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Peptidylarginine deiminases (PADs) convert arginine within a peptide (peptidylarginine) into peptidylcitrulline. Citrullination by human PADs is important in normal physiology and inflammation. Porphyromonas gingivalis, a major pathogen in periodontitis, is the only prokaryote described to possess PAD. P. gingivalis infection may generate citrullinated peptides, which trigger anti-citrullinated peptide antibodies. In susceptible individuals, host protein citrullination by human PADs in the joint probably perpetuates antibody formation, paving the way for the development of chronic arthritis. Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis.
Arginine is a positively charged, hydrophilic amino acid that is often found on the surface of proteins, where it participates in ionic interactions with other amino acid side chains and forms stabilizing hydrogen bonds with both the peptide backbone and amino acid side chains. These characteristics make it a key amino acid in the three-dimensional organization of proteins and in the interaction with other biological molecules. Hence, post-translational modification of arginine can alter the three-dimensional protein structure and function and potentially expose previously hidden epitopes to the immune system. Deimination (citrullination) of arginine side chains (peptidylarginine) to form peptidylcitrulline is one of many recognized post-translational modifications of this amino acid. This post-translational conversion is catalyzed by the family of peptidylarginine deiminase (PAD) enzymes. The process of protein citrullination plays a vital role in normal physiology, in which it is involved in the formation of rigid structures such as hair, skin, and myelin sheaths [1]. Aberrant citrullination has been observed in diseases of the skin and nervous system and in inflammatory arthritides, of which rheumatoid arthritis (RA) is one example [1]. Despite the ubiquity of citrullinated proteins, the autoantibody response to citrullinated proteins is largely restricted to RA [2]. The switch that leads to the generation of antibodies to citrullinated peptides and thus loss of immune tolerance to citrullinated proteins is likely to involve a complex interplay of individual genetic and environmental factors.
Citrullination by human and bacterial peptidylarginine deiminases
In humans, a family of five PAD enzymes (PAD1 to 4 and PAD6), encoded by five genes clustered on chromosome 1p35-36, has been described [3]. Apart from PAD4, which can translocate to the nucleus, PAD enzymes are typically found in the cytoplasm of various cell types and show a characteristic tissue distribution. The localization and functions of each of the human PAD enzymes are summarized in Table 1. Homologous amino acid sequences for some or all of these PADs exist in other eukaryotic species, such as the mouse, chicken, frog, and bony fish. Among prokaryotic species, PAD activity has, to date, been described in Porphyromonas gingivalis only [4]. P. gingivalis is a major pathogen in periodontitis, a disease that (akin to RA) is a chronic inflammatory disorder characterized by pro-inflammatory cytokine production and erosion of bone.
Table 1. Localization and function of human peptidylarginine deiminase enzymes
As protein citrullination in the joint is not specific to RA [5] and auto antibodies to citrullinated proteins precede the clinical signs of RA [6], it has been proposed that oral citrullination of human and bacterial proteins by P. gingivalis PAD (PPAD) in an infectious context prior to the onset of RA could break tolerance and trigger a latent antibody response against citrullinated protein [7]. Once tolerance is breached, citrullination of host proteins by human PADs perpetuates the immune response through epitope spreading and cross-reactivity, resulting in chronic inflammatory disease (Figure 1). Citrullination by both human and bacterial PAD enzymes may thus provide a target for inhibiting the immune response at an early stage in the inflammatory pathway of RA.
Figure 1. Simplified model illustrating the hypothesis that Porphyromonas gingivalis-mediated citrullination triggers anti-citrulline autoimmunity in rheumatoid arthritis. Citrullination by P. gingivalis peptidylarginine deiminase (PAD) in the inflammatory context of periodontitis produces bacterial and host-derived citrullinated peptides to which the immune system mounts a humoral immune response with the production of peptidylcitrulline antibodies. Inflammation-induced citrullination by human PAD enzymes in the gingiva is also possible (dashed arrow). Tissue injury and inflammation in the joint lead to activation of human PAD enzymes and citrullination of host proteins, such as a-enolase, vimentin, fibrin(ogen), and collagen type II. Peptidylcitrulline antibodies bind citrullinated host and bacterial peptides, which may show molecular mimicry, and in genetically susceptible individuals (presence of the certain HLA alleles), intra- and intermolecular epitope spreading leads to a sustained immune response with the formation of high-affinity antibodies to host citrullinated proteins.
The best-established autoantigens in RA include α-enolase, fibrinogen, vimentin, and type II collagen (reviewed in [1]) and all are efficiently deiminated by mammalian PADs. In theory, citrullinated peptides from these antigens could also be generated by PPAD, although this has yet to be demonstrated experimentally. Alpha-enolase is of particular interest in this respect because it is highly conserved among eukaryotes and prokaryotes. A sequence of nine amino acids (Asp-Ser-Arg-Gly-Asn-Pro-Thr-Val-Glu) spanning the immunodominant epitope on the peptide known as citrullinated enolase peptide-1 (CEP-1) is 100% identical to the corresponding region in P. gingivalis enolase, and affinity-purified antibodies to CEP-1 react with recombinant enolase citrullinated in vitro from both humans and P. gingivalis [8], providing an attractive target for molecular mimicry between human and bacterial species.
Etiological association between periodontitis and rheumatoid arthritis
The rationale for considering both human and P. gingivalis PADs in the etiology and pathology of RA is also based on epidemiological data suggesting an association between the two diseases (reviewed in [9]). Periodontitis and RA are chronic inflammatory disorders characterized by erosion of bone and production of pro-inflammatory cytokines. The reported prevalence of periodontitis is highly variable; in one large study of the American population, the prevalence was 4.2% [10]. Epidemiological studies have shown that RA is more prevalent among patients with periodontal disease (3.95%) than in the general population (1%) [11]. In addition, patients with RA have a higher frequency of advanced periodontal disease than the general population [12]. P. gingivalis, Treponema denticola, and Tannerella forsythia are some of the major Gram-negative bacteria that exist as part of a complex bacterial biofilm in the gingival crevice and are linked to the development and progression of periodontitis but can also be found in lower numbers in periodontally healthy subjects [13]. Long-term plaque accumulation and an interplay of host and bacterial factors result in chronic inflammation and tissue damage. Destruction of the adjacent bone and periodontal ligament attachment may eventually lead to tooth loss [14]. P. gingivalis antibody levels have been shown to correlate with anti-CCP (anti-cyclic citrullinated peptide) antibody titres [15], making this periodontopathic oral bacterium an attractive candidate environmental trigger in the development of RA.
Several research groups have reported an increased variety and number of oral bacterial DNA and antibodies targeting these bacteria in serum and synovial fluid of patients with RA and other inflammatory joint diseases compared with controls (non-inflammatory arthritides or healthy donors) [15-19]. Oral bacterial DNA could reach the joint as free DNA or intracellularly in immune cells. Owing to the stringent growth requirements of live oral bacteria, their presence in the joint is unlikely, and no viable organisms have been obtained from synovial fluid [19]. However, these observations need to be interpreted with caution since many bacterial antibody assays using whole-bacterium lysates are of questionable specificity, and the same applies to polymerase chain reaction-based detection and DNA-DNA hybridization using a complex nucleic acid mixture containing an excess of human DNA. A number of antibiotics used in the treatment of periodontitis, such as tetracyclines and clarithromycin, are efficacious in the treatment of RA [20-24], although to date there has been no direct evidence that this therapeutic effect is due to their anti-bacterial activity. For example minocycline has anti-inflammatory and anti-apoptotic effects that are separate from its anti-bacterial role and that are mediated by inhibition of nitric oxide synthase [25], matrix metalloproteinases [26], and caspases [27]. As will be discussed below, minocycline and other tetracycline derivatives may also be direct inhibitors of human PAD4 [28] and P. gingivalis arginine-gingipains [29], which are potent proteinases and major virulence factors in periodontal disease.
Human peptidylarginine deiminases in disease
In normal physiology, PAD enzymes are involved in regulatory processes such as epidermal differentiation, maturation of hair follicles, insulation of nerve fibers, and epigenetic regulation. Aberrant citrullination contributes to skin diseases such as psoriasis and neurological disorders such as multiple sclerosis, Alzheimer disease, and prion disease [30-32]. Citrullination of histones and other nuclear proteins by PAD4 is involved in transcriptional regulation and response to cellular stresses and contributes to the innate immune response through the formation of neutrophil extracellular traps [33-36]. Recently, citrullination of various chemokines has been shown to have functional roles in receptor binding and signalling, proteolytic cleavage, and extravasation of neutrophils [37,38]. Furthermore, citrullination appears to play a role in the coagulation system and associated pathways, and this is supported by the findings that in vitro citrullinated fibrinogen shows impaired thrombin-catalyzed fibrin polymerization [39] and in vitro citrullination of antithrombin with PAD4 abolishes its thrombin-inhibitory activity [40]. Both citrullinated fibrin(ogen) and citrullinated antithrombin were detected in patients with inflammatory arthritis [40,41].
Citrullination is thus a widespread phenomenon in normal physiology and inflammation, although targeting citrullinated proteins for an autoimmune response is relatively restricted to RA as shown by the high specificity of anti-citrullinated peptide antibodies for RA [2]. Therefore, it is important to consider which of the deiminases are used for generating the antigens that drive this autoimmunity. On the transcriptional level, various single-nucleotide polymorphisms in the PADI4 gene have been associated with RA in Asian but not in Caucasian populations (reviewed in [42]). Suzuki and colleagues [43] showed that the presence of the disease-associated PADI4 haplotype led to a more stable mRNA, which they suggested increased PAD4 expression and thus levels of citrullinated proteins. However, as PAD inhibitors would work on the post-transcriptional level, we will focus on the expression of PAD enzymes. PAD2 and PAD4 expression has been demonstrated in rheumatoid synovium [44] and synovial fluid cells [45] and extracellularly in synovial fluid [46]. PAD4 differs from other PAD isotypes in its capacity to undergo nuclear translocation due to the presence of a nuclear localization sequence and this translocation has been shown to be induced by tumor necrosis factor-alpha in murine and human oligodendroglial cell lines [47]. PAD expression in the synovial tissue is not specific to RA. It occurs in a variety of inflammatory synovitides [41] and diseases such as inflammatory bowel disease, polymyositis, and interstitial pneumonia [48]. While PAD2 is expressed in the synovia of both patients with inflammatory arthritis and osteoarthritis (OA), PAD4 is predominantly expressed in the synovia of patients with inflammatory arthritides rather than OA [44]. The converse was observed in the extracellular compartment, where Kinloch and colleagues [46] showed the presence of PAD4 in the synovial fluid of patients with RA, spondyloathropathies, and OA, while PAD2 expression was found in both groups of patients with inflammatory arthritis but was notably absent in those with OA. PAD2 and PAD4 expression in the synovium correlates with inflammatory cell infiltration, synovial lining thickness, and vascularity of the deep synovium [44]. Foulquier and colleagues [44] demonstrated PAD2 and PAD4 in close proximity to citrullinated fibrin deposits, although simultaneous detection of the two enzymes in the same area was rare.
Bacterial peptidylarginine deiminase
P. gingivalis, considered a primary pathogen in chronic periodontitis, is a Gram-negative, non-motile anaerobic bacterium that is the only prokaryote described to date to express a functional endogenous PAD enzyme [4]. To date, investigations of bacterial deiminases have focused mainly on enzymes that use free, non-peptidyl arginine or arginine derivatives such as arginine deiminase (ADI). ADIs are enzymes that catalyze the deimination of free arginine to citrulline, releasing ammonia. They are key enzymes in the widespread anaerobic pathway of arginine degradation and many pathogenic microorganisms use this pathway for energy production. Since ADIs are missing in higher eukaryotes, the enzyme constitutes a potential anti-parasitic and anti-bacterial drug target [49]. The other group of structurally and functionally related enzymes produced by most bacterial species consists of agmatine deiminases (agmatine iminohydrolases, or AIHs). AIHs deiminate agmatine (a decarboxylation product of arginine) to N-carbamoylputrescine and ammonia.
On the amino acid sequence level, PPAD shows no relation to eukaryotic PAD; instead, position-specific iterative-basic local alignment search tool (PSI-BLAST) search connects PPAD to the AIH family (Figure 2). Although the molecular structure of PPAD is unknown, its sequence similarity to AIHs with conservation of key catalytic and guanidino-binding residues indicates that the catalytic domain shares the common α/β-propeller fold of the guanidine-group modifying enzyme (GME) superfamily, which includes human PADs, microbial ADI, aminotransferases, dimethylarginine dimethylamino hydrolases, and AIH [50]. Of note, the database annotation of AIH is confusing since these enzymes are often referred to as 'Porphyromonas-type peptidyl-arginine deiminases' although they most likely do not possess PPAD activity. The three-dimensional structure of PPAD was predicted to consist of the amino-terminal catalytic α/β-propeller domain, followed by an immunoglobulinlike β sandwich. In comparison, the published structure of human PAD4 is composed of two amino-terminal immunoglobulin-like β sandwich domains, followed by the catalytic α/β-propeller domain [51].
Figure 2. Alignment of amino acid sequence of catalytic domains of Porphyromonas gingivalis PAD (PPAD) (residues 86 to 363), AIH from Dyadobacter fermentans DSM 18053 (locus Dfer_2630, residues 60 to 352), and human PAD4 (residues 306 to 556). Residues identical in PPAD and AIH and/or PAD4 are highlighted. Guanidino-binding (#) and catalytic residues (*) that are conserved in all families of guanidino-group modifying enzyme superfamily are indicated. The amino-terminal sequence of each enzyme is unique. In PAD4, the amino-terminal portion is folded into two consecutive immunoglobulin-like β-sandwich domains preceding the catalytic domain harboring the α/β-propeller fold [51]. A long 200-residue carboxy-terminal extension of PPAD is predicted to adopt an immunoglobulin-like β-sandwich structure [50]. AIH, agmatine iminohydrolase; PAD, peptidylarginine deiminase.
Unlike mammalian enzymes, PPAD is able to deiminate both free arginine and peptidylarginine ([4] and our own unpublished observations) and preferentially targets carboxy-terminal arginine, although internal citrullination cannot be excluded. Furthermore, deimination by human PAD is calcium-dependent in contrast to that by PPAD, which does not appear to require any specific cofactors ([4,52] and our own unpublished observations). P. gingivalis has been shown, however, to increase intracellular calcium concentrations by cleavage of proteinaseactivated receptor 2 (PAR 2), a G protein-coupled receptor found on the neutrophil surface, which may in turn promote human PAD activation [53].
The physiological role of PPAD is unclear. It was suggested that production of ammonia during deimination enhances the survival of P. gingivalis within the periodontal pocket [4]. Indeed, ADI- and AIH-catalyzed ammonium production among bacterial species is known to act as a virulence factor, promoting the survival of microbial pathogens in the host environment. Ammonia neutralizes acidic environments and thereby optimizes gingipain and PPAD function, inactivates hemagglutinins, promotes ATP production, and has negative effects on neutrophil function [4,54]. Furthermore, it can be speculated that PPAD acts as a virulence factor by generating citrullinated peptides, which may assist the bacterium in spreading and circumventing the humoral immune response. However, the requirements for citrullination by PPAD have not been well investigated to date and it is unknown whether the citrullinated peptides are immunogenic.
Thus, we conclude that PPAD may be more relevant to the initiation of autoimmunity at a site distant from the joint, such as the gingiva, and that PAD2 and PAD4 are important in generating autoantigens that perpetuate autoimmunity in RA once tolerance is breached. Further work is required to identify the regulation and substrate specificity of each enzyme in order to establish a more precise role in the autoimmune response.
Therapeutic peptidylarginine deiminase blockade in rheumatoid arthritis
Although PAD4 has been most extensively studied as a potential therapeutic target in RA (mainly based on the availability of a crystal structure [51]), PAD2 may also be important. It is proposed that selective inhibition of PAD would reduce the levels of citrullinated proteins and consequently suppress the humoral immune response directed to citrullinated antigens in RA. Because PAD4 has an important physiological role in regulating gene expression and PAD4 translocates into the nucleus from the cytosol, potential inhibitors may need to be selective for the extracellular compartment or other PAD isotypes to avoid unwanted effects on gene transcription. It is, however, not known whether intracellular or extracellular PAD is important in the pathophysiology of RA.
Paclitaxel is a chemotherapeutic agent that was initially derived from the bark of the Pacific yew tree. It inhibits angiogenesis by interfering with microtubule function in cell mitosis, migration, chemotaxis, and intracellular transport [55]. In addition, in the millimolar range (half-maximal inhibitory concentration [IC50] = approximately 5 mM), paclitaxel inhibits PAD isolated from bovine brain [56]. It has been shown to prevent the induction of collagen-induced arthritis (CIA) and cause significant regression of existing CIA [57]. An open-label multicenter phase II study of paclitaxel in patients with RA was completed in July 2008, although results of this are still pending [58].
Other PAD inhibitors include F-amidine [N-α-benzoyl- N5-(2-fluoro-1-iminoethyl)-l-ornithine amide], Cl-amidine [N-α-benzoyl-N5-(2-chloro-1-iminoethyl)-l-ornithine amide], and 2-chloroacetamidine, of which Cl-amidine was reported to be the most potent (IC50 = 5.9 μM) [59]. Ex vivo studies with F-amidine and Cl-amidine, using a cell line and an assay measuring PAD4-mediated citrullination of a nuclear protein and the resulting enhancement in binding to another protein, indicated that these inhibitors are bioavailable [59,60]. F-amidine irreversibly inhibits PAD4 via the specific modification of Cys 645, an active-site residue that is critical for enzyme catalysis. Cys 645 acts as a nucleophile to form a thiouronium intermediate that is hydrolyzed to form citrulline. Cl-amidine and 2-chloroacetamidine are thought to act via a similar mechanism [59,61]. Inactivation by F-amidine and Cl-amidine is calcium-dependent [60]. In vitro studies with PAD4 have shown that calcium binding leads to a conformational change that moves Cys 645 and His 471 into positions that are competent for catalysis [51] and presumably reactive with F-amidine and Cl-amidine. This is of therapeutic importance as these compounds would therefore be expected to inhibit PAD4 in its activated state only at sites of inflammatory activity such as the synovium and not the inactive enzyme at other sites in the body, limiting toxicity [59]. Willis and colleagues [62] recently showed that Cl-amidine treatment in CIA is able to inhibit clinical disease activity scores by 55%, 53%, and 42% in the 50, 10, and 1 mg/kg per day groups, respectively. Histological severity scores and complement C3 deposition scores paralleled the decreases in disease activity. In addition, mice receiving Cl-amidine showed reduced epitope spreading by peptide microarray, especially to citrullinated joint antigens. Interestingly, there were no changes in the percentages of T-cell, B-cell, or monocyte populations in treated mice compared with controls [62]. These results suggest that Cl-amidine may represent a novel class of RA therapeutics that specifically target citrullination.
Bhattacharya and colleagues [63] demonstrated that human astrocytes subject to pressure showed elevated PAD2 levels, increased intracellular calcium concentrations, and increased citrullination. Treatment with the cell-permeable calcium chelating agent BAPTA-AM (1,2-bis-(o-Aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester) resulted in decreased intracellular calcium concentration and PAD2 levels. These results suggest that calcium modulation may be an alternative therapeutic strategy in modulating PAD activity and citrullination, although we would argue that this mechanism is too broad to be applicable in practice.
On the basis of the therapeutic use of tetracyclines in RA [23], Knuckley and colleagues [28] screened tetracycline derivatives (minocycline, doxycycline, tetracycline, and chlortetracycline) for their potential to inhibit PAD4 activity. Chlortetracycline was identified as the most potent inhibitor (IC50 = 100 μM) and was suggested to bind to a region distal from the active site [28]. Streptomycin, an aminoglycoside antibiotic, was also tested because of its two guanidinium groups that could act as inhibitors of PAD4. Streptomycin was found to inhibit PAD4, though with a lower potency (IC50 = approximately 1.8 mM), and was suggested to bind within or in close proximity to the active site. The data suggest that these compounds could provide a valuable scaffold for engineering inhibitors with greater potency and selectivity.
Porphyromonas gingivalis peptidylarginine deiminase as a target for treatment in rheumatoid arthritis
The unique nature of PPAD in terms of its different amino acid sequence, cofactor requirement, and domain organization compared with human PADs (Figure 2), along with its location on the bacterial cell surface [4], would make this enzyme a potential target in the treatment of RA provided that its possible involvement in disease etiology or pathology is substantiated in future studies. Development of therapeutics targeting PPAD is further encouraged by advances in design and synthesis of inhibitors against parasite-derived ADI with potentials to be used as anti-parasitic agents [64]. Since ADI, PADs, and PPAD are likely to use the same catalytic machinery to deiminate (peptidyl)arginine (Figure 2), a similar chemistry may be applied to develop PPAD inhibitors. The calcium-independent deimination of carboxy-terminal arginine residues specific to PPAD can be explored to develop highly selective compounds with little or no cross-reactivity with host enzymes.
McGraw and colleagues [4] reported that native PPAD, purified from the bacterial culture supernatant, was missing the N-terminus inferred from the DNA sequence because of proteolysis at the Arg43-Ala44 peptide bond. This might have been an artifact caused by the potent proteases, arginine-gingipains, which co-purified with PAD at the initial stages of protein purification, or might have true biological significance (for example, arising during export of the enzyme from the cell to form the mature protein). A recent paper on PPAD reported that the full-length, uncleaved form was unstable and had only 40% activity when compared with the truncated form of the enzyme [52]. Future studies aimed at identifying the mature, in vivo form of PPAD and its enzymology are required in order to pin down the biologically relevant form of the enzyme and as such the more appropriate target for therapeutic blockade.
As the PPAD enzyme is not well studied, there are no published studies on possible therapeutic inhibitors. To gain insight into the catalytic mode of PPAD, McGraw and colleagues [4] tested various compounds that might interfere with the catalytic cysteine residue (Cys 351) or substrate binding. They reported that the serine- and cysteine-protease inhibitor leupeptin is able to completely inhibit PPAD at millimolar levels (5 mM), with other inhibitors such as thiourea, thio-L-citrulline, and the serine- and cysteine-protease inhibitor TLCK (N-alpha-p-tosyl-L-lysine chloromethyl ketone) being inhibitory at higher concentrations (12.5 to 50 mM) [4]. Apart from the relatively low inhibitory potency, these compounds are either toxic (thiourea) or unselective (thio-L-citrulline is a potent inhibitor of nitric oxide synthase) [65] but nonetheless provide a basis for the development of more potent, specific inhibitors.
We have summarized a possible role for PPAD in breaking tolerance to citrullinated proteins, with human PAD2 or PAD4 or both maintaining the generation of citrullinated antigens in the joint. However, the evidence remains speculative and clearly requires further investigation of the mechanisms of activity of the enzymes involved and how the apparently unique PAD encoded by P. gingivalis could generate immunogenic peptides. If these hypotheses are further substantiated, PAD blockade has the potential to switch off autoimmunity at the point of initiation and inhibit the maintenance of the pathology in RA. Thus, inhibition of bacterial and human PADs could become the first treatment targeting the generation of the actual antigens that drive the disease.
ADI: arginine deiminase; AIH: agmatine iminohydrolase; CEP-1: citrullinated enolase peptide-1; CIA: collagen-induced arthritis; Cl-amidine: N-α-benzoyl- N5-(2-chloro-1-iminoethyl)-L-ornithine amide; F-amidine: N-α-benzoyl- N5-(2-fluoro-1-iminoethyl)-L-ornithine amide; IC50: half-maximal inhibitory concentration (concentration of inhibitor that yields 50% inhibition); OA: osteoarthritis; PAD: peptidylarginine deiminase; PPAD: Porphyromonas gingivalis peptidylarginine deiminase; RA: rheumatoid arthritis.
Competing interests
The authors declare that they have no competing interests.
This work was supported by the Arthritis Research Campaign (NW and PJV) and in part by grants DE 09761 and 1642/B/P01/2008/35 from the National Institutes of Health (Bethesda, MD, USA) and the Department of Scientific Research of the Polish Ministry of Science and Education, respectively (JP). The Faculty of Biochemistry, Biophysics, and Biotechnology of the Jagiellonian University Krakow is a recipient of structural funds from the European Union (grant number POIG.02.01.00-12-064/08 - 'Molecular biotechnology for health').
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J Cell Biol 2009, 184:205-213. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
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Neeli I, Khan SN, Radic M: Histone deimination as a response to inflammatory stimuli in neutrophils.
J Immunol 2008, 180:1895-1902. PubMed Abstract | Publisher Full Text
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Loos T, Mortier A, Gouwy M, Ronsse I, Put W, Lenaerts JP, Van Damme J, Proost P: Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation.
Blood 2008, 112:2648-2656. PubMed Abstract | Publisher Full Text
Okumura N, Haneishi A, Terasawa F: Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin polymerization catalyzed by thrombin.
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Chang X, Yamada R, Sawada T, Suzuki A, Kochi Y, Yamamoto K: The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis.
Rheumatology (Oxford) 2005, 44:293-298. PubMed Abstract | Publisher Full Text
Chapuy-Regaud S, Sebbag M, Baeten D, Clavel C, Foulquier C, De Keyser F, Serre G: Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides.
J Immunol 2005, 174:5057-5064. PubMed Abstract | Publisher Full Text
Suzuki A, Yamada R, Yamamoto K: Citrullination by peptidylarginine deiminase in rheumatoid arthritis.
Ann N Y Acad Sci 2007, 1108:323-339. PubMed Abstract | Publisher Full Text
Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis.
Nat Genet 2003, 34:395-402. PubMed Abstract | Publisher Full Text
Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Méchin MC, Vincent C, Nachat R, Yamada M, Takahara H, Simon M, Guerrin M, Serre G: Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation.
Arthritis Rheum 2007, 56:3541-3553. PubMed Abstract | Publisher Full Text
Vossenaar ER, Radstake TR, Heijden A, van Mansum MA, Dieteren C, de Rooij DJ, Barrera P, Zendman AJ, van Venrooij WJ: Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages.
Ann Rheum Dis 2004, 63:373-381. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Kinloch A, Lundberg K, Wait R, Wegner N, Lim NH, Zendman AJ, Saxne T, Malmstrom V, Venables PJ: Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis.
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Mastronardi FG, Wood DD, Mei J, Raijmakers R, Tseveleki V, Dosch HM, Probert L, Casaccia-Bonnefil P, Moscarello MA: Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation.
J Neurosci 2006, 26:11387-11396. PubMed Abstract | Publisher Full Text
Makrygiannakis D, af Klint E, Lundberg IE, Lofberg R, Ulfgren AK, Klareskog L, Catrina AI: Citrullination is an inflammation-dependent process.
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J Biol Chem 2004, 279:14001-14008. PubMed Abstract | Publisher Full Text
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Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M: Structural basis for Ca(2+)-induced activation of human PAD4.
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Rodriguez SB, Stitt BL, Ash DE: Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization.
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Lourbakos A, Chinni C, Thompson P, Potempa J, Travis J, Mackie EJ, Pike RN: Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis.
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Belotti D, Rieppi M, Nicoletti MI, Casazza AM, Fojo T, Taraboletti G, Giavazzi R: Paclitaxel (Taxol(R)) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells.
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Pritzker LB, Moscarello MA: A novel microtubule independent effect of paclitaxel: the inhibition of peptidylarginine deiminase from bovine brain.
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ClinicalTrials.gov: search of: paclitaxel AND rheumatoid: a study using intravenous paxceed to treat patients with rheumatoid arthritis [http://clinicaltrials.gov/ct2/results?term=paclitaxel+AND+rheumatoid] webcite
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Luo Y, Knuckley B, Lee YH, Stallcup MR, Thompson PR: A fluoroacetamidinebased inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation.
J Am Chem Soc 2006, 128:1092-1093. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Stone EM, Schaller TH, Bianchi H, Person MD, Fast W: Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase.
Biochemistry 2005, 44:13744-13752. PubMed Abstract | Publisher Full Text
Willis V, Gizinski A, Knuckley B, Banda N, Cordova K, Luo Y, Causey C: Treatment with Cl-amidine, a peptidyl arginine deiminase (PAD) inhibitor significantly reduces collagen-induced arthritis (CIA) [abstract].
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Curr Eye Res 2006, 31:1063-1071. PubMed Abstract | Publisher Full Text
Li L, Li Z, Chen D, Lu X, Feng X, Wright EC, Solberg NO, Dunaway-Mariano D, Mariano PS, Galkin A, Kulakova L, Herzberg O, Green-Church KB, Zhang L: Inactivation of microbial arginine deiminases by L-canavanine.
J Am Chem Soc 2008, 130:1918. PubMed Abstract | Publisher Full Text
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J Biol Chem 1994, 269:26083-26091. PubMed Abstract | Publisher Full Text
Nachat R, Mechin MC, Takahara H, Chavanas S, Charveron M, Serre G, Simon M: Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin.
J Invest Dermatol 2005, 124:384-393. PubMed Abstract | Publisher Full Text
Nachat R, Mechin MC, Charveron M, Serre G, Constans J, Simon M: Peptidylarginine deiminase isoforms are differentially expressed in the anagen hair follicles and other human skin appendages.
J Invest Dermatol 2005, 125:34-41. PubMed Abstract | Publisher Full Text
Mechin MC, Enji M, Nachat R, Chavanas S, Charveron M, Ishida-Yamamoto A, Serre G, Takahara H, Simon M: The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations.
Cell Mol Life Sci 2005, 62:1984-1995. PubMed Abstract | Publisher Full Text
Sambandam T, Belousova M, Accaviti-Loper MA, Blanquicett C, Guercello V, Raijmakers R, Nicholas AP: Increased peptidylarginine deiminase type II in hypoxic astrocytes.
Biochem Biophys Res Commun 2004, 325:1324-1329. PubMed Abstract | Publisher Full Text
Ishigami A, Ohsawa T, Hiratsuka M, Taguchi H, Kobayashi S, Saito Y, Murayama S, Asaga H, Toda T, Kimura N, Maruyama N: Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease.
J Neurosci Res 2005, 80:120-128. PubMed Abstract | Publisher Full Text
Urano Y, Watanabe K, Sakaki A, Arase S, Watanabe Y, Shigemi F, Takeda K, Akiyama K, Senshu T: Immunohistochemical demonstration of peptidylarginine deiminase in human sweat glands.
Am J Dermatopathol 1990, 12:249-255. PubMed Abstract | Publisher Full Text
Ishigami A, Ohsawa T, Asaga H, Akiyama K, Kuramoto M, Maruyama N: Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin.
Arch Biochem Biophys 2002, 407:25-31. PubMed Abstract | Publisher Full Text
Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ: PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease.
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Hagiwara T, Nakashima K, Hirano H, Senshu T, Yamada M: Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes.
Biochem Biophys Res Commun 2002, 290:979-983. PubMed Abstract | Publisher Full Text


text:
NMSU also honored its five seniors; Malia Magazzeni, Stefanie Gilbreath, Kelsie Rozendaal, Chrissy Fletcher and Camila Rosen on senior night.
As a team, the Aggies shot 41.7 percent from the floor but just 4-of-23 from beyond the 3-point arc. Gilbreath led the Aggies with 26 points and four rebounds, while Rozendaal added 15 points and seven rebounds. Rosen led the Aggies with 11 boards.
NMSU opened up the second half on a 12-5 run to cut the Denver lead to 41-38 with 15:258 left in the game. The Aggies were 5-of-8 during the stretch, while forcing four Denver turnovers.
Abby Scott cut the lead to two points at 47-45 but the Pioneers came right back with a basket, extending the lead to four at 49-45 with 11:05 remaining in the game. After the timeout the Aggies were fouled which put them into the bonus for the remained of the game with 1:57 to go. Two made free throws and the Aggies were down just two at 49-47. The Aggies got to within one at 52-51 before a 5-0 run by Denver gave the Pioneers a six point advantage with 8:06 to go in the contest, 57-51. The Aggies continued to pressure cutting the lead to 57-55 with 6:45 left but NMSU turnovers and hot shooting by the Pioneers pushed the Denver lead to 64-59 with 3:50 remaining in the game.

subset: commoncrawl


text:
First Known Use: 14th century
noun imag·i·na·tion \i-ˌma-jə-ˈnā-shən\
: the ability to imagine things that are not real : the ability to form a picture in your mind of something that you have not seen or experienced
: the ability to think of new things
: something that only exists or happens in your mind
Full Definition of IMAGINATION
: the act or power of forming a mental image of something not present to the senses or never before wholly perceived in reality
a : creative abilityb : ability to confront and deal with a problem : resourcefulness <use your imagination and get us out of here>c : the thinking or active mind : interest <stories that fired the imagination>
a : a creation of the mind; especially : an idealized or poetic creationb : fanciful or empty assumption
See imagination defined for English-language learners
See imagination defined for kids
Examples of IMAGINATION
- You can find a solution if you use a little imagination.
- The author does not tell us what happens to the characters. We have to use our imagination.
- He's a competent writer, but he lacks imagination.
- Is it just my imagination, or is it getting warm in here?
Origin of IMAGINATION
Middle English, from Anglo-French, from Latin imagination-, imaginatio, from imaginari
Related to IMAGINATION
- Synonyms
- contrivance, creativity, fancy, fantasy (also phantasy), ideation, imaginativeness, invention, inventiveness, originality
Other Psychology Terms
Rhymes with IMAGINATION
abbreviation, abomination, acceleration, accentuation, accommodation, accreditation, acculturation, accumulation, actualization, adjudication, administration, adulteration, affiliation, agglomeration, alienation, alleviation, alliteration, amalgamation, amelioration, amplification, anglicization, annihilation, annunciation, anticipation, appreciation, appropriation, approximation, argumentation, articulation, asphyxiation, assassination, asseveration, assimilation, association, atomization, attenuation, authentication, authorization, autoxidation, balkanization, bastardization, beautification, bowdlerization, calcification, canonization, capitulation, centralization, certification, cicatrization, civilization, clarification, classification, coagulation, codification, coeducation, cogeneration, cohabitation, collaboration, colonization, colorization, commemoration, commiseration, communication, concatenation, conciliation, confabulation, confederation, configuration, conglomeration, congratulation, consideration, consolidation, contamination, continuation, cooperation, coordination, corroboration, cross-pollination, crystallization, deactivation, debilitation, decapitation, deceleration, deconsecration, de-escalation, defenestration, defibrillation, deforestation, defragmentation, degeneration, deification, deliberation, delineation, demonization, denomination, denunciation, depopulation, depreciation, deracination, deregulation, desegregation, despoliation, determination, devaluation, digitization, disapprobation, discoloration, discrimination, disembarkation, disinclination, disinformation, disintegration, Disneyfication, dissemination, dissimulation, dissociation, documentation, domestication, dramatization, echolocation, edification, ejaculation, elaboration, elimination, elucidation, emaciation, emancipation, emasculation, enumeration, enunciation, equalization, equivocation, eradication, evacuation, evaluation, evaporation, evisceration, exaggeration, examination, exasperation, exhilaration, exoneration, expropriation, extenuation, extermination, extrapolation, facilitation, falsification, felicitation, feminization, fertilization, feudalization, finalization, Finlandization, formalization, fortification, fossilization, gasification, gentrification, gesticulation, globalization, glorification, gratification, habituation, hallucination, harmonization, humanization, humiliation, hyperinflation, idolization, illumination, impersonation, implementation, improvisation, inauguration, incarceration, incineration, incorporation, incrimination, indoctrination, inebriation, infatuation, initiation, inoculation, insemination, insinuation, instrumentation, internalization, interpretation, interrelation, interrogation, intimidation, intoxication, invagination, invalidation, investigation, invigoration, irradiation, itemization, justification, legalization, liberalization, magnetization, magnification, maladaptation, manifestation, manipulation, matriculation, maximization, mechanization, memorization, miscegenation, mobilization, modernization, modification, mortification, multiplication, mystification, nationalization, naturalization, negotiation, normalization, notification, novelization, nullification, obliteration, organization, origination, orientation, ornamentation, ossification, oxygenation, pacification, paralyzation, participation, pasteurization, perambulation, peregrination, perpetuation, personalization, petrification, polarization, pontification, precipitation, predestination, prefabrication, prefiguration, premeditation, preoccupation, preordination, preregistration, prettification, privatization, procrastination, prognostication, proliferation, propitiation, purification, qualification, ramification, randomization, ratification, realization, reciprocation, recombination, recommendation, recrimination, recuperation, redecoration, reduplication, reforestation, refrigeration, regeneration, regimentation, regurgitation, reification, reincarnation, reintegration, reiteration, rejuvenation, remuneration, renunciation, repatriation, representation, republication, repudiation, retaliation, reverberation, sanctification, scarification, sedimentation, sensitization, Serbo-Croatian, signification, simplification, socialization, solicitation, sophistication, specialization, specification, stabilization, standardization, sterilization, stratification, subordination, subpopulation, supplementation, synchronization, systemization, teleportation, tergiversation, transfiguration, transliteration, transvaluation, triangulation, uglification, unification, unionization, urbanization, verification, versification, victimization, vilification, vituperation, vocalization, vulgarization, westernization, x-radiation
IMAGINATION Defined for Kids
noun imag·i·na·tion \i-ˌma-jə-ˈnā-shən\
Definition of IMAGINATION for Kids
: the act, process, or power of forming a mental picture of something not present and especially of something a person has not known or experienced <Her imagination kept her entertained on the long ride.>
: creative ability <Her story shows great imagination.>
: a creation of the mind <Is it just my imagination or are we moving?>
Medical Dictionary
noun imag·i·na·tion \im-ˌaj-ə-ˈnā-shən\
Medical Definition of IMAGINATION
: an act or process of forming a conscious idea or mental image of something never before wholly perceived in reality by the one forming the images (as through a synthesis of remembered elements of previous sensory experiences or ideas as modified by unconscious defense mechanisms); also : the ability or gift of forming such conscious ideas or mental images especially for the purposes of artistic or intellectual creation
Learn More About IMAGINATION
Next Word in the Dictionary: imaginationalPrevious Word in the Dictionary: imaginary unitAll Words Near: imagination
Seen & Heard
What made you want to look up imagination? Please tell us where you read or heard it (including the quote, if possible).


text:
By Lloyd Gray
By Lena Mitchell
Daily Journal
Severe late-night storms cut a swath across the northeast corner of Mississippi late Monday night, downing dozens of trees and clipping power lines across Alcorn, Prentiss and Tishomingo counties.
Beginning about 11 p.m., crews from the Corinth street department and Alcorn County volunteer fire departments received calls about toppled trees and limbs.
Crews cleared five trees that fell across Shiloh Road in Corinth and trees and limbs from a total of 24 sites in east Corinth and neighborhoods off north Madison Street, said Street Commissioner Jim Bynum.
The damage extended through the town of Farmington, said Alcorn Emergency Management Director Ricky Gibens, with trees falling across power lines and through the roofs of four or five homes.
At one time the whole east side of the county was without power, he said. Crews were still out working after 5 p.m. Tuesday to restore power.
Similar damage struck Tishomingo County, said Emergency Management Agency Director Bill Strickland.
The county worked about 30 different calls for trees and power lines downed, with two trees falling on houses.
The storm appeared to come into the county from McNairy County, Tenn., he said, and did its damage in the Burnsville and Iuka areas north, then continued south through Tishomingo before turning east toward Alabama.
Damage reports from Prentiss County were in the east area in the Cairo community, which is south of Burnsville, said Prentiss EMA Director Ralph Lauderdale.
Tishomingo County Electric Power Association crews began working after 11 p.m. Monday when the first storm front moved through and damaged the Holcutt substation in the middle of the county, said General Manager Robert Grisham.
A second storm front that came through about 2 a.m. Tuesday took out additional power customers, with a total of about 4,500 customers affected in various areas of the county.
Most had power restored later in the morning and all had service back by mid-afternoon Tuesday, he said.


text:
Scientists have created a network which various smart devices and artificial intelligences will use autonomously to share information and learn from each other – increasing their capabilities. Should we just surrender now? The BBC reports:
… Read the rest
A world wide web for robots to learn from each other and share information is being shown off for the first time. The system has been developed by research scientists from Philips and five European universities including Eindhoven.
It is the culmination of a four-year project, funded by the European Union. The eventual aim is that both robots and humans will be able to upload information to the cloud-based database, which would act as a kind of common brain for machines.
"At its core RoboEarth is a world wide web for robots: a giant network and database repository where robots can share information and learn from each other," said Rene van de Molengraft, the RoboEarth project leader.


text:
- Filed Under
Your chance of developing breast cancer can come down to a single gene. And the good news is it's easy to track.
BRCA 1 and 2 genes belong to a class called tumor suppressors, says Dr. Andrew Quong, a cancer genetics researcher at Jefferson's Kimmel Cancer Center in Philadelphia.
"Their normal role is to help protect and allow natural processes to repair damage to your DNA," Dr. Quong explains. "So what happens is, these people that have mutations in BRCA 1 and BRCA 2, the protein doesn't function as it normally would. Then you have more DNA damage building up, which then can lead to cancer." ...


text:
Posted December 18, 2012 on AP on Fox
ATLANTA - OCTOBER 29: Ron Hainsey #6 of the Atlanta Thrashers against the Washington Capitals at Philips Arena on October 29, 2009 in Atlanta, Georgia. (Photo by Kevin C. Cox/Getty Images)
Winnipeg Jets defenseman Ron Hainsey is getting antsy. Not only is he anxious to get back to the bargaining table with the NHL, he really wants to be on the ice with his teammates. As part of the negotiating committee for the players' association, Hainsey has kept busy during the lockout by taking part in the ongoing talks with the NHL. But ongoing is now a relative term, because nothing has been going on between the sides since talks broke down again last week, despite the presence of a federal mediator for two days in New Jersey. ''We've said it a number of times, but it's worth repeating: It's obviously very difficult to make a deal if you're not meeting or negotiating,'' Hainsey told The Associated Press in a telephone interview Tuesday. ''I've yet to see a way we can do it without sitting down across a table from each other.'' Two weeks ago, progress was made during several consecutive days of negotiations between players and owners in New York. The sides disagree on how clo...
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text:
*Blows off cobwebs*
Oh heroo
I'll come to the meet, but i'm already going to fordfair like a few others!
Summer Meet Anyone?
Started by Flic, Jun 29 2011 12:37 PM
33 replies to this topic
Posted 12 July 2011 - 08:13 PM
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Posted 14 July 2011 - 08:08 PM
Sorry for the vanishing act, had a hectic week!
So Mid/Late August then anyone?
So Mid/Late August then anyone?
Posted 14 July 2011 - 09:23 PM
Earlier the better for me - the wedding's on August 20th...
Posted 14 July 2011 - 09:31 PM
Oooh, not long to go then!! Bet you're excited
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text:
Picked up all three for $158 (49.00 each plus tax)
Exxon Graftek's specs:
dura ace 7400 rear derailleur
dura ace 7400 brake calipers
dura ace 7401 brake levers
dura ace 7400 bottom bracket
suntour superbe crankset
tange g master headset
shimano 600 rear hub laced to mavic g40 rim ss spokes
sachs front hub laced to SUP rim ss spokes
Peugeot's specs:
531 frameset with internal brake cable routing
no brake calipers
dia compe brake levers(?)
campagnolo super record non drive side crank arm
tange g master headset
campagnolo 26.8 seat post(record?)
mavic g 40 rims
front hub is unknown right now
rear hub is phill
bluemels popular fenders
anyone know the model of this one?
Mountain bike:
xtr brake calipers
xtr front derailleur
xtr pedals
dura ace 7400 rear deralleur
tricor seatpost
deore lx hubs
deore xt shift levers/brake
specialized stem
specialized flag logo crankset
y&t 541 headset (any info on this?)
I am thinking it is a cannondale, not sure though, any info would be great!
photos are all on my flikr page: http://www.flickr.com/photos/68793830@N06/


text:
The cast of 'Honeymoon in Vegas'' in an exuberant moment.
- Filed Under
This time Rob won't get robbed.
Last season, Rob McClure made quite an impression on Broadway - and quite a name for himself - for playing the title role in "Chaplin." Yes, a Tony nomination is always an excellent reward, but the Millburn native should have won.
Now McClure has the lead in "Honeymoon in Vegas" at his hometown's Paper Mill Playhouse. As was the case with "Chaplin," the superb song 'n' dance man is rarely off-stage and is thoroughly winning every second he's on it. ...


text:
In My Mailbox is hosted by The Story Siren. I got a couple of books this week!
Shrimp by Rachel Cohn
Goodreads Description:
"With Shrimp, pop culture wordsmith Rachel Cohn successfully resurrects Cyd Charisse, the irrepressible punk princess from her breakout hit, Gingerbread. C.C. is back from an emotional summer in NYC where she met her biological father for the first time and nursed her karmic wounds after a messy breakup with her short-statured surfer boyfriend, Shrimp. Now, it is the start of senior year in San Francisco, and C.C. is determined to get the surfer boy of her dreams back. She is aided and abetted by new friends, Helen and Autumn, and "old" girlfriend, sunny octogenarian Sugar Pie. When Cyd's cool half-sib Danny invites her back to NYC for a long weekend, will C.C.'s turn eastward--away from Shrimp's surfer dreams? Shrimp's bright cover belies the frank, sexy narrative within that is definitely not for the tween audience of Cohn's middle-grade novel, The Steps. But older teen fans are going to love guessing what their unapologetic, espresso- and Nestle Crunch bar-addicted antiheroine will do next. Are Shrimp and C.C. destined to move in together after graduation? Or will Shrimp's brother's wedding give them second thoughts? Whatever happens, Cyd Charisse is convinced that "at the end of the road, there will always be a Shrimp." Cohn's Shrimp is a witty, sparkling sequel that was definitely worth the wait."
I liked Gingerbread, but I hope this sequel is better.
North of Beautiful by Justina Chen Headley
Goodreads Description:
"Born with a port-wine stain birthmark covering her entire right cheek, Terra Rose Cooper is ready to leave her stifling, small Washington town where everyone knows her for her face. With her critical, reproachful father and an obese mother who turns to food to deflect her father's verbal attacks, home life for Terra isn't so great either. Fueled by her artistic desires, she plans to escape to an East Coast college, thinking this is her true path. When her father intercepts her acceptance letter, Terra is pushed off-course, and she is forced to confront her deepest insecurities. After an ironically fortuitous car accident, Terra meets Jacob, a handsome but odd goth Chinese boy who was adopted from China as a toddler. Jacob immediately understands Terra's battle with feeling different. When Terra's older brother invites her and her mother to visit him in Shanghai, Jacob and his mother also join them on their journey, where they all not only confront the truth about themselves, but also realize their own true beauty. North of Beautiful is the engaging third YA novel by Justina Chen Headley. This is a gorgeously-written, compelling book featuring universal themes of defining true beauty, family bonds, personal strength, and love."
This book looks really awesome, and I love the cover. When I saw it at the library I had to grab it.
Peaches by Jodi Lynn Anderson
Goodreads Description:
"Three Georgia peaches are in for one juicy summer . . .
. . . but Birdie would rather eat Thin Mints and sulk in the A/C.
Leeda would prefer to sneak off with her boyfriend, Rex.
And Murphy would much rather cause a little mischief.
Together these three very different girls will discover the secret to finding the right boy, making the truest of friends, and picking the perfect Georgia peach."
I saw this at my library's used book store, and I got hardback for only four bucks! I'm eager to start it.
That's it, everyone! What did you get this week?
Emma Out!


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The Argus (Melbourne, Vic. : 1848 - 1957)(about)
Previous issue Wednesday 26 April 1893 Next issue
Previous page of 10 Next page
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2 corrections, most recently by LizWhelan - Show corrections
STAWELL, Tuesday.
A promising boy named Charles Mason aged 10 years, son of highly respected resi- dents in this locality, lost his life yesterday through being bitten by a tiger snake. With other boys he.was passing along a bush track about 9 o clock in the morning, when he trod upon the snake without having seen that it was lying across the path. The reptile doubled up instantaneously and bit him on the leg. He was taken back home and a ligature applied by the mother who also roughly scarified the wound, giving him whisky and other stimulants. As soon as possible he was removed to the Stawell Hos- pital, reaching the institution fully two hours after the occurrence. He was attentively treated by the resident surgeon, Dr. Hopkins, but although no fatal result was feared at first, a change for the worse took place at 3 p. m. and the boy died about 5 oclock ín the afternoon.


text:
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text:
Rob Rogers' Gaza cartoon screams of propaganda and half-truthsAugust 13, 2014 12:00 AM
Share with others:
I was appalled to see Thursday's cartoon in my hometown newspaper. It screamed of propaganda, telling half-truths that don't even attempt to tell two sides of a story.
It is appalling to suggest that Israel is attacking Gaza unprovoked; it is well documented that Hamas shoots rockets indiscriminately at an alarming rate. It is no less appalling to suggest that Israel is targeting civilians; it is well documented that Hamas hides behind children while it shoots at Israel.
That civilians are dying in this horrible battle is catastrophic, but to place blame solely on Israel is simply irresponsible. It ignores the nuances of the political situation and screams of bias and lazy reporting.
Squirrel Hill


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She's the literary cousin to Katherine Heigl's uptight TV producer in that movie The Ugly Truth, with one major exception.
"It paints the women as shrews, as humorless and uptight, and it paints the men as lovable, goofy, fun-loving guys," she said.
But the aforementioned "uptight" chick would have a hard time making a case for sexual assault under these specific circumstances.
One of the characters I played was an uptight whackjob, so that was probably written for me.
The ad inspired the ire of the Parents Television Council, and uptight, humorless people everywhere.
We hear about the death of her mother, her father, we hear about her uptight yuppie brother, and her sad, damaged friend Ruby.
I also have a small onscreen role as an uptight nerd, which for some mysterious reason the guys felt certain I could play.
Read another way, she is a horrible mother, an uptight snob, and a bit of a shrew.
In reality, a pimp may be as uptight, jealous, and, indeed, puritanical as any other man.
For Cummings, who was born within an uptight intellectual haven, it was no wonder that he would grow out of that shell.
adjective phrase
Crazy; wild; nutty: It doesn't drive us crazy. At least, I don't know anybody who is up the wall about it
Related Terms
[1951+; fr the image of insane persons, frantic and deprived drug addicts, wild animals, etc, trying to climb a wall to escape]


text:
Veterinary Hospital
106 Cam Ct.
Lima, OH 45805
(419) 228-1010
Fax: (419) 228-1019
Book an appointment at
(419) 228-1010
Shawnee Veterinary Hospital is an animal hospital in Lima, OH. Our experienced veterinarian and efficient staff make sure that your special friend receives the best pet healthcare in the area. If your dog or cat needs medical attention, bring it to our animal hospital immediately.
Conveniently located just off Shawnee Road behind Ikes Restaurant, Shawnee Veterinary Hospital provides compassionate pet healthcare. We offer complete hospital facilities to our furry patients. William T. Collins Jr. DVM, our doctor, also performs surgery on small animals. Rest assured that your pet is in excellent care at our veterinary hospital.
We are accepting new patients. So call today to schedule an appointment.


text:
- Overview
- Apps
- Themes
- HD Wallpapers
- Ringtones
- Screensavers
- Flash
- Operator Logos
- Videos
- Manga
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SE flash menu grouped
Your original file link
para que sirve
it's all here http://flash-lite-tutorial.blogspot.com/2007/03/how-to-implement-flash-lite-menus.html
You can add flash files in Others folder or Pictures folder. Should work!
To use flash menus Flash your Phone(ONLY Sony Ericsson) . For More info refer Mobile 9 Sony Ericsson FAQ in Mobile9 Forum.
You cannot activate like a theme on a phone, in stead you can use like screensaver or wallpaper(on Nokia)
HEY WHO !! VERY VERY VERY VERY Please help me !! Where i need put the swf files? and how can i run theese? PLS REPLY !!!!
so i just dl this...transfer it to my phone and select it under themes? sometimes it wont allow me to select it as a theme...why is this?


text:
Nurofen Plus
Generic Name: Codeine phosphate, Ibuprofen
Product Name: Nurofen Plus
Pain and inflammation such as: headaches; muscular or bone pain (including rheumatoid arthritis and back pain); period pain; and toothache.
Nurofen Plus contains two active ingredients. Ibuprofen has an antiinflammatory effect, so it can relieve the pain, redness and swelling that result from inflammation, and it is also effective against fever.Codeine phosphate relieves pain and may cause some sedation (sleepiness).
Dose advice
12's, 24's: S2; 48's: S3, except NSW: S2
Common side effects
Uncommon side effects
For further information talk to your doctor.
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text:
Andretti Autosport has signed E.J. Viso to drive a fourth car for the IndyCar team this season.
Viso will drive the No. 5 Team Venezuela PDVSA Chevrolet as a teammate to defending IndyCar champion Ryan Hunter-Reay, James Hinchcliffe and Marco Andretti.
The No. 5 car is a joint effort between HVM Racing and Andretti, and it pushes the Andretti organization back to its traditional four-car, full-time lineup.
The deal announced Thursday allows HVM Racing to continue its participation in IndyCar in anticipation of a potential return to the series in 2014. The Keith Wiggins-owned HVM team was not planning on racing this season in IndyCar.
Viso is entering his sixth season in IndyCar. He has 16 career top-10 finishes.
Copyright 2015 Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.


text:
Jennifer Lawrence didn't have to worry about tripping over her party dress at Vanity Fair's Oscar party.
After taking at tumble in a floor-length Dior dress when she arrived at the Hollywood & Highland Center Sunday, the 23-year-old Best Supporting Actress nominee changed into a less fussy Tom Ford mini-dress. The embellished design featured sheer side and back panels, letting everyone know that the American Hustle star had ditched her underwear and decided to go commando on the red carpet.
Lawrence, who lost to 12 Years a Slave's Lupita Nyong'o, also upgraded to a smoky eye.
Earlier that night, the blond star laughed off her latest Oscar spill. "I don't want it to start looking like it's my thing, so I've got to be careful," said Lawrence, who famously tripped during 2013's ceremony.
The actress reveled in the opportunity to get glammed up after getting into character as Katniss Everdeen to shoot The Hunger Games: Mockingjay. "I've been away in Atlanta filming, so I kind of feel like I'm jumping into some random party," Lawrence told E! News' Ryan Seacrest. "It's nice. It's fun."
NEWS: Jennifer Lawrence (jokingly) tries to steal Lupita Nyong'o's Oscar
While she always manages to land on her feet, the Silver Linings Playbook star couldn't escape her slip-up during host Ellen DeGeneres' opening monologue. "I'm not going to bring up what happened last year," DeGeneres joked. "It's ridiculous. Something like that happens and it's embarrassing, and then people just talk about it. For those of you who don't know what I'm talking about, last year she fell on her way up. Let's just show the clip," she said, without actually cuing up the video footage.
NEWS: She's just being J.Law! Jennifer Lawrence's best Oscar moments
"And you know the thing about when you fell out of the car tonight when you were getting out the car? No one needs to know about that," DeGeneres continued, as Lawrence laughed. "I'm not going to mention that. She fell on the way out of the car," the comedienne informed the audience. "Like, on an orange cone, you tripped or something. If you win tonight, I think we should bring you the Oscar."


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By Bruce Hooley
Browns quarterback Brandon Weeden stopped by the ESPN Cleveland stage at the Cleveland Auto Show on Monday and expressed confidence in his ability to hang onto the starting job he filled for all but one game as a rookie.
Weeden stepped carefully around whether former head coach Pat Shurmur allowed him to audible last season and hinted the abundance of short throws in the West Coast Offense led to the high number of passes he had knocked down at the line of scrimmage.
As for the tepid endorsement of his abilities from the Browns' new regime, Weeden said he understands that approach in light of the Browns' 5-11 record.
Q: What's it been like hearing very little complimentary about your abilities in media interviews when Joe Banner, Mike Lombardi, Rob Chudzinski and Norv Turner discusses your performance?
A: "I know what's going on with the organization. Everything I hear is from buddies. I don't watch SportsCenter. I don't watch that stuff. I'm busy. I have a lot going on. I don't want other people telling me about myself. I kind of stay out of the loop.
"All the moves that have been made so far have been very positive for the organization. Bringing in Chud and Norv and all these other great coaches with a ton of experience is going to be great for this organization.
Q: Grade your performance from last season. What did you learn, and is there anything you would do differently?
A: "Average. I know I am a better player than what I played all year. I'm not satisfied with how I played all year. Being the competitor that I am, I see a lot of areas of improvement. I know I have to get better for us to win games…and reach our ultimate goal of getting to the playoffs and winning the Super Bowl. I feel like, personally, it starts with me. I have to get better.
"I would not change anything. I think I prepared well week in and week out. I felt I put myself in position…but I didn't play as well as I was used to. I have to get better."
Q: There was a lot of speculation last year about whether you had the freedom to audible at the line of scrimmage. Did you have that freedom?
A: "Our goal last year was to play fast and not let the defense dictate what we did, so we tried to get to the line of scrimmage and get the plays in and out as fast as possible. I can't speak for the system we're about to learn, because I've never been in it one day yet. I'm anxious to learn it. I can tell from San Diego, seeing Phillip (Rivers) do what he's done, it looks like they give the quarterback free dome to put that team and that offense in the best position, whether it's audibling at the line of scrimmage or getting into the two-minute offense and playing fast, whatever it may be, it looks like they put a lot on the quarterback….I hope I get that freedom."
Q: Can you explain the high number of passes you had batted down at the line of scrimmage?
A: "I've watched several games from last year so far this off season. Looking back, it may be two things. Number one, I need to speed up my drops. I need to get to the top of my drop faster. That's one thing I've already stressed a lot.
"We threw a lot of those shallow crossing routs. They develop pretty fast. Those defensive tackles knew they weren't going to get home. They knew they weren't going to get to the quarterback, so they just threw their hands up. These guys were 6-4 or 6-5. I could be 6-11 and it still would be hard for me to get ball over those guys. You're throwing balls at the line of scrimmage or just beyond it. Regardless, there's no excuse for it. I have to find a way to find throwing lanes to complete balls.
Q: How do you feel about your treatment in the media from the Browns' new management structure?
A: "I get it, because they haven't been here the last year. These aren't the guys who set their draft room and drafted me. They did their scouring report on me a year ago at this time, but they didn't actually draft me. I get it.
"If I had played better, we would have won more games. If I would have done more to help the team win games, it might be a different case. But I'm confident in my abilities. I'm very confident in my ability to get better in Year 2.
"I kind of know how it works on a daily basis and a weekly basis. It's a totally different league than playing college football. We're going to be a better team this year. We have guys with more experience. We have guys who have a year under their belt. They're key guys like Trent and Josh and other guys, so it's an exciting time. I'm not discouraged by it."
To listen to the entire interview with Weeden and former Browns quarterback Bernie Kosar, click here.
Bruce Hooley hosts The Hooligans from 3-6 p.m. weekdays on ESPN 850 WKNR. He is the author of, "That's Why I'm Here: The Chris and Stefanie Spielman Story."
Email Bruce firstname.lastname@example.com
Follow Bruce on Twitter @bhoolz
Return to: Cleveland Browns Blog
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Scott and Lisa Woosley had talked for years about doing foster care. Then the southeast Kansas couple did something about it.
Scott and Lisa Woosley had talked for years about doing foster care. Then the southeast Kansas couple did something about it.
"We contacted TFI Family Services about classes, and took it from there," Lisa Woosley said.
The free Partnering for Safety and Permanence Model Approach to Parenting (PS-MAPP) training is designed to help interested persons make an informed decision about becoming a resource foster care parent.
"We took the classes in February of 2012, and they were not difficult at all. There were 10 weeks of classes, every Tuesday evening for just a few hours. We got to meet other people looking to be foster parents and made some new friends. We really enjoyed it."
She and her husband have four children of their own, along with seven grandchildren.
"We didn't need more children in our family, but there are children out there who need families, and we can provide that short-term," Woosley said. "It's very rewarding."
She said they currently have four foster children, all girls, aged 10 to 16.
"Four other girls were placed here, and two have returned to their homes," Woosley said. "We still keep in touch with them, and one of them spent the night here recently. Once you walk through our door, you're part of our family, even if it is just extended family."
She said that her grandchildren are always excited when it's time to visit Gram's house.
"They really like to see the other kids," Woosley said.
She said that so far they have fostered girls.
"The few calls I've got for boys have come when we were full of girls," Woosley said.
She and her husband strive to help the youngsters feel comfortable as soon as they arrive.
"I ask what their favorite food is, and try to have that food for their first meal here," Woosley said. "I find out what their favorite color is, and try to get bedding in that color. We just try to do some small thing to make them feel welcome when they get here."
Some youngsters come from unhappy situations and may have issues.
"You have to support them and try to build their self-esteem back up, meet them where they're at and build on their strengths," Woosley said. "We had one 10-year-old who was very apprehensive about male figures, so Scott built on what her strengths were. She loved to cook, so he baked cookies with her."
Some children, she said, have had to be mini-adults in their home situations.
"They don't know how to play, and we have to teach them that," Woosley said. "We just try to give them a kid experience. We use a lot of humor in our house, and some kids who come to our home haven't experienced a lot of laughter. We have structure here, but we're not a boot camp. We work together for the common good as a team."
Page 2 of 2 - That team may include others in the community.
"We had to build a village to support our kids," Woosley said. "My hairdresser will give them haircuts, and one of our girls got a beautiful hairstyle for prom."
She and her husband try to keep the youngsters social and involved in activities around the community. They also encourage them to continue pursuing their own interests when that's possible.
"One girl plays clarinet, but she couldn't bring her clarinet here," Woosley said. "We went and got her one so she could continue it."
Foster parents do receive monthly reimbursement, depending on the level of care a child requires. TFI Family services also provides a yearly clothing allowance, along with assistance with Christmas gifts and special needs items.
Foster families have their own case manager as well as 24-hour local on-call support.
"I call my resource worker once a day with a question," Woosley said.
Respite care can also be arranged when foster parents need someone to temporarily take care of their foster children.
Woosley noted that she and her husband have taken in respite children several times. However, when Scott Woosley was recently hospitalized, his wife turned down TFI's offer of respite services. She felt that the foster children could learn something very valuable by remaining in the home with her.
"I think it's important kids learn to deal with a crisis without dysfunction," Woosley said. "This is how a family operates in time of need. We all pitch in and support one another."
Parenting experience is not required to become a resource care foster parent. Interested persons must be at least 21, have a permanent residence, an outside source of income and be a legal U.S. citizen. They must complete the PS-MAPP training course and pass Kansas Bureau of Investigation and Child Abuse Registry background checks. Their home must pass inspection and be licensed by the Kansas Department of Health and Environment to ensure that it is safe and suitable for children. Finally, interested persons must be sponsored by a child placing agency.
Anyone needing additional information may call TFI Family Services, Inc., at 800-279-9914 or online at www.tfifamilyservices.org.
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text:
-or- Register at the Citadel
The Barbed Arms
Lifeforms (Ethereal) (Plains)
's comment on 2007-10-12 01:37 AM
This is good stuff! Just the sort of thing that might want to make your typical ''hack and slash'' adventurer reconsider the old wisdom that a good blade is always useful wherever he may go.
Go to Comment
Void Golem
Lifeforms (Constructed) (Any)
's comment on 2007-10-09 11:54 PM
This is certainly the most unique golem that i have ever seen. It's ability to alter the very nature of space/time elevate it above the rest of the mediaeval's fantasy automaton crowd.But what did Uhrzeit intend to use this creation for?
Go to Comment
Shark Island
Locations (Area) (Water)
's comment on 2007-10-10 12:41 AM
Only voted
Go to Comment
Staff of the Swarm
Items (Wand/Staff/ Arcane) (Magical)
's comment on 2007-10-06 03:46 AM
You could have so much of fun with this. Imagine throwing this in a desert scenario where scorpions are abundant, and then letting some wandering PC use this when his caravan is attacked by bandits. Chaos would ensure!
Cheka,I'm assuming that if the wielder wants to call on more than once species of bug, he has to picture each individually as a swarm of its own? And what happens if the bugs he summons like spiders, tend to be highly cannibalistic in nature?
Go to Comment
Living Stones
Lifeforms (Intelligent Species) (City/ Ruin)
's comment on 2007-10-04 11:23 PM
Only voted
Go to Comment
Yughort Burial Towers
Locations (Ruins) (Plains)
's comment on 2007-09-22 01:58 AM
Is the fear of reverent dead pervasive among all the steppe tribes?
Go to Comment
Temple Of Inaha
Locations (World) (Water)
's comment on 2007-09-16 06:10 AM
I don't how it happened, but this is not supposed to be part of the on-going quest.
Go to Comment
Small Gods
NPCs (Mythic/ Historical) (Mystical)
's comment on 2007-09-16 06:34 AM
Oh,I'm so liking it.. Can't wait to add a couple of my own submission to this.
Go to Comment
Small Gods
NPCs (Mythic/ Historical) (Mystical)
's comment on 2007-09-17 07:35 AM
Great work with the Dwarf tree gods, Captain. I certainly enjoyed reading about them! They'd make an awesome submission to any primitive jungle culture.
Go to Comment
Ran, the Sorrow of Curiosity
NPCs (Minor) (Knowledge/Lore)
's comment on 2007-09-17 07:46 AM
Just out of curiosity, how did the Schoolmaster end up becoming his thrall?
Go to Comment
Dwarven Beard Golem
Lifeforms (Constructed) (Underground)
's comment on 2007-09-16 02:40 AM
A unique tomb-guardian whose existence springs from the deep love and adoration that its creators possessed for the deceased. While I have never taken hair as a threat seriously, I have to say that you've done a very good job with this.
By the way, is it considered a great honor for a loyal dwarf to contribute his beard for the construction of this being?
Go to Comment
The Green Ladies
Lifeforms (Intelligent Species) (Forest/ Jungle)
's comment on 2007-09-08 03:11 AM
Now this is an awesome idea! I can imagine remote villages on the fringes of enchanted forests being continuously under siege by these murderous creations of nature. A perfect explanation for why some ancients forests might be considered ''cursed'' or ''forbidden'' by local priests or sages.
Go to Comment
The Tarakhen Sea
Locations (Regional) (Water)
's comment on 2007-09-02 07:33 AM
Only voted
Go to Comment
The Matakos
Lifeforms (Unique) (Mountains)
's comment on 2007-08-26 12:24 AM
Does the Matakos hunt trespassing humans because it fears that they might attempt to hunt it?
Go to Comment
Cinque-Parte Polygnostic
Locations (Establishment) (Any)
's comment on 2007-08-19 02:32 AM
Only voted
Go to Comment
The Forgochi
Items (Armor) (Sentient)
's comment on 2007-08-25 03:15 AM
Ok guys, it's been finished.
Go to Comment
Timberwing Eagle
Lifeforms (Fauna) (Forest/ Jungle)
's comment on 2007-08-15 11:59 AM
These are some noble beasts with a rather remarkable history. I love the way you've closely connected the fate of this species with the history of the elven race.
Go to Comment
The Zhardun
Society/ Organizations (Ethnic/Cultural) (World Wide)
's comment on 2007-08-11 05:09 AM
What Cheka said. Necromancers who actually serve the forces of virtue. Now that is truly something!
Go to Comment
Clochardshire Shambler
Lifeforms (Constructed) (City/ Ruin)
's comment on 2007-08-09 03:36 AM
The specters that frequent the most destitute parts of a city, preying on the poor and defenseless,eh? I love them for the unique flavor they would add to any city slum, interesting parts of the local setting that the heroes don't have to slaughter. (Unless they actually care for the homeless, which is unlikely). I could even see them fitting well into the land-scape of a modern metropolis. Which city doesn't have it's ignored population of the homeless?
On the subject of spawning, do their victims who succumb to the infected wounds inflicted by the Shambler, stand an increased chance of becoming one themselves?
Go to Comment
Dal Nastro
Locations (Ruins) (Mountains)
's comment on 2007-08-05 12:35 AM
Poignant and sad. I wonder if insanity has not begun to ravage the minds of its animated stone sentinels?
As for the Mareb people, is it possible that feral remnants of them might yet be lurking unseen in the wilderness?
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- Filed Under
The NBC reality series "The Biggest Loser" returns for its 15th season Oct. 8, introducing America to a new crop of weight-losing hopefuls.
Among those planning to tune in are Patrick House and Gina McDonald, who know the ups and downs of the "Biggest Loser" journey through and through.
McDonald, 47, a Vicksburg native who now resides in Birmingham, was a Season 14 contestant and won the show's $100,000 at-home prize. The wife, mother and attorney, who recently celebrated her 30-year Warren Central High School class reunion, spoke candidly in a phone interview about reacclimating to ...


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Lady Gaga is clearly pumped up ahead of the opening night of her monster tour of Asia and Europe later this week. Since she touched down in Seoul last Friday — dressed in a ball-gown and pearl mask, of course — fans and media have been tracking her, a job made easier by her own Twitter updates. Read More »
Apr 24, 2012


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In honor of Mother's Day, "Working Mother" magazine has put together a list of the 50 Most Powerful Working Moms. Here are the names you'd recognize . . .
Jessica Simpson
Jennifer Lopez
Gisele Bundchen
Mariah Carey
"Hunger Games" author Suzanne Collins
"Twilight" author Stephenie Meyer
Katie Couric
Tina Fey
Gabrielle Giffords
Olympic volleyball star Kerri Walsh Jennings
Angelina Jolie
Julia Louis-Dreyfus
Melissa McCarthy
Gwyneth Paltrow
Gwen Stefani
(Check out the complete list here.)
© Copyright © 2015 Americom Broadcasting. All rights reserved.


text:
by Jake Fish
U.S. Junior Women's Singlehanded Championship 2011.
US Junior Women's Singlehanded Championship 2010 -
A competitive fleet of 57 youth sailors are preparing for US Sailing's 2011 U.S. Junior Women's Singlehanded Championship (USJWSC), hosted by Richmond Yacht Club in Point Richmond, Calif.
The first of three days of racing in Laser Radials on San Francisco Bay starts on Tuesday, June 28 and concludes on Thursday, June 30.
Kaitlyn Baab (Saratoga, Calif.) and Kelly McGlynn (Flourtown, Pa.), two returning competitors from last year's top five, will take another shot at winning the Nancy Leiter Clagett Memorial Trophy. Baab, who will be competing in the Laser Radial division at the 2011 Youth Sailing Championship later this summer in Newport, R.I., finished fourth out of 46 in 2010.
McGlynn has two top ten finishes at this championship. She finished fifth last year and sixth in 2009.
US Junior Women's Singlehanded Championship 2010 -
Sarah Stubbs (Rye, N.Y.) was second in the women's division at US Sailing's 2010 U.S. Singlehanded Championship. She was also the winner at the 2011 New England High School Singlehanded Championship for the Healy Trophy. Another notable returning competitor from last year is Kaylee Schwitzer (Annapolis, Md.) who was tenth last year.
Two days of clinics for the competing sailors led by US Sailing's National Junior Coach Frank Ustach and a team of distinguished junior and college sailing coaches will precede competition.
U.S. Junior Women's Singlehanded Championship website
Sailors for the Sea - Clean Regattas certification event website


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Happening now: West Seattle Girl Scouts' cookie sales, Day 2March 2, 2013 at 11:09 am | In West Seattle news, West Seattle people | 3 Comments
Thanks to Girl Scout Troop 43774 for sharing a photo from their cookie-sale station outside West Seattle Thriftway (WSB sponsor) – they're there till noon, but other Scouts will be there later too (all the way till 8 tonight), and other stores and sites are hosting cookie sellers as well. You can find them all – dates, times, places, troops – via the Cookie Locator. This is day two of cookie-selling season, which continues through March 17th. P.S. See the sign for "Operation Cookie Drop"? Here's what that's about.
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I just checked out the cookie locator. The Girl Scouts must have a Database Management Badge. What an enterprise! I'm going to score some Samoas right now.
Comment by Marko — 1:58 pm March 2, 2013 #
We have been out and about the past few hours taking photos of various events – as well as running some family errands – and I believe we've seen at least 10 separate tables of cookie-sellers, including at least one not on this list (a couple of Scouts on a corner on Charlestown Hill) – TR
Oooooooooo, I need to get some thin mints!
Comment by Mike — 8:23 pm March 2, 2013 #
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