Cellular and Molecular Biology

Level: Introductory

Checkpoints in the Cell Cycle

Rithika Vutukuri

Cells go through a process called cell division to replicate themselves. There are checkpoints in cell division that check certain aspects of the cell to ensure it is going through the process properly. Checkpoints are necessary in cell division to create a true replica of a cell without unwanted characteristics; one example of an unwanted characteristic in the replica of a cell is damage to the cell, especially damage in its DNA. The 3 main checkpoints that exist in cell division are G₁, G₂, and M.

G₁ Checkpoint

The G₁ checkpoint occurs at the G₁/S transition. If this checkpoint is passed, the cell irreversibly commits to the cell division process unless some major problem occurs. This makes this checkpoint the deciding factor of whether or not a cell continues the cell division process. Some of the main aspects that are checked at this checkpoint are the cell’s size, amount of energy and nutrients, and DNA strength. If the cell’s size is not large enough to able to divide, the amount of energy and nutrients it has is not sufficient for the cell to be able to divide, or there is damage to the cell’s DNA, the cell will halt in the cycle and find a solution or will die to prevent it from causing from. Cell death is known as apoptosis and can occur often in cell division. If the cell has met all the requirements it will move on to the next phases in the process.

G₂ Checkpoint

The G₂ checkpoint occurs at the G₂/M transition. At this checkpoint, the main aspects checked are the DNA’s integrity and whether DNA replication occurred without issues. If the DNA is not damaged, the replication fully occurs, and all other requirements are met, the cell will continue on the cell division cycle. If the cell does not meet all the requirements, it will halt in the process and either fix the issues and move on with the process or it will go through apoptosis.

M Checkpoint

The M checkpoint, which is also known as the spindle checkpoint, occurs near the end of metaphase which is a part of mitosis. The M checkpoint checks whether all the sister chromatids are correctly attached to the spindle microtubules. This is why is it also called the spindle checkpoint. Cell division will not continue unless all sister chromatids are firmly and properly attached to the spindle microtubules because the separation of the sister chromatids during anaphase is an irreversible step. This will allow a smooth division of the cell.

Genetics

Level: Intermediate

DNA Replication

Aaron Chang

Introduction: 

One characteristic that defines whether a thing is living or not is reproduction– also known as the ability of an organism to make more of itself– and DNA is no exception. In this case, cells have to divide in order to make the organism grow and renew itself. However, before cell division can occur,  genetic material must replicate itself to ensure that its daughter cells have identical genetic material and the same number of chromosomes.

Structure of DNA:

DNA, or deoxyribonucleic acid, is a type of nucleic acid and is made up of smaller subunits called nucleotides. These monomer nucleotides each consist of a 5-carbon deoxyribose sugar, a phosphate, and a nitrogenous base. In the case of DNA, the nitrogenous bases can be adenine, thymine, cytosine, or guanine, while the pentose sugar is always deoxyribose. Figure 1 shows a picture of a single nucleotide.

Together, these nucleotides make up DNA. At the molecular level, the nitrogenous bases are held together by hydrogen bonds and the pentose sugar bonds to the phosphate group, creating the phosphate backbone. Figure 2 shows the molecular structure of DNA, where one side of DNA runs from the 5’ end to the 3’ end, and the other side runs from the 3’ end to the 5’ end. Because they run in different directions, we can call DNA antiparallel. The nitrogenous bases also bond in specific ways– with adenine to thymine, in which there are two hydrogen bonds, and with cytosine bonds to guanine, in which there are three hydrogen bonds. In the case of RNA, adenine bonds instead to uracil.

Overview of DNA Replication:

DNA replication is a process in which a cell makes an identical copy of its DNA. Each chromosome copies itself, and the total amount of chromatids thus doubles. DNA replication occurs in several steps and involves multiple proteins to ensure accuracy. In eukaryotic cells, such as animal cells and plant cells, DNA replication occurs in the S phase of the cell cycle, as shown in Figure 3. Most of the time, DNA is loosely packed in the nucleus and called chromatin. However, before cell division occurs, it condenses into visible structures called chromosomes.

DNA Replication Preparation:

Before DNA replication begins, it must be unwound from its double helix formation into two single strands. To do so, the hydrogen bonds that hold the nitrogenous bases together must be broken. This task is completed by the enzyme helicase, which separates the strands into a Y shape in what is known as a replication fork. This area is where DNA replication will take place. Figure 4 shows helicase untwisting and unwinding DNA. 

The strand that runs 5’ to 3’ towards the replication fork is known as leading strand, and the strand that runs 5’ to 3’ away from the replication fork is known as the lagging strand.

DNA Replication:

Once the replication fork has been made, a short piece of RNA called a primer binds to the 3’ end of DNA. Primers are generated by the enzyme called DNA primase. This marks the starting point of replication. DNA polymerases are responsible for creating a new strand from the unwound template through the process of elongation. Replication then proceeds in the 5’ to 3’ direction of the leading strand towards the replication fork. This process is continuous as DNA polymerase adds corresponding bases in the 5’ to 3’ direction. However, the lagging strand runs 5’ to 3’ away from the replication fork, so it is replicated in the opposite direction of the leading strand. The lagging strand does not replicate continuously as the leading strand does. The lagging strand begins replication by the binding of multiple primers. Each primer is several bases apart. DNA polymerase then adds pieces of DNA between the gaps of the primers. These pieces of DNA are known as Okazaki fragments. This is a discontinuous process and the fragments are disjointed. Figure 5 shows a summary of DNA replication.

Termination:

Once all of the corresponding bases are added, an enzyme called exonuclease removes all of the primers and adds the appropriate DNA sequences. Another exonuclease checks the DNA to make sure that the DNA is copied correctly. Then, DNA ligase glues the Okazaki fragments together creating a single unified strand of DNA. During the process of DNA replication, there is tension on the replication fork. Topoisomerase mitigates this problem by unwinding or rewinding DNA to prevent DNA from tangling or supercoiling. The replication fork serves as a template for DNA replication. This makes DNA replication semiconservative, as the original template is used. The result of DNA replication is two identical strands of DNA. This ensures that each of the daughter cells will receive the same genetic material.

Ecology

Level: Introductory

Keystone Species and their Ecological Roles

Jaycee Yang

The word "keystone" in architecture describes a wedge-shaped stone at the summit of an arch, which locks the whole piece together. Keystone species in an ecological context echo the same sentiment. They are species which disproportionately affect the structure of their community. In other words, the presence of these species creates a large structural impact on their community. Keystone species hold the whole ecosystem together much like the keystone of an arch. When describing the role of species in their ecosystem, it is important to understand that organisms are flexible. For example, a population that is a keystone species in one ecosystem may not be a keystone species in another. One prime example of a keystone species in New Zealand is mussels in the Hauraki Gulf.

Extra information about green-lipped mussels:

Hauraki Gulf, located in the north island of New Zealand is home to the green-lipped mussel (Perna Canaliculus), a bivalve mollusk endemic to New Zealand. Mussels in the Hauraki Gulf form one of the most diverse and productive ecosystems in the intertidal zone. Despite this, there remains only 10% of the population of mussels in the Hauraki Gulf before the 1960’s. Due to the growth in New Zealand’s aquaculture and mussel industry, keeping up with the demand for mussels became difficult, so in the late 1960’s, dredges were used to scrape the ocean floor, destroying everything as they harvested the mussels. This unsustainable harvesting impacted not only the mussels but their entire ecosystem. Examining the effects of mass mussel removal in the Hauraki Gulf, the importance of keystone species is displayed.

Impacts of mussels:

The importance of green-lipped mussels is clearly depicted by comparing the seabed with and without their presence. With the mussels, there is more water clarity and more biodiversity in the ecosystem. Without them, the seabed is quite empty. This emptiness can be attributed to the mussels’ structure and feeding habits. When they feed on phytoplankton, they also filter water, making it clearer as they secrete the sediments back to the seabed. This cycle creates a bidirectional effect where mussels maintain water clarity and increase the rate of photosynthesis for phytoplankton growth. As mussels feed on phytoplankton, their population also grows, allowing the maintenance of water clarity. As primary producers, phytoplankton growth is essential to much more than just mussels. Due to incomplete digestion, consumption, and heat loss, energy from an ecosystem is lost from each trophic level: only 10% of energy is maintained from level to level. Due to the successive energy loss, primary producers are very important as the energy they produce determines the biodiversity that can be supported. If there are fewer primary producers, the amount of organisms that can be supported reduces drastically. This effect can be seen in the pictures of ecosystems with mussel beds and those without.
  

What has been done:

Reversing human impacts is called rewilding. Rewilding includes reintroducing keystone species, creating wildlife corridors, and reducing human impacts. In the Hauraki Gulf, one action taken to reintroduce green-lipped mussels was returning eaten mussel shells to the ocean, creating a living space for organisms (including more green-lipped mussels) and increasing biodiversity by successfully reintroducing keystone species.
  

This is a reminder that humans are a part of the ecosystem and that we humans must minimize our harmful impacts, such as harvesting keystone species, if we want to prevent climate instability on a global scale.

Biotechnology

Level: Intermediate

Gene Knockout Strategies

Shutong Xu

Genetic knockout is a gene editing strategy that involves inactivating or removing a specific gene within an organism. Common methods to achieve such effects include transcription activator-like effector nuclease (TALENs), RNA interference (RNAi), and Crispr-Cas9. Although the mechanisms and functions of these three processes are significantly different, they all ultimately achieve similar effects.

Gene knockout through TALENs starts with the TAL protein which is fused to the Fok1 nuclease. Each of the repeats in the TALENs’ repeat domain can be customized by scientists to match with a specific strand of DNA. In order to perform a gene knockdown, a pair of TALENs must create a double strand break in the double helix structure of the DNA. The body then uses the Non Homologous End Joining (NHEJ) mechanism to repair the cut section of DNA. Through the efforts of multiple proteins including Artemis 4 and Ligase 4, the section of DNA is ultimately repaired. However, this repair mechanism leads to an accumulation of insertions, deletions, and other mutations which will ultimately produce a genetic knockout. 

As opposed to TALENs, which result in complete gene knockout, the use of RNAi commonly results in gene knockdown. Rather than eliminating the expression of certain genes, gene knockdown suppresses expression. In addition, the RNAi editing method targets RNA instead of DNA. Short strands of RNA, such as siRNA, are designed to match with the corresponding mRNA. These strands of siRNA are then guided by RISC, a multi-protein complex, to cleave the target strand of mRNA. The nuclease of the RISC then degrades the target mRNA, thus knocking down expression of the gene. 

CRISPR-cas9 is able to both knockout and knockdown genes. CRISPR is primarily composed of two parts, a single guide RNA (sgRNA) and a Cas9 protein. The sgRNA has both a 5 prime (5’) and 3 prime (3’) end. Of these two, the 5’ end binds to the target site, recognizing it through a Protospacer-adjacent motif (PAM) sequence congruent to the target. CRISPR then creates a double stranded break similar to TALENs, relying on NHEJ for knockdown or knockout. 

All three designs have their own advantages and disadvantages. For instance, siRNA and sgRNA are significantly easier for scientists to customize and work with as compared to TALENS. In addition siRNA can be designed to target any mRNA sequence while CRISPR is related to sites adjacent to the PAM sequence. However sgRNA commonly results in more off site mutations as compared to CRISPR or TALENs. The usage of Cas9-Nickase along with CRISPR can also be used to help minimize off target effects. In addition RNAi gene knockout methods tend to result in less dramatic changes in phenotype as compared to other options. Therefore all three methods are commonly used in different situations, depending on the experimental design.

Microbiology

Level: Introductory

Microbiomes 101

Zachary Yuan

It’s eight AM. Alarms sound in households as people get ready for school. On the street below, cars and buses honk in the streets as people rush to get to work or their appointments. Students ride the bus to school. If you imagine what this could look like at a microscopic level, you might have a slight idea of what a microbiome looks like. But what exactly are microbiomes? 

What are microbiomes? 

Microbiomes are large collections of microbes, including bacteria, viruses, fungi, and microorganisms. These microbes coexist naturally inside our bodies, and together, they can greatly contribute to our health. The human body is home to around 39 trillion microbes, which is more than the number of cells we have! 

Some have even referred to microbiomes as a supporting organ in our body due to their importance in maintaining their function and operations. Every human being has a unique group of microbiota that depends on their DNA. The human microbiome potentially holds 500 times more genes than our cells!

The microbiome consists of a lot of microbes that are beneficial to our health– most microbes being symbiotic, meaning the benefits are shared between the body and the microbes– but some can be harmful. Occasionally, the microbes are pathogenic and are able to lead to disease. Usually, pathogenic and symbiotic microbiota can coexist, and disease doesn’t occur. However, if the body they exist in isn’t healthy, or there is an external factor that affects the balance, including diseases, antibiotics, medication, or unhealthy habits, the balance can be thrown off, and the body may be more susceptible to disease. 

Where do these microbes come from? 

Most of your microbes come from your mother when you exit the birth canal during birth, and research has shown that these bacteria are vital to a healthy first few years in life. Babies who are born through a cesarean section are more likely to develop allergies, asthma, obesity, and other health issues later in life. Scientists suspect that many common allergies, like hay fever, happen due to the lack of exposure to microorganisms when young. 

In addition to your mother’s microbes, every single bite of food we consume is home to millions of microbes, and so our diet can have a massive impact on our gut microbiome. If we constantly change diets, the bacteria in our gut microbiomes change as well. Similarly, environmental changes can also affect our microbiomes, as different people and places are home to different microbes. Furthermore, people who live in houses with pets are exposed to a lot more microbes, which isn’t a bad thing. 

Where can you find these microbiomes? 

Microbiomes can be found in almost every body site, as microbes are capable of living in many different environments. Our body is somewhat like a planet with different climates and biomes– each part of our body like different habitats– and each inhabitant adapts to their location. For example, there are microbiomes in our hands, under our armpits, on our scalp, and many more. One of the most interesting microbiomes is the gut microbiome, which can be found in the small and large intestines. The microbes here live in a dark environment of low oxygen and high acidity. 

What do our microbiomes do? 

So much! The gut microbiome is incredibly important to our body, and one of the main reasons why is its ability to break down food and aid digestion. The gut microbiome controls the storage of fat and assists in activating genes that break down toxins and absorb nutrients. Moreover, the gut microbiome can create new blood vessels and replenish the linings of the gut and skin when cells get damaged or die during digestion. 

Furthermore, the microbiome plays a crucial role in preventing illnesses. When humans are born, their immune systems are only partially formed. It’s through interacting with microbes that our body learns to tell the difference between a harmless symbiont and a pathogen, and exposing our body to new foods is an easy way to introduce new microbes to our body through the gut microbiome!

Our microbiomes even affect how we smell, with different microbe species conveying different scents. This highly personal scent can then act as a unique identification for people. Studies have found that people can be identified just from their sweaty T-shirts! 

Scientists also think that our microbiome could affect our mood and behavior, including through sleep and jet lag. When one experiences jet lag, it’s because the change in sleep time puts our gut bacteria out of sync, and our microbiome may be active at the wrong times. In fact, the microbiome even helps us after death. As the immune system stops working, our microbes can spread freely, and our gut bacteria start digesting all our organs inside out, feeding on the chemicals of the damaged cells. 

How do our microbiomes affect us? 

Our microbiome affects our health in many ways that we are still not certain about. Scientists have found that our microbiomes could influence the brain and specifically our mental health in several ways, as microbes can stimulate nerves, regulate neuro-immune signaling, mediate metabolism, control our neuroendocrine system, and produce neuroactive compounds. In addition, the gut microbiota could produce and regulate neurotransmitters, such as serotonin, dopamine, and glutamate, which play important roles in neurological and immunological activities in the brain. 

Furthermore, differences in the landscape of different peoples’ microbiomes may determine their vulnerability to certain diseases and health effects. For example, different environmental exposures can disrupt a person’s microbiome, which might increase the chance of diabetes, neurological and cardiovascular diseases, obesity, allergies, and inflammatory bowel disease. Our microbiota also aid in breaking down toxic food compounds and synthesizing vitamins and amino acids that we digest. For instance, key enzymes needed to form vitamin B12 are found only in our bacteria. Some carbohydrates like starches and fibers are not easy to digest, so the microbiota help to break down these compounds with their digestive enzymes. 

The microbiota also protects us from pathogens that enter the body through drinking or eating contaminated water or food. Some microbes that live in our colon prevent the overgrowth of harmful bacteria by competing for nutrients and attachment sites to the mucous membranes of the gut, a major site of immune activity and the production of antimicrobial proteins. 

Molecular Biology

Level: Introductory

Autophagy

Eileen Li

What is Autophagy?

Autophagy is the process of recycling and degrading cells, in which cells dispose of misfolded, aggregated proteins and old or dysfunctional organelles. Often likened to a cell’s recycling “trash chute”, autophagy plays a crucial role in maintaining homeostasis by keeping the cell healthy and clean.

There are three types of autophagy: microautophagy, chaperone-mediated autophagy, and macroautophagy. Of these, macroautophagy is the most extensively studied. It’s been found that macroautophagy is maintained at a low level during normal cellular activity, but can be activated by stressful conditions. 

A Brief History of Autophagy

The concept of autophagy first emerged in the 1960’s, but its detailed mechanisms were not known until Yoshinori Ohsumi, a Japanese researcher, demonstrated the mechanism of autophagy in yeasts, and then later again in humans.

Yoshinori Ohsumi also identified specific genes related to autophagy, which are classified as ATGs (autophagy-related genes). These genes contain code for ATG proteins– specific proteins that are necessary for the formation of the autophagosome; these proteins play a crucial role in the molecular mechanisms of autophagy.

The basic molecular mechanism of autophagy can be described in five steps: 

1. Initiation

2. Nucleation in autophagosome

3. Elongation and maturation

4. Closure and fusion with lysosome

5. Degradation of intravesical products

During initiation, a phagophore is formed at an omegasome, a structure associated with the endoplasmic reticulum. The process of initiation starts with a set of proteins, called the ULK1 Complex (Figure 1), which form a preautophagosome (PAS for short). 

The ULK1 complex then activates the PI3K Complex, which results in nucleation (step 2) and the formation of the phagophore. The phagophore is a cup shaped membrane structure. Although it is currently unclear where this double-membrane of the phagophore originates from, research has suggested that the plasma membrane, endoplasmic reticulum, golgi complex, or mitochondria may be the original source. 

During the process of elongation and maturation, another set of proteins that are classified as ubiquitin-like conjugation systems are activated. The reaction of the lipid in phosphatidylethanolamine (PE) and microtubule-associated protein light chain 3 (LC3) causes the elongation of the phagophore and fusion to a lysosome. An autophagolysosome is formed.

During this stage, some intracellular contents become trapped in this vesicle. Through selective autophagy, these intracellular contents can be selectively trapped. Once the autophagosome is formed, a nearby lysosome and the autophagosome fuse. Thus, the intracellular contents of the autophagosome become engulfed by the lysosome. Finally, cellular degradation occurs. 

Genetics

Level: Introductory

Chromosomal Abnormalities

Rithika Vutukuri

Chromosomal abnormalities are irregularities within an individual’s chromosomes that can lead to various genetic conditions. These abnormalities can be categorized into two groups: numerical abnormalities and structural abnormalities. Numerical abnormalities occur when an individual is missing a chromosome from a pair or has a pair with more than two chromosomes. Normally, chromosomes come in 23 pairs within an individual’s cells. However, if someone has a chromosomal abnormality, they may not have the standard number of chromosomes. If the chromosome count is normal but there is still an abnormality, it is likely due to a structural abnormality. Structural abnormalities occur when there is an alteration in the chromosome's structure, with common types including deletions, duplications, inversions, and translocations. Deletions involve the removal or absence of a portion of a chromosome. Duplications occur when a segment of a chromosome is repeated. An inversion happens when a part of a chromosome breaks off and reattaches upside down. Translocations occur when a segment of a chromosome breaks off and attaches to another chromosome.

The effects of chromosomal abnormalities vary depending on the type of abnormality and its location on the chromosome. These effects can include diseases, growth issues, developmental problems, birth complications, and syndromes such as Down Syndrome and Turner Syndrome.

Chromosomal abnormalities often result from errors in cell division, which can occur during mitosis or meiosis. During these processes, cells divide to form two new cells, necessitating DNA replication. Errors during this replication can lead to chromosomal abnormalities, which may be detected or remain unnoticed, ultimately determining their presence in an individual and in newborns.

Neuroscience

Level: Introductory

Glial Cells

Jaycee Yang

While neurons, the primary message transmitters of the nervous system, often get the spotlight when thinking about brain cells, up to 90% of brain cells are actually glial cells, which play essential but underappreciated roles in supporting brain function. The role of glial cells is to help regulate the environment of the brain for neural activities in various different ways. Many different kinds of glial cells, including astrocytes, Schwann cells, ependymal cells, oligodendrocytes, satellite cells, and microglial cells, contribute to maintaining the brain’s environment in various ways, which we will explore now.

Astrocytes: 

Astrocytes have several functions, such as delivering nutrients to neurons and removing waste products, as well as helping to repair damaged or scarred nerve cells in the central nervous system. Beyond these, astrocytes regulate and control the extracellular environments. Recent research has also suggested that astrocytes play a role in memory within the hippocampus, indicating that their effects on brain function extend beyond just maintaining the environment. 

Ependymal cells:

Ependymal cells line the brain's fluid spaces (ventricles) and help produce cerebrospinal fluid while forming a barrier between these fluid spaces and the cells. Their cilia, hair-like organelles facing the cavity of the ventricles, time their movement to direct cerebrospinal fluid and are also able to influence the distribution of neurotransmitters to neurons. 

Some ependymal cells can divide and form neurons throughout the lifespan of a cell, allowing neuro-regeneration to occur. These cells also provide an environment that protects axon stumps from degeneration after damage, fostering the growth of alternate neuronal connections and restored function. Essentially, this allows the brain to replenish a portion of dead neurons with them.

Microglial cells:

Microglia make up the main active immune defense in the central nervous system. As a type of macrophage (which is a kind of white blood cell) exclusive to this system, their primary role is to respond to injuries and infectious agents, protecting neurons by preventing build-up of toxic waste substances. Microglia cells have also been found to play a role in multiple sclerosis, a neurodegenerative disease where the immune system malfunctions and attacks its own tissues.

Oligodendrocytes:

Oligodendrocytes are a type of glial cell in the central nervous system that produce an insulation layer called myelin sheath on the neuron's axons. Myelin helps increase the speed of electrical signaling in neurons.

Schwann cells (PNS):

Schwann cells perform the same function of Oligodendrocytes, also producing myelin sheath. However, Schwann cells are found in the peripheral nervous system. 

Satellite cells (PNS):

Satellite cells reside on neuron cell bodies in the peripheral nervous system to protect them and maintain their chemical environment.

Neuroscience

Level: Intermediate

Neurodegenerative Disorders: Parkinson's

Jaycee Yang - Edited by Tess Chan

Parkinson's disease is a progressive neurological disorder. In the beginning, symptoms are mild and quite unnoticeable, but later, people can develop symptoms that include stiffness, slowness, tremors, and overall impaired balance and coordination. However, keep in mind that everyone has a different biological makeup, so some people may have symptoms that others don’t. There is currently no cure for this neurodegenerative disorder, although there are some medical treatments for it. 

This disorder affects the basal ganglia, a structure in the brain critical for fine movement control. It specifically affects the substantia nigra, one of the 4 nuclei (collections of neurons) in the basal ganglia. They mainly communicate through the neurotransmitter, dopamine. Due to 70% -80% loss of dopaminergic neurons in the substantia nigra, other areas in the basal ganglia become overactive. This is due to the loss of these neurotransmitters, which results in dysfunction in the basal ganglia circuitry; this in turn disrupts the communication and coordination between the basal ganglia and the motor cortex, leading to impaired motor control. 

The neurons in the Locus coeruleus nucleus located in the pons are also affected. The Locus coeruleus is where the neurotransmitter/hormone: norepinephrine is made. Norepinephrine is involved with stress and panic responses; it is a part of the sympathetic nervous system responsible for reactive involuntary responses (these cause the body to involuntarily react instead of relaxing). The loss of norepinephrine explains some of Parkinson's symptoms such as fatigue, irregular blood pressure, and decreased movement of food through the digestive system.

Parkinson's can also cause cellular death. It can be caused by external factors and is hard to predetermine and treat. Parkinson’s can be genetic or caused by external factors. In Parkinson’s, many neurons in the substantia nigra contain Lewy bodies. They are unusual clumps of protein alpha-synuclein, and they transmit between neurons and spread throughout the brain. 

Neuroscience

Level: Intermediate

Neurodegenerative Disorders: Alzheimer's 

Jaycee Yang - Edited by Tess Chan

Alzheimer's disease (AD) is a common type of dementia involving the loss of cognitive function. It is a fatal progressive neurodegenerative disorder because there is currently no cure. Contrary to popular belief, AD is not a disease of old age, and no one is immune. There are different stages of AD that can develop over the course of 8-10 years.  At first, patients may only experience short-term memory impairment; however, this can later impair long-term memory, and eventually the part of the brain that regulates heartbeat is destroyed. At the most severe stages, Alzheimer's patients completely depend on others to perform basic everyday tasks. 

Brain atrophy (shrinkage of the brain tissue) occurs in Alzheimer's due to 2 abnormal protein fragments, namely amyloid plaques and Neurofibrillary tangles, spreading around the brain and causing cell death. These begin to accumulate in the hippocampus and the entorhinal cortex, which are areas essential for memory formation.

The Amyloid precursor protein (APP) is a large membrane essential for neural growth and repair. However, APP can be mutated. As it is changed through enzymatic processes, it can become beta-amyloid 42, which is toxic to the brain because it can't be broken down naturally. Beta-amyloid 42 accumulates between neurons and disrupts cell function. This causes abnormal glucose regulation which leads to cortical shrinkage. Some recent research done about Alzheimer’s shows that a non-invasive eye exam can detect excess amounts of this amyloid protein in the retina.  

Neurofibrillary Tangles are abnormal accumulations of Tau protein as it collects inside neurons. Tau proteins help stabilize neurons, but in AD, abnormal chemical changes cause Tau proteins to detach from microtubules and stick to each other, forming threads that tangle inside neurons. These blockages harm synaptic communication by preventing the delivery of nutrients.

Chronic inflammation in AD is caused by a build-up of glial cells. The normal TREM2 gene usually triggers microglia (a type of supporting brain cell) to clear up the beta-amyloid plaques. Due to a mutation, this function is impaired and causes the build-up of plaques. The function of astrocytes is also compromised by plagues. The function of glial cells is also impaired, but they still release chemicals due to the innate immune response, which causes inflammation. Chronic inflammation can lead to neural decay.

The build-up of beta-amyloid deposits in brain arteries (atherosclerosis) and mini-strokes can lead to the reduction of blood flow and oxygen to the brain. This causes the breakdown of the blood-brain barrier. 

Health and Immunology

Level: Introductory

A Simple Introduction to the Life Cycle of a Virus

Rithika Vutukuri - Edited by Dominic Gulaya

Although viruses are not classified as living, it is important to understand the life cycle of a virus in order to create techniques for the prevention of infections. The first part of the cycle is the virus’s entry, in which the virus enters a host cell. In order to gain entry, the virus utilizes various mechanisms to attach to specific receptors on the host cell’s surface. This is often done through endocytosis, the fusion of the virus with the cell membrane. Once inside the host cell, the virus releases its genetic material and becomes available for replication. This step is called uncoating. Then, the genetic material enters the nucleus and takes control of the host cell’s mechanisms. With this new power, it can now use the mechanisms of various organelles to direct the cell to replicate its genetic material and form new virus particles. These virus particles are assembled within the host cell and then released to infect other cells, continuing the cycle of infection and replication. In order to combat the virus, the host organism mounts a defense response against the infection. This often involves the activation of the immune system, which attempts to eliminate the virus and infected cells.

Immunology

Level: Intermediate

Killer T cells and Regulatory T cells

Taili Gao

Killer T cells induce apoptosis of infected host cells by releasing granzymes and perforin. Granzymes activate caspases, which leads to DNA destruction. Because of the destructive abilities of killer T cells, they also produce FAS, a surface receptor. A few days after their activation, killer T cells will also produce FAS ligand, which binds to FAS and promotes the apoptosis of killer T cells. Killer T cells are also inhibited through other means, such as by regulatory T cells. Deficiency in regulatory T cells causes autoimmune diseases and allergies. The activation of the FOXP3 gene is important for the development and maintenance of regulatory T cells. Perforin functions similarly to the membrane attack complex induced by the complement system. 

Immunology

Level: Introductory

Introduction to Leukocytes

Taili Gao

Leukocytes, or white blood cells, include neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The first three cell types are known as granulocytes, characterized by having granules when observed under the microscope. Lymphocytes include B cells and T cells. At a site of infection, neutrophils are the first to arrive, followed by monocytes and T cells. Monocytes can differentiate into macrophages and dendritic cells. Dendritic cells are the main antigen-presenting cells in the body. The other antigen-presenting cells are macrophages and B cells. Antigen-presenting cells have class II MHC showcasing bits of the infectious agent to activate helper T cells. Helper T cells can then activate cytotoxic or killer T cells and stimulate B cells to turn into antibody-releasing plasma cells. Plasma cells have extensive rough endoplasmic reticulum for the production of antibodies. There are five classes of antibodies or immunoglobulins: IgG, IgA, IgE, IgM, and IgD (listed in decreasing abundance). Helper T cells are central players in the immune system. In HIV, the virus uses reverse transcriptase to integrate its genome into those of helper T cells. By infecting helper T cells, HIV increases the risk for developing AIDS. Antiretroviral therapy (ART) can treat HIV, especially early on in the infection. ART uses two reverse transcriptase inhibitors and a protease (needed to assemble the viral coat) inhibitor. 

Cell Biology

Level: Introductory

Cells: The Building Blocks of Life

Rithika Vutukuri - Edited by Tess Chan

Types of cells

There are three domains of life: Archaea, Bacteria, and Eukarya. The first two domains consist of prokaryotic cells, and the last domain consists of eukaryotic cells. The main difference between prokaryotic and eukaryotic cells is that prokaryotic cells lack membrane-bound organelles. For instance, prokaryotic cells do not have a nuclear envelope (the membrane that separates the nucleus from the cytoplasm), endoplasmic reticulum, or Golgi apparatus; some other examples of membrane-bound organelles are the mitochondria and chloroplast. On the other hand, eukaryotic cells, which are found in plants and animals, contain membrane-bound organelles and are more complex than prokaryotic cells. Despite their differences, all cells consist of a cell membrane, cytoplasm, and ribosomes.

What Cells Do

Cells play a vital role in the functioning of organisms. Cells can perform a wide range of functions from simply dividing to regulating metabolism. Many cells work together in humans to carry out metabolism, growth, and reproduction. Additionally, cells can also communicate with each other through chemical signals, allowing them to coordinate and respond to changes in their environment. Without cells, organisms wouldn’t be able to adapt to changes or survive.

Cells are the foundation of life. Although they are small, cells are a key component of our daily activities and support the functions of all life. 

Neuroscience

Level: Introductory

Action Potential

Taili Gao

Electrical signals are transported in neurons through action potentials. On the cell membrane, potassium (K+) and sodium (Na+) channels grant these ions entry into the cell. A higher concentration of K+ is found inside the cell than outside, whereas a higher concentration of Na+ exists outside the cell. K+ channels can be gated or leakage channels. Leakage channels are always open, allowing the passive transport of K+ out of the cell. On the other hand, Na+ channels are all gated. Gated channels usually open in response to a stimulus when the membrane potential reaches its threshold or a certain voltage. When the threshold is reached, gated Na+ channels open, allowing Na+ into the cell, rapidly depolarizing or increasing the membrane potential. Depolarization is followed by repolarization, where gated K+ channels open. The flow of K+ channels out of the cell decreases the membrane potential and causes repolarization, where the membrane potential is brought back to normal. The gated Na+ channels are inactivated, and the gated K+ channels cause an overshoot or hyperpolarization, where the membrane potential is lower than the resting state (-70mV in a neuron). 

Local anesthetics such as cocaine, procaine, and lidocaine function by reversibly binding to Na+ channels in the axon membrane, preventing the opening of these channels to create depolarization and thus inhibiting sensory neurons to propagate action potentials. Local anesthetics also often contain epinephrine or other vasopressors to counter the effects of vasodilation (the dilation of blood vessels) these drugs (except for cocaine) bring. Vasodilation limits the duration of the anesthetics. 

The answer is B. Essential amino acids cannot be synthesized in the body!