Writing in Biology - Section 1

Chikungunya is an infection caused by the chikungunya virus (CHIKV). This is spread by a mosquito, like Zika and dengue.  The most common symptoms of this virus are joint pain along with a fever. It can become very severe leading to severe headaches, swelling of limbs and even death. There are recent outbreaks in the United States, but this virus is primarily spread in parts of Africa, the Caribbean’s and India. Researchers from the University of Bristol and the French National Centre for Scientific Research (CNRS) in Grenoble, France, have come together and created a vaccine that can withstand very warm temperatures.  They worked with a synthetic protein scaffold with no genetic material inside that is still extremely stable, even without refrigeration. Additionally, it can be easily engineered which is a great step in the medical industry. The greatest part about their discovery is that they can insert harmless bits of the Chikungunya to generate a mimic to further use as a vaccine. Although they are still figuring out the logistics of it, computers and technology have helped them create a digital model of the vaccine. Intriguingly, because of this great beginning to fight again CHIKV, they can now rapidly engineer similar vaccines that can combat many other infectious diseases.

The goal of the research is to use the bioinformatics and homology model to obtain three dimensional native and mutated PMP22 models, and show how it is anchored to the cell membrane to determine how L16P and T118M mutation affect the conformational behavior of PMP22.

The conclusion obtained in the experiment tells that there is less stability with mutated protein compared to the normal proteins, resulting specifically from residue 16 and in alpha-helix h1-h2. The data obtained in the experiment also concluded that there was less hydrogen bonding at the side near the mutated site and as a result of this deviation from the normal protein, the mutated protein has a harder time getting out of the ER.   

The impact on the disease is that when the structure and how the protein complex interacts, it would make the mechanism of the disease easier to understand, and by understanding the mechanism of the disease at a molecular level, a relatively noninvasive treatment can be created to combat the effect of mutated proteins. 

The data from anchoring the protein complexes into the membrane tells that there is no spacial difference between the converged area per lipid values (table1).  In addition, there is a higher delta g binding in the mutated protein compared to the normal protein(table 2,3). Another difference includes the delta g total was higher in the mutated protein compared to the normal proteins (table 2,3). The results of the experiment also showed that residue 16 was crucial for changes that are induced by the mutation, and both of the mutations alter the structure and the interaction of the proteins by changing the binding properties. In the PCA, it’s revealed that PMP L16P hsd more negative eigenvalues on the first PC and PMP22 T118M had a more positive eigenvalue (figure 2). Revealing that the mutants are more flexible compared to that of the mon mutated protein, which suggests a higher number of conformational states.  The data that the mutated system is more flexible is supported by the data that the mutated systems have are less stable than the normal protein. The PCA also showed that the highest fluctuation was concentrated along the alpha helix 3 loop and the alpha-helix 4 loop in normal protein and in the mutated protein, the fluctuation was highest at lppo alpha-helix 1-2. In both of the mutations, there was a reduced number of hydrophobic contact and less hydrogen bond around the mutated parts of the protein (figure 2,4,5). The mutated complexes also have a higher delta g binding, leading to the inability of the protein to leave the ER(table3).

The first step of the experiment that they did is to obtain a 3D model of PMP22 and RER1. The three-dimensional structure was determined by homology modeling using mouse PMP22 protein which shares 29% of its PMP22 genes with humans. The 3D model was then mutated at L16P and T118M to generate the mutant protein. RER1 was then docked to the constructed protein to simulate its behavior in the ER. The PMP22 system was then anchored to POPC bilayer membrane and submitted for .5ul MD simulations, which mimics what happens in real cell membranes.  

    The second step was the analysis that was done with the data that was obtained in the MD simulations (figure 1). The researchers did Principal component analysis, which reduces the complexity of the data and extracts the relevant motions of the atoms examined (figure 2, 6). In this analysis, eigenvectors, which describes the motion of the protein and eigenvalues, which in this case describes the total mobility associated with each eigenvector, were identified. The protein-protein docking calculations were also performed (figure 3,4,5). This calculation generates a detailed model that indicates where each atom is at any time. The effective binding energy was also obtained through the MMGBSA approach.  This allows for the estimation of effective binding free energy, which is the energy needed to disassemble a protein or a molecule. The researchers then calculated the effective binding free energy for each of the PMP22- RER1, which is a measure of total free energy differences in the molecules that are involved (table 2,3). Clustering calculation was also performed to identify the most popular conformations. 

Abstract. Plants adapts to varying climates based on their varying geographical locations. Photosynthetic rates sometimes vary among plants within a habitat, and across habitats... [and are]...correlated with species composition, habitat preference, or growth rates (Guerevitch, 2006). An experiment is conducted to determine the effects of latitude and elevation on vegetation patterns of Vaccinium vacillans. The density of Vaccinium vacillans is measured in 11 4x4m plots within three sites: Mt. Norwottuck, Amherst, Massachusetts,  Plum Creek, Amherst, Massachusetts and at Deer Brook, Swanton, Vermont. Each site is varying in latitude and elevation. It is predicted that a widespread, common species will show parallel changes in abundance as elevation increases and as latitude increases in New England.

During fractional distillation, a steady, slow rate of one drop every twenty to thirty seconds is necessary for the proper separation and purification of the compounds.  The thermometer of the apparatus will keep track of the temperature of the vapors as they reach the top and condense into the vial at this consistent drop rate.  While the drops are being collected, there will be one plateau of drops at one consistent temperature.  Then, a slight dip in temperature will be observed.  During this part of the distillation, the first component of the mixture has been used up and the higher boiling point substance is being vaporized.  Because of the higher boiling point, more energy is needed to achieve this explaining the dip in temperature.  This was seen in both the known mixture and the unknown mixture.  In the transition phase between the first plateau and the second plateau, the drops, if any are produced, are not pure and should be separated from the first plateau's drops and the second plateau drops to ensure two pure compounds are formed.  To continue distillation, additional heat needed to be added to both distillations. 

Blood doping has been an issue in the athletic community for quite some time now. Oxygen is a key component when it comes to taking part in any athletic competition. It allows the muscles to create energy and assist the athletes in taking part in their sport. In most cases, blood doping allows the person to increase the amount of hemoglobin in their blood. This helps because hemoglobin is responsible for transporting oxygen in the red blood cells. It can be done through blood transfusions, injections of erythropoietin (EPO) or injections of synthetic oxygen. Our kidneys normally produce EPO to activate the production of red blood cells and so when additional amounts are injected, they allow more oxygen to be transported to our muscles. However, what the athletes sometimes do not realize that they are at a risk for heart attacks, strokes or blood clots through these methods of blood doping. Other alternative methods for increasing oxygen levels in the blood should be taken into consider. For example, training in higher altitudes slowly but surely start increasing the amount of red blood cells we have to compensate for the lack of oxygen there and so it can really help when taking part in a sport later. 

The Field research was conducted on September 16th, 2015. The sites used to conduct the research were Mt. Norwottuck, Amherst, Massachusetts (42o 18'N, elevation 400 m),  Plum Creek, Amherst, Massachusetts (42o 19'N, elevation 60 m) and at Deer Brook, Swanton, Vermont (44o 06'N, elevation 50 m). The density of Vaccinium vacillans was measured on 11 4x4m plots within each site. The 4 x 4 m plots were randomly chosen on each site. The number of individual Vaccinium vacillans per site, were counted, recorded and compared. 

Action potentials are the units of transmission across nerve cells. Action potentials were first observed by Hodgkin & Huxley in a squid’s giant axon. Through experimentation and mathematics, they hypothesized a namesake model that suggested that there were gated channels controlling the rise and fall in membrane potential. As technology developed, this model was vindicated. Through the application of suction to a microscopic region of the axon, ion channels could be isolated and their current measured. When current was run through the axon, it was shown that the channels produced a short-term inward current that stops until the membrane returns to below resting membrane potential. Later studies using tetrodotoxin and other poisons yielded information about the structure of these channels. Today, the canonical information taught about action potentials is that there is a resting membrane potential around -65 mV, an action potential threshold of -40 mV, a rising phase, an overshoot above 0 mV, a falling phase, an undershoot under -65 mV, and a return to resting potential. The action potential is often referred to as an all-or-nothing response, as a neuron will fire once the membrane potential reaches threshold. Whether or not this occurs within a neuron is a complicated process that often involves thousands of computations. However, once the action potential reaches threshold, voltage-gated sodium channels open, sodium floods into the axon due to the concentration gradient and the electrical gradient, causing membrane depolarisation. Then, voltage-gated potassium channels open approximately 1 ms later - a system known as a delayed rectifier - allowing potassium to go down its electrochemical gradient to rush out of the axon, causing hyperpolarisation. The sodium channels lock preventing re-depolarisation, forcing the depolarisation to travel down the axon in a chain reaction of opening and closing voltage-gated channels. Then the sodium/potassium pump returns the membrane to resting potential, allowing for the next action potential to fire.

The use of bacteriophages in modern medicine has proved to be useful. The term “bacteriophage” stands for bacteria eater. Bacteriophages occasionally remove a portion of their host cells' bacterial DNA during the infection process and then transfer this DNA into the genome of new host cells. This process is known as transduction. Phage therapy is the use of bacteriophage to treat bacterial infections. Phage therapy is typically used when conventional antibiotics are not effective.

https://www.nature.com/scitable/definition/bacteriophage-phage-293/

https://en.wikipedia.org/wiki/Phage_therapy