Patients exhibiting a resistance to existing therapies regarding BCR-ABL inhibition which leads to cancer programmed cell death and other long-term responses. A common observed mechanism of resistance is the acquisition of a second site mutation in the BCR-ABL itself. A mutation in the ATP binding pocket at the ‘gatekeeper’ residue theorine 315. This mutation results in the inhibition of optimal binding of inhibitors like imantinib, however, still permitting ATP hydrolysis, and this restores BCR-ABL signaling in the presence of inhibitors. Another example involves resistance to oncogene-targeted drugs which results as a mutation of alternate components of oncogene-induced signaling pathways. Mutant BRAF signal through the MAPK signaling pathways stimulates melanoma growth. One resistance mechanism to BRAF inhibitors is the acquisition of activation mutations in other MAPK pathways components like NRAS. These types of mutations restore MAPK oncogenic pathways signals despite continued therapeutic techniques of inhibitions of mutant BRAF. We know that activated RAS activates MAPKKK by binding to it and then this leads to the activation of MAPKK by phosphorylation, and then MAPK which then proceeds to activate proteins or transcription regulators in order to change protein activity or gene expression.
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Walking is an activity we all perform throughout every day. Ranging from walking to grab a tissue or walking to class. I love to walk because it’s a good start to the day and also a good way to stay healthy. Throughout my Thursday schedule, an activity that I engaged in an abundant amount of time is walking. I walk to all my classes and extracurricular activities throughout the day. Starting from the morning I wake up and do my usual routine and then head out to my Cancer Genetics lecture at Goodell. Then I walk to the library to do any assignments or get breakfast. Then I walk to my Population Genetics course located in Morrill III and after that walk to a seating area in Morrill II. Then walk to my Mammalogy course in Morrill II. Then walk to the gym to a group fitness class. Overall, throughout my day I do an abundant amount of walking. This is a common activity in my everyday lifestyle.
In the article titled, “Origin matters: widely distributed native and non-native species benefit from different functional traits,” there are a variety of headings and it follows the IMRAD format as discussed in our book. This contains an Introduction, Materials and Methods, Results, Discussion section and sometimes an abstract is included. Since the paper is formatted this way it aids readers in identifying a particular section they want. In choosing such a format it shows that the paper illustrates structure and organization. Their abstract addresses the topic they will be addressing and what they were looking to find in the studies performed. This research paper also shares similar features that are included in the article, “Non-native species and rates of spread: lessons from the brackish Baltic Sea.”
The phenomenon of oncogene addiction describes cancer cell dependence on individual oncogenes to sustain the malignant phenotype. There has been clinical evidence to support the idea of oncogene addiction. One area oncogene addiction has been seen is in Chronic myeloid leukemia also known as CML. In CML there is an abnormality in chromosome 22. A translocation event happens where RAG cuts some of the Abl gene and more of the Bcr gene. When they come together and combine, it forms an alternative chromosome 22 referred to as Philadelphia chromosome. CML is essentially driven by the BCR-ABL mutant oncogene as its addiction. This was demonstrated in patients through the clinical responses attained with the kinase inhibitor imatinb, which targets BCR-ABL. It is further supported by genetic mechanisms of resistance that vastly led to reactivation of BCR-ABL kinase activity. Another example is antiandrogens. These are used as a treatment for prostate cancer. They are also known to be ‘lineage addicted’ to AR and have recurrent AR amplifications or mutations upon resistance to first line therapeutic techniques. Overall, medicine continues to advance and we are seeing other ways to support the phenomenon of oncogene addiction.
There is clinical evidence that oncogene addiction exists. This could be seen in CML. CML is referred as Chronic myeloid leukemia. This involves chromosome 22 and an abnormality. A translocation event happens between chromosome 9 and chromosome 22 and there are RAG’s. When there is a mutation it causes RAG to cut some of the Abl gene and more of the Bcr gene. When combined it forms a changed chromosome 22 (Philadelphia chromosome). CML is essentially driven by the BCR-ABL mutant oncogene so it is addicted. This was demonstrated in patients through the clinical responses attained with the kinase inhibitor imatinb, which targets BCR-ABL. It is further supported by genetic mechanisms of resistance that vastly led to reactivation of BCR-ABL kinase activity. Another example is antiandrogens and using them for the treatment of prostate cancers, which are known to be ‘lineage addicted’ to AR and have recurrent AR amplifications or mutations upon resistance to first line therapeutic techniques.
Oncogenes are essentially dominant growth enhancing genes and if overexpressed can augment growth in one cell type but impede growth or stimulate programmed cell death in another cell type. The phenomenon of oncogene addiction describes cancer cell dependence on individual oncogenes to sustain the malignant phenotype. Oncogenic functions are activated by them. Cancer cell survival relies on quite a few key genetic driver events. When an oncogene is turned off this means that the cancer cells will undergo programmed cell death. For instance, in transgenic mice when there is the expression of an inducible form of the H-ras oncogene it develops melanomas. When the ras gene was switched off apoptosis occurred and regressed. Another instance is with the expression of a Bcr-Abl fusion gene which results in the development of leukemia and killed mice. When switched off, even at advanced stages of disease, the leukemic cells underwent rapid apoptosis and this resulted in mice surviving. In cancer cells the regulation of signal transduction and gene expression is rather crazy and distinct of normal cells. Since they have a different form of regulation it is said that cancer cells may be more reliant on the activity of specific oncogenes. In addition, they are more sensitive to the growth-inhibitory effects of specific tumor suppressor genes like p53 versus normal cells.
For Biome 2 I found that the biome that was most suitable to fit this graph was temperate and in particular temperate Evergreen Forest. The graph illustrates little variation in precipitation and temperature. There is also the absence of sub-freezing and drought periods which makes it even more suitable to be predicted as a temperate evergreen forest biome. There are no drought periods because in the graph one could see that the temperature line is always above the precipitation line and never drops staying consistent. There are no sub-freezing points because the temperature never drops below zero or even below 18℃. In January, it has a temperature of 18℃ and the highest temperature reaching to about 22℃ in May and October. The annual precipitation is 691 mm which is way lower than biome 1 and this could predict that not much variation and abundant amounts of precipitation is present in this biome. As depicted in the illustration, precipitation is 60 mm in April, July, August, and September and the lowest reaching 58 mm in January and December. In a temperate evergreen the average temperature ranges from 10-25℃ and in the graph its 17-21℃. In a temperate evergreen the precipitation average is about 45-75 mm. In the graph, we could see an average of 55-60 mm. After analyzing, it could be concluded that the temperature and precipitations fall relatively close to the data presented in the graph. Of the nine biomes known it could be said that this is the best suited one.
Ernst Mayr defined a species as, “species are groups of interbreeding natural populations that are reproductively isolated from other such groups.” With this in mind we know that all three species are able to interbreed. However, they are not necessarily reproductively isolated from other such groups. These three species are able to mate and findings have shown that eastern Canis latrans have been found to more likely kill a dog than breed with it and their species continue to increase. Canis lupus populations found in the Great Lakes have recovered, and Canis lupus are the worst enemy of the Canis latrans. When these two-distinct species are interbreeding there is the creation of variation and mixing of genes. This is also known as a requirement for evolution. As mentioned in the article, “Gene flow continues in all directions, keeping things mixed up, and leading to continual variation over their range, with no discrete boundaries.” I believe that these three organisms are indeed separate species, however, they share a variety of similar characteristics that make them closely related. When these characteristics mix and interbreeding occurs it creates a viable and fertile offspring that might be able to catch their pray faster and make them stronger. As supported by the article, we could see that over time it could be possible that evolution would lead to a Canis latrans so specialized for eastern forests that they would be considered a unique species. But this would require a variety of things like cutting off gene flow with nonhybrid animals resulting in a variety of types of Canis latrans that almost never interbreed.
In temperate grasslands, the dominant type of vegetation are grasses. Temperate Grasslands are a key focus for agricultural and pastoral development. Grasses have to grow more roots than stems in order to obtain enough water and be able to grow. This biomes soil is so rich and as a result it enhances fertility which leads grasslands soil to be a great fit for agricultural development. Since they possess the feature of being suitable for agriculture it has resulting in grasslands, the most human-influenced biome of the nine knowns. Some of the threats temperate grasslands face is overgrazing by livestock and plowing. These threats are results of its key characteristic of having rich nutrient soil. Trees don't make it in grasslands because it’s too dry and they need way more water compared to grasses. They also can’t cope with water stress over long periods of time. However, with some grasslands one can find trees. In addition, disturbances like fires and grazing by herbivores like bison prevent the establishment of trees as well. As a result, grasses hold a dominance of the temperate grassland biome.
After closely observing and using the tools given to me I have concluded that it is some larvae like creature. The organism contains a tail, what appears to be little legs in pairs, and the body is covered in a layer of tissue. The tail attached to the specimen reminds me of a flagellum. This makes me conclude that the tail contributes to the organism’s movement and could also be of use for sensing the environment. It scrunches in and then out to continue moving around the tray. In addition, it has a light brown color that is transparent and one could see the inside of the organism. It has a white core inside it and a layer over it to protect the main body. The organism moves around the specimen tray to get a sense of its new environment and its surroundings. It is bilaterally symmetrical. It’s layer of tissue surrounding it appears to be sticky since the bits of shredded tree bark stick to the organism. The body is about 1.5 cm long. The tail came out to be about 1.6 cm. A total of about 3.1 cm long in length. It is a small organism whose defenses seem to be minimal. Some of the questions that arose while observing were what kind of environment is preferable for the organism to sustain life? What is it closely related to? What kinds of foods does it eat? Is it an herbivore or a carnivore? What is its method of reproduction? Is it a male or female? Is the tail essential?