gap junctions

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During the course of evolution of single cells to multicellular organisms, new genes and functions were developed to assure coordinated regulation of cellular processes within these more complex entities. In multi-cellular organisms a delicate balance of regulatory and integrative mechanisms has to be achieved in order to maintain a relatively stable internal environment in the face of variations in the external conditions. This state of equiliium, termed homeostasis, is controlled by three major communication processes 1) extracellular communication, ) intracellular communi-cation, and ) intercellular communication. The integrated control of these three communication routes permits an organism to proliferate, to differentiate, to undergo apoptosis (programmed cell death) and to adapt/respond to stimuli (Trosko and Ruch, 18).

It has been suggested that the gain in ability of more complex organisms to regulate cell growth, differentiation and apoptosis is directly related to the appearance of intercellular communication. This notion is supported by several studies that have shown that this type of communication is severely impaired in cancers, which often exhibit behavior characteristic of a single-cellular organism. Processess typical to these organisms such as uncontrolled cell proliferation, inability to terminally differentiate and an altered apoptosis rate are often found in cancerous cells (Trosko and Ruch, 18). Besides growth control, intercellular communication plays an essential role in a variety of physiological processes including electrical coupling, tissue response to hormones, and regulation of emyonic development.

The diversity and the vital character of these functions for the survival of an organism clearly demonstrate the importance of understanding the mechanisms involved in the control of intercellular signaling. Intercellular communication is mediated through the gap junction communication channel, which has become one of the focal points of the research in the field with a particular emphasis on the regulatory aspects of gap-junctional intercellular communication (GJIC). The insight gained from these studies can lead to the development of new therapeutic approaches to a variety of patho-physiological states caused by abnormal intercellular communication. Write my paper on gap junctions for me

1.1 The Gap Junction Communication Channel

1.1.1 Gap Junctions

Gap junctions are sites between adjoining cells that allow for direct intercellular passage of molecules smaller than 1 kDa. These channels are relatively non-specific and the observed selectivity is based mainly on molecular size, allowing the passive diffusion of small molecules and ions such as water, cAMP, sugars, nucleotides, amino acids, fatty acids, small peptides and drugs, but blocking the transfer of proteins, complex lipids, polysaccharides, nucleic acids and other large molecules. Recent studies have challenged the apparent non-specificity of GJs hinting at more complex regulatory mechanisms behind the control of GJ permeability to certain compounds. Gap junctions are found in almost all multicellular organisms of the animal kingdom, both inverteates and verteates, and in almost all tissues with the exception of a few terminally differentiated cells such as erythrocytes, lymphocytes, skeletal muscle and adipocytes (Kumar and Gilula, 16).

An integral memane protein called a connexin is the main structural unit of the gap junction channel (Fig. 1, A). Connexins comprise a multi-gene family with at least twenty mammalian connexin genes discovered to date. The expression of a particular connexin type is strictly correlated with the cell type and tissue in which it is found. Gap junctions have a relatively simple molecular organization they display a hierarchy of assembly with six connexin subunits forming an integral complex called a connexon (Fig. 1, B). The connexons from the plasma memane of the neighboring cells align and interact to form the gap junction channel (Fig. 1C). In turn, gap junctions cluster in specific regions resulting in the formation of gap junction plaques (Fig. 1D).

Figure 1. The Structure of a Gap Junction. Schematic model of gap junction showing the arrangement of six connexin subunits to form a connexon, which contains the central channel connecting the cytoplasm of the two adjoining cells.

All connexins appear to have the same topology in the plasma memane with the polypeptide spanning the lipid bilayer four times, with both N- and C- termini located in the cytoplasm. One of the four transmemane domains, M, is amphipatic in nature and contributes to the lining of the channel. The two extracellular loops (E1 and E) (Fig. 1A) negotiate the docking of the two opposing connexons by facilitating the initial interactions between them. Each loop contains a characteristic arrangement of three cysteine residues that are thought to enhance the rigidity of these extracellular segments necessary for the docking of the two connexons and formation of a gap junction. The intracellular loop between the transmemane domains M and M as well as the C-terminus exhibit the greatest variability among different connexins and therefore are believed to be important for regulation of the protein (Kumar and Gilula, 16).

The X-ray crystallographic study of a recombinant gap junction memane channel lacking its C-terminus has revealed that the outer diameter of a GJ within a memane has a diameter of ~ 70 Å with the intercellular portion of the channel narrowing to ~ 50 Å (Unger et al., 1). The vertical cross-section of the interior of the channel disclosed that its diameter narrows down from ~ 40 Å to ~ 15 Å within its transmemane region in proceeding from the cytoplasmic to the extracellular portion of the bilayer. The channel widens again to ~ 5 Å within its extracellular section. Taking into account the contributions from the amino acids side chains, the narrowest diameter of the GJ is about 5 Å (Unger et al., 1).

1.1. Assembly and Degradation

Similarly to other integral memane proteins, "connexins are synthesized at the endoplasmic reticulum (ER) memane in a typical process that involves a signal recognition particle, an integral signal anchor sequence, docking of the nascent-chain/ribosome complex to the translocon, and cotranslational integration of the connexin polypeptides into the ER memane" (Falk, 000). The final topological organization of the connexins is attained at the level of their ER memane integration (Falk et al., 14; Ahmad et al., 1; Diez et al., 1). The exact location at which connexin oligomerization takes place has not been clarified. Several studies have reported that connexins are assembled into oligomers within specialized region of the ER (George et al., 18, 1), either the intermediate compartment or ER-Golgi Intermediate Compartment (Schweizer et al., 10). However, other studies in NRK and CHO cell lines suggested that oligomerization of endogenously expressed Cx4 takes place after exit from the ER in late Golgi memanes (Musil and Goodenough, 1). These observations strongly suggest that the process is likely cell - type specific. Connexins are trafficked to the plasma memane by a consecutive series of vesicle fusion and budding from the ER through the Golgi apparatus by following the general secretory pathway (Musil and Goodenough, 11). The process of targeting connexons to the plasma memane is not currently understood but two general models have been proposed. The first involves the direct transport of the connexon to the GJ site whereas the other entails an indirect transport of the connexon by lateral movement within the plasma memane towards the gap junction site following its insertion at a distant location (Falk, 000). Once localized into the plasma memane, the connexons from the neighboring cells dock with each other via interactions of their connexin subunit extracellular loop domains forming a complete GJ channel. GJ channels in turn aggregate to form GJ plaques. The formation of plaques is assisted by calcium-dependent cell-adhesion molecules such as E-cadherins (Laird et al., 15; Laird 16). The cytoskeletal proteins ZO-1 and --spectrin have also been reported to play a role in this process (Toyofuku et al., 18).

The degradation and turnover of gap junctions are the least understood aspects of connexin processing within the cells. The turnover of connexins is relatively fast compared to other integral memane proteins with the reported half-lives in the range of 1 h for Cx4 and Cx45 in cultured cells or tissues (Beardslee et al., 18; Saffitz et al., 000) contrasted with 17 100 h for integral memane proteins measured in hepatocytes (Chu and Doyle, 185). The current evidence suggests that gap junctions are removed from the memane by internalization of entire channels within large fragments of GJ plaques (Severs et al., 18). The subsequent degradation process involves both lysosomal as well as proteasomal pathways (Laing and Beyer, 15; Laing et al., 17; Laird, 16; Rahman et al., 1; Musil et al., 000).

1.1. Gap Junctions and Their Role in Human Diseases

Gap junctions play an essential role in a number of diverse physiological processes. Charcot-Marie-Tooth (CMTX) disease was the first pathology associated with a connexin. This progressive neuropathy results from myelin disruption and axonal degeneration of peripheral nerves and is caused by a mutation in Cx (Martin et al., 000). This connexin has a wide tissue distribution and is one of the major GJ proteins in liver as well as in oligodendrocytes. The fact that a mutation in Cx results in only a mild neuropathy suggests that connexins can compensate for the loss of other connexins in different tissues. Other diseases associated with mutations in various connexins include dominant and recessive hearing loss (Cx6, Cx1, Cx0), dominant epidermal disease (Cx1, Cx0., Cx0), dominant skin disease caused by abnormalities in keratinization, cataracts (Cx46, Cx50), and abnormal cardiac development (Cx4) (Table 1) (Bennett, 14; Kelsell et al., 001). Aberrant regulation of GJIC has been implicated in several types of neoplasia (Andrade-Rozental et al., 000). The majority of tumors express less connexin, have fewer gap junctions and exhibit a decrease in GJIC (Cesen-Cummings et al., 18; Yamasaki, 10).

Table 1. Human diseases associated with mutations in connexin genes (adapted from Kelsell et al., 001)

Connexin (gene) Human disorder

Cx (GJB1) X-linked Charcot-Marie-Tooth Disease neuropathy often associated with hearing loss

Cx6 (GJB) Dominant and recessive non-syndromic moderate-profound sensorineural hearing lossDominant epidermal disease (palmoplantar keratoderma) and Vohwinkels syndrome

Cx1 (GJB) Recessive non-syndromic moderate-profound sensorineural hearing lossDominant non-syndromic high frequency hearing lossDominant skin disease (Erythrokeratoderma variabilis)Dominant sensorineural hearing loss and neuropathy

Cx0. (GJB4) Dominant skin disease (Erythrokeratoderma variabilis)

Cx0 (GJB6) Dominant hearing lossCloustons hidrotic ectodermal dysplasia skin disease (palmo-plantar keratoderma), hair loss, nail defects and often mental deficiency

Cx4 (GJA1) Association with visceroatrial heterotaxy

Cx46 (GJA)Cx50 (GJA8) Dominant zonular pulverant cataract

1. REGULATION OF GAP JUNCTIONS

1..1 General Aspects of GJ Regulation

GJ regulation is a complex process that can be achieved by aoad range of mechanisms that can generally be categorized into two major groups. The first category includes all the processes that affect the formation and levels of GJs starting with Cx gene expression through translation, oligomerization into connexons, transport to the memane, assembly into GJ and plaques, gating and finally degradation. The impaired GJIC caused by down-regulation of Cx in certain types of neoplasia is illustrative of this type of regulatory mechanisms. The second group includes all the modes of regulation that do not alter the cellular levels of GJ but affect its functionality, which is directly related to the fluctuation of the channel between the open and closed states. This GJ gating can be effected by a variety of exogenous and endogenous factors including extracellular soluble factors (mitogens, hormones, anesthetics and drugs) and biomolecules (oncogenes, growth factors, tumor promoters) (Berthoud et al., 000; Evans and Boitano, 001). These agents can exert their GJIC modulatory action either directly by introducing structural modifications to the channels, or indirectly for example by perturbing the lipidic environment in the vicinity of the channel and thus affecting its conformation (Hossain and Boynton, 000). The majority of GJIC modulators act by initiating complex signaling pathways leading to the activation of various kinases, phosphatases and adaptor proteins.

1.. Regulation of Gap Junctions by Phosphorylation of Connexins

Most connexins (including Cx1, Cx, Cx7, Cx40, Cx4, Cx45, Cx46, Cx50, and Cx56) contain protein kinase "consensus phosphorylation sequences" and have been demonstrated to be phosphoproteins (Lampe and Lau, 000). The majority of the phosphorylation events occur on the C-terminal cytoplasmic tail, which has been shown to be important for regulation (Fig. ). It is interesting to note that the Cx4 truncated mutant that lacks a C-terminal retains its ability to form functional channels in Xenopus oocytes or SKHep1 cells, albeit with altered permeability and electrophysiological properties compared with those of a wild type Cx4 channel (Fishman et al., 11; Dunham et al., 1). A Cx mutant that is truncated at its C-terminal has been linked to CMTX disease (Rabadan-Diehl et al., 14). The above examples emphasize the important regulatory role of the C-terminal domain in channel gating and possibly in the rates of connexin transport, assembly and turnover.

A variety of protein kinase modulators have been applied to investigate the effects of phosphorylation on gap junction function, revealing that phosphorylation events are connexin and cell-type specific. However, some general trends have been observed across different connexins. For example, compounds that increase levels of intracellular cAMP tend to enhance GJIC. This observation has been attributed to increased rates of connexin transcription, increased levels of connexin RNA or protein (Darrow et al., 16), changes in connexin phosphorylation status (Traub et al., 187), as well as changes in Cx4 transport (Atkinson et al., 15) and GJ conductance (Spray et al., 11; Jongsma et al., 000). On the other hand, agents that activate PKC such as phorbol esters generally diminish GJIC. Staurosporine, a protein kinase inhibitor, has been shown to increase GJIC in SKHep cells expressing Cx4, whereas okadaic

Figure . A schematic representation of the primary structure of rat Cx4. Phosphorylation sites in Cx4 targeted by V-Src, MAP kinase and PKC are indicated.

(Borrowed from Lampe et al., 000)

acid, a phosphatase inhibitor, has had the opposite effect on GJIC (Moreno et al., 14). These studies taken together demonstrate that phosphorylation is an important regulatory mechanism for GJ function. However, the signaling pathways responsible for these observations have not yet been fully deciphered.

1.. Phosphorylation of Cx4

Cx4 is the most common connexin expressed across aoad range of cell lines and tissues. The phosphorylation of Cx4 can have both an inhibitory and stimulatory effect on GJIC. The primary sites of Cx4 phosphorylation are multiple serine residues (1 residues) on its C-terminal domain (Fig. ). The extent of phosphorylation on threonine residues is significantly smaller (Kanemitsu et al., 17). Cx4 phosphorylation on tyrosine has been reported only in cells expressing oncoproteins such as v-Src or v-Fps (Kurata and Lau, 14). The protein kinases PKC, MAP kinase and pp60src were shown to phosphorylate Cx4 (Lau et al., 000). Many other protein kinases could also be involved in Cx4 phosphorylation.

Cx4 extracted from untreated mammalian cells and separated by SDS-PAGE can generally be resolved into several bands corresponding to its different isoforms. Typically observed are a nonphosphorylated (NP ~ 4 kD) form that migrates faster on the gel and two slower bands that correspond to the most common phosphoisoforms (P1 and P, ~44 kD and ~46 kDa respectively), which have been shown to be phospho-rylated mainly on serine residues (Musil and Goodenough, 11). However, neither the protein kinase(s) isoforms responsible for these phosphorylations nor their target sites in untreated cells have been identified.

1...1 Phosphorylation of Cx4 During Its Life Cycle

Phosphorylation events have been associated with the localization of Cx4 to the plasma memane as well as with aggregation of connexons into GJ plaques, pointing to the possible role of this post-translational modification in the regulation of Cx4 transport and/or the assembly or disassembly of GJs (Musil and Goodenough, 11). Phosphorylation has been demonstrated to occur as soon as 15 min after Cx4 synthesis in cultured fioblast cells, clearly showing that it can occur before the proteins arrival at the memane (Crow et al., 10). The fact that a nonphosphorylated form of Cx4 can be detected at the memane suggests that either these early phosphorylations are transient in nature or that dephosphorylation occurs at the memane (Musil and Goodenough, 11). Although Cx4 does not have to be phosphorylated in order to be localized to the memane, Cx4 present in GJ plaques has been found to be phosphorylated almost exclusively to its P form and selectively resistant to solubilization by Triton X-100 (Musil and Goodenough, 11). However, it is not known if these phosphorylation(s) play a role in the formation and stabilization of GJs in plaques.

1... Phosphorylation of Cx4 by PKC and PKA

The stimulation of PKC by the short exposure to phorbol ester TPA results in a marked decrease in GJIC, as indicated by a reduction in dye transfer in different cell types (Rivedal and Opsahl, 001). PKC can phosphorylate Cx4 on S68 and S7 in vitro (Saez et al., 17; Lampe et al., 000). It has also been shown that S68 is a major site of phosphorylation in vivo (Lampe et al., 000). The cells expressing the site-directed mutant S68A were resistant to dye transfer inhibition by TPA. Examination of the channel conductance in cells treated with TPA has further supported the notion that the PKC-mediated phosphorylation of S68 in Cx4 is involved in the mechanism of GJIC inhibition by TPA since the S68A mutant (unlike wild-type Cx4) showed no decrease in the full open conductance state of GJ channels (Lampe et al., 000). PKA does not appear to phosphorylate Cx4 in vitro. However, compounds that stimulate an increase in cAMP levels generally enhance Cx4 intracellular levels. Additionally, studies in which PKA or PKC were introduced into L cells transfected with either wild type or S64P mutant Cx4 cDNA have implied that both kinases may play a complex role in GJIC regulation (itz-Cunningham et al., 15).

1... Phosphorylation of Cx4 by Tyrosine Protein Kinases

Both EGF and PDGF receptor tyrosine kinase activation through ligand binding negatively affected GJIC causing a rapid inhibition of dye transfer and a significant increase in the phosphorylation of Cx4 on serine residues (Kanemitsu and Lau, 1; Hossain et al., 18). The effect of EGF receptor on Cx4 GJIC was shown to rely on activation of MAP kinase but not to be related to PKC activity (Kanemitsu and Lau, 1). MAP kinase seems to phosphorylate Cx4 directly in EGF-treated cells by targeting Ser55, Ser7, and Ser8 residues (Warn-Cramer et al., 16; 18). A triple mutant of these three residues formed functional GJs but was not affected by MAP kinase in response to EGF-stimulation (Warn-Cramer et al., 18). Evidence supporting the role of MAP kinase in the regulation of GJIC also comes from experiments in which purified MAP kinase was demonstrated to phosphorylate Cx4 channels reconstituted into liposomes and to induce a decrease in their conductance (Kim et al., 1).

The inhibition of GJIC by activation of the PDGF receptor involves more complex mechanisms and is less understood. The process appears to depend on both PKC and MAPK activity and may be regulated by other signaling pathways in addition to Cx4 phosphorylation (Hossain et al., 18; 1a; 1b). The potential sites of serine phosphorylation following stimulation of the PDGF receptor, the effective downstream serine protein kinase(s), and potential other regulatory protein(s) have not been determined.

Activation of non-receptor cytoplasmic kinases, such as pp60src, potentiates phosphorylation of Cx4 on tyrosine residues, resulting in a marked inhibitory effect on GJIC. The v-Src tyrosine kinase seems to phosphorylate Cx4 directly in vitro and in vivo (Loo et al., 15). Cx4 has been shown to interact directly with v-Src tyrosine kinase through the interactions between phosphotyrosine sites and proline-rich regions on Cx4 and the SH and SH domains on v-Src respectively (Kanemitsu et al., 17). Phosphorylation of Y65 and possibly Y47 may play a role in the observed impairment of GJIC. The current body of evidence strongly supports the importance of the Y65 residue in this process as a Y65F mutant was not able to associate with the activated pp60src kinase in Xenopus oocytes although it formed functional channels.

Another model of GJIC disruption by v-Src kinase has been recently proposed based on findings that are in direct conflict with the above mentioned results. In these studies, the activation of v-Src affected a Y65F mutant by decreasing junctional conductance in Xenopus oocytes (Zhou et al., 1). Additionally, the ability of v-Src to inhibit GJIC was eliminated by a treatment with the MEK inhibitor, PD805, implying that phosphorylation on a serine rather than a tyrosine residue can be of significance (Zhou et al., 1). MAP kinase may be a potential enzyme through which v-Src exerts its action although further studies are needed to clarify the mechanisms involved (Zhou et al., 1).

1...4 Dephosphorylation of Connexins by Protein Phosphatases

The role of protein phosphatases in the regulation of gap junctions is only beginning to emerge. The recent studies of selective inhibition of different classes of protein phosphatases in stimulated cells have highlighted the importance of these enzymes in the regulatory nature of the connexin phosphorylation-dephosphorylation cycle. Okadaic acid, an inhibitor of protein phosphatases PP1 and PPA, has been reported to stimulate the phosphorylation of Cx4 in cultured rat myocytes, a process affecting GJ communication as indicated by an accompanying decrease in the unitary channel conductance (Moreno et al., 14). In another study the treatment of EGF-stimulated rat liver epithelial cells with okadaic acid slowed down the recommencement of GJIC and the dephosphorylation of Cx4 (Lau et al., 1). Similarly, the usually observed dephosphorylation of Cx4 upon treatment with 18-glycyrrhetinic acid was prevented in the presence of okadaic acid (Guan et al., 17).

The inhibitors of PPB protein phosphatases exhibited properties similar to those of PP1 and PPA classes in that they retarded the restoration of GJIC and prevented the dephosphorylation of Cx4 in cells treated with TPA (Cruciani et al., 1). However, only PPB class inhibitors were able to induce the above effect in cells that were subjected to hypoxia (Li et al., 000). Although the above evidence strongly supports the function of protein phosphatases in GJIC control, little is known about the exact identity of the enzymes involved. In addition, most of the studies to date have examined the impact of phosphatase inhibition in stimulated cells. The insight into the role of phosphatases in GJIC regulation in untreated cells is lacking mostly due to the fact that phosphatase inhibitors such as okadaic acid failed to alter GJIC in several unstimulated cell lines (Lau et al., 1; Guan et al., 17; Saez et al., 1). This implies a more subtle level of control that protein phosphatases maintain on GJIC regulation in unstimulated cells. It is also reasonable to expect that the mechanisms of phosphatase function in the regulatory process are cell type specific.

In summary, the following aspects of the role of the Cx phosphorylation/ dephosphorylation in the regulation of GJIC have been established (Lampe and Lau, 000)

1. After the arrival of a connexon at the plasma memane, Cx phosphorylation is not always essential for the formation of a functional GJ channel,

. phosphorylation of specifc residues (Ser or Tyr) reduces GJIC, implicating the "gating" of GJ channels,

. phosphorylation may facilitate protein-protein interactions important for Cx regulation,

4. phosphorylation is important for Cx processing, i.e. trafficking, assembly and/or turnover,

5. dephosphorylation by protein phosphatases may be important for modulating the effects induced by phosphorylation.

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Adolf Eichmann

If you order your custom term paper from our custom writing service you will receive a perfectly written assignment on Adolf Eichmann. What we need from you is to provide us with your detailed paper instructions for our experienced writers to follow all of your specific writing requirements. Specify your order details, state the exact number of pages required and our custom writing professionals will deliver the best quality Adolf Eichmann paper right on time. Out staff of freelance writers includes over 120 experts proficient in Adolf Eichmann, therefore you can rest assured that your assignment will be handled by only top rated specialists. Order your Adolf Eichmann paper at affordable prices! If I were to say the word "Nazi" the first few things to pop into your mind would most likely be killing Jews, World War II, Adolf Hitler, and theutality towards Jews. Although all of these were big parts to the Nazi party there was still one more hug factor. The most crazed,utal man, who still would claim he was just following orders, was Adolf Eichmann. He, with the help of his "Eichmann Hobby Shops" or gas chambers, ended up killing millions of Jews while serving under Adolf Hitler.

Born in 106 in Solingen, Germany, thisother- to-five seemed to be merely another normal child destined to grow up to be some average business man. His father was a stern and an accountant and it seemed as though little Eichmann would grow up to be like his father. Trouble began toew, though, as he moved to Linz, Austria after his father remarried. When Adolf Eichmann grew to be 16 years of age and ended up dropping out of school. Ironically, the school he dropped out of was the same exact school Adolf Hitler dropped out of just 0 years or so before. As time went on during the 10s Adolf needed to get money so he began to do odd jobs, and while working as a traveling salesman he first heard Hitler speak on the radio and instantly became intrigued. That was it, the one moment that decided his fate, the moment when he decided that he wanted to join the Nazi party.

The National Socialist German Workers Party (Nazi) started out as a small anti-Jewish group in 118 but when Hitler became the leader of the Nazis in 11 he began to improve upon it. Finally, in 14, Adolf Eichmann joined the Nazis in the SS section of military section. Through his training his discovered his great ability to endure severe pain as well as his love for precision and order. After a few hard years in the SS he decided to join the SD, the special operations section of the Nazi party, and as a result moved to Berlin, Germany, the capital. Throughout his work he read to very important books suggested by his boss in the SD. They were both on Zionism, the belief that Jews should live in their own nation while others live in theirs. This goes along with how he always said that he enjoyed sending Jews out of the country. Later on he became the SDs expert on Jews after learning Heew and Yiddish, and finally, after being promoted four times between 17 and 141, became the director of the Jewish Emigration Office.

Exterminating Jews became the Nazis greatest problem. Exterminating them with standard shooting got very expensive and ores for the bullets got scarce. This is where Adolf Eichmann comes in. He was assigned the task of finding a cost efficient way of exterminating large amounts of Jews. Although he and many other members of the Nazi party felt sympathy for the Jews and if it were up to them they wouldnt kill the Jews, he still went on looking for a new way of killing the Jews. Finally after a few weeks of hard thinking he came up with large rooms that would fill up with poisonous gas. These rooms, most well known as gas chambers or "Eichmann Hobby Shops," were made to look like showers with shower head-like objects hanging from the ceiling. The Jews were tricking into thinking they could be cleaned and wereought into the large dark room. Then when they least expected it the gases would leak into the room and the Jews would be in for a long and painful death. As the Jews were dieing, though, Nazi officers would stand in the same room with gas masks on and did this as a training exercise. The Nazis kept on killing even though the war was surely over for them. After the war was over Eichmann knew he would be searched for by Israel as well as America. To avoid being caught in the first place he would always keep a low rank even if he could easily make it to the top the SD. Many other officers were very confused about this and couldnt quite understand why he wouldnt except a higher position. He has even been compared to a weasel by his fellow Nazi members because he could kill and the disappear quickly and without accusing. Finally his luck changed and the Americans caught him but let him go after being convinced by him that he was a clerk.

After realizing that he could be caught now he moved to Argentina to avoid secret agents in 150. His family later followed in 15. To further throw off agents he changed his name to Richard Klement and took a job at a local automobile factory.

It is , of course, impossible to hide forever and this showed as Adolf Eichmann or Richard Klement was arrested by Israeli agents. While in jail he couldnt even eat of go to the bathroom unless specifically ordered to. After a few long years in an Israeli prison he finally executed by hanging in 150.

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Blacks and the Media

If you order your cheap custom paper from our custom writing service you will receive a perfectly written assignment on Blacks and the Media. What we need from you is to provide us with your detailed paper instructions for our experienced writers to follow all of your specific writing requirements. Specify your order details, state the exact number of pages required and our custom writing professionals will deliver the best quality Blacks and the Media paper right on time. Out staff of freelance writers includes over 120 experts proficient in Blacks and the Media, therefore you can rest assured that your assignment will be handled by only top rated specialists. Order your Blacks and the Media paper at affordable prices! Black news mediums are important not only to the Black community, but to all races and ethnicities. They are important because they allow a better understanding of a great culture that has not only existed since the beginning of time, but has also built the United States into what it is today. They also allow Blacks to address issues in the Black community, properly educate individuals on Black culture and history, and provide Blacks with something that they can relate to and call their own.

Throughout history news mediums have attempted to properly discuss and educate the world on Black culture and Black history, however, these mediums have failed miserably. Not only do most news mediums erroneously portray Blacks as being unintelligent, lazy, chicken-eaters, they also only scratch the surface of the rich culture that constitutes not only Black history, but American history.

Blacks should be recognized not only as the engineers and designers of the United States, through their blood, sweat and tears during slavery, but also the inventors of modern day society with the plethora of Black inventions. Had it not been for slavery and the inventions of Blacks, the United States, as we know it today, would not be the same, or even worse, not exist. What is even more astounding, is that most people do not know that Blacks have had any part in shaping the United States, nor can they imagine, or possibly live life, without Black inventions, such as the fire extinguisher by Tom J. Marshal, the improved refrigerator by John Standard, the heating furnace by Alice H. Parker, or the electric elevator by Alexander Miles.

News mediums such as Ebony Magazine, Jet Magazine, BET, The Chicago Defender, Blackplanet.com, Blackvoices.com and various other Black radio stations have aided in the strive for public knowledge of Black history and culture. They do this by not limiting Black history to the month of Feuary, not limiting the people who contributed to Black history to just Martin Luther King Jr. and Malcolm X, and by involving Blacks who appeal to the younger generation such as music artists and athletes in conveying the message of Black culture. As a child growing up in the predominantly white public school system, I was exposed to many fallacies about Black history and culture. For years I thought that Martin Luther King Jr. and Malcolm X were the only ones who made a difference in Black history. If anyone were to ask me about either of the two I could recite one of their speeches, give a detailed description of their lives, and even provide photos and a page paper, but let them ask me who Alice Parker was or who invented the apparatus for transmissions of messages by electricity, and I would have no other choice but to give them a look of confusion. It was not until I was in my latter years in high school that I began researching other Blacks, and their accomplishments, and also realizing the true significance and importance of the Black experience. Apparently, other Blacks felt the same way, which is why there are so many news mediums today.

BET, or Black Entertainment Television, is a prime example of such a medium. Not only is it a station for Black people, but it is also a station owned and founded by Black people. It has shows that appeal to the younger generation, such as 106th and Park, Rap City and How Im Living, as well as shows that appeal to the older generation, such as BET Nightly News, Soul Food, and BET Jazz, just to name a few. Incorporated within all of the shows and even during commercialeaks are messages concerning the AIDS epidemic, which is plaguing the Black community, the war on Iraq and updates on famous Blacks who are making a difference. Whatever your interests are, BET has a show about it.

Black news mediums are essential in accurately portraying the Black community as well as keeping, not only Blacks, but the whole world informed on issues in the community and around the world. Without these mediums Blacks would still be perceived in a negative light because their contributions and achievements would be overlooked oriefly discussed.

Please note that this sample paper on Blacks and the Media is for your review only. In order to eliminate any of the plagiarism issues, it is highly recommended that you do not use it for you own writing purposes. In case you experience difficulties with writing a well structured and accurately composed paper on Blacks and the Media, we are here to assist you. Your cheap college papers on Blacks and the Media will be written from scratch, so you do not have to worry about its originality. Order your authentic assignment and you will be amazed at how easy it is to complete a quality custom paper within the shortest time possible!

A family that prays together , stays together, do you agree

If you order your cheap custom paper from our custom writing service you will receive a perfectly written assignment on A family that prays together , stays together, do you agree. What we need from you is to provide us with your detailed paper instructions for our experienced writers to follow all of your specific writing requirements. Specify your order details, state the exact number of pages required and our custom writing professionals will deliver the best quality A family that prays together , stays together, do you agree paper right on time. Out staff of freelance writers includes over 120 experts proficient in A family that prays together , stays together, do you agree, therefore you can rest assured that your assignment will be handled by only top rated specialists. Order your A family that prays together , stays together, do you agree paper at affordable prices! The Family That Prays Together

Stays Together

This statement can be agreed with and disagreed with depending on what a persons arguments towards this statement is. For the following statement I have put together a few points that are in favour of it, and a few that are against it.

For The family might be a religious family so by praying together i.e. at church they are also spending time with each other, this time together can help the family sort out their differences and communicate with one another telling one another their feelings on certain subjects that have beenought up either in the family or on the news etc.

The parents of the family, or the elders can teach the younger members of the family about religious teachings, this might help the younger ones to understand and try and solve any problems they may come across in later life or problems within the family. They take the knowledge and apply it.

The children might want to learn more about the world so they make an agreement with their parents to take them to church every Sunday. The family is happy to do this and get to spend time with each other.

Against

One or more of the members or all of the members in the family may not be religious, by going to church etc. may be boring for the non religious part of the family.

The members of the family may want to pray in their own time when the others may not, they may wish to pray in their own way by themselves, so by making them pray with the rest of the family they are not going to be able to solve their own problems, e.g. personal problems.

Even if the family all pray together their may still be arguments going on in the family to split them up, prayer doesnt solve everything, it also involves coming clean which in some cases is a bad thing.

Conclusion

After looking at the above points and considering the statement I am against this statement along with probably many other people, my main argument being that a member of the family may not be religious, so by making that person go to church etc. with the rest of the family may have an impact on that individual. For example they may begin to argue with members of the family about having to go to church when they find it boring.

Please note that this sample paper on A family that prays together , stays together, do you agree is for your review only. In order to eliminate any of the plagiarism issues, it is highly recommended that you do not use it for you own writing purposes. In case you experience difficulties with writing a well structured and accurately composed paper on A family that prays together , stays together, do you agree, we are here to assist you. Your cheap college papers on A family that prays together , stays together, do you agree will be written from scratch, so you do not have to worry about its originality. Order your authentic assignment and you will be amazed at how easy it is to complete a quality custom paper within the shortest time possible!

Unchecked Power in Shakespeares Macbeth and King Lear

If you order your cheap essays from our custom writing service you will receive a perfectly written assignment on Unchecked Power in Shakespeares Macbeth and King Lear. What we need from you is to provide us with your detailed paper instructions for our experienced writers to follow all of your specific writing requirements. Specify your order details, state the exact number of pages required and our custom writing professionals will deliver the best quality Unchecked Power in Shakespeares Macbeth and King Lear paper right on time. Out staff of freelance writers includes over 120 experts proficient in Unchecked Power in Shakespeares Macbeth and King Lear, therefore you can rest assured that your assignment will be handled by only top rated specialists. Order your Unchecked Power in Shakespeares Macbeth and King Lear paper at affordable prices! Unchecked Power in Shakespeares Macbeth and King Lear

In many of the plays by William Shakespeare, the central character goes through internal and external changes that ultimately shake their foundations to the core. Numerous theories have been put forth to explain the sequence of tragedies Shakespeare wrote during this period by linking it to some experience of melancholy, anger, despair, and the antagonists ultimate fall from grace in their lust for power. But such theories overlook the fact that it is in this very same period and in the same tragic works that portray the heights to which human nature can rise and fall in its purest and noblest, if not happiest terms. Surely the creation of so much light alongside the darkness and the perfection of the artistic medium through which Shakespeare gives them expression argues against the idea that the greedy side of human nature is his chief concern. His efforts to portray human life in its rarest form and not only the dark depths, but also the treasure rooms of our being. He tries to pierce beneath the superficial motives and forces of surface behavior, social, and cultural expressions and to the deeper levels of individual character and human nature. Shakespeare then places these aspects of human existence in their true relation to the wider field of universal life. In relation to the tragic hero, there are many similarities between the tragic heroes in Macbeth and King Lear. However, the differences between the two outline the re-occurring themes in both plays. In Shakespeares plays the central characters own weaknesses and lust for power lead to corruption. The unchecked power in Shakespeares Macbeth and King Lear ultimately leads to corruption, tragedy, and the heros fall from grace.

In Macbeth, Macbeths power goes unchecked within himself, his wife, and within the kingdom. The title character is a tragic hero, a person of high rank who isought to eventual ruin by his desire for power. At the beginning of the play, Shakespeare defines Macbeth as a valiant hero very clearly. His courage is unquestionable in defense of Scotland in the opening scene. When King Duncan names Malcolm Prince of Cumberland, Macbeth decides to murder Duncan. Macbeth is loyal to the King and he imagines murder but rejects the idea. Macbeth is aware that his thoughts are corrupt and he knows that justice will somehow punish him. Then in Act I Scene , Macbeth considers killing King Duncan to make the witches prophesy come true. He says, "Why, if fate will have me king, why chance may crown me." Yet increasingly his ambition defeated his good nature. Macbeths limited power as Thane of Cawdor ignites his desire for complete and absolute power at any cost. The most apparent flaw, and perhaps the most tragic in Macbeths character, is his lack of patience and hunger for total power.

Macbeth tries to upset the natural order established by the gods. Most important to the theory that Macbeth is responsible for his own actions would be a point that the infamous witches and Macbeth agree upon. Such an element exists in the form of Macbeths ambition. In the soliloquy Macbeth gives before he murders Duncan, he states, ...I have no spur/To prick the sides of intent, but only/Vaulting ambition,"(Act I, Scene .). These are not the words of a man who is merely being led down a self destructive path of doom, with no will of his own, but words of a man who realizes not only the graveness of his actions. Later the head witch, Hecate, says," Hath been but for a wayward son,/Spiteful and wrathful, who, as others do,/Loves for his own ends, not for you. (Act III, Scene 5), which again highlights Macbeths inward nature. The most significant part of the play is the paradox between Macbeths ambitions and desire for power as he simply succumbs to natural urges, which take him to a fate of his own making. Everyone has character flaws that he must live with and Macbeth simply allowed those flaws to destroy him. These flaws ultimately haunt Macbeth and cause him to let his overvaulting ambition rush fate, and hasten his doom. He acknowledges his guilt in several places in the story. After Macbeth becomes king, his sanity begins to unravel. In Act III, Scene 4 he sees images of his dead friend Banquo at the banquet. Lady Macbeths questioning of Macbeths manhood is crucial in fueling his ambition and desire to be king after he becomes Thane of Cawdor. Then his wife plants the initial seed of a "new" king in the thoughts of Macbeth. The reversal of control and power between he and his wife strikes Macbeths manhood. She is well aware of the discrepancy between their respective resolves and understands that she will have to manipulate her husband into acting on the witches prophecy. Her violent, blistering soliloquies in Act I, Scene 7, testifies to her strength of will, which completely eclipses that of her husband. Her soliloquy in Act I, scene V, begins the plays exploration of gender roles, particularly of the value and nature of masculinity. In the soliloquy, she spurns her feminine characteristics, crying out unsex me here and wishing that the milk in hereasts would be exchanged for gall so that she could murder Duncan herself. These remarks manifest Lady Macbeths belief that manhood is defined by murder. When, in Act I, scene vii, her husband is hesitant to murder Duncan, she goads him by questioning his manhood and by implicitly comparing his willingness to carry through on his intention of killing Duncan with his ability to carry out a sexual act (I.vii.8�41). Throughout the play, whenever Macbeth shows signs of faltering, Lady Macbeth implies that he is less than a man. By goading Macbeth, the "unseen power" she appears to have over Macbeth recalls the idea that Macbeth has no power or control in his own home or over his wife. He gains power by his murdering King Duncan, but in the end he loses it all even in death.

By killing Duncan, Macbeth unleashes a kind of primal chaos upon the realm of Scotland, in which the old order of benevolent king and loyal subjects is replaced by a darker relationship between a tyrant and his victims. However, even with all his power, Macbeth ceased to be a sympathetic hero once he made the decision to kill Duncan but by the end of the play he has become so morally repulsive that his death comes as a powerful relief. Ambition and bloodlust must be checked by virtue for order and form to be restored to the sound and fury of human existence. Macbeth makes no attempt to reverse the situation and is thereby responsible for his tragic fate. His tragic flaw is his lust for power, which leads him to a series of bloody and increasingly indefensible acts.

Shakepeares King Lear, in contrast to Macbeth, begins with absolute power held by King Lear. He wants to be treated as a king and enjoy the title, but he doesnt want to fulfill a kings obligations of governing for the good of his subjects. The aging King ofitain, decides to step down from the throne and divide his kingdom evenly among his three daughters. First, however, he puts his daughters through a test, asking each to tell him how much she loves him. Goneril, and Regan, Lears older daughters, give their father flattering answers. But Cordelia, Lears youngest and favorite daughter, remains silent, saying that she has no words to describe how much she loves her father. Lear flies into a rage and disowns her. By the end of the play King Lear has transformed from a conceited and self-righteous king with all power, to a humble and caring individual with no power at all. Unchecked power in King Lear leads to internal tragedy first within himself, the relationship with his daughters, and to corruption within the kingdom.

As the play opens one can almost immediately see that Lear

begins to make mistakes that will eventually result in his downfall. The very first words that he speaks in the play, ...Give me the map there… know that we have divided in three our kingdom, and tis our fast intent to shake all cares and business from our age, conferring them on younger strengths while we unburdened crawl to death…" As Lear bears the status of King he is, as one expects, a man of great power but sinfully he surrenders all of this power to his daughters as a reward for their demonstration of love towards him. This untimely abdication of his throne results in a chain reaction of events that send him through a journey from powerful to powerless.

Please note that this sample paper on Unchecked Power in Shakespeares Macbeth and King Lear is for your review only. In order to eliminate any of the plagiarism issues, it is highly recommended that you do not use it for you own writing purposes. In case you experience difficulties with writing a well structured and accurately composed paper on Unchecked Power in Shakespeares Macbeth and King Lear, we are here to assist you. Your cheap custom research papers on Unchecked Power in Shakespeares Macbeth and King Lear will be written from scratch, so you do not have to worry about its originality. Order your authentic assignment and you will be amazed at how easy it is to complete a quality custom paper within the shortest time possible!

Creation vs. Evolution

If you order your cheap custom paper from our custom writing service you will receive a perfectly written assignment on Creation vs. Evolution. What we need from you is to provide us with your detailed paper instructions for our experienced writers to follow all of your specific writing requirements. Specify your order details, state the exact number of pages required and our custom writing professionals will deliver the best quality Creation vs. Evolution paper right on time. Out staff of freelance writers includes over 120 experts proficient in Creation vs. Evolution, therefore you can rest assured that your assignment will be handled by only top rated specialists. Order your Creation vs. Evolution paper at affordable prices! How do you think the world came to be, a Big Bang or a process that took 7 days? If you believe in the Big Bang theory, what exploded and where did it come from?

The question is did God create the universe billions of years ago (in order to let the light naturally reach us) or did He create the universe fully functioning (with the light instantly visible to us)? In my opinion, creating a fully functioning universe is the most logical approach. For example, "If I wanted to make a botanical garden, I would not plant seeds and wait 0 years for the vegetation to mature before I opened it to the public. I would harvest fully mature vegetation and start out with a fully functioning garden." (onson, 001) Its just more realistic.

As most people know, I was raised to read the Bible and to believe what it said about God and how He created the universe. But when I became old enough to think for myself I started to question religion and if God even existed. For a few years I had many doubts, that were mostly put in my head be friends, and really didnt care anymore. But then some things happened in my life and I turned back to God. I then began to realize that what I had been taught made a lot of sense and that, from my point, was the only logical way this world could have gotten here.

When I began my research for this paper, I came across so many different arguments for the beginning of the universe; some were so comical and unbelievable. But I did come across a few interesting ones based upon creation by God. The first was written by William Lane Craig in his book The Existence of God and the Beginning of the Universe, Truth A Journal of Modern Thought "The kalam cosmological argument, by showing that the universe began to exist, demonstrates that the world is not necessary being, therefore, not self-explanatory with respect to its existence… Since whatever begins to exist has a cause, there must exist a transcendent cause of the universe." (Craig, 11)

Although I dont know exactly what the authors belief is about creation vs. evolution, this one seems to me to be pointed towards creation and seems to be very logical.

The second argument is the cosmological argument defended by philosopher Saint Thomas Aquinas, but was invented long before

"It has many variations, but the simplest one is this Everything has to be caused by or created from something else. Therefore, there must have been a first cause, or what Aristotle called a prime mover, and this is God." (BQ, R. Solomon, 18)

The book states that Aquinas did believe in God as "the most reasonable thing to

believe in".

Another argument is the argument from design (for Gods existence) defended byitish philosopher William Paley. I think this is the closet argument that I came across that is the closet to what the Bible teaches and what I believe in. It is defined as "an argument that attempts to prove that God exists because of intricacy and design of nature." ( BQ glossary) The reasoning behind this is that since the world is so unique it most have been created by someone.

The last argument I wanted to mention is the ontological argument formulated by a monk named Saint Anselm. It is defined as "an argument (or set of arguments) that tries to prove the existence of God from the very concept of God "

(BQ glossary). Its reasoning is that if God has all possible perfection and existence is perfection, then God must exist.

All of these arguments have to do with God creating the universe, but each is showing slightly different perspectives.

In conclusion, I dont look down on people who believe in evolution or the Big Bang theory because everyone is entitled to their own opinions and beliefs, but I cant understand how logically they can agree with it. There is so much information and research on the internet defending creation that has such logical reasonings behind them. I know there is the same information out there about evolution, but there always seems to be gaps in there research that cant be explained or questions that cant be answered. Creation by God just makes perfect sense to me.

"CSE sets out to demonstrate the fallacies and deceptions of modern evolutionary thinking. We believe the Bible is literally true and scientifically accurate. We believe the earth was created in six literal, 4-hour days, about 6000 years ago. We believe dinosaurs have always lived with man. They were called dragons throughout most of human history. Noah took them on the ark (probably juveniles--just be sure to get a pink one and a blue one!). After the Flood, people killed most of them. There are probably a few small ones still alive today in remote parts of the world." (Hovind, 18)

"Evolutionism is a religious worldview not supported by science, Scripture, popular opinion, or common sense. The exclusive teaching of this dangerous, mind-altering philosophy in tax-supported schools, parks, museums, etc. is a clear violation of the First Amendment."

--Dr. Kent Hovind (CSE Ministry, www.drdino.com)

The following time-line charts show the time differences presented. If the evolution chart were drawn to the same scale as the creation chart (1 inch = 750 years--at least in our printed material), the evolution chart would have to be 41 miles long!! The entire theory of evolution is built upon the faulty assumption that the origin of the universe was billions of years ago (BYA). The human mind cannot grasp billions of years. As with most fairy tales, evolution relies on long ago and far away to make the impossible seem true. My advice Dont bet your life on evolution!

Ten years is a long time. On the creation chart it would be .01 inch (the thickness of a piece of paper); on the evolution chart it would be invisible.

Few people will live 100 years. Lincoln was President over 10 years ago which is only .17 inch on the creation chart and invisible on the evolution chart.

Columbus sailed more than 500 years ago (/ of an inch). The entire creation chart of 6,000 years would be .000004 inches (still invisible) on the evolution chart! The entire fictitious geologic column of 600 millions years would be only .4 inch (less than 1/4 inch on the evolution chart at the scale it is drawn here.

(CSE Ministry Creation Science Evangelism, 18, www.drdino.com)

Works Cited

1. "7-Day Creation Figurative or Literal?", Michaelonson, 001, www.biblehelp.org

. "The Existence of God and the Beginning of the Universe, Truth A Journal of Modern Thought ", William Lane Craig, 15, Leadership U., www.evcforum.net

. Cosmological Argument, The Big Questions, Robert C. Solomon, 18

4. Argument from Design, The Big Questions, Robert C. Solomon, 18

5. Ontological Argument, The Big Questions, Robert C. Solomon, 18

6. Creation/Evolution Time Lines, CSE Ministry Creation Science Evangelism, 18, www.drdino.com

Please note that this sample paper on Creation vs. Evolution is for your review only. In order to eliminate any of the plagiarism issues, it is highly recommended that you do not use it for you own writing purposes. In case you experience difficulties with writing a well structured and accurately composed paper on Creation vs. Evolution, we are here to assist you. Your cheap college papers on Creation vs. Evolution will be written from scratch, so you do not have to worry about its originality. Order your authentic assignment and you will be amazed at how easy it is to complete a quality custom paper within the shortest time possible!