Drafts

I have a biochem exam this week so I have been using my thirty minutes of writing each day to go further in depth with topics that I don’t fully understand and want to get a better grasp on. I went to a review session for it to try and help me with some of the topics and one of the questions that the SI asked us really confused me. She asked if the pKa of an amino acid could change and then said the answer to the question was no. She started to explain why it was no then said the question didn’t make sense and scrapped it all together. I made a note of it and tried to figure it out when I got back home. It turns out that in fact the pKa of amino acids can be altered. That is the pKa of the R-group. The pKa’s get altered when a neighboring R-group, which is ionizable, has a similar pKa. This means that the R-groups will be similarly protonated at similar pH levels which means that they will have similar charges. This will cause the R-groups to repel each other and can alter the folding of a protein which will alter the structure. So if an amino acid like glutamic acid (pKa of 4.25) is located close to aspartic acid (pKa of 3.86) they will have the same negative charge at around the same pH. If they are in a cell at physiological pH of 7 they will both be fully deprotonated and have negative charges, this will cause the two groups to repel. Since aspartic acid has a lower pKa it will become deprotonated first and in an effort to prevent repulsion the pKa of glutamic acid will be raised so it doesn’t acquire a negative charge from deprotonation. This helps maintain protein structure.

An estimated 10-15% of pancreatic adenocarcinomas are attributed to genetic causes (Klein 2012). Germline mutations in the BRCA1 and BRCA2 genes are the most common, occurring in 13-19% of families (Lal et al. 2000). The PALB2 and ATM genes are also some that are commonly mutated in hereditary pancreatic adenocarcinomas (Jones et al. 2009). These mutations could be further examined in an effort to detect pancreatic adenocarcinoma earlier in those that are at higher risk. An early screening mechanism of detecting pancreatic adenocarcinoma in patients, regardless of family history, would be significantly beneficial in increasing survivability.

In terms of resistance to the developed ONC201 liposome treatment, a fluorinated-ONC201 analogue, ONC212, has been developed and has shown preclinical efficacy in melanomas and hepatocellular models. A study demonstrated ONC212’s efficacy in in vivo models with ONC201-resistant tumors (Lev et al. 2017). The researchers found an effective combination of ONC212 with the inhibitor AG1024 in vivo for pancreatic adenocarcinoma. ONC212 is effective in pancreatic adenocarcinomas alone and in combination with other drugs such as 5-fluorouracil, irinotecan, oxaliplatin, and RTK inhibitor crizotinib (Lev et al. 2017). This may serve as a backup treatment if resistance to ONC201 develops, and another synergistic combination may be developed from these drugs.

It is a common misconseption that arteries carry oxygenated blood and veins carry deoxygenated blood. This is true in the systemic pathway, where blood is delivered to the body, but it is not true in the pulmonary pathway. The pulmonary system is when the blood is delievered to the lungs. Here deoxygenated blood is carried by arteries and oxygenated blood is carried by the viens. Ultimately, viens carry blood towards the heart and arteries carry blood away from the body. The arteries have a greater amount of pressure than viens due to the fact that blood is pumped out of the heart. Because of that, there is also significantly less blood volume in the arteries than the viens. 

This first chapter introduces the concept of virtual water, which we have already touched upon in class. Pearce defines it here as the water beyond standard household use, but instead the water that is needed during the manufacturing, growing, or feeding of a given product. He explains that food requires the most virtual water, do to the water needed to tend to crops as well as bathe or grow the grain to feed livestock, and then process and preserve their meat. I found Pearce’s enumeration of the amounts of water that go into common products was eye opening, especially that, when factoring in virtual water, the average westerner consumes 360,000 and 480,000 gallons a year. The fact provided in this chapter that I found the most surprising was that the United States was the world’s largest exporter of virtual water. I also found it interesting when Pearce presented a more nuanced view of the virtual water trade that while the current system is untenable, some virtual water trade will always be necessary for particular regions, like those of the Middle East or the Sahara.

Regarding the liposome decorated with TAB004 and an antibody for CA 19-9 on the exterior and ONC201 along with another synergistic drug on the interior, blood tests for antigen biomarkers could be run and evaluated. The CA 19-9 radioimmunoassay (RIA) measures the amount of CA 19-9 in the blood (Pancreatic Cancer Action Network, 2019). CA 19-9 can either be bound to the surface of pancreatic adenocarcinoma cells or secreted by them, so this test can serve as a marker for treatment success. Changes in the levels of CA 19-9 in the blood would allow the researchers to assess the progression of the tumor and see if it is growing, shrinking, or maintaining its size. The normal CA 19-9 range in a healthy individual is 0-37 units per millimeter. Rising levels would indicate progression of the cancer, consistent levels would indicate the cancer has stabilized, and declining CA 19-9 levels would indicate shrinkage (Pancreatic Cancer Action Network, 2019). The researchers would assess this biomarker biweekly. An analogous test for MUC-1 will also be developed and performed by the researchers in an effort to fully assay the targeted treatment. An increase of MUC-1 in the blood would indicate growth, consistent levels would indicate stability, and decreasing levels would imply shrinkage of the tumor. The researchers would also like to develop a method to assess binding affinities of pancreatic adenocarcinoma-specific antigens to the respective antibodies in order to determine the efficacy of the treatment.

An acid base extraction involves looking at a mixture and separating the two solvents within to extract pure compounds.The compounds, when mixed with two different solvents of different densities will separate into two layers. After the compounds are mixed and layers are formed in test tubes, the two phases are separated via pipet. Once the solvents are evvaporated, the separated, we get a yield of the solid compounds. Once the solids are aquired, purification may be done by recrystalization to remove any impurities.

Nonpolar molecules tend to clump together when in aqueous environments. A nonpolar molecule tends to have a majority of nonpolar covalent bonds that occur between molecules of similiar electronegativity causing it to be hydrophobic. For example, carbon-carbon and carbon-hydrogen bonds are examples of bonds between two molecules that have a similar electronegativity. These molecules can generate some temporary, partical charges that allow the molecule to make very weak nonpolar interactions, which are called Van de Waal interactions. However, when in aqueous environments these molecules tend to clump together in order to increase the entropy of the water molecules. Greater entropy is favored in natural environments due to the fact that it requires less energy. When the nonpolar molecules clump together, this decreases the surface area of nonploar molecules that are surrounded by water. A cage of water molecule forms around the hydrophobic molecules preventing the nonpolar and polar molecules from interacting. If the nonpolar molecules were not clumped, there would be more organized water molecules involved in these individual cages. Molecules that are amphipatic contain both hydrophobic and hydrophilic molecules. In aqueous environments, the hydrophobic molecules will clump and the hydrophilic molecules will arrange themselves on the outside. 

I took a picture of a tree named “Honey Locust” near the parking lot next to the Life Science Building. First I took a wide shot of the tree from the ground to the top of the tree before the branches extend from it. The tree was in front of a gray fence with the Life Science Building in the background. Then I took a picture of the tree with the camera focused on the words “Honey Locust. ” There is the Life Science Building and a tree on the right that is visible in the background. Next, I took a picture of the tree very close up showing the moss and the bark. This picture did not include the sign on it and the fence is only barely visible to the left of the tree. ​

First, I imported the 3 pictures into Inkscape. Then I set the width of each picture to 500 mm. I aligned the pictures from corner to corner. Then I made a text box of width 40 mm and typed in the letter “a.” Then I made a white rectangle of width 80 and layered it under the letter. I then centered the letter “a” in in the rectangle. I dragged the rectangle with the centered letter to the top left corner of the figure. I repeated this process with letters “b” and “c” for the next two figures. Then I made two freehand lines of width 6. I put a marker on both of them to make them arrows. I put a white filling on the markers. I positioned the first arrow to point to the moss and the second arrow to point to the bark on the tree. Then I exported the file to create a PNG image. I saved this image onto my computer. 

I agree that artificial selection should be used as a tool in medicine. No one deserves to be born with a life-threatening disease. If we have the capability to prevent that, then we should. But there is a difference between selecting traits to save someone's life and selecting traits based on personal whim. The latter is changing fundamental parts of someone's core identity without their permission. What if a parent designed their kid to have amazing hearing but it backfires by causing anxiety due to noise sensitivity? Or what if a parent chooses for their child to have a beautiful eye color, but it somehow limits the child's visuo-spatial skills? Because many genes control more than one factor I agree that we need more research to be done.