CULTURAL QA 02202429
Q5 What are some of the mind-blowing facts that you have ever come
across?
KR Is it possible to mutate animals?
Yes. In the strictest possible sense we can induce cancer (which is a
mutation) in an individual animal in order to study the effects of cancer
and cancer treatment. More generally though, we'll mutate a population, nit
an individual.
On average, mutation rates per generation are higher in reptiles
(average of all species 1.17 × 10−8, 95% CI of the mean = 5.34 × 10−9 to
1.80 × 10−8) and birds (average of all species 1.01 × 10−8, 95% CI of the
mean = 6.10 × 10−9 to 1.42 × 10−8) than in mammals (average of all species
7.97 × 10−9, 95% CI of the mean = 7.04 × 10−9 to 8.90 × 10−9) and fishes
(average of all species 5.97 × 10−9, 95% CI of the mean = 4.39 × 10−9 to
7.55 × 10−9). However, the difference among the four major classes of
vertebrates is not overall statistically significant (analysis of variance
(ANOVA): F = 1.86, P = 0.15). Furthermore, the amount of variation in
µgeneration among species tends to be higher for birds and lower for
mammals and fishes (Fig. (Fig.1a),1a), although this variation is arguably
modest given large differences in life-history traits among these species
(for example, there is a 2.8-million-fold difference in the body mass of
killer whales and Siamese fighting fish, and there is a 93-fold difference
in the generation time between humans and Texas banded geckos).
The lifetime probability of being diagnosed with invasive cancer is
slightly higher for men (41.6%) than for women (39.6%; Table 3). It is
believed that the higher risk in men for most cancer types largely reflects
greater exposure to carcinogenic environmental and lifestyle factors, such
as smoking, although a recent study suggests that other nonmodifiable
differences also play a large role.29 These may include height,30, 31
endogenous hormone exposure, and immune function and response.32 Although
age is the strongest determinant of cancer risk, the proportion of new
diagnoses in adults aged 65 years and older decreased from 61% in 1995 to
58% during 2019–2020 despite the growth of this age group in the general
population from 13% to 17%. In contrast, the proportion of adults aged
50–64 years increased in both the cancer patient population, from 25% to
30%, and the general population, from 13% to 19%. The shift toward more
middle-aged patients likely in part reflects steep decreases in incidence
of prostate and smoking-related cancers among older men and increased
cancer risk in people born since the 1950s associated with changing
patterns in known exposures, such as higher obesity, as well as others yet
to be elucidated.33 Notably, people aged younger than 50 years were the
only one of these three age groups to experience an increase in overall
cancer incidence during this time period.
How many people will have cancer by 2050?
The latest report from the World Health Organization predicts that there
will be over 35 million new cases of cancer in 2050, a significant rise
from the approximate 20 million cancer cases that occurred in 2022.
World population projected to reach 9.8 billion in 2050, and 11.2
billion in 2100 | United Nations. So roughly 0.3% of the population will be
AFFECTED BY CANCER. That means 99.7% will be healthier.
Approximately 1 in 4 dogs will, at some stage in their life, develop
neoplasia. Almost half of dogs over the age of 10 will develop cancer. Dogs
get cancer at roughly the same rate as humans, while there is less
information about the rate of cancer in cats.
However, several species are known to be extremely cancer
resistant. These include the naked mole rat, blind mole rat, elephant and
bowhead whale. The age of onset of cancer also varies greatly depending on
the lifespan of the species.
As species evolve a large body mass, their cancer risk increases
due to the greater number of cells in the body that may acquire oncogenic
mutations. To counteract this risk, large-bodied species, with body mass
greater than 10 kg, evolved repression of somatic telomerase activity and
replicative senescence as an additional tumor suppressor mechanism. Replicative
senescence represents a late-acting barrier for tumor progression, since it
allows the formation of small tumors prior to the activation of the
telomere checkpoint. A long lifespan also increases the risk of cancer, and
small (body mass less than 5 kg), long-lived species, which cannot tolerate
the formation of small tumors, evolve telomere-independent tumor suppressor
mechanisms. These mechanisms offset hyperplasia and manifest in slow cell
proliferation in vitro. (b) Small- and large-bodied animals have a
different tolerance to tumor size. Mouse and capybara are drawn to scale
with a 3 g tumor. Such a tumor would likely affect fitness of a 30 g mouse
but would be inconsequential for a 55 kg capybara.
In 1977, Peto noted that it is surprising that while humans have
1000 times more cells than a mouse and are much longer-lived, human cancer
risk is not higher than that in the mouse. This observation was seemingly
inconsistent with the multistage carcinogenesis model63 according to which
individual cells become cancerous after accumulating a specific number of
mutational hits. This contradiction became known as Peto’s paradox. It has
been proposed that an answer to Peto’s paradox is that different species do
not need the same number of mutational hits. In other words, large-bodied
and/or long-lived animal species have evolved additional tumor suppressor
mechanisms to compensate for increased numbers of cells. Furthermore, many
large animals are also long-lived, hence they need additional protection
from cancer over their lifespan. As discussed above, animals larger that
5-10 kg of body weight evolved replicative senescence as an anticancer
defense. But what additional tumor suppressors have evolved in animals with
body masses a thousand times bigger, such as elephants and whales?
Recently, two groups simultaneously identified 19 extra copies of the
TP53 gene in the elephant genome66, 67 . All additional copies of TP53
appear to be pseudogenes and contain various deletions. Some of these novel
forms of the TP53 gene are transcribed from neighboring transposable
element (mobile DNA) derived promoters. Transcripts from two of the 19 TP53
pseudogenes are translated in elephant fibroblasts66. However, all the
additional copies of TP53 are missing DNA binding domains and the nuclear
localization signal and, therefore, cannot function as transcription
factors.
Remarkably, elephant cells have an enhanced p53-dependent DNA damage
response leading to an increased induction of apoptosis, compared to
smaller members of the same family, such as armadillo, hyrax and
aardvark66. Although the precise mechanism of action of the novel forms of
TP53 is not known, it was proposed that their protein products may act to
stabilize the wild type p53 protein by binding to either the wild type p53
molecule itself or to its endogenous inhibitors, the MDM2 proteins. It is
also possible that the extra copies of TP53 have some novel functions.
Notably, the elephant TP53 copies appear to be under positive selection
further suggesting they play a functional role
The increased sensitivity of elephant cells to genotoxic stress may
act as an anticancer mechanism through a more aggressive elimination of
damaged cells prior to them becoming precancerous. However, cell death by
apoptosis occurring more frequently would deplete the stem and progenitor
cell pools in the tissues by increasing the need for cell replacement.
Therefore, an enhanced apoptotic response needs to be balanced by other
adaptations to ensure that it does not lead to premature stem cell
exhaustion. Mouse models with constitutively active p53 display premature
aging and loss of stem cells and tissue cellularity. Therefore, elephants
may hold additional adaptations related to stem cells and tissue
maintenance. Interestingly, mice engineered to carry extra copies of wild
type Trp53 transgenic alleles consisting of large genomic segments
containing the intact Trp53 gene were protected from cancer and did not
display premature aging70. When these transgenic Trp53 alleles were
combined with a transgenic Cdkn2 allele the mice showed cancer resistance
and even an increased median lifespan71.
Interestingly, sequencing and characterization of several whale genomes,
including the longest-lived bowhead whale75, which has a maximum lifespan
of 211 years76, did not reveal similar duplications of TP53 as in
elephants. Whales are very large creatures with an adult bowhead whale
weighing 100 tons, compared to only 3 tons for an adult elephant, and just
under 0.1 ton for an adult human Thus, whales have likely evolved novel
anticancer adaptations that are not even found in elephants or humans.
Comparative genomic and transcriptomic studies in the bowhead whale
identified genes under positive selection linked to cancer and aging, as
well as bowhead whale-specific changes in gene expression, including genes
involved in insulin signaling78. Notable examples of positively selected
genes are excision repair cross-complementation group 1 (ERCC1), which
encodes a DNA repair protein and uncoupling protein 1 (UCP1), which encodes
a mitochondrial protein of brown adipose tissue75. In addition, these
studies identified copy number gains and losses involving genes associated
with cancer and aging, notably a duplication of proliferating cell nuclear
antigen (PCNA)75. Since both ERCC1 and PCNA are involved in DNA repair,
these proteins may protect from cancer by lowering mutation rates; thus
whales may not need extra copies of TP53 because their cells do not
accumulate cancer causing mutations and do not reach a pre-neoplastic stage.
KR Now when we have so much data on cancer resistance and percentage of
human cancer, how it is MIND-BLOWING? TINY nair must know all these. K R
IRS 29224
---------- Forwarded message ---------
From: 'gopala krishnan' via KeralaIyers <[email protected]>
Date: Thu, 29 Feb 2024 at 03:31
Subject: [KeralaIyers] CULTURAL QA 02-2024-29
To: Patty Thatha <[email protected]>, Kerala Iyer <
[email protected]>, Iyer <[email protected]>
CULTURAL QA 02-2024-29
All the below QA are from Quora DIGEST to me on 29-02-2024.
Selected quora answers generally interesting including jokes are included
.Still they need not be 100% correct answers. I am only a compiler.
Compiled and posted by R. Gopala Krishnan, 80, on 29-02-2024.
Q1 What is the funniest joke you've been told that you still think
about to this day?
A1 Steve Gilbert,Oct 25
A guy is in a job interview, the interviewer says to him “You’re asking for
an awful lot of money for having so little experience”.
He answers “Of course I am. Think about how much harder I’ll have to work
not knowing how to do the job”.
Q2 What are some of the best real life examples of presence of mind
witnessed by you?
A2 Priya C,Lives in Bengaluru, Karnataka, IndiaFeb 19
Yesterday, we had been to a kitchenware store to exchange my old pressure
cooker for a new one.
Once at the store, I remembered that I needed to buy an iron bowl to mix my
henna for hair that was long pending.
I asked him to display some.
He showed me a couple of them in different sizes with corresponding price
range.
There was one that was mid size with quite a width and just about deep
enough to do the mixing.
They all had handles like in a kadai, but I was fine with it as they would
help me hold.
But the insides as they appear in the pic, were coated black unlike the
other two that appeared silvery white.
I didn't know if the shopkeeper was telling the truth about the container
being made of pure iron although they felt quite heavy.
I have had a bad experience of being conned by one such store keeper where
he sold me an aluminium griddle in place of iron.
Hence I wasn't sure if I should go ahead with the purchase.
It was precisely at this moment that the shopkeeper did something very
astute, sensing my uncertainty.
He quickly pulled out a “magnet” from a shelf and put it below the
container.
The magnet neatly stuck to the bottom and stayed where it was.
It was quite unexpected I must say!
But as a buyer I had to more sure. The inside of the container was what
mattered and not the outer layer.
I asked him to put it even in the inside.He did and the effect was the same.
I was satisfied and made the purchase, my mind appreciating and
complimenting the seller for his quick presence of mind!
I feel every shopkeeper who sells iron wares should have a magnet handy to
prove the credibility of the items to their customers.
Q3 What are some of the greatest examples of presence of mind?
A3 Shrey Parth, Updated 5y
Killing two birds with one stone!
Back in 10th standard , a new Geography teacher was assigned to our class.
Now, this teacher was as interesting as the subject itself. (sarcasm
intended). All he used to do was to copy the text from book and write it on
the blackboard.
Needless to say, half of the class slept (literally) during his lecture.
Coming to the story.
I was sitting on the first bench that day, he started teaching and I was
fast asleep within 10 minutes. He was least bothered by it and continued
with whatever he was doing.
Now as fate would have it, the principal was on a round. And, yes he walked
into our classroom.
Imagine the scenario here! The principal walked inside, everyone stood up
except one boy who was sleeping on the first bench.
That’s not it even! He tapped me 3–4 times on my shoulder before I woke up.
As I opened my eyes and looked around, everyone was looking at me, the
teacher, every student and the principal and at that instant I knew I was
fucked.
Principal : “What’s going on? Why were you sleeping?”
Me: “umm.. uh..!” (I was trying to speak, but words were not coming out.)
But at that moment, the teacher spoke.
He said : “He was not feeling well, so I told him to sleep!”
Me(confused) : “Yes, sir!”
Principal : “Better go to the infirmary and take rest there. Class is not
the place to sleep”
Me: “Yes, Sir! Sorry Sir!”
After the class, I went up to my teacher to thank him for saving me.
But what he said was “I didn’t do it to save you boy, I had to save my
reputation as a teacher!”
I was like, “Thank God for his presence of mind!
Q4 What are your favourite blonde jokes?
A4 George Kingsley,11h
A blonde is speeding down the highway and a blonde cop pulls her over.
“License and registration ma’am”
“I’ve got the registration right here. Remind me what my license looks
like?”
“You keep it in your purse and it looks like you,” responds the cop.
The blonde driver roots around in her purse and pulls out a makeup compact.
She opens it and hands it to the blonde cop.
The cop looks at the mirror, closes the compact, and hands it back to the
driver.
“Why didn’t you tell me you were in law enforcement? Have a nice day!
Q5 What are some of the mind blowing facts that you have ever come
across?
A5 Tiny Nair, Cardiologist at PRS Hospital, Trivandrum1y
Richard Peto, a British statistician came up with a theory, widely known as
the ‘Peto’s paradox’, wherein he proposed that despite its larger size,
more cell mass, and consequently, more cell divisions, (logically leading
to a conclusion of more mutations) larger animals like whales and elephants
DO NOT HAVE more cancer, compared to humans.
The first sign of trouble was a swelling in her breast, which turned out to
be cancer. The family was devastated but stood together and slowly pulled
through the tough challenge of cancer treatment, complimented by loss of
hair, bouts of nausea and destruction of self-esteem.
By the time the light at the end of the tunnel seemed brighter, trouble
came as a painful swelling in her right leg.
A biopsy showed that it was sarcoma, an unusual tumour involving bones and
muscles. More scars and more medications followed. An year later, detection
of an abnormal blood count during a routine lab-work showed features of
leukemia.
It was then that her doctors asked for a detailed genetic analysis. It
showed that the girl had a mutation of her p 53 gene in chromosome 17; the
tumour suppressor gene. She was suffering from a rare disease called ‘Li
Fraumeni Syndrome’.
Li Fraumeni syndrome occurs because of loss of function of p 53 ‘tumour
suppressor gene’.
Despite all the carefully set algorithm, cell division can go wrong; and if
it goes unchecked, there is always a chance of mutation and cancer. P 53
gene tries its best to repair the damaged DNA, and if it fails, it destroys
the cell, preventing it from multiplying. Essentially it is the ‘police
against cancer’ in our body.
While humans have just one copy of p 53, elephants have 10 pairs. That’s
why elephants don’t get cancer. Richard Peto was right.
Why didn’t God give us a dozen more copies of the ‘police gene’.
May be because he thought that his best creations would know how to take
care to prevent cancer.
But instead, we atom-bombed Hiroshima, created a billion dollar cigarette
industry (lung cancers), drowned ourselves in alcohol (hepatic cancers) and
pollute the atmosphere and destroy the ozone hole (skin cancers, melanoma).
It is estimated that up to 60% cancers are preventable.
And yes, God gave us a mindset with a built-in blind-spot which make us
believe that ‘But it will never happen to me’.
For God, it is like watching Tom & jerry from top and laughing his heart
out.
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