text:
EP300 (E1A binding protein p300)
|Jean-Loup Huret
|Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
|Gloria Negri, Cristina Gervasini
|Department of Health Science, Medical Genetics, Universita degli Studi di Milano, Milano, Italy
(Note : for Links provided by Atlas : click)
1. Identity
|Alias_symbol (synonym)
General Information
|Other alias
|HGNC (Hugo)
|LocusID (NCBI)
|22q13.2 [Link to chromosome band 22q13]
|Starts at 41092610 and ends at 41180077 bp from pter ( according to hg19-Feb_2009) [Mapping EP300.png]
|Fusion genes
(updated 2017)
|Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
|ARHGEF17 (11q13.4) / EP300 (22q13.2)
|DHX9 (1q25.3) / EP300 (22q13.2)
|EP300 (22q13.2) / BCOR (Xp11.4)
|EP300 (22q13.2) / COL26A1 (7q22.1)
|EP300 (22q13.2) / DAZAP2 (12q13.13)
|EP300 (22q13.2) / EP300 (22q13.2)
|EP300 (22q13.2) / IPO5 (13q32.2)
|EP300 (22q13.2) / KAT6A (8p11.21)
|EP300 (22q13.2) / KMT2A (11q23.3)
|EP300 (22q13.2) / MCHR1 (22q13.2)
|EP300 (22q13.2) / SPPL3 (12q24.31)
|EP300 (22q13.2) / TNRC6B (22q13.1)
|EP300 (22q13.2) / TTC28 (22q12.1)
|EP300 (22q13.2) / ZNF384 (12p13.31)
|KAT6A (8p11.21) / EP300 (22q13.2)
|KMT2A (11q23.3) / EP300 (22q13.2)
|LPAR5 (12p13.31) / EP300 (22q13.2)
|LYRM1 (16p12.3) / EP300 (22q13.2)
|RNF220 (1p34.1) / EP300 (22q13.2)
|SPHK1 (17q25.1) / EP300 (22q13.2)
|TNRC6B (22q13.1) / EP300 (22q13.2)
|TSPAN16 (19p13.2) / EP300 (22q13.2)
|TTC28 (22q12.1) / EP300 (22q13.2)
|Schematic representation of EP300 gene. Black boxes represent exons and gray ones 5' and 3' UTRs. Thin black lines represent introns. (Modified from Zimmerman et al., 2007).
|p300 was first discovered on the basis of its interaction with the adenoviral protein E1A and EP300 locus was subsequently mapped to the long arm of chromosome 22, spanning about 88 kb (Whyte et al., 1989; Eckner et al., 1994).
|EP300 has only one splice variant derived from the splicing of its 31 exons with an mRNA of 9585 bp which includes 1219 and 1121 bp of 5'UTR and 3'UTR, respectively.
|No pseudogenes are known.
3. Protein
|Schematic structure of p300 protein including its functional and structural domains and their localization. NLS (nuclear localization signal), CH1 (cysteine/histidine-rich region 1, also known as transcriptional-adaptor zinc-finger domain 1 or TAZ1), KIX (kinase inducible domain of CREB interacting domain), BROMO (bromodomain), PHD (plant homeodomain finger), KAT11 (lysine acetyltransferase domain), ZZ (ZZ-type zinc finger domain), TAZ2 (transcriptional-adaptor zinc-finger domain 2; ZZ and TAZ2 together are sometimes referred to as CH3 or cysteine/histidine-rich region 3), and IBiD (IRF3-binding domain). Aminoacid positions are from UniGene NP_001420.2.
| p300 is a large size protein of about 264 kDa belonging to the KAT3 (lysine or K-acetyltransferase) family (Valor et al., 2013).
p300 shares a modular organization consisting in several conserved domains including a central chromatin association and modification region which includes the bromodomain/PHD finger module and the KAT11 domain (Rack et al., 2014) which is flanked by four transactivation domains (TADs): i) the CH1 that encompasses the TAZ1 domain, ii) the KIX domain, iii) another CH3 containing the TAZ2 domain and a ZZ domain, and iv) the IBiD (Bedford et al., 2012; Wang et al., 2013).
The Bromodomain mediates p300 binding to acetylated histones, nucleosomes and transcriptional factors and could therefore play a role in tethering p300 to specific chromosomal sites (Kalkhoven et al., 2004; Rack et al., 2014) moreover, the associated PHD finger is an integral part of the enzymatic core of the protein influencing its ability to recognize and acetylate both itself as well as histones and non-histone substrates (Kalkhoven et al., 2004; Wang et al., 2013; Rack et al., 2014). The KAT11 catalytic domain can acetylate p300 itself and a variety of histonic and non-histonic proteins and the CH rich regions are able to bind zinc and are involved in protein-protein interaction (Valor et al., 2013; Wang et al., 2013).
p300 has also multiple specific interaction domains for different transcriptional factors such as the KIX domain that mediates CREB-p300 interaction and CREB phosphorylation at serine 133 residue but also for the Retinoic Acid Receptor-related orphan receptor A (RORA) and for ALX1 at the N-term end of the protein and for Interferons at C-term end.
|p300 is ubiquitously expressed in human tissues (Kalkhoven et al., 2004; Valor et al., 2013). p300 is highly evolutionary conserved and present in many multicellular organisms including flies, worms and plants but not in lower eukaryotes such as yeasts (Kalkhoven et al., 2004).
|p300 is a nuclear protein which resides in a specific nuclear structure called nuclear body (Chan and La Thangue, 2001).
| p300 is a transcriptional coactivator with intrinsic lysine acetyltransferase activity able to regulate transcription and gene expression in different ways.
1) Acetylation of histones tails: p300 can enable transcription through the catalytic activity of its KAT domain which is able to acetylate promoter nucleosomal histones resulting in chromatin remodelling and relaxation and in increased accessibility of the DNA to other essential regulators (Kalhoven et al., 2004; Wang et al., 2013). Thanks to its ability in modifying chromatin structure by histone acetylation, p300 can be defined as "writer" of the epigenetic code (Berdasco et al., 2013).
2) Acetylation of other target proteins: p300 can also acetylate other kinds of proteins, such as transcriptional factors, modulating their activity positively or negatively, or coactivators.
Acetylation of non-histone substrates can result in either positive or negative effects on transcription by affecting protein-protein interactions (activator of thyroid and retinoid receptors ACTR), protein-DNA interactions (the high mobility group protein HMGI), nuclear retention (the hepatocyte nuclear factor HNF4) or protein half-life (E2F).
For example some acetylated p300 targets regulate the expression of histone methyltransferase leading to chromatin condensation and gene silencing.
3) RNA Polymerase II stabilization: p300 functions as a "bridge" linking the DNA-bound transcription factors (activators) to the basal transcription machinery through direct interaction with TFIID, including TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs) and TFIIB promoting the pre-initiation complex (PIC) assembly (Wang et al., 2013).
p300 has also some more indirect chromatin-related roles:
|Comparison of p300 and CBP amino acidic sequences. The blue regions indicate the areas of highest homology with the percentage of amino acid identity specified in between. Position of the corresponding domains are taken from UniGene (NP_001420.2 for EP300 and NP_004371.2 for CREBBP). (Modified from Chan and La Thangue, 2001).
|p300 is highly homologous to the cyclic AMP response element-binding (CREB) binding protein (CBP) with 63% identity and 75% similarity at amino-acid level (Narayanan et al., 2004; Wang et al., 20113). CREBBP/CBP locus was mapped on 16p13.3, a region of extensive homology to the one on chromosome 22 where EP300/p300 resides (Chan and La Thangue, 2001; Gervasini, 2010).
4. Mutations
|The identification of mutations in epigenetic genes, classified as writers, readers and erasers based on their function (Berdasco and Esteller, 2013), represents a link between the cancer epigenome and genetic alterations acting as "driver" or "passenger" mutations in cancer development. Actually, many genetic alterations in cancer epigenetic regulators cause cancer-associated phenotype via epigenetic dysfunction (Roy et al., 2014).
|Rubinstein-Taybi Syndrome (RSTS; OMIM #180849, #613684).
|Cancers derived from almost all tissues and organs, such as those of hematopoietic and lymphoid organs, cancers of eye, skin, bones, thyroid, salivary and adrenal glands, central nervous system (CNS) including meninges, and nervous system (NS) including automatic ganglia, esophagus, upper aerodigestive tract, lung and pleura, stomach, liver, pancreas, biliary tract, large and small intestine, kidney, urinary tract and breast, endometrium, cervix, ovary and prostate.
5. Implicated in
|Rubinstein-taybi syndrome (RSTS; OMIM #180849, #613684)
|Germinal mutations leading to loss of function/haploinsufficiency.
|Rubinstein-Taybi syndrome is a rare (1:125000 live birth) autosomal dominant neurodevelopmental disorder. It is characterized by postnatal growth retardation, intellectual disability (ID), skeletal anomalies (broad and/or duplicated distal phalanges of thumbs and halluces are a landmark sign) and distinctive facial dysmorphisms including down-slanting palpebral fissures, broad nasal bridge, beaked nose and micrognathia (Hennekam, 2006).
|All EP300-mutated RSTS patients described in literature are alive (Roelfsema et al., 2005; Bartholdi et al., 2007; Zimmermann et al., 2007; Foley et al., 2009; Bartsh et al., 2010; Tsai et al., 2011; Negri et al., 2014).
|Hybrid/Mutated Gene
|The identification of EP300 as the second RSTS causative gene in 2005 (Roelfsema et al., 2005) disclosed the heterogeneous nature of the syndrome. EP300 heterozygous point mutations and intragenic deletions have been detected in about 8% of RSTS CREBBP-negative cases (Negri et al., 2014). Fourteen patients are clinically and genetically described (Roelfsema et al., 2005; Bartholdi et al., 2007; Zimmermann et al., 2007; Foley et al., 2009; Bartsh et al., 2010; Tsai et al., 2011; Negri et al., 2014), while 12 additional alterations are reported in the LOVD database .
|EP300 germline mutations in Rubinstein-Taybi patients (2014 update). A) Point mutations, B) intragenic deletions and C) schematic of the gene with type and localization of all 26 mutations reported so far. (Modified from Negri et al., 2014).
|RSTS patients (estimated incidence 5%) have an increased predisposition to malignancies like leukemia, neuroblastoma, meningioma and pilomatrixoma, developed either in the first years of life or in mid-adulthood (30-40 years) (Siraganin et al., 1989; van de Kar, 2014). Glaucomas and keloids are reported too; in particular, EP300-mutated RSTS patients show a slight increase in developing skin anomalies such as keloids (Van Genderen et al., 2000; van de Kar, 2014; Negri et al., 2014).
|Various cancers
|All data are taken from COSMIC database (Catalogue of Somatic Mutations In Cancer) ( Release v70 August 2014).
|EP300 point mutations, copy number variations (CNVs) but also gene expression profile alterations have been detected in almost all human cancers independently of the embryonic origin. Out of >14.000 tumor samples tested, those derived from hematopoietic and lymphoid organs, lung, central nervous system (CNS), breast, intestine and ovary show the highest prevalence of EP300 mutations.
|Hybrid/Mutated Gene
| The majority of EP300 point mutations detected in tumoral samples are heterozygous (Aumann et al., 2014).
With about ~400 unique somatic alterations reported, point mutations appear to be the most represented kind of EP300,mutations: in particular, missense mutations account for >60% of all mutations, followed by synonymous (~13%) and nonsense (~11%) mutations. In detail, transitions justify about 70% of all substitutions. Out of frame insertion/deletions (ins/del) represent together 38% and in frame ins/del about 4%.
Mutations are widespread across the gene with a great concentration in the large KAT11 domain, which clusters about 26% of all alterations. Few recurrent mutations are reported: the most frequently mutated amino acid residue is the aspartic acid at position 1339 in the KAT11 domain which is replaced by either asparagine (eight samples) or tyrosine (four samples).
CNVs are described too. In particular, losses are reported in 31 samples including breast, endometrium, ovary, large intestine and lung cancer, while gains seem to be rarer being described in 11 samples including breast, hematopoietic and lymphoid, and lung cancer.
Alterations in EP300 gene expression are recorded too: in particular over expression was described in 94 samples, while under expression in 104 samples, both in cancers derived from breast, endometrium, ovary, CNV, haematopoietic and lymphoid organs, kidney, large intestine and lung.
|EP300 somatic point mutations load. A) Pie chart of the main kinds of point mutations and relative numbers, B) bar chart of the distribution of the mutations within the gene domains and C) recurrent mutations and localization. Data are reworked from COSMIC database.
|The oncogenic mechanism by which EP300 mutations act is not yet clear, but as the most frequently mutated region is the lysine acetyltransferase domain, which catalyzes acetylation of histones and other essential proteins, aberrant acetyltransferase activity may be a key feature. In vitro studies demonstrated reduced H3K18 acetylation, as well as decreased ability to acetylate p53 and BCL6, in p300- mutated cells (Peifer et al., 2012). Because of p300 multiple functions and diverse interactions, many intertwisted mechanisms could play a role in the different mutations' effects.
|t(11;22)(q23;q13) --> resulting in KMT2A -EP300 fusion gene
|Somatic mutations.
|Therapy-related leukemias and myeloid neoplasms.
|Ida et al., described the first patient presenting the karyotype 48,XY,+8,+8,(11;22)(q23;q13); the same group (Ohnishi et al.) described a second patient with 46,XX,t(1;22;11)(q44;q13;q23), t(10;17)(q22,q21), while a third patient, with 46;XY,t(11;22)(q23;q13)[15]/47,idem,+8[2], was reported by Duhoux et al.
|Hybrid/Mutated Gene
| Rearrangements of the mixed lineage leukemia (MLL1 or KMT2A; gene ID: 4297) locus are frequently encountered in acute leukemias and at least 104 different chromosomal rearrangements involving MLL1 itself with more than 64 translocation partner genes have been described (Meyer et al., 2009) while rearrangements of EP300 gene locus seem to be rare events.
Only three cases of MLL1-EP300 fusion genes have been described, all in therapy-related leukemia patients following chemoterapy with topoisomerase II inhibitors. The first patient was initially diagnosed as having non-Hodgkin lymphoma and, after conventional chemotherapy, he developed secondary AML which was cytogenetically characterized as t(11;22)(q23;q13) producing a chimeric MLL1-EP300 gene in which the exon 9 of MLL1 was juxtaposed to EP300 exon 15 (Ida et al., 1997). The second case is a girl who developed AML after chemotherapy for neuroblastoma. She presented a complex karyotype 46,XX,t(1;22;11)(q44;q13;q23),t(10;17)(q22,q21) with the fusion of MLL1 exon 8 to EP300 exon 15 and also a less expressed clone in which exon 7 of MLL1 is fused with exon 15 of EP300, which was considered to be generated by alternative splicing (Ohnishi et al., 2008). The third patient presented AML with myelodysplasia-related changes evolving after chemotherapy in acute myelomonocytic leukaemia (AMML). Leukemic cells were cytologically characterised as 46;XY,t(11;22)(q23;q13)[15]/47,idem,+8[2] including the fusion of exon 10, or exon 11 resulting from alternative splicing, of MLL1 with exon 13 of EP300 (Duhoux et al., 2011).
All chimeric proteins retain almost the same part of both MLL1, including the AT-hook, the DNA methyltransferase and the transcriptional repression domains and p300, i.e. the bromodomain, the catalytic KAT and TADs
|t(11;22)(q23;q13) leads to fusion of MLL1 gene to EP300. A) Schematic representation of MLL1, p300 and the predicted MLL1-p300 fusion proteins of all reported cases (Ida et al., 1997; Ohnishi et al. 2008; Duhoux et al., 2011). B) Nucleotide sequences of the hybrid junctions of the chimeric MLL1-EP300 genes and relative references. Breakpoints are indicated by arrows; AT: AT hooks, NLS: nuclear localization signals, CxxC: motif recognizing unmethylated CpG dinucleotides, PHD: plant homeodomain fingers, TAD: transactivation domain, SET: histone methyltransferase active sites; CH: cystidine/histidine-rich; KIX: kinase inhibitory domain, Bromo: bromodomain, KAT: Lysine acetyltransferase domain. (Modified from Duhoux et al., 2011).
| The fusion of MLL1 with the lysine-acetyltransferase p300 supposedly leads to hyperacetylation of chromatin which contributes to increase the transcriptional output conferring a significant oncogenic advantage to the cells. Furthermore, nuclear factors, such as p300, have transcriptional activity and their function might be deregulated by the fusion with MLL1 (Ohnishi et al., 2008; Duhoux et al., 2011).
The translocation t(11;22)(q23;q13) involving MLL1-EP300 is characteristic of therapy related leukemias where it is likely driven by topoisomerase II inhibitors, rather than of de novo leukaemias.
|t(8;22)(p11;q13) resulting in KAT6A - EP300 fusion gene
|Somatic mutations.
|de novo, progression or therapy-related AML.
|The t(8;22)(p11;q13) is a rare translocation found in acute myeloid leukaemia (AML) described in only three patients (Lai et al., 1992; Soenen et al., 1996; Chaffanet et al., 2000; Kitabayashi et al., 2000; Tasaka et al., 2002). The first patient was diagnosed as having a de novo AML with karyotype 47, XY,+8,t(8;22)(p11;q13), while the second patient suffered from a chronic myelomonocytic leukaemia (CMML) which evolved in AML with the abnormal karyotype: 46,XY,t(8;22)(p11;q13)/idem,+der(8)t(8;22)(p11;q13)del(17)(p11) (Lai et al., 1992; Soenen et al., 1996; Chaffanet et al., 2000). The third case is a man with primary macroglobulinemia who developed a secondary AML during chemotherapy, with the karyotype: 47, XY, t(8;22)(p11.2;q13.1),+der(8)t(8;22)(22qter→22q13.1::8p11.2→8q13::8q22→8qter),add(19)(p13.3) (Kitabayashi et al., 2001; Tasaka et al., 2002).
|Hybrid/Mutated Gene
| Monocytic leukemia zinc finger gene (MOZ, Gene ID: 7994) codifies for a Myst (MOZ, Ybf2 (Sas3), Sas2, Tip60)-type lysine acetyltransferase (KAT) also named KAT6A (lysine acetyltransferase 6A).
The gene underlies chromosomal translocation with different partners, generating fusion genes, such as MOZ-TIF2, MOZ-CBP and MOZ-EP300 in acute myeloid leukemia (AML). All MOZ fusion partner genes are involved in histone modification and transcriptional regulation (Katsumoto et al., 2008).
To date, only three cases of t(8;22)(p11;q13) involving MOZ and EP300 have been reported and investigated at DNA and RNA levels in two of them (Lai et al., 1992; Soenen et al., 1996; Chaffanet et al., 2000; Kitabayashi et al., 2001; Tasaka et al., 2002).
In Chaffanet et al., and in Kitabayashi et al., MOZ-EP300 fusion genes result from the hybrid junction between exon 16 and exon 15 of MOZ with exons 2 and 3 of EP300, respectively.
In both cases, the MOZ breakpoints are located in or around its acidic domain resulting in the retention of its N-terminal region and the replacement of the C-terminal end with the p300 fusion partner. The N-terminal region of MOZ contains a H15 (histone H1/H5) domain related to nuclear localization, a PHD (plant homeobox-like domain) zinc finger involved in binding to methylated histones, a basic domain and a Myst-type KAT domain. The KAT domain contains C2HC zinc finger and helix-turn-helix motifs that bind to nucleosomes and DNA. Because of the early truncation of EP300 , almost all its functional domains are conserved, including the KAT, the bromodomain and the CH1-3, resulting in a fusion protein with both MOZ and p300 KAT domains.
In the reciprocal fusion genes, EP300-MOZ, exon 1 or 2 of EP300 are juxtaposed to exons 17 and 16 of MOZ, respectively. In both cases, the N-terminal region including only the nuclear receptor interaction domain (NID) of p300 and the C-terminal of MOZ encompassing its serine, proline-glutammine and methionine-rich regions are conserved (Chaffanet et al., 2000; Kitabayashi et al., 2001).
| Schematic representation of the p300, MOZ, MOZ-p300 and p300-MOZ proteins. A) p300, MOZ, p300-MOZ and MOZ-p300 diagram of the first case and B) p300, MOZ, p300-MOZ and MOZ-p300 diagram of the third one.
Red arrows indicate the breakpoints of the translocations and nucleotide sequences of WT and hybrid junctions are reported. The functional domains of MOZ and p300 as well as those of fusion proteins are indicated above and beneath the diagrams.
NID: nuclear receptor interaction domain, CH1-3: cysteine/histidine-rich domain, CID: CREB-interaction domain, B: bromodomain, KAT: lysine acetyltransferase domain, Q: glutamine-rich region, PH: PHD class zinc finger, MYST: MOZ, YB1, SAS, TIP homology domain, S: serine-rich region, PQ: proline/glutamine region, M: methionine-rich region. (Modified from Kitabayashi et al., 2001).
|The conservation of MOZ and p300 KAT catalytic domains in the hybrid proteins MOZ-p300 may result in abnormal acetylation of histonic and non histonic proteins with a consequent alteration in gene expression regulation, leading to leukaemogenesis; furthermore, MOZ-p300 fusion proteins retain the domains required for the interaction with AML1 thus affecting AML1-dependent transcription whose deregulation may be implicated in leukaemogenesis too (Kitabayashi et al., 2001).
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|Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer.
|Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, Plenker D, Leenders F, Sun R, Zander T, Menon R, Koker M, Dahmen I, Muller C, Di Cerbo V, Schildhaus HU, Altmuller J, Baessmann I, Becker C, de Wilde B, Vandesompele J, Bohm D, Ansen S, Gabler F, Wilkening I, Heynck S, Heuckmann JM, Lu X, Carter SL, Cibulskis K, Banerji S, Getz G, Park KS, Rauh D, Grutter C, Fischer M, Pasqualucci L, Wright G, Wainer Z, Russell P, Petersen I, Chen Y, Stoelben E, Ludwig C, Schnabel P, Hoffmann H, Muley T, Brockmann M, Engel-Riedel W, Muscarella LA, Fazio VM, Groen H, Timens W, Sietsma H, Thunnissen E, Smit E, Heideman DA, Snijders PJ, Cappuzzo F, Ligorio C, Damiani S, Field J, Solberg S, Brustugun OT, Lund-Iversen M, Sanger J, Clement JH, Soltermann A, Moch H, Weder W, Solomon B, Soria JC, Validire P, Besse B, Brambilla E, Brambilla C, Lantuejoul S, Lorimier P, Schneider PM, Hallek M, Pao W, Meyerson M, Sage J, Shendure J, Schneider R, Buttner R, Wolf J, Nurnberg P, Perner S, Heukamp LC, Brindle PK, Haas S, Thomas RK.
|Nat Genet. 2012 Oct;44(10):1104-10. doi: 10.1038/ng.2396. Epub 2012 Sep 2.
|The PHD finger of p300 Influences Its Ability to Acetylate Histone and Non-Histone Targets.
|Rack JG, Lutter T, Kjaereng Bjerga GE, Guder C, Ehrhardt C, Varv S, Ziegler M, Aasland R.
|J Mol Biol. 2014 Dec 12;426(24):3960-72. doi: 10.1016/j.jmb.2014.08.011. Epub 2014 Aug 23.
|Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease.
|Roelfsema JH, White SJ, Ariyurek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, den Dunnen JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ.
|Am J Hum Genet. 2005 Apr;76(4):572-80. Epub 2005 Feb 10.
|Driver mutations of cancer epigenomes.
|Roy DM, Walsh LA, Chan TA.
|Protein Cell. 2014 Apr;5(4):265-96. doi: 10.1007/s13238-014-0031-6. Epub 2014 Mar 14.
|Keloids and neoplasms in the Rubinstein-Taybi syndrome.
|Siraganian PA, Rubinstein JH, Miller RW.
|Med Pediatr Oncol. 1989;17(6):485-91.
|Identification of a YAC spanning the translocation breakpoint t(8;22) associated with acute monocytic leukemia.
|Soenen V, Chaffanet M, Preudhomme C, Dib A, Lai JL, Fletcher JA, Birnbaurn D, Pebusque MJ.
|Genes Chromosomes Cancer. 1996 Mar;15(3):191-4.
|Secondary acute monocytic leukemia with a translocation t(8;22)(p11;q13).
|Tasaka T, Nagai M, Matsuhashi Y, Uehara E, Tamura T, Ishida T, Kakazu N, Abe T.
|Haematologica. 2002 May;87(5):ECR19.
|Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein-Taybi syndrome detected by aCGH.
|Tsai AC, Dossett CJ, Walton CS, Cramer AE, Eng PA, Nowakowska BA, Pursley AN, Stankiewicz P, Wiszniewska J, Cheung SW.
|Eur J Hum Genet. 2011 Jan;19(1):43-9. doi: 10.1038/ejhg.2010.121. Epub 2010 Aug 18.
|Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders.
|Valor LM, Viosca J, Lopez-Atalaya JP, Barco A.
|Curr Pharm Des. 2013;19(28):5051-64. (REVIEW)
|Transcriptional/epigenetic regulator CBP/p300 in tumorigenesis: structural and functional versatility in target recognition.
|Wang F, Marshall CB, Ikura M.
|Cell Mol Life Sci. 2013 Nov;70(21):3989-4008. doi: 10.1007/s00018-012-1254-4. Epub 2013 Jan 11. (REVIEW)
|Cellular targets for transformation by the adenovirus E1A proteins.
|Whyte P, Williamson NM, Harlow E.
|Cell. 1989 Jan 13;56(1):67-75.
|Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.
|Zimmermann N, Acosta AM, Kohlhase J, Bartsch O.
|Eur J Hum Genet. 2007 Aug;15(8):837-42. Epub 2007 Feb 14.
|Ocular features in Rubinstein-Taybi syndrome: investigation of 24 patients and review of the literature.
|van Genderen MM, Kinds GF, Riemslag FC, Hennekam RC.
|Br J Ophthalmol. 2000 Oct;84(10):1177-84. (REVIEW)
|Keloids in Rubinstein-Taybi syndrome: a clinical study.
|van de Kar AL, Houge G, Shaw AC, de Jong D, van Belzen MJ, Peters DJ, Hennekam RC.
|Br J Dermatol. 2014 Sep;171(3):615-21. doi: 10.1111/bjd.13124. Epub 2014 Aug 21.
7. Citation
|This paper should be referenced as such :
|Gloria Negri, Cristina Gervasini
|EP300 (E1A binding protein p300)
|Atlas Genet Cytogenet Oncol Haematol. 2015;19(11):633-642.
|Free journal version : [ pdf ] [ DOI ]
|On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/P300ID97.html
|History of this paper:
|Huret, JL. EP300 (E1A binding protein p300). Atlas Genet Cytogenet Oncol Haematol. 2000;4(1):1-2.
8. Other Leukemias implicated (Data extracted from papers in the Atlas) [ 7 ]
t(8;22)(p11;q13) KAT6A/EP300
t(11;22)(q23;q13) KMT2A/EP300
t(7;22)(p15;q13) EP300/HOXA7
t(12;22)(p13;q13) EP300/ZNF384
t(12;22)(p13;q13) EP300/ZNF384
t(12;22)(p13;q13) LPAR5/EP300
t(22;22)(q13;q13) EP300/EP300
|Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 8 ]
t(X;22)(p11;q13) EP300/BCOR
t(11;22)(q13;q13) ARHGEF17/EP300
t(13;22)(q32;q13) EP300/IPO5
t(22;22)(q12;q13) EP300/TTC28
t(22;22)(q12;q13) TTC28/EP300
EP300/MCHR1 (22q13)
EP300/TNRC6B (22q13)
TNRC6B/EP300 (22q13)
9. External links
|REVIEW articles
|automatic search in PubMed
|Last year publications
|automatic search in PubMed
|© Atlas of Genetics and Cytogenetics in Oncology and Haematology
|indexed on : Thu Jan 17 19:03:35 CET 2019
For comments and suggestions or contributions, please contact us email@example.com.


text:
Beyond Worms
Supporting Sustainable Farming
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Organic matter in the soil can reduce erosion and nutrient leaching, increasing water holding capacity by adjusting the chemical and physical properties of the soil.
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text: Category List Schedules (5)From the Diocese (5)Notes from Father Mike (4)Archive 2014 Jul Aug Sep Oct Nov Dec 2015 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2016 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2017 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2018 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2019 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 2020 Jan Feb Mar Apr Search RE Class http://www.stedstjoe.org/events/re-class/ Catholic Charities Presentation A program "Creating Your Own Bucket List" will be presented by Catholic Charities. http://www.stedstjoe.org/events/catholic-charities-presentation/ Re Classes Resume RE Classes for 2015-2016 resume today at 4 p.m. Welcome back! http://www.stedstjoe.org/events/re-classes-resume4/ Outdoor Mass & Picnic St. Edmund's will be holding an Outdoor Mass & Picnic on Sunday, September 20 at 10:30 a.m. at Legion Park. If inclement weather, Mass & Picnic will be held indoors at the Church. All are invited! http://www.stedstjoe.org/events/outdoor-mass-picnic/ Catechetical Sunday http://www.stedstjoe.org/events/catechetical-sunday2/ Knights of Columbus Tootsie Roll Drive Our Knights of Columbus will be conducting their annual Tootsie Roll Street Sales. http://www.stedstjoe.org/events/k-c-tootsie-roll-drive1/ Parish Council Meeting http://www.stedstjoe.org/events/parish-council-meeting13/ Finance Council Meeting http://www.stedstjoe.org/events/finance-council-meeting7/ RE Registrations Due RE registrations, along with payment, are due today. http://www.stedstjoe.org/events/re-registrations-due/ Mass/Meeting for RE Staff http://www.stedstjoe.org/events/massmeeting-re-staff/ CCW Salad Supper Please bring a salad to share and a wrapped prized for BINGO. Dessert & drinks will be provided. http://www.stedstjoe.org/events/ccw-salad-supper1/ Labor Day Church Office will be CLOSED. http://www.stedstjoe.org/events/labor-day/ ST. EDMUND'S RELIGIOUS EDUCATION COLLECTION http://www.stedstjoe.org/events/st-edmunds-religious-education-collection/ « Previous Next »


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Green tea, originating in southern Japan
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Matcha Tea is completely different from the green tea available in stores, marketed by many brands in the form of tea bags with chopped leaves. Those who really know this drink are aware of the importance of obtaining an organic tea straight from the traditional source – Japan.
It is said that Matcha, also known as "Green Gold", was drunk by the japanese monks centuries ago, because it helped them to maintain their focus and state of calm during meditation. The reason is that the green tea powder contains L-theatine, a rare amino acid that increases the activity of the alpha waves of the brain and creates a quieter and more alert state, ideal for the working periods, study, exams, etc.
Matcha green tea is rich in amino acids, but also in polyphenols, among the strongest antioxidants that give the body a better protection than vitamins C and E, boosting the immune system to its fullest.
The tea has a soft, velvety, sweet flavor and a gentle, vegetable smell. For a consistent drink, only a small amount of water is needed. Invigorate your senses and enjoy the experience of an exquisite flavor.
Matcha is the best and rarest type of green tea. In Japan, it is used during the tea ceremony and on special occasions, representing, for instance, the equivalent of a Bordeaux wine very special for the French.
Am cumparat si este chiar de calitate. E diferit de tot ce gasesti in magazine. Foarte bun!
Matcha is a tea consumed as powder, obtained from the best tea leaves harvested in the region ISE from the MIE Prefecture in Japan. Before harvesting, the tea bushes rest in the shadows, thus producing a large amount of chlorophyll, which gives it a shade of bright green, which is also the guarantee of tea quality. After harvesting, the leaves are steam-treated, dried and ground to their finest. During the preparation of the tea, the fine powder is measured with a small bamboo spoon and then mixed with a bamboo brush like a broom in a porcelain bowl.
Although it is obtained from leaves of the same plant - Camellia Sinensis – the green tea is much healthier than regular black tea. The difference between the two relies in the production method. The process of light steam treatment of freshly harvested leaves, in the case of the green tea, allows the intact storage of polyphenols. In the case of black tea, the leaves are roasted, which leads to the loss of these substances. Different studies have shown that polyphenols in green tea are particularly powerful, acting as a shield for the body. In addition, it has been shown that green tea helps to regulate the cholesterol and glucose levels. Another reason to drink green tea is that it can help you lose weight by stimulating your metabolism. In addition, it has only ... zero calories!
Matcha is very well tolerated by the body. In Japan, the average green tea consumption is about 3 cups a day, equivalent to 240-320 mg of polyphenols. Because it contains theine (tea caffeine), Matcha has a slightly stimulating effect, thus it is not recommened to drink it before bedtime. For a successful drink, the foam should be as firm as possible. Place between 1-2 grams of Matcha in the cup (about a third of the teaspoon), then pour 70-80 ml of hot water at 80° C over the powder and mix with the special "broom" or with a whisk until the sparkling appearance of the tea is achieved. There are many people who prefer animal or vegetable milk, such as rice, soy, peanuts, almonds instead of hot water. In addition, Matcha can be used and successfully mixed with other ingredients in ice cream, cakes, famous Japanese Moshi, noodles, cheesecake, Green-Tea-Latte, etc.
In southern Japan, in the MIE province of ISE Bay, tea leaves are collected and prepared for consumption by the same families, from generation to generation, for over 800 years, only through traditional methods.
After the Camellia Sinensis plant has stayed in the shadows of bamboo mats for three weeks, only its peaks are harvested, dried, then ground with millstones until a very fine powder is obtained.
Matcha Tea is rarely found, being constantly sought after by those who value its unique health qualities.
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University of Cambridge researchers have built the world's smallest working engine. The device, powered by light, could be the basis of future nanoscale machines that are just billionths of a meter in size. Fantastic Voyage, here we come! From the University of Cambridge:
The prototype device is made of tiny charged particles of gold, bound together with temperature-responsive polymers in the form of a gel. When the 'nano-engine' is heated to a certain temperature with a laser, it stores large amounts of elastic energy in a fraction of a second, as the polymer coatings expel all the water from the gel and collapse. This has the effect of forcing the gold nanoparticles to bind together into tight clusters. But when the device is cooled, the polymers take on water and expand, and the gold nanoparticles are strongly and quickly pushed apart, like a spring. The results are reported in the journal PNAS.
"It's like an explosion," said Dr Tao Ding from Cambridge's Cavendish Laboratory, and the paper's first author. "We have hundreds of gold balls flying apart in a millionth of a second when water molecules inflate the polymers around them."
"We know that light can heat up water to power steam engines," said study co-author Dr Ventsislav Valev, now based at the University of Bath. "But now we can use light to power a piston engine at the nanoscale."
"Little ANTs: researchers build the world's tiniest engine" (Thanks, Brad Wieners!)
"Light-induced actuating nano transducers" (PNAS)


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Mood Oils
Mood Oils
What is it Mood Oils™ are mood-enhancing aromatherapy rollers you carry in your pocket to balance your mind and emotions on the go. Indulge Mood Oil is a sensual and invigorating blend of floral and spicy oils to stimulate, inspire, and harmonize the senses. Made with mindfulness by Essential Rose Life.
Why I love it These mood oils come with me everywhere. They are in my car, my handbag, and my home. I am not a perfume girl, but I do love to smell good (who doesn't) and these scents are subtle enough where people often ask if I just left a spa!
RITUELLE for MINDFULNESS Rub the mood oil on your wrists, your temples, your neck. Close your eyes and inhale the essential oils deeply. Repeat the mantra "I move from my power an intuition". Feel yourself become centered and allow yourself to be guided by what is true to you.
Choose your favorite or get the set (and save)
Love Potion: This beautiful blend is luminating and magnetic attracting love, passion, and sensuality. Jojoba (Simmondsia chinensis) Seed Oil, Essential Oils of Rose (Rosa damascena) Absolute, Rose Geranium (pelargoniu, graveolens var. roseum), Black Pepper (piper nigrum), Petitgrain sur fleurs (Citrus aurantiu, var. amara)
Sedate: This ultra-cooling and tranquilizing blend of sweet, herbaceous, and citrusy oils deeply soothes the senses. Jojoba Seed Oil (Simmondsia chinensis), Tocopherol Vitamin E. Essential oils of Lavender (Lavandula angustifolia), Bergamot Bergapten Free (Citrus bergamia), Cedarwood (Cedrus himalayana), White Spruce (Picea apiana), Petitgrain Sur Fleurs (Citrus aurantium var. amara), Blue Chamomile (Chamomilla Recutita), Roman Chamomile (Anthemis Nobilis)
Indulge: This sensual and invigorating blend of floral and spicy oils to stimulate, inspire, and harmonize the senses. Jojoba Seed Oil, Tocopherol Vitamin E. Essential oils of Cardamom (Elettaria cardamomum), Rose Geranium (Pelargonium graveolens), Black Pepper (Piper nigrum), Ginger (Zingiber officinale), Rose Otto (Rosa damascena), Vetiver (Vetiveria zizaniodes)


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Pennsylvania's Business and Website Directory | Home | Add Your Link |
Featured Sites:
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1. Trop Gun Shop
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3. Grove United Methodist Church
4. Honey Brook Fire Company
5. Community Volunteers In Medicine
6. DeFilippo Brothers Motor Cars
7. Bugs No More Exterminating
8. Animal Hospital of Chester County
9. Kevin Gallagher REMAX Town and Country
10. Ottos BMW
Locations: Categories:
Pennsylvania > Chester
Search took 0.03 seconds. Displaying: 1 - 10 of 192 results.Eagle Dumpster Rental West Chester
Eagle Dumpster Rental is the leading rental dumpster company serving West Chester, PA and surrounding communities. Over the past two decades, Eagle Dumpster Rental has built a credibility for on-time distributions and budget-friendly prices. Customers include professionals, homeowners, renovators, construction companies, and others in the West Chester neighborhood....
West Chester > Construction and Maintenance > Maintenance
http://eagledumpsterrental.com/chester-county/west-chester-pa/ City of Chester
Official site. Settled in 1644, nestled on the edge of the state's southeastern region, Chester is a prime location for businesses that value direct access to the Greater Philadelphia region. Just minutes from the Philadelphia International Airport, Chester is a regional transportation hub with direct access to major roadways including, I-95, I-476, and I-295 and the New Jersey Turn...
Chester > Government and Law > Local Municipalities
http://www.chestercity.com/ The Inn at Chester Springs
The Inn at Chester Springs is the only full service hotel in the Exton, Lionville, Chester Springs area....
Exton > Lodging > Hotels and Resorts
http://www.innatchestersprings.com Arleen Pecone REMAX Leaders
Find all the information you need about West Chester, Chester County, PA. Whether you are looking for a new home, looking to sell your home in West Chester or would like information on schools, businesses or fun activities and events, you can trust that HomeYours.com will provide you with the right information....
West Chester > Real Estate > Residential Real Estate
http://homeyours.com Historic Chester County
This intent of this web site is to provide historical pictures and information about the city of Chester, located in Delaware County, PA...
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http://www.oldchesterpa.com Brewers Heating and Air Conditioning
Air Conditioning - Heating service company serving Chester County, West Chester, Caln, East Goshen, West Goshen, Westtown, Glen Mills, Pocopson, East Bradford, West Bradford, Exton, Downingtown, Coatesville, Thorndale Frazer, Paoli, Malvern, Chester Springs, Parkesburg, Honey Brook, Charlestown, Phoenixville, Lionville, Kennett Square, Chadds Ford....
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providing 24 hour veterinary care for your pet. Our new addition houses our West Chester Veterinary Rehabilitation Specialty Center....
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The pets we see at the Animal Hospital of Chester County include; Dogs, Cats, Pet Birds, Ferrets, Rabbits, Small Mammals (rats, mice, gerbils, guinea pigs, chinchillas, hedgehogs), Amphibians (frogs), Turtles and Lizards....
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Chester County Web is YOUR local community portal. Find a business, a job, start a Blog, join the Forums or sell something to a neighbor today!...
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http://www.chestercountyweb.com Law Office of Kraut and Kraut
Kraut & Kraut is a general practice law firm located in West Chester PA. West Chester is the county seat of Chester County, and we are located east of Lancaster, PA, west of Philadelphia and Media, and north of Wilmington, DE. Our firm gives counsel and advice on a wide range of legal matters to both individual and corporate clients. We service both national and local clie...
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Contact: Gary Hubbard, 202-778-4384; 202-256-8125; firstname.lastname@example.com
Pittsburgh (Nov. 9) – USW President Leo W. Gerard issued the following statement after today's remarks by President Obama for action, not politics as usual:
"President Obama declared today let's get to work on jobs and growth for the middle class. The United Steelworkers agrees and we stand ready to help. The President's election victory on Tuesday said voters want our leaders to pull together around the shared belief that working families need job and income security now.
"The House of Representatives are coming back to Washington next week in a 'lame-duck' session, and they should join the re-elected President to enact the middle-class tax cut that has already passed the U.S. Senate.
"The voters need more economic security, not less. The wealthy must pay their fair share. No more Bush tax cuts for the richest 2 percent. No benefit cuts for Social Security, Medicare and Medicaid.
"We have also joined 146 national organizations in a letter sent today to President Obama that calls on Congress to work together with the President to prioritize job creation, oppose benefit cuts to social insurance programs, protect the safety net and require corporations and wealthy individuals to pay their fair share."
For the the full text of the letter and list of signers, Click Here.
# # #


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In celebration of the 2014 Video Music Awards MTV tasked Entertainment tabloid TV host, Dave Skylark , and his dynamic production team lead by Aaron Rapoport, to sit down with some of this year's biggest VMA celebrities. In this half-hour special Skylark literally gets up close-and-personal with VMA performers Nicki Minaj and Iggy Azalea, and VMA nominee Jason Derulo to ask the questions people REALLY want to know.
James Franco hilariously interrogates the most talked about celebrities for his using his character from the movie "The Interview". "Dave" started by making Jason Derulo sing his name but Derulo refused.
Dave also took on VMA nominee Iggy Azalea! He started by making fun of her accent, making offensive remarks about Australia. Finally Dave moved on to this elegant "Fancy" quiz to see how fancy Iggy really is.
He also asked Nicki Minaj the question on everyone's mind, if her ass is natural. Also asked about her album "Superb Ass" (Super Bass).
Watch the funny video below.
Dave Skylark's Very Special VMA Special from sheree shu on Vimeo.


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The Supreme Court on Monday heard the appeal of a 29-year-old man who asked for a reduction of his 10-year prison sentence for the murder of a Vietnamese national who was thrown off a bridge in Svay Rieng town in 2016.
At the hearing on Monday, Suos Chanra told the court that he did not kill Vietnamese national Le Van Trung but was forced by his friend – named To – to help throw him off the bridge.
He said did not know Trung, but his friend had had a disagreement with him.
"After I knew of the death of the victim, I was very upset. On the day of the incident, I did not intentionally kill the man, but my friend threatened to kill me if I did not do as he said. I ask the Supreme Court to reduce my punishment," Chanra said.
Chanra and To were driving from a casino in a Toyota Camry on November 3, 2016, when To saw the victim, Chanra told the Supreme Court. To pushed the 33-year-old Vietnamese into the car.
To stopped the car as it drove on a bridge across a river. He dragged Trung out of the vehicle and started beating him.
To tried to push Trung off the bridge into the river, but he held onto the railing. To called on Chanra for help and he got out of the car. To grabbed the victim's arms while Chanra took his legs as the victim was thrown off the bridge. The two men then drove off.
After Trung's body was found floating in the river, a police investigation led to the arrest of the two men on November 7, 2016.
Svay Rieng provincial court found the two men guilty of murder under Article 199 of the Criminal Code on September 20, 2017, and sentenced them each to 10 years in prison.
The two men filed cases with the Appeal Court, which upheld the original ruling on July 12 last year.
Supreme Court Prosecutor Chan Dara Raksmey said the lower court's verdict was accurate and complied with legal procedure.
"The appellant has asked the court to reduce his sentence. He needs to compare a person's life and his punishment of 10 years in prison."
If we exchange [10 years in prison] for the life of a person, it is not equal, so I would like the Supreme Court to uphold the Appeal Court's ruling,"he said.
Defence lawyer Ok Oudom told The Post that his client did not have the intention to kill the victim and had not taken part in assaulting him. He had only helped To throw him off the bridge.
"My client confessed and cooperated with police at every stage to find and detain the offender in this case, so I would like to ask the court to reduce his sentence because he has a wife and a small child to look after," Oudom said.
Presiding Judge Khim Ponn said the Appeal Court will announce its decision on Monday.


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Tour Description
The Rainforest, Beach & Bio Bay Kayak Adventure Tour begins with a guided tour of El Yunque rainforest. This tour begins at the visitor's center, where you can see up close our vegetation, and the small wildlife hiding in between these. We will proceed to Coca falls, where we will see the roadside waterfall. Followed by the Yokahu tower where you can see the entire Eastern coast of Puerto Rico. And lastly, La Mina Falls, where we go into the trail to go to the waterfall, where you can take a dip.
After this we will give you something to eat, then head to Luquillo beach, where you will have time to yourselves to simply enjoy the beauty of the beach.
After a relaxing time at the beach, we go kayaking at night in one of the most famous natural wonders in the world, the bioluminescent bay. Learn about the ecosystem of the bay and what make's it glow in the dark.
Bio Bay Monday-Sundays
Booking must be made in advance because the spots are taken very quickly.
Approximately 12 hours
Days and Hours of Operation
- Monday-Saturday
- 10 am to 10:30 pm approx.
Tour Includes
- Transportation
- Tour guide
- No Pregnant women
- Ages 6 years and older
- Weight must not exceed 240 lbs.
What to wear
- 2 Towels per person
- Bathing suit (top+bottom)
- Change of clothes to return with dry clothes
- Sneakers (any terrain shoes) or water shoes
- Flip flops
- Small bag to leave things in van
- Big breakfast
- Snacks
Price Per Person
$139 + tax
Book now! By using the availability calendar below:
Searching Availability...
Tour duration and return times are approximate and may vary slightly due to weather, traffic conditions and circumstances beyond the tour operator's control.
Cancellation Policy
Cancellations must be made 48 hours before the scheduled tour date and local time via EMAIL ONLY. A sales representative will respond with validation of requested cancellation. Those who intend to cancel within the 48 hour time frame will be fully charged by the designated tour operator. There will be absolutely NO EXCEPTIONS under any circumstance to waive any fees.
After submittion of requested tour, you agree to our 48 hour cancellation policy and acknowledge any cancellations made within the given time frame are to be considered a FINAL SALE. There will be No Re-scheduling, and NO REFUNDS will be given.
Please note some tours depend on weather conditions to function and may be affected. Unfortunately, mother nature is out of our control, any changes required will be notified to you immediately. For safety concerns, if a tour operator cancels the scheduled tour, the option of re-scheduling will be given or a refund will be provided.


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I've been doing a lot of soul searching lately, trying to tap in to the bigger picture of why I do what I do.
'Cause truth is, meal plans are boring. Food restriction is boring. Biochemical pathways... kinda fascinating, but kinda boring.
What ignites me is moving people... shifting their perspective. Getting them unstuck. Showing them a different way. Helping them find their power.
I don't want you to be compliant to my nutritional recommendations, I want you to be empowered to embrace change. I want you to become the master of your family's health.
I've spent my entire adult life working with families. I've worked with children, with parents, with special needs, with 'A' students, with drop outs, with troubled kids, with motivated kids...
Brené Brown talks about how she watches and creates theories out of peoples' lived experiences....
Well, when I watch the lived experience of children here's what I see....
Every single child holds a boatload of possibility. They each hold the capacity to do great things and truly change the world. They just have no idea (until they do... and then... watch OUT for the explosion!)
Is this maybe why we smile when we see babies and toddlers? It's not just because they're cute. Is this why we find it so heartbreaking when a child retreats into autism or depression? Is this why we get so frustrated and scared when a child lashes out in aggression?
I think our job is to help them discover their power.
And here comes the theory.... children can only find their power and do great things if they are healthy.
They need healthy minds, healthy bodies, healthy relationships.
They need to know who they are, what they're capable of, feel a strong sense of agency. They need to be seen. Heard. Loved. Accepted. Nourished. That is what builds health. Then... and only then... they can do great things.
Abilities, disabilities, slow learners, fast learners, deficiencies, disorders... whatever the label... when our kids are healthy they can do great things.
It's parents - you and me - who can build health for our kids. We are the ones who can teach them what healthy eating is, what healthy living is, what taking care of their bodies and minds looks like, what healthy relationships are.
We are the ones who can bolster their intuitive sense of self and compassion and greatness.
Our kids are sentinels. Super absorbers. Reflectors. And this makes parenting the most profound self-development course of all time. It is what makes our kids our greatest teachers.
This is why I work with parents to build health inside their families.
In order to build you have to nourish. You have to clean up and put in place a solid structure. Then you fill in the rest.
So that's what we do in my coaching program and that's what my book's about.
Yes I focus on how to use food. My books and programs are about healthy eating and healthy bodies; about the connection between food and behaviour and about adopting a way of eating that supports the brain.
But really, the process of Raising Resilience is an invitation to listen. Listen to the call your children and making. Pay attention to what they're reflecting. Get back to basics and clean up so you can build.
Join our mailing list to stay connected and receive the latest news & updates so you can raise healthy, resilient kids. Your information will never be shared.
Jess is a Registered Holistic Nutritionist™ and Family Health Expert, specializing in brain health & resilience for kids. She is the author of Raising Resilience: Take the stress out of feeding your family & love your life, a mother and an advocate for children's health. Her book and online resources have helped families all over the world improve the lives of their children with learning differences, anxiety, ADHD, autism and mood disorders by fitting the food and feeding piece into their health puzzles. She is the 2019 recipient of the CSNNAA award for Clinical Excellence for her work helping families get healthier, and she continues to work at bringing an understanding of the power of good nutrition to the mainstream conversation about children's mental health, learning, and overall resilience through her blog, courses and as a contributor to print and online magazines. You can reach Jess at www.jesssherman.com
It takes a village, and you've found one! C'mon and join us...


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POSTPONED: BEYOND2020 The Health Roundtable's Annual Innovation Event
Select Hospital In The Home on your Improvement Group member subscription and return by email to email@example.com
For more information please contact Ben Wakeling on firstname.lastname@example.com or 0468993080
Please contact Ben Wakeling for subscription cost details.
The 2020 HITH brochure will be available soon.
For more information please contact Ben Wakeling at email@example.com or on 0468993080
Hospital in the Home Improvement Group
Our exclusive Hospital in the Home reports provide a detailed analysis of your facilities service, crucially benchmarking against your peers across Australia and New Zealand.
The 2020 HITH Improvement Group will continue the successful progress made in previous years by:
The Health Roundtable has developed detailed benchmarking reports to assist services to highlight key insights and review the success and opportunities in their HITH referrals against peers.
HITH Benchmarking Reports
Specifically the suite of benchmarking reports includes the following HITH specific reports produced annually:
The current traditional healthcare model is unsustainable. Hospital in the Home services provide an alternative to traditional hospital-based care, delivering patient centred care where patients report higher satisfaction, superior clinical outcomes and less complications of care.
Delivering Acute Care in the home offers many advantages to your service by:
Our members share successful innovations through our online innovation library.
For existing HITH services benchmark your facility with the exemplars.
For new HITH services, learn and adapt existing models of care and develop peer networks that will help you implement and grow HITH services in your facility.
Join this growing group and share your wisdom as well as gaining new knowledge from your peers.
For more information please contact Ben Wakeling at firstname.lastname@example.com or on 0468993080.
What do you need to do?
1. Subscribe to the HITH Improvement Group
2. Nominate a key liaison to Health Roundtable for HITH
3. Submit your additional coded data
4. Regularly review and analyse your reports, identify your opportunities and celebrate your success with your team
What does The Health Roundtable do?
1. Collate your data
2. Produce your reports highlighting your HITH performance within the total patient journey
3. Enable you to identify your opportunities and success
4. Help develop your Aim Statement and Improvement Plan
5. Provide ongoing support around your data and reports
In Australia: +61 (02) 8041 1421
In New Zealand: +64 3741 3123


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MasterProtect FL 749: Acrylic copolymer block filler
Formerly: Thoro Block Filler
How does MasterProtect FL 749 work?
MasterProtect FL 749 is a ready-to-use, VOC compliant, 100% copolymer-based block filler resin used to prime and fill porous masonry before the application of MasterProtect coatings.
Recommended uses:
- Substrates where absorbency is not uniform
What are the unique features of MasterProtect FL 749?
- Heavy-bodied
- Breathable
- Moisture-resistant
- Excellent workability
- Moisture tolerant
- Easy to apply
- VOC compliant
What are the benefits of MasterProtect FL 749?
- Fills pores; excellent surface closure
- Allows substrate moisture vapor to escape from the structure; prevents peeling and blistering
- Will not degrade in the presence of wet-dry cycles
- Ease of application; lower labor cost
- Can be applied to damp substrates
- Can be sprayed with airless equipment
- VOC compliant for EPA and most regional authorities
On the Job Videos
How to Apply MasterProtect® FL 749 block filler
How to Apply MasterProtect® FL 749 block filler (Spanish)
How to Apply MasterProtect® FL 749 block filler (French)
US / Canada Product Information
Direct contact
Master Builders Solutions Technical Support
Construction Systems
Related Literature
Certification Letter
Data Guide
LEED Letter


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Send prepaid credits to your family in Morocco and receive 7x/10x Bonus for Orange phone numbers!
Terms and conditions:
– Valid from 13th until 18th of October, 00:59 CET;
-7x/10x Bonus will be added for MAD 30, 75, 150 and 300 denomination;
-Please access the website of Orange Morocco for more details.
Click link below for instant access;


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Our complete summer 2020 schedule will take place fully online and registration is open - sign up to secure a space in your preferred session! See our COVID-19 page for more details.
2-Week Core Limited Prep Events Program
Start your season with us and experience national championship caliber coaching combined with the highest caliber resources all in the beautiful, safe and relaxing atmosphere of the Stanford University campus. Our challenging curriculum ensures that speakers starting out their forensic careers will learn the basic skills necessary to become competitive immediately while providing them with a firm foundation for growth. Experienced speakers will master advanced techniques to improve their performances and make them more successful at local, state and national competitions.
Program Curriculum: SNFI features an experienced faculty prepared to provide students with an exceptional educational experience in any event. Unlike many individual events camps which require students to pay extra to work on a second event, at SNFI students can choose one major event AND attend electives on other events during their time at camp for the same low price!
Students will primarily focus on their "major event" and can expect to leave SNFI with that event "tournament ready." Students will have the option to attend several elective seminars in which they will have the option to work on a minor event. Focus on the electives/minor evenst will be in theory, piece selection and speaking exercises, but students should not expect to leave camp with a prepared piece from any electives/minors chosen .
Courses of Study: Extemp; Original Oratory; Original Advocacy; Dramatic Interp, Humorous Interp; Duo Interp (Both students must attend); Prose; Poetry; Oratorical Interp; Expository Speaking; Thematic Interp; Impromptu Speaking or Original Prose and Poetry*
Limited Preparation Events: This track includes extemporaneous speaking, commentary and impromptu speaking. Students will focus on strategies to make the most out of prep time while working to develop skills necessary for both effective argumentation and delivery. Significant time will be spent mastering thesis development, research skills and introductions, as well as fine-tuning skillls that seperate competitors in final rounds. In addition, all students in the extemp lab will take part in lecture and discussion focused on today's most relevant events, and will explore topics pertinent to both US and international extemp.
Oratory/Writing Events: This track includes original oratory, original advocacy, exoposity/informative, etc. Students will work to select a topic area, progress through the drafting and refinement of the writing that underlies their performative piece, and practice the delivery. The program provides an in-depth focus on the entire process from start to finish.
Interpretative Events: This track includes humorous interp, dramatic interp, duo interp (both students must be present), thematic interp, oratorical interp, prose/poetry. Interp students will learn how to choose an appropriate performance piece, cut it down to fit the event requirement and then how to bring it to life through a variety of interpretive techniques. In addition to learning competitive techniques, students will participate in lab activities and lectures which will help them develop their interpretive skills.
*Note: Additional events based on regional requirements may be added upon request
2020 2-Week Core Limited Prep Events Program Staff Members Include:
Check back closer to the start of camp for details on our 2020 staff
We will continue to add additional staff members as enrollment and availability dictate. Details are posted on additional staff members as they are confirmed and as we have complete biographic information available. Staff listing may not be fully up to date or reflect all hires to date.
2019 2-Week Core Limited Prep Events Program Staff Members Included:
Luis Cardenas, Competitive Speech Programs Coordinator
With combined winning experience of over 40 years, Sarah Rosenberg and Luis Cardenas have coached students to hundreds of final rounds across the country. Their students have won DUO at CFL Nationals and have tied for 1st in DUO at NFL Nationals twice. They have had over 30 National Finalists at both CFL and NFL and have won countless State Championships in California, New York, Philadelphia and Florida. Current projects center on The Festival of New American Musicals and Future Fest, working with composers such as Stephen Schwartz, Jeff Marx, Jason Robert Brown and Stephen Sondheim. NYC credits include the Off-Broadway musicals Fools in Love and Tempest Toss'd, one a doo-wop re imagining of A Midsummer Nights Dream and the other, a re imagining of The Tempest. Both are designed to make watching Shakepeare a family event and have won rave reviews in major newspapers across the country. These musicals have also been showcased at BAM, The New York Musical Theater Festival, El Portal, Theatre Row in Hollywood, and The Wheeler Opera House in Aspen, CO. they also have a new professional theater company in New York City called Open Hydrant. This is the first Equity ensemble theater company in the Bronx serving under-served artists. Their work also can be seen in the new film, Shakespeare High Executive Produced by Kevin Spacey, which premiered at Robert DeNiro's Tribeca Film Festival in NYC and will premiere on Showtime this fall. Rosie/Lou have coached for Stuyvesant High School, Bronx High School of Science, Florida Forensic Institute, Bronx Prep, Holy Ghost Prep, San Marino High School, Cleveland High School, James Logan and The PUC Schools. For more info visit: www.shakespearehigh.org www.lafestival.org http://thepoint.org http://openhydrant.org
Upcoming Sessions
* Tentative and Subject to Change
|Price Range
|On Monday July 20 - Jul 31st
|Online Virtual Programs
|$1,695.00 – $3,495.00
Pricing Options


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Driftwood Flooring Laminate - Wood flooring is the most sustainable stuff we could utilize to construct floorings. The level of sustainable forest management makes it possible for us to harvest wood without the serious effect on our environment. Trees are a renewable resource we could use to get quite a long time in the future. According to the US Department of Agriculture Forest Service, today's typical net of yearly increase for hardwood is greater than typical yearly of removal.
Some say sustainable flooring really helps create a more healthy and safer building. According to the Asthma and Allergy Foundation of America, people who have allergies to dust or other particulates, regularly select a flooring with smooth surfaces like hardwood, linoleum, vinyl, natural slate or stone tile.
Manufacturers engineer Hardwood floorings to give a fit that is uniform and stable. A great deal of dirt do not gather and are reasonably simple to wash. The natural beauty of wood will never venture out of fashion. Selecting a high quality wood flooring will consistently help increase the value of your property. Since home buyers it so appealing that the likelihood of a quicker sale, and higher sale price, are significantly raising. The carbon consumed throughout the growth cycle of a tree remains even after it is installed.
Folks use recycled wood to construct flooring from distinct sources like wood seen in mine shafts, old warehouses, barns, wine barrels, boxcars, and rivers. The National Association of Home Builders says that wood floors can last for centuries, and WOn't need replacing nearly as regularly as every other flooring choice available.


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The subtle and sublime as the whisper of the soul, Lapis Lazuli and Clear Quartz pendant in chrome, from Rubycharm jewellery. Crystal that will invoke spirits of nature in you, and you will hear its soft whispers of wisdom.
In the dark ages, Lapis Lazuli was being carried to Europe where it was powdered and made into one of the most excellent and priciest blue pigment, Ultramarine....Read more about Lapis lazuli in history
In Europe rhinestones were made from quartz pebbles that were found on the shores of river Rhine, hence the name rhinestone. Although it can be as clean and transparent as a diamond, it is much more common and abundant, so it was usually used for production of less valuable jewelry and beautiful items, ornaments, various figurines, decorative crystal balls, and similar items....Read more about Clear quartz gemstone
This pendant is part of RubyCharm:
Crystal Jewellery collection
All crystal jewellery collection. Explore and understand the power of crystal influence of your mind, body, chakra and spirit.
All crystals were hand picked before we set them into various form of jewellery and crafts. We have searched for alive and vivid energy in crystals. Enjoy the wonderful world of Rubycharm crystals.
Many interesting facts are related to this mineral. So for example, a controversial crystal skull was made of quartz. It caused turmoil at the end of the 20th century as it was believed to be a relict of an old civilisation. Scientists, researchers, and writers flared into fierce debates about the origin and purpose...Read more about Clear quartz crystal
© Copyright Rubycharm. All rights reserved


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Product Description
Jaguar is an authorized retailer for all Lamm Industries gear. These products, designed by Vladimir Lamm and built at the Lamm New York city headquarters, are legendary, for amazing sound...there's nothing else like it.
Lamm produces three models of linestage preamplifiers that fit in distinct budget categories. At each level, these are some of the finest linestage preamps in the world.
- LL2.1 Deluxe - A great value, not inexpensive, but most definitely world-class. This is the best choice for most audiophiles.
- L2.1 Reference - This model provides reference-level performance. This model uses a more intensive power supply, in a separate chassis.
- LL1.1 Signature - The Signature is the ultimate Lamm preamplifier and uses four chassis, with a separate control and power supply unit for each channel.
The Lamm LL1.1 Signature is a direct replacement of the LL1 Signature which has been the ultimate statement of perfection among the line level LAMM preamplifiers since its introduction in 2010. The LL1.1 proudly continues this tradition.
Although the LL1 Signature integrated everything its designer had at his disposal to make it the best-sounding preamp, a true creator never rests on his laurels. There is always a yearning to do better even though it seems unrealistic at the time. The LL1.1 Signature is an end result of this yearning.
The LL1.1 Signature includes the following upgrades and modifications as compared to the LL1 Signature:
- increased immunity to unwanted radio frequency interferences propagated via both radiation and conduction over signal lines & AC power systems
- increased amount of energy storage in the power supply
- certain modifications in protection and time delay circuitry
- improved signal/noise ratio
- replacement of a number of critical components with newly available types of better quality
- utilization of a technologically new type of pc-boards of superior quality, with gold-plated traces and thru-holes.
Considering that the LL1 Signature was practically a flawless design, it was difficult to make that next step to the near perfection. When all technical issues for proper reproduction of the entire frequency range have been solved, the potential improvements shift to a different sphere – the one where the measuring criteria of the sound quality is its degree of approximation to the sound of live concert and the depth of its effect on the listener. The modifications catapulted the LL1.1 Signature precisely into that sphere -- with this preamplifier in the all-Signature Lamm system the discerning listener can't help but get pulled right into the essence of music. The experience is almost shockingly involving and it is also an incredible chance to experience a different reality which may otherwise be nearly out of our reach.
While the LL1.1 Signature had been designed to complement the ML3 Signature amplifier to show what a sonic "match made in heaven" is like, the LL1.1 Signature will perform magic with any other appropriate power amplifier. The LL1.1 Signature features a topology that brings out the most natural sound performance in the audio path. In principle, it is a single-stage unit that basically represents the shortest possible signal path. The preamplifier contains four very linear low impedance triodes paralleled into a single inverting gain stage. The LL1.1 Signature employs a pure single-ended class A operation, with no overall feedback applied. Also featured are specially selected high-transconductance dual triodes 6N30P-EB/ 6Н30П-EB in the signal path and TKD stepped potentiometers for volume control -- the best available on today's market.
The preamplifier's audibly neutral power supply features a full-wave vacuum rectifier. This rectifier, together with a choke-containing filter, allows to practically get rid of the hum and buzz and, in the end, to ensure the verity of dynamic range without coloration. Two solid-state analog voltage regulators supply dc voltage to the tube filaments (heaters).
Other features include 3 inputs, one tape/HT processor loop, attenuator (-12 dB) switch, output 1/output 2 switches, protection circuitry designed to enable manual muting of the output signal, and built-in remote on/off for LAMM power amplifiers. The main distinction of the LL1.1 Signature from any other comparable type of preamplifiers is its practically inaudible sonic signature. When connected to an appropriate type of power amplifiers, especially LAMM power amplifiers, it assures the extraordinary transparency of perceived sound and recreation of a three-dimensional soundstage in the home, recording studio, etc., without boundaries and limitations.
Each preamplifier is handcrafted of the finest materials and top quality parts like military-grade DALE metal-film resistors, RCD wire-wound resistors, BOURNS multi-turn potentiometers, VISHAY electrolytic capacitors, ELECTROCUBE, ELCON and KEMET/RIFA film capacitors; HAMMOND chokes, gold-plated NEUTRIC connectors, and military-grade low-noise long-life vacuum tubes. A custom-designed massive damping panel installed in the preamplifier unit significantly reduces all types of mechanical vibrations which, in turn, leads to a more extended, coherent and natural bass reproduction. The LL1.1 Signature features a custom-designed super-low noise power transformer. The LL1.1 Signature works on all world AC line voltages (100/120/220/230/240V).
The following Lamm products received the 2016 Editor's Choice Award from The Absolute Sound:
- ML2.2 single-ended amplifier
- ML3 Signature amplifier
- LL1 Signature preamplifier
- M1.2 Reference amplifier
- LP2.1 phono preamplifier
- LL2.1 line-level preamplifier
Lamm LL1.1 Reviews
Check out all the Lamm product reviews, here.


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How to Change How Many Notifications are Visible per App in Windows 10 Action Center
The Action Center in Windows 10 collects and shows notifications and alerts from traditional Windows applications and system notifications, alongside those generated from modern apps. Notifications are then grouped in the Action Center by app and time. When the Action Center gets a new notification, it will briefly show a notification banner above the taskbar notification area to let you know.
Starting with Windows 10 Insider Preview Build 14316, you can adjust how many notifications are visible per app in the action center. The default is now 3 per app. If an app has more than 3 notifications, just click or tap to expand and see all notifications for that app.
This tutorial will show you how to change how many notifications are visible per app in the Action Center for your account in Windows 10.
EXAMPLE: Visible Notifications in Action Center
Here's How:
1. Do step 2 (Action Center) or step 3 (Settings) below for how you would like to open notification settings for an app.
2. Open Action Center, right click or press and hold on a notification from an app (ex: Mail) you want to change its priority level, click/tap on Go to notification settings, and go to step 4 below. (see screenshot below)
3. Open Settings, and click/tap on the System icon.
A) Click/tap on Notifications & actions on the left side, click/tap on an app (ex: Mail) under Show notifications from these apps you want to change its priority level, and go to step 4 below. (see screenshot below)
4. Under Number of notifications visible in action center, select the number you want to set for this app (ex: Mail). The default is 3. (see screenshot below)
5. When finished setting the number of notifications visible per app you want, you can close Settings if you like.
That's it,


text: Ved Nursing College is located in Haryana. The education institution was established in the year 1979. The College was affiliated to PT. B.D. Sharma University of Health Sciences, Rohtak. It is approved by INC (Indian Nursing Council). Ved Nursing College offers various courses like Nursing. The college has a well developed infrastructure and facilities like Medical lab, Auditorium, Sports and more. The college has well trained and experienced faculty members. Ved Nursing College address, contact number is provided in contact details.


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Born in 1891, Gwen Ffrangcon-Davies enjoyed an illustrious theatrical career, which saw her working with some of the UK's leading actors and companies throughout the twentieth century. She is best known as performing with John Gielgud in Shakespeare's plays and also starred alongside Ivor Novello, Alan Bates and Peggy Ashcroft. She performed in works by many leading playwrights, including Noel Coward, Eugene O'Neill, Terence Rattigan, Tennessee Williams, Chekhov, T.S. Eliot and G.B. Shaw. Retiring from the stage in the 1970s, she continued to occasionally appear on radio and television, her final appearance being at the age of 100. She died in 1992, aged 101.
The collection offers a compelling insight into Gwen Ffrangcon-Davies' professional and personal life, as well as the performing arts scene of her time. There is correspondence with most of the leading performers and writers, including John Gielgud, Vivien Leigh, Ellen Terry, Edward Gordon Craig, Ian McKellen and Peggy Ashcroft. Photograph and press cutting albums further illustrate the career of this remarkable British actress. Her diaries, address books and memorabilia including some belonging to her father, the baritone David Ffrangcon-Davies, provide further insight into her life.


text: Media Releases › NSL Consolidated View All NSL Consolidated News NSL Consolidated Announces Infinity Ores 20,000 Tonne Purchase Order Update 10 May 2017 10:37 AM HIGHLIGHTS - 20,000 tonne Purchase Order received for premium 63% Fe from new customer, with A$65 (equivalent) ex gate sales price. - IFO higher grade feed for blending commenced arriving on site for use in supplying the existing and expected future Purchase Order's. - Higher grade feed being incorporated into plant feed process for routine production of 63%Fe product. NSL Consolidated Limited (Company, ASX:NSL), wishes to update the market regarding the progress of its Phase Two Wet Beneficiation Plant. For further information please download PDF attached: Download this document


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Blogging is the new resume. That is, creating your own personal blog.
Especially if you are starting out, a personal blog can showcase your strengths, your expertise and your personality.
What should the blog be about? Ideally whatever field it is you hope to work in. If you are a writer, designer or photographer this is much easier. As an example, check out this awesome blog from a college student, who is showcasing her talent already. If you wanted a go-getter, wouldn't she be at the top of your list?
But what if you are a salesperson? Are you going to blog about the great sale you made? Eh, maybe. But think of what else you can write about. Your blog can focus on
- Best practices in sales.
- Your opinion of new regulations.
- Books you recommend with a short synopsis or takeaway.
- Timely news articles.
See how this works? The blog doesn't have to showcase your particular talent but should show that you are interested and up on the news/best practices in your preferred industry.
Here are five reasons to start a blog:
- You will turn up in search. We don't have to beat this dead horse. Even if your social media profiles are scrubbed of unfortunate photos and comments, you still want something to come up. So if you Bing your name, do you want it to show that random comment you made on a video game fan site, or a smart take on the news in your industry?
- You are more than your resume. A resume is almost an afterthought anymore. Of course, you have a robust LinkedIn profile (don't you?), but a blog allows you to express much more of your expertise and show you are interested and invested in your chosen field.
- You can express yourself in more than 140 characters. Perhaps Twitter is your venue of choice for sharing your expertise, but it's hard to really showcase yourself in 140 characters. (Though it's a perfect venue for sharing a link to your blog!) Twitter is casual. Twitter is a cocktail party. Twitter leaves people wanting more. Give it to them on your blog.
- You can show that you know how to write (and spell). It's sad, but many in the younger generation are painted with the broad brush that they only know how to talk in shorthand or acronyms or phonetics. U R so much more! Prove it with a blog that shows you can pick a theme and discuss it coherently.
- You are interesting. Aren't you? The truth is that most employers want to work with people who are smart, hopefully funny and definitely have opinions. If you are job hunting, you are undoubtedly keeping up on your industry. Why not showcase those relevant links and discussions by sharing them with others and providing your own person spin. If you can add a little personality all the better!
I always start with the positive but the truth is, for the five reasons I think you should start a blog, there are probably five reasons you think you shouldn't. We'll cover those in the next post!
by Cathie Ericson


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Villa Demetra is the first house on the left hand side facing the sea.
It is situated high at the most privileged place in the compound offering the guest unique views of Ornos, Korfos and all the way to Tinos island. Its west orientation shelters it from intense sunshine during the day and offers wonderful views of the sunset in the afternoon.
The exterior grounds have been carefully designed so that the guest will enjoy private moments sheltered from the north wind and from indiscrete eyes. Inside simple lines stay true to the traditional Mykonian architecture. On the ground floor there are a kitchen and a living room, on the same level with the pool and the outdoor resting area.
On the upper floor there is a master bedroom with a stone-built king-size bed. It has its own bathroom and a wonderful balcony with stone benches offering unlimited views. On the lower floor there are 3 comfortable bedrooms with their own bathrooms, all traditionally built and painted in ochre or sky blue color.
Every bedroom contains heat and air conditioning system. On the same floor the villa has two external, independent and fully equipped guest rooms accommodating 4 more persons.
The villa is equipped with satellite TV, Wi-Fi internet connection, security lighting and an alarm system.
Panoramic view of sunset, Ornos beach, Korfos beach and Delos island.
The property features a large and elegant infinity swimming pool of 50 sqm2. The wonderfully structured outdoor area of the property, surrounded by rocky hills and Mediterranean herbs, can provide relaxation and recreation for the guests, providing multilevel lounging and dining area. Sitting areas in the front of the villa, to all which guests have access to, are designed, so that guests can break off into small groups and enjoy their own private space with a feeling of exterior independence enjoying panoramic sea and sunset views.
The main features include white plaster, local stone, natural rocks, built-in couches, and wooden pergolas intertwined with Cycladic arches. The villa is surrounded by specially designed areas paved with lush gardens: olive trees, bushes, shrubs, ornamental plants, and cacti among the rocks form beautiful landscapes, creating a particularly relaxing mood.
Middle Floor
Top Floor
Ground Floor
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