Blogs

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 this experiment, a purified sample of 1, 2-diphenylethane-1, 2-diol was obtained through the reduction of benzoin with sodium borohydride and the recrystallization of the product with acetone, resulting in 71.73% yield. The product was identified to be 1, 2-diphenylethane-1, 2-diol via TLC analysis and comparison of the experimental melting point to the known melting point. The known melting point of 1, 2-diphenylethane-1, 2-diol is 138 °C, while the experimental melting point was 135-137 °C. That the experimental range is slightly lower than the known range indicates the presence of impurities in the sample, but the relatively narrow experimental range indicates that whatever impurities remain in the final sample are likely present in only small amounts. During TLC analysis, visualization was achieved via short-wave UV light and iodine staining. Iodine produced yellow stains when reacted with the pure benzoin sample, but not the samples of only the recrystallized or crude product. This contributed to the identification of the spots derived from a mixture of benzoin and my experimental samples. Rf numbers were obtained for benzoin, the crude product, and the recrystallized product. Higher Rf numbers indicate higher polarity. Benzoin is less polar than 1,2-diphenylethane-1,2-diol because alcohols are more polar than carbonyls and 1,2-diphenylethane-1,2-diol has two alcohol groups where benzoin only has one. Since benzoin is less polar, it would be expected to travel farther on the TLC plate and have higher Rf values because it has less absorption with the polar silica gel on the TLC plate than 1,2-diphenylethane-1,2-diol. In the experimental TLC analysis, spots derived from benzoin did move further than spots derived from 1,2-diphenylethane-1,2-diol. 

Obesity is not only a problem within itself but it can cause more problems later on such as type 2 diabetes, heart disease and more. Knowing that a single disease can lead to may other diseases sparked my interest as there may be a solution. Ghrelin is a peptide hormone that increases a person's hunger and causes the pituitary gland to secrete a growth hormone. Blocking the receptor for ghrelin would not be a wise choice because it could also cause changes in behavior and mood. Scientists then thought about blocking the pathway of ghrelin, which led them to find the molecule YIL781. YIL781 is specifically a molecule that is released by ghrelin that causes the feeling of hunger. Therefore, ghrelin can change the intensity or probability of behaviors. Which influences the number of ghrelin being released and binding to the receptors changes throughout the day as the person eats and doesn't eat. Ghrelin would have different intensities depending on the time of day. 

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.  

Mycospondylus mesanyctus is a small nocturnal carnivore that belongs to the family Felidae and the subfamily Felinae. Standing at a height of between 15 and 20cm, with a length of 25-30cm (excluding its tails) and weighing about 1 kg, it is one of the world’s smallest wild cats. It is a digitigrade quadruped with elongated phalanges and laterally ridged paw pads that—alongside the modified ball and socket joints in its shoulders and hips, and hyper flexible ligaments that increase its range of rotational motion—enable it to climb huge trees with trunks made of smooth bark. The midnight cat has sleek blue-black fur that helps it blend into shadows, and a hairless circle in the center of its forehead: this is its “moon”, a patch of specialized bioluminescent skin cells that the midnight cat uses to lure in its prey when hunting at night. Its primary tail is framed by four highly flexible secondary tails that are packed with electroreceptors, and mushroom-like growths line the top of its body from its head to the base of its tails. It has large eyes and ears, giving Mycospondylus both excellent vision and hearing. Males and females of the species look pretty much identical, except for the “antlers” that females have on their heads in between their ears. These are not actually antlers, but are flexible tubes of muscle and skin with pheromone glands at the base. They are usually held down and tucked flat against the head and neck; females will only raise their “antlers” to signal when they are in heat.

Karyotyping is a representation of chromosomes captured at metaphase during meiosis or mitosis. When the chromosomes reach the metaphase phase, the division is halted and then the chromosomes are arranged by size into a karyotype. Several kinds of banding exists including, G-banding, Q-banding, C-banding, and R-banding. G-banding dyes heterochromatin in the chromosomes, Q-banding finds areas rich in A-T vs. G-T and dyes them to identify the homologous chromosomes. C-banding dyes centromeric heterochromatin and R-banding is the reverse of G-banding . With today’s modern technology, softwares can analyze the banding types once it is dyed and arrange them. Moreover, DNA in the nucleus are found in two forms, heterochromatin and euchromatin. Heterochromatin is tightly packed DNA material, whereas euchromatin is loosely packed chromosomes that become active during transcription. Many of these features can be visible with karyotyping method.

About 90% of the birds are monogamous. In order to choose the best fit mate must be done carefully. The quality females look for depends on the species. For example, the red-winged blackbird females will bese their choice depending on how much resource the male has in his territory. The more territory and resources the male has, the more females are attracted. On the other hand, the long-tailed widowbirds females are attracted to males that have a longer tail. The preference of usually is besed on appearance or territory for most females but some species ask for both qualities to be sufficient. Most females will stay with one male and the male will do the same. However, if the female decides that the male is not good enough, she will reproduce with a different male to increase the success in reproducing.

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.