Prions are the suspected cause of a wide variety of neurodegenerative diseases in mammals. According to prevailing theory, prions are infectious particles made only of protein and found in high concentrations in the brains of infected animals. All mammals produce normal prion protein, PrPC, a transmembrane protein whose function remains unclear.

Infectious prions, PrPRes, induce conformational changes in the existing PrPC proteins according to the following reaction:

PrPC + PrPRes → PrPRes + PrPRes

The PrPRes is then suspected to accumulate in the nervous tissue of infected patients and cause disease. This model of transmission generates replicated proteins, but does so bypassing the standard model of the central dogma of molecular biology. Transcription and translation apparently do not play a role in this replication process.

This theory is a major departure from previously established biological dogma. A scientist decides to test the protein-only theory of prion propagation. He establishes his experiment as follows:

Homogenized brain matter of infected rabbits is injected into the brains of healthy rabbits, as per the following table:

Rabbit 1 and 2: injected with normal saline on days 1 and 2

The above trials serve as controls.

Rabbit 3 and 4: injected with homogenized brain matter on days 1 and 2

The above trials use unmodified brain matter.

Rabbit 5 and 6: injected with irradiated homogenized brain matter on days 1 and 2

The above trials use brain matter that has been irradiated to destroy nucleic acids in the homogenate.

Rabbit 7 and 8: injected with protein-free centrifuged homogenized brain matter on days 1 and 2

The above trials use brain matter that has been centrifuged to generate a protein-free homogenate and a protein-rich homogenate based on molecular weight.

Rabbit 9 and 10: injected with boiled homogenized brain matter on days 1 and 2

The above trials use brain matter that have been boiled to destroy any bacterial contaminants in the homogenate.

Which intermediates of the central dogma of molecular biology below are present in normal cellular replication, but apparently absent in the above model of prion replication?

I. mRNA

II. tRNA

III. Protein

Prions are the suspected cause of a wide variety of neurodegenerative diseases in mammals. According to prevailing theory, prions are infectious particles made only of protein and found in high concentrations in the brains of infected animals. All mammals produce normal prion protein, PrPC, a transmembrane protein whose function remains unclear.

Infectious prions, PrPRes, induce conformational changes in the existing PrPC proteins according to the following reaction:

PrPC + PrPRes → PrPRes + PrPRes

The PrPRes is then suspected to accumulate in the nervous tissue of infected patients and cause disease. This model of transmission generates replicated proteins, but does so bypassing the standard model of the central dogma of molecular biology. Transcription and translation apparently do not play a role in this replication process.

This theory is a major departure from previously established biological dogma. A scientist decides to test the protein-only theory of prion propagation. He establishes his experiment as follows:

Homogenized brain matter of infected rabbits is injected into the brains of healthy rabbits, as per the following table:

Rabbit 1 and 2: injected with normal saline on days 1 and 2

The above trials serve as controls.

Rabbit 3 and 4: injected with homogenized brain matter on days 1 and 2

The above trials use unmodified brain matter.

Rabbit 5 and 6: injected with irradiated homogenized brain matter on days 1 and 2

The above trials use brain matter that has been irradiated to destroy nucleic acids in the homogenate.

Rabbit 7 and 8: injected with protein-free centrifuged homogenized brain matter on days 1 and 2

The above trials use brain matter that has been centrifuged to generate a protein-free homogenate and a protein-rich homogenate based on molecular weight.

Rabbit 9 and 10: injected with boiled homogenized brain matter on days 1 and 2

The above trials use brain matter that have been boiled to destroy any bacterial contaminants in the homogenate.

Which of the following findings would most strongly refute the protein-transmission hypothesis of prion propagation?

Temperature sensitive (Ts) mutations are a powerful genetic tool in yeast and fruit flies. Ts mutations allow researchers to examine biological functions of specific genes at permissive (phenotypically normal) and restrictive (phenotypically abnormal) temperatures. What is the likely result of the Ts mutation at the restrictive temperature?

A surface protein would most likely be translated from mRNA by the __________.

In the crusade to create a vaccine for Poliomyelitis, Jonas Salk and Albert Sabin created two separate vaccines that proved to be successful in preventing Polio onset.

The Salk vaccine, which is given by standard injection, contained virus particles inactivated by an organic solvent. This method has the advantage of inactivating each of the three Polio strains with no bias.

Albert Sabin's vaccine, given by oral inoculation via sugar water, contained live virus particles that had been genetically attenuated. With this method, each of the three Polio strains acquired separate mutations that made them unable to infect the human host cells. Strain 2 in particular contained one single nucleotide polymorphism in the internal ribosomal entry site (IRES) that prevented successful viral replication.

What is the function of the internal ribosomal entry site (IRES) utilized by the Poliovirus?

In 2013, scientists linked a cellular response called the unfolded protein response (UPR) to a series of neurodegenerative diseases, including such major health issues as Parkinson’s and Alzheimer’s Disease. According to their work, the unfolded protein response is a reduction in translation as a result of a series of enzymes that modify a translation initiation factor, eIF2, as below:

In the above sequence, the unfolded protein sensor binds to unfolded protein, such as the pathogenic amyloid-beta found in the brains of Alzheimer’s Disease patients. This sensor then phosphorylates PERK, or protein kinase RNA-like endoplasmic reticulum kinase. This leads to downstream effects on eIF2, inhibition of which represses translation. It is thought that symptoms of neurodegenerative disease may be a result of this reduced translation.

Which of the following is true of the ribosomes central to translation, as discussed in the passage?

Protein is translated from __________ transcripts.

Type 1 diabetes is a well-understood autoimmune disease. Autoimmune diseases result from an immune system-mediated attack on one’s own body tissues. In normal development, an organ called the thymus introduces immune cells to the body’s normal proteins. This process is called negative selection, as those immune cells that recognize normal proteins are deleted. If cells evade this process, those that recognize normal proteins enter into circulation, where they can attack body tissues. The thymus is also important for activating T-cells that recognize foreign proteins.

As the figure below shows, immune cells typically originate in the bone marrow. Some immune cells, called T-cells, then go to the thymus for negative selection. Those that survive negative selection, enter into general circulation to fight infection. Other cells, called B-cells, directly enter general circulation from the bone marrow. It is a breakdown in this carefully orchestrated process that leads to autoimmune disease, such as type 1 diabetes.

When activated, T-cells use a number of proteins to kill cells that they recognize as foreign. A scientist develops an experimental drug to treat autoimmune disease by disrupting one of these proteins. The drug degrades the cytosolic mRNA for this protein in a T-cell. Which of the following is true if this drug is used successfully?

I. The protein is synthesized, but in an inactive form

II. The protein gene is transcribed

III. The total complement tRNA used for synthesis of the protein is not mobilized to active ribosomes

Most scientists subscribe to the theory of endosymbiosis to explain the presence of mitochondria in eukaryotic cells. According to the theory of endosymbiosis, early pre-eukaryotic cells phagocytosed free living prokaryotes, but failed to digest them. As a result, these prokaryotes remained in residence in the pre-eukaryotes, and continued to generate energy. The host cells were able to use this energy to gain a selective advantage over their competitors, and eventually the energy-producing prokaryotes became mitochondria.

In many ways, mitochondria are different from other cellular organelles, and these differences puzzled scientists for many years. The theory of endosymbiosis concisely explains a number of these observations about mitochondria. Perhaps most of all, the theory explains why aerobic metabolism is entirely limited to this one organelle, while other kinds of metabolism are more distributed in the cellular cytosol.

Scientists studying endosymbiosis often support the theory by referencing the differences between mitochondria and other membrane-bound organelles, as the passage discusses. Which of the following is NOT a membrane-bound organelle?

Cryptosporidium is a genus of gastrointestinal parasite that infects the intestinal epithelium of mammals. Cryptosporidium is water-borne, and is an apicomplexan parasite. This phylum also includes Plasmodium, Babesia, and Toxoplasma.

Apicomplexans are unique due to their apicoplast, an apical organelle that helps penetrate mammalian epithelium. In the case of cryptosporidium, there is an interaction between the surface proteins of mammalian epithelial tissue and those of the apical portion of the cryptosporidium infective stage, or oocyst. A scientist is conducting an experiment to test the hypothesis that the oocyst secretes a peptide compound that neutralizes intestinal defense cells. These defense cells are resident in the intestinal epithelium, and defend the tissue by phagocytizing the oocysts.

She sets up the following experiment:

As the neutralizing compound was believed to be secreted by the oocyst, the scientist collected oocysts onto growth media. The oocysts were grown among intestinal epithelial cells, and then the media was collected. The media was then added to another plate where Toxoplasma gondii was growing with intestinal epithelial cells. A second plate of Toxoplasma gondii was grown with the same type of intestinal epithelium, but no oocyst-sourced media was added.

The scientist in the passage develops an effective treatment for cryptosporidium infection. The treatment exploits a difference in the rRNA structure between cryptosporidium and its human hosts. In which organelle is this difference most likely to directly manifest?