DNA supercoiling occurs in all cells that undergo genetic processing. This event blocks replicative and transcriptional machinery from binding to the DNA helix, which proves detrimental to the cell. However, current research is beginning to show that not all affects of supercoiling produce negative results. These studies prove that different coiling patterns increase the efficiency of epigenetic processes such as methylation and acetylation. Topoisomerase, a post-transcriptional monomeric enzyme, solves the winding problem of the double helix by implementing transient cuts in the genome. As these cuts build up, the genome is essentially fragmented by the enzyme and the cell is unable to express essential genes; this genomic degradation by topoisomerase serves as a viable pathway into cancer research. This review article synthesizes the many ideas surrounding topological cellular events, and presents a new direction for research on chromatin modification in cancerous cells. However, due to the time constraints of the project, this article will not thoroughly discuss the mechanistic process of the replication pathway.
INTRODUCTION:
A linear strand of DNA experiences tremendous torsional forces when undergoing replication. The replicative machinery applies a force as it unwinds the double strand and splits the DNA apart to expose the genetic information. The helicase enzyme is responsible for putting such tension on the double helix and causing the event known as supercoiling (1). This event is troublesome for the cell because it can cause certain regions of the genome to be inaccessible to the replicative enzymes. As a result, the vital genetic information contained in these locations goes unread, leading to mutation in the daugh...
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...ertions, deletions, and aberrations. Introducing the proper inhibitory factors would force topoisomerase to leave a mutated genome partially degraded, thus blocking the replication of cancerous cells (3). Catalytic topoisomerase inhibitors are a heterogeneous group of compounds that interfere with the binding of DNA and topoisomerase, stabilize noncovalent DNA-topoisomerase complexes, or inhibit ATP binding (9). Most catalytic inhibitors have additional targets and activities that likely contribute to their biological effects. Topoisomerase poisons can be used, along with inhibitors, to induce cellular tumor suppression. Poisons increase the steady-state concentration of their covalent DNA cleavage complexes; this action converts topoisomerase into a physiological toxin that introduces high levels of transient protein-associated breaks in the genome of treated cells.
... in glioma cells (suppression of autophagy, mentioned above, is often accompanied by activiation of apoptosis). Silencing eEF-2 kinase expression with the inhibitors (NH125) remarkably increased the TMZ-activated apoptosis in human glioma cells. One other important discovery of this experiment was that the combination of TMZ and NH125 did not cause TMZ to destroy normal human astrocytes. Essentially, co-treatment of TMZ with NH125 made TMZ more effective against glioma and produced a better survival benefit for the mice, but could not cure the mice. This may be because the amount of NH125 (eEF-2 inhibitor) used was not enough, or the dosages of TMZ and NH125 were not optimal. Nonetheless, development of better and more effective inhibitors of eEF-2 kinase may help in finding the cure for glioblastoma multiforme, the malignant and extremely aggressive brain tumor.
Out of the plays that we could have chosen to produce, I have decided to go with Molière’s, “Tartuffe.” This play is a comedy that comes from 17th century France and is heavily influenced by two large sources of experience for Molière. Those sources are the rules and structure for a play put in place by the French academy and the lessons of improvisation taught by the Commedia dell’Arte. This piece is written in fives acts that are in a unique alexandrine style of verse which have 12 syllables in a line and usually ends with rhyming words. The reason I chose this play is because, in my opinion, things like television, movies, plays, and other forms of media and entertainment are meant to transport you away from all the bad things happening in real life and focus you on something fun and/or interesting. I find this play to have a lot of fun moments that can be mined for even more comedy and I think it has the good chance to keep a large audience entertained for a long period of time. To accomplish my goal I will use elements of situational comedies, France in the 1660’s, and one of Molière’s plays, “A school for girls.”
Themistocles contribution to the defence of Greece was more significant than any other Greek individual. To what extent do you agree?
If you ask any Canadian what they were doing on september 28 1972, there it a good chance they will say watching the Canadians and soviets battling it out for the title of the summit series. It was one of the largest rivalry games in Canadian history. Kids in school watched the games during class, People across the nation sat on the edge of their seats for the month of september and were thrilled when Canada pulled off the victory. All of the hype leading up to the event made people wonder if the summit series was the biggest event in Canadian sports history or even Canadian history in general.There is no doubt that the summit series was a huge milestone for Canada and brought the nation together for an exciting ride, even to this day we still see the effects of this great event, it sculpted the game of hockey that we know and love today.
Cancer has been an active concern in our society for the past couple decades, since we truly discovered the nature of cancer and the potency it brings along with it. However, it was not until the mid-20th century that scientists were beginning to truly understand the origin of cancer. Scientists dating back all the way to the Renaissance, when they first began performing autopsies to learn more about the human body and form, noticed abnormalities but it never clicked that it was something much worse than it seemed. Research has continued since then, and it has continued to thrive even to this day. When James Watson and Francis Crick discovered DNA and it’s chemical structure in 1962, it opened up doors that even they could not expect. With the understanding of DNA and how it affected the way we look at life, came the beginning of the understanding of mutated DNA (which is a cause of the growth of cancerous cells). In this past century, researching scientists discovered that cancer is linked with the DNA that resides in a cell’s nucleus. By ways of damage to the cells via chemicals or radiation, or even introduction of a new DNA, the cancerous cells begin to form and duplicate. We are learning more and more about cancer and how to fight it, but we still have much more to learn.
Raymo uses for this is DNA and its ability to reproduce itself. This tiny double-helix
Hypermethylation of CpG islands at tumor suppressor genes turns them off, while hypomethylation leads to the instability and inappropriate activation of oncogenes and transposable elements. Methylation can be directly related to genetic mutations, an example of this case is methylated cytosine. Methylated cytosine mutates spontaneously in vivo through deamination to give thymine. According to Andy Bannister (n.d.), “37% of somatic p53 mutations and 58% of germ line mutations occur at methylated...
All organisms are made of cells that grow by cell division. An adult human being consists of about 100000 billion cells. Dying cells are replaced by a large number of unceasingly dividing cells. A cell duplicates its chromosomes, segregates the chromosomes, and divides into two. These ordered sequences of events are called a cell cycle. 2001 Nobel Prize in Physiology or Medicine to Hartwell, Hunt, Nurse and 1998 Lasker Prizes in Basic Medical Research to Hartwell, Masui, Nurse have made important discoveries about the regulation of a cell cycle. Understanding the regulation of a cell cycle is seminal to understanding why and how cancer cells are formed. In this review, I focus on how these crucial discoveries made progress in understanding cell cycle regulation and leading to understanding cancer cell and cancer therapy.
Precise chromosomal DNA replication during S phase of the cell cycle is a crucial factor in the proper maintenance of the genome from generation to generation. The current “once-per-cell-cycle” model of eukaryotic chromosome duplication describes a highly coordinated process by which temporally regulated replicon clusters are sequentially activated and subsequently united to form two semi-conserved copies of the genome. Replicon clusters, or replication domains, are comprised of individual replication units that are synchronously activated at predetermined points during S phase. Bi-directional replication within each replicon is initiated at periodic AT-rich origins along each chromosome. Origins are not characterized by any specific nucleotide sequence, but rather the spatial arrangement of origin replication complexes (ORCs). Given the duration of the S phase and replication fork rate, adjacent origins must be appropriately spaced to ensure the complete replication of each replicon. Chromatin arrangement by the nuclear matrix may be the underpinning factor responsible for ORC positioning. The six subunit ORC binds to origins of replication in an ATP-dependent manner during late telophase and early G1. In yeast, each replication domain simply contains a single ORC binding site. However, more complex origins are characterized by an initiation zone where DNA synthesis may begin at numerous locations. A single round of DNA synthesis at each activated origin is achieved by “lic...
Telomere are special DNA structure that consist of repetitive nucleotide sequences, which serves as a “cap” to protect the ends of the chromosomes. These repetitive sequences can range from thousands of base pairs in Vertebrates to about a few hundreds of base pairs in yeast cells (Oeseburg, et al. 2009). Located at the ends of the chromosomes, the telomeres serves as a biological life line for cells. Once the telomeres reach a certain length, the cell will cease to divide. Oeseburg, et al (2009) suggested that the telomere has a crucial length, once reached, it could result in chromosome end-to-end fusion and chromosome dysfunction; which may eventually lead to cell apoptosis, c...
Throughout human history power imbalances have been prevalent in almost every civilization. One method of controlling people, in addition to power power, is to control how much knowledge gets out to the masses. This paper examines how iconoclasm is used in the Middle East as a method of controlling popular opinions and thoughts on race,sex and many other important details of everyday life. Iconoclasm is the systemic destruction of religious or cultural pieces of artwork for political or religious reasons. The destruction of artifacts can rewrite cultural history and change opinions on how the history of a nation is perceived. This also results in extensive loss of cultural history which can never be recovered. The Middle East is of particular interest in this research paper as it has been in the news recently for such acts. Most Middle Eastern countries have Islam listed as their official religion. In Islam it is forbidden to show the face of Allah, the God of Islam, in any form of artwork. It is also seen as taboo to have any living creatures such as humans or animals depicted in a mosque, the Islamic place of worship. As such, many buildings which have been converted into mosques have been defaced to suit the proper Islamic code. One such incident of this happening is the Hagia Sophia in Istanbul. Once a Roman Catholic church, it was converted into a mosque after the conquer of the Byzantine Empire by the Ottoman Turks and all mosaics depicting Jesus, His mother and saints were removed. Another popular incident attributed to iconoclasm within Middle Eastern countries include the missing nose of the Sphinx in Egypt(World Heritage Site). One confirmed incident of iconoclasm in within the past few decades is of the defacing and d...
Iconoclasm refers to the opposition and destruction of religious images by religious and imperial authorities. It is believed that Byzantine iconoclasm occurred in two waves, the first being during the 8th century and the second during the 9th century. There are many theories as to how and why iconoclasm started during the Byzantine Era and these will be debated. The methods and reasons of Byzantine iconoclasm will also be compared to modern day iconoclasm.
David Almond explores the theme of imagination throughout his novel Skellig. From the first sentence to the very last, the theme of imagination was expressed through subplots and ideas. Questions and theories arose when Michael discovered Skellig in his garage. There were many situations throughout the novel where the reader has to think, ‘can this situation get better? do I believe that it can get better?’ David Almond activates the readers mind further by adding in winged creatures, both real and mythological, this allows each readers imagination to experience different thoughts about each activity in the novel. David Almond ties in belief and disbelief into the theme of imagination, complemented with excellent imagery, to create a vivid picture of the story in the readers mind. The story relates to David Almond more than most readers know. He had an ill sister when he was a child and Michael’s new house is very similar to the house that David Almond bought, right down to the toilet in the dining room.
1. El uso de fuerza física para derrotar alguien, pelea. "Ayer había una bronca entre los hombres de octavo."
DNA (deoxyribonucleic acid) is a self-replicating molecule or material present in nearly all living organisms as the main constituent in chromosomes. It encodes the genetic instructions used in the development and functioning of all known living organisms and many viruses. Simply put, DNA contains the instructions needed for an organism to develop, survive and reproduce. The discovery and use of DNA has seen many changes and made great progress over many years. James Watson was a pioneer molecular biologist who is credited, along with Francis Crick and Maurice Wilkins, with discovering the double helix structure of the DNA molecule. The three won the Nobel Prize in Medicine in 1962 for their work (Bagley, 2013). Scientist use the term “double helix” to describe DNA’s winding, two-stranded chemical structure. This shape looks much like a twisted ladder and gives the DNA the power to pass along biological instructions with great precision.