BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: DNA (Page 1 of 6)

CRISPR Quits Coronavirus Replication

The gene-editing CRISPR has now been utilized by scientists to prevent the replication of Coronavirus in human cells, which can ultimately become a new treatment for the contagious virus. However, since these studies were performed on lab dishes, this treatment can be years away from now.

Firstly, CRISPR is a genome-editing tool that is faster, cheaper, and more accurate than past DNA editing techniques whilst having a much broader range of use. The system works by using two molecules: Cas9 and guide RNA (gRNA). Cas9 is an enzyme that acts as “molecular scissors” that cuts two strands of DNA at a specific location. gRNA binds to DNA and guides Cas9 to the right location of the genome and ultimately makes sure that Cas9 cuts at the right point.

 

CRISPR'S Cas9 enzyme in action

CRISPR’S Cas9 enzyme in action

In this instance, CRISPR is used to allow the microbes to target and destroy the genetic material of viruses. However, they target and destroy the RNA rather than the DNA. The specific enzyme they use for this is Cas13b, which cleaves the single strands of RNA, similar to those that are seen in SARS-CoV-2. Once the enzyme Cas13b binds to the RNA, it destroys the part of the RNA that the virus needs to replicate. This method has been found to even work on new mutations of the SARS-CoV-2 genome, including the alpha variant.

COVID-19 vaccines are being distributed around the world, but an effective and immediate treatment for the virus is necessary. There are many fears that the virus will be able to escape the vaccines and become a bigger threat. Although this treatment is a step in the right direction for effective treatment of COVID-19, this technique will ultimately take a long time for the treatment to be publicly available.

CRISPR is greatly relevant to AP Bio, as seen through its use of enzymes in DNA replication. CRISPR utilizes Cas9, an enzyme that is similar to helicase. In DNA replication, the helicase untwists the DNA at the replication fork, which after the DNA strands are replicated in both directions. 

This article is fairly outdated since there have now been immediate treatments created for COVID-19. But, what do you think about the use of CRISPR for future viruses and pandemics? Personally, I believe that CRISPR will ultimately become a historical achievement in science due to its various uses. Thank you for reading and let me know what you think in the comments! 

 

The Redesigning of CRISPR

Cas9, a key component of a widely used CRISPR-based gene-editing tool has been redesigned by scientists at The University of Texas at Austin to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version. This could potentially make gene replication safer and more abundant for medical use.

The CRISPR-Cas9 system consists of an enzyme that introduces a change or mutation into DNA. Cas9 enzymes can cut strands of DNA at a specific location in the genome so parts of the DNA can then be added or removed. CRISPR-based gene-editing tools are adapted from naturally occurring systems in bacteria. In nature, Cas9 proteins search for DNA with a very specific sequence of 20 letters. When most of the letters are correct, Cas9 could still change these DNA fragments. This is called a mismatch, and it can have disastrous consequences in gene editing.

The challenge with using CRISPR-based gene editing on humans is that the molecular machinery occasionally makes changes to the wrong section of a host’s genome. This could possibly repair a genetic mutation in one spot in the genome but may accidentallyDna, Analysis, Research, Genetic Material, Helix create a dangerous new mutation in another.

SuperFi-Cas9 is the name of the new version of Cas9 which has been studied and proven to be 4,000 times less likely to unnecessarily cut off-DNA sites but operates just as fast as naturally occurring Cas9. In the Sauer Structural Biology Lab, scientists were surprised to discover that when Cas9 encounters a type of mismatch, there is a “finger-like structure” that swoops in and holds on to the DNA, making it act like the correct sequence. Usually, a mismatch leaves the DNA unorganized since this “finger-like structure” is mainly used to stabilize the DNA. Based on this insight, scientists redesigned the extra “finger” on Cas9 so that instead of stabilizing the part of the DNA containing the mismatch, the finger is stored away which prevents Cas9 from continuing the process of cutting and editing the DNA. This result in SuperFi-Cas9, a protein that cuts the right target just as readily as naturally occurring Cas9, but is much less likely to cut the wrong target.

This applies to our unit on mitosis when cells are replicating DNA in the S-phase. When chromosomes are duplicated, gene replication occurs. Sometimes gene replication could result in mutations which could lead to a cell not functioning properly. A cancerous cell is an example of cell not performing normally since it rapidly performs mitosis causing the cell to duplicate uncontrollably. This results from an abnormality in gene replication where CRISPR technology can locate this mutation and restore the cell back to normalcy.

CRISPR Mini | New Territory Unlocked

For over a million years, DNA has centered itself as the building block of life. On one hand, DNA (and the genes DNA makes up) shapes organisms with regard to physical appearance or ways one perceives the world through such senses as vision. However, DNA may also prove problematic, causing sickness/disease either through inherited traits or mutations. For many years, scientists have focused on remedies that indirectly target these harmful mutations. For example, a mutation that causes cancer may be treated through chemotherapy or radiation, where both good and bad cells are killed to stop unchecked cell replication. However, a new area of research, CRISPR, approaches such problems with a new perspective.

The treatment CRISPR arose to answer the question: what if scientists could edit DNA? This technology involves two key components – a guide RNA and a CAS9 protein. Scientists design a guide RNA that locates a specific target area on a strand of DNA. This guide RNA is attached to a CAS9 protein, a molecular scissor that removes the desired DNA nucleotides upon locating them. Thus, this method unlocks the door to edit and replace sequences in DNA and, subsequently, the ways such coding physically manifests itself. Moreover, researchers at Stanford University believe they have further broadened CRISPR’s horizon with their discovery of a way to engineer a smaller and more accessible CRISPR technology.

This study aimed to fix one of CRISPR’s major flaws – it is too large to function in smaller cells, tissues, and organisms. Specifically, the focus of the study was finding a smaller Cas protein that was still effective in mammalian cells. The CRISPR system generally uses a Cas9 protein, which is made of 1000-1500 amino acids. However, researchers experimented with a Cas12f protein which contained only 400-700 amino acids. Here, the new CasMINI only had 529 amino acids. Still, the researchers needed to figure out if this simple protein, which had only existed in Archaea, could be effective in mammals that had more complicated DNA.

To determine whether Cas12f could function in mammals, researchers located mutations in the protein that seemed promising for CRISPR. The goal was for a variant to activate a protein in a cell, turning it green, as this signaled a working variant. After heavy bioengineering, almost all the cells turned green under a microscope. Thus, put together with a guide RNA, CasMINI has been found to work in lab experiments with editing human cells. Indeed, the system was effective throughout the vast majority of tests. While there are still pushes to shrink the mini CRISPR further through a focus on creating a smaller guide RNA, this new technology has already opened the door to a variety of opportunities. I am hopeful that this new system will better the general well-being as a widespread cure to sickness and disease. Though CRISPR, and especially its mini version, are new tools in need of much experimentation, their early findings hint at a future where humans can pave a new path forward in science.

What do you think? Does this small CRISPR technology unlock a new realm of possibility or does it merely shed light on scientists’ lack of control over the world around us?

CRISPR Causes Cancer, Sort Of

          Scientific researchers are always looking for ways to improve modern science and help create new treatments. Currently, CRISPR, “a powerful tool for editing genomes,” holds the ability to help advance medicine, specifically gene editing, so long as the kinks in this specific method are worked out. One of these problems is the DNA damage caused by CRISPR “activates the protein p53,” which tries to protect the damaged DNA. This raises not one, but two concerns as present p53 can diminish the effectiveness of this technique, however when there is no p53 at all cells grow rapidly and become cancerous. As we learned in AP Biology class, typical cells communicate through chemical signals sent by cyclins that ensure the cell is dividing the right amount. Cancer cells, however, contain genetic mutations that prevent them from being able to receive these signals and stop growing when they should. “Researchers at Karolinska Institute” have discovered that “cells with inactivating mutations of the p53 gene” have a higher survival rate when contingent on CRISPR. To further their research, they discovered genes with mutations similar to those of the p53, and also “transient inhibition” of the gene could help prevent “the enrichment of cells” that are similar. Although seeming antithetical, these researchers proved that inhibiting p53 actually makes CRISPR work better and prevent enrichment of mutated p53 and other similar genes. 

CRISPR logoDNA animation

           These results give crucial information, helping advance CRISPR and make it more usable in current medicine. Additionally, the researchers have uncovered the possibility that the damage CRISPR causes to DNA might be key in creating a better RNA sequence (the RNA sequence tells us the “total cellular content of RNAs”) guide, showing where DNA should be changed. In future tests, these researchers want to try and get a better idea of when the enhancement of mutated p53 cells from CRISPR becomes a problem.    

Unnatural Selection: The Future of The Future?

Imagine it’s Saturday night, you are snowed in until the morning and you need a way to pass the time. Like many people, you resort to Netflix. Upon browsing through the vast selection of horror, comedy, and romantic films, you decide you are in the mood for a documentary. Scrolling through the options, you stop at a title that grabs your attention: Unnatural Selection.

Since you are an AP Biology student, you immediately connect the words “Natural Selection” to the work of Charles Darwin, the study of genetics, and most importantly: evolution. In brief, natural selection is the survival and reproduction of the fittest, the idea that organisms with traits better suited to living in a specific environment will survive to reproduce offspring with similar traits. Those with unfavorable traits may not be able to reproduce, and therefore those traits are no longer passed down through that species. Natural selection is a mechanism for genetic diversity in evolution, and it is how species adapt to certain environments over many generations.

If genetic diversity enables natural selection, then what enables unnatural selection? Well, If natural selection eradicates unfavorable traits naturally, then unnatural selection essentially eradicates unfavorable traits or promotes favorable traits artificially.

The Netflix docuseries “Unnatural Selection” focuses on the emergence of a new gene-editing technology named CRISPR (an acronym for “Clustered regularly interspaced short palindromic repeats”). CRISPR is a revolutionary new method of DNA editing, which could help cure both patients with genetic diseases and patients who are at risk of inheriting unwanted genetic diseases. The two pioneers of this technology, Emmanuelle Charpentier and Jennifer Doudna, recently won Nobel Prizes in Chemistry for their work on CRISPR.

CRISPR illustration gif animation 1

Animation of CRISPR using guide RNA to identify where to cut the DNA, and cutting the DNA using the Cas9 enzyme

CRISPR works with the Cas9 enzyme to locate and cut a specific segment of DNA. Scientists first identify the sequence of the human genome, and locates a specific region that needs to be altered. Using that sequence, they design a guide RNA strand that will help the Cas9 enzyme, otherwise known as the “molecular scissors” to locate the specific gene, and then make precision cuts. With the affected region removed, scientists can now insert a correct sequence in its place.

Using the bacterial quirk that is CRISPR, scientists have essentially given anyone with a micropipette and an internet connection the power to manipulate the genetic code of any living thing.

Megan Molteni / WIRED

CRISPR is just the beginning of gene editing, introducing a new field of potential gene editing research and applications. But with great power comes great responsibility — and great controversy. Aside from the obvious concerns, people speculating the safety, research, and trials of this new treatment, CRISPR headlines are dominated by a hefty ethical dilemma. On one hand, treating a patient for sickle cell anemia will rid them of pain and suffering, and allows their offspring to enjoy a normal life as well. However, by eliminating the passing down of this trait, sickle cell anemia is slowly eliminated from the human gene pool. Rather than natural selection choosing the path of human evolution — we are. We are selecting which traits we deem “abnormal” and are removing them scientifically. Although CRISPR treatment is intended to help people enjoy normal lives and have equally as happy children, putting evolution into the hands of those evolving can result in more drastic effects in the future.

For our generation, CRISPR seems like a magical cure for genetic diseases. But for future generations, CRISPR could very well be seen as the source of many problems such as overpopulation, low genetic diversity, and future alterations such as “designer babies.” Humans have reached the point where we are capable of our future. Is CRISPR going to solve all of our problems, or put an end to the diverse human race as we know it? Comment how you feel down in the comments.

 

Redesigned Cas9 protein provides safer gene editing than ever before!

Gene editing is a group of technologies that give scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

One of the challenges that come using CRISPR-based gene editing within humans is that the molecular machinery may sometimes make edits to the wrong section of a host’s genome. This is problematic because it creates the possibility that an attempt to repair a genetic mutation in one location in the genome could accidentally create a dangerous new mutation in another spot. Scientists at The University of Texas at Austin have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short ‘guide’ sequence that binds to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Although Cas9 is the enzyme that is used most often, other enzymes can also be used. Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

Other labs have redesigned Cas9 to reduce off-target interactions, but so far, all these versions improve accuracy by sacrificing speed. SuperFi-Cas9, as this new version has been named, is 4,000 times less likely to cut off-target sites but just as fast as naturally occurring Cas9. Scientists say you can think of the different lab-generated versions of Cas9 as different models of self-driving cars. Most models are really safe, but they have a top speed of 10 miles per hour.

In my opinion, setting aside any and all ethical concerns, genome editing is of great interest in the prevention and treatment of human diseases. Currently, most research on genome editing is done to understand diseases using cells and animal models. Scientists are still working to determine whether this approach is safe and effective for use in people. It is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosis, hemophilia, and sickle cell disease. It also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection.

Could Christmas Island rats make a comeback? Thanks to CRISPR gene editing, they might!

From climate change to overhunting by humans, there are many factors which contribute to the extinction of species in the animal kingdom. The Christmas Island rat, also known as Maclear’s rat, went extinct a century ago in what is believed to be the first and only case of extinction of a species due to disease. It has always been believed that once a species goes extinct, it is gone for good. That is until recently when scientists began experimenting with “de-extinction” efforts to bring back the Christmas Island rat.

As published March 9 in the science journal, Current Biologya team of paleo geneticists from the University of Copenhagen recently conducted a study into gene sequencing the Christmas Island rat, in order to estimate the possibilities of future gene editing experiments which could bring the species “back to life”. The process of genetic editing for de-extinction efforts, as explained by the research team in their abstract, consists of first identifying the genome of the species and then editing the genes of similar species to make it more similar to that of that extinct one. The team used frozen somatic cells of the extinct rats, cells with a 2n number of chromosomes which are made during the process of mitosis. The team was able to sequence the rats’ genome, aside from some small portions which remain missing. They then had to identify the modern species which they could gene edit. Their findings established that the Christmas Island rat shares around 95% of DNA with the modern Norway brown rat. At this point, it

Now that the rat’s genome has been sequenced to the best of the team’s ability and a similar species has been identified, the gene editing possibilities are endless, especially with CRISPR technologies and techniques. “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats in DNA sequencing. This system was discovered by a group of scientists, led by Dr. Emmanuelle Charpentier. CRISPR uses Cas9, an enzyme which cuts DNA at specified sections as guided by RNA. There are three different types of edits drone with CRISPR technology: disruption, deletion, or correction/insertion. Disruption editing is when the DNA is cut at one point and base pairs are either added or removed to inactivate a gene. Deletion editing is when the DNA is cut at two points and a larger sequence of pairs is removed. Correction/insertion editing is when a new gene is added into a sequence using homology directed repair.

Thomas Gilbert, the lead scientist on the team, says that he would like to conduct CRISPR gene editing experiments on living species of rats before attempting to replicate the DNA of an extinct species. For example, attempting to mutate the DNA of the Norway brown rat into that of the common black rat. Once this experiment is conducted, the possibilities of reviving the Christmas Island rat will be more clear. Until then, we can only hope! Do you think it’s possible to see the Christmas Island rat revived anytime soon?

How Does Activation of p53 Effect the Use of CRISPR?

In a study conducted at Karolinska Institutet in Sweden, researchers looked into CRISPR gene editing and how that can play a critical role in mutated cancer cells as well as the medical field. CRISPR is “programmed to target specific stretches of genetic coding and to edit DNA at the precise location;” specifically, the CRISPR system binds to the DNA and cuts it, therefore, shutting the targeted gene off. Researchers can also permanently alter genes in living cells and organisms, and in the future, using this method they may even be used to treat genetic causes of diseases. Although CRISPR sounds amazing, will it really be as great as it seems?

CRISPR CAS9 technology

CRISPR

There are a few obstacles that need to be overcome before CRISPR can even become regularly administered in hospitals. The first is to understand how cells will behave once they are subjected to DNA damage which is caused by CRISPR in a controlled manner. When cells are damaged they activate a protein called p53 which has negative and positive effects on the procedure. The technique is less effective when p53 is activated, however, when p53 is not activated cells can grow uncontrollably and become cancerous. Cells, where p53 is not activated, have a higher survival rate when subjected to CRISPR and because of this can accumulate in mixed cell populations. Researchers have also found a network of linked genes that have a similar effect to p53 mutations, so inhibiting p53 also prevents these cells from mutating. 

Long Jiang, a doctoral student at the Department of Medicine at Karolinska Institutet, says that “it can be contrary to inhibit p53 in a CRISPR context. However, some literature supports the idea that p53 inhibition can make CRISPR more effective.” By doing this it can also counteract the replication of cells with mutations in p53 as well as genes that are associated with the mutations. This research established a network of possible genes that should be carefully controlled for mutations during CRISPR. This will hopefully allow for mutations to be regulated and contained more efficiently.

DNA, or deoxyribonucleic acid, is a long molecule that contains a genetic code; “like a recipe book it holds all the instructions for making the proteins in our bodies.” Most DNA is found in the nucleus of the cell, but a small amount can also be found in the mitochondria. DNA is a key part of reproduction because genetic heredity comes from the passing down of DNA from parents to offspring. Altering this DNA can have an impact on a number of someone’s physical characteristics. CRISPR does just that. It can be used to edit genes by finding a specific piece of DNA inside a cell and then modifying it. Since CRISPR is so new, it has its positives and negatives, but overall it is a groundbreaking discovery. 

DNA double helix horizontal

DNA

In conclusion, even though cells seem to gain p53 mutations from CRISPR, it has been discovered that most of the cell mutations were there from the start. Even though this is still an issue, we don’t know to what extent it can cause greater harm, so it will be exciting to see the new discoveries in the future!

Researchers at UT Austin tweak cas9 to make CRISPR gene-editing 4,000x less error-prone

A huge stride in ensuring the efficacy of CRISPR genome-editing has been made by researchers at the University of Texas at Austin. The CRISPR gene editing tool is a new genetic engineering technique that can, by using an enzyme called Cas9, correct problematic genomes in a person’s DNA. It finds the genome that its programmed to and cuts it out of the DNA, leaving the organism without that DNA, and inhibiting the organism from spreading that gene to their offspring. There have been studies have shown CRISPR has been effective in editing genomes that may cause disease. In a study where the Cas9 enzyme was injected into the bloodstream of six people with a rare and fatal condition called transthyretin amyloidosis, those who received the higher dose saw a decline around 87% in production of the misshapen protein that causes this condition.

For many diseases, Gene therapy is the “Holy Grail”. For treatment of Sickle-Cell Anemia, CRISPR has been thought of as a definitive cure. In 2017, it was reported that a 13-year-old boy with HbSS disease had been cured with gene therapy. This treatment also allows the carrier of this gene to reproduce without any risk of their offspring being affected by SCD.

GRNA-Cas9However, there are concerns that when performing the genome editing, the wrong segment of DNA could be targeted by scientists and removed, resulting in potentially drastic consequences. Another concern is that editing out certain genes is societally damaging, as it is considered unnatural to be able to edit the genomes of human bei

ngs. Another major safety concern is mosaicism (when some cells carry the edit but others do not); this could result in many different side effects. Due to the many uncertain aspects around the danger of genome-editing, there has been delay in passing legislation approving genome-editing.

 

In a study published on March 2nd 2022 at the University of Texas at Austin, researchers have found a previously unknown structure in the Cas9 protein that is thought to attribute to these genetic mistakes. When using cryo-electron microscopy to observe the Cas9 protein at work, the researching team noticed a strange finger-like structure that stabilized the off-target gene section to be edited instead of editing the target gene.

The researchers at the University of Texas at Austin were able to tweak the protein, preventing Cas9 from editing the wrong sequence. This change has made the tool 4,000 times less likely to produce unintentional mutations; the team calls the new protein ‘SuperFi-Cas9’.

While other researchers have made similar edits to make the Cas9 protein more accurate in its editing, these often result in slowing down the genome editing process. At UT Austin, the researchers say that SuperFi-Cas9 still is able to make edits at the normal speed.

The researchers plan to test SuperFi-Cas9 further in living cells as opposed to the testing thats been done with DNA in test tubes. Hopefully they’re able to cement the accuracy of SuperFi-Cas9, and that this may accelerate us on our way to implementing CRISPR gene editing in the current medical world. Let us know in the comments below what your thoughts are on CRISPR editing, and if you think we should continue researching it!

Can Gene Edited Tomatoes Save Your Life?

In a new invention by Hiroshi Ezura, the chief technology officer at Sanatech and molecular biologist, Tomatoes can now lead to lower blood pressure and higher relaxation.

This invention is based off a new phenomenon that is becoming more and more popular in Japan, food that is genetically edited using CRISPR technology. This technology is used to increase the amount of GABA in foods. GAMA, or gamma-aminobutyric acid, is a neurotransmitter and amino acid that “blocks impulses between nerve cells in the brain” (Waltz, Scientific American).

GAMA is being tested by many groups, including Ezura and his crew, for positive correlations between available GAMA, and health benefits. So far, there have not been any confirmed guaranteed health benefits, but the data from other genetically modified foods shows generally there are health benefits. People eating the food should feel more relaxed. Other tests have been done in the human, or animal bodies. GAMA is a natural substance found in humans, so the genetic mutations do not add a foreign substance to the body – it is safe to consume.

CRISPR technology is at the heart of this. This is a genetics technology in which one can add, take away, or alter sections of DNA. DNA is a double helix which consists of the nucleotide bases, Adenine, Cytosine, Guanine, and Thymine. When certain sections of the genetic code, represented in letters, are replaced by others, certain genes can change. Genes are certain pieces of DNA that carry genetic information which can alter how someone looks or functions. When worked on a tomato, it is able to alter a gene that gets rid of a pathway called the GABA shunt, which through a series of events limits GABA in cells.

Basepairs Graphic Public Domain

This technique has been used before, but it is so special because this is the first time it has been a commercial food product. This is exciting; genetic engineering can have negative effects in some areas, but so far the data shows that it is effective. Personally, I hope there is a rigorous series of tests that has to be conducted in the future for each CRISPR modified food to be commercially produced and sold.

New research further advances the understanding of DNA repair

In a study recently published in Nature Cell Biology, there’s been a discovery that alters our understanding of how the body’s DNA repair process works and may lead to new chemotherapy treatments for cancer and other disorders. Because DNA is the repository of genetic information in each living cell, its integrity and stability are essential to life. DNA, however, is not inert. Rather, it is a chemical entity subject to abuse from the environment and any resulting damage, if not repaired, will lead to mutation and possibly disease.

The fact that DNA can be repaired after it has been damaged is one of the great mysteries of medical science, but pathways involved in the repair process vary during different stages of the cell life cycle. In one of the repair pathways known as base excision repair (BER), the damaged material is removed, and a combination of proteins and enzymes work together to create DNA to fill in and then seal the gaps. In addition to genetic insults caused by the environment, the very process of DNA replication during cell division is prone to error. The rate at which DNA polymerase adds incorrect nucleotides during DNA replication is a major factor in determining the spontaneous mutation rate in an organism.

Researchers discovered that BER has a built-in mechanism to increase its effectiveness, it just needs to be captured at a very precise point in the cell life cycle. In BER, an enzyme called polymerase beta (PolyB) fulfills two functions: It creates DNA, and it initiates a reaction to clean up the leftover chemical waste. Through five years of study, scientists learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme will create new genetic material at a speed 17 times faster than when the two are not cross-linked. This suggests that the two functions of PolyB are interlocked, not independent, during BER.

Cancer cells replicate at high speed, and their DNA endures a lot of damage. When a doctor uses certain drugs to attack cancer cells’ DNA, the cancer cells must cope with additional DNA damage. If the cancer cells cannot rapidly fix DNA damage, they will die. Otherwise, the cancer cells survive, and drug resistance appears. This research examined naturally cross-linked PolyB and DNA, unlike previous research that mimicked the process. Prior to this study, researchers had identified the enzymes involved in BER but didn’t fully understand how they work together. This research improves the understanding of cellular genomic stability, drug efficacy, and resistance associated with chemotherapy, which, as previously stated, can lead to new chemotherapy treatments for cancer and other disorders.

CRISPR Gene Editing: The Future of Food?

Biology class has taught me a lot about genes and DNA – I know genes code for certain traits, DNA is the code that makes up genes, and that genes are found on chromosomes. I could even tell two parents, with enough information, the probabilities of different eye colors in their children! However, even with all this information, when I first heard “gene editing technology,” I thought, “parents editing what their children will look like,” and while this may be encapsulated in the CRISPR gene editing technology, it is far from its purpose! So, if you’re like me when I first started my CRISPR research, you have a lot to learn! Let’s dive right in!

CRISPR

Firstly, what is CRISPR Gene Editing? It is a genetic engineering technique that “edits genes by precisely cutting DNA and then letting natural DNA repair processes to take over” (http://www.crisprtx.com/gene-editing/crispr-cas9).  Depending on the cut of DNA, three different genetic edits can occur: if a single cut in the DNA is made, a gene can be inactivated; if two separate DNA sites are cut, the middle part of DNA will be deleted, and the separate cuts will join together; and if the same two separate pieces of DNA are cut, but a DNA template is added, the middle part of DNA that would have been deleted can either be corrected or completely replaced. This technology allows for endless possibilities of advancements, from reducing toxic protein to fighting cancer, due to the countless ways it can be applied. Check out this link for some other incredible ways to apply CRISPR technology!

In this blog post however, we will focus on my favorite topic, food! Just a few months ago, the first CRISPR gene-edited food went on the market! In Japan, Sicilian Rouge tomatoes are now being sold after the Tokyo-based company, Sanatech Seed, edited them to contain an increased amount of y-aminobutyric acid (GABA). “GABA is an amino acid and neurotransmitter that blocks impulses between nerve cells in the brain” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). It supposedly (there is scarce scientific evidence of its role as a health supplement) lowers blood pressure and promotes relaxation. In the past, bioengineers have used CRISPR technology to “develop non-browning mushrooms, drought-tolerant soybeans and a host of other creative traits in plants,” but this is the first time the creation is being sold to consumers on the market (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/)!

Tomatoes

So, how did Sanatech Seed do it? They took the gene editing approach of disabling a gene with the first method described above, making a single cut in the DNA. By doing so, Sanatech’s researchers inactivated the gene that “encodes calmodulin-binding domain (CaMBD)” in order to increase the “activity of the enzyme glutamic acid decarboxylase, which catalyzes the decarboxylation of glutamate to GABA, thus raising levels of the molecule” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). These may seem like big words, but we know from biology that enzymes speed up reactions and decarboxylation is the removal of carbon dioxide from organic acids so you are already familiar with most of the vocabulary! Essentially, bioengineers made a single cut in DNA inside of the GABA shunt (a metabolic pathway) using CRISPR technology. They were therefore able to disable the gene that encodes the protein CaMBD, and by disabling this gene a certain enzyme (glutamic acid decarboxylase) that helps create GABA from glutamate, was stimulated. Thus, more activity of the enzyme that catalyzes the reaction of glutamate to GABA means more GABA! If you are still a little confused, check out this article to read more about how glutamate becomes GABA which will help you better understand this whole process – I know it can be hard to grasp!

After reading all of this research, I am sure you are wondering if you will soon see more CRISPR-edited food come onto the market! The answer is, it depends on where you are asking from! Bioengineered crops are already hard to sell – many countries have regulations against such food and restrictions about what traits can actually be altered in food. Currently, there are some nutritionally enhanced food on the market like soybeans and canola, and many genetically modified organisms (GMOs), but no other genome-edited ones! The US, Brazil, Argentina, and Australia have “repeatedly ruled that genome-edited crops fall outside of its purview” and “Europe has essentially banned genome-edited foods” (https://www.scientificamerican.com/article/crispr-edited-tomatoes-are-supposed-to-help-you-chill-out/). However, if you are in Japan, where the tomatoes are currently being sold, expect to see many more genome edited foods! I know I am now hoping to take a trip to Japan soon!

Thank you so much for reading! If you have any questions, please ask them below!

Do Genetics Play A Role In Attraction?

Have you ever met someone with whom you instantly wanted to be friends but couldn’t put your finger on why or how you felt so drawn to them? There is a reason why you might be drawn to a specific person or group of people that may be explained by biology.

Double stranded DNA with coloured basesChromosome Terminology

According to a book by a well-known author, Malcolm Gladwell, a “unconscious” region of the human brain helps us to digest information spontaneously while encountering someone or something for the first time or making a rash decision. The University of Maryland School of Medicine has expanded on this hypothesis with a new study, indicating that these reactions may have a biological foundation related to heredity. The experiment was carried out on a group of mice. Variations in a particular enzyme discovered in a portion of the brain that affects mood and drive appear to influence which mice desire to actively engage with other mice; genetically related mice favored one another. Similar circumstances, such as disorders linked with social withdrawal, such as schizophrenia or autism, might also influence people’s decisions. Consequently, researchers do not agree with the phrase “opposites attract,” because genetics have a significant role in attraction. Instead, experts propose that we choose friends based only on their similarities to ourselves. Unlike the concept of “opposites attracting,” the expression “people like their own kind” is accurate. While genes definitely contribute to an individual’s attractiveness, they only account for around one-third of the reasons why we choose someone else to be our friend.

In a separate study, researchers examined a range of variables, that often are most inheritable and those that are less inheritable, to evaluate the role genes function in our human conduct, and they discovered that “people are genetically inclined to choose as social partners those who resemble themselves on a genetic level.” Rushton discovered in this study that humans prefer to choose partners based on inheritable attributes, even when we are unaware that such characteristics are genetically determined. For example, the middle-finger length is inherited, although the upper-arm circumference is not. Spouses who took part in the study had identical middle finger lengths but not the same upper-arm circumference. The function of heredity also influences personality, which explains why “people like their own kind.” What you inherited biologically from your parents, which is defined by the genes in your DNA, is the key to personality traits. Genetic heredity accounts for almost half of our cognitive differences, from personality to mental capabilities.

Love-heart-hands

Genetics is the scientific study of genes and heredity, which transfer particular characteristics from parents to offspring due to variations in DNA sequences. The genome contains all of an organism’s genetic code, including its genes and additional components that govern the activation of those genes. We are drawn to others because of the features that we share with them through genetic material. Our DNA is stored in chromosomes, and each of the 23 pairs of chromosomes has the same genes that are handed down from parent to offspring. When a baby is being formed, DNA is handed down, and each parent sends half of their chromosomes to their kid, thus each of your parents contributes 50% of your DNA. The term “genetic love” refers to the idea of matching partners for romantic relationships based on their biological compatibility. “Genetic love” describes the notion of attraction based on heredity.

Difference DNA RNA-EN

Is it possible that you want to be friends with someone of the same genetics as yourself? Yes! It is! However, it is not the only thing that accounts for maintaining a friendship.

Do Mitochondria contribute to neurological and psychiatric disorders?

Mitochondria have had a deep history through the evolution of eukaryotic cells. A primitive bacterium was engulfed by another free floating prokaryotic cell. Many think that this was originally how eukaryotic cells were formed and why mitochondria have their own DNA different from a their cells nucleus. Endosymbiotic theory has been used to understand the intricacies of Mitochondria and leaves many clues as to how their relationship with their cell affects its overall performance  The mutually beneficial relationship between both has lasted for over two billion years by fueling the processes for everyday life.

Mitochondria are membrane-bound cell organelles which generate majority of the chemical energy needed to power a cell’s biochemical reactions. Cell, Mitochondria, Biology, Organelle, ScientificChemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate or ATP. This is only one of the many essential jobs mitochondrion hold as an organelles in our cells.

Since mitochondria have their own set of DNA different from their cells, it makes it both a critical element of our cells and a potential source of problems. Mitochondrial DNA can harbor mutations similarly to ones in our nuclei. These can either be detrimental to their function powering our bodies or have little to no effect whatsoever. Age, stress and other factors may disrupt mitochondria’s many functions. On top of that, mitochondrial injury can release molecules that, due to their similarities to those made by bacteria, can be mistaken by our immune system as foreign invaders, triggering a harmful inflammatory response against our own cells.

One of our most important organs, the brain, needs mitochondria the most for its power driven functions. “The more energetically demanding a cell is, the more mitochondria they have, and the more critical that mitochondria health is — so there’s more potential for things to go wrong,” says Andrew Moehlman, postdoctoral researcher who studies neurodegeneration at the US National Institute of Neurological Disorders and Stroke (NINDS). Some estimates assume that each neuron can have up to two million mitochondria meanwhile there are eighty-six billion neurons in our brain.

Researchers have then linked dozens of disorders to alterations in mitochondrial DNA and nuclear DNA related to mitochondrial function. The majority of these are either neurological in nature or have some effect on the brain because of how dominant mitochondria is in the brain. According to Douglas Wallace, a doctoral student at Yale University, despite making up only 2 percent of a human’s body weight, the brain uses roughly a fifth of the body’s energy. These small reductions in mitochondrial function can have large effects on the brain, Wallace explains.

ATP gives us the energy we need for our body to function as we learned through our cellular respiration unit. Without this form of energy, our body simply cannot function which is why mitochondria play a key role in brain function. Mutations which affect the flow of ATP synthase seem most detrimental to cell function and as we know is where ADP and a Phosphorus join together to create ATP. Mitochondria’s own set of DNA makes it difficult to pinpoint a mutation and leaves animals vulnerable to neurological disorders.

New research exposes and demonstrates how damaged cells survive the cell cycle

In recent news, the Center for Cancer Research have recently discovered a previously unknown phenomenon, which allows certain cells to continue through the cell cycle despite experiencing DNA damage. This also includes past natural safety checkpoints within the cell cycle that are designed to stop the problem from occurring. On January 13, 2021 researchers, in Science Advances, suggested that the timing of DNA damage was crucial for determining whether a faulty cell would survive the cycle.

When cells begin to divide and replicate as part of their natural cycle, they transition from their resting state to one called the G1 phase. In this phase, cells have several important checkpoint mechanisms to ensure that the cell is healthy enough to proceed onto the next stage of the cell cycle. If/when these mechanisms fail due to genetic mutations, cells can progress through the G1 phase unobstructed, which can ultimately lead to cancer.

It was previously believed that cells with DNA damage could not pass through these safety checkpoints in the G1 phase and that the cells would either repair the DNA damage or die. However, scientists helped uncover evidence proving that cells with damaged DNA can actually progress past these critical checkpoints. A team of scientists studied individual cells for days at a time, using live cell time-lapse microscopy, single-cell tracking software, and fluorescent biosensors to detect the cell’s safety checkpoint mechanisms. They added a substance to induce DNA damage for cells of different ages in the cell cycle. Strikingly, the majority of cells seemed to ignore the DNA damage because they failed to trigger the checkpoint between G1 and the next phase, and proceeded into the next phase anyway.

Further investigation revealed that the timing of DNA damage during the cell cycle influenced the likelihood that damaged cells would slip past the checkpoints. The researchers found that the cell’s response to DNA damage is relatively slow compared to the speed of the cell cycle. This means if cells were already very close to the next phase of the cell cycle at the time DNA damage happened, they were more likely to continue into that phase. If the cells were still early in the G1 phase, they were more likely to revert back to a resting state. These observations are a form of inertia, where the cell will continue moving towards the next phase regardless of safety checkpoint signals.

It was also discovered that cells which were genetically identical were more likely to share the same cell cycle fate than non-identical cells. This suggests that factors specific to the cells themselves influence their fate during the cycle, rather than random chance. More studies are needed to understand how these findings apply to cancer. Testing is also extremely important in order to fully understand what the long-term consequences of the checkpoint failures are and find out if the cells that entered the next phase despite considerable DNA damage can become cancerous and eventually form a tumor, which, in my opinion and most likely the opinion of others, will be groundbreaking for cancer research.

Could These Blood Proteins Be The Key To Extending Human Lifespan?

All around the world, companies profit off of the idea of “anti-aging” products; but could these various serums, skincare products, and supplements even have an impact? A study from the University of Edinburgh, in which researchers analyzed six different genetic studies surrounding human aging, suggests otherwise. Instead, after analyzing 857 proteins from genetic information from hundreds of thousands of people, scientists have reason to believe that two distinct blood proteins have negative effects on aging. As we know from AP Bio, different individuals naturally have higher or lower levels of certain proteins depending on their genetics, and the DNA they inherit from their parents. Additionally, we know that each parent provides 23 chromosomes, which encode the same genes, totaling to 46. This means that if your parent has high levels of specific proteins, you have a significant chance of inheriting that.

Ácido desoxirribonucleico (DNA)

 In the case of these two blood proteins, LPA and VCAM1, people who inherited DNA that causes raised levels of these proteins were overall much more weak, unhealthy, and less likely to live a long life. Lipoprotein (a), a lipoprotein variant containing a protein called Apolipoprotein (a), is made in the liver. High levels of this protein are associated with a vast increase in the risk of atherosclerosis, which is a cardiovascular disease in which there is a​​ thickening or hardening of the arteries caused by a buildup of fatty substances in the inner lining of the arteries. Additionally, LPA is also linked to coronary heart disease and strokes. The second protein, vascular cell adhesion protein 1, or VCAM1,  is a protein found mainly on endothelial cells lining the blood vessels. It primarily controls blood vessel expansion and retraction. Elevated levels of VCAM1 are associated with long-term risk of heart failure.

Currently, there are clinical trials working to reduce the risk of heart disease through testing a drug to lower LPA. While there are no trials surrounding VCAM1 at the moment, there has been some animal testing done on mice to see the effects of lowering this protein. In these tests, researchers found that antibodies lowering VCAM1 levels improved cognition in old age for the mice.

The scientific progress and research regarding these two blood proteins is profoundly important, for it has revealed two key targets for future drugs to extend the lifespan of humans who aren’t genetically blessed. It is medical progress and news like this that continuously help us remain hopeful as we, and our loved ones, age.

How are new COVID variants identified?

COVID variants are of high concern for scientists studying the disease. Some variants can be more infectious or cause more severe illness. Additionally, some variants can evade vaccines by having different surface proteins than the variant the vaccine was created for. This causes the antibodies produced from the vaccine to be less effective against other variants. In AP Biology class we discussed how the Delta Variant, first identified in December 2020, has a different spike protein structure than the original virus from which the vaccine was created from. This allows the variant to be more infectious, and make the vaccine less effective against it. But, what are COVID variants? And how are they discovered? Hand with surgical latex gloves holding Coronavirus and A Variant of Concern text

COVID variants are “versions” of the virus with a different genetic code than the original one discovered. However, not every mutation leads to a new variant. This is because the genetic code of the virus codes for proteins. Some mutations will not change the structure of the protein and thus not change the virus. So, COVID variants can be defined as versions of the virus with a significantly different genetic code than the original virus.

To detect new COVID variants, scientists sequence the genetic code of virus which appears in positive COVID tests. Scientists look at the similarity of the genetic sequences they find. Then, if many of the sequences they get look very similar to each other, but different to any other known virus, a variant has been discovered.

To sequence the RNA of the virus, scientists use what is called Next Generation Sequencing (NGS). To understand how NGS works, it is best to start with what is called Sanger Sequencing. Sanger Sequencing utilizes a modified PCR reaction called chain-termination PCR to generate DNA or RNA fragments of varying length. The ending nucleotide of each sequence is called a ddNTP, which contains a florescent die corresponding to the type of nucleotide. The addition of a ddNTP also terminates the copying of the particular sequence. The goal of this PCR reaction is to generate a fragment of every length from the start to the end of the sequence. The sequences can then be sorted by length using a specialized form of gel electrophoresis. The sequence is then read by using a laser to check the color of the fluorescent die at the end of each sequence. Based on the color and size, the nucleotide at that position of the genomic sequence can be found.

Sanger Sequencing Example

The difference with NGS is that many sequences can be done in parallel, allowing for very high throughput. In other words, with NGS many COVID tests can be sequenced in once.

Quit Hogging All the Kidneys

Xenotransplantation is defined as the process of transplanting organs between members of different species. Saying it out loud it sounds like mad science but the it’s not as crazy you might think. Xenotransplantation has actually been a process that has been used for many years, even dating back to the 1960s. This journey began with apes and monkeys. Scientists believe that it would make the most amount of sense to use because they were essentially the most promising source of organs and tissue due to their being primates. However, this unraveled into a series of problems that were due to them being contaminated with viruses that are pathogenic to human beings. Baby monkeys were also researched but the idea was dismissed due to ethical reasons. This consequently led to the study of pig tissue.

We have actually been utilizing things from pigs that most people may not even be aware of. One example of this is pig insulin. It would replace the insulin that your body would usually make in order to get blood sugar into your cells. We obviously can’t take just any part of a pig and use it. We can, however, utilize a pig’s kidneys and transplant it into a human body. On September 25th, scientists and researchers  successfully transplanted a kidney from a genetically altered pig into a human patient and discovered that it functioned normally.

Little piggies

How Did It Work?

According to the an article by the New York Times, the pig needed to be genetically altered in order to be transplanted into the patient. What was altered? Essentially the kidney in the procedure was obtained by removing a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. Interestingly enough, the genetic difference between pig DNA and human DNA is 98 percent.

What Were The Risks?

While pigs and humans may share a lot of DNA, they are not a match right away. A non altered pig would cause many risks if any part of it were transplanted into the human body. A way it could pose an issue is through the viruses they may contain. Pig viruses may not cause disease in pigs, but they can in fact be pathogenic to humans. The human proteins that are expressed onto the transgenic pig cells can be receptors for viruses. An article on pig DNA from PMC explains that CD55 is a receptor for human Coxsackie B and ECHO viruses (these are relatives of poliovirus), and these cause a disease called myocarditis. The protein CD46 can act as as a receptor for the measles virus, so it is possible that morbilliviruses of animals could be preadapted in the same pigs used for xenotransplantation.

Another way that these transgenic pigs may heighten risk of virus is through viruses with lipid envelopes that are from host cell membranes would be less likely to inactivated by human compliment. What could have been a protective mechanism against infections from viruses derived from farm animals could be broken down in attempts to make xenografts for humans (The tissue or organ being transplanted from the other species).

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Diagram of a pig kidney

The future of xenotransplantation looks promising. While it may have worked, scientists are still doing studies and still trying to find out more about the viruses pigs may carry. While we can weed out the viruses we are aware of, we still can’t account for the ones we don’t know exist. There is a reason this topic is somewhat new and that is because of ethics. Apes and Monkeys could’ve actually been genetically altered the same way these pigs were, however it was deemed unethical. I personally agree that apes and monkeys shouldn’t be harvested, but that begs the question of whether harvesting organs from pigs is ethical. And with that I ask you what you ate for breakfast, lunch or dinner. Pigs and other animals are already being harvested for food and I believe that if there is a problem with xenotransplants, there would be a problem with the food industry. With that being said, if you’re ever in the market for a kidney, you have options.

Are Artificial Chromosomes the Key to Future Medicine?

Our DNA is packaged intricately by proteins in order to make up chromatin. If DNA were like a thread, these proteins are the spools that the DNA thread winds around to keep itself neat, organized, and compact inside of a microscopic cell. If a foreign, naked DNA thread with no spool is introduced into the environment, the cell is armed and ready to supply this new thread with its own self-made spools, allowing this naked DNA thread to be stably maintained in the cellular environment as part of the cell’s new collection. This process is known as artificial chromosome formation.

Prospects for the Use of Artificial Chromosomes include the potential to overcome problems in gene therapy protocols such as immunogenicity, insertional mutagenesis, oncogene activation, or limitations in capacity for transgene expression. One case where artificial chromosomes can be useful is found with someone dealing with Cystic Fibrosis. This fatal chronic lung disease is caused by a mutation in the CFTR gene and is currently a disease without a known cure. Scientists have been studying the use of bacterial and yeast artificial chromosomes as a transmitter to implement the normal functioning CFTR gene and overcome the defective CFTR gene in patient cells.

Almost two trillion cells divide every day in an average human body. This means that two trillion cells have to make a perfect copy of themselves every time. In our class, we’ve gone over the importance of cell division and have discussed the Mitochondria and Chloroplast’s ability to replicate independently within cells. The cost of cell division that comes short of flawlessness is undoubtedly humankind’s worst enemy yet: cancer, in which many are characterized by chromosome instability. One important player in ensuring the inheritance of our chromosomes during cell division is the centromere. The current studies of artificial chromosomes provide novel insights into the chromosomal processes required for de novo centromere formation and chromosome maintenance.

Ultimately, the results of these studies could help advance the synthetic biology field by exploring how some characteristics can be designed to optimize the establishment of an artificial chromosome by improving the efficiency of de novo centromere formation through accurate segregation to improve the applications of artificial chromosomes as large-capacity transmitters for cloning and gene therapies.

 

A New Way to “Tangle” with Diseases? British Scientists Think They’ve Stumbled Upon the Future

A team of scientist from the Universities of Bath and Birmingham have made a discovery that is making noise in the world of Biology. Ironically, they had the realization while studying silent mutations in DNA. What they found is a new method of evolution. Well not a new method per say as the scientists predict this method is being used in all forms of life; however, new in the sense that it was only recently realized. What they have discovered is a trend of tangles in DNA strands. This tangling occurs in DNA strands that are not in a double helix as DNA typically is. However The DNA strands are separated during copying. This task is done by DNA polymerase enzymes. During the copying process, the enzymes are often disrupted by the tangles in the strand. The resulting skipping of genes causes specific mutations to the DNA.

DNA replication split horizontal

The scientists then tested their hypothesis by way of experiment. They did so by studying the evolution of soil bacteria called Pseudomonas fluorescens (SBW25 and Pf0-1). They began by removing the gene that give the bacteria the ability to swim. They then observed the re-evolution of the strains to regain the ability swim. Both strains evolved quickly; however, there was a clear differences in predictability. One strain (SBW25) mutated the same part of a particular gene in every trial. The other strain (Pf0-1) varied in which gene and where the mutation occurred in each trial. Upon further observation, this contrast coincided with a hair-pin shaped tangle in the SBW25 strain. As the DNA polymerase enzymes would pass this tangle they would be effected in a predictable manner that would disrupt copying of DNA and result in a mutation that allows for the bacteria to swim. The scientists tested the theory by removing the tangle. They did so using 6 silent mutations so that the DNA sequence would not have a relevant change. The trials after the change showed that both strains showed inconsistent areas being mutated.

 

DNA are the dictators of protein synthesis in the body. The DNA sequences code for the types of proteins that are created. Proteins perform many of the bodies function. This means that even the slightest change in the sequencing of DNA can have major effects on the functioning of a human body or any organism. The process of evolution was thought to be caused by random errors in DNA sequencing that coincidentally gave an organism a survival advantage. These mutations would then be tested in the concept of survival of the fittest. While this is still thought to be the most prevalent form of evolution, especially with eukaryotic organisms, the tangling of DNA strands proposes a form of evolution that would be easier to study and predict.

 

The predictability of such a phenomenon is where the intrigue in viruses arises. “If we knew where the potential mutational hotspots in bacteria or viruses were, it might help us to predict how these microbes could mutate under selective pressure.” says Dr. Tiffany Taylor, from the Milner Centre for Evolution. Mutational hotspots have already been found in cancer, and the new information on their significance is getting scientists excited about the opportunities present. The new ways to understand and predict evolution of bacteria and viruses may allow scientists to be a step ahead on vaccines and be able to anticipate and understand new variants. It’s hard not to think this information would’ve been nice before the rise of SARS-CoV-2.

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