jonathanrubi's blog

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.

Walking is necessary to complete tasks on campus throughout the day. Between the hours of 10:30am and 8pm which I was on campus, I walked to Newmans center, Morrill Science building, Blue Wall, and Draper Hall. The purpose was either to attend class or consume food. I was able to navigate using my previous experiences and knowledge of the layout of the campus.  

The organism being observed consists of a body and tail structure covered by a translucent coating. The length of both the tail and body are roughly 15mm and the height of the body is roughly 3mm. The organism is able to move in a wave-like manner, utilizing its ability to contract and expand as well as six leg-like stumps on the bottom of the organism that seem to provide added traction. The six legs counted on the bottom of the organism also seem to provide stabilization and help to turn the organism over when on its back. Also observed through the translucent underside of the organism were white intestine-like organs lining the body, that could have digestive or nervous system functions. Despite being able to move, the organism seemed to lack direction and some sensory skills, moving around the perimeter of the container primarily, and frequently running into the edge. The organism is clearly aware of its surroundings however, when the container was shaken or moved, the organism stopped moving and only resumed when presumed safe. This stopping of movement when in presumed danger could be an important mechanism for evading the detection of predators. Many questions remain about the development of the organism as well as its habitat, place in its ecosystem and sensory and physiological capabilities. 

One specific paragraph in Non-native species and Rates of Spread that flows exceptionally well is that regarding the New Zealand mud snail, Potamopyrgus antipodarum. First the authors give background on the migration of the mud snail over time, then going into specifics on rates and dates. They then go into the significance of this non-native species and its distinction from others in the area. In Origin Matters, one paragraph that was written very clearly was that regarding the multiple models they used in the experiment. They provided sufficient details and descriptions for a methods paragraph and also clearly stated the purpose for using multiple models in their experiment.

This review, authored by Dr. Hingorani and Dr. Gierasch, aims to link fundamental research regarding in vitro and in vivo protein folding in an evolutionary context. Since RNaseA was first denatured and re-folded sixty years ago, studies regarding in vitro protein folding have advanced our understanding of the process of protein folding specifically of small fast-folding domains, which could shed light on their in vivo folding properties and function in large proteins and the proteome as a whole. Strides have also been made in understanding the purpose and nature of unfolded protein states in vitro. Despite tremendous advances in the understanding of protein folding in vitro, there are still so many factors manufactured by the cells diverse and adaptive environment that cannot be simulated in highly diluted conditions. Factors such as chaperone and degradation enzyme aided folding, co-translational folding, crowding/ protein-protein interactions are all vital factors that affect how a protein folds and can only exist in vivo.

The organism being observed consists of a body and tail structure covered by a translucent coating. The length of both the tail and body are roughly 15mm and the height of the body is roughly 3mm. The organism is able to move in a wave-like manner, utilizing its ability to contract and expand as well as six leg-like stumps on the bottom of the organism that seem to provide added traction. The six legs counted on the bottom of the organism also seem to provide stabilization and help to turn the organism over when on its back. Also observed through the translucent underside of the organism were white intestine-like organs lining the body, that could have digestive or nervous system functions. Despite being able to move, the organism seemed to lack direction and some sensory skills, moving around the perimeter of the container primarily, and frequently running into the edge. The organism is clearly aware of its surroundings however, when the container was shaken or moved, the organism stopped moving and only resumed when presumed safe. This stopping of movement when in presumed danger could be an important mechanism for evading the detection of predators. Many questions remain about the development of the organism as well as its habitat, place in its ecosystem and sensory and physiological capabilities. 

- this organism appears to have a body-like structure with a long wirey tail 

- there appears to be a coated translucent layer surrounding the organism 

 - it propells itself forward in a wave-like amnner beginning with the back of the body up the length and ends with the stretching of the head forward

- the end of the tail is not covred by the translucent coating 

- 6 leg-like cilia propell it forward 

- the body is roughly 15 mm and the tail is roughly 15 mm in length as well. The body is also 3 mm in height 

- It tends to lack direction, circling the perimeter of the container and it appears to stop when moved or shaken 

- The underbelly of the organism shows intestinal-like organs that are symmetrical and white on both sides 

- A couple of questions remain including if the organism is fully developed, what does it feed on? what is its natural habitat? how does it interact with other organisms?