Drafts

CPI-613 is a lipoate derivative that inhibits pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (Anderson et al. 2018). These enzymes in the Krebs cycle allow for carbons from either glucose or glutamine to enter cellular respiration, thereby preventing oxidative phosphorylation. CPI-613 activates pyruvate dehydrogenase kinase, which phosphorylates and inactivates pyruvate dehydrogenase. CPI-613 activates a redox process through a burst of reactive oxygen species that blocks α-ketoglutarate dehydrogenase’s activity (Stuart et al. 2014). A maximum tolerated dose of 500 mg/m² of CPI-613 in combination with the chemotherapy FOLFIRINOX approximately doubled the response rate of patients with metastatic pancreatic adenocarcinoma and showed promising effects for median survival rates (Alistar et al. 2017). The researchers imagine similar effects to be possible in combination with phenformin. By eliminating mitochondrial OXPHOS in PaCSCs, these cells will have no energy to survive and will undergo apoptosis. Since these PaCSCs are the main drivers of metastasis, eradicating them also exterminates their EMT, metastatic niche, chemoresistant, and plastic functions, resulting in an overall greater prognosis for the patient.

The study “Convergent evolution in mechanical design of lamnid sharks and tunas” by Jeanine M. Donley and colleagues explores the convergent evolution between lamnid sharks and tunas. The goal of this study was to gain information on the swimming kinematics of lamnid sharks and demonstrate the convergent evolution by looking at the similarities between morphology and functionality. Because of the great size and risk of studying these sharks, there is little information prior to this study about the movement of these sharks. To study this, in vivomechanisms, such as electromyography and sonomicrometry, were used to examine the contractions of red and white muscles while swimming I. oxyrinchus,shortfin mako sharks, in a swim tunnel. This was done to test if the lamnid sharks, like tunas, uncoupled the shortening of red muscles from the shortening of white muscles and deformation of the skin and backbone. Also, a combination of mechanisms were used to study the 3-demnsional morphology of the myosepta, a tendinous connective tissue.

Phenformin is a potent biguanic OXPHOS complex I inhibitor that has shown greater than 30% tumor growth inhibition in 5 out of 12 pancreatic adenocarcinoma xenograft models (Rajeshkumar et al. 2017). It is more potent than metformin, another OXPHOS complex I inhibitor, which only suppressed tumor growth via mitochondrial membrane inhibition to the same degree in 3 out of 12 pancreatic adenocarcinoma xenograft models with a five-fold higher dose (Rajeshkumar et al. 2017). Additionally, phenformin does not require a cellular transporter, unlike metformin (Iversen et al. 2017). OXPHOS inhibitors, such as phenformin, have also been shown to resensitize previously therapy-resistant cancer cells (Matassa et al. 2016). Due to its high efficacy, the Pancreass Kickers plan to incorporate phenformin into their treatment in conjunction with a Krebs cycle inhibitor, devimistat (CPI-613).

In biochem we are currently going over metabolic pathways. There are anabolic pathways, these pathways require a net input of energy and are endergonic. They are the pathways that are responsible for building complex molecules from less complex molecules. There are also catabolic pathways, these pathways require a net input of energy and they are exergonic. They are the pathways that are responsible for break down of complex molecules into smaller less complex molecules. There are also oxidation and reduction reactions, these are involved in the transfer of electrons between molecules. Oxidation is a reaction when the molecule loses electrons. This would create a more positive charge for the over all molecule, this is because electrons carry a negative charge and without them the molecule loses it’s negative charge. A reduction reaction is when the molecule gains electrons. This would mean that the molecule becomes more negatively charged. Hence why it is called reduced because the charge is decreased. The term that is referring to the affinity a molecule has for electrons is called the reduction potential. This must be tested experimentally in every situation. The metabolism has many complex parts and is incredibly interesting.  

Lek is an occasion for those single birds that need a mate. Birds like manakin will gather to one place and start to show off their displays in terms of plumage, color, vocalization, or dances. In a lek, the male will perform and the female will follow if they like the performance. It is found that these males that form leks have a innate kinship to group up together to win a female to mate. But in the Wild Turkey it is found that these males will form a kinship to collect females but only one of these males have the privilege to mate with the female they like. The kinship appears to be unfair for those males that are only there to assist the one male. However, this kinship does improve the reproduction to be more efficient than one male trying to mate with their desired female.

Sieve Cells are called this because the tubes act as one continuous cell. Sieve tubes are a collection of sieve tube elements that tend to look empty, have very prominent joints, and are very long. They don’t have a nucleus (like xylem, but are living cells), don’t have a cytoskeleton, have very few organelles  (no Golgi, plastids or lignin; some ER, few mitochondria, have plasma membrane). There are companion cells next to sieve cell-ordinary cell that feeds sieve cell/keeps it alive. A ‘Sieve plate’ is the wall in between each cell. Sieve plates are almost like slime/goo and are very prominent-these are phloem clots (like a blood clot in a plant) stops the flow of nutrients. This is how plants keep nutrients from being lost if it is damaged/cut. They contains special clotting proteins and polysaccharides.

Covariates are continuous and natural, a block is discrete. Blocks need one of each treatment and must be decided before experiment is started. Blocking affects how replicates are assigned to treatments. Thus, once a decision has been made, it cannot later be decided to remove ‘block’ as a term in the analysis (some people would today if it does not explain significant variation). The decision to measure covariates can be made at any point. Many potential covariates can be measured. If the analysis shows that they do not explain significant variation in your response, they can be dropped from the model.

 A split-plot design is defined as one factor assigned at the level of main plots (water or none), which are then subdivided into subplots that are the level of replication for a second factor (corn type). A nested design is defined as a research design in which levels of one factor are hierarchically subsumed under levels of another factor. As a result, assessing the complete combination of A and B levels is not possible. Like a split plot design, replication differs for different factors within the same experiment. However, in a nested design each level of one factor is NOT crossed with all levels of the other factor. An example we could use to understand this is to compare differences between 6 cities, 3 on the west and 3 on the east. We can’t analyze the interaction between city and coast because Boston is only on the east coast, Seattle is only on the west.

          The Socioecological Model is a method of categorizing female social relationships through agonism. This is further examined along three social dimensions. The first dimension seeks to establish whether or not a dominance hierarchy is present in the given group being analyzed. A group which lacks a strict hierarchy is defined as egalitarian, in which there are undetectable or poorly defined dominance relationships, or in which the dominance hierarchy is not clear or nonlinear. In these groups, food is often dispersed in a way such that patches cannot be defended, resulting in scramble competition in which the first female to arrive at a food resource may get a larger share of the food simply because she got there first. This means there is nothing to gain from contesting the resource, and thus typically produces weak social relationships in females, with no need for post conflict resolution like grooming. In contrast, a group which exhibits a strict hierarchy is known as despotic, in which there are clearly established, formalized dominance relationships that are usually linear. When there is competition over essential resources, aggressive interactions maintain dominance hierarchy and contest competition is high. High rank can provide priority of access to resources, and potentially higher reproductive success, and may may also result in alliances or affiliative behaviors like grooming. The second dimension aims, once a hierarchy has been observed, to further classify the type of hierarchy present. There may be a nepotistic hierarchy, in which female relatives rank close together due to coalitions and often don’t disperse, or individualistic hierarchies, in which the rank of female relatives are independent of each other, and females do disperse. The third and final dimension seeks to assign the degree of tolerance within the group structure, and generally assumes that as tolerance increases, the severity of aggression decreases while threats toward dominant individuals increases.

The randomization procedure to choose the territories may give us more large territories than small or vice versa. It could also generate coordinates that are close to one territory, both decreasing the randomization. A better randomization procedure would be to assign a number to each possible territory, (1-10 for the large territories, 11-20 for the small territories, for example) that could be used and use a random number generator, then generate 5 numbers for larger territories and 5 for smaller ones. This way, there is an even amount of territory sizes and each territory experimented on is randomized.