions
Using EST counts as a rough measure for the frequency of splicing at the minor splice site, we considered a minor splice site as strong if more than 25% of the ESTs support the minor splice variant and otherwise as weak (note that by definition >50% of the ESTs support the major variant). For tandem donors, only 33% of the 52 events with a strong minor site affect ordered regions compared to 57% of the 317 events with a weak site (Fisher's exact test: P = 0.0009). Likewise, for tandem acceptors, only 22% of the 454 events with a strong minor site affect ordered regions compared to 36% of the 1,312 events with a weak site (Fisher's exact test: P < 0.0001). Thus, ordered regions are under a strong selection against events that involve an efficient minor site.
Location of tandem splice sites with respect to protein secondary structures
To further test the underrepresentation of tandem splice sites in ordered regions, we focused on Pfam domains since these domains usually fold into a well-defined 3D structure. We obtained the protein secondary structure as well as the surface accessibility of residues from known 3D structures of Pfam domains. We mapped the position of 21 and 49 introns with tandem donors and acceptors, respectively, as previously described [28]. For comparison, we mapped the position of 4,015 introns without a Δ3/Δ6/Δ9 tandem donor or acceptor motif (called control introns) since small in-frame splice site variations cannot occur in these introns. Comparing the location of introns with respect to alpha-helices, beta-sheets, and non-regular elements, we found no difference between control introns and introns with tandem donors. However, introns with tandem acceptors are significantly biased against a location in helices and sheets (Figure 2A). This tendency is even more pronounced for NAGNAG acceptors (Additional File 7). As the exact boundaries of structural elements are sometimes difficult to determine, we further analyzed a broader context of ± 1 residue around the intron location. We considered an intron to be 'inside a structural element' if this broader context is completely inside a helix or inside a sheet. If the complete context is inside a non-regular element or in two different structural elements, the context is considered to be 'outside a structural element'. In this comparison, both tandem donors and acceptors show a noticeable avoidance of structural elements (Figure 2B). The average surface accessibility scores are indistinguishable between control intron and tandem donor regions, while regions with tandem acceptors have a significantly higher surface accessibility (Figure 2C). Finally, we found polar residues to be slightly enriched in tandem donor and strongly enriched in tandem acceptor protein contexts (Figure 2D), which is further evidence that protein variations caused by tandem acceptors are preferentially located on the surface of folded domains.
Additional file 7. Avoidance of NAGNAG sites in structured regions of Pfam domains.
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Figure 2. Avoidance of tandem acceptors in structured regions of Pfam domains. The distribution of exon/exon junctions derived from control introns, introns with tandem donors and acceptors (A) in alpha-helices, beta-sheets, and non-regular elements, (B) 'inside' or 'outside' structural elements (see text), (C) with respect to the average surface accessibility, and (D) with respect to the average inverse hydropathy scores. Kyte-Doolittle values were used to compute hydropathy scores for the ± 5 amino acid contexts. The values were inverted so that positive values indicate polar residues. To avoid potential biases, we excluded the insertion sequence of tandem donors and acceptors from the context. Different context lengths of ± 3, ± 10, or ± 15 residues give consistent results in D (Additional File 11). P-values using a χ2 test in A and B and a Wilcoxon rank sum test in C and D are indicated as *: P < 0.05, **: P < 0.001, ***: P < 0.0001.
Strong bias against plausible NAGNAG acceptors in human CDS
To further investigate selection against tandem splice sites, we focused on NAGNAG acceptors for two reasons. First, these acceptors comprise the largest tandem class with a total of 7,835 acceptors. Secondly, the NAGNAG motif is highly predictive for alternative splicing [7,19,29]. That is, sites with the motif HAGHAG (H = A, C, or T, in the following called 'plausible' NAGNAG acceptors) are preferentially alternatively spliced (1,253 of 2,787; 45%). In contrast, only a small fraction of the acceptors with a HAGGAG, GAGHAG, or GAGGAG (called 'implausible') motif allow alternative splicing (143 of 5,048; 2.8%). Thus, we can use the motif to classify all NAGNAG acceptors into those that are likely and unlikely alternatively spliced, independent of available transcript data.
First, we compared the percentage of CDS and UTR introns that have a plausible or implausible NAGNAG acceptor. The frequency of plausible NAGNAG sites is 1.9-fold lower in CDS introns compared to UTR introns (Figure 3A). In contrast, the frequency of implausible sites is very similar in CDS and UTR introns. This shows a significant depletion of plausible sites in CDS introns (Fisher's exact test: P < 0.0001). Consistently, AAG and CAG but not the synonymous codons AAA and CAA have been found to be avoided at the 5' exon boundary [30,31], although AAG/CAG is more often part of splicing enhancer motifs than AAA/CAA [32]. Furthermore, GAG is not underrepresented at the 5' exon boundary compared to the synonymous GAA codon [31].
Figure 3. Distribution of plausible and implausible NAGNAG acceptors. (A) Human and (B) C. elegans UTR vs. CDS introns; (C) Human CDS introns divided into a location in ordered or disordered regions. Each bar is the percentage of introns having a plausible (blue) or implausible (green) NAGNAG acceptor. Absolute intron numbers are given above the bars.
To further test this, we considered NAGNAG sites in C. elegans, which is the only metazoan species found so far that lacks widespread alternative splicing at NAGNAG sites [4,19]. Two points indicate that the simple classification plausible/implausible is also valid for C. elegans. First, C. elegans acceptor AGs have exactly the same preference for the preceding nucleotide (C > T > A > G) as seen in mammals [33]. Secondly, all of the 33 alternatively spliced NAGNAG acceptors in C. elegans are plausible [19]. Thus, although the frequency of alternative splicing at NAGNAG sites is exceptionally low in C. elegans (20-fold lower compared to humans), those that are alternatively spliced have the same characteristics as in humans. Thus, we can use C. elegans as another control for the underrepresentation of plausible NAGNAG acceptors in human CDS introns. As expected, in C. elegans, we found that the frequency of plausible and implausible NAGNAG sites in UTR and CDS introns is very similar (Figure 3B). Interestingly, plausible NAGNAG acceptors are even more abundant than implausible ones both in UTR and CDS introns of C. elegans. This is presumably caused by a lower frequency for G at the 5' exon boundary in C. elegans (~25%) as opposed to humans (~50%) [33].
Next, we analyzed the frequency of NAGNAG sites in ordered and disordered regions. The frequency of introns with plausible NAGNAG sites is 3.2-fold lower in ordered compared to disordered regions. In contrast, the frequency of introns with implausible NAGNAG acceptors is only 1.6-fold lower in ordered regions (Figure 3C), which is a significant difference (Fisher's exact test: P < 0.0001). The frequency of NAGNAG sites in the other protein features is shown in Additional File 8.
Additional file 8. Distribution of plausible and implausible NAGNAG acceptors in different protein features.
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Moreover, we analyzed the distribution of evolutionary 'young' and 'old' plausible/implausible NAGNAG acceptors in ordered/disordered regions. As shown in Figure 4, plausible NAGNAG sites that are human specific (not conserved in the orthologous chimpanzee, rhesus, and mouse introns) or human-chimpanzee specific (not conserved in rhesus and mouse) have a significant tendency to avoid ordered regions compared to the respective implausible ones (Fisher's exact test: P = 0.02, P < 0.0001, respectively). A stronger underrepresentation was observed for evolutionary old (conserved between human, mouse, dog, and chicken) plausible NAGNAG acceptors (Fisher's exact test: P < 0.0001). It is noteworthy that implausible NAGNAG acceptors resemble the expected distribution, which is the overall number of introns in ordered/disordered regions (Figure 4). Thus, young and old plausible NAGNAG sites are underrepresented in ordered regions, indicating that selection against such sites is universal and more effective over large evolutionary distances.
Figure 4. Distribution of evolutionary 'young' and 'old' plausible vs. implausible NAGNAG acceptors in ordered and disordered regions. The expected distribution is the overall number of introns in ordered/disordered regions.
Selection against NAGNAG creating mutations
We have previously shown that a single nucleotide mutation can create an alternatively spliced NAGNAG acceptor [29]. We asked whether selection acts against single nucleotide substitutions creating plausible NAGNAG acceptors by comparing CDS with UTR as well as ordered with disordered regions. We considered only base exchanges that create a second AG dinucleotide in the context of a non-NAGNAG acceptor. To dissect selection against NAGNAG creations from other evolutionary pressures, we focused only on cases where the required mutation has to occur (i) within the exon and is synonymous (Figure 5A) or (ii) within the intron (Figure 5B). Controlling for different distributions in the required mutations and using implausible NAGNAG creations as a control (see Methods), we estimated the relative risk (RR) for the creation of an implausible vs. plausible NAGNAG acceptors using the Cochran-Mantel-Haenszel (CMH) test. An RR of 1 indicates that the creation of plausible and implausible NAGNAG sites is equally likely, which is consistent with the absence of selection, while an RR > 1 indicates how much more likely the creation of an implausible site is. Using the RR, we can estimate how many mutations that create plausible NAGNAG sites have been eliminated by selection.
Figure 5. The percentage of plausible NAGNAG creating mutations eliminated by selection. (A) exonic and synonymous mutations, (B) intronic mutations. The relative risk (RR) indicating how much more likely the creation of an implausible NAGNAG is compared to the creation of a plausible NAGNAG is given above the columns. P-values of the CMH test are indicated as ***: P < 0.0001, **: P < 0.001, *: P < 0.01.
First, we investigated the exonic creation of mouse NAGNAG sites inferred by comparing human acceptors with mouse and the outgroup dog. We found that the creation of an implausible NAGNAG site in the CDS is 2.6-fold more likely than the creation of a plausible NAGNAG, indicating that 62% of plausible NAGNAG creating mutations have been eliminated by selection (Figure 5A). In contrast, the creation of plausible/implausible acceptor motifs is equally likely in UTRs (RR = 1.1). In ordered regions, the RR of 3.3 (70% elimination) is substantially higher than the RR of 2 (50% elimination) in disordered regions (Figure 5A). This provides evidence for a selection pressure against the creation of plausible NAGNAG sites in the CDS, in particular against creations in ordered regions.
Next, we investigated NAGNAG creation by intronic mutations. The RR is higher for the CDS region compared to UTRs (Figure 5B). UTRs also exhibit an RR > 1, however the RR is estimated from sparse data and P = 0.11 does not suggest a significant deviation from the expected RR of 1. Consistent with our above results, ordered regions exhibit a noticeable higher RR than disordered regions (84 vs. 66% elimination). In general, intronic mutations that create plausible NAGNAG sites seem to be under stronger selection than exonic synonymous ones (compare Figure 5A with 5B). This might be explained by the fact that the upstream acceptor in a NAGNAG motif is generally the preferred splice site [3,4]. Thus, the creation of a new AG upstream of an existing acceptor is expected to result in the usage of the novel acceptor in the majority of transcripts. In contrast, a novel acceptor downstream should be the minor splice site, consequently the established transcript is predominantly expressed.
Since plausible NAGNAG sites in nematodes are rarely alternatively spliced [4,19], we would expect a much weaker or no selection against the creation of plausible NAGNAG sites. To test this, we examined the creation of NAGNAG sites in C. remanei using the genomes of C. briggsae and the outgroup C. elegans. Considering exonic synonymous mutations, CDS introns have an RR very similar to UTR introns (Figure 5A). While the RR for nematode CDS introns is significantly different from 1 (P < 0.0001), it is substantially lower than the RR for human CDS introns. This is consistent with a much weaker selection against plausible NAGNAG creations in nematode CDS. Nearly identical results were observed for NAGNAG creation in C. briggsae (Additional File 1). Compared to mammals, C. elegans introns have an unusual acceptor site that lacks a branch point consensus but contains a highly conserved TTTTCAG acceptor motif, which is a high affinity binding site for the U2AF heterodimer [34]. Deviations from this consensus were shown to affect U2AF binding [34]. Consistent with this, we found not a single case among 5,375 nematode introns where a NAGNAG is created by an intronic mutation.
We presented multiple lines of evidence that human coding sequences are under selection against in-frame tandem splice events. In particular, ordered regions are under strong selection, suggesting that even small changes (one to three amino acid differences) might affect protein folding and function. For example, the deletion of a few residues from the Piccolo C2A domain leads to a structural change with marked consequences for Ca2+ binding [35]. We also found that tandem acceptor caused protein variations in functional domains are preferentially located at the surface and outside structural elements such as alpha-helices and beta-sheets. Similar results were reported for protein indels [26,36] and exon skipping events [28]. The frequent class of NAGNAG acceptors, which mostly result in the indel of only one amino acid [4], is also under strong evolutionary constraints. Consistently, a splicing-independent case study found phenotypic effects for two thirds of random triplet deletions [37].
Our findings of selection against tandem splice sites suggest that existing tandem sites are either (effectively) neutral or might have a functional role. Alternative splicing frequently affects protein regions that are intrinsically disordered [38]. Consistently, we found that tandem splice sites preferentially affect disordered regions. While alterations of disordered regions should not cause changes in protein structure in general, it can change the function of proteins [38], as disordered regions are often associated with regulation and signalling [39].
UTRs contain secondary structures and binding sites for proteins and non-coding RNAs that influence mRNA export, localization, stability as well as translational efficiency [40]. Thus, functional sites in UTRs are also expected to be under selection. However, our results on tandem sites in UTRs are consistent with neutral evolution, although individual introns can still be under selection against tandem sites.
We found that CDS introns but not UTR introns are under selection against tandem sites. Thus, we can use the frequency of tandem sites in UTRs to provide a rough estimation of the number of CDS introns under selection against tandem splice sites. We found that 3.68% of the UTR and 1.98% of the CDS introns have a plausible NAGNAG (Figure 3). Under neutrality, we would expect that the percentage for CDS introns equals that for UTR introns, consequently we estimate 2,397 (1.7% = 3.68%–1.98%) of the 140,975 CDS introns to be under selection against a plausible NAGNAG acceptor. Likewise, we estimate that 536 (0.38% = 0.64%–0.26%, see Figure 1) and 1,819 (1.29% = 2.54%–1.25%) CDS introns are under selection against tandem donor and acceptor sites, respectively. In summary, we conclude that ~2,400 human introns are under selection against possessing a subtle tandem splice site inserting/deleting 3, 6, or 9 nt.
Data sets
We downloaded from the UCSC Genome Browser [41] the human genome assembly (hg17, May 2004) and the RefSeq annotation (refFlat.txt.gz, November 2006). We excluded all transcripts that have only one exon, that are candidates for NMD (stop codon >50 nt upstream of the last exon-exon junction), that lack a start or stop codon, or that have in-frame premature stop codons according to the RefSeq to genome mapping. Furthermore, transcripts with ambiguous characters were excluded. We also discarded transcripts that have exons shorter than 5 nt or introns shorter than 30 nt as they might have incorrect exon-intron structures. To get a set of non-redundant transcripts, we extracted RefSeq transcripts so that they do not overlap any other transcript on the same strand. To remove redundancy and strong similarity of the proteins encoded by a RefSeq transcript, we used NCBI BLASTClust to cluster the proteins by sequence similarity using 80% coverage and 80% identity (parameters -L 0.8 -S 80). Then, we kept only one protein from each cluster with more than one entry as well as all proteins from single clusters. This yields 15,511 non-redundant transcripts/proteins. For C. elegans, we downloaded the genome assembly ce2 (March 2004) and the RefSeq annotation (refFlat.txt.gz, May 2007). All transcripts were filtered as for human, except for omitting the NMD filter. We got 15,652 non-redundant C. elegans transcripts/proteins.
For all transcripts, we screened all splice sites for the presence of a tandem donor and acceptor Δ3, Δ6, and Δ9 motif. Annotated donors without GT/GC and acceptors without AG intron termini were omitted. The RefSeq annotation of the open reading frame was used to decide if a tandem site affects the CDS. A tandem site was considered as alternatively spliced if there is at least one EST/mRNA each that match the short and the long transcript. For Δ3 donor and acceptor sites, we downloaded EST information from TassDB [42]. For Δ6 and Δ9 tandem sites, we used BLAST against all ESTs and mRNAs. From the analyses, we omitted 35 introns where a Δ3/Δ6/Δ9 tandem splice event leads to the direct insertion of a stop codon (e.g. a CAGTAG acceptor in intron phase 0), since most of these events result in an NMD target and our aim is to analyze only splice events causing subtle mRNA and protein changes. Conservation of tandem sites was detected by analyzing the genome-wide pairwise alignments downloaded from the UCSC genome browser (assemblies: human hg17, chimpanzee panTro2, rhesus rheMac2, mouse mm7, dog canFam2, chicken galGal2) using the genomic locus of the human tandem sites to select the respective alignment chain.
We determined characteristic protein features for the protein sequence that corresponds to the annotated exon-intron structure. Given that the major splice site (inferred from EST counts) is annotated for 91.2% and 89.2% of the tandem donors and acceptors, respectively, the annotated exon-intron structure reflects the predominant protein isoform in the great majority of cases. Ordered and disordered regions were predicted by VSL2B [25]. See Additional File 9 for the other protein features.
Additional file 9. Supplementary Methods
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Location of tandem splice sites in Pfam domains structures
We considered all Pfam domains to which at least five tandem splice sites were mapped and that have a known 3D structure. As previously described [28], pdb2pfam was used to obtain the protein secondary structure assignment and the surface accessibility for each residue of a domain with known 3D structure (target domain). Then, we compared the Pfam alignment (the Viterbi path) of the target domain with the alignment of the query domain to map the position of the query intron. Specifically, we considered the exon-exon junction that represents this intron. If the exon-exon junction splits a codon, only this amino acid was marked as the exon junction. If the exon junction is located between two codons, we marked both neighboring amino acids. From the mapped exon-exon junction, we inferred the location in the secondary structure and the surface accessibility. We discarded cases where the exon-exon junction maps to an insert or delete state. For introns with tandem splice sites, we used the annotated exon-exon junction, since the annotated splice site is mostly the major site. The secondary structure assignment from the eight DSSP states was done as follows: H, G, I helix, E sheet, and T, S, C, B non-regular. The two states BC are converted to EE.
NAGNAG creating mutations
We define as a 'pre-NAGNAG' acceptor a non-NAGNAG acceptor motif that requires a single base exchange to become a NAGNAG acceptor (e.g. AA
Additional file 10. Unequal distribution of the target mutations between plausible and implausible human pre-NAGNAG sites and between CDS/UTR and order/disorder.
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C. elegans is the only nematode with a sufficiently large transcript coverage and lacks widespread alternative splicing at NAGNAG acceptors. We assume that other nematodes also lack widespread alternative splicing at NAGNAG sites. This is supported by previous experimental observations that splicing regulation between both C. elegans and C. briggsae is highly conserved [43] and by a high conservation between C. elegans and C. briggsae acceptor sites [44]. Using the same procedure as above, we analyzed the C. elegans pre-NAGNAG acceptors using UCSC pairwise alignments of C. elegans (assembly ce4) with C. briggsae (cb3) and C. remanei (caeRem2) to infer NAGNAG creation in C. briggsae as well as C. remanei (note that C. elegans is the outgroup here [45]).
nt, nucleotides; NMD, nonsense-mediated mRNA decay; CDS, coding sequence; UTR, untranslated region; EST, expressed sequence tag; TM helix, transmembrane helix; NLS, nuclear localization signal; RR, relative risk; CMH test, Cochran-Mantel-Haenszel test.
Authors' contributions
MH designed and performed all analyses, analyzed the data and drafted the manuscript. KS and KH contributed analysis tools. RB and MP were the principal investigators. All authors contributed to the final manuscript, read and approved it.
Additional file 11. Average hydropathy scores for introns without tandem donor or acceptor motifs (control introns) and for introns with tandem donors and acceptors.
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We thank Rileen Sinha and Anke Busch for helpful comments. This work was supported by grants from the German Ministry of Education and Research (01GR0504, 0313652D) as well as from the Deutsche Forschungsgemeinschaft (SFB604-02, HU498/3-1).
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Lareau LF, Inada M, Green RE, Wengrod JC, Brenner SE: Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements.
Nature 2007. PubMed Abstract | Publisher Full Text
Ni JZ, Grate L, Donohue JP, Preston C, Nobida N, O'Brien G, Shiue L, Clark TA, Blume JE, Ares M Jr: Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay.
Genes Dev 2007, 21(6):708-718. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sorek R, Shamir R, Ast G: How prevalent is functional alternative splicing in the human genome?
Trends Genet 2004, 20(2):68-71. PubMed Abstract | Publisher Full Text
Mendell JT, Sharifi NA, Meyers JL, Martinez-Murillo F, Dietz HC: Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise.
Nat Genet 2004, 36(10):1073-1078. PubMed Abstract | Publisher Full Text
Zhang XH, Chasin LA: Computational definition of sequence motifs governing constitutive exon splicing.
Genes Dev 2004, 18(11):1241-1250. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Wang Z, Xiao X, Van Nostrand E, Burge CB: General and specific functions of exonic splicing silencers in splicing control.
Mol Cell 2006, 23(1):61-70. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hiller M, Huse K, Szafranski K, Rosenstiel P, Schreiber S, Backofen R, Platzer M: Phylogenetically widespread alternative splicing at unusual GYNGYN donors.
Genome Biol 2006, 7(7):R65. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Tadokoro K, Yamazaki-Inoue M, Tachibana M, Fujishiro M, Nagao K, Toyoda M, Ozaki M, Ono M, Miki N, Miyashita T, Yamada M: Frequent occurrence of protein isoforms with or without a single amino acid residue by subtle alternative splicing: the case of Gln in DRPLA affects subcellular localization of the products.
J Hum Genet 2005, 50(8):382-394. PubMed Abstract | Publisher Full Text
Tsai KW, Lin WC: Quantitative analysis of wobble splicing indicates that it is not tissue specific.
Genomics 2006, 88(6):855-864. PubMed Abstract | Publisher Full Text
Hu CA, Lin WW, Obie C, Valle D: Molecular enzymology of mammalian Delta1-pyrroline-5-carboxylate synthase. Alternative splice donor utilization generates isoforms with different sensitivity to ornithine inhibition.
J Biol Chem 1999, 274(10):6754-6762. PubMed Abstract | Publisher Full Text
Koenig Merediz SA, Schmidt M, Hoppe GJ, Alfken J, Meraro D, Levi BZ, Neubauer A, Wittig B: Cloning of an interferon regulatory factor 2 isoform with different regulatory ability.
Nucleic Acids Res 2000, 28(21):4219-4224. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Szafranski K, Schindler S, Taudien S, Hiller M, Huse K, Jahn N, Schreiber S, Backofen R, Platzer M: Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns.
Genome Biol 2007, 8(8):R154. PubMed Abstract | BioMed Central Full Text
Peng K, Radivojac P, Vucetic S, Dunker AK, Obradovic Z: Length-dependent prediction of protein intrinsic disorder.
BMC Bioinformatics 2006, 7:208. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Taylor MS, Ponting CP, Copley RR: Occurrence and consequences of coding sequence insertions and deletions in Mammalian genomes.
Genome Res 2004, 14(4):555-566. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Akerman M, Mandel-Gutfreund Y: Alternative splicing regulation at tandem 3' splice sites.
Nucleic Acids Res 2006, 34(1):23-31. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hiller M, Huse K, Platzer M, Backofen R: Non-EST based prediction of exon skipping and intron retention events using Pfam information.
Nucleic Acids Res 2005, 33(17):5611-5621. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hiller M, Huse K, Szafranski K, Jahn N, Hampe J, Schreiber S, Backofen R, Platzer M: Single-Nucleotide Polymorphisms in NAGNAG Acceptors Are Highly Predictive for Variations of Alternative Splicing.
Am J Hum Genet 2006, 78(2):291-302. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Parmley JL, Hurst LD: Exonic Splicing Regulatory Elements Skew Synonymous Codon Usage near Intron-exon Boundaries in Mammals.
Mol Biol Evol 2007, 24(8):1600-1603. PubMed Abstract | Publisher Full Text
Eskesen ST, Eskesen FN, Ruvinsky A: Natural selection affects frequencies of AG and GT dinucleotides at the 5' and 3' ends of exons.
Genetics 2004, 167(1):543-550. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Stadler MB, Shomron N, Yeo GW, Schneider A, Xiao X, Burge CB: Inference of splicing regulatory activities by sequence neighborhood analysis.
PLoS Genet 2006, 2(11):e191. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sheth N, Roca X, Hastings ML, Roeder T, Krainer AR, Sachidanandam R: Comprehensive splice-site analysis using comparative genomics.
Nucleic Acids Res 2006, 34(14):3955-3967. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hollins C, Zorio DA, MacMorris M, Blumenthal T: U2AF binding selects for the high conservation of the C. elegans 3' splice site.
Rna 2005, 11(3):248-253. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Garcia J, Gerber SH, Sugita S, Sudhof TC, Rizo J: A conformational switch in the Piccolo C2A domain regulated by alternative splicing.
Nat Struct Mol Biol 2004, 11(1):45-53. PubMed Abstract | Publisher Full Text
Pascarella S, Argos P: Analysis of insertions/deletions in protein structures.
J Mol Biol 1992, 224(2):461-471. PubMed Abstract | Publisher Full Text
Jones DD: Triplet nucleotide removal at random positions in a target gene: the tolerance of TEM-1 beta-lactamase to an amino acid deletion.
Nucleic Acids Res 2005, 33(9):e80. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Romero PR, Zaidi S, Fang YY, Uversky VN, Radivojac P, Oldfield CJ, Cortese MS, Sickmeier M, LeGall T, Obradovic Z, Dunker AK: Alternative splicing in concert with protein intrinsic disorder enables increased functional diversity in multicellular organisms.
Proc Natl Acad Sci USA 2006, 103(22):8390-8395. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Dyson HJ, Wright PE: Intrinsically unstructured proteins and their functions.
Nat Rev Mol Cell Biol 2005, 6(3):197-208. PubMed Abstract | Publisher Full Text
Hughes TA: Regulation of gene expression by alternative untranslated regions.
Trends Genet 2006, 22(3):119-122. PubMed Abstract | Publisher Full Text
Kuhn RM, Karolchik D, Zweig AS, Trumbower H, Thomas DJ, Thakkapallayil A, Sugnet CW, Stanke M, Smith KE, Siepel A, Rosenbloom KR, Rhead B, Raney BJ, Pohl A, Pedersen JS, Hsu F, Hinrichs AS, Harte RA, Diekhans M, Clawson H, Bejerano G, Barber GP, Baertsch R, Haussler D, Kent WJ: The UCSC genome browser database: update 2007.
Nucleic Acids Res 2007, (35 Database):D668-673. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Hiller M, Nikolajewa S, Huse K, Szafranski K, Rosenstiel P, Schuster S, Backofen R, Platzer M: TassDB: a database of alternative tandem splice sites.
Nucleic Acids Res 2007, (35 Database):D188-192. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Rukov JL, Irimia M, Mork S, Lund VK, Vinther J, Arctander P: High qualitative and quantitative conservation of alternative splicing in Caenorhabditis elegans and Caenorhabditis briggsae.
Mol Biol Evol 2007, 24(4):909-917. PubMed Abstract | Publisher Full Text
Kent WJ, Zahler AM: Conservation, regulation, synteny, and introns in a large-scale C. briggsae-C. elegans genomic alignment.
Genome Res 2000, 10(8):1115-1125. PubMed Abstract | Publisher Full Text
Kiontke K, Gavin NP, Raynes Y, Roehrig C, Piano F, Fitch DH: Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss.
Proc Natl Acad Sci USA 2004, 101(24):9003-9008. PubMed Abstract | Publisher Full Text | PubMed Central Full Text


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Find records of Roy Cashatt
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Roy G Cashatt (1931 - 2007) was born on November 27, 1931. He was born into the Cashatt family.
There are no known marriages or children on file for Roy. Roy died on March 1, 2007 at 75 years old.
Roy G Cashatt's last known residence is at Asheboro, Randolph County, North Carolina.
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Possible Relatives
- Robert S Cashatt
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- Marvin W Cashatt
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- Jerry W Cashatt
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- Daniel Cashatt
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- George C Cashatt
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- Mildred P Cashatt
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- Jay Cashatt
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- Robert R Cashatt
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- Ella R Cashatt
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- Gary A Cashatt
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- C A Cashatt
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subset: commoncrawl


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would you be interested in...
Discussion in 'Tournaments' started by onion, Dec 25, 2005.
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Album Rating: 4.5but it is so good
Album Rating: 3.0worn off
Digging: Waxahatchee - Cerulean Salt
Album Rating: 4.5Nah
September 19th
Album is gorgeous. the opening track is my favorite but it's all pretty brilliant
But this album isn't even that good
Digging: Azealia Banks - Broke With Expensive Taste
Album Rating: 4.0Makes me think of a more experimental, less sunny Young the Giant. I deeeeeg it.
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Digging: Ariel Pink - Pom Pom
Bands: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z


text:
Is the govt doing enough to contain food inflation?
Asked by cyrus irani, 06 Feb '11 11:24 am
Earn 10 points for answering
Answers (11)
Not at all, sir!! Food inflation has continued to rage even in 2010 with prices increasing by a whopping 17-18%. India wastes a huge amount of Food due to an antiquated supply structure which involves middlemen and mandis - and govt. have no control on them. The last couple of months witnessed sudden food inflation. The way the price of food items and vegetables soared, it created doubts in the minds of common people and economist alike. Winter is generally the time when fruits and vegetables are at the lowest prices. This was not so this year. The prices were way above the expected normal. Inflation in the food sector spilled to other sectors causing the rise in overall inflation.Answered by sumati gayki, 06 Feb '11 11:26 am
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Your vote on this answer has already been received
NoAnswered by Manju Sikri, 08 Feb '11 07:59 pm
Not at all, sir!! Food inflation has continued to rage even in 2010.Govt. have no control on it.........Answered by J K, 06 Feb '11 08:56 pm
It does not even know for sure what it should doAnswered by anil garg, 06 Feb '11 12:46 pm
and it does not have the inclination to do
and it does not have the inclination to do
No ---The Government is not at all sincere in its efforts to control food inflation.Answered by anantharaman, 06 Feb '11 12:44 pm
Leaders try to make more money to meet out Election expenditures.
Leaders try to make more money to meet out Election expenditures.
What more u want govt. to do? they r already voicing grave concern about prices as their household is also affected.Answered by shyamvanwari, 06 Feb '11 12:17 pm
only thing they r not bothered about others!
only thing they r not bothered about others!
No ,,,,,,,,,, rather some--- in government &, minister/s are hand in gloves in black marketing and hoarding ,,who will catch them they themselves are plundering the people .Answered by lolita mansfield, 06 Feb '11 11:34 am
Yes. They have shifted the responsibility from one ministry to another and from the Centre to the State Governments. And also they are saying repeatedly that the UPA is very much concerned with high inflation.Answered by Dharmarajan, 06 Feb '11 11:32 am
Certainly notAnswered by krish, 06 Feb '11 11:31 am
The government is not at all concerned about this as the ministers etc. do not have to face any difficulty due to this.Answered by HEMANT MEHTA, 06 Feb '11 11:29 am


text:
Carhartt.com offers an additional 40% off their Outlet Items with promotional code OUTLET40. Some members are reporting getting Free Shipping with promotional code x74wp6, yet others are not having success. There is also an option of signing up for email list and possibly receiving a Free Shipping code that way. Thanks deepfriedskunk, FakeMike, & fishmurdrr
A popular Item (limited sizes):
Frontpage Deal
Carhartt Coupon for Additional 40% off Already-Reduced Outlet Items: Men's Sandstone Thermal Lined Active Jacket $40.50 & more (expired)
Original Post
deepfriedskunk ( ) Nov. 5, 2012 at 9:49am
Carhartt Outlet sent out an email for an extra 40% off their outlet inventory with the code OUTLET40. [carhartt.com] This is a good chance to get some quality outerwear before it gets chilly! It ends 11/11/2012. The sizes are a little limited, but it's worth digging through. Here's an example:
MEN'S SANDSTONE ACTIVE JAC/THERMAL LINED [carhartt.com] Reg. $90, Sale $67.50 - 40% = $41
MEN'S SANDSTONE ACTIVE JAC/THERMAL LINED [carhartt.com] Reg. $90, Sale $67.50 - 40% = $41
View Forum Thread
102 Comments
MrBlackFriday ( ) Nov. 6, 2012 at 6:41am
Even with 40% off these jackets are still regular priced compared to local retail stores having sales on the same items.
bobbylight17 ( ) Nov. 6, 2012 at 7:02am
Are any of these good for rain?
kalrith ( ) Nov. 6, 2012 at 7:05am
Used both codes to get a jacket for my wife and me for $81.25 after tax. I was elated to find jackets in size medium tall for me! I usually have to buy large to fit my arms, but then I get a nice pooch where my gut's supposed to be
Really? Where are these retailers with women's Carhartt jackets for less than $40 like the following:
Edit: I got the first link above for my wife for $33 and the following for me in medium tall for $45: http://www.carhartt.co
Edit: I got the first link above for my wife for $33 and the following for me in medium tall for $45: http://www.carhartt.co
PSYCHOSTEVO ( ) Nov. 6, 2012 at 7:31am
Jesus, all out of what I wanted. I am pissed.
Think they will get more in before the 12th??
Think they will get more in before the 12th??
Looks like a lot of the shirts are oos, wish they would remove them from the results but that's not going to happen. Found a few flannel shirts in my size for sub $20, not going to get them though, I don't think.
m00ky ( ) Nov. 6, 2012 at 8:03am
I did. It took about an hour or so after I made my purchase
slicksteals1109 ( ) Nov. 6, 2012 at 9:02am
Mike_Diako ( ) Nov. 6, 2012 at 9:34am
No email here yet..
Got a raincoat for my husband from here with the 40% off and free shipping code...only $27.00...great deal.
Lookin4sumBargains ( ) Nov. 6, 2012 at 10:35am
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text:
wastewater treatment plants Companies in Bahrain
Business type: Technology - Manufacturer ×
Keyword: wastewater treatment plants ×
Industry: Agriculture ×
Location: Asia & Middle East ×
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AWAS GmbH Bayern Wastewater Treatment Plants
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AWAS has been in research, development and manufacturing of industrial waste water treatment plants for over 30 years and owns several patents and patent rights. We manufacture: - Flotation plants (DAF) - Emulsion splitting plants - Oil-Water separators, patented AWAS Galaxie Vortex separators - Filter systems - Wash water recycling plants, wash halls - Bio reactors We ...
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With 40 years experience within the sewage treatment sector, EUROPELEC is the n°1 French manufacturer of aeration system intended for wastewater treatment plants. EUROPELEC offers a full range of diffusers, aerators and mixers for both industrial and municipal applications. Our designed and manufactured in France products have been equipping WWTP over the five continents ...
Canamidex International
based in Richmond Hill, ONTARIO (CANADA)
We provide engineering, design, procurement, and construction services to the water and wastewater treatment and transfer Industry.We have a strong alliance with international manufacturers, who allow us to provide customized end- to-end turnkey solutions suited to our customer's requirements.Today we specialize in, Water Treatment, Waste Water treatment and reuse, Sludge ...
ThermoEnergy Corporation
based in Worcester, MASSACHUSETTS (USA)
ThermoEnergy is an integrated technologies company engaged in the worldwide development and sales of sustainable technologies for wastewater recovery and reuse. The company's water division is a leading provider of custom designed, turn-key systems for wastewater treatment and reuse, chemical/metals recovery, and water conservation. ThemoEnergy`s CAST® and RCAST ...
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Treatment a leading manufacturer provides water and waste water treatment products systems and services fmanufacturer OF water & waste water treatment products systems & Servior industrial, institutional, and municipal customers. Products such as membranes, filters, and deionization units. Systems for high purity process water, potable and wastewater treatment. Services ...
IPEC Consultants Ltd.
based in Burnaby, BRITISH COLUMBIA (CANADA)
IPEC Consultants Ltd. has been providing quality wastewater equipment since 1979. All IPEC equipment is designed and manufactured in Vancouver, British Columbia, Canada. IPEC equipment is widely accepted across North America for effective, economical treatment of process and wastewater streams. IPEC screening equipment is used for solid/liquid separation in the meat, ...
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based in Yokohama, JAPAN
AMCON Inc., team of professionals of dewatering, provides rich variety dewatering equipment from low priced micro compact dewatering equipment to high-capacity king-size dewatering equipment to meet your request.
BiOWiSH Technologies
based in Chicago, ILLINOIS (USA)
BiOWiSH Technologies owns exclusive and global intellectual property rights to the development, manufacturing, sales, marketing and distribution of BiOWiSH. BiOWiSH Technologies has created innovative products to serve needs in the consumer, wastewater treatment, agriculture, aquaculture, agronomy, solid waste management, soil and water remediation and industrial cleaning ...
DWT Group Oy
based in LAITILA, FINLAND
DWT Group Oy, is an innovative company specialized in providing sophisticated range of DEWACO and CAVIA brand equipment & solutions for the sludge and waste water treatment in industries and municipalities. The product range includes a variety of belt thickeners, belt filter presses and chain and flight type sludge and scum collector equipments. Thanks to the recent ...


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I was very impressed that every request I had with this service was completed. Even had my car washed!! Service even utilized my out-dated coupon for my complete oil change and tire rotation. I really appreciate them keeping the final charge reasonable! The service work was completed within the hour time frame given to me. Time went so fast as I visited with Pat C, my sales person, that I very surprised a hour had passed. Thanks to Brandon for being so helpful with this service visit. I give them all a 10 rating.


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The Search Marketing Shop are a search marketing agency offering excellence in SEO, AdWords Management, Social Media and Email Marketing. Our core service is ensuring websites are found on Google's first page when people search for the products or services that the site is offering and AdWords accounts are being optimised to maximum effect. Google is considered the number one source of information for people who are looking online to find what they require. It is therefore imperative that a business owner or marketing director utilises this powerful search engine. Consequently making sure they are found first, in front of their competitors. View Marketing Services
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2012 Kawasaki Ninja ZX-6R The Top Contender in the Middleweight Category Power. Speed. Handling. Dominance. The Ninja ZX-6R packs all this and more underneath its 599 cc engine twin spar aluminum frame and advanced Showa suspension. Whether you& ...
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Versys ABS A Multitalented Middleweight Motorcycle for the Masses The Kawasaki Versys is a rare exception to the old adage "jack of all trades master of none." This motorcycle's relaxed riding position makes it ideal for ...
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The Original Hooligan!To publicly suggest that one "ride naked" may seem a little risqué at first – until the listener sees the Kawasaki Z1000 motorcycle. With its emphasis on power backroad agility and obvious lack of ...
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Now that's what I call a comeback
12:01 am U.S. ET | Nov. 24, 2014It's official. The comeback that has followed the bottoming out of auto sales in 2009 has some serious legs. In fact, it's the longest-lasting post-recession sales rebound in modern history....
Read More »
Cardinale group makeover flexes digital muscle
12:01 am U.S. ET | Nov. 24, 2014In 2008, the recession was raging, and dealer Joe Cardinale decided to make some changes. He committed heavily to online sales and marketing, and parted ways with third-party lead providers, developed his own systems and software to manage his online presence. And he set stringent goals for his staff and held them accountable for results. It has worked wonders....
Read More »
Carmakers face uncertainly from EU's 2030 CO2 goals
Nov. 1, 2014 06:01 CETThe EU's new 2030 climate and energy targets create uncertainty for automakers because they let member states decide whether to include transport pollution in the EU's carbon emissions trading system....
Read More »
BILL LIA: Keep stores modern
12:01 am U.S. ET | Oct. 20, 2014"People keep asking us for our store designs," says Bill Lia, the 78-year-old CEO of Lia Auto Group in Albany, N.Y., which just finished building its 19th dealership. "We want to keep everything modern and up to date."...
Read More »
Timeline: Regrowing pains
12:01 am U.S. ET | Oct. 20, 2014A look back at the events of August, September and October, 2009...
Read More »
GM's loss, Hyundai's gain
12:01 am U.S. ET | Oct. 20, 2014Stores targeted for closure by one troubled brand were snapped up by a rising brand....
Read More »
A long, painful trip
12:01 am U.S. ET | Oct. 20, 2014U.S. auto dealers have been on a difficult, painful journey for the past five years. But it has been a positive one -- at least in the aggregate. That qualifier is important....
Read More »
MIKE WOOD: How hard are you willing to work?
12:01 am U.S. ET | Oct. 20, 2014Long hours and hard work in the past few years turned Mike Wood from a dealership manager into a dealer with four stores. The market has been loaded with acquisition opportunities, he says, provided the buyer is willing to put in the sweat and hustle....
Read More »
Ford to cut Fiesta output in Germany
Sept. 19, 2014 10:47 CETFord said it will cut production of its Fiesta subcompact at its plant in Cologne, Germany, in the fourth quarter because of slowing demand in some of the region's key markets....
Read More »
China's Brilliance mulls Italy car plant, prime minister says
Aug. 14, 2014 22:13 CETItalian Prime Minister Matteo Renzi said that Chinese carmaker Brilliance China Automotive had expressed an interest in opening a plant in Italy. Renzi is trying to encourage foreign investment in Italy, which has fallen back into recession....
Read More »
Europe's slump creates new opportunities at the top
Aug. 13, 2014 06:01 CETEurope's car sales slump took its toll on the executive ranks at automakers active in the region. Just 13 of the 37 executives who topped their organizational charts before the crisis are still there....
Read More »
European plant capacity usage improves, but breakeven still years away
June 10, 2014 06:01 CETCapacity utilization at Europe's vehicle plants should reach 70 percent this year. A return to the 2007 high of 85 percent is not expected until 2020 – if ever – forecasters say....
Read More »
No margin for error
12:01 am U.S. ET | June 2, 2014Even with the industry on a roll, dealers must keep working to control costs and protect their profitability....
Read More »
Toyota named most valuable car brand
May 21, 2014 06:15 CETToyota defended its title as the world's most valuable car brand. BMW was No. 2 while Ford made the biggest improvement, leaping past VW brand and Nissan into the top five, according to a study....
Read More »
European car market rebound on track, but discounting persists
April 11, 2014 06:01 CETWestern Europe's 7 percent first-quarter rise in new-car sales has some market watchers adjusting their full-year forecasts upward, but economic risks remain and profit-robbing car discounting continues....
Read More »
2009 Timeline: March massacre
12:01 am U.S. ET | March 31, 2014A timeline of the events that made up the industry collapse...
Read More »
Recession's lessons boost used-car sales
12:01 am U.S. ET | March 24, 2014Mike Cimino, vice president of Phil Long Dealerships in Colorado Springs, Colo., says his group has made a lot of changes in the way it runs its used-vehicle department in recent years....
Read More »
Help wanted: Industry restocks for recovery
12:01 am U.S. ET | March 17, 2014Showing increasing confidence in the pace and durability of the recovery, automakers are spending to restock depleted departments in core areas, such as sales, marketing, distribution, product planning and administration....
Read More »
Ferrari bets big on Europe's rebound
1:35 pm U.S. ET | March 14, 2014Ferrari's decision to open a theme park in Spain rather than China or another growing market is a big bet that Europe's slump is really over....
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Valeo second-half earnings rise 16% on strong China, U.S. demand
Feb. 21, 2014 09:43 CETValeo said second-half earnings rose 16 percent as demand for cars increased in China and North America and the European vehicle market improved....
Read More »
Growth of 2% forecast for Europe car market
Jan. 28, 2014 17:04 CETEurope's car market will probably expand 2 percent this year as demand recovers, ACEA said....
Read More »
December's rising incentives could signal dangers ahead
12:01 am U.S. ET | Jan. 12, 2014As auto sales return to pre-recession levels, some of the industry's old incentive games may be creeping back, too....
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This time, 16 million sales forecast is on merit
12:01 am U.S. ET | Dec. 28, 2013New U.S. light-vehicle sales are widely expected to surpass 16 million in 2014 for the first time since 2007, the culmination of a long recovery from the disastrous recession....
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Fiat says Italian plants strategy is showing 'positive' results
Dec. 20, 2013 16:42 CETThe first results of Fiat's move to use its plants in Italy to focus on higher-margin brands and build vehicles for export are encouraging, Fiat Chairman John Elkann and CEO Sergio Marchionne said....
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European car sales rise as VW, Renault make Nov. gains
Dec. 17, 2013 08:34 CETEuropean new-car sales rose a third consecutive month in November, the longest period of gains in four years, as demand for autos from VW and Renault contributed to signs that an industrywide decline is ending....
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How 3 dealerships are connecting with tech-savvy shoppersThree dealers have found ways to forge bonds with car shoppers who are short on time and long on Web smarts. A Honda store has mobilized a young sales team hired from Starbucks and Best Buy. Mon., November 17
» Watch the Video


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Bog-Standard Britain: How Mediocrity Ruined This Great Nation (Paperback)
|Paperback 237 pages
In stock
Usually despatched within 24 hours
No one would attack equality, would they? Quentin Letts just might. Not the notion of equality itself but the way it has become an industry for lobbyists, class warriors and New Labour's ageing Trots. Egalitarianism is a mania for today's policymakers and the soupy-brained halfwits we contrive to elect to public office. Appalled by free thinking, these equality junkies want to crush all individualism in our nation of once indignant eccentrics. Equality has been defiled by the ethnic grievance gang, by the harpies of feminist orthodoxy, by those risk-averse jackboots of town-hall bureaucracy with their quotas and creeds. Fair damsel Liberty has been whored by the best practice brigade, by the proceduralists of multinational corporatism in their company ties, by the glottal-stopping, municipal bores who insist that everyone must have prizes and that no culture can be dominant. Tilters against convention are assailed for their 'inappropriate' behaviour. Supporters of grammar schools are 'snobs'. Social nuance, once a vital lure to self-improvement, is deemed 'unacceptable'. Twenty-first century Britain's political cadre is so paralysed by class paranoia that it stops us attaining the best in schools, manners, language, fashion, popular culture. Elitism is a dirty word. The BBC stamps out the Queen's English because it is not 'accessible'. Celebrity morons are cultural pin-ups. Thick rools, OK. The glottal-stopping oikishness of our urban streets can be linked to modern equality's refusal to deplore. The prattishness of Jonathan Ross arises from a mad insistence that vulgarity is valid. Still think equality is such a great thing? You might not after reading this urgent, exasperated, witheringly funny book. Praise for 50 People Who Buggered Up Britain: '[Quentin Letts] discharges his duty with flair and tracer precision...an angry book, beautifully written.' The Spectator
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By Margaret McKinney
Highlands University
The New Mexico Bach Society Chorale and three Highlands University choirs take the stage at 2 p.m. Sunday at Ilfeld
Auditorium for Bach Fest 2014, the biggest celebration of the classical composer's work ever performed at the university.
Tickets prices are $8 for general admission. The price is $6 for seniors, students and Highlands University faculty and staff. Highlands students with valid IDs are free.
Ilfeld Auditorium is at 900 University Ave., Las Vegas.
On the heels of the program's deepest run in school history (matching the one made with many of those present on board two years prior), the Robertson girls' soccer team landed a dozen players on the All-District 5 1A-4A team for 2014.
Senior forward Caitlin Diefendorf earned one of two Player of the Year honors, while Ian Williamson was named Coach of the Year.
Submitted to the Optic
Fire managers at Santa Fe National Forest are planning to conduct a prescribed burn in the Gallinas Watershed on the Pecos/Las Vegas Ranger District this week.
The Gallinas Watershed burn may be conducted today through the month of December, only on favorable days as conditions allow.
A total of 1,000 acres may be treated in the Gallinas Canyon area approximately 20 miles northwest of Las Vegas. Small blocks may be treated each day to decrease the daily smoke volume.
Robertson will be one of four Class 4A football teams who'll get to sit out the first round of the state playoffs and wait for the outcome of this weekend's games.
The Cardinals are the defending state champions and No. 1 seed, having wrapped up an undefeated regular season (and District 2-4A title) with a 10-0 record. Coach Leroy Gonzalez's team will host a quarterfinal against the winner of Friday night's Hatch Valley-New Mexico Military contest.
A near-capacity crowd jammed the Frank Herrera Complex for the annual East-West football game on Nov. 8.
Visiting Robertson, the defending state champion and No. 1 ranked team in Class 4A, completed an undefeated regular season and clinched the district title with a 41-0 win.
Joseph Paul Griego rushed for three touchdowns, Dominic Lucero ran for two and Marcelo Cedillo scored one for Leroy Gonzalez's Cardinals (10-0).
West Las Vegas finished 3-7 in Adrian Gonzales' first season at the helm.
Last year's national runner-up and the preseason No. 1 team in NCAA Division II women's basketball, West Texas A&M never could shake pesky New Mexico Highlands on Wednesday night.
The Cowgirls led late in the first half and — despite falling behind by double digits in the second — they stayed within striking distance in an 84-73 defeat at the Wilson Complex.
Four Cowgirls finished in double figures. Jenny Johnson scored a team-high 18 points, followed by Claudia Meneses (13), Brittany Brown (12) and Giulia Simioni (10).
The Mora Rough Riders 4-H club gathered last Saturday at the Mora VFW to end their year with an annual banquet. As a youth development program, the 4-H organization can be found in almost every school community. By supporting youth from elementary school through high school with programs and hands-on activities, the 4-H club is designed to engage them in science, citizenship and healthy living.
The Robertson High School football team has a lot to be proud of, given its undefeated record so far this season and last year's state championship.
But the conduct of two of its key players this past weekend during the East-West game was disappointing and not befitting of the extraordinary team that the Cardinals have become.
Dominic Lucero and J.R. Gonzalez were ejected from Saturday's game after incurring unsportsmanlike conduct penalties.
And they will have to sit out the Cardinals' first playoff game.
• Memorial Middle School girls at Pojoaque tournament, TBA, Pojoaque
• West Las Vegas Middle School girls host sixth grade tourney, TBA, WLV
• NMHU women at Texas-Permian Basin, 1 p.m., Odessa, Texas
• Memorial Middle School girls at Pojoaque tournament, TBA, Pojoaque
• West Las Vegas Middle School girls host sixth grade tourney, TBA, WLV
Cross country
• NMHU at NCAA regionals, 11 a.m., Denver
William Hendrickson began his job as executive director of the Las Vegas San Miguel Economic Development Corporation on Nov. 17, having just arrived from Kuwait where he has spent the last eight years working for a government contractor as a project supervisor.
Copyright © 2014
The Las Vegas Optic is your source for local news, sports, events, and information in San Miguel County and Las Vegas, NM, and the surrounding area.


text: [ Crazed Driver Tries to Run People Over at Murder Scene [VIDEO] By Drew Weisholtz May 13, 2014 A tense scene became even more volatile on Wednesday when a driver sent pedestrians scurrying by barreling through a crowd gathered at the scene of a murder. Read More|Comment Category: National News Tags: crime, houston, murder, texas Send to a friend! Share on Facebook Share on Twitter Pin it! Reddit This! Share on Tumblr!


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Thank Barbara Bush for Speaking Out for Marriage Equality
February 1, 2011 by HRC staff
Post submitted by Michael Cole-Schwartz, Former HRC Director of Communications
As we told you about yesterday, former first daughter Barbara Bush is the latest high-profile New Yorker to speak out for equal marriage as part of our "New Yorkers for Marriage Equality" campaign. She was named CNN's "Person of the Day" as news of the video bounced around the world. The New York Times has a great story from last night about Bush's participation. When our allies speak up for our equality, we should say thank you. We've created a simple way for you to send a note to Barbara expressing your appreciation for her speaking out for equal rights. Click here to send your message of thanks.
Top Posts
Marriage Equality Coming to Arizona
October 17, 2014
Federal Judge Blocks Kansas's Ban on Marriage Equality
November 4, 2014
Shameful Sixth Circuit Decision Upholds Discriminatory Marriage Bans
November 6, 2014
Seismic Shift in Rome: New Catholic Church Document Praises Committed Gay and Lesbian "Partnerships"
October 13, 2014
Marriage Equality Coming to Wyoming
October 17, 2014


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Why Does the Bible Tell Husbands Specifically to Not Be Bitter with Their Wives (Colossians 3:19)?
Matt Redman - 10,000 Reasons (Bless the Lord) (Official Music Video)
What Does It Mean for a Christian to "Will and Work for [God's] Good Pleasure"? (Philippians 2:13)
See BURIAL, IV, 4, 5, 6.
Bibliography Information
Orr, James, M.A., D.D. General Editor. "Entry for 'WEEPING'". "International Standard Bible Encyclopedia". 1915.


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Home » Opinion » Columns
Another View - Jon Cowan: The left's four fiscal fantasies
In the mid-1960s, the federal government spent $3 on public investments for every $1 on the major entitlement programs. By the early 1970s, the ratio was one to one. Last year, it flipped. The federal government spent $3 on Social Security, Medicare and Medicaid for every $1 on federal investments, according to our analysis of data from the Office of Management and Budget. By 2022, the ratio will be one to five. In other words, entitlement programs are drowning out public investments just as international competition and technology demand that we need these investments the most.
Jon Cowan is president of the centrist think tank Third Way, where Jim Kessler is senior vice president.
- Kayla Bullwinkel: Schools must go after cyber bullies while respecting the First Amendment - 3
- George Will: Obama uses a bludgeon in Wisconsin - 2
- Jonah Goldberg: Feminists freak out over a guy's clothes - 1
- Another View -- Ted Cruz: Don't turn the Internet into a public utility - 8
- Charles Arlinghaus: Divided government keeps bad things from happening - 2
- Thomas Sowell: How race obsession can hurt minority students - 2
- Another View -- Tom Szold: After a 2014 GOP loss, some reflections and second guesses - 14
- Pat Buchanan: The oil weapon in America's hands - 0
- David Harsanyi: A terrible climate deal that doesn't matter - 1
John Stossel: Don't put control freaks in control of your governmentREADER COMMENTS: 4
- Police obtain warrants for suspect wanted in Dover, Manchester bank robberies - 0
- Abby Dion, 9, records a 10 in gymnastics meet - 0
- St. A skaters fall to Norwich - 0
- Monarchs lose in OT; win streak stops at 6 - 0
- Police searching for person stealing from cars in Manchester - 1
- College Football: Maine seniors want the coveted musket - 0
- College Hockey: Ice-making problem postpones UNH-PC - 1
- Pinkerton backfield a combination of power and speed - 0
- John Habib's City Sports: State Legion rejects Post 79's request for senior team - 2
Physician reprimanded after baby's brain damaged in deliveryREADER COMMENTS: 0
Jury acquits Mont Vernon driver, who was checking text, in death of former Amherst fire chief
Offend someone? To jail with you!
Obama to illegals: Come out of shadows
Plaistow town planner arrested
Driver acquitted in Amherst ex-chief's death
A kinder, gentler House Speaker?
College Football: Wildcats are CAA champs
College Hockey: Providence blanks UNH


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1602 Alton Rd Ste 608,
Miami Beach, FL, 33139-0305
Miami Beach, FL, 33139-0305
Tel: (305)704-7827
Stone Coast Academy offers a comprehensive online High School Diploma program that can allow you to earn your diploma from the comfort and convenience of your home or office.
Our program tests the individual for High School Equivalency in all subject areas including math, science, social studies, and language arts.
School Overview
|School Type
|Alternative School
|School Membership(s)School Assoc.
|Other school association(s)
|Religious Affiliation
|Grades Offered
Student Body
|Total Students
|491 students
|Student Body Type
|Students by Grade
Academics and Faculty
Nearby Schools:
All Schools | High Schools | Elementary Schools | Preschools | Public Schools
Show me:
- School Location Miles Students Grades
Miami BeachTemple Beth Shmuel Montessori
1719 Lenox Ave
Miami Beach, FL, 33139
(305)604-91010.3 mi | 8 students | Gr. PK-KG
All-girls | Montessori School (Jewish)
Miami BeachCongregation Beth Medrash Levi
1140 Alton Rd
Miami Beach, FL, 33139
(305)673-56640.5 mi | n/a students | Gr. 7-12
All-boys (Jewish)
Miami BeachLandow Yeshiva/lubavitch Educational Center
1140 Alton Road
Miami Beach, FL, 33139
(305)653-8770(Jewish)0.5 mi | 414 students | Gr. 1-11
Miami BeachRasg Hebrew Academy
2400 Pine Tree Dr
Miami Beach, FL, 33140
(305)532-6421(Jewish)1.1 mi | 488 students | Gr. PK-12
Miami BeachSt Patrick Elementary School
3700 Garden Ave
Miami Beach, FL, 33140
(305)534-4616(Roman Catholic)1.6 mi | 250 students | Gr. KG-8
School Reviews
Area Statistics
Recent Articles
Updated October 26, 2014
What do you do when you are dissatisfied with your local public schools? Homeschool your children? Send them to private school? Let's look at your options.
Your religion matters to you. You want your child to attend a school which will combine academics and religious education. Here is an overview of what is available together with some links to denominational web sites.
Add things up and you'll quickly find the answer- math is crucial both in academics and the real world. By following these strategies and following personal training programs, students can uncover their weaknesses and conquer math.


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pHrenzy pHucked: pH Productions' R-Rated Comedy Competition
* Additional fees apply.
The last date listed for pHrenzy pHucked was Saturday June 2, 2012 / 11:59pm.
Most Popular Comedy Event Nearby
Greg Proops' Podcast Taping: The Smartest Man in the World
- Full Price:
- $20.00
- Our Price:
- $10.00
Greg Proops tapes his unique podcast The Smartest Man in the World live at UP Comedy Clu...Learn More
Venue Details
There is a column blocking a portion of stage left where some action takes place. Try to avoid it when you choose your seat.Set Up info • Sep 30 2013 star this tip starred
BYOB - no restrictions, bring what you want!Stand Up & Toast info • Jan 14 2013 star this tip starred
Reviews & Ratings
Featured review from Goldstar Member
view more less of this review
Had some really good laughs! The audience consisted of about 10 folks, which made the experience very personal, but the host and contestants were hilarious! BYOB was a big plus. Show lasted an hour and a half. Priced at $5 on GoldStar, it was well worth it.
star this review starred report as inappropriate
Vote for your favorite comedian and help make them the king or queen of Phrenzy phucked! R-rated fun. It was totally awesome and the freedom made dumb comments from the audience awesome! Highly recommended.
star this review starred report as inappropriate
This was a fun show and I had a great time. I went to the midnight show so I expected more graphic content and it was pretty raunchy at times - but in a good way!
star this review starred report as inappropriate
The show was nice, really funny.
On Saturday nights, pH Productions gets a little naughtier, with pHrenzy pHucked — a dirtier, more adult version of their regular pHrenzy show. The audience is tougher, the comedy is more raw, and the host of the show is always someone crazy. Gone are the second chance rounds of the Friday night pHrenzy, the audience jumps right in at the beginning and starts voting out players right away! A spectacle that has to be seen to be believed. pHrenzy pHucked is not for the faint of heart!
About the Ticket Supplier: pH Productions
pH Productions is a performance ensemble dedicated to educating and exposing non-traditional audiences to live theater. pH's original comedic productions continually test the boundaries of form, humor and audience participation to provide the highest quality entertainment.


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Posts Tagged 'kristen'
Protected: Everything Is Different Now
This post will be put under a password in two days. Written on the 12th. If you need the password,... more
Protected: I don't want to tell you these things.
I don't want to tell you what's been going on for the past few months. I don't want to go... more
Protected: Love Letter #26
Dear Kristen, You come in to Summer Camp tomorrow, and I think we're both getting nervous. I talked to you earlier... more
Dirty Filthy Nasty
This story contains Daddy/girl language, rough sex, and lots of body fluids. This has been your trigger warning. "Will you pause... more
Protected: Love Letter #24
Dear Kristen, As I'm sitting here staring at this blank box in which to write to you, you're doing the dishes,... more
The Femme Conference in Photos
Kristen's Friday Femme Conference outfit Jessica Halem hosts FemmeSpeak, the spoken word night Fran Fucking Varian reads at FemmeSpeak my outfit for Saturday Kristen... more
Protected: Love Letter #23
Dear Kristen, It's been more than a month since I've written, almost two months. Last time I did, we were getting... more
Kristen & Sinclair Answer Your Questions, Episode 3: "How Can I Be More Open About Kink?"
Kristen & I answered Laura's question on video this morning from Seattle ... hopefully our colds don't make us sound... more
Protected: Flying
"There's so much beauty in the world. Sometimes I feel like I'm seeing it all at once, and it's too... more
Kristen & Sinclair Answer Your Questions, Episode 2: "How To Have a Successful Threesome"
Following up Episode 1, "I Want to be Taken", Kristen and I answered another question for y'all, this time about... more


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All Schools
(2) All Schools
(2) High Schools
(1) High Schools
(1) Elementary Schools
(2) Elementary Schools
(2) Public Schools
(13) Public Schools
(2) All Schools
(2) High Schools
(1) High Schools
(1) Elementary Schools
(2) Elementary Schools
(2) Public Schools
(13) Public Schools
There are 2 private schools in zipcode 48843, MI, serving 187 students.
Minority enrollment is 1% of the student body, which is less than the MI state average of 14%.
The student:teacher ratio of 11:1 is equal to the state private school average of 11:1.
48843, Michigan Private Schools
- School Location Students Grades
HowellNorthbridge Christian Academy
915 N. Michigan Ave.
Howell, MI, 48843
(517)552-0218n/a students | Gr. 6-12
All-boys | Special Program Emphasis (Christian)
HowellSt. Joseph School
425 E Washington St
Howell, MI, 48843
(517)546-0090(Roman Catholic)187 students | Gr. K-8
Zipcode Statistics
|About This Zipcode (48843)
|Zipcode Statistics
|(MI) State Statistics
|Population (Approximate)
|42,931 people
|9,643,732 people
|Age 25+ w/College Degree
|Median Household Income
Recent Articles
Updated October 26, 2014
What do you do when you are dissatisfied with your local public schools? Homeschool your children? Send them to private school? Let's look at your options.
Your religion matters to you. You want your child to attend a school which will combine academics and religious education. Here is an overview of what is available together with some links to denominational web sites.
Add things up and you'll quickly find the answer- math is crucial both in academics and the real world. By following these strategies and following personal training programs, students can uncover their weaknesses and conquer math.


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NMCADV Administrative Assistant – Santa Fe
Posted on 20. Nov, 2014 by alishac in Jobs
Job Title: Administrative Assistant Employee Type: Non-Exempt, Part-time Benefits: Full Reports to: Director of Finance and AdministrationPosition OverviewThe purpose of the position is to support the activities of the Director of Finance and Administration and the Executive Director.Skills, Knowledge and AbilitiesAbility to organize, plan and prioritizeKnowledge of administrative and clerical proceduresAbility to communicate effectively with […]
NMCADV joins YWCA New Mexico in a Week Without Violence
Posted on 13. Oct, 2014 by alishac in Events, News
During the third week of Domestic Violence Awareness Month, October 13-17, the NMCADV is proudly partnering with YWCA New Mexico and other local co-sponsors in a Week Without Violence. A Week Without Violence has been sponsored by YWCA's across the country for the past 20 years to raise awareness about domestic violence and inspire communities […]
Children's Life Skills Facilitator – Enlace Comunitario
Posted on 07. Oct, 2014 by alishac in Jobs
ENLACE COMUNITARIO seeks bilingual (SP/ENG) Children's Life Skills Facilitator with BA in related field to work with immigrant child witnesses of domestic violence. Facilitator will also back up crisis phone line. Competitive salary and excellent benefits. Email resume and cover letter to firstname.lastname@example.com. Job Description:Children's Life Skills FacilitatorDepartment: Supportive ServicesReports to: Volunteer and Supportive Services CoordinatorSupervises: […]
Valencia Shelter Services Executive Director Alexandria Taylor – "We Don't Need to See It to Believe It"
Posted on 02. Oct, 2014 by alishac in Articles, News
Member program executive director and NMCADV board member shares her thoughts on our responsibility take action against violence.
Animal Abuse & Domestic Violence – Pam Wiseman & Daniel Abram on KSFR
Posted on 24. Sep, 2014 by alishac in Events, News, Projects
NMCADV Executive Director Pam Wiseman and Animal Protection of New Mexico Deputy Director Daniel Abram give their informative views on animal abuse and domestic violence and talk about our project the Companion Animal Rescue Effort (CARE).
NMCADV attends the first meeting of the Conceptual Clarity Project
Posted on 23. Sep, 2014 by alishac in Articles, Events, Meetings, News
Last week in Ann Arbor, MI experts from around the country met to explore the future of Batterer Intervention Programs. NMCADV executive director Pam Wiseman was proud to attend and be part of this project. The Conceptual Clarity Project will be ongoing and continue to develop advancements and innovations to batterer programs. There has been some skepticism […]
NMCADV Executive Director Pam Wiseman comments on the Ray Rice incident
Posted on 10. Sep, 2014 by alishac in Events, News
September 10, 2014Advocates around the country reacted with surprise and relief when the Ray Rice domestic violence incident received so much media attention. After all, this is the sort of thing – and worse – that domestic violence advocates see every day. Unfortunately, in many places, the commission of an act of domestic violence is […]
Housing Coordinator – Valencia Shelter Services, Los Lunas
Posted on 22. Jul, 2014 by alishac in Jobs
Valencia Shelter Services is seeking a uniquely talented, compassionate, and professional individual to provide advocacy and support for assessing and educating all Valencia Shelter Services' client's housing needs. The position requires outreach, advocacy and case management proficiency. Candidates will be considered who demonstrate a working knowledge and experience with issues pertaining to trauma informed service delivery, domestic violence, and sexual […]
Esperanza Shelter – Residential Services Supervisor
Posted on 12. May, 2014 by alishac in Jobs
Esperanza Shelter for Battered Families, Inc.Job Title: Residential Services SupervisorProgram: Residential ShelterReports To: Executive DirectorHours: 40 Hours a week; benefits available Description: The Residential Services Coordinator of Esperanza is responsible for workingcollaboratively with the Executive Director, the Non-Residential Supervisor and agency staff to develop, maintain and oversee the residential services […]
Esperanza Shelter – Bilingual Advocate/Case Manager
Posted on 12. May, 2014 by alishac in Jobs
Esperanza Shelter for Battered Families, Inc.Job Title: Bilingual Advocate/Case ManagerProgram: Residential ShelterReports To: Residential Services CoordinatorSalary Range: $14.00 per hour, medical/dental benefits available; paid leave; Employer-sponsored retirement plan.Hours: 40 Hours a weekRequirements: Bachelor's Degree in Human Services related field or a combination of relevant education, training, and experience totaling 4 years. […]


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Submitted by ATruepatriot on Sat, 10/05/2013 - 07:43. Permalink
4 b : an ideal or hypothetical set of facts, principles, or circumstances — often used in the phrase in theory.
6 a : a hypothesis assumed for the sake of argument or investigation.
If I disappear from a discussion please forgive me. My 24-7 business requires me to split mid-sentence to serve them. I am not ducking out, I will be back later to catch up.
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HEAD Maria Sharapova Tennis Racquet Bag
Our Price$99.99
Item #: 331511497
The bag carried by Maria Sharapova on court. This bag ideally suited towards the female tennis player looking to carry everything she needs to the tennis court.
- Carries 4-6 tennis racquets
- One pocket lined with CTT (Climate Control Technology)
- Inside mesh pocket
- Detachable padded shoulder straps
- 3 zippered compartments
- Includes a shoe bag
- Inside mesh pocket for keys and valuables.
- Items may be returned within 60 days of the order date to a Sport Chek retail store or a Sport Chek warehouse. Items must be returned unused/unworn and electronics unopened. See Online Return Policy & Return Instructions for more information.