Drafts

One pathway for protein misfolding and pathogenesis is improper degradation of proteins. Improper degradation occurs when proteins that are partially functional and can actually benefit cellular processes are degraded despite it being detrimental to the cell. This is seen in the case of cystic fibrosis, where a deletion of a phenylalanine in CFTR leads to partial functionality but is still targeted for degradation by CHIP, a molecular chaperone which ubiquitylates the protein. CFTR is an important membrane channel for the production of mucus, which is why this improper degradation is seen in a large number of cystic fibrosis patients.  Another way in which improper folding can lead to disease is through improper localization. Improper localization occurs when misfolded proteins cannot get to where they need to go, leading to not only a loss-of-function but potential toxicity if aggregated in the wrong place. One example of this is misfolded antitrypsin, which becomes retained in the ER of liver cells and accumulates, preventing synthesis of other proteins resulting in liver damage. Also, since antitrypsin does not get secreted to its proper location, it is unable to inhibit protease activity in the lungs leading to damage in the alveoli and emphysema. Another mechanism for pathogenesis as a result of protein misfolding is dominant-negative mutations. Dominant-negative mutations are characterized by mutant proteins that compromise the function of wild-type proteins, most often in a dimer or quaternary structure. An example of this process is seen in the connective tissue disorder epidermolysis bullosa simplex. When mutant forms of keratin proteins are present, they disrupt the function of the entire keratin composed filament, leading to fragile skin that blisters easily in response to minor friction. Gain of toxic function and amyloid accumulation are two other mechanisms for pathogenesis as a result of misfolding and play a big role in neurodegenerative disorders.

In this article, researchers wanted to learn about the conformational changes of Cas9. Conformation changes can be caused by binding of single guide RNA (sgRNA). These researchers wanted to figure out which molecular components of sgRNA caused the conformation change in Cas9 from inactive to active. In order to do that, the researchers removed different parts of the sgRNA to see how much it changed the change in conformation. When they removed the entire target recognition sequence, the sgRNA was unable to find the Cas9 and there was no change in conformation. However, when they only removed pieces of the recognition sequence, there was some conformational change. This showed that the target recognition sequence could still work if there was some pieces missing, although it would not work consistently. In addition to that, they tried removing the hairpins at the 3’ end of the sgRNA. When they removed the hairpins, they observed intermediate levels of conformation change. These intermediate levels of conformation change indicate that there was incoverting from closed to open in the Cas9 sample.

- The researchers in this study are trying to treat the motor problems and issues associated with the Parkinson’s disease. Parkinson’s disease is caused by a lack of dopamine, which is a neurotransmitter in the brain. Dopamine is directly connected to movement, thus a lack of dopamine can cause some motor issues. As stated in article, “a low level of dopamine causes the basal ganglia to severely inhibit target neurons in the thalamus, called an inhibition.”

- Optogenetics is the usage of lights to control specific target neurons in the brain. The scientists found out that when signals from are more active in the basal ganglia, the neurons in the thalamus become hyperactive. This hyperaction causes the muscle stiffness and muscle tremors that are usually seen with parkinson’s patients. However, when they used the light to suppress this hyperactivity, movement in the mice became normal again.

- Based on the results, I think the light treatment did in fact cure the motor issues in the mice with parkinson’s disease. However, this treatment was used only to confirm that this certain hyperactivity of neurons was the cause of the muscle tremors. As a result, this study was more for a research purpose than a treatment purpose.

According to the article titled, “Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis,” “Approximately 20% of KRAS-mutant LUAD tumors carry loss-of-function mutations in the KEAP1 gene encoding Kelch-like ECH-associated protein 1, a negative regulator of nuclear factor erythroid 2-like 2 (NFE2L2; hereafter NRF2), which is the master transcriptional regulator of the endogenous antioxidant response.” This article essentially states that we should look at a glutaminase inhibition approach. After doing some research, I have learned that if we were to remove glutamine from the body then this would mean a reduction in cell growth or prompt cell death. But what if we remove it and it leads to increase in cell death where there shouldn’t be. I remember from lecture it being mention how in some patients they affected red blood cells and then led to high risk patients with anemia. I am having a hard time wrapping my mind in figuring ways where we won’t be affecting other functions and cells. In my research it also mentions how this indicates that these cells are dependent on, or “addicted” to, glutamine. 

The KRAS gene provides instructions for making a protein called K-Ras. It’s part of a signaling pathway known as the RAS/MAPK pathway. In RAS/MAPK we know that an activated RAS activates MAKKK by binding to it. Then activates MAPKK by phosphorylation and then MAPK. Then MAPK activates proteins or transcription regulators in order to either change protein activity or alter gene expression. The protein relays signals which instruct the cell to grow, divide, and differentiate. The K-Ras protein is a GTPase. When the protein is bound to GDP, it does not relay signals to the cell's nucleus and when its bound GTP it does. The KRAS gene belongs to the oncogene class. From lecture we have learned that when mutated, oncogenes have the potential to cause normal cells to become cancerous. 

In conclusion, carrying capacity and competition plays a huge role whether it can be seen on the surface or if it’s a hidden motive in certain ideas such as racism. Carrying capacity can limit many species, but humans have found a way to manipulate this concept. For example, humans have developed ways to control food supply in the agricultural industry. If they need more food, they can easily intensify or improve their already massive food supplies. Also humans have developed the ability to expand their habitat, an ability not many species on the earth possess. For example, humans have developed the technology of air conditioning and heating, which allows them to expand their habitat into hotter and colder regions respectively. Competition also was a huge factor in racism, as the whites were given majority of the better supplies. The DVD explained that of the $120 billion the government spent on new houses, less than 2% of those homes went to non-whites. All in all, whether we like to admit it or not subconsciously competition and carry capacity play a significant role in the actions we make.  

A plant leaf is composed of several layers. On the outside of the leaf, both top and bottom, the is a waxy layer called the cuticle. This layer helps to prevent water loss from the leaf so that the plant can have more control over its transpiration rates. The next layer is the epidermis, which is also on the top and bottom of the leaf. This layer serves primarily for protection of the internal structures of the leaf. The next layer from the top is the palisade layer. This layer is denesly packed and is primarily used for photosynthesis. The final layer from the top is the spongy mesophyll layer. This layer is thick, but loosely packed together. While it has some photosynthetic function, its primary purpose is to facilitate the gas exhanges within the leaf.  

Humidity has a major impact on the movement of water in plants. Since water movement is passive in plants, its transfer is largely dependent on outside factors. For instance, the humidity of the outside air has a major impact on how quickly water can move through the plant. Humidity in the air makes evaporation more difficult. With higher concentrations of water in the air, the leaf has a harder time transpiring, thus reducing water movement in the plant.

When I first discovered this article, I did not know what to expect when reading the title. I did not know of the egg based vaccine growth process so that was my first spark of interest, but then with further reading learning about the setbacks of the process also drew me in. I find this predicament to be relatable to the problem of antibiotic resistance, bacteria are becoming resistant and gaining advantageous adaptions in order to survive and beat its competitors. The virus in the same way are gaining mutations due to its exposure, advancing so they can survive longer in certain environment. It is the job of scientists and future scientists to find ways to combat these problems and find other suitable alternatives and reliable sources in keep the human population healthy.

In a recent discovery, the process of growing the components of an influenza vaccine in chicken eggs disrupts the major antibody target site on the surface of the virus, thus causing the vaccine to be less effective in humans. The vaccine is injected into the eggs, allowing for replication and then purification of the fluids to extract the virus. However, as the prevalence of the H3N2 virus increases, only 33% of flu vaccines are effective against it. When H3N2 is grown in eggs a specific mutation named LI94P disrupts the region on the protein that is usually recognized by the immune system. Because of this, a vaccine with the mutated protein cannot generate an efficient immune response. Researchers are still further studying the virus and its response, they are also hoping for a substitute in egg base vaccine inoculation.