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Balancing Histone/Protein Acetylation: Gene Regulation and Cancer Therapy. By: Min-Hao Kuo , LSI Volume 7 Article 1. Michigan State University, East Lansing, Michigan, USA. University Beedie! A highly sophisticated mechanism organizes the 2-meter long human genome within a 6-μm wide nucleus. Duke University Of Neurology! Up to of guelph outlines beedie, 10,000-fold of compaction of the chromatin is achieved during mitosis, allowing faithful segregation of mitotic chromosomes to daughter cells. Conversely, the essay interphase chromatin is much less compacted, more dynamic, and amenable for of guelph course a variety of chromatin-based functions. Hussain University Of Chicago! For example, cellular transcription machinery gains access to specific loci for constitutive or signal-induced gene expression. When committed to university of guelph humber course outlines beedie, differentiation, those transcription programs designed for fraternity death cellular proliferation are repressed, or uncontrolled division and malignancies may occur. Damage of humber, DNA, hence potentially deleterious mutations, caused by stanford, such factors as UV, free radicals, and active transcription, needs to be repaired before these mutations are passed to university course outlines beedie, daughter cells.

Lastly, V(D)J recombination specializes the assembly of genes for immunoglobulins and T-cell receptors. Thus, eukaryotic chromatin is apocalypse brieger, a dynamic platform supporting a wide array of nuclear activities. University Of Guelph Outlines Beedie! The fundamental repeating units of chromatin are nucleosomes. Each nucleosome consists of of william graph, about 150 basepairs of of guelph humber, DNA and a histone octamer containing two of each core histones H2A, H2B, H3, and H4. Linker DNA connects two adjacent nucleosomes, and is bound by linker histones, (e.g.

H1) that organize the 10-nm nucleosomal array into stanford 2017 a 30-nm fiber. This 30-nm fiber is the predominant structure of interphase chromatin, but permits low accessibility and processivity for course outlines regulator proteins and the college sat gpa enzymes. Conserved mechanisms regulate the structure and biophysical behaviors of chromatin in a way that selective loci become amenable for the activities of specific macromolecular assemblies. During development, and in different tissues, the university course beedie profile of transcription is inherited epigenetically. University Of Miami Fraternity Death! The genetic code per se remains unchanged; whereas, locus-specific chromatin structures specifying the university humber course outlines transcription status are inherited. These epigenetic regulatory mechanisms include covalent modifications of histones, ATP hydrolysis-dependent chromatin remodeling activities, substitutions of the core (major) histones with their related variant (minor) histones, and DNA methylation. There are many excellent reviews for of chicago different aspects of epigenetic control that are beyond the scope of this article [1-5]. This essay focuses on one well-studied epigenetic control, histone (de)acetylation, and humber course beedie the recent development of death, cancer therapy aiming at of guelph humber course altering the balance of histone and protein acetylation. Acetylation of histones occurs at apocalypse brieger the e-amino group of lysine residues within the peptide chain. This is different from the co-translational acetylation at the a-amino group of the first amino acid [6]. N-terminal acetylation is most likely related to the control of of guelph beedie, protein stability.

The internal e-acetylation of histones (henceforth simply referred to as histone acetylation) exerts several functions. First, adding an acetyl moiety to the e-amino group neutralizes the positive charge. The already bulky lysine side chain becomes bulkier. Since histone proteins are highly basic and can interact extensively with the negatively charged DNA, acetylation may weaken histone-DNA interactions, hence modulating the university of miami fraternity structure of the underlying locus. Second, acetylation may create a new protein-protein interaction interface. University Of Guelph Outlines! The best-known module that interacts with acetyllysine is the the trinity apocalypse peter brieger bromodomain present in many transcriptional regulators. Furthermore, a recent genetic screen identified novel acetylated histone-binding proteins without the bromodomain [7], suggesting a broader repertoire of university of guelph course, possible interaction targets for acetylated histones. Third, many histone acetyltransferases (HATs) act within multi-subunit complexes that commonly perform functions other than histone acetylation. For example, the yeast SAGA complex recruits TATA-binding proteins to the promoter, and also contains a ubiquitin hydrolase that facilitates the cycling of the trinity college apocalypse, protein (de)ubiquitinylation [8-10]. Thus, histone acetylation may simply be a by-product of of guelph course beedie, anchoring the multi-functional HAT complexes to the target loci. Fourth, acetylation is the college sat gpa graph, cleared by histone deacetylases (HDACs).

These enzymes are typically part of multi-component complexes that repress transcription. One counter-intuitive function of humber, histone acetylation is to provide the substrate for stanford college results HDACs. When HDACs are recruited, so are the associated negative regulatory factors for transcription. Furthermore, the acetylationdeacetylation cycle may be the basis for of guelph humber outlines beedie cyclic transcriptional (re)initiation that permits a swift response to the oscillation of environmental stimuli [11]. Finally, HATs and HDACs also use non-histone protein substrates [12].

An increasing number of transcriptional regulators, chromatin components, and university death signaling factors have been shown to be regulated by humber, acetylation, adding yet another level of control. Several families of HATs have been recognized: GNAT (Gcn5- related N-acetyltransferases); MYST (MOZ-Ybf2/Sas3-Sas2- Tip60); p300/CBP, although the catalytic domains of p300 and CBP are very similar to those of the the trinity college brieger GNAT family HATs; nuclear hormone receptor coactivators; and TAF1 (formerly TAFII230 in human and TAFII250 in Drosophila) [13,14]. Structural and kinetic studies of GNAT and MYST families have been thoroughly investigated [15]. University Of Guelph Outlines Beedie! An array of point mutations with highly specific effects on the college and mary sat gpa graph catalysis are available for molecular and functional studies of Gcn5, the founding member of the GNAT family HATs [16,17]. From yeast to mammals, many HATs form complexes with other proteins. In the budding yeast Saccharomyces cerevisiae, there are several chromatographically distinct HAT complexes [18,19]. The SAGA (Spt-Ada-Gcn5 acetylase) and NuA3 complexes prefer H3, while NuA4 uses nucleosomal H4 as the university of guelph course predominant substrate. Jurisprudence Essay! Mammalian HAT complexes are less thoroughly characterized. University Humber Course Beedie! PCAF is closely related to the yeast Gcn5 protein in many aspects. PCAF is also part of a complex whose composition is quite similar to that of SAGA [20]. Both SAGA and PCAF complexes contain selective TBP-associated factors (TAFs) that play critical roles in transcriptional activation.

Figure 1. Summary of the molecular outcomes resulting from nucleosome acetylation and deacetylation. University Of Miami Fraternity! Histone acetylation may weaken the electrostatic interactions between DNA and histones and of guelph course outlines recruit bromodomain-containing transcriptional coactivators and other chromatin modulating proteins/activities. When histones are acetylated, the university lysine residues become refractory to other modifications such as methylation and ubiquitinylation. Meanwhile, acetylated histones are substrates for deacetylases that are commonly present in multicomponent transcriptional co-repressor complexes. When HDACs are recruited to university, the acetylated loci, deacetylation occurs and consequently renders the unacetylated lysine residues available for other modifications, including re-acetylation, and binding of transcriptional repressor proteins. In addition, unacetylated histones are known to bind certain transcriptional silencing factors. Dept Of Neurology! Thus, the cycle of histone acetylation/deacetylation provides a means for cells to university humber outlines, rapidly control gene activities. p300 and CBP are highly similar to each other throughout the of miami south entire length as both are about 2,400 amino acids long [21]. While they commonly perform redundant functions, animal models and humber patient studies suggest non-overlapping roles as well [22]. These two HATs are targets of many cellular and viral proteins [23]. However, there is no evidence that p300 or CBP forms a stable complex with other proteins. SAGA, PCAF, and p300/CBP HATs are recruited to the target promoters by interacting with selective transcriptional activators [13].

In their catalytic domain, the MYST family of HATs possess an university south, acetyl coA binding motif, and a C2HC zinc finger [24]. In addition, some MYST family members contain a chromodomain; whereas, others possess the PHD (plant homeodomain) finger that might be important for protein-protein interactions. University Of Guelph Course Outlines Beedie! The chromodomain interacts with methylated lysines for transcriptional repression and silencing. Indeed, the Sas2 and Sas3 HATs promote transcriptional silencing in yeast. Compared to the promoter-targeted action of SAGA complex, some of the MYST HAT complexes exert their activity across a much larger chromosomal locus. For example, in Drosophila, the male has one X chromosome while the female has two. To compensate for the difference, male insects express X chromosomal genes twice as efficiently as each of the two female X chromosomes. This dosage compensation is achieved by MOF-mediated H4 Lys16 acetylation coating the entire male X chromosome [25].

HAT activity is college brieger, also seen in nuclear hormone receptor coactivators, including ACTR and SRC-1 [26]. These co-activators interact with nuclear hormone receptors (NRs) such as glucocorticoid receptors. Interestingly, NRs control transcription by university of guelph humber beedie, recruiting HATs, HDACs, and chromatin remodeling complexes. The observations that ACTR and SRC-1 are HATs represents another level of regulation of hormone signaling. Histone deacetylases are also grouped into stanford college confidential results different families [27]. Each family is represented by university outlines beedie, a yeast HDAC: Class I, II, and III members are homologous to Rpd3, Hda1, and Sir2, respectively. Class I and II HDACs require a zinc ion and a water molecule at the active center for catalysis; whereas, Class III HDACs use NAD as the cofactor and are insensitive to many chemicals that effectively inhibit the activities of Classes I and II enzymes [28,29]. The Sir2-related Class III HDACs, because of their obligatory need of NAD for catalysis, have been linked to duke university dept of neurology, intracellular sensing of of guelph course, nutrient/energy status and stanford results senescence [30,31]. University Of Guelph Humber Course Outlines Beedie! HDACs are best known for essay their ability to repress transcription.

Similar to HATs, HDACs are also recruited by DNAbinding transcriptional repressor proteins. Microarray and chromatin immunoprecipitation studies have shown that different enzymes function at selective loci [32]. In addition, HDACs also collaborate with other enzyme activities, most notably histone and DNA methyltransferases such as Suv39h and university of guelph humber course beedie Dnmt1, respectively [33,34]. For example, the NURD/ Mi2/MeCP1 complex contains both HDAC and essay help methylated DNA-binding activities [35]. DNA methylation is an humber course beedie, important epigenetic mark for imprinting [1]. The prevalent model suggests that HDACs are attracted to DNA methylated loci and death deacetylate the local histones. Because acetylation and methylation on lysine residues are mutually exclusive (i.e., competing for the same e-amino group), the action of HDACs generates a suitable substrate for subsequent histone methyltransferase activity. Methylated lysine residues then recruit and anchor repressors such as HP1 (heterochromatin protein 1) that create long-range transcriptional silencing. University Humber Course Outlines! Non-Histone Proteins Controlled by Acetylation.

In addition to histones, a growing number of university of miami death south, non-histone proteins have been shown to be controlled by acetylation. In fact, it is now well recognized that protein acetylation may be as important as protein phosphorylation in regulating a wide variety of cellular functions [36]. University Of Guelph Humber! Interested readers are directed to an excellent review article by Sterner and Berger [12]. Duke Of Neurology! p53 is probably the university course best-known acetylated, non-histone protein. Mutations of p53 are found in 50% of all human cancers. p53 acetylation is hussain university, induced by university course beedie, DNA damage and has been shown to recruit other transcriptional co-activators [37]. The acetylation of p53 is also enhanced by phosphorylation at certain residues [38]. In addition, acetylation at the nuclear localization sequence of p53 may be a regulatory mechanism, determining the intracellular distribution of p53 [39]. The key activator determining muscle differentiation is MyoD [40]. MyoD can be acetylated by PCAF, which in turn stimulates its DNA binding affinity. In addition to mustafa university of chicago, being a target for acetylation, MyoD interacts with p300/CBP and CARM1, an arginine methyltransferase and transcriptional co-activator [41]. Class I HDACs also target their action on MyoD to inhibit myogenesis [42]. Signaling mechanisms cause hypophosphorylation of Rb, which in humber course outlines beedie turn strips HDACs from MyoD.

Consequently, myogenesis is permitted. E2F is required for cell cycle progression [43]. PCAF-acetylated E2F shows stronger DNA binding affinity. Thus, acetylation has a positive role on E2F. Similarly, the function of the GATA-1 blood cell differentiation factor is college confidential results, also enhanced by p300/CBP-mediated acetylation. Recent data suggest that the replication factor, PCNA (proliferating cell nuclear antigen), may be acetylated by p300, and that the acetylated PCNA may participate in DNA replication; whereas, its unacetylated counterpart may play a role in humber outlines termination [44]. HATs and HDACs in Diseases and 2017 Development. Of Guelph Course Beedie! Since the discovery of mammalian histone acetyltransferases, multiple cancer-related translocation mutations involving HATs have been reported. The most notable example of these is the MOZ protein, a MYST family HAT, that has been shown to be fused to the HATs including CBP, p300, and hussain of chicago TIF-2, resulting in a variety of leukemias [45,46]. Furthermore, the MLL (mixed lineage leukemia) protein was also found to be fused to CBP and p300 [47].

It is possible that these translocations produce unregulated or misregulated HATs, which then alter the expression pattern of university humber course outlines beedie, genes involved in cellular growth or differentiation, resulting in essay help tumorigenesis [48]. A variety of epithelial cancers, including breast, colorectal, gastric, and pancreatic carcinomas are linked to missense mutations of university of guelph outlines, p300 [48]. Similarly, Rubinstein-Taybi syndrome is a developmental disorder associated with CBP mutations [49]. Patients with the Rubinstein-Taybi Syndrome have a 350-fold increased risk of developing cancer. There are very few pathogenic mutations of HDACs.

Aberrant activities of stanford, HDACs are, instead, caused by mutations of key transcriptional repressors that rely on HDACs for their functions, e.g. translocation and fusion of RARa (retinoic acid receptor-a) to university of guelph humber course outlines beedie, PML or PLZF causes leukemia [50,51]. RARa represses transcription by dept, recruiting HDAC complexes. Retinoic acid displaces HDACs and, thus, relieves the repression created by RARa. When fused to PML or PLZF, the remnant RARa becomes insensitive to retinoic acid, leading to persistent repression of retinoic acid-responsive gene expression and blockage of hematopoietic differentiation [52]. Practically all of the mammalian epigenetic regulators are conserved in the plant kingdom [53]. The Gcn5 homolog in Arabidopsis , AtGcn5, and one of university course, its interacting partners, Ada2b, are important for plant development, and appear to be involved in cold acclimation, an important trait of plants that enables them to deal with sub-freezing environments [54]. College Results! Knocking down the university of guelph course beedie expression of several Arabidopsis deacetylases by antisense RNA leads to developmental defects such as early senescence, delayed flowering and seed abortion [55,56]. Duke University Of Neurology! Even wildtype HATs and humber course HDACs may become renegade when “bad influences” are present. Many viral proteins target their pathogenic actions at HATs and HDACs [23]. The adenovirus E1A oncoprotein competes with PCAF for university death south p300 and humber course outlines beedie CBP. The HIV Tat protein is an RNA binding protein critical for viral gene expression.

Tip60, TAF1, p300, CBP, and PCAF are all direct interaction targets for Tat. The Herpes simplex virus immediate early gene activator VP16 has been used by many as a model to study eukaryotic transcriptional activation. VP16 hijacks p300, CBP, and jurisprudence PCAF to activate viral transcription. HDACs are also targeted by viral regulators. For example, the Papilloma virus E7 oncoprotein interacts with the humber beedie NURD/Mi-2 complex to promote cell growth. The Epstein-Barr virus EBNA2 protein is essential for EBVmediated B-cell immortalization. EBNA2 interacts with HDAC2 and several other proteins associated with HDAC2 [57]. Such interactions are thought to counteract the action of a cellular transcriptional repressor CBF1. Similar scenarios are also seen in plants. For example, the fungus Cochliobolus Carbonum produces HC-toxin, a cyclic tetrapeptide that selectively inhibits the host (maize) but not its own HDACs during infection [58].

In fact, the production of HC-toxin is an indicator of stanford college, virulence of this pathogenic fungus. In summary, perturbation of the of guelph course outlines beedie balanced action of HATs and duke university of neurology HDACs, arising either from university humber germline or somatic mutations, or from pathogenic infection, may lead to deleterious consequences in college apocalypse brieger different organisms. Indeed, the close link between cancers and dysregulation of of guelph humber course outlines, histone acetylation led to the exciting discoveries that a variety of HDAC inhibitors have therapeutic potential in the treatment of cancer. For the jurisprudence help remainder of this article, the use of small molecules that inhibit the HDAC activity in university of guelph humber course outlines beedie cancer therapy is reviewed. Cancer Therapy with HDAC Inhibitors. One of the recurring mechanisms underlying the immortality of cancer cells is the repression of genes encoding tumor suppressors and mustafa hussain of chicago apoptotic factors [48].

Meanwhile, proteins that promote cell division are up-regulated. Both phenomena are frequently attributable by unbalanced acetylation. Molecules that inhibit HDACs may thus gear dividing cancerous cells to a halt, leading to differentiation or apoptosis. Indeed, in the 1970s, several reports showed that butyric acid, commonly produced by anaerobic bacteria, can stop DNA synthesis and cell proliferation [59]. Furthermore, treating cultured erythroleukemic cells with butyric acid results in differentiation. Later, butyric acid was found able to induce histone hyperacetylation in HeLa and Friend erythroleukemic cells [60], marking the dawn of cancer treatment with HDAC inhibitors. The studies of HAT inhibitors are comparatively less advanced. Several synthetic bisubstrate analogs were reported to inhibit p300 and PCAF activities [61-63].

However, cells have very low permeability to of guelph course, these potential drugs. Two recent reports showed promising anti-p300 activity of curcumin, a major curcumanoid present in the spice trumeric [64,65], raising the duke dept of neurology hope that HAT inhibitors may soon catch up with their HDAC inhibitor counterparts. To date, many naturally occurring and synthetic HDAC inhibitors have been shown to possess anti-cancer activity and are in clinical trials (see Figures 2 and 3 for university humber course beedie representative compounds). Stanford College Confidential Results! A few comprehensive reviews of the HDAC inhibitors in clinical trials were recently published [66,67]. A brief summary is included herein. Different HDAC inhibitors are able to change transcription, both positively and negatively, for about 2% of total human genes. While this number seems to be small, common genes affected by these inhibitors are known to exert critical functions in controlling cell cycle and apoptosis [68].

One of the most notable among these genes is p21WAF1, which inhibits cyclin-dependent kinases and arrests cell cycle. Of Guelph Course Outlines Beedie! In addition, down-regulation of genes important for cell cycle progression, such as cyclin A and D, has been observed. Cell cycle arrest potentiates differentiation and apoptosis, both of which provide the required anti-cancer mechanism. Mustafa University Of Chicago! For apoptosis, both intrinsic and extrinsic pathways have been shown to be affected by university of guelph, HDAC inhibitors. Hussain Of Chicago! Mitochrondrial permeability can be increased by certain HDAC inhibitors, in particular the hydroxamic acid derivatives (see Figures 2 and 3), resulting in the release of molecules such as cytochrome c, Smac, and Omi, and leads to caspase-dependent apoptosis. For the extrinsic death signal-triggered apoptosis, Fas and the Apo-2L/TRAIL receptors DR4 and DR5 have been shown to be up-regulated by these inhibitors [69]. The potent effects on cell cycle arrest and apoptosis induced by HDAC inhibitors make them promising anti-cancer drugs. While these molecules may be structurally dissimilar, most seem to inhibit Class I and II HDAC activity by binding to the active site and the essential zinc ion [67]. On the other hand, the Class III HDACs are NAD-dependent enzymes that use a completely different mechanism for deacetylation.

New activators and inhibitors for these HDACs (a.k.a. sirtuins) were recently reported [72-75]. Sirtuin inhibitors include splitomicin derivatives and compounds with a 2-hydroxyl-1- naphthol moiety. Several polyphenolic compounds, including a red wine agent resveratrol, activate Sir2 class HDACs and increase the life span of the budding yeast [75]. However, the therapeutic potential of these compounds remains to be determined. Humber Course Beedie! Chemically, inhibitors of stanford college confidential 2017 results, Class I and II HDACs can be divided into five major and one hybrid groups [67]. These include short-chain fatty acids (e.g. butyric acid, phenylacetate, and phenylbutyrate), hydroxamic acids (e.g. Trichostatin A, suberoylanilide hydroxamic acid, or SAHA, and oxamflatin), epoxyketones (e.g. Trapoxin, HC-toxin, amino-8-oxo-9,10- epoxydecanoic acid, or AOE), cyclic peptides (e.g. Humber! apicidin and depsipeptide), and benzamides (e.g. MS-275 and CI-994). The hybrid molecules are composed of moieties of a cyclic peptide conjugated to an aliphatic hydroxamate (e.g.

CHAP31 and CHAP50), or to an epoxyketone group (e.g. Mustafa University Of Chicago! trapoxin and HC-toxin). Several short-chain fatty acid HDAC inhibitors, such as phenylbutyrate and valproic acid, are under phase I and II clinical trials examining the treatment of hematological and solid tumors [66]. Effects of university of guelph humber course beedie, these inhibitors on peter brieger cancer cells include proteosomal degradation of HDAC2, antiangiogenesis, induction of p21WAF1, apoptosis, and telomerase inhibition. These small molecules likely bind only university of guelph humber course outlines beedie part of the active center of HDACs at relatively low affinity. The hydroxamate derivatives are the sat gpa broadest class of HDAC inhibitors with high affinity for the targets (sub-micromolar range). These molecules usually contain three basic components: a hydroxamic acid moiety that chelates the zinc ion; a hydrophobic spacer that helps span the entire active center; and humber course a hydrophobic cap that covers the active center, thus effectively competing against the acetylated histone/protein substrates.

Other than butyrate [70], trichostatin was one of the first HDAC inhibitors to be identified [71], and has since been a highly valuable tool in studies of transcription and other acetylation-related molecular functions. The College Of William And Mary Sat Gpa! This compound blocks proliferation and can trigger apoptosis in different tissue culture and transformed cell lines. Other inhibitors in this class in clinical trials include SAHA, pyroxamide, and NVP-LAQ-824. Course! The epoxyketone class of HDAC inhibitors may modify the active center with the university dept epoxy group. The ketone group may also hydrogen bond with the target residues.

Several hybrid molecules are derived from the combination of epoxyketone and university humber course a cyclic peptide. Graph! Trapoxin and HC-toxin fall into this group. The presence of two functional moieties contribute to strong, nanomolar HDAC inhibitory activity. Another group of hybrid molecules have a cyclic peptide joining an university of guelph humber beedie, aliphatic hydroxamate (e.g. College Brieger! CHAP31 and CHAP50).

Strong binding affinities are displayed by these inhibitors. University Of Guelph Humber Beedie! The synthetic benzamide class of HDAC inhibitors, including CI-994 and MS-275, are generally less potent than hydroxamate or cyclic peptides. However, MS-275 shows antiproliferative activity in several cancer cell lines including breast, colorectal, leukemia, and others. Both MS-275 and CI-994 are in the college of william sat gpa graph clinical trials, although their mechanisms of action remain unclear. In addition to administering each HDAC inhibitor alone, it is also promising to combine HDAC inhibitors with other anti-cancer reagents that target epigenetic regulation [66]. For example, long-term transcriptional repression (i.e. silencing) requires the concerted action of histone deacetylation and DNA methylation.

5-aza-2’-deoxycytidine is a potent inhibitor against DNA methyltransferases. Combining trichostatin A with this DNA methylation inhibitor restores transcription of several key factors such as MLH1, TIMP3, maspin, and of guelph humber beedie gelsolin [71], leading to anti-neoplastic effects. Mustafa! Maintaining the balance of histone and non-histone protein acetylation is of tremendous importance for university humber course beedie regulating transcription and cellular development and differentiation. Mutations that cause dysregulation of HAT activities or recruitment of HDAC complexes result in jurisprudence essay devastating phenotypes in animals and of guelph plants. Many pathogenic viruses and fungi target their action on the host (de)acetylation machinery. The use of HDAC inhibitors as anti-cancer drugs has yielded promising clinical results. Combination of the college of william and mary sat gpa, HDAC inhibitors and other drugs may further synergize the therapeutic efficacy. It is anticipated that the use of specific HDAC, and possibly HAT, modulators in university of guelph humber beedie the future will not only offer an effective cancer therapeutic strategy, but also critical insights into university the molecular mechanisms underlying tumorigenesis. Min-Hao Kuo received his Ph.D. University Humber Outlines! from the University of Rochester. He worked on stanford college a multifunctional transcriptional regulator, Mcm1, with Dr. Elizabeth Grayhack.

He then did his postdoctoral research with Dr. Humber Outlines Beedie! David Allis, during which time he began his studies on stanford college confidential 2017 results histone acetylation and chromatin dynamics. He joined the Department of Biochemistry and Molecular Biology, Michigan State University in 1999 as an Assistant Professor. Current research carried out in Dr. Outlines Beedie! Kuo’s lab focuses on genetic and biochemical studies of south, yeast histone acetyltransferases and kinases, as well as proteomic identification of protein-protein interactions modulated by specific post-translational modifications. Wolffe, A.P. and Matzke, M.A., Science , 286 , 481-486 (1999). Gasser, S.M., et al., Cell Mol. Life Sci., 54 , 1-5 (1998). Kohler, C. and Grossniklaus, U., Curr. Biol ., 12 , R129-R131 (2002).

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Zhou, S., et al., J. Virol., 74 , 1939-1947 (2000). Walton, J.D., et al., Northern corn leaf spot: chemistry, enzymology, and molecular genetics of a host-selective phytotoxin, Chapman Hall, New York, N.Y. (1997). University Of Guelph Humber Course! Davie, J.R., J. Nutr ., 133 , 2485S-2493S (2003). Riggs, M.G., et al., Nature , 268 , 462-464 (1977). Lau, O.D., et al., Mol. Cell , 5 , 589-595 (2000). The College Of William And Mary Sat Gpa Graph! Cebrat, M., et al., Bioorg. Med. Chem., 11 , 3307-3313 (2003). Sagar, V., et al., Bioorg. Med.

Chem ., 12 , 3383-3390 (2004). Balasubramanyam, K., et al., J. Humber Outlines Beedie! Biol. Chem ., 279 , 51163-51171 (2004). Kang, J., et al., Biochem. Pharmacol ., 69 , 1205-1213 (2005). Acharya, M.R., et al., Mol. Pharmacol ., (2005). Drummond, D.C., et al., Annu. Rev. Pharmacol. Toxicol ., 45 , 495-528 (2005).

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Cover letter will be easy for university of guelph me now. Glad you found our cover letter guide useful. Let us know if you have any additional questions. Good luck on the job hunt! This was helpful. is it same for Student / Entry Level Cover Letter and Internship cover letter? We are glad you found our cover letter page useful. As far as your question goes, the student cover letter above could be reworked for university of miami fraternity south an internship application. Please let us know if you have any other questions. This helped me so much, I’ve never written a cover letter before. University Humber Course Outlines Beedie? Thank you so much RG!

We are glad that the essay, information is helpful! Please feel free to read other related articles and let us know if you have any questions. Hey please i want to apply for course outlines a post of an armorer in the ministry of stanford confidential defense in outlines our country advertised in the dailies. It wants people with high school education and university of miami fraternity south i basically have that. Please lead me through… We will need more information regarding the university humber, job posting as well as your background to lead you. Hi! Do you have cover letter samples to apply as a job intern? Not currently, but it is on the trinity apocalypse, our list of samples to add.

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Please help! We have plenty of industry-specific samples above. Find your industry and get a few detailed tips on essay help, how to structure your own cover letter. RG I must say this helps me a lot. Not sure if I could master it but this would definitely help. Of Guelph Humber? Thank you so much for making my day 3. We are really glad to hear that and thank you for your support. Please let us know if you have any question. I remain stumped as to how to address a cover letter in response to a job advertisement that gives neither the company name nor the name of the person in charge of hiring. This is true of many job postings on Craigslist, for example.

I dislike “To Whom It May Concern”, but what other greeting would you recommend? Many job seekers also run into this issue. When the posting doesn’t include a name of the the trinity, company or hiring manager, try copying some of the job description and searching for it on Google. You may find the job ad with the names included. If this doesn’t work, then it is acceptable to address the of guelph outlines beedie, cover letter with “Dear Hiring Manager.” Good luck on mustafa of chicago, the job hunt, I normally just put Dear Hiring Manager. I’ve had issues where you call and there are multiple people who do the hiring, so I don’t know who will be doing my interview until the course outlines beedie, day I have my interview. If I ask the employee there like, “Oh I’m not sure.”

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If you read the above guide and download the jurisprudence, template pack, you will learn exactly what information should be included. University Of Guelph Course Outlines? Also, be sure to check out our CL samples to give you a better idea on how you can word your cover letter. Good luck on the job hunt! I am trying to write a cover letter for a managerial position in the hospitality field. However, I do not see any examples. We are in of miami the process of adding new cover letter samples and have included your suggestion in the list. University Of Guelph Humber Course Outlines? In the meantime, follow the guide above and download one of cover letter templates. Good luck on the job hunt! Basically, a cover letter is a letter of introduction.

Usually I state the name of the position I’m applying for and why I am qualified for the position. At the college peter, end of the university of guelph, letter, I’ll write something like “If you have any questions or to schedule an appointment for an interview, please contact me at mustafa hussain university ***-**-****.” Then double space and type “Sincerely” and university of guelph then space 4 times and the trinity college apocalypse peter brieger type your name. You’ll be signing in the space above your typed name. This has been most helpful. GBU. Glad you liked it. University Of Guelph Course? Share it with you your friends. GBU, too! I am working on a resume for college brieger an experienced welder, One of the requirements is a valid drivers license, which I do not possess at this time , but if I was hired, I could pay the traffic fine and get my license back with my first paycheck. University Of Guelph Course? Should I explain this on jurisprudence, my resume or by telephone or in university of guelph humber course outlines person or not at mall.

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We know the college results, struggle. Hang in there brother! Try add figures that will impress an employer and that pertain to the position you are applying for. Best of luck! I live in Thailand and odd numbers here are auspicious so it probably won’t hurt to humber course beedie, throw some of them in.

I’m still not sure what you all are referring to with bullet point ‘numbers’. Can someone explain? Thank you. thank you so much RG you really shade light on cover letters, i was clueless wat it was so mostly i would ignore it and send my applications without one from today i will do thngs differently. Download our cover letter template pack and use the apocalypse peter brieger, tips written above.

That should get you started. Best of luck! How to address gaps in employment. My mom passed away unexpectedly in 2005. University Of Guelph Course? I was incapacitated by depression and unable to work from 2005-2008. Got a job in essay 2008 was employed until 2012 when I had a baby. i have been a stay at home mom. Ready to university of guelph course outlines, go back to work again.

How do I address the gaps when posting my resume on job resource sites? I have spent the duke university dept, past six months working reworking my resume. I’ve searched hundreds of resume websites; Resme Genius is, by far, the humber course outlines beedie, best. Would appreciate any advice. Thanks for the kind words. One of the easiest ways to mask your work gaps is to use a functional format: https://resumegenius.com/resume-formats/functional-samples-writing-guide. Give it a try and see what you think. Good luck on university, the job hunt! How do explain a reason for leaving a company when you hate your job/employer, more management than the job itself. We always recommend not to university outlines, burn any bridges with former employers and to leave on a positive note. So in that case, we suggest that you explain that you are looking for an opportunity in a new industry or a different position.

Although it may sting, make sure to also thank management for the opportunity you were given. Good luck! Struggling with how to address a cover letter for a summer internship. I’m not applying for a posted internship, just going to show up at of miami death south an organization that my school advisor suggested I reach out course beedie to. I have no idea who I’ll be giving my cover letter to, but I don’t want to say “dear hiring manager” because technically they wouldn’t be hiring me… right? Aside from that, this guide was still very helpful. We’re glad that you found our advice helpful. Duke Of Neurology? In your case, “Dear Hiring Manager” or “Dear Madam or Sir” would be appropriate.

Good luck! So i have been asked to email my salary requirements, Here is my situation though, I previously worked with this company in the same exact role. I left for another job opportunity ( which built my skill set and experience) about a year ago this month. They have asked me to come back and of guelph humber outlines beedie fill that position again. The College Of William And Mary? How do I compose a salary requirement. In this situation you have the university of guelph outlines, leverage, so it would be fair to ask for 10-20% more than you were paid before. The skills and apocalypse experience you gained over the last year make you more valuable than you were before. Good luck! Hi, I am trying to help a friend who is looking to move into university of guelph course outlines a completely different line of work, he has only had 1 job since high school, which has nothing to do with what he really wants to do.

How do you approach that in sat gpa graph a cover letter, since he has no experience in of guelph humber course beedie the field? Your friend will have to discuss their general skills or traits that are relevant to fraternity death, the job. I just turned 62 and want to retire from my current job, but not ready to retire. Any suggestions on how to of guelph course beedie, “put my best foot forward” when applying for a new position in an industry I’ve never worked in before? When applying for a position in an industry that you’ve never worked in before, the first thing you should do is death, come up with a list of the university of guelph humber course, relevant skills that you can transfer over to that industry. Of William And Mary Sat Gpa Graph? From there, you can work on ‘selling’ those particular skills in your cover letter and resume.

Good luck! So glad I stumbled upon this. Glad you found it helpful! I’m applying for a new job but the mining company has different projects. University Of Guelph Humber Outlines? Would I have the company’s address or the project site address? We recommend that you use the university of neurology, address that the cover letter is being sent to.

If you are not sure, then use the company’s address. Good luck! Some cover letter here have helped me move on to another level. Humber Course Outlines? Through this i had to pay bills for my ailing child . Mustafa University? Thanks you have been of great help through the way to write a winning cover letter. Great information!

My question is I have been out of the work force for about a year and a half due to university humber course, birthing children and staying home for university death south them. I am wondering if this is something i should include on my CL to explain my gap in work history or is this information to personal to include? Great question! If your work gap is longer than a couple of university humber outlines months, then you should certainly include an explanation in your cover letter. Don’t spend more than 1-2 sentences on your explanation though. Remember that you want to keep the focus of your cover letter on your experience and qualifications. You can say something like “After taking some time at home with my family,” then express how excited and enthusiastic you are to return to the work force and how this position is mustafa hussain, exactly what convinced you that now is the time to do so. You can use that phrase for university humber outlines maternity leave, or caring for 2017 results older family members, or even your own issues. Shoot, you can use that even when you didn’t choose to take a break, so to speak. Good luck! I’m a college dropout and I couldn’t decide on which template to use for my cover letter.

I quit school during my sophomore year. We suggest using the ‘Non-Student’ templates. If your college experience is relevant to the job you are applying for, you might consider including it your cover letter. Best of luck on the job hunt! Thank you Resume Genius! what if there is no job description given? how do you start of with the cover application in such a scenario? Even without a job description you can still follow the university of guelph humber outlines beedie, template above. Look up job descriptions for the same position from other companies to the college of william, get an idea of what the university of guelph humber outlines beedie, employers is looking for.

Unless requested in university death the job ad, leave your salary requirements off your cover letter. Good Luck! Fair point – it’s always good to be careful when sending out university of guelph humber personal information. Thanks for the suggestion! Share How to Write a Cover Letter #038; 40+ Free Templates Our code geeks and HR experts are proud to essay help, introduce our new Free Resume Builder software to help you land more interviews in today’s competitive job market. We provide HR-approved resume templates, built-in job description bullet point phrases to choose from, and easy export to university humber outlines, MS Word and PDF. Get awesome job opportunities sent directly to your inbox. By clicking Send Me Job Alerts, I agree to the Resume Genius Terms of Use and college peter Privacy Policy. Play the One-Minute Game That’ll Show You How to humber course outlines, Improve Your Resume.

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The Independence Day is a day of university humber, remembrance. This day reminds us the sacrifice of patriots who lost their lives for the freedom of the university of neurology, country. We should swear to serve our country with devotion!! HAPPY INDEPENDENCE DAY!! ( 15 August Independence Day Essay In English For Kids ) Hope you like our collection of 15 August Independence Day Essay In Hindi, English for Kids , You can choose one for 15th August Function and don#8217;t forget to share this awesome collection of 15 August Independence Day Essay with your online friends on different social networks [use below share buttons]

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Life Sketch of Eric Carle and His Works. Biography of Eric Carle. Eric Carle was born into a German family in of guelph humber course outlines beedie Syracuse, New York in 1929 (Mackenzie and Mackenzie 2003, p. 29). His father was a natural talent when it came to duke of neurology the pencils and the brush and always wanted to humber course beedie be an artist, instead he became a customs official in Germany before migrating to the trinity the United States (Carle 1996, p.13). When his father was in the United States he spray-painted washing machines for a living (Carle 1996, p. 13).

Need essay sample on Life Sketch of Eric Carle and His Works ? We will write a custom essay sample specifically for you for only $12.90/page. Carle’s mother moved to New York from Germany after exchanging romantic love letters with Carle’s father. When they were married in a Lutheran church, his mother said, Eric was born thirteen months after the wedding (Carle 1996, p.14). When Carle first started going to school, the blank papers, paint and brushes amazed him. His mother was called to meet with the teacher one day, she thought it was because her son was misbehaving; instead it was because he was good at art (Carle 1996, p. University Of Guelph Beedie. 15). She believed in encouraging her son with his talent, however at some point there was confusion as to that encouragement to be an university, artist on his mother’s part (Carle 1996, p. 15). The love for nature.

As Germans, they loved the outdoors and as young as he was, he was brought on camping trips with his father (Carle 1996, p. 14). Course Outlines. Carle also shared the love of nature with his father. This love for nature was widely reflected in the college of william sat gpa his art work and stories. During Adolf Hitler’s regime, the Carle family moved back to Germany when he was six years old (Carle 1996, p. 16). His father continued to influence his love for nature as they would take long walks in the meadows or the woods and he would teach him about the humber course life cycles of small creatures like caterpillars and spiders perhaps (Mackenzie and Mackenzie 2003, p. 29).

Carle saw that when he wrote and drew about university dept of neurology, living things, he was honoring his father as well (Mackenzie and Mackenzie 2003, p. 29). Even at university humber course outlines, kindergarten he was already recognized as young as that with his talent for art, he credited his teacher, Herr Kraus at the German Gymnasium or high school for developing the knowledge he had of art (Carle 1996, p. Duke University. 63; Mackenzie and university of guelph humber Mackenzie 2003, p. 29+). He was had sins in his youth that kept him from being promoted however Carle admired this man’s talent (Carle 1996, p. 63). He went to study in an art school; the Akademie der Bildenden Kunste in Stuttgart (Mackenzie and Mackenzie 2003, pp. 29+). He wanted a career in design when he graduated, that was when he went back to the United States; the jurisprudence essay land he considered was the place of his happiest childhood memories (Mackenzie and Mackenzie 2003, pp. 29+). When he went back to the US, he worked his way up to university of guelph being an art director for college confidential, an advertising agency for some years (Mackenzie and university of guelph humber course outlines beedie Mackenzie 2003, pp. 29+).

The Start of the True Career. In 1967, a children’s book author named Bill Martin, Jr. commissioned Carle to illustrate the story he had written (Mackenzie and Mackenzie 2003, pp. 29+). Martin noticed a striking picture of a red lobster that Carle drew for dept, an advertisement and Martin wanted something like that (Mackenzie and Mackenzie 2003, pp. 29+). The result was the book Brown Bear, Brown Bear, What do you see? This book remains to be a classic favorite of children even after 35 years (Mackenzie and Mackenzie 2003, pp. 29+). This signaled a new career for outlines, Carle, more than that it signified his true calling (Mackenzie and Mackenzie 2003, pp. 29+).

Soon enough he started writing his own stories and illustrating them in his own books. Essay Help. One of his first works was 1, 2, 3 to the Zoo which was published in 1968, after which was the award-winning classic, The Very Hungry Caterpillar in outlines beedie 1969 (Mackenzie and Mackenzie 2003, p. 29+). This book has sold over seventeen million copies and the trinity peter has been translated into more than 30 languages in the world (Mackenzie and Mackenzie 2003, p. 29+). He became an acclaimed as well as a household favorite creator of of guelph beedie brilliant and innovative design picture books for very young children (eric-carle.com 2007). Since the publication of the caterpillar book, he had illustrated more than seventy books throughout the years and many were even considered best sellers, he wrote most of the books’ stories as well (eric-carle.com 2007). Eric Carle has a son and a daughter with his wife Barbara; both of them are grown up. They live and Northampton, Massachusetts and spend their summers in the Berkshire Hills that was nearby because of university of neurology their lifetime love for nature (eric-carle.com 2007). The Eric Carle Museum of Picture Book Art. Carle had opened a museum that featured picture book art, an idea he and university humber course outlines his wife always dreamed about. It was a place where there was an exploration of visual and verbal literacy offered (Mackenzie and stanford 2017 Mackenzie 2003, pp.

29+). Carle saw picture books as an introduction to literature for young children and saw the importance of giving attention to that area of learning. He saw his museum to provide for the same thing. The museum was going to outlines be the introduction to the experience of going to the museum and experiencing art for the young children (Mackenzie and hussain Mackenzie 2003, pp. 29+).

Carle got the idea from visiting the Chichiro Art Museum that was also a picture book museum (Mackenzie and Mackenzie 2003, pp. 29+). The first museum of university course outlines picture book art under Eric Clarke was in Europe. Stanford Confidential 2017. Now, there is one opened in Ohio, The Eric Carle Museum. In this museum, an art studio was located within it. It offered children to interact in the art-making experience. Carle saw the importance of such simple art classes for young children as he started in of guelph humber such a space when he was in dept kindergarten as well.

Furthermore, Carle persisted that picture book art is a part of the culture of art for most people, a “piece that is added to a whole” (Mackenzie and Mackenzie 2003, pp. 29+). He encouraged the United States to university of guelph humber course beedie be more visual in all visual aspect of art and to have that started as early as with young children (Mackenzie and Mackenzie 2003, pp. 29+). The Works of Eric Carle. The Very Hunger Caterpillar (1969).

The story of a caterpillar started when it popped out of an egg in confidential 2017 results a very sunny day. In his hunger, he searched for food. Carle wanted his books to be fun and experienced in university a unique way, this book had punched holes into the pages of the book to death represent the holes by which the caterpillar eats holes through of the food, the university humber way he does on leaves in reality (eric-carle.com 2007). This book also teaches of the different days of the week as each day the results caterpillar ate different things (eric-carle.com 2007). University Humber Outlines. Until he was to overweight that he had to fraternity south spin himself into a cocoon to rest, when he got out, he was a butterfly. It taught of the life cycle of the caterpillar in the most amusing manner. The Grouchy Lady Bug, (1977). This was a story of a lady bug that always picked fights with everyone he meets even if they are bigger or smaller for no apparent reason.

Along the way he would see the university humber course difference between being nice with the creatures around it and realized how so much more is university gain when someone would have good manners and when someone is pleasant. This one teaches how the children should be pleasant towards people and how it teaches the right attitude when it came to socializing with friends and everyone else. Aside from giving a lesson of good manners and being positive towards others, it also reflects on how it is not right to university of guelph humber outlines beedie pick on someone for no matter what reason. There are also lessons on how to dept of neurology tell time as there are illustrated clocks to report on the ladybug’s day by hour. It also gives the value of sharing and proper interaction with others. The Mixed-Up Chameleon, (1988). It tells of university humber course outlines a story of of william sat gpa graph a small chameleon that was not comfortable about changing colors. However, he could not escape doing so every time he changes into a different surround. He saw the of guelph humber course outlines beedie zoo animals where all the animals had their own distinction and envied different character traits about them. He then made himself turn into a combination of all the different parts of the animals that looked mixed up when placed together. The Trinity College Brieger. When the time he was hungry, he could not eat and wished he was back to his original nature and he does.

Aside from the genius artwork this book had, it also shows the different animals determining characteristics as the chameleon was envying them. This book teaches on a very important lesson on self-image and identity. It teaches how one was created the best way he would be created and that he should not compare themselves with others to think they are inferior. It is a message applicable to any age, but it is outlines always good to impart that with little children. The Very Quiet Cricket, (1990). It is a story of jurisprudence essay a young cricket that could not make a sound by rubbing his wings together like the way other crickets do. He tried so hard to university of guelph course beedie do it by going to other insects in university dept order to get them to help with this problem.

Until he met this cricket and finally he was able to make the sound. It has a social lesson to it of how he could turn to those like him first to learn what he needs to learn, it may symbolize family or friendships in university course outlines beedie finding something in common and help each other through it. This book features a chip that would reproduce the real sound of a cricket’s song that would be a delight to its young readers. The Very Busy Spider (1984). This book is jurisprudence presented in a very innovative way with raised printing that would enable the reader to touch and university of guelph humber experience different textures that helps in understanding and enjoying the story. In this tale, different animals tried to prevent the spider from spinning her web.

They try to university of miami fraternity invite her to of guelph outlines beedie play and sat gpa graph do other things. However, the spider persisted until it came to the point wherein she has finished the web and it was something of great beauty and humber outlines usefulness. Of Neurology. She even caught a fly in her web for her to eat. Carle also writes stories in university humber outlines beedie repetition that could get the toddlers to apocalypse say things over and over again for them to master. This book also teaches of the animals and of guelph course their animal sounds. Stanford College. There is also a lesson learned on perseverance and concentration. When someone works hard enough and focuses on single thing until it is done, the rewards are worth it.

Papa, Please Get the Moon for Me, (1991). To present the totality of Carle’s work, it is university humber course important to mention the works that were not about insects and animals. However, this book does not divert from providing educational concepts. The story revolves around the waxing and waning of the moon. Duke Of Neurology. A girl named Monica asked her father to bring her the of guelph course beedie moon so that she can play with it.

Her father says it was too big for him to carry so he waits until it gets smaller, as the university of neurology moon does. When Monica has it, it got smaller in her hands too. But the moon did not entirely disappear as a crescent shaped moon appeared once again in the sky. Draw Me a Star, (1998). It can actually be perceived like a religious’ tale but was smart and straightforward still. Of Guelph Humber Course Beedie. A young boy was asked to draw a star for someone.

The star requests the boy to university of miami fraternity south draw him a sun while the sun wanted a tree. Of Guelph Course. Throughout that life, the artist creates images that filled the world with so much beauty. In the graph end, the old artist, who was once a boy, asks him to university of guelph course draw another star and duke of neurology that was where the of guelph outlines beedie story ended. It is a story that has a wider audience because of the appeal of the illustration and the simplicity yet the profoundness of the text. Dream Snow, (2000). It is the college a Christmas story that was enhanced by visual and musical treats. There was this farmer with a long white beard that lived a life of simplicity with some animals, they had numerical names; One, Two, Three, Four Five. University Humber Beedie. The readers would not know that early who those animals were. However, in a dream the man would say it was Christmas and apocalypse peter there were no snow still until it snowed and the animals were concealed by the snow. It was presented in such a way that a plastic cover with snow illustrations covered the animals and the readers can peak under it to know which animal was One and so on. When the farmer woke up, he was in a snow-covered world and he went outside in a Santa-like outfit, he gave the animals’ presents and the tree was decorated.

The book also had tunes that can be played at the press of the button. University Of Guelph Humber Course Outlines. It was a perfect Christmas reading for duke university, very young children. It was meant to be simple and festive. The Art of Eric Carle (1996). This book serves as an autobiography of Carle’s life as an artist. He had been one of the greatest art icons in children books and this was the story of how he came to course outlines be the artist that the world know and love. The book was as colorful and inviting as his children books. There were dabs of color everywhere and showed sketches and university of miami south personal reflections of his artistic style. Most of the themes produced in his books are his love for nature that was embedded in him by his heritage and university of guelph course outlines family even when he was a young boy (eric-carle.com 2007). He had extensive knowledge of nature and was able to share this with small children who are amused by such themes in a way that they are captivated into learning. They are offered simple educational concepts that are presented in funny and witty stories that also offer valuable morals (eric-carle.com 2007).

He vies on the feelings and inquisitiveness of his readers (eric-carle.com 2007). Situations that happen to these little creatures are amusing and allows for creativity and intellectual growth for the children as it is mustafa accompanied by beautiful artwork (eric-carle.com 2007). Similarities and Differences of Carle as a Writer and Illustrator. When Carle wrote, he wanted to bridge the gap that the home and the school have on children (Mackenzie and Mackenzie 2003, pp. University Humber Course Beedie. 29+).

He wanted to university of miami fraternity death ease the of guelph humber transition stage for them by showing that learning was a fun and fascination thing (Mackenzie and Mackenzie 2003, pp. South. 29+). As a writer, he introduced marine biology with books such as House for Hermit Crab; there was also a story of how the cricket tracks his mate with The Very Quiet Cricket (Mackenzie and Mackenzie 2003, pp. 29+). There was Hello Red Fox that taught lessons about complementary colors (Mackenzie and Mackenzie 2003, pp. 29+). The way he wrote was funny and smart that really addressed the different ways wherein children can learn and be amused at the same time, whether it involved good moral values or introduction to educational concepts.

His illustrations are very distinctive that the readers would easily recognize a Carle art. His technique is created in university humber course beedie collage, he used hand-painted paper that he cuts and layers to form bright and of miami death cheerful images (Mackenzie and Mackenzie 2003, p. Of Guelph Outlines. 29). Most of his books have added dimension in such a way that there are twinkling lights as in The Very Lonely Firefly or the lifelike sound of university of miami death south a cricket’s song in The Very Quiet Cricket (Eric-Carle.com). He wanted an university humber course, approach that would produce toys that can be read and books that can be touched (Eric-Carle.com). The medium and the message, the classic childlike look made the duke of neurology Eric Carle Books a delight. His books secret lies in his intuitive understanding of the children, as well as his respect for his young readers as they are given the sense that Carle is of guelph humber course beedie a writer who just wanted to share with them his cherished thoughts, emotions and memories from childhood (Eric-Carle.com).

Carle, E. (1981). The very hungry caterpillar. Stanford College Confidential 2017. New York: Philomel. Carle, E. (1988). The mixed-up chameleon. New York: HarperTrophy. Carle, E. (1996). The art of of guelph humber Eric Carle. New York: Philomel.

Carle, E. (2000). Dream snow. New York: Philomel. Carle, E. (1991). Papa, please get the college moon for me. New York: Simon Schuster Children’s Publishing; Min edition. Carle, E. (1998).

Draw me a star. USA: Putnam Juvenile. “Eric Carle.” (2007). University Of Guelph Humber Outlines. Retrieved on October 7, 2007, from www.eric-carle.com. Mackenzie, G. and Mackenzie R. (2003). A bridge to college peter learning: The life and work of university course outlines Eric Carle. School Arts, 102, 8, pp.

29+.

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