If you watch Diamond No Ace, please research the history of Japanese baseball!! Almost everything in the show is based off of reality, a lot of the players are based off Japanese baseball legends, especially those who made their mark at Koshien (YES, Koshien is real and it is bigger than March Madness NCAA in America for comparison). Every year high school baseball players put in all the blood, sweat, tears, pride and hard-work for the chance at a dream just like in DNA. The training for Koshien is based off samurai-bushido principals, and the players push themselves farther than any pro player does during that 9-day tournament that represents their dream.
Here are some characters that are likely based off these legendary players (any player with a ? means I’m not entirely sure):
Eijun Sawamura - Eiji Sawamura (Eiji died early after joining the army, and this is why Eijun calls Kataoka “General!” and Ochiai “Sergeant!”)
I’m sure there are many more and I probably only scratched the surface! If you have any corrections or contributions to the list I’d gladly take them! If you’d like to discuss any of my choices or the reason I chose the player I did, I’d be happy to do so!
In other news, my bio dad just decided to leave his second wife high and dry and hightail it out west (across the country) and he told me and @larrymama via Facebook message. He sent it to both of us and literally copy/pasted the message from one to the other. So ya know. Yaaaay dads!
I was taking a walk through the lab across the hall when I noticed Dr. Reed Goodwin had done a blue white screen. They’re not cutting edge or anything but they sure are pretty.
Blue white screens are used to determine if DNA that you introduced to the cell (plasmids) accept the sequence you insert or if they get screwed up in the process. If the colony is blue the sequence didn’t get accepted and if it’s white, it worked. This plate was the negative control, so they’re all blue.
As it turns out, the data produced by the program used to map Mota’s DNA came in a format that had to be tweaked before the scientists used a second program to compare it with other genomes. In the Mota study, no one did the tweaking.
That little oversight had a big impact. Dr. Manica and his colleagues unknowingly ignored some spots in the genome where Mota’s DNA was identical to that of Eurasians. As a result, Mota appeared not to be as closely related to Eurasians as he really was.
The mistake also created the false impression that many Africans outside of East Africa shared a lot of genes with Eurasians, DNA not found in Mota’s genome.
Dr. Manica and his colleagues last week posted a statement about the error, which was first reported in the journal Nature. They have asked Science, where their study appeared, to publish an erratum, and the journal is considering it.
Still, Dr. Reich noted, other parts of the original study, such as the reconstructed sequence of the Mota genome, stood up to scrutiny. The Ari do appear to be close kin to Mota.
What’s more, the Eurasian backflow did indeed occur — but only East Africans carry DNA from that event. “At least the general story still stands,” said Dr. Manica.
DNA damage and repair are necessary mechanisms put in place by the cell to ensure genomic stability and inheritance of only undamaged DNA. Our DNA is constantly being challenged by spontaneous and environmental sources of damage, and multiple pathways are invoked by the cell to reverse the damage, if possible. If that is not possible, the cell can choose to become senescent or to undergo apoptosis.
Telomeres are at the ends of chromosomes. When not bound by a protein complex called shelterin, they cause cell senescence in a pathway that converges with the DNA damage response (DDR). Telomeres also get shorter with each DNA replication cycle; this gives a mechanism of cellular ageing and cancer control. Telomeres prevent cells from replicating from too many times, and when they reach their limit (the Hayflick limit), the cell exits from the cell cycle forever.
On a grander scale, nature has made DNA not invincible for a reason. Replication errors and environmental mutagenesis introduce the mutations required for evolution. If DNA was not susceptible to damage, it could never evolve.
Types of DNA damage and repair
Spontaneous sources of DNA damage are those that originate from within the cell: replication error, reactive oxygen species, or mutagenic metabolites. Base tautomerisation allows A-C base-pairs, and base deamination turns Cs into Us - or more dangerously, 5Me-Cs into Ts (5Me-Us). These are fixed by mismatch repair (MMR). Oxidative damage includes formation of abasic sites and single-strand breaks - these are fixed by base excision repair (BER).
Environmental damage comes from ultraviolet light, ionising radition, and chemicals. Ultraviolet light causes formation of adducts between bases, which can be reversed directly, or repaired by nucleotide excision repair (NER). Left unchecked, these adducts can cause helix distortions and can block a progressing DNA polymerase or RNA polymerase machine. In fact, NER is sometimes coupled to transcription; TFIIH has some activity in repairing DNA. Ionising radiation crosslink DNA or cause double- or single-strand breaks. Double-strand breaks are the most cytotoxic type of DNA damage to the cell as DNA ends are highly recombinagenic. They are repaired by homologous recombination (HR) or nonhomologous end joining (NHEJ). Alkylating agents add alkyl groups to DNA - these are usually fixed by direct reversal or BER. Crosslinking agents introduce intra- or interstrand crosslinks - repaired by NER or via the Fanconi anaemia pathway.
Double-strand break repair
Double-strand breaks are detected by the MRN complex or the Ku complex - the two are in competition. The MRN complex contains Mre11, Rad50, and Nbs1. The Ku complex contains Ku70 and Ku86. MRN activates ATM, which repairs the damage by HR through BRCA1/2 in S- or G2 phase, when a sister chromatid is present. If not, ATM repairs by NHEJ, which is also the favoured pathway of the Ku pathway. NHEJ is available at any time in the cell cycle.
Telomeres and the DNA damage response
Naked telomeric DNA is recognised as a double-strand break because there is no DNA past the very terminal base-pairs on the chromosome. If not for the shelterin complex, this would elicit the same DDR as for any double-strand break. In the absence of shelterin, DDR against telomere ends is constitutive, and eventually leads to cell cycle exit and senescence.
Shelterin, at its core, is composed of TRF1, TRF2, and POT1. The TRFs bind telomeric dsDNA while POT1 binds the ssDNA - that is, the 3’ overhang. Loss of shelterin elicits the DDR. This happens naturally as telomeres get shorter, and the amount of bound shelterin decreases accordingly. Experimentally, it has been demonstrated that a dominant-negative allele of TRF2, which can assemble shelterin but cannot bind DNA, also causes DDR.
Telomeres get shorter with each replicative cycle. This gives an indication of cellular age. The molecular basis of telomere shortening is encapsulated in the end-replication problem. At a replication fork approaching the end of a chromosome, the leading strand can run cleanly off the end of the chromosome, but the lagging strand cannot fully replicate its template. This is because the final Okazaki fragment cannot be primed - even if the final RNA primer binds flush with the 3’ end of the lagging strand template, there is no downstream 3'OH from which to elongate DNA into it. Thus, the lagging strand is shorter than the parental lagging strand template, which now features a 3’ overhang.
Critically short telomeres inevitably trigger the DDR. Double-strand breaks are recognised by the MRN complex, which recruits ATM to the telomeres. ATM phosphorylates histone variant H2A.X on serine 139 - the histone is now called γH2A.X. γH2A.X recruits MDC1, which recruits more MRN; in this manner, the signal propagates along the telomere into subtelomeric regions. ATM activates checkpoint kinases which arrest the cell at cell cycle checkpoints until the DNA damage is repaired… But it can never be repaired, so the cell enters senescence.
Houtgraaf, J.H.; Versmissen, J.; van der Giessen, W.J. 2006. “A concise review of DNA damage checkpoints and repair in mammalian cells.” Cardiovascular Revascularization Medicine7:165-172.
Maser, R.S.; Monsen, K.J.; Nelms, B.E.; Petrini, J.H.J. 1997. “hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.” Molecular and Cellular Biology17 (10):6087-6096.
d'Adda di Fagagna, F.; Reaper, P.M.; Clay-Farrace, L.; Fiegler, H.; Carr, P.; von Zglinichi, T.; Saretzki, G.; Carter, N.P.; Jackson, S.P. 2003. “A DNA damage checkpoint response in telomere-initiated senescence.” Nature423:194-198.
van Steensel, B.; Smogorzewska, A.; de Lange, T. 1998. “TRF2 protects human telomeres from end-to-end fusions.” Cell92:401-413.
de Lange, T. 2009. “How telomeres solve the end-protection problem.” Science326 (5955):948-952.
Fumagalli, M.; Rossiello, F.; Clerici, M.; Barozzi, S.; Cittaro, D.; Kaplunov, J.M.; Bucci, G.; Dobreva, M.; Matti, V.; Beausejour, C.M.; Herbig, U.; Longhese, M.P.; d'Adda di Fagagna, F. 2014. “Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation.” Nature Cell Biology14 (4):355-365.
The process that lets your brain learn new things also leads to its deterioration. Every time you learn something, your brain cells make memories by breaking their own DNA and forcing the neurons to repair it. But as you age, you lose your ability to repair these breaks, which can cause a buildup of damage in your brain cells. Source