Tuesday, February 21, 2023

Pineal gland, the mystical third eye

Pineal gland 

It is a very small unpaired midline brain structure of endocrine gland, tiny as a rice grain size, situated laterally (anatomically asymmetrical) in the epithalamus, between two hemisphere, near the center of the brain, but devoid of blood-brain barrier (so having profuse blood flow, second only to kidney), well referred as pineal body, pineal word came as due its resemblance of a pine cone or pine apple shape.

Role of pineal gland
It has a role of maintaining circadian rhythm (are physical, mental, behavioral changes that follows a 24-hour cycle) and seasonal cycle in the body. When eyes are not stimulated with light (signals from retina of lightning environment), Serotonin neurotransmitter is converted to a hormone Melatonin to initiate sleep cycle by this tiny gland. That way Melatonin is called sleep hormone, whose secretion level is highest in the middle of the night.

Function
Due to it's resemblance of Parietal eye & the Photoreceptor cell in lower animal kingdom, it could phylogenetically regarded as vestigial remnant. 

Biomolecules Serotonin and Melatonin are structural analogies to DMT (dimethyltryptamine) released in REM phase, responsible for visualization of images and dreams, where a travel through time & space dimension occurs. DMT is most powerful hallucinogen found in naturally.

In the immediate state before death, large amount of DMT is produced.

As this endocrine gland/body, secreting Melatonin/DMT, works on similar pattern of our external eye being a photoreceptor in nature, seems an ancestral Parietal eye, vestigial to us, but still doing a powerful chemical production site which maintains circadian rhythm and a balance between wakefulness & sleep cycles. Many a time this has been referred as mythical Third eye, this is a door between our known to the unknown world. Due to the small size, it is most delayed discovered endocrine gland and still remains less understood, seems to many a mystical due to it's role in higher realm transcendental spiritual perception, perhaps due to triggering on of DMT production by controlled meditation or such willful activity by humans, as it receives the Sympathetic innervation from superior cervical ganglion.

Clinical aspects
Excessive calcification of Pineal gland disrupts its function. Aging is another reason of reduced Melatonin level causing disruptive sleep cycle.   

Wednesday, February 1, 2023

Happy chemicals of human body

Happiness is a very illusive term in human case as affecting variable are many. 
But for sure, happy people are more successful in multiple life domains.

  • Physical, mental, emotional well-being is being governed or influenced by many external and internal factors, more often not in our control. 
  • That's why this subject spans a lot many areas of external environmental factors and inner body chemistry. 
  • Subjective well-being is all in the center of evaluation of happiness, positive and negative emotions are the end results.

Primary signaling chemicals of mood in humans are 4 (Neurotransmitter Hormones) as below:
  1. Serotonin, the mood stabilizer (neurotransmitter).
  2. Oxytocin, the love hormone (hormone).
  3. Dopamine, the rewarding chemical (neurotransmitter).
  4. Endorphins, the pain killer (neurotransmitter).







Tips for living a happy life:
  • Eat nourishing food, be in nature, exposure to sun shine, meditate for the feel good hormone (Serotonin).
  • Keep company with good people, family, pet, love, laugh for the love hormone (Oxytocin).
  • Do something meaningful each day with short and long term goal for the reward chemical (Dopamine).
  • Get regular exercise, avoid news overdose, switch off bright screen - hours before bedtime, goodnight sleep of 6 to 8 hours every night for relaxing, pain killer (Endorphins).

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Interesting notes:
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Endorphins evolved in nature for survival. 
Injured animal run from predator or our ancestor's ran for help or to search for a source of water at any undisclosed distant places or a runner push through a race even in injury and likewise. 
Endorphin is produced in pain doesn't mean that one should inflict pain or harm oneself or over exercising beyond one's limit to feel good. Laughing out loud, meditation, working out in moderate, watching your favorite drama could help you to achieve this endorphin feel good effect.
Endorphins and dopamine: Endorphins relieve pain and dopamine motivates to push through challenges and provides a reward for doing so.
Opiates trigger the same receptor in the brain that triggers the release of endorphins. 
As endorphins binds pain signals and relieves, dopamine will motivate you to do same thing over and over again. So endorphins and dopamine actually work together. 
Out of more than 20 endorphins in our body, Beta endorphin is having stronger effect than morphine. That way the 'runner's high' exercise addiction and self harm could be understood

Thursday, January 26, 2023

Sleep, neuronal activity and thrombotic events

Sleep stages & autonomic nervous system:
1. NREM sleep:
    1. Parasympathetic drive increases.
    2. Decline in Sympathetic drive, blood pressure, heart beat.

2. REM sleep:
    1. Profound Sympathetic nerve activity (increase).


Autonomic Nervous System, regulates involuntary physiologic processes like heart rate, blood pressure, respiration, digestion, sexual arousal etc. This is part of peripheral nervous system, comprising of Sympathetic, Parasympathetic and Enteric nervous system.

1. Sympathetic N.S.
    1. Afferent fibers -- Sensory input. 
                                                           } Central Nervous System
    2. Efferent fibers -- Motor output. }        ---->           motor pathway with 2 neuron series;
                                                                                       1. a Preganglionic neuron with a cell body in                                                                                                                         CNS.                                                                                                                                                                          
                                                                                       2. a Post ganglionic neuron with a cell body in 
                                                                                           the periphery that innervates target tissues. 

2. Parasympathetic N.S. 
    1. Afferent fibers -- Sensory input. 
                                                           } Central Nervous System
  2. Efferent fibers -- Motor output. }       ---->              1. S.N.S. activation
                                                                                           SNS innervates every every tissue in the body.
                                                                                           causes:
                                                                                           Elevated activity & attention.
                                                                                           "flight or fight" response,
                                                                                           b.p. & hear rate increases,
                                                                                           glycogenolysis ensues,
                                                                                           gastrointestinal peristalsis cease.

                                                                                        2. P.N.S. activation,
                                                                                            PNS innervates only the head, viscera,
                                                                                            external genitalia (smaller than SNS).
                                                                                            promotes: 
                                                                                            "rest & digest" response,
                                                                                            b.p. & heart rate lower,
                                                                                            gastrointestinal peristalsis/digestion restarts,

  • Presynaptic neurons of both SNS and PNS utilize acetylcholine(ACh) as neurotransmitter.
  • Postsynaptic Sympathetic neurons generally produce norepinephrine (NE) as their effector transmitter to act upon target tissue while Postsynaptic Parasympathetic neurons use ACh throughout.
  • Enteric neurons use several neurotransmitters as ACh, Nitrous Oxide, Serotonin etc.
      Neurotransmitter, are chemical signals from one neuron to the next target cell, to quote a few:
  • Acetylcholine is often used in Parasympathetic N.S. to have an inhibitory effect.
  • Norepinephrine (Noradrenaline; neurotransmitter and a hormone as well) often works with Sympathetic N.S.to have a stimulating effect on the body.

1  S.N.S. activation > increasing blood flow > decreasing food processing in the bowels > in turn would increase blood availability for genital engorgement.
2. P.N.S. activation > branches from Sacral plexus of Spinal nerves > arteries supplying erectile tissues. Nerves release Acetylcholine > Nitric Oxide from endothelial cells of trabecular arteries, eventually causes Nocturnal Penile tumescence. This NPT phenomena is of spinal regulation, brain or testosterone is not involved.

Sympathetic activity and REM sleep:
A research conclusion thankfully quoted here as, "REM sleep is associated with profound sympathetic activation in normal subjects, possibly linked to changes in muscle tone. The hemodynamic and sympathetic changes during REM sleep could play a part in triggering ischemic events in patients with vascular disease.



REM sleep is most manifest toward the end of sleep, before arousal. Sympathetic and hemodynamic alterations during REM sleep could conceivably initiate increased platelet aggregability, plaque rupture, or coronary vasospasm, thus acting as a triggering mechanism for thrombotic events that may present clinically only after arousal."

Tuesday, January 24, 2023

Brain waves, sleep stages and functional pathology

Brain waves are oscillating electrical voltage in the brain. Brain does not operate with any single frequency wave. Full spectrum of all brain wave frequencies are always there to be found. Only the dominant frequency determines our mental state.
EEG (Electroencephalogram) reveal their following types:

Frequency band    Frequency      Brain state              Notes
1. Gamma (γ)        35-44Hz    Concentration             High-level information processing is a 40 Hz
Problem solving,                                                          activity, 40 Hz deficiency creates learning
concentration.                                                               disability. Only a quiet mind access Gamma.
                                                                                      Gamma relates to expanded consciousness,                                                                                                                   spiritual emergence, higher virtues.

2. Beta (ß)              12-35 Hz     Anxiety dominant,    Normal dominant rhythm in alert, anxious, open
Busy,                                           active, external          eye, listening, thinking, judgment, processing  
active mind.                                attention, relaxed       information around us.

3.Alpha (α)            8-12 Hz          Very relaxed,          8-13 Hz, a bridge from external world to internal
Reflective,                                  passive attention        world, ability to shift states from external to 
restful.                                                                           internal and vice versa.
                                                                                     Our brain uses 13 Hz (high Alpha or low Beta)
                                                                                     for 'active' intelligence. Deficiency of 13 Hz
                                                                                     activity causes learning disability & attention
                                                                                     problem.
                                                                                      } Alpha-theta protocol, hypnogogic imagery.
4. Theta (θ)             4-8 Hz       Deeply relaxed,            
Drowsiness.                                 inward focused

4. Delta (δ)            0.5-4 Hz          Sleep                       Slowest wave
Sleep,
dreaming.


Sleep and brain waves:
  1. During sleep stages, brain waves vary from alpha to theta to delta and again to alpha state to complete one cycle of 90 minutes.
  2. 8-13 Hz frequency range of Alpha wave is a bridge from external world to the internal world, (A frequency range having ability to shift from external to internal world and vice versa).
  • Sleep stages N1 to N3 of NREM are 'slow' waves.
  • N1 and N2 mainly comprising Theta wave while N3 is deep Delta wave.
  • REM sleep is of 'fast' Alpha rhythm.


Sleep stage and their frequency:
Sleep stage       Voltage and frequency     Physiology                    
1. REM sleep    Low amplitude (small),      Eye movement, dream,    
                          high frequency (fast),        arm/leg muscles               
                           Alpha rhythm.                  paralyzed, respiration &
                                                                    heart beat maximum.

2. NREM sleep   High amplitude (large),    Slow wave, Deep-/Delta
    (N1 to N3)       (i.e. high voltage),            sleep, No eye movement,
                            low frequency (slow),       respiration & heart beat 
                            (i.e. slow waves),              minimal.
                            waves & spindles.
                            Theta & Delta rhythm.

Alpha rhythm dominant effects; 'Creative', daydreaming, meditating, helps reduce stress and anxiety, relaxed state, mental readiness role in focus and attention.
 
Theta rhythm dominant effects; Deep relaxation, light sleep, improves mood and reduce stress level.

Delta rhythm dominant effects; Deep sleep, improves immune system and reduce stress level, state of 'physical healing', tissue repair and regeneration.

Brain waves, cranial nerves & functional pathology:
Apart from sleep and wakeful activity, some other very interesting phenomenon occurs:
"A brain wave extends through perineural system as far as injured part of the body. This is physiological justification for the placebo effect as tissue repair, internal recovery, powerful vector of homeostasis." 
Positive attitude of patient plays a vital role in healing. A significant role of nerve manipulation have been reported in recovery, rehabilitation and rebalancing.






Tuesday, January 10, 2023

Sleep architecture

Sleep:
    EEG shows, sleep is a dynamic behavior, not a passive activity.
    Neuroendocrinological structures and chemicals responsible for sleep regulation are:
  • Sleep promoting neurons in anterior hypothalamus acts through cerebral cortex with neurotransmitters
  • Sleep promoting hormone Melatonin produced in the pineal gland.
Sleep stages:
1. NREM sleep:
    No rapid eye movement.
    Restorative sleep, bodily recovery and growth
    Boosts immune system
    As you age, less NREM sleep
    N3 for insightful thinking and creativity.
2. REM sleep:
    Rapid eye movement.
    Essential to cognitive functions like memory, learning, creativity & vivid dreams.
    Deprived of REM sleep shortens life span.
    REM declines with growing age.

Sleep cycle:
    A hypnogram based on brain waves shows:
    1. 4-6 sleep cycles in a night.
    2. Each cycle last 90 minutes on average.
    3. Each cycle with 4 sleep stages;

Stage 1  NREM  N1       wake-sleep transition state                           1-5 mins          
Stage 2  NREM  N2       most of NREM sleep occurs in this stage   10-60 mins      
Stage 3  NREM  N3       slow wave-, delta-, deep sleep                     20-40 mins     
Stage 4   REM   REM    active sleep                                                    10-60 mins     

               N1, N2, N3 amounts 75%, while REM amounts 25% of all sleep.

Some other terms used, less often:
  1. Core sleep: Slow wave sleep, mainly N2 and Deep sleep N3.
  2. Optional sleep: rest of the sleep is grouped as Optional.



Wednesday, August 18, 2021

Monoclonal antibody treatment for Covid-19

Monoclonal antibody
They are the lab made protein, mimicking the natural immune system of the human body, to fight any infection like SARS-CoV-2. It is advised as to avoid hospitalization while being found with the positive Covid test.


Restrictions
It is restricted to people of 65 or more years in age. So fairly the Covid-19 patients are always asked to get tested quickly and then get advise for the treatment of monoclonal antibody infusion.

FDA has also now advised for the monoclonal antibody treatment for SARS-CoV-2 in a recent FDA news release. One can see the list of qualification for the Monoclonal antibody treatment on certain website of hospital.

More recommendations
"It's the best treatment we have to keep you out of the hospital. It keeps people out of the hospital 70 percent of the time," said Montgomery-area pulmonologist Dr. David Thrasher. "It's really a great treatment and everybody needs to ask for it."

Sunday, August 15, 2021

The fifth nucleobase

Basic ingredient in genetic recipe
Four letter A,T,C,G of genetic alphabet forming three letter words (codon), specifying for 20 amino acids, makes the basic molecular foundation of all life forms. 
But some viruses show a fundamental genomic change, a modified novel fifth base in nucleotide.

Z genome with a noncanonical modified base
In a strategy to escape bacterial restriction enzyme, it was found in the genome of  200 phage virus like one as cyanophage S-2L, out of the four canonical Watson-Crick nucleobases A,T,C,G; A is replaced by the diaminopurine (Z) forming three hydrogen bonds with T, which makes it more stable and rigid from bacterial defenses than double bond A=T. It was first reported in 1977 by soviet researcher. Further study suggest that aminoadenine in place of adenine was included in the phylogeny of these bacteriophage since archaic.
Jordana Cepelewicz in her article further states that: 'Z and other modified DNA bases seem to have evolve to help viruses evade the defenses with which bacteria degrade foreign genetic material. The eternal arms race between bacteriophages and their host cells probably provides enough selection pressure to affect something as seemingly "sacrosanct" as DNA, according to Romesberg.'

Thursday, August 12, 2021

Fear memories and neuronal disorders

Rapid gene expression and DSBs
In a research study, it was found that the neuronal activity induced DNA double strand breaks (DSBs) to cause a change in neuronal activity regulated genes, when an organism is exposed to new sensory experience due to change in organism's external environment. That is a process of quick access to store genetic instructions as store memories.
Neuronal damage
But Li-Huei Tsai, the Picower professor of neuroscience found in her lab studies that fear memories induced repeated DSBs causes severe neuronal damage results neurological diseases causing neurodegenerative disorders impacting learning and memories. As routinely repair process of breaks become flawed and fragile with age, as repair mechanism falters.

In a research article Aging brain initiative, Tsai says, "We wanted to understand exactly how widespread and extensive this natural activity is in the brain upon memory formation because that can give us insight into how genomic instability could undermine brain health down the road," "Clearly, memory formation is an urgent priority for healthy brain function, but these new results showing that several types of brain cells (including Glia called astrocytes), break their DNA in so many places to quickly express genes is still striking." It was found that Glia DSBs response to hormone glutocorticoids, secreted in response of stress in fear conditioning, shows robust transcriptional response of glia to stress through hormone.

Brain sites of fear memories 
Author in their study found that creation of fear memories doubled the number of DSBs in variety of cell types in prefrontal cortex and hippocampus regions essential for formation and storage of conditioned fear memories, affecting more than 300 genes in each region for making synaptic connections due increased transcriptionally induced loci, a phenomenon called 'synaptic plasticity'. So such new groups of neurons connected together cause formation of new memories, called engrams. 
 
Damages due to frequent DSBs
The researchers wrote, 'Overall we have identified sites of DSBs at genes important for neuronal and glial functions, suggesting that impaired DNA repair of these recurrent DNA breaks which are generated as part of brain activity could result in genomic instability that contribute to aging and disease in the brain'.

*This blog is inspired by the MIT news from Picower institute for learning and memory. Many more research paper links are also thankfully inserted in blog, from public domain publication for detail study if needs. Graphic is by blog author.

Saturday, August 7, 2021

Father of nuclear bomb and Sanskrit scripture Bhagavat-Gita

"I have always been curious to know the inspiration behind those brains of key nuclear physicist, working in the 'Manhattan Project' in 1945, resulting in nuclear bomb then code named 'Gadget'.

And here comes a book, from the 'Hindu' scripture 'Bhagavat-Gita', which 'Oppenheimer' quoted before and after the 'Trinity test', many a time.

Hard it is to conclude if the 'Gita' was/is a book inspiring for a decisive fight against enemy or a truce resulting after the war of such a ferocious magnitude.

What an irony, the war referred in this scripture was finally fought with 'Brahmastra', a name in 'Sanskrit', believed to be a nuclear weapon of that time." 
--Author 
(Storyline: J. Robert Oppenheimer/ Nuclear bomb/ Inspiration/ Bhagavat-Gita/ Indology)



July 16th:
Every year this date reminds us about first nuclear detonation, code named 'Trinity' (assigned by Oppenheimer), tested successfully in 1945 on the culmination of 'Manhattan Project' which later used against humans in shorter than a month time, i.e. 6th August 1945 on Hiroshima, killing 126,000 civilians instantly.


It is recorded that more than 130,000 strong human force were employed in this Nuclear weapon research project, secretly conducted at various sites in US, Canada and UK, in the World War II years ranging from 1942 to 1946.


What an irony:
1. The German chemists were the pioneer scientist namely Otto Hahn and Fritz Strassmann discovering Nuclear fission which theoretically explained by Lise Meitner and Otto Frisch. 

But it was the party opposite to use this technology to win and end the second world war lastly.

2. Those who were involved in the Project may not be knowing the full impact of destruction it was going to cause and whole concept of war and peace was going to change there on.

3. It is said that two days before the 'Trinity' test, Oppenheimer expressed his hope and fear by citing a quote from the Hindu scripture Bhagavat-Gita, as: "In battle, In the forest, at the precipice in the mountains, On the dark great sea, in the midst of javelins and arrows, In sleep, in confusion, in the depths of shame, The good deeds a man has done before defend him."

4. Later in 2016 US President Barack Obama was in Hiroshima, recalled; "Death fell from the sky and the world was changed" where 80,000 lives were lost instantly on 9th August 1945 as the second Nuclear bomb was dropped over Japan.

That reminds the warning wordings of then President Truman saying, "expect a rain of ruin from the air, the like of which has never been seen on this earth."

Julius Robert Oppenheimer: (Physicist and Professor at the University of California Berkeley)
Oppie, as his friends called him, the war time head of the Los Alamos laboratory, was among many who worked in the 'Manhattan Project', he is the one credited as the 'Father of the Atomic bomb.'

While witnessing the 'Trinity' explosion he thought about a verse from a Hindu scripture Bhagvat Gita (XI, 12): "If the radiance of a thousand suns were to burst at once into the sky, that would be like the splendor of the mighty one.."

His Gita connection: 
It was way back in 1933, much before the 'Manhattan Project', Oppenheimer, a Jewish by birth, learned Sanskrit from an Indologist, Professor Arthur W. Ryder at Berkeley, read Gita in Sanskrit. Later he recalled that this was the book that shaped his philosophy of life.


Oppenheimer persuaded to quote again for a television broadcast in 1965:
"We knew the world would not be the same. A few people laughed, a few people cried. Most people were silent. I remembered the line from the Hindu scripture, the Bhagavad-Gita (verse 32 of chapter 11). Vishnu is trying to persuade the Prince that he should do his duty, and, to impress him, takes on his multi-armed form and says, 'Now I am become death, the destroyer of worlds.' I suppose we all thought that, one way or another."

Link for text, translated-audio, Oppenheimer's video:
http://www.bhagavad-gita.org/Gita/verse-11-30.html

'Bhagvat-Gita' scripture showing page with a verse 11-30, with an English translation by Oppenheimer, which is being quoted more often.


Life after: 
As quoted by author Robert Monk in his book, Oppenheimer reportedly told the then President Truman on October 25, 1945: "Mr.President, I feel I have blood on my hands."

Such was the sorrow !
it enveloped everyone !! 
even those who created it !!!

*A related article by the author:

Thursday, August 5, 2021

Hiroshima, Nagasaki in ethical perspective of nuclear bomb creator

"Out of curiosity, I have always thought about the minds of scientists working 76 years back in 'Manhattan project' then in 1948 and whose labor was materialized in less than a month time after 'Trinity' test, into a man hunting arsenal causing massacre at large in Hiroshima and Nagasaki on 6th and 9th August 1945, culminating into the last bloodiest scar for humanity to remember for generations, if they do not learn any lesson from.

From their statements, some being quoted below for easy reference, one can easily conclude their utter frustration from this outcome with a collective sense of regret." 
--Author
(Storyline: Second world war/ Nuclear bomb/ Aesthetic and ethical judgement)

Life is lot more fragile than we think. So you should treat others in a way that leaves no regrets. Fairly, and if possible, sincerely. It's too easy not to make the effort, then weep and wring your hands after the person dies. 
--Haruki Murakami 

J. Robert Oppenheimer: 'We have made a very grave mistake', and 'in some sort of crude sense..the physicist have known sin.'

In a famous quote about his meet with President Henry Truman, he has said then, 'Mr. President, I feel I have blood on my hands.'
Well, then he was referring the future too.

Henry Wallace, then the Vice President, recalls about him in his diary, 'I never saw a man in such an extremely nervous state as OppenheimerHe seemed to feel that the destruction of the entire human race was imminent.'

Later he vocalize his fear by saying, 'the people of this world must unite or they will perish.'

Reminiscing his earlier days while working in Los Alamos Laboratory, 'To me (the task at hand) is primarily the development in time of war of a military weapon of some consequences,....concern was as if to save the civilization.'

Perhaps when he referred through his famous quote of the Gita after the Trinity test:   'I am become deaththe destroyer of the worlds,' ..was perhaps pointing his concern for humanity in posterity.

Albert Einstein: He did not play a direct role but his discoveries did and he was in regret for the letter he wrote to Roosevelt . 'Had I known that the Germans would not succeed in producing Atomic bomb', he said, 'I would have never lifted a finger.'

In 1954, 5 months before his death, he has said, 'I made one great mistake in my life ..when I signed the letter to President Roosevelt recommending that atom bombs be made.'

'Politics is more difficult than physics', was the answer of Albert Einstein when he was asked, why one can discover the atomic power and not to control it.

Sunday, August 1, 2021

CRISPR-Cas9 gene editing tool can cause chromothripsis leading to oncogenes

CRISPER-Cas9 an ancient immune system in bacterium
Microbiologist in 1993 identified some unique repetitive, well preserved DNA sequences in Prokaryotes, appearing over and over again. Between repetitive  DNA sequences there are unique sequences that differs. These repetitive sequences are called as 'clustered regularly interspaced short palindromic repeats', abbreviated as CRISPER. Those non repetitive sequences matches with the genome of their pathogenic phage viruses. "So the hypothesis were put forward that bacterium succeeded in surviving from the virus infection by adding a piece of virus genetic code into it's genome as the memory of the infection. Perhaps the mechanism used by bacterium to neutralize a virus is by RNA interference." These were named as trans-activating crispr RNA (tracrRNA). That's an ancient immune system that protects bacterium from the infection of viruses.

Genetic scissor
Emmanuelle Charpentier and Jennifer Doudna, found that apart from CRISPER there are special CRISPER associated (cas9) genes, known for coding of a protein which unwinds and cleaves DNA (perhaps for the virus genetic material). Both scientists realized that the CRISPER-cas9 system could be programmed to cut other pieces of DNA and were awarded Nobel Prize 2020 in Chemistry "for the development of a method for genome editing". This precise molecular tool, like a scissor to make precise incision in DNA , to rewrite the code of life i.e. the genetic material.

Emmanuelle (left) and Jennifer (right)
Thankfully shared from Nobel Media in public domain

It also raises ethical, social and safety concerns as it's controversial use on human cells. This genetic scissor opened a new era of possibilities in the field of life sciences, biochemistry, cell biology, like as a gene editor, knowing the functions of genes and editing them for desired characters in plant breeding or controlling hereditary diseases etc.

CRISPER-Cas9 and genotoxicity
CRISPER-Cas9 based therapies have reported many genotoxic incident causing clinical complications like large scale DNA deletionsp53 tumor suppressor proteinchromosomal truncationspreexisting antibodies and T cells induced problems.

This happens because in clinical applications the possible safety concern and care are not being taken, resulting in break of d-DNA that results in genomic rearrangement, that means individual arrangement of chromosome is shattered which may also result in subsequent rejoining in haphazard order.

It is found that mostly cells do not survive due to these alterations and if they do, then may result in oncogenic fusion proteins or dysregulated expression of a particular gene that may bring more unwanted complications in individual cell.

Monday, July 26, 2021

'Code in Place', a computer coding course in Covid time

Learning during a grim phase of Covid Delta wave in India 
My log in page
When India was simmering with Delta wave of Covid-19, deaths were reported everywhere from one's neighbor to distant places, medical/social assisting system of every kind was disrupted completely, human dignity touched it's lowest point in our recent history; we sat in our homes with doors and windows closed and  mask on, isolating self in rooms possibly available, as if 'Covid-19 was in the air'. Hardly there was any home left where the family members were not with viral infective symptoms of some kind. People ran from one medical store to other in search of counter top medicine of some sort as there was no one to prescribe or guide to. This peak period ranged from mid April to the end of the May 2021. It was a period when 'Code in Place' came as rescue & refuge for many of us, here in India.

Shelter in Place vs Code in Place 2021 
OhYay for virtual Section
Phrase well suited to the situation when we all needed 'Shelter in place' and Stanford University provided us with 'Code in Place'. One can hardly imagine that how beneficial it was to us to engage us mentally for hours without any Covid-19 fear or isolation pressure from rest of our world. I sat transfixed to computer monitor, pouring attention to, unaware to the grim world outside, in my room at least for that much of the period. Thank you to all the distinguished team members of Stanford University for saving us from the rigorous pressure of the Covid Delta wave with unique opportunity of learning as well, a new skill set.

Coding in Places
Screenshot of a lecture video by Prof Mehran Sahami
It was a computer course in learning for coding and programming for Python language, based on Stanford University's CS106A, like the one they had in previous year in peak Covid-19 time of 2020. This was an online course, conducted for five weeks duration, requiring at least 10 hours per week, from April 19th to May 28th, 2021.


Karel commands from Karel Reader
For me it provided an unique experience of learning Coding in computer language Python. Each week with 3 days lecture videos, 1 day for 1 hour Section teaching, learning, problem solving activity with assigned  Section Leader of a Section around 10 students. Every week there were due assignments to solve and submit in due period. 'Karel' robot for initial learning of Python language, 'Ed' an online IDE hosting CIP community, 'OhYay' access for live Section for 1000+ section meetings around the clock across the globe engaging in virtual experiences were a huge shoutout. Hangout campfire by Section leaders was so useful to sort out and debugging of code written by any individual. Handouts, Lecture Videos, Lecture Slides, Files are still there for 'Life after Code in Place'.

While working on PyCharm IDE


Teaching by Mehran Sahami, Chris Piech, Julie Zelenski was a life time experience for the Coding. 
Meeka's design was selected by voting 
My experience was that the 'Content delivery' in teaching is a crucial part in communicating learning; while 'content', 'resource' and 'language-medium' matters little.



  Learning Coding was like getting magical tool along with 12,000 students, 1125 Section Leaders from all across the globe in a Community Service gesture of Stanford University in the testing time of Covid-19.

Getting my final project published in the showcase of Code in Place 2021 was a real reward and a great opportunity of participation.

Thank you Mehran Sahami, Chris Piech, Julie Zelenski, Brahm Capoor and many more in the entire team of this project at Stanford University, expanding in all 7 continents and countries.

Map of Code in Place 2021, thankfully shared from 

Sunday, July 18, 2021

Genetic code, Codon, Anti Codon, expression in Translation and Laws of heredity

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Basic molecular code of life:
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Genes on Chromosome in the cell nucleus carry instructions for amino acids in the form of chemical alphabets. They are four nitrogenous bases: A, G, T, C; namely Adenine, Guanine, Thymine, Cytosine. U (Uacil) is found only in RNA, replacing T. 

These 4 nucleotides (A, G = Purines; T, C = Pyrimidines) of the DNA combine in various ways to form 3 letter code for any specific amino acid to the synthesis of protein.

Making of protein: Gene expression for the synthesis of protein is in two ways:

1. Transcription: Gene sequence of DNA strand is rewritten on mRNA with the help of transcriptase enzyme inside nucleus of the cell.

2. Translation: mRNA Nucleotide sequence is rewritten on tRNA with the help of polymerase enzyme, which in turn picks up a specific amino acid to form a polypeptide in Ribosome of the cell.

We encounter Codon and Anti Codon at the time of Translation.

Codon: A sequence of 3 nitrogenous Bases in a row on mRNA, as a message for the specific Amino acid.

Anti Codon: A sequence of 3 nitrogenous Bases in a row on tRNA on it's anti codon loop. They also have pseudo bases apart from the regular bases. These codon recognize the correct codon on mRNA by its complementary sequence.

Amino acid activation:
Amino acid + ATP --------> Amino acyl AMP +2Pi
Amino acyl + tRNA  --------> Amino acyl tRNA +AMP
                                               (tRNA loaded with Amino acid)
                                                   (cognate or charged tRNA)
Correct amino acid recognisation here by tRNA base (3' 5'), with complementary match with the base sequence on mRNA (5' 3').           

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Code crackers:
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1. Physicist George Gamow in mid 1950s proposed the triplet hypothesis, this insight was mathematically suitable to code for essential 20 amino acids. 
This three nucleotide triplet code was the minimum to cover all the amino acids, later proved correct.
2. American biochemists Marshall W. Nirenberg, Robert W. Holley, Hargobind Khorana in 1960s did the pioneering work.
Nirenberg in 1961 with mRNA consisting poly-U, synthesized Phenylalanine (concluding UUU code for Phenylalanine) and later with poly-C mRNA translated to Proline (concluding CCC code for Proline).
Later Khorana experimented with poly-UC mRNA generated Serine and Leucine (concluding UCU code for Serine and CUC for Leucine).
In 1965 this code researcher  team deciphered the entire genetic code, including stop code, initiation code and received Nobel Prize in 1968.
(above modified image from nobel.org, in public domain)

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Gregor Johann Mendel (1822-1884), Father of Genetics
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Mendel (Czech) did his experiments on 10,000 pea plants for eight years (1856-1863), published his results in 1865. He concluded that genes come in pair and inherited as distinct units, one from each parent. He tracked the segregation of parental genes and their appearance as dominant or recessive traits in offspring.
He clearly recognized the mathematical pattern of inheritance from one generation to the next.
Mendel's Laws of Heredity are:
1, The Law of Segregation,
2. The Law of Independent Assortment,
3. Law of Dominance.
After his death, most of his personal papers and documents were burnt by the monks except few which remained in the archive of monastery.
Mendel on a postal stamp
      His laws were not understood until 1900 when independently three Botanist namely Hugo de Vries (Netherland), Correns (Germany) and Tschermak (Austria) rediscovered the findings of Mendel. 
      So Mendel put a blue print of things to come in the field of Genetics by deducing the laws of inheritance. 

       Meiosis, Chromosomes, Crossing Over, Genes, Linked Genes, Triplet Code were unknown in his time but his finding explains all this. His experimental results were rediscovered 16 years after his death and 34 years after he first published it. Triplet code came to be known only 100 years after his publication. Such was his genius as if he foresee all that. A friar, abbot who became 'Father', leaving no descendants behind, died at the age of 61 due to kidney ailment.

Pineal gland, the mystical third eye

Pineal gland   It is a very small unpaired midline brain structure of endocrine gland, tiny as a rice grain size, situated laterally (anatom...