Research Proposal The role of perivascular macrophages in...

Research Proposal: The role of perivascular macrophages in breast cancer metastasis. 1. Specific Aims The tumour microenvironment is comprised of both malignant and non-malignant cells. Increasing evidence suggests that the fate of malignant cells is altered by the behaviour of the surrounding nonmalignant cells. Together, the diverse composition of the microenvironment, including immune cell infiltration, stromal cells and extracellular matrix, as well as nutrient and oxygen supply, shape the fate of cancerous cells. In particular immune cells impact on tumour growth and metastasis. The co-evolution of tumour cells along with the immune system results in a continually changing and immune-suppressive or -permissive environment (1).†¦show more content†¦Conceivably, the rapidly changing tumour landscape alters tissue resident macrophages by hijacking their physiological functions resulting in a pro-tumourigenic immunosuppressive milieu. Certain tissue resident macrophages localise along blood vessels (referred to as perivascular macrophages, PVM), which are therefore strategically positioned to regulate extravasation of circulating leukocytes (7). Indeed, a recent report from our laboratory using a transgenic reporter strain specific for PVM has highlighted a unique role for these cells in recruiting neutrophils during bacterial infection that was dependent on their ability to generate chemokines (8). Similarly, previous studies have implicated the role of PVM in tumour cell invasion into blood vessels and subsequent metastasis (9), but no clear understanding of this process or any mechanistic detail exists. In this project, we aim to dissect the precise role of PVM in hematogenic and lymphatic spread of tumour cells. We will make use of cutting edge intravital multi-photon microscopy in combination with genetically engineered mice to further our understanding of PVM during tumour pathophysiology. We expect to delin eate the role of PVM in tumour cell dissemination and metastasis. Hypothesis and aims: Due to the strategic location of PVM adjacent to post-capillary venules and also lymphatics we

Epigenetics - 1340 Words

ONE of biology’s hottest topics is epigenetics. The term itself covers a multitude of sins. Strictly speaking, it refers to the regulation of gene expression by the chemical modification of DNA, or of the histone proteins in which DNA is usually wrapped. This modification is either the addition of methyl groups (a carbon atom and three hydrogens) to the DNA or of acetyl groups (two carbons, three hydrogens and an oxygen) to the histones. Methylation switches genes off. Acetylation switches them on. Since, in a multicellular organism, different cells need different genes to be active, such regulation is vital. What has got a lot of people excited, though, is the idea that epigenetic switches might be transmitted down the generations.†¦show more content†¦The term itself covers a multitude of sins. Strictly speaking, it refers to the regulation of gene expression by the chemical modification of DNA, or of the histone proteins in which DNA is usually wrapped. This modification is either the addition of methyl groups (a carbon atom and three hydrogens) to the DNA or of acetyl groups (two carbons, three hydrogens and an oxygen) to the histones. Methylation switches genes off. Acetylation switches them on. Since, in a multicellular organism, different cells need different genes to be active, such regulation is vital. What has got a lot of people excited, though, is the idea that epigenetic switches might be transmitted down the generations. Some see this as contrary to Darwinism, since it would permit characteristics acquired during an organism’s lifetime to be passed on to its offspring, as suggested by a rival theory of evolution put forward by Jean-Baptiste Lamarck. This is an exaggeration. The DNA sequence itself is not being permanently altered. Even those epigenetic changes that are inherited seem to be subsequently reversible. But the idea that acquired characteristics can be inherited at all is still an important and novel one, and a worrying example of the phenomenon has been published this week in BioMed Central Medicine. In this section * Lake monsters * A third-world dimension *Show MoreRelatedEpigenetic Modifications to the Human Genome523 Words   |  2 PagesEpigenetic modifications to the human genome have increasingly become the subject of scientific research due to a presumptive role in the pathology and progression of degenerative diseases. Conventionally, methylation of a nucleotide residue is associated with gene repression, whereas acetylation of a nucleotide residue is associated with gene expression. Through a member of the DNA methyltransferase protein family, the formation of 5-methylcytosine (5mC) from a previously unmodified cytosine residueRead MoreWhat ´s Epigenetic Landscape?943 Words   |  4 Pagesit can do for us but, thanks to the works of Dr. Conrad H. Waddington â€Å"Epigenetic Landscape† 1939, which was followed up and expanded on by Dr. Adrian Bird and Danny Reinberg (1975~) we know that it does exist and it has far reaching implications for future development in medical research and biological development fields. ï‚ § Risk assessment ï‚ § Prevention ï‚ § Progression analysis ï‚ § Prognosis and biomarker development Epigenetics ~ is the term coined to explain a variety of â€Å"bizarre† phenotypic phenomenaRead MoreThe, Genetic And Epigenetic Mutations1064 Words   |  5 Pagescommon diseases in the world, is a result of genetic and epigenetic mutations. Where genetics was at first used to explain phenotypes and disease, genetics alone could not explain the sheer amount of phenotypic diversity in a population—nor could it explain phenomenon such as how, â€Å"monozygotic twins or cloned animals [could] have different phenotypes and different susceptibilities to a disease.† Thus entered the field of epigenetics. Epigenetics is, â€Å"the study of heritable changes in gene expressionRead MoreIntroduction:. Epigenetics Studies The Biological Information1364 Words   |  6 PagesIntroduction: Epigenetics studies the biological information that can be inherited in addition to the DNA, through biochemical changes such as methylation and histone modifications that can affect gene expression and lead to a particular phenotype [9]. Epigenetic plasticity can be influenced by internal and external factors, such as the in utero environment of early development [9]. The intrauterine environment can have short and long term effects on the health and future disease state of offspringRead MoreThree Main Pathways Of Epigenetic Modification1783 Words   |  8 PagesEpigenetic Modifications in Cancer Scientists have known for several decades that cancer may be caused by mutations in the DNA of cells. These mutations may result from exposure to certain substances (e.g. radiation, benzene) or they may occur spontaneously in the process of cell division, especially in the context of aging. Recently, researchers have discovered another level of inherited cellular information separate from the genes themselves. Epigenetics is the study of modifications to genesRead MoreBehavioral Epigenetics : Biological Heredity And Nurture1428 Words   |  6 Pagesothers do not? Behavioral epigenetics examines how nurture shapes nature, where nature refers to biological heredity and nurture refers to everything that occurs during the animal s lifespan. Epigenetics is the study of alterations in an organism caused by modifications of gene expressions instead of alterations of the genetic code itself. Behavioral epigenetics is the field of study, which analyzes the role epigenetics have in shaping h uman or animal behavior. Epigenetics works by wrapping DNA aroundRead MoreDiet Mediated And Transgenerational Epigenetic Effects1186 Words   |  5 PagesDiet-Mediated and Transgenerational Epigenetic Effects An offspring’s microbial composition is initially determined through maternal transmission in utero and during birth, however, after delivery, the microbiota is not fixed and may be changed by a multitude of environmental factors. The mode of delivery (vaginal or caesarean section), diet, and many other factors continue to play dynamic roles throughout an individual’s lifetime (Marques et al., 2010). Recent studies have indicated that maternalRead MoreBackground Explanation Of Epigenetics By Conrad Waddington883 Words   |  4 PagesMorimoto, 2004). Background Explanation of Epigenetics Epigenetics What is epigenetics? Epigenetics is a term that was coined by Conrad Waddington that describes the heritable changes in the cellular phenotypes that are observed independently of alterations that occurs in the DNA sequence (Dawson Kouzarides, 2012). He proposed that there was a link between development and genetics, which is where the field of epigenetics came from. The word epigenetics itself was derived from a Greek word epigenesistRead MoreAnalysis Of The Article Epigenetics And Human Disease 1764 Words   |  8 Pagesenvironment can be very different? (Coutney Griffin 2012) Cortney Griffin elaborated on how her journey of having twins lead her to a deeper understanding of what epigenetics truly is. This talk, although vastly viewed in biochemistry classes including at the University of Texas of El Paso, differs from the scholarly article â€Å"Epigenetics and human disease: translating basic biology into clinical applications† by David Rodenhiser and Mellissa Mann. The ir most prominent similarities and differencesRead MoreEssay about What is Epigenetics and How Can It Effect Me?772 Words   |  4 PagesBefore conducting research and watching numerous informational videos on epigenetics, I would have never believed that when my grandmother was my age, she made dietary decisions that have affected me. Technically speaking, epigenetics simply means above genetics. In other words, epigenetics is the traits that you and I inherit, but do not necessarily necessitate the sequence of genes. I took me a while to actually grasp the concept until I thought of it from a musical perspective. Imagine our DNA

George Washington Essay free essay sample

As a soldier George Washington demonstrated enough courage to become the commander of the Virginia troops that defended the states western frontier during the French and Indian War. He was also a successful tobacco planter at his family plantation. In 1787 Washingtons concerns about the crumbling of the nation prompted him to serve as a delegate to the Constitutional Convention in Philadelphia. He presided over the convention and his support was very important to the ratification of the newly proposed Constitution. In 1789, Washington became the first president of the United States. He served two terms guiding the new government through the organization of the executive branch, founding the nations capital, and opening the west for settlement. George Washingtons stance toward slavery changed as he grew older. George Washington was a slave owner himself since the age of 11. Like a Virginia plant owner he lived off of slavery and his views were very conventional. We will write a custom essay sample on George Washington Essay or any similar topic specifically for you Do Not WasteYour Time HIRE WRITER Only 13.90 / page In letters he is shown to be humane and caring towards his slaves but in others shown as a Virginia Slave owner. By the time of his presidency, he mostly believed that slavery was wrong and against the principles of the new nation. As President, Washington did not lead a public fight against slavery because he believed it would tear the new nation apart. Abolition had many opponents especially in the South. George Washington feared that if he took such a public stand, the southern states would withdraw from the Union. He thought he had worked too hard to build the country and then risk tearing it apart. In his private life, Washington could and did lead by example. In his will, he arranged for all of the slaves he owned to be freed after the death of his wife, Martha. He also left instructions for the continued care and education of some of his former slaves, support and training for all of the children until they came of age and continuing support for the elderly. In 1792, George Washington exercised the first presidential veto of a Congressional bill. The bill introduced a new plan for dividing seats in the House of Representatives that would have increased the amount of seats for northern states. In the end, after consulting with his cabinet, Washington, who came from the southern state of Virginia, decided that the plan was unconstitutional because, in providing for additional representatives for some states, it would have introduced a number of representatives higher than that in the Constitution. George Washington believed that all human beings possess natural rights. He believed the purpose of the government was to protect the rights of individuals. The challenge of human government is that the government must be able to control the governed, but at the same time it must control itself. In order to ensure that government protects, but does not threaten, individual rights, the government must be limited by a constitution or written law. As a private citizen, Commander in Chief, and President of the United States, George Washington repeatedly demonstrated his respect for the principle of the rule of law.

The Ironies In Orwells 1984 Essays - Nineteen Eighty-Four

The Ironies in Orwell's 1984 The novel 1984, by George Orwell, has many examples of irony throughout it. The two major types of irony: verbal irony and situation irony, are demonstrated again and again in this novel. In the following essay I will discuss these types of ironies and give examples of each from the book. The first type of irony is verbal irony, in which a person says or does something one way, but the true meaning is the opposite. One of the first example of this irony is discovered when the main character, Winston Smith, uses the "Memory hole" to deposit things -- one would think that this would be where things are remembered ("Memory"), but it's actually an incinerator. The next example of irony comes when you learn about the departments of Government in Oceania. The Ministry of Truth is actually the maker of lies for the history books, the Ministry of Love discourages love, and the Ministry of Peace is actually quite violent. The final example of verbal Irony can be seen in the name of the leader of Oceania, "Big Brother." The concept of a big brother is one whom is older and wiser and helps the "littler siblings" -- this not the case with 1984's Big Brother. The Big Brother in this novel completely watches over every move a person makes keeping them controlled with fear. The next type of irony is Situation irony, which is when a character or a sequence of events appears to be headed one way, but it ends up as the opposite of what was thought. One example of this is Winston's general health. From the beginning of the book, it is shown how horrible his health is and is continually getting worse and more difficult, but as Winston gets involved with Julia then he begins a metamorphosis into a more healthy person. Another major example is the betrayal of many of the people whom Winston thought were his friends, such as Mr. Charrington and even O'Brien- -who both worked for the Thought Police. This book is stuffed full of irony, the entire plot of the beginning would makes the reader expect one reaction and instead, the reader gets twisted the complete opposite direction at the end for surprise. George Orwell uses irony as sort of an exhibit, making it virtually the "how to write irony" novel for me. Throughout the book, all of the irony used became negative and depressing, I still thought this book made its point successfully and was an incredible novel.