What caused Calvin sudden seizures?
A Case Study by Vanessa Wong
Part 1-Background Story:(This is a true story from petcureonlogy.com site,every event and data and characters detail is taken from the website,all credits belong to them)
Gretchen and David May’s first ever pet, a French Bulldog named Olive was two years of age when they determined she wished for a younger brother. Once they laid their eyes on 4-month-old Calvin,they were captivated an unable to keep their eyes off him.
Calvin used to be 7-½ years when his cancer journey begin. A normal Sunday morning in late September 2015 turns out to be one of the May's worst nightmare. Gretchen was getting ready to leave for her class when she noticed Calvin shaking suddenly. At first, she thought Calvin was choking when she didn't want to imagine the worst case scenario that was about to strike her family. However, he wasn’t choking ,he was having a sudden seizure and was shaking, a common symptom of a brain tumor commonly known as Glioma. When Calvin endured to have small seizures for an hour, the Mays rushed him to an animal emergency hospital, the place he was given medicinal drug and saved overnight.
Background:Calvin's Diagnosis
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A few hours passed,it was concluded Calvin had a brain tumor called as Glioma.
Gretchen recollects the moment they heard the first cancer diagnosis.This is not some thing new for them due to the fact earlier than this,his sister Olive was once in fact a cancer survivor and she used to be solely 6 when they observed a tumor in her toe. A few unexpected tragedies striked their family that year, however nothing hit them harder than listening to Calvin had cancer,while they had been shaken by the painful news, the Mays weren’t about to give up on Calvin. If there’s one thing they’ve learned from Olive’s previous cancers experience, it’s that a cancer diagnosis doesnt mean a death sentence.
Background:Calvin's Health History and Suspected Tumor Histology
Experiencing as many as 8-10 focal and grand mal seizures within a 24-hour time frame. MRI imaging revealed a well-demarcated 1.2 cm spherical tumor located in the left piriform lobe of the brain, suspected to be glioma . Previous health history was limited to severe upper airway disease (Brachycephalic Syndrome) with no prior history of seizure activity.
(petcureonlogy.com)
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Calvin's Post treatment and Outcome:A miracle ending
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Calvin skilled one seizure episode following the first fraction, successfully completed three SRS sessions,” said Dr. Boshoven. “He suffered a small seizure after his first treatment but none ever since the intial treatment. Besides from fur shedding, he has had no side effects. An MRI at four months post-treatment showed virtually no sign of the tumor.”The rest of the procedure were tolerable for Calvin and went uneventfully. No regions of abnormal contrast were sighted.He did not experience any aspect effects from the radiation treatments. His medication, on the different hand, made him very hungry. The Mays humorously recalled that he pressumably gained weight that month.
Following the 4-month,post-treatment MRI scan showed that Calvin’s tumor decreased in size tremendously that it almost nearly dissapeared.
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Detailed information of Calvin's journey on Glioma is based on these sources:
-Suspected Glioma- PetCure Oncology. (n.d.). Retrieved September 7, 2020, from https://petcureoncology.com/wp-content/uploads/-Calvin-May-v.2.pdfG. (2020, March 18).
- French Bulldog Thrives Following Treatment Of Brain Tumor Via New Technology. Retrieved September 07, 2020, from https://petcureoncology.com/calvin-a-french-bulldog-thrives-following-treatment-of-brain-tumor-via-new-technology-stereotactic-radiosurgery/
-Pet Hero: Calvin the Miracle Dog. (2017, May 02). Retrieved September 07, 2020, from https://petcureoncology.com/pet-hero-calvin-miracle-dog-brain-tumor/
Steps in DNA Replication
Step 1 -Initation
Replication Fork Formation
A replication fork is shaped by way of the opening of the start region of replication. Helicase chemical isolates the DNA strands and annihilate hydrogen holding between the bases,contributing in unwiding of double fold helix. An RNA primer is synthesized by way of primase and is stretched by utilizing the DNA polymerase. On the main strand, as it were a single RNA primer is required, and DNA is synthesized consistently, whereas on the lagging strand, DNA is synthesized in brief extends, each of which must start with its individual RNA primer.
The DNA parts are joined by utilizing DNA ligase
Topoisomerase II-release strain from unwiding process
Single strand binding proteins-to stabilize the loosened up single strands
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Step 2=Elongation
Here is the step by step process that occur in the Eukaryotes:
-Helicase isolates the DNA to make a replication fork at the root region of replication where DNA replication begins. Replication forks expand bi-directionally as replication proceeds.
-Okazaki fragments are formed on the lagging strand, while the leading strand is replicated continuously.
DNA ligase seals the gaps between the Okazaki fragments.
-Primase synthesizes an RNA primer with a free 3′-OH, which DNA polymerase III uses to synthesize the daughter strands.
DNA polymerase are only able to synthesize new strands in the 5′ to 3′ direction. The two newly-synthesized strands develop in opposite instructions because the template strands at every replication fork are antiparallel.
Leading strand
-Leading strand is synthesized always toward the replication fork as helicase unwinds the template double-stranded DNA.
Lagging strand
-Lagging strand is synthesized in the direction aside from the replication fork and away from the DNA helicase unwinds.
-Synthesized in pieces because the DNA polymerase can synthesize in the 5′ to 3′ direction, and so it continuously encounters the previously-synthesized new strand are referred to as Okazaki fragments.
-Every fragment starts with its own RNA primer.
(Boundless. (n.d.). Boundless Biology. Retrieved September 07, 2020, from https://courses.lumenlearning.com/boundless-biology/chapter/dna-replication/)
Step 2-
Elongation
History Fundamental Discoveries of DNA structures ,mechanism in DNA replication through a timeline:
1909-1929-Phoebus Levene-Discovered ribose sugar in 1909 and deoxyribose sugar in 1929
1920-Friedrich Mescher-Contributes in the discovery of nuleic acids-DNA.
1946-Hermann Muller-Best known for his work on how mutation can be caused by X-Ray radiation
1940s-Erwin Chargaff- ratios of DNA's nitrogen bases which are adenine (A) to thymine (T) and guanine (G) to cytosine (C) are equal(1:1).
1955-59-Francis Harry Compton Crick-responsible for the term "Central Dogma" the term is use to emphasize the idea of"the final step in the flow of information from nucleic acids to proteins is irreversible."
1950s-Linus Pauling-Build the triple helix DNA which is a catalyst for James Watson and Francis Crick to solve the structure of DNA in 1953(double helix).
1952-Martha Chase and Alfred Day Hershey-proved that DNA contains genetic information with the use of bacteria and viruses.
1977-Frederick Sanger-Involve in his work for DNA and protein sequencing
(DNA Interactive: Discovering the DNA Structure and beyond. (n.d.). Retrieved September 07, 2020, from http://www.dnai.org/)
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Step 3:
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Termination of translation starts when the stop codon enters the A site of the ribosome. Stop aminoacyl tRNAs don’t recognize codons. Instead, the stop codon is recognized by an enzyme called release factor. Release factor enters the ribosome and catalyzes the breaking of the bond between the growing polypeptide chain and the tRNA that holds it. Release factor will release the polypeptide chain from the ribosome so that it can go out into the cell and be converted into a finished protein.
Enzymes used-
-Aminoacyl-tRNA-synthetase-attaches amino acid to tRNA
-Peptidyl transferase
-Initiation factor
-Release factor
-Translocase-elongation factor that uses GTP
-Elongation factors-carries aminoacyl-TrNAto ribosome
(Boundless. (n.d.). Boundless Biology. Retrieved September 07, 2020, from https://courses.lumenlearning.com/boundless-biology/chapter/dna-replication/)
There are two template strands: the leading strand and the lagging strand. formed in the origin of DNA replication where DNA unwinds.According to the statements below,Which of this statement is a fact?
DNA polymerase can only synthesize DNA on the leading strand.
Synthesis of DNA leading strand using Okazaki fragments.
The lagging strand can only be synthesized under the condition where leading strand has been completed.
Non-stop synthesis of DNA's leading strand .
There are two template strands: the leading strand and the lagging strand. formed in the origin of DNA replication where DNA unwinds.Which of this statement is true?
Click here to view the answer
Leading strand of DNA is synthesized continuously.
The leading strand is made as one single strand piece in the 5' to 3'direction.
Let's go back to the process of DNA replication :Elongation to see the step by step to review!
Lets analyze what error occured during the DNA Replication?(through this image)
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What error occured during DNA Replication?
ANS-End Replication Problem
For lagging-strand DNA replication, brief RNA preliminaries are made by RNA primase which are stretch by DNA polymerase to make Okazaki fragments. When the RNA primers are unattached, it is incapable to synthesize lagging-strand sequence are complementary to the region at the end of the chromosone(chromatids) . So, with persistent cell division, the sequence is inhibited from the ends of linear chromosomes. A few blunt-ended daughter molecules(in this case are telomeres) are delivered, whether or not the N-terminal is blunt-ended or incorporates a 3' extension.
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What caused End Replication Problem in the Eukaryotes?
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What caused End Replication Problem in the Eukaryotes?
Ans-Uncontrolled Elongation of Telomeres
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Now,what precisely is uncontrolled stretching of telomeres?
Let's begin with telomeres,these same arrangements of non-coding DNA found at each chromosones particularly chromatids and are moreover dependable to avoid them from damage, or will cause chromosonal mutation,in detail, essential work of telomeres is to compensate for inadequate DNA replication at chromosome closes, caused by the eukaryotic “end replication problem.” Telomeres are abbreviate in length with each mitotic division.Telomerase is the protein/enzyme that's able to elongate telomeres. Transformations within the switch transcriptase can be shown in diffuse oligodendrogliomas and lead to abnormal mutation of telomerase, leading to uncontrolled extension of telomeres length and an interminable replication potential in tumor cells.
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Fun Fact:
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The “end replication problem” amid DNA replication are responsible for the deletion of approximately 20 base sets per cell division and are a fundamental factor that contribute to telomere shortening amid cell division.Another calculate that includes up are oxidative stress or an individual's way of living.
https://www.nature.com/articles/39210
https://www.sciencedirect.com/science/article/pii/S1097276514002135
What mutations occur here?
a)Nonsense Mutation
b)Missense Mutation
c)Silent mutation
d)Noisy mutation
What gene mutations occur here?
Ans-Missense mutation
There is a DNA error where there is a mistake in the amino acid combined into a protein due to a conversion in the DNA sequence,therefore leads to a different amino acid in which the ribosome acknowledge.A change in the aminoacid will affect the protein way of functioning .(Missense Mutation,Genome)
What specific missense mutation is involved here?
What specific missense mutation is involved here?
Specifically IDH mutation,IDH are actually an enzyme or protein that mutates in variety of plasmas,they are functioned as a catalyst in the process of Oxidative Decarboxylation and forms NADH/NADPH which are the main enzymes of the Krebs cycle.These mutations are somatic and heterozygous.
What DNA repairation mechanism is involved here?
a)Mismatch Repair
b)Nucleotide Excission Repair
c)Base Excission Repair
What DNA repairation mechanism is involved here?
a)Mismatch Repair
When a protein group acknowledges and binds to the mispaired base .
New DNA strand is removed and mispaired nucleotide are deleted.
Missing region replaced with appropriate nucleotide by DNA polymerase .
A dna ligase enzyme recovers the gap in the DNA backbone.(Khan Academy,DNA repair)
These sequence displays the forward primer sequences for IDH 1 GENE
F 5-CGGTCTTCAGAGAAGCCATT-3'
Now,find the reverse primer sequence
These sequence displays the forward primer sequences for IDH 1 GENE
F 5-CGGTCTTCAGAGAAGCCATT-3'
Now,find the reverse primer sequence
Ans-
R 5'-GCAAAATCACATTATTGCCAAC-3'
(PRIMER SEQUENCE TABLE,PLOSONE)
LETS TRACE BACK TO REVIEW THE DNA TRANSLATION PROCESS
Initiation of translation begins once the little sub unit of the cell organ binds to the ribosomal binding region on the ribonucleic acid. Then, the aminoacyl ribonucleic acid that carries essential amino acid binds by its anticodon to the beginning sequence. Finally, the big sub unit of the cell organ binds to the little sub unit along with the ribonucleic acid. At the tip of initiation, the cell organ is complete, and therefore the 1st ribonucleic acid is positioned within the P website of the cell organ. The second sequence within the ribonucleic acid is positioned within the A region of the cell organ.
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Elongation of translation happens as amino acids are brought along and joined to create a peptide chain. Elongation has many steps, that repeat till the peptide chain is complete:
a. AN aminoacyl RNA enters the A region of the cell organ. The RNA that enters the A has the complementary anticodon to the sequence within the A site. because the 2 RNA molecules besidewithin the P and A sites of the cell organ, their amino acids are neighbours.
b. The cell organ catalyzes bond formation between the 2 adjacent amino acids. The aminoalkanoic acid carried by the RNA within the P site is connected to the aminoalkanoic acid carried by the RNA within the A site. The growing macromolecule chain is briefly held by the RNA within the A site.
c. The cell organ and informational RNA slide relative to each other. Translocation is the process refered . The RNA that was within the P site| is pushed into the E site, whereas the RNA that was within the A site is pushed into the P site. This forms a brand new sequence within the A site and therefore the growing peptide chain within the P site. The RNA within the E region exits the cell organ, and therefore the A region is accessible for a brand new aminoacyl RNA to enter, and therefore the steps of elongation repeat.
(Molecular&Cell Biology for dummies)