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Publications (34)188.73 Total impact
Article: Differential Regulation of Cyclin D1 Expression by Protein Kinase C α and ϵ Signaling in Intestinal Epithelial Cells.[Show abstract] [Hide abstract]
ABSTRACT: Cellular accumulation of cyclin D1, a key regulator of cell proliferation and tumor-igenesis, is subject to tight control. Our previous studies have identified PKCα as a negative regulator of cyclin D1 in the intestinal epithelium. However, treatment of non-transformed IEC-18 ileal crypt cells with PKC agonists has a biphasic effect on cyclin D1 expression. Initial PKCα-mediated downregulation is followed by recovery and subsequent accumulation of the cyclin to levels markedly higher than those seen in untreated cells. Using protein overexpression strategies, siRNA and pharmacological inhibitors, we now demonstrate that the recovery and hyperinduction of cyclin D1 reflect the combined effects of (a) loss of negative signals from PKCα due to agonist-induced PKCα downregulation, and (b) positive effects of PKCϵ. PKCϵ-mediated upregulation of cyclin D1 requires sustained ERK stimulation and transcriptional activation of the proximal cyclin D1 (CCDN1) promoter, without apparent involvement of changes in protein stability or translation. PKCϵ also upregulates cyclin D1 expression in colon cancer cells, through mechanisms that parallel those in IEC-18 cells. While induction of cyclin D1 by PKCϵ is dependent on non-canonical NF-κB activation, the NF-κB site in the proximal promoter is not required. Instead, cyclin D1 promoter activity is regulated by a novel interaction between NF-κB and factors that associate with the cyclic AMP response element (CRE) adjacent to the NF-κB site. The differential effects of PKCα and PKCϵ on cyclin D1 accumulation likely contribute to the opposing tumor suppressive and tumor promoting activities of these PKC family members in the intestinal epithelium.Journal of Biological Chemistry 06/2014; 289(32). DOI:10.1074/jbc.M114.571554 · 4.60 Impact Factor
Article: Heat Shock Proteins Regulate Activation-Induced Proteasomal Degradation of the Mature Phosphorylated Form of Protein Kinase C.[Show abstract] [Hide abstract]
ABSTRACT: Although alterations in stimulus-induced degradation of PKC have been implicated in disease, mechanistic understanding of this process remains limited. Evidence supports the existence of both proteasomal and lysosomal mechanisms of PKC processing. An established pathway involves rate-limiting priming site dephosphorylation of the activated enzyme and proteasomal clearance of the dephosphorylated protein. However, here we show that agonists promote downregulation of endogenous PKCα with minimal accumulation of a non-phosphorylated species in multiple cell types. Furthermore, proteasome and lysosome inhibitors predominantly protect fully phosphorylated PKCα, pointing to this form as a substrate for degradation. Failure to detect substantive dephosphorylation of activated PKCα was not due to rephosphorylation since inhibition of Hsp70/Hsc70, which is required for re-priming, had only a minor effect on agonist-induced accumulation of non-phosphorylated protein. Thus, PKC degradation can occur in the absence of dephosphorylation. Further analysis revealed novel functions for Hsp70/Hsc70 and Hsp90 in control of agonist-induced PKCα processing. These chaperones help to maintain phosphorylation of activated PKCα, but have opposing effects on degradation of the phosphorylated protein: Hsp90 is protective, whereas Hsp70/Hsc70 activity is required for proteasomal processing of this species. Notably, downregulation of non-phosphorylated PKCα shows little Hsp70/Hsc70 dependence, arguing that phosphorylated and non-phosphorylated species are differentially targeted for proteasomal degradation. Finally, lysosomal processing of activated PKCα is not regulated by phosphorylation or Hsps. Collectively, these data demonstrate that phosphorylated PKCα is a direct target for agonist-induced proteasomal degradation via an Hsp-regulated mechanism, and highlight the existence of a novel pathway of PKC desensitization in cells.Journal of Biological Chemistry 07/2013; DOI:10.1074/jbc.M112.437095 · 4.60 Impact Factor
Article: Agonist-Induced Downregulation of Endogenous Protein Kinase C α through an Endolysosomal Mechanism.[Show abstract] [Hide abstract]
ABSTRACT: Protein kinase C (PKC) isozymes undergo downregulation upon sustained stimulation. Previous studies have pointed to the existence of both proteasome-dependent and -independent pathways of PKCα processing. Here we demonstrate that these downregulation pathways are engaged in different subcellular compartments: proteasomal degradation occurs mainly at the plasma membrane, while non-proteasomal processing occurs in the perinuclear region. Using cholesterol depletion, pharmacological inhibitors, RNA interference, and dominant-negative mutants, we define the mechanisms involved in perinuclear accumulation of PKCα, and identify the non-proteasomal mechanism mediating its degradation. We show that intracellular accumulation of PKCα involves at least two clathrin-independent, cholesterol/lipid raft-mediated pathways that do not require ubiquitination of the protein: one is dynamin-dependent and likely involves caveolae, while the other is dynamin- and small GTPase-independent. Internalized PKCα traffics through endosomes and is delivered to the lysosome for degradation. Supportive evidence includes (a) detection of the enzyme in EEA1-positive early endosomes, Rab7-positive late endosomes/multivesicular bodies, and LAMP-1-positive lysosomes, and (b) inhibition of its downregulation by lysosome disrupting agents and leupeptin. Only limited dephosphorylation of PKCα occurs during trafficking, with fully mature enzyme being the main target for lysosomal degradation. These studies define a novel and widespread mechanism of desensitization of PKCα signaling, which involves endocytic trafficking and lysosome-mediated degradation of the mature, fully phosphorylated protein.Journal of Biological Chemistry 03/2013; 288(18). DOI:10.1074/jbc.M112.437061 · 4.60 Impact Factor
Article: Elevated Expression of the Serine-Arginine Protein Kinase 1 Gene in Ovarian Cancer and Its Role in Cisplatin Cytotoxicity In Vitro[Show abstract] [Hide abstract]
ABSTRACT: Alternatively spliced variants of several oncogenes and tumor suppressors have been shown to be important for their tumorigenicity. In the present study we have tested whether serine-arginine protein kinase 1 (SRPK1), a major regulator of splicing factors, is involved in ovarian cancer progression and plays a role in chemo-sensitivity. By Western blot analyses, SRPK1 protein was found to be overexpressed in 4 out of 6 ovarian cancer cell lines as compared with an immortalized ovarian surface epithelial cell line; and in 55% of ovarian tumor samples as compared with non-neoplastic ovarian tissue samples. Reduction of SRPK1 expression using small interfering RNA (siRNA) encoding small hairpin RNA in ovarian cancer cells led to (i) reduced cell proliferation rate, slower cell cycle progression and compromised anchorage-independent growth and migration ability in vitro, (ii) decreased level of phosphorylation of multiple serine-arginine proteins, and P44/42MAPK and AKT proteins, and (iii) enhanced sensitivity to cisplatin. Together, these results suggest that elevated SRPK1 expression may play a role in ovarian tumorigenesis and SRPK1 may be a potential target for ovarian cancer therapy.PLoS ONE 12/2012; 7(12):e51030. DOI:10.1371/journal.pone.0051030 · 3.53 Impact Factor
Article: Ubiquitin-dependent regulation of phospho-AKT dynamics by the ubiquitin E3 ligase, NEDD4-1, in the IGF-1 response.[Show abstract] [Hide abstract]
ABSTRACT: AKT is a critical effector kinase downstream of the PI3K pathway that regulates a plethora of cellular processes including cell growth, death, differentiation and migration. Mechanisms underlying activated phospho-AKT (pAKT) translocation to its action sites remain unclear. Here we show that NEDD4-1 is a novel E3 ligase that specifically regulates ubiquitin-dependent trafficking of pAKT in IGF-1 signaling. NEDD4-1 physically interacts with AKT and promotes HECT domain-dependent ubiquitination of exogenous and endogenous AKT. NEDD4-1 catalyzes K63-type polyubiquitin chain formation on AKT in vitro. Plasma membrane binding is the key step for AKT ubiquitination by NEDD4-1 in vivo. Ubiquitinated pAKT translocates to perinuclear regions, where it is either released into the cytoplasm, imported into the nucleus or coupled with proteasomal degradation. IGF-1 signaling specifically stimulates NEDD4-1-mediated ubiquitination of pAKT, without altering total AKT ubiquitination. A cancer-derived plasma membrane-philic mutant AKT(E17K) is more effectively ubiquitinated by NEDD4-1 and more efficiently trafficked into the nucleus compared with wild type AKT. This study reveals a novel mechanism by which a specific E3 ligase is required for ubiquitin-dependent control of pAKT dynamics in a ligand-specific manner.Journal of Biological Chemistry 11/2012; DOI:10.1074/jbc.M112.416339 · 4.60 Impact Factor
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ABSTRACT: A link between T cell proliferation and the protein kinase C (PKC) family of serine/threonine kinases has been recognized for about 30 years. However, despite the wealth of information on PKC-mediated control of, T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in other systems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s) and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks), cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1 → S and/or G2 → M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling in T cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCθ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted in T cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in T cells.Frontiers in Immunology 01/2012; 3:423. DOI:10.3389/fimmu.2012.00423
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ABSTRACT: Previous studies have demonstrated that curcumin induces mitochondria-mediated apoptosis. However, understanding of the molecular mechanisms underlying curcumin-induced cell death remains limited. In this study, we demonstrate that curcumin treatment of cancer cells caused dose- and time-dependent caspase-3 activation, which is required for apoptosis as confirmed using the pan caspase inhibitor, z-VAD. Knockdown experiments and knockout cells excluded a role of caspase-8 in curcumin-induced caspase-3 activation. In contrast, Apaf-1 deficiency or silencing inhibited the activity of caspase-3, pointing to a requisite role of Apaf-1 in curcumin-induced apoptotic cell death. Curcumin treatment led to Apaf-1 upregulation both at the protein and mRNA levels. Cytochrome c release from mitochondria to the cytosol in curcumin-treated cells was associated with upregulation of proapoptotic proteins such as Bax, Bak, Bid, and Bim. Crosslinking experiments demonstrated Bax oligomerization during curcumin-induced apoptosis, suggesting that induced expression of Bax, Bid, and Bim causes Bax-channel formation on the mitochondrial membrane. The release of cytochrome c was unaltered in p53-deficient cells, whereas absence of p21 blocked cytochrome c release, caspase activation, and apoptosis. Importantly, p21-deficiency resulted in reduced expression of Apaf-1 during curcumin treatment, indicating a requirement of p21 in Apaf-1 dependent caspase activation and apoptosis. Together, our findings demonstrate that Apaf-1, Bax, and p21 as novel potential targets for curcumin or curcumin-based anticancer agents.Cell cycle (Georgetown, Tex.) 12/2011; 10(23):4128-37. DOI:10.4161/cc.10.23.18292 · 5.24 Impact Factor
Article: Protein kinase Cα signaling regulates inhibitor of DNA binding 1 in the intestinal epithelium.[Show abstract] [Hide abstract]
ABSTRACT: Increasing evidence supports a role for PKCα in growth arrest and tumor suppression in the intestinal epithelium. In contrast, the Id1 transcriptional repressor has pro-proliferative and tumorigenic properties in this tissue. Here, we identify Id1 as a novel target of PKCα signaling. Using a highly specific antibody and a combined morphological/biochemical approach, we establish that Id1 is a nuclear protein restricted to proliferating intestinal crypt cells. A relationship between PKCα and Id1 was supported by the demonstration that (a) down-regulation of Id1 at the crypt/villus junction coincides with PKCα activation, and (b) loss of PKCα in intestinal tumors is associated with increased levels of nuclear Id1. Manipulation of PKCα activity in IEC-18 nontransformed intestinal crypt cells determined that PKCα suppresses Id1 mRNA and protein via an Erk-dependent mechanism. PKCα, but not PKCδ, also inhibited Id1 expression in colon cancer cells. Id1 was found to regulate cyclin D1 levels in IEC-18 and colon cancer cells, pointing to a role for Id1 suppression in the antiproliferative/tumor suppressive activities of PKCα. Notably, Id1 expression was elevated in the intestinal epithelium of PKCα-knock-out mice, confirming that PKCα regulates Id1 in vivo. A wider role for PKCα in control of inhibitor of DNA binding factors is supported by its ability to down-regulate Id2 and Id3 in IEC-18 cells, although their suppression is more modest than that of Id1. This study provides the first demonstrated link between a specific PKC isozyme and inhibitor of DNA binding factors, and it points to a role for a PKCα → Erk ⊣ Id1 → cyclin D1 signaling axis in the maintenance of intestinal homeostasis.Journal of Biological Chemistry 03/2011; 286(20):18104-17. DOI:10.1074/jbc.M110.208488 · 4.60 Impact Factor
Chapter: PKC and Control of the Cell Cycle[Show abstract] [Hide abstract]
ABSTRACT: Members of the PKC family have been widely implicated in control of cell proliferation. Consistent with this role, PKC signaling can negatively or positively modulate the cell cycle at multiple stages, including cell cycle entry and exit, progression through G1 and S phases, and transit through the G1 and G2 checkpoints. The cell cycle-specific effects of PKCs are dependent on the timing and duration of PKC activation, the specific PKC isozyme(s) involved, and the cellular context. Various cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (Cdks), and Cdk inhibitors, have been implicated in PKC-induced cell cycle effects, with p21Waf1/Cip1 and cyclin D1 emerging as key targets of PKC control. p21Waf1/Cip1 can be targeted by distinct PKC isozymes at different stages of the cell cycle to control both the G1→S and G2→M transitions, while cyclin D1 expression is modulated by transcriptional or translational mechanisms to regulate progression through G1 phase. PKC signaling can also phosphorylate lamin B to promote nuclear lamina disassembly and G2→M progression. Although understanding of the specific functions of individual PKC isozymes in regulation of the cell cycle remains a major challenge for the future, accumulated evidence indicates that PKCα and δ can either inhibit or promote G1→S and G2→M progression in a highly context-dependent manner, while PKCβII and ε are predominantly cell cycle stimulatory, and PKCη is generally inhibitory. Elucidation of the complex mechanisms underlying PKC isozyme-mediated control of the cell cycle is critical for the development of novel anticancer therapies targeting individual PKCs or their downstream effectors. KeywordsPKC-Cell cycle-G1 progression-G1 and G2/M arrest-Cell cycle exit-G2/M progression-Senescence-S phase-Cyclin D1-p21Waf1/Cip1-PKCalpha-PKCd-PKCbII-PKC¼-PKCq-PKCz and i12/2009: pages 155-188;
Article: PKCalpha tumor suppression in the intestine is associated with transcriptional and translational inhibition of cyclin D1.[Show abstract] [Hide abstract]
ABSTRACT: Alterations in PKC isozyme expression and aberrant induction of cyclin D1 are early events in intestinal tumorigenesis. Previous studies have identified cyclin D1 as a major target in the antiproliferative effects of PKCalpha in non-transformed intestinal cells; however, a link between PKC signaling and cyclin D1 in colon cancer remained to be established. The current study further characterized PKC isozyme expression in intestinal neoplasms and explored the consequences of restoring PKCalpha or PKCdelta in a panel of colon carcinoma cell lines. Consistent with patterns of PKC expression in primary tumors, PKCalpha and delta levels were generally reduced in colon carcinoma cell lines, PKCbetaII was elevated and PKCepsilon showed variable expression, thus establishing the suitability of these models for analysis of PKC signaling. While colon cancer cells were insensitive to the effects of PKC agonists on cyclin D1 levels, restoration of PKCalpha downregulated cyclin D1 by two independent mechanisms. PKCalpha expression consistently (a) reduced steady-state levels of cyclin D1 by a novel transcriptional mechanism not previously seen in non-transformed cells, and (b) re-established the ability of PKC agonists to activate the translational repressor 4E-BP1 and inhibit cyclin D1 translation. In contrast, PKCdelta had modest and variable effects on cyclin D1 steady-state levels and failed to restore responsiveness to PKC agonists. Notably, PKCalpha expression blocked anchorage-independent growth in colon cancer cells via a mechanism partially dependent on cyclin D1 deficiency, while PKCdelta had only minor effects. Loss of PKCalpha and effects of its re-expression were independent of the status of the APC/beta-catenin signaling pathway or known genetic alterations, indicating that they are a general characteristic of colon tumors. Thus, PKCalpha is a potent negative regulator of cyclin D1 expression and anchorage-independent cell growth in colon tumor cells, findings that offer important perspectives on the frequent loss of this isozyme during intestinal carcinogenesis.Experimental Cell Research 03/2009; 315(8):1415-28. DOI:10.1016/j.yexcr.2009.02.002 · 3.37 Impact Factor
Article: Forced expression of survivin-2B abrogates mitotic cells and induces mitochondria-dependent apoptosis by blockade of tubulin polymerization and modulation of Bcl-2, Bax, and survivin[Show abstract] [Hide abstract]
ABSTRACT: It has been previously shown that both survivin and the survivin splice variant survivin-2B are localized in mitochondria. Whereas the mechanism involved in blockade of mitochondria-mediated apoptosis by survivin has been extensively studied, the role of survivin-2B in regulation of apoptosis has not been well defined. In the present study, we report that in addition to mitochondria, survivin-2B is also localized in the microtubule organization center (MTOC) and, in contrast to other survivin isoforms (i.e. survivin and survivin-DeltaEx3), behaves as a proapoptotic molecule. We show that forced expression of survivin-2B blocks tubulin polymerization, ablates mitotic cells, and induces mitochondria-dependent apoptosis. The mitochondria-mediated apoptosis induced by survivin-2B was indicated by Smac release from mitochondria, activation of caspases 9 and 3, and loss of mitochondrial potential, while caspase-8 remained inactive. Further analysis of the mechanism for the mitochondria-associated events of apoptosis induced by forced expression of survivin-2B revealed down-regulation of the pro-survival factor Bcl-2 and up-regulation of the pro-apoptotic factor Bax in mitochondria, while the apoptosis-inducing factor (AIF) remains unchanged. Our studies further showed that taxol (paclitaxel) treatment of cancer cells not only up-regulates survivin but also down-regulates survivin-2B and that forced expression of survivin-2B sensitizes cells to taxol-induced cell growth inhibition and cell death, while silencing of endogenous survivin-2B transcripts by survivin-2B-specific siRNA made cells resistant to taxol treatment. These findings advance our current knowledge about survivin-2B and may help to develop novel approaches for cancer treatment.Journal of Biological Chemistry 10/2007; 282(37):27204-14. DOI:10.1074/jbc.M705161200 · 4.60 Impact Factor
Article: Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-Kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells[Show abstract] [Hide abstract]
ABSTRACT: We reported previously that protein kinase Calpha (PKCalpha), a negative regulator of cell growth in the intestinal epithelium, inhibits cyclin D1 translation by inducing hypophosphorylation/activation of the translational repressor 4E-BP1. The current study explores the molecular mechanisms underlying PKC/PKCalpha-induced activation of 4E-BP1 in IEC-18 nontransformed rat ileal crypt cells. PKC signaling is shown to promote dephosphorylation of Thr(45) and Ser(64) on 4E-BP1, residues directly involved in its association with eIF4E. Consistent with the known role of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway in regulation of 4E-BP1, PKC signaling transiently inhibited PI3K activity and Akt phosphorylation in IEC-18 cells. However, PKC/PKCalpha-induced activation of 4E-BP1 was not prevented by constitutively active mutants of PI3K or Akt, indicating that blockade of PI3K/Akt signaling is not the primary effector of 4E-BP1 activation. This idea is supported by the fact that PKC activation did not alter S6 kinase activity in these cells. Further analysis indicated that PKC-mediated 4E-BP1 hypophosphorylation is dependent on the activity of protein phosphatase 2A (PP2A). PKC signaling induced an approximately 2-fold increase in PP2A activity, and phosphatase inhibition blocked the effects of PKC agonists on 4E-BP1 phosphorylation and cyclin D1 expression. H(2)O(2) and ceramide, two naturally occurring PKCalpha agonists that promote growth arrest in intestinal cells, activate 4E-BP1 in PKC/PKCalpha-dependent manner, supporting the physiological significance of the findings. Together, our studies indicate that activation of PP2A is an important mechanism underlying PKC/PKCalpha-induced inhibition of cap-dependent translation and growth suppression in intestinal epithelial cells.Journal of Biological Chemistry 06/2007; 282(19):14213-25. DOI:10.1074/jbc.M610513200 · 4.60 Impact Factor
Article: A phase I pharmacokinetic and pharmacodynamic study of intravenous calcitriol in combination with oral gefitinib in patients with advanced solid tumors[Show abstract] [Hide abstract]
ABSTRACT: In preclinical models, calcitriol and the tyrosine kinase inhibitor gefitinib are synergistic and modulate extracellular signal-regulated kinase (Erk) and Akt pathways. Therefore, we conducted a phase I study of calcitriol and gefitinib to determine the maximum tolerated dose (MTD) of this combination. Calcitriol was given i.v. over 1 h on weeks 1, 3, and weekly thereafter. Gefitinib was given at a fixed oral daily dose of 250 mg starting at week 2 (day 8). Escalation occurred in cohorts of three patients until the MTD was defined. Pharmacokinetic studies were done for calcitriol and gefitinib. Serial skin biopsies were done to investigate epidermal growth factor receptor (EGFR) pathway pharmacodynamic interactions. Thirty-two patients were treated. Dose-limiting hypercalcemia was noted in two of four patients receiving 96 mug/wk of calcitriol. One of seven patients developed dose-limiting hypercalcemia at the MTD 74 mug/wk calcitriol dose level. The relationship between calcitriol dose and peak serum calcitriol (C(max)) and systemic exposure (AUC) was linear. Mean (+/-SD) serum calcitriol C(max) at the MTD was 6.68 +/- 1.42 ng/mL. Gefitinib treatment inhibited EGFR, Akt, and Erk phosphorylation in the skin. Calcitriol did not have consistent effects on skin EGFR or its downstream elements. The combination of gefitinib and calcitriol did not modulate tumor EGFR pathway in patients with serial tumor biopsies. High doses of weekly i.v. calcitriol can be administered safely in combination with gefitinib. Calcitriol concentrations achieved at the MTD 74 mug calcitriol exceed in vivo concentrations associated with antitumor activity in preclinical models.Clinical Cancer Research 03/2007; 13(4):1216-23. DOI:10.1158/1078-0432.CCR-06-1165 · 8.19 Impact Factor
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ABSTRACT: Overexpression of signaling proteins including epidermal growth factor receptor (EGFR), Akt, mitogen activated protein kinase (MAPK) and cyclooxygenase-2 (COX-2) occurs in cholangiocarcinoma cell lines. However, the prognostic value of these markers is unknown. No prior study correlated the expression of these signaling proteins with clinical outcome. Further, co-expression of these proteins has not been reported. Co-expression may reflect cross-talk between signaling pathways. The aim of this clinicopathological study was to investigate the overexpression and co-expression of EGFR and related signaling proteins in cholangiocarcinoma and explore their relationship to clinical outcome. Twenty-four consecutive cases of cholangiocarcinoma treated from 1996 to 2002 at Roswell Park Cancer Institute were included. Immunohistochemical staining of paraffin-embedded tissue sections was performed using antibodies against Akt, p-Akt, MAPK, p-MAPK, COX-2, EGFR and p-EGFR. Two pathologists independently scored the protein expression. Cyclooxygenase-2, Akt, and p-MAPK were commonly expressed in biliary cancers (100%, 96% and 87% of malignant cells, respectively). EGFR (60%) and p-EGFR (22%) overexpression was also detected. There was a significant association between EGFR and p-EGFR (P = 0.027) and between Akt and p-Akt (P = 0.017) expression in tumor tissue. A noteworthy association was shown between MAPK and p-Akt (P = 0.054). Multivariate analysis using the Cox proportional hazard model identified the use of chemotherapy (hazard ratio [HR] = 0.039, P = 0.0002), radiation (HR = 0.176, P = 0.0441) and Akt expression (HR = 0.139, P = 0.006) as the best predictors of overall prognosis. Epidermal growth factor receptor signaling intermediates are commonly expressed in cholangiocarcinoma. Expression of Akt and use of systemic chemotherapy or radiation may correlate with improved survival.Journal of Gastroenterology and Hepatology 12/2006; 21(11):1744-51. DOI:10.1111/j.1440-1746.2006.04373.x · 3.63 Impact Factor
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ABSTRACT: Long-term survival of surgically resectable pancreatic cancer patients is uncommon. The epidermal growth factor receptor (EGFR) and the phosphoinositol-3-kinase pathways are often activated in pancreatic cancer, and an understanding of their role in resected cases may help refine adjuvant therapy. We investigated the expression of EGFR, Erk, Akt, and their phosphoforms (p-) in pancreatectomy specimens and correlated these with survival. Thirty-nine consecutive surgically resected pancreatic adenocarcinoma cases were included. Immunohistochemical staining of paraffin-embedded blocks was performed by using monoclonal antibodies against EGFR, Erk, p-Erk, Akt, and p-Akt. A standard immunoperoxidase technique was used to detect the avidin-biotin peroxidase complex. Immunostaining was visually scored with the histoscore method by two surgical pathologists. Patient characteristics were as follows: 17 men and 22 women; median age, 66 years; and American Joint Committee on Cancer stage I, 5 patients; stage II, 4 patients; stage III, 27 patients; and stage IV, 3 patients. The tumor was World Health Organization grade 1 in 4, grade 2 in 17, and grade 3 in 18 cases. Adjuvant therapies were chemotherapy (n = 6), radiotherapy (n = 1), and chemoradiotherapy (n = 17). Immunohistochemistry revealed positive expression of EGFR in 30.8%, Erk in 92.3%, p-Erk in 45.9%, Akt in 71.8%, and p-Akt in 20.5% of cases. On univariate analyses, tumor grade (P = .0098), p-Akt (P = .0003), and p-Erk (P = .0052) expression correlated with survival. On multivariate analyses, age (P = .0002; hazard ratio [HR], 1.8), grade (P = .00318; HR, 3.0), Akt (P = .0433; HR, .4), p-Akt (P = .0002; HR, .2), and p-Erk (P = .0003; HR, 3.5) expression correlated significantly with survival. p-Erk and p-Akt expression may have prognostic and therapeutic implications in pancreatic cancer.Annals of Surgical Oncology 08/2006; 13(7):933-9. DOI:10.1245/ASO.2006.07.011 · 3.94 Impact Factor
Article: Protein kinase C alpha signaling inhibits cyclin D1 translation in intestinal epithelial cells[Show abstract] [Hide abstract]
ABSTRACT: Cyclin D1 is a key regulator of cell proliferation, acting as a mitogen sensor and linking extracellular signaling to the cell cycle machinery. Strict control of cyclin D1 levels is critical for maintenance of tissue homeostasis. We have reported previously that protein kinase C alpha (PKCalpha), a negative regulator of cell growth in the intestinal epithelium, promotes rapid down-regulation of cyclin D1 (Frey, M. R., Clark, J. A., Leontieva, O., Uronis, J. M., Black, A. R., and Black, J. D. (2000) J. Cell Biol. 151, 763-778). The current study explores the mechanisms underlying PKCalpha-induced loss of cyclin D1 protein in non-transformed intestinal epithelial cells. Our findings exclude several mechanisms previously implicated in down-regulation of cyclin D1 during cell cycle exit/differentiation, including alterations in cyclin D1 mRNA expression and protein turnover. Instead, we identify PKCalpha as a novel repressor of cyclin D1 translation, acting at the level of cap-dependent initiation. Inhibition of cyclin D1 translation initiation is mediated by PKCalpha-induced hypophosphorylation/activation of the translational suppressor 4E-BP1, association of 4E-BP1 with the mRNA cap-binding protein eIF4E, and sequestration of cyclin D1 mRNA in 4E-BP1-associated complexes. Together, these post-transcriptional effects ensure rapid disappearance of the potent mitogenic molecule cyclin D1 during PKCalpha-induced cell cycle withdrawal in the intestinal epithelium.Journal of Biological Chemistry 06/2006; 281(21):14596-603. DOI:10.1074/jbc.M601959200 · 4.60 Impact Factor
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ABSTRACT: TACC1 is the founding member of the evolutionarily conserved transforming acidic coiled coil genes. These genes play a role in normal development and tumorigenesis through interactions with multiple complexes involved in transcription, translation, and centrosomal dynamics. Despite its importance, detailed examination of the expression of TACC1 and splice variants has not previously been performed. In this study, the spatiotemporal distribution of the Tacc1 protein was examined immunohistochemically in cross-sections of mouse embryonic tissues. We also report the distribution of currently known/predicted TACC1 splice variants in adult humans. These results indicate that Tacc1 is regulated in a dynamic manner during embryogenesis. In adult humans, ubiquitous expression of at least one TACC1 splice variant is noted, although specific combinations of variants are evident in individual differentiated tissues. An important observation is that in the in vivo three-dimensional tissue architecture of the growing organism, both the human and mouse TACC1 protein can be localized to different subcellular compartments in a cell- and tissue-specific manner. This indicates that exploration of TACC1 function must take into account the temporal expression of specific splice variants that may perform different cell-type and tissue-specific functions. Furthermore, this analysis will provide the groundwork from which future Tacc1 knockout strategies can be designed and properly interpreted.Developmental Dynamics 06/2006; 235(6):1638-47. DOI:10.1002/dvdy.20724 · 2.67 Impact Factor
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ABSTRACT: Dysregulation of the human Transforming Acidic Coiled Coil (TACC) genes is thought to be important in the development and progression of multiple myeloma, breast and gastric cancer. Recent, large-scale genomic analysis and Serial Analysis of Gene Expression data suggest that TACC1 and TACC3 may also be involved in the etiology of ovarian tumors from both familial and sporadic cases. Therefore, the aim of this study was to determine the occurrence of alterations of these TACCs in ovarian cancer. Detection and scoring of TACC1 and TACC3 expression was performed by immunohistochemical analysis of the T-BO-1 tissue/tumor microarray slide from the Cooperative Human Tissue Network, Tissue Array Research Program (TARP) of the National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Tumors were categorized as either positive (greater than 10% of cells staining) or negative. Statistical analysis was performed using Fisher's exact test and p < 0.05 (single comparisons), and p < 0.02 (multiple comparisons) were considered to be significant. Transgenomics WAVE high performance liquid chromatography (dHPLC) was used to pre-screen the TACC3 gene in constitutional DNA from ovarian cancer patients and their unaffected relatives from 76 families from the Gilda Radner Familial Ovarian Cancer Registry. All variant patterns were then sequenced. This study demonstrated absence of at least one or both TACC proteins in 78.5% (51/65) of ovarian tumors tested, with TACC3 loss observed in 67.7% of tumors. The distribution pattern of expression of the two TACC proteins was different, with TACC3 loss being more common in serous papillary carcinoma compared with clear cell carcinomas, while TACC1 staining was less frequent in endometroid than in serous papillary tumor cores. In addition, we identified two constitutional mutations in the TACC3 gene in patients with ovarian cancer from the Gilda Radner Familial Ovarian Cancer Registry. These patients had previously tested negative for mutations in known ovarian cancer predisposing genes. When combined, our data suggest that aberrations of TACC genes, and TACC3 in particular, underlie a significant proportion of ovarian cancers. Thus, TACC3 could be a hitherto unknown endogenous factor that contributes to ovarian tumorigenesis.BMC Women's Health 06/2005; 5:8. DOI:10.1186/1472-6874-5-8 · 1.66 Impact Factor
Article: Cell cycle- and protein kinase C-specific effects of resiniferatoxin and resiniferonol 9,13,14-ortho-phenylacetate in intestinal epithelial cells.[Show abstract] [Hide abstract]
ABSTRACT: We have previously reported that protein kinase C (PKC) signaling can trigger hallmark events of cell cycle withdrawal in intestinal epithelial cells, including downregulation of cyclin D1, induction of p21(Waf1/Cip1), and activation of the growth suppressor function of pocket proteins. In the current study, we compared the cell cycle- and PKC-specific effects of the vanilloid resiniferatoxin (RTX), its parent diterpene resiniferonol 9,13,14-ortho-phenylacetate (ROPA), and the PKC agonist PMA in the IEC-18 non-transformed intestinal crypt cell line. ROPA and PMA were found to produce strikingly similar alterations in cell cycle progression and PKC activity in IEC-18 cells, although PMA was approximately 1000-fold more potent in producing these effects. Both agents induced a transient PKC-dependent blockade in G1---> S progression associated with transient downregulation of cyclin D1 and induction of p21(Waf1/Cip1). In contrast, RTX produced a prolonged PKC-independent cell cycle arrest in G(0)/G(1) phase which was maintained for longer than 24h. This arrest was vanilloid receptor-independent and associated with prolonged downregulation of cyclin D1 mRNA and protein, with little effect on levels of p21(Waf1/Cip1). Combined exposure to RTX and ROPA produced a sustained and complete cell cycle blockade in IEC-18 cells, associated with depletion of cyclin D1 and sustained enhancement of p21(Waf1/Cip1) levels. PMA, ROPA, RTX and the RTX/ROPA combination were capable of activating ERK1/2 signaling in IEC-18 cells, albeit with different kinetics. In contrast, only PMA and ROPA activated JNK1/2 and p38 in this system. Notably, some preparations of commercially obtained RTX produced effects indistinguishable from those of the RTX/ROPA combination, suggesting that certain batches of the compound may contain significant amounts of ROPA (or another PKC agonist activity). Together, these data demonstrate that structurally related compounds can produce similar cell cycle-specific effects but through distinct mechanisms. In addition, they add to a growing body of evidence that vanilloids can have antiproliferative effects in a variety of cell types.Biochemical Pharmacology 06/2004; 67(10):1873-86. DOI:10.1016/j.bcp.2004.02.006 · 4.65 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Krüppel-like transcription factors have been linked to cell growth regulation and tumorigenesis in a number of systems. In the intestinal epithelium, expression of KLF5 (IKLF/BTEB2) is limited to proliferating crypt cells, indicating a growth-promoting role. Consistent with this role, we demonstrate that expression of KLF5 in non-transformed intestinal epithelial cells (ileal IEC-18 and Immorto-Min Colon Epithelial (IMCE) cells) enhances colony formation, cyclin D1 transcription, and cell growth. However, in contrast to these effects in non-transformed cells, KLF5 reduced colony number, failed to enhance cyclin D1 transcription, and was negatively correlated with cell growth in colon cancer cell lines. The relationship between tumor progression and KLF5 was further investigated using Ras-mediated transformation of IEC-18 and IMCE cells as syngeneic models. Ras-transformation recapitulated differences in the effects of KLF5 on cell growth and cyclin D1 transcription, providing a direct link between intestinal tumor progression and altered function of KLF5. Ras-transformation also markedly down-regulated KLF5; further analysis indicated that reduced expression of KLF5 mRNA and destabilization of KLF5 protein occur in intestinal tumors. Reduced levels of KLF5 mRNA were also detected in APC(min) mouse and human familial adenomatous polyposis adenomas compared with normal crypt epithelium, indicating that down-regulation of KLF5 is an early event in intestinal tumorigenesis in vivo. Collectively, these data indicate that intestinal tumor progression is associated with a change in the growth-related functions of KLF5 and that intestinal tumors down-regulate KLF5 expression by multiple mechanisms.Journal of Biological Chemistry 04/2004; 279(13):12093-101. DOI:10.1074/jbc.M311532200 · 4.60 Impact Factor
Top Journals
University of Nebraska Medical CenterOmaha, Nebraska, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
- • Department of Pharmacology and Therapeutics
- • Grace Cancer Drug Center
- • Department of Experimental Therapeutics
University of Nebraska at Omaha
Omaha, NE, United States
- Eppley Institute for Research in Cancer and Allied Diseases
Gynecologic Oncology GroupBuffalo, New York, United States


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Hi everyone,
My kitty Olivia is in a local online Halloween contest, if you wouldn't mind voting - we'd appreciate it.
She is listed as "#1 Olivia" and she is the only cat on there This contest is all in good fun. Here is the entered picture:
KSTT Pet Costume Contest 2009
Also, another of our lovely MCers doggies are in a contest - please vote for them as well
SCUBAbe's doggies: KTLA Furry Frights

subset: commoncrawl


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The crooner's former estate in the Coachella Valley is back on the market, and you won't believe who once stayed in the guest house.
Secrets of a Storyteller
My sister and I have been going to Glastonbury music festival since 2007. I highly recommend it to people who love music and of course camping and roughing it. You never know what kind of music you will find.
This year we stayed in the field of teepees overlooking one of the main stages. I got to see Haim and Alabama Shakes—now I'm crazy about them.


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Freedom is not free. The best of us always leave too soon.
Yes you can shoot Foster type slugs through your field barrel but not sabots. Improved Cylinder would be the best choke to use but some guns shoot better with modified chokes. I would suggest that you try several different brands of slugs to see which one your gun likes best.
A gun is like a wife. If you can't love the one you have get a divorce from it and go find one you can lovel
The stock on mine broke right where it mates to the receiver after considerable use and I have seen a few others that are operating under taped conditions. Probably the birch (i think) stock. Those can be replaced however. Never had any problems with the actual function and I've had both a 20 and a 12.
NRA Member
Sustaining Member Southern Poverty Law Center
"Lighten Up Francis"
Semper gero sub gero


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left over BBQ
We bought some pre-made BBQ in a tub (not frugal, but on sale) and have maybe a half cup or so left over. Any ideas what I can do with it?
Take a can of bisquits & roll each one out into a small circle put it into a cupcake pan add your bbq & top with cheese & bake. This is also good for left over taco meat. YUMMM BUT TRUTHFULLY THERE IS NO SUCH THING AS A HALF CUP OF ANYTHING LEFT AT THIS HOUSE !!! LOL TO MANY KIDS HANGING AROUND !! :)
OH I love corn, what is your recipe? one of my favorites is Corn Bake:
Mix together
1 can whole kernel corn undrained
1 can creamed corn
1 small pkg jiffy corn muffin mix
3 eggs
Mix & Spread over the top:
1 8oz carton of sour cream
1 cup of grated cheese
Bake at 350 for 45 minutes in a greased 9x13 pan
Mine is the same except the corn is drained,
2 eggs
mix the sour cream in
1/4-1/2 tsp garlic powder optional
My recipe does not call for cheese, but I will sprinkle on whatever I have, or use some Velveta strips.
I made it last weekend, and I'm wanting to use up the sour cream that is opened, and the box of Jiffy Mix that went out last month.
I've taken inventory of the things that are outdated a bit, or nearing a going out date. That determines what I've been eating lately, until I get all of the older stock used up.
I've been eating out of the freezer too, since I hope to have a deer or two in the next couple of weeks.
Sue, ain't that a good recipe ??? I can eat the whole pan by myself LOL Do you do the deer huntin ? I just like jiffy mix all by itself, really like it with tater soup or veggie soup OH! can't forget the white beans with it YUMMM I'm starting to get hungry :)
lilly ")
You can use leftover bbq as a topping for a baked potato, add some cheese and a dollop of sour cream, if you want.
Add a bit of leftover bbq to your mac and cheese or spread on top of scalloped potatoes.
Add some cheese, heat, and use as a dip for chips/crackers.
Spread a little on a grilled cheese sandwich before grilling (I'd use sharp cheddar or Monterey Jack)


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News and Events
$10 InBody Assessments on March 28!
BC Rec is offering $10 InBody Assessments (typically $15) on Saturday, March 28 from 10a.m.-2p.m. as part of the Learn the Burn event! The Inbody Assessment assesses your segmental muscle mass, body fat, resting metabolic rate, and more! Learn more here. Also check out their FAQ page. This event is for graduate and undergraduate BC Rec members only.
BC Rec Day at the Plex!
Campus Recreation will be holding it's BC Rec Day for members on Friday, March 27 at the Plex! Mark your calendars! The day will include:
Paddleboard Yoga
Time: 7:00p.m. – 8:00p.m.
Location: Pool Lanes 1-6
Sign-up required at recconnect.bc.edu
Kayak Polo
Time: 3:00p.m. – 6:00p.m.
Location: Dive Well
Sign-up required at recconnect.bc.edu
Glow Yoga (normal class with glow)
Time: 5:30p.m. – 6:30p.m.
Location: MPR
Sign-up Not Required
Glow Zumba
Time: 6:45p.m. – 7:45p.m.
Location: MPR
Sign-up Not Required
Intramural Combine
Time: 1:00p.m. – 3:30p.m.
Location: Basketball Wing
Sign-up Not Required


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Happy Saturday! Here's a sweet little (vegan) weekend treat.
I just realized, for as much as I love to bake cookies, this blog is seriously lacking recipes to show for it. And then I realized why – the camera can hardly snap fast enough before Jack reaches his hand in and they all disappear. Waiting for me to arrange warm cookies nicely on a plate is just not something this guy I'm with has patience for.
These cookies are made with coconut oil instead of butter. I like using it because it's a great healthy non-dairy fat that's less processed than vegan butter substitutes. A flax "egg" holds these together but if you're not vegan and don't have flax – you can just use an egg.
You'll notice, this is sort of a small batch. This recipe makes 12 cookies, so just double it if you are making cookies for your family. For Jack and I (who will eat these all in one day), less is just more.


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Jobs and Internships
Join the fight to eradicate hunger in our region with Greater Pittsburgh Community Food Bank
Available Jobs & Internships
Summer Music Festival – Production Internship
Come join our team at Greater Pittsburgh Community Food Bank and be a part of the planning process for the 21st Music Festival at Hartwood Acres, held July 24 – 26. The Food Bank is looking to develop its first ever creative cohort of 5 – 6 interns looking to lend their talent and expertise to help organize and plan our 21st music festival, which is our annual flagship fundraiser. This internship opportunity is ideal for students looking to gain experience related to the music industry, event planning and marketing. Interns will work within a creative team to develop fresh, new ways to make this our most successful Music Festival ever, all while helping to feed our hungry neighbors.
Communications & Social Media Intern
The Communications & Social Media Intern will assist the Food Bank's Communications Department in creating and sharing content through social media in order to carry out our mission. A successful intern will work in tandem with the Communications Technology Coordinator to effectively target social media campaigns to increase donor, volunteer and advocacy activity online. The passionate individual in this position will interact with all areas of the Food Bank, from fundraising to the distribution of food, in order to better share the organization's story. This position will require engagement with Food Bank staff members, volunteers, partner organizations, donors and the families we serve.
Truck Driver / Warehouse Worker
Make food available to hungry people in Southwestern Pennsylvania while developing community awareness and upholding Food Bank values.
Responsible for warehouse product care including receiving, storage, distribution, pickup and/or delivery.


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The history of the American West is written not in blood, but in water. Without imported water, Colorado Springs, Las Vegas, Los Angeles and Phoenix would have remained as they were during the early years of the 20th century — pleasant, sleepy backwaters, footnotes to a larger history. Continue Reading One river, so little waterContinue reading …
Built in 1964, the Pikes Peak Summit House is too small to handle the half million visitors it receives each summer.
In addition, improper thermodynamic engineering during construction has triggered a melting of the permafrost, resulting in an uneven and unpredictable sinking of the building. By 1992, its foundation was so compromised that the structure had to be supported by dozens of heavy-duty jacks. Continue Reading America's Mountain looks more like a junk yard
The men and women who serve as the eyes and ears of our leaders should be informed, dispassionate, smart and thoroughly familiar with both Iraq and the Middle East. Continue Reading Finding the right info is not that toughContinue reading …
The city is seeking $1 million annually from a new Pikes Peak concessionaire, but will the increased revenue make a difference?
Past performance suggests that it will not.
During 2007, the city projected operating revenue from tolls and concessions of $2,708,069 — and estimated operating expenses at exactly the same number. Continue Reading Additional revenue might not make a difference
Fifteen years ago, the Colorado Springs City Council voted to replace the Carle family, who had been the concessionaires on Pikes Peak for 99 years, with a national firm, ARA Services.
ARA, which has since changed its name to Aramark, won the contract with a bid that was substantially higher than any other. Not only would the city's yearly revenue from the peak almost double, to $500,000, but ARA also would invest $1 million in the peak's aging infrastructure. At the time, city leaders believed that the mountain environment would be dramatically improved and that a new summit house would be erected in time for the new millennium. Continue Reading City seeking to make 'peak' pay off
All over the length and breadth of our great nation, lefty blogs such as Dailykos and Huffington Post have found a new target/victim: rookie Congressman Doug Lamborn. For those of you with actual lives who don't follow petty political spats, here's some background. A Monument couple, Jonathan and Anna Bartha, one of whom had worked… Continue Reading Swiftboating the CongressmanContinue reading …
Crass? Clueless? Just plain dumb? All of the above? Yup, all of 'em are good descriptors of the Fine Arts Center's midnight teardown of the historic Carpenter mansion last week.
And why did they tear it down? For a parking lot!
According to FAC public relations flack Charlie Snyder, the decision had been made years before, but they just now got around to doing it. Continue Reading FAC joins the growing list of vandals
Here's an email from Senator Salazar's office that was forwarded to me a couple of days ago. From: Richard Skorman, Regional Director and Angela Joslyn, Regional Representative for U.S. Senator Ken Salazar Re: Invitation to Forum for Military Issues in the Pikes Peak Region When: Wednesday, August 29th 10:00 A.M.-11:30 Where: City Council Chambers, 107… Continue Reading Managing Community InputContinue reading …
Watching the Broncos stumble haplessly around during last week's preseason game against the 'Boys was, unless you are a Cowboys fan, a painful experience.
The Donksters, who just last week were anointed as Super Bowl contenders by the Denver media, looked more like pretenders, destined to finish at or near the bottom of the AFC. Continue Reading Let's admit we're licked on the water front
As a native of our fair city, I appreciate both its extraordinarily beautiful setting and its enduring quirkiness. General Palmer, poised gracefully in the saddle of his noble bronze steed at the intersection of Nevada and Platte, is part of that quirkiness. The statue, which was funded by citizen contributions, was placed in its present… Continue Reading Leave the General Alone!Continue reading …


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South Dakota hitter signs with Jimmies
Karlea Stahl of Onida, S.D., has signed with the Jimmie volleyball team.
Stahl, a multi-sport standout at Sully Buttes High School, totaled 375 kills, 301 digs, 83 blocks and 48 aces in her senior season. She is a 5-foot-8 outside hitter.
She also surpassed the 1,000-point plateau in basketball. She's also active in track, band, chorus and student council.
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Recent data on organized violence shows that conflicts between a state and one or more nonstate armed groups (NSAGs) vastly outnumber interstate conflicts. As a result, argues former international affairs fellow Payton L. Knopf in a new CFR Working Paper, the State Department needs clear guidelines as to why, when, and how its diplomats should conduct outreach to these groups.
From the Taliban in Afghanistan to Hamas in the Middle East, nonstate armed groups are critical players in the world's conflicts. ōLittle work has been done to prepare U.S. diplomats for analyzing and engagingö with NSAGs, despite their direct effect on U.S. interests around the world, Knopf writes in ōEnhancing U.S. Diplomatic Engagement with Nonstate Armed Groups.ö He acknowledges the challenges the State Department faces in engaging armed groups, such as a lack of institutional capacity and concerns about conferring legitimacy to terrorist organizations.
ōTo advance U.S. interests in a world in which nonstate actors play a pivotal role . . . the State Department should develop a formal analytical frameworkŚrather than an ad hoc processŚto plan for official engagement with NSAGs.ö
For the full report, visit www.cfr.org/nonstate_armed_groups_paper.


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Browns Summit Homes for Rent
BusinessWeek "Best of the Web" Winner 3 Years Running
Search Browns Summit Home Rental Market
Thanks for including so many properties in your rental search. My new rental is really close to downtown and has all the amenities that I would ever need. - Browns Summit,NC
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Browns Summit is full of a good variety of charming houses just spend some time using MyNewPlace's home rental search and you will come upon the exact right one. House rentals can be the best recourse to have a lot of extra space for you and your family.
Want the inside scoop on Browns Summit? Check out our Browns Summit Local Talk for local tips and information about Browns Summit. You can also get answers to your Browns Summit questions from our local experts by using the "Ask a Question" feature.
Houses for Rent in Cities Near Browns Summit, NC
MyNewPlace can help you find the Browns Summit, NC home rental that will work best for you. Using our rental home search, you can view townhomes or condos for rent if you want to live downtown, or check out the rental listings for single family house rentals in the surrounding areas. Try one of these cities below for more rental houses near Browns Summit, NC.


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I want to sell my templates on themeforest, but the problem is, that i don't know how to pay taxes in Norway when you are a freelancer, and don't know exactly how much money you will earn. I tried to find the answer on google, but there's not much information about freelancers.
Hope there are some norwegians(or not ) that will help me.
Hi, not from Normway (Skøl!) but I'm sure you'll have some kind of chamber of commerce or interest grouping for self-employed people. Or simply google for it. Sure you have to pay taxes and it doesn't differ much from any other self-employed activity.
How much you earn depends on how much effort you put in + how talented you are – no one will be able to tell you that. But take a look at the top 500 authors here, I'm sure they earn a decent living from themeforest sales.
Well, i think you misunderstood me. The second part of your post didn't help me, but the first did, at some point. Anyway, thanks.
On your second half .. this is exactly like in any other business where you offer a service! You have no idea how much money you will earn. If you are an employee you have a fixed salary. But if you are offering a service no matter what it is, you can't know how much money you'll earn, but you may estimate and pay your taxes after that estimation, or after your real income..i have no idea! You need to talk with a lawyer in your country about all this stuff.
I am not from Norway nor speaking Norwegian but I was able to read this: You will have to pay 7.8% National insurance contribution, Surtax 9-12% (if your gross income exceeds level1 NOK 490 ,000 or level2 NOK 796 ,400), and the basic 28.0% tax.http://no.wikipedia.org/wiki/Skatt_i_Norge#Direkte_skatter
I would suggest you to visit your local finance or tradesman bureaus, or you can pay for an hour of a professional tax counselor and set up a meeting where you will get all the information you need.
Either way there are plenty of basic info on Google, for more detailed information you need to talk face to face I would also suggest you read the actual work and tax law as many people can be wrong about things and it's best to know the laws a little so you can navigate yourself through the vast amount of information and bureaucratic nonsense.
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OP Account currently disabled
Thanks Meter: 1,253
2,471 posts
Join Date:Joined: Aug 2011
My goal with this thread is to contribute some insight and experience with customizing android devices in the way we all do... at square one, clicking the download button.... we also do not have a thread dedicated to this one subject alone, so here it is. I feel stickying this thread would be extremely useful, as so many people could see it right from the get-go and get valuable information from it.
Just getting right into it, I will say this, I have flashed (I'm sure) damn near 1,000 ROMs to various devices. Mine. Friends. Etc. And never once have I installed a corrupt zip file to these devices. This should never happen, and among other important details to any installation of a ROM, this one is the most important...
How do you do this??? Well I will show you... it is with this handy little app called md5 checker from the play store. EVERY. SINGLE. ONE OF US.... should have this app, guys (and gals, because I know you are out there it is a free app. No excuses
What is an MD5 checksum? Trusty link to get the gist of it.. http://www.fastsum.com/support/md5-c...5-checksum.php
Making this simple - I will break this down into steps. Follow this meticulously and 99.9% of the time you will not have an issue or be one of the random bugs popping up when everyone else seems fine.
1. Download md5 checker.
2. Download all zip files needed for your ROM. (whether you do this from your mobile device or a desktop/laptop it doesn't matter, because you WILL verify the file AFTER you have transferred it to where it needs to be allocated - your device). Basically, download it, transfer it.
3. Open md5 checker, the app is pretty easy to use. Much like a file explorer in its layout with the obvious differences.
4. Retrieve md5 for your zip files.
5. Verify them with ROM developer, or others using that particular ROM. Any discrepancies - back to step 2.
6. All is well? Boot to recovery.
7. Wipe data 3 times (you don't need to wipe dalvik cache, that directory is found in the data partition - wiping data = wiping dalvik cache)
8. Wipe cache 3 times (this sometimes does not need to be done either depending on whether or not your recovery wipes cache with data.. most recoveries will spit out some text during the wiping phase letting you know the details of the process and you'll see see something like this when wiping data)..
"Wiping /data...
"Wiping /cache
If you see cache being wiped, you are good. No need to manually wipe cache.
9. Format your system partition through recovery 3 times
10. Install your ROM. Reboot. Let it sit for a minute or two, reboot it again. If you are not installing a custom kernel, stop here. You are done, and winning.
11. Reboot to recovery, wipe cache partition 3 times AND dalvik cache. They are both there as options, for this reason - the goodies we install after a full ROM install.
12. Flash kernel zip. Reboot. Let it sit for a minute or two, reboot it again. You are done, and winning.
Interesting fact about all the ROMs I have installed over the years, NOT ONCE, have I ever installed something corrupted, and every issue/bug I have ever had with a ROM was a known issue. This also doesn't mean your particular device is always going to be able to run for weeks on end without needing a quick reboot. Sometimes its good to do the dishes, I get that. But my disclaimer here is for all to note, if you follow these steps meticulously, you will ALWAYS be able to say to yourself with confidence "nope, did it right, there is something else going on here." And thus you will be a greater problem solver and contributor to the community as a whole every single time you pose a thought or question regarding any problems you are having.
"Do it right once, instead of doin it wrong twice before doing it right."
We are nothing useful without useful information. Useful information = posting in a thread in this tone...
"Hey, installed ROM correctly/thoroughly, verified downloads, XXX is buggy blah blah etc etc... can somebody else here verify if they are or aren't having this issue? Thanks!"
Based on people's response you'll know if it is just you or a legitimate issue, in which case, you brought it to the attention of us all, and the dev(s), and you have now been very useful.
What you don't want to do is this....
"My phone keeps rebooting!!! Haaaalp"
The reason why you shouldn't post like that is because you will ALWAYS get a sour response or people will just ignore you. Or, they will reply with questions you should have already asked yourself... "did you verify your downloads were good??? Did you do a clean and thorough install???"
Long post, but I hope somebody will find it useful and utilize it. It will increase your experience with your android device in a positive way, as it has for me. Cheers
Last edited by cobraboy85; 20th October 2012 at 05:06 PM.


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Reader comments are listed below. Comments are currently closed and new comments are no longer being accepted.
I wonder what evidence supports the assertion that migration to the US might be a force pushing more socially liberal attitudes in Mexico. It does not seem clear to me that these days the US (especially some of the places where more Mexicans live, such as California's Central Valley or Texas) is any more socially liberal than Mexico. Interestingly, Mexico's regions where emigration has been historically high encompass some conservative strongholds (deeply catholic Aguascalientes, Guanajuato and rural Jalisco rank high on emigration). On the other hand, Mexico City's emigration rate to the US is certainly among the lowest nationally. Furthermore, Mexicans do not need to live abroad to get exposure to different lifestyles, they have plenty of TV sets. As elsewhere, Mexican producers, journalist and TV stars are on the liberal side. Sony and Warner Channel are also ubiquitous. Hence, domestic and international media (and Ricky Martin!), may be playing a more significant role than migration in the liberal surge, as well as in the conservative backlash.
Nezahualcóyotl pretty much exemplifies the utter contempt that certain Mexico City dwellers (usually self-ascribed to the "liberal left" and to the "intellectually") show for the rest of the country as well as their overgrown self-importance, and then they go on wondering why they are so little liked among the rest of their fellow country-men. So it always come handy to remind chilangos that none of the great Mexican nation shaping movements (the Independence, the Reform Wars, the Revolution) were born in Mexico City.
I'm pretty sure prostitution is not illegal in Mexico. What is illegal is "pimping", the exploitation by a third party (lenocinio).
As a Brit-Chilango (resident for thirty years), I agree with the previous comments. I consider myself a "liberal" thinker but have serious concerns on the abortion issue.
I must admit I have changed my views on Mayor Marcelo Ebrad. He is a a shrewd political operator with his eyes on being the next PRD (left-wing-popularist) presidential candidate. He projects himself as a modern-progressive that is cleaning up graft and corruption and gets things done: makes headline grabbing proclamations on gay-rights and public works projects.
But Mexico city is still beset by a horrendous crime rate, lack of investment, a tottering infrastructure, shortage of water, chronic unemployment and poor education. Oh yes, and cops that are as easy to bribe as they ever where.
But this is still "Chilangolandia" and, as mega-cities in the developing world go, it's still a great place to live; if you have a good job and live in a secure neighborhood.
Well I'm proud to be a Chilango (a native of Mexico City). The rest of the country still clings to medieval, pre-Enlightenment notions of "morality" and does not understand, nor accept, the concept of "individual" in a modern sense (i.e. that every human should be autonomous and do as he likes, as long as he does not harm others). It's frustrating. Luckily Chilangos tend to be much more enlightened and liberal than your average Mexican.
Mexico City is a really fun place once you settle in. I have spent nearly 10 months non-consecutively in the DF. Its gigantic Zona Rosa (pink zone) certainly shows that it is a city that has room for gay people.
There's always a problem when packaging of a whole bunch of ideas (gay marriage, abortion, etc. etc.) and classify them all as "liberal", "conservative", from the right, left, etc.
As a Mexico City habitant I do support the issues commented (gay marriage, their adoption rights, legalizing prostitution, etc.), but what holds me of publishing this on my facebook wall is that as long as science doesn't reach the point where we know when a life starts (something I doubt I'll see in my lifetime) I'll never support abortion.
We can have a whole debate over here about every issue, my point is that when someone agrees with the whole bunch of assumptions that comes with being "conservative" or "liberal" it's, well, maybe more a matter of leaving the thinking effort to an ideology instead of doing the work oneself issue by issue...
The PRI is a pretty corrupt bunch, but I don't think the PAN is any better. Anyways, like the late-era USSR it was a sort of dictatorship without a dictator, since no leader could serve longer than 6 years. This is still in place, which means every election in Mexico does not include an incumbent. This will be interesting in a prolonged democratic situation.
"The Institutional Revolutionary Party, which ran Mexico for seven decades until 1990, persecuted the church with varying vigour and imposed secularism. Divorce was notoriously free and easy (Marilyn Monroe was one satisfied customer). It is an irony that "the dismantling of an authoritarian regime has led to the emergence of intolerance" regarding homosexuality, reproductive rights and religious minorities, notes Soledad Loaeza, a political scientist at the Colegio de México, a graduate school."
It is better to argue and fight about this issues than to have an authoritarian government impose their will on the people.
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Bam ET1005XL L'Etoile 2.9 Hightech Slim Cello CaseProduct #J06726 Bam J06726 LFTA Cello Cases & Gig Bags https://www.esnapw.com/rses/ESnapServlet?MerchantNumberSent=63655
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VIEWS: 23 PAGES: 1 CATEGORY: Business POSTED ON: 11/15/2010
Arizona Real Estate Laws document sample
Sonoran Lifestyle Real Estate Buyer Disclosure Statement PROFESSIONAL ADVICE. Buyer(s) execute this Disclosure/Waiver with the understanding that they should consult with a professional of their choice regarding any questions or concerns before its execution. LEGAL ADVICE: Buyer(s) acknowledge that this waiver does not attempt to offer legal advice. If buyer(s) feel the need for legal advice they should consult an attorney of their choice prior to the execution of this document. □ ______ ______ 1. I/We have received a copy of "The Buyers Advisory". The "Buyer Advisory" contains various information important to home buyers. You will find different website addresses for information on numerous topics to help educate you as a buyer. □ ______ ______ 2. I/We have received a copy of "Understanding The Pool Barrier Laws". Arizona Legislature has passed a law requiring that new occupants of dwellings with pools, and persons having a pool installed, receive this safety message about steps to prevent drowning and the legal responsibilities of pool ownership. "Pool" means an in-ground or aboveground swimming pool or other contained body of water 18 or more inches in depth, wider than 8 feet, and intended for swimming. Phoenix, Peoria, Tucson and some other cities, and unincorporated areas of Maricopa, Pima and Pinal Counties have different pool barrier requirements. Check with your city and county governments to see if they have adopted different pool barrier requirements. □ ______ ______ 3. I/We have received a copy of "Mold in My Home: What Do I Do?". Mold contaminants may exist in the Property of which the Broker Agent(s) is unaware. These contaminants generally grow in places where there is or may have been excessive moisture, such as where leakage may have occurred in roofs, pipes, walls, plant pots, or where there has been flooding; these conditions may be identified with a typical home inspection. Broker recommends BUYER obtain a home inspection to better determine the condition of the property. Neither the Broker nor the Broker's Agents are experts in the field of mold contaminants. In the event suspect mold contamination is discovered, it is recommended that our buyers satisfy themselves as to property condition by having a mold inspection performed. The cost and quality of such inspections may vary. Companies able to perform appropriate inspections may be found in the Yellow Pages or on the World Wide Web under "Microbial or Mold Inspections" or "Environmental and Ecological Services." □ ______ ______ 4. I/We understand the importance of getting a "C.L.U.E. Report". Previous insurance claims on a property can impact insurance rates and the ability of homebuyers to insure that home. When purchasing a home it is advised to ask the seller of the property for a written five year claims history from the Seller's insurance company OR a Comprehensive Loss Underwriting Exchange ("C.L.U.E.") report regarding the premises ( available at www.choicetrust.com ). □ ______ ______ 5. I/We understand that the property may require Flood insurance. If the property is located in a flood zone, your home owners insurance may require additional insurance with an annual premium of several hundred dollars. □ ______ ______ 6. I/We understand that the property may be located in a Community Facilities District. A Bond may have been issued by the District to be used to finance various improvements for a community. If the property is located in a Community Facilities District (CFD), every property owner in that district is responsible for repayment of that bond. The calculation for repayment is typically based on the assessed value of each property owner. □ ______ ______ 7. I/We understand that the property may have Lead Based Paint. If the premises were built prior to 1978 every buyer should be made aware that they may be exposed to lead from lead-based paint. Lead poisoning poses a particular risk in pregnant women and may cause permanent neurological damage in young children. It is highly recommended that if the premises were built prior to 1978 that you have a qualified home inspector test for the presence of lead-based paint. □ ______ ______ 8. I/We understand that the property is governed by a Home Owners Association (H.O.A.). I/We understand that the property is governed by _______________________________________________ home owners association. The H.O.A. fee is _____________ per ______________. It is also understood that by purchasing a property governed by a Home Owners Association we are agreeing to pay the H.O.A. fees and abide by the rules and regulations set forth by that Home Owners Association. I/We acknowledge that this Buyer Disclosure Statement was explain to us by our agent and by signing below we fully understand the contents of this disclosure. _________________________________________________ _________________________________________________ BUYER DATE BUYER DATE Created on 7/9/2004 11:43 AM
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• First Lady Michelle Obama loves to wear Wolford headbands, and the folks at Wolford love that Michelle Obama loves to wear their headbands. So, to show their appreciation, they've created custom jeweled pieces for the FLOTUS. The hair accessories were created in collaboration with MObama's stylist, who frequents NYC Wolford's showroom. The Sparkle Fatal Headband is a version of Wolford's regular Fatal style, except this one is bedazzled…and also not available for purchase. But! If you still want to get the First Lady's look, you can buy their plain style and embellish it yourself. The Fatal headband retails for $46, and comes in black or white. (WWD)
• With the way black men and women are being accosted for buying expensive accessories, or gunned down for asking for help/existing, you would wonder why anybody would want to live the "black lifestyle." But for hip Japanese twentysomethings, hip-hop music, fashion, and dance is enough incentive. Introducing B-Style, a small subculture that's captured the interest of Japanese youths fascinated by black culture. They tan to darken their skin, listen to and dress in the hip-hop style, and go to African salons to get braids. Vice UK followed Hina, a self-professed B-Styler to find out more about this trend in the video above. Hmm… what do you think of this one, Bombers and Bombshells? (Vice UK)
• I guess being a makeup mogul just isn't enough for Bobbi Brown! The cosmetics queen is delving into the editorial world as Yahoo's beauty editor-in-chief. But don't get it twisted–the new site, which will launch in June, isn't going to be another platform for Brown to promote her label. "This is not going to be the Bobbi Brown Cosmetics channel," she told WWD. "I am approaching this as a journalist. I've appeared on Good Morning America and the Today show for the last 15 years and I've never taken the opportunity to just push my own brand. This will be a brand-agnostic site." Brown sees this new gig as an opportunity to share her beauty knowledge to women…and to learn a few new things herself. "They've given me free rein to create a modern platform, and I'm very excited about teaching women and learning new things myself," she said. "Yahoo has more than 800 million users, and it's a great opportunity to get smart, approachable news out to a wide variety of women." (WWD)
• Investigators are still looking in to the cause of 25-year-old Peaches Geldof's sudden death. Kent Police say they've run post-mortem and toxicology tests, but results are still inconclusive. (Page Six)
• Are you a student with dreams of becoming a creative professional? Zandile Blay's got a workshop for you. On Saturday, April 19th, #blaystudio will present Made in America: Success Stories From The Diaspora; a one-day event that's a series of workshops, led by influential black professionals from Sierra Leone, Ghana, and South Africa. The event will be from 9AM-5PM (with a dinner from 7-11), and will feature talks from Memsor Kamarake, stylist for the Wendy Williams Show, Stanley Lumax, brand director for Nike, Dr. Yaba Blay, author of Shifting Lens on Race, and Yolanda Sangweni, founder of AfriPop magazine. If you're interested, hurry and get your tickets! The workshop is only available to 100 students! Visit www.blaystudio.info for registration information and ticket pricing. Bonus: Fashion Bomb readers can enjoy the full #blaystudio experience for just $100 by entering promo code BLAYSTUDIO14. Enjoy!
(Fashion Bomb Inbox)
• Veet's gotten itself in a little trouble for their latest ad campaign, which suggests that women are manly if they don't wax their body hair.The spots use an overweight, hairy man to play a woman who has not shaved in one or two days. In one commercial, a man and his girlfriend wake up together in bed. When he feels her leg (which haven't been shaved in a day), said hairy guy emerges from the covers, with the tagline 'Don't risk dudeness,' beacuse, you know, IT'S NOT LADYLIKE TO HAVE BODY HAIR. Thanks to several complaints and at least a day of internet outrage, the video has been removed, but you can still view a clip at the Daily Mail. (Daily Mail)
So I love that these Japanese girls want to look like and emulate hip-hop culture. I'm actually down for that. FLOTUS has custom headbands? Go woman, go! I am hoping that Peaches died of natural causes…. I honestly don't think it's DUDENESS to have body hair, but since hair holds scent I'd want to be clean-shaven as much as possible.
Why is Vice talking about B-style in Japan? Hina, that respective video, and B-style were first introduced to Americans almost THREE YEARS AGO.
Talk about horrible reporting.
Oh, and the Baby Shoop store is kind of cute. A bit gaudy, but they definitely have some cute pieces. The salesgirls were fun to look at too — they were all tan with cornrows. lol I wish I had asked them to take a photo with me.
Ok so I just wasted 5:11 mins of my time watching why Japanese girls want to embrace "black/hip hop" culture. Really? I'm happy for Bobbi Brown! I really love her make up almost obsessed over it. Its the only foundations that matches my skin tone :) Loves!
That b-style report is so old -__-.
I did not like the first ladies look for whatever reason


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start a commitee
Submitted by freedomordeath on Wed, 06/11/2014 - 14:52. Permalink
or something and get a treasurer and get actors that support him to be part of committe as their talents will no dount add to experience required to get funding in industry.
patience is needed as no point starting until you get real money ($20million +) and their will be a return on investment if done properly, if done in true hollywood style without the hollywood dirty fingerprints.
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- Clara Jobson and her brother made very different adult lives despite equally traumatic childhoods....Thursday 19 February 2015
- Anne Manne has been studying the causes and implications of our increasing narcissicism. ...Wednesday 9 July 2014
- A Perth program designed to keep disadvantaged kids engaged and off the streets using basketball is in jeopardy due to a lack of funding. ...Friday 4 July 2014
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- Lawyers and welfare workers have criticised the use of move-on notices and prohibitive behaviour orders, saying they unfairly affect Aboriginal people, the homeless and those with a mental illness. ...Tuesday 3 December 2013
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- Of all illicit drugs, the Crime Commission says ice poses the biggest risk to the Australian community. And it's not a problem isolated to the big cities but is gripping regional and remote areas across the country. Even the outback city of Broken Hill, in the far west of New South Wales, can't escape ...Thursday 26 March 2015
- Police in Nauru deny allegations children were taken into custody during the mass arrests of refugees this week. More than 170 refugees have been arrested after they held two protests over their living conditions and uncertain future. The refugees have been living in the community after being ...Friday 6 March 2015
- Clara Jobson and her brother made very different adult lives despite equally traumatic childhoods....Thursday 19 February 2015
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- A governor in Papua New Guinea says corruption is leading to shocking levels of violence throughout society. Gary Juffa, Governor of Oro Province, says people are increasingly turning to vigilante justice, as they feel beset by crime, but don't trust the police. He says the violence has recently ...Wednesday 24 December 2014


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Ever have one of those really weird dreams where everything looks like an old circus or carnival with freak shows?Continue Reading
A poem about the size of things.Continue Reading
My hands are not strong enough…Continue Reading
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I wrote this poem about this tiny lil man in the next city over, whom thinks he is something but sadly he is a laugh to everyone.Continue Reading
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When the ruler of the earth was not humble enough and is outrageous, Lord Vishnu takes the shape of a dwarf, who teaches that nobody is above nature and should never get pride enter into the head!Continue Reading
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This poem was written about the person whom my wife left me for, he had committed adultery on his first wife, he doesn't work so our government takes care of him, he stand's about 5′5′, he is bald, and he is so scared of other men that he calls the police on them, and he also gets people to fight his battles.Continue Reading
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The Memory Keeper's Daughter
From Library Staff
When a doctor delivers his newborn twins and discovers that his baby has Down Syndrome, he turns her over to a nurse, who secretly raises the child.
Kim Edwards writes short stories and women's fiction about how people interact, their inevitable miscommunication, and familial connections. In a tale spanning twenty-five years, a doctor delivers his newborn twins during a snowstorm and, rashly deciding to protect his wife from their baby daught... Read More »
From the critics
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I found the pace of this novel to be excellent, the themes very well developed (family ties, secrets, barriers to intimacy) but I did not get caught up in it as I expected. Nevertheless, it's worth a read and covers a subject that is either uncommonly written about or I simply had never read a book focussing on families with mentally delayed children. The prose is a perfect bland of complexity and simplicity.
A real touching story. Although a slow pace, it keeps a steady beat as it walks us through the journey between two families. I really loved this book because it is a story totally relatable to modern day and age.
I could not put this book down. A period of twenty years is spanned in this tale and at each new point, different characters are narrating the story.
Amazing and poignant. I thought it ended a bit too abruptly.
Well and Beautifully written.... this is a special story that captures a terrible,heart wrenching, sad ,tragic,and so emotionally touching situation. It touches my heart and reaches into my very soul. this book deserved 5*****stars. For me it 's a must read! I now know things about down syndrome that I never knew before.
This was a moving movie from start to finish. I disagree with what the doctor did by sending away the girl with problems. I think the wife could have handled the downs syndrome very well. I am glad the nurse took her to raise instead of putting her in a uncaring instuition for the rest of her life. It was a emotional book but i enjoyed it and learned about downs syndrome from the book too. We should be patient and loving to our children no matter what their handicaps are;. They are part of us no matter what .
In a tale spanning 25 years, a doctor delivers his newborn twins during a snowstorm and, rashly deciding to protect his wife from their baby daughter's affliction with Down syndrome, turns her over to a nurse, who secretly raises the child.
A very sad and touching story - you wonder how a father can do what he did but at the same time, can understand his motivations behind it. The story would have been so different if more communication had been present. My heart went out to the son Paul who really lost the most by his parent's lack of honesty and communication with each other... a lesson for most marriages. Phoebe was the champion along with Caroline, who gave Phoebe what she really needed - Love - and got it back a hundredfold.
Too syrupy.
I enjoyed this book, but was somewhat disappointed in the ending. There was so much build up and character development throughout the rest of the book that the ending somehow didn't seem to fit.
This was a beautiful and sad story. Some other reviewers may find it has a "slow" pace, but I do not feel this is a reason to fault it. The book deals with emotion, reaction and consequence of decisions from the characters' past decisions. It is a story of the torment of the mind and heart. It is realistic and takes the time to investigate each character's sentiments thoroughly. If you're into this intimate human perspective, you will definitely enjoy this read.
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imaginethat thinks this title is suitable for 16 years and over
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"After all, a picture could be a thousand different things"
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SummaryAdd a Summary
A family drama, The Memory Keeper's Daughter explores every mother's silent fear: What would happen if you lost your child and she grew up without you? It is also an astonishing tale of love and how the mysterious ties that hold a family together help us survive the heartache that occurs when long-buried secrets are finally uncovered.
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Upcoming Services
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Visitation Monday Jan. 15, 2015 9 A.M. - Noon at Perryman's Mortuary Graveside Service at 1:00 P.M. at Green Meadows Cemetery
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Visitation Thursday Jan. 15, 2015 Noon - 2:00 P.M. at Mt. Carmel Baptist Church, Funeral Service at 2:00 P.M. at Mt. Carmel Baptist Church
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Visitation Friday Jan. 15, 2015 11 A.M. - 1:00 P.M. at Perryman's Mortuary, Funeral Service at 2:00 P.M. at Perryman's Mortuary
Burial at Green Meadows Cemetery
A family with deep committment to serving you and your family. As the Owner and Manager of Perryman's Mortuary, I want you to be satisfied with the choice that gives you and your family peace of mind. At Perryman's Mortuary, we want you to know that our committment to this community is to serve you well.
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Property to rent near Cadeleigh, Tiverton EX16
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3 bed terraced house to rentArnold Crescent, Tiverton EX16
A great three bedroom family home in the palmerston park area with a rear garden. More details
Note: Distances are straight line measurements
- Tiverton Parkway (6.3 miles)
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1 bed terraced house to rentBary Lane, Cheriton Fitzpaine, Crediton EX17
Your move are pleased to offer to the market this newly built cottage located in the popular village of Cheriton Fitzpaine. Only a short commute to Exeter city centre and Crediton this property is a must see. Accommodation comprises, open plan living ... More details
Note: Distances are straight line measurements
- Newton St Cyres (4.6 miles)
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Marketed by Your Move, EX4. Call 01392 976230£750 pcm (£173 pw)
2 bed bungalow to rent1 Bary Close, Cheriton Fitzpaine, Crediton EX17
A three Bedroom Detached Bungalow in a Pleasant Village Location with Enclosed South Facing Garden, Oil Central Heating, Parking and Garage. More details
Note: Distances are straight line measurements
- Crediton (4.6 miles)
- Newton St Cyres (4.6 miles)
Marketed by Devon Sales & Lettings Ltd, EX17. Call 01363 779057
Latest Cadeleigh, Tiverton EX16 property to rent
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Keolanui Chu Pole Jammin the hawaiian hills
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