February 28, 2019 Thursday

Bedtime Story 

My Experience at Animal Module for the Wilmer Core

At the Animal Module for the Wilmer Core there were dedicated personnel to timely feed the model organisms including veterinarians who could be called (and they did respond promptly) whenever the researchers felt that their experimental animals needed medical care.

It is understood that most of them (model organisms that is and not the veterinarians) would eventually be sacrificed since most tissue and cellular analysis are done on histopathological samples laid out on slides that are prepared once the eyeball has been enucleated.

It is less brutal to perform such destructive procedures on a culled animal rather than a living one.

Yes, it is true that animal studies are a gory process where sometimes one has to fight and suppress the ethical and emotional conflicts that by default are bound to arise.

I found it quite painful to place a gentle furry white New Zealand Rabbit into a gas chamber and then lift out its carcass and perform destructive surgical procedures on it.

But it had to be done for the progress of knowledge.

The only solace I have is that I subjected my own body to experimental tests on untested drugs and dyes though that in no way can be compared to that of experiments on animals since the most crucial aspect of it – the consent – was overlooked in them.    

The other aspect is even more crucial – drugs injected into my organism did not turn out to be lethal and even to begin with they were safe to a large extent.

Now how would I know or the doctors who injected the drugs into me know that the drug is relatively safe?

For this you should know a little bit about how drugs that you consume are determined for their safety and efficacy.

“Efficacy” is an interesting word.

Even though it has its origins in the “effectiveness” it has slightly different meaning from it in pharmacology where it is denoted by the symbol E_max.

You may get a hint from the subscript about the meaning of this pharmacological term in which efficacy denotes the maximum response achievable from a pharmacological agent especially in a research setting.

Clinical research of any novel pharmaceutical agent takes place through five phases that are termed as Phase 0, Phase I, Phase II, Phase III and Phase IV.

Phase 0 is the stage where very low number of healthy volunteers (may be 10 or less) is subjected to the drug of very low concentrations that is definitely below the therapeutic levels.

The key parameter that is studied at this phase is the pharmacokinetics of the drug, oral bioavailability and half-life of the drug.

Pharmacokinetics is not the study of how the drug affects the organism but rather how the body affects a drug.     

Pharmacokinetics is a very interesting subject that will take way of several nights of ours and so I will not do into the detail discussion of the subject.

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

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Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 27, 2019 Wednesday

Bedtime Story 

Speciation and Genetic Relatedness

By now massive evidence has accrued of common descent of all life on earth from the last universal common ancestor. 

This fact has allowed the conservation of genetic material over the course of evolution.

The conservation of genes were accompanied with conservation of crucial metabolic and developmental pathways displaying themselves all over the animal and plant kingdom.

Most wise men of various civilizations had long understood this to be true; in fact, it had to be true.

Only thing was that they were not sure or rather ignorant was the exact mechanism for the speciation process.

Speciation process is, as you will very well know, is the process of evolution of a new species from a single ancestral population which can happen through several mechanisms.

I shall not go into the mechanisms of speciation for now.

We all animals on this planet share at least 6331 groups of genes that belong to a common ancestor which lived about 650 million years ago.

This was the time of intensive glaciations and ice age where the primary forms of life was amoebae, algae and sponges.

It is simply quite astonishing to know the percentage of genome that has been conserved across species whose extent can be understood with the simple example of human apes sharing 90% of the genome with the common house mouse (Mus musculus).

This is the fundamental basis of use of model organisms; the evolutionary principle and our genetic relatedness.

It is therefore not surprising that this humble and often despised creature has served as one of the most important model organisms in biology and medicine.

I myself had the honor of experimenting on their eyes (along with New Zealand rabbits) at the Wilmer Research Institute that has now developed Wilmer Core Research Centers that is a leading recipient of generous research grants in the United States.

I was fascinated and dumbstruck when I first entered the Animal Module for the Wilmer Core sometime in the July of 2007. 

The manner in which the animals of all sorts starting from house mouse, New Zealand rabbits and even dogs were housed and taken care stunned me.

I did not see any non-human primates over there though since ethically they are most objectionable to experiment upon since genetically they are extremely close to us.

The next laboratory where I did happen to work upon simultaneously along with Gavin Herbert Eye Institute of University of Irvine which was that of Allergan Incorporated at Irvine did house several non human primates.

As per the US Department of Agriculture report of 2017 Allergan at Irvine had 175 nonhuman primates.

A section of public till this day continues to protest against the use of animals for research purpose. 

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

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Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 26, 2019 Tuesday

Bedtime Story 

Zea mays vs Drosophilia melanogaster

Tonight we shall continue with the first paragraph of the 1950 paper of Barbara McClintock that was published in PNAS titled “The origin and behavior of multiple loci in maize”.

“The terms mutable genes, unstable genes, variegation, mosaicism, mutable loci or “position effect” have been applied to this phenomenon.

Its occurrence in a wide variety of organism has been recognized.

The most extensive investigations of this phenomenon have been undertaken in Drosophilia melanogaster.

In this organism, the conditions associated with the origin of genic instability have been well defined.

The part played by the heterochromatic materials of the chromosomes, in inducing and controlling the type of variegation and its time and frequency of occurrence, has been established.

It has not been generally recognized that the instability of genic expression in other organisms may be essentially the same as that occurring in Drosophilia.”

Note the use of the word “genic” as contrast to today’s genetic which reflects that genetics was at its extremely nascent stage then.

Drosophilia melanogaster as you would be aware is the common fruit fly though it is neither very commonly seen nor is it truly a fruit fly in any meaningful way.

It has been one of the most famous subjects of study by the geneticists with eight Nobel Prizes been conferred for work done on this organism which is largely a pest for humans.

The American entomologist who founded and established the Entomology Department at the University of California, Berkeley was the first person to propose this rather unattractive fly to be the model organism for genetic researchers.

Considering from the way genetics has evolved after him there is no doubt that his suggestion was taken seriously.

It is important that you as an ape understand the concept behind the model organism for it has profound implications.

Model organism is any non-human species that is extensively studied by us apes with the hope that what will be discovered in them will be and can be broadly generalized to the biological systems of others organisms with humans being the prime beneficiary eventually.

They also serve as in vivo models on which experimentation is conducted for medical reasons when it is not feasible to do so on humans or not recommended on us apes on ethical grounds.   

A lot of medicines that you consume and on which we survive have come through such experimentations.

But why do you think this kind of modeling works?

What is the basis for constituting the concept of model organism?

This, Mon Ami, is evolution by natural selection and thereby common descent of all living organisms.

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 25, 2019 Monday

Bedtime Story 

"The Origin and Behavior of Multiple Loci in Maze" 1950 PNAS 

Barbara McClintock, after a series of careful micro analysis, came to the conclusion that there were two dominant and interacting genetic loci on the 9^th chromosome that were interacting and manifesting phenotypically in a very strange manner.

When there was no Activator or Ac element present in the chromosome then the Ds inhibits the synthesis of anthocyanins and the seed is colorless.

When one copy or the allele of the Ac is present then the suppression effect of the Ds is taken off from the aleurone-color gene which is then able to produce pigments.

What she further observed was that the presence of Ac gene did not generate a fixed color pattern on the maize seeds but a very variable one.

Her genetic analysis of these variable colored or mosaic patterned seeds shows that the genetic element of Ds was mobile on the chromosome 9.

Not only was the Ds gene mobile on the chromosome but its mobility was controlled at least to some extent by the Ac gene.

She found that the movement or the transposition (this is the formal genetic term for such mobile genes) of the element Ds depended on the number of elements or copies of Ac gene present.

The different locations of Ds gene that in turn depended on the number of copies of Ac gene resulted in the mosaic color pattern of maize seeds.

She further generalized the basic idea from this experiment and extrapolated to a much larger scale, in fact, to the entire biology.

She proposed that this genetic transposition and its control was a general method of gene regulation through transposition of genetic elements that allowed multicellular organisms having cells of identical genomes to function differently.       

   

This idea challenged the established orthodoxy of a genome being a static set of instructions that was passed from one generation to other.

She published this study in 1950 in PNAS in the paper titled “The origin and behavior of multiple loci in maize”.

I shall quote to you the just the first paragraph of the entire paper as it gives a general idea what she was implying.

I also find it interesting to read through the style of writing of the original author as that speaks something about the personality.

It is of course impossible to read all the original papers of all the scientists that we discuss in these bedtime stories but whenever time permits it is worth it as that gives you a more realistic idea how scientific knowledge gradually accrues over time through the tiny contributions of unknown and lost apes.

“In the course of an experiment designed to reveal the genetic composition of the short arm of chromosome 9, a phenomenon of rare occurrence (or recognition) in maize began to appear with remarkably high frequencies in the cultures.”   

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 24, 2019 Sunday

Bedtime Story 

Mendel was Largely Overlooked 

Gregor Mendel’s two talks at the Natural History Society did get some attention in the popular media which meant brief reports in the local news papers which considering the literacy rates of those days even in Europe would not have been read widely.

The scientific societies though largely ignored his work.

The very next year, that is 1866, he got his paper published in the journal “Proceedings of the Natural History Society of Brünn.”

Can you imagine how the paper was perceived then by even those few who took care to read the paper?

It was seen more as a description of plant hybridization which means sexual combination of traits of two organisms of different breeds to produce a hybrid off spring.

Animal and plant breeders had been conducting such artificial hybridization since ages (for instance mule which is a hybrid of a male donkey and a female horse).

In contrast to natural selection such kind of selective breeding by humans for their agriculture and animal domestication purpose is called artificial selection.

This was the reason why when seen from the perspective of hybridization the paper seemed to be presenting nothing new.

Genetics never crossed the minds of the readers as they were blind to it.

This paper, as far as it is known, was cited just about three times in the next thirty five years was largely ignored.

Barbara McClintock in contrast to Mendel faced outright hostility quite ironically because her studies showed new findings that contradicted simple Mendelian genetics.

McClintock was in essence was merely treading on the trail or continuing to walk on the trail left behind by Mendel but only to show that genetical inheritance was not as black and white as shown and proposed by him.     

McClintock in her studies targeted two gene loci that she named as Dissociation or Ds in short and Activator or Ac in short.

These genetic loci influenced the synthesis of colored pigments called anthocyanins which are water-soluble pigments found in the vacuoles of plant cells.

A lot of flower colors are due to these anthocyanins as are the patterns on maize seeds and kernels.  

Her study began first with plantation of corn kernels that were self pollinated.

Self-pollination in plants is supposed to have happened when the stigma of the plant (stigma, style and the ovary together constitutes the gynoecium or the female reproductive organ of the plant) receives pollen from its own stamen which is the male reproductive organ of the plant.

In an animal it is equivalent to an organism fertilizing his/her own ovum with his/her sperms.

Because of long line of repeated pollination these plants had developed chromosomal damage in the form of broken arms at the end of the ninth chromosomes.           

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 23, 2019 Saturday

Bedtime Story 

Barbara McClintock was Following the Steps of Gregor Mendel

Corporate funding is pathetically meager at the Cold Spring Harbor Laboratory even though eventually it would be giant pharmaceutical and biotechnology corporations who would go on to exploit and profit from the discoveries that are coming out from laboratories such as these.

It would be in this laboratory in the 1940s and 1950s through the war years where Barbara McClintock made extremely interesting but “controversial” observations of those times that would be received by the establishment with “puzzlement, even hostility”.    

Can you even guess what was she interested at?

Some of the seeds of the maize plant exhibited mosaic color patterns that seemed to show no consistency or rather large variability in their inheritance.

It would not be something that would grab the attention of an average mind, isn’t it?

For some reason it grabbed the attention of Barbara McClintock and she began to study this queer and unstable inheritance of these mosaic patterns of the maize seeds very systematically.

She reminds me of the Austrian friar Gregor Mendel who had taken similar but extraordinary interests in the traits of pea plants including the pod shape and color.

For those of who hold the view that Mendel was simply an amateurish botanist who took a vague interest in inheritance of pea plant characteristics I will let you have know that not only did he take meticulous notes but also presented it in a form of paper, not once but twice.

This I am talking about the year of 1865 when ordinary Hindus and Europeans were struggling for making a decent living, and by “decent” it is nothing close to which even an average citizen of a third-world enjoys (think about running water in your tap and toilets, electricity in your home, a heater or an air-conditioner to manipulate your local climate and of course, your beloved smart phones that you can never get enough of).  

In not one but two meetings of the Natural history Society of Brno in Moravia (now in Czech Republic) on February 8 and March 8 of 1865 Mendel presented his paper titled “Experiments on Plant Hybridization”.

It is said of Mendel that his results were “too good” which implies that Mendel was selective in data that he chose.

The basic essence of the paper can be summarized in the form of the following table:

CHARACTERSTICS CONTRASTINGTRAITS OFFSPRINGTRAITS

Flower color            Violet and White            Violet

Flower position        Axial and Terminal         Axial

Plant Height            Tall and Dwarf               Tall

Seed Texture           Round and Wrinkled       Round

Seed Color              Green and Yellow           Yellow

Pea Pod Texture      Inflated and Constricted  Inflated

Pea Pod Color          Green and Yellow           Green    

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 22, 2019 Friday

Bedtime Story 

Barbara McClintock  

The work or rather the observation of the Belgian priest Frans A. Janssens was later continued by many men the most notable of them being Thomas Hunt Morgan the American evolutionary biologist, geneticist and embryologist who was awarded the Nobel Prize in Physiology and Medicine for firmly establishing the role of chromosomes in heredity.

But the idea that genetic recombination by crossing over during meiosis was essentially a DNA repair mechanism which later got incorporated accidentally into meiosis was proposed by the American female cytogeneticist Barbara McClintock who primarily worked with maize.

During the course of the work she developed ways to visualize and characterize maize chromosomes and thereby as a byproduct of it was the first to describe the cross-shaped interaction of homologous chromosomes during meiosis.

In 1931 she along with another American female geneticist Harriet Creighton published a very influential paper that not only described chromosomal crossover but also proved that it was associated with recombination of genetic traits.

At that time both these scientists were affiliated to the Botany Department of the Cornell University.

The paper was published in the PNAS or Proceedings of the National Academy of Sciences of the United States of America and it was titled “A Correlation of Cytological and Genetical Crossing-Over in Zea Mays”.

McClintock also proposed the idea that DNA repair and crossing over are very similar in principle utilizing same protein complexes.

This would not be her greatest work for that would come much later while working at the Cold Spring Harbor Laboratory situated in the village of Laurel Hollow in Nassau County in the state of New York.

This Mon Ami is what the great nation of the United States is about – housing a private, non-profit genetic research laboratory and institute in a village.

This village, I must add, is unlike any village that one may relate to that of a third-world country.

Laurel Hollow, according to the Bloomberg BusinessWeek, is the 8^th wealthiest village-town in America with a median household income of being more than 200,000 USD.

The per capita income of this village is an astounding 83,366 USD! 

You may wonder (at least I do being a baniya) that from where does a research laboratory (which houses 52 research laboratories, 600 research staff and 500 administrative and support personnel) that is not for profit gets it finances from.

I can tell that you a large chunk of its funding comes from the public.

In the year of 2015 about 34% of its finances came from the federal agencies of National Institutes of Health and National Science Foundation.

Another 22% of it came from private philanthropy with a mere 3% coming from the corporate.

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg

February 21, 2019 Thursday

Bedtime Story 

Homologous Recombination and Meiosis

DNA breaks that involve rupture of both the strands simultaneously are known as (quite unimaginatively) double-strand breaks.

Although homologous recombination is a cellular method to solve the problem of double-stand breaks we are more concerned with the effect that it has on the production of sperms or eggs that are together known as gametes.

It is possible, though not certain, that during the course of evolution chromosomal crossover was primarily a DNA repair mechanism that accidentally got incorporated in the pachytene phase of prophase I of meiosis.

The entire process of meiosis (which is a Greek word for lessening and therefore very apt as you see shortly), involves production of four haploid cells from one diploid parent cell each of whom are genetically distinct and unique from the parent cell that gave rise to them and eventually form the gametes for the organism.

In human male apes this single cycle of meiosis or sperm formation in the testes takes around 74 hours (in females meiosis and thereby egg formation is far more complex as everything is in their case and this has not been said in any deprecatory sense or intent).

As an aside it may surprise some of you that human apes may be the only species on this planet whose fairer counterpart consider it normal to live decades after menopause (and if desirous of it to enjoy hassle-free sex too).

This has allowed grandmothers to rear the children of their children thereby increasing their survival rate manifold and giving our species a tremendous advantage over other species.

It might come equally as a revelation to some of you to know (against all the prevailing notions about glorious past) that during the time of traditional medicines such as ayurveda, naturopathy and Hippocratic humorism members of our species rarely survived beyond menopause and middle age succumbing beforehand to disease, microbial pathogens, accidents and predators.

A simple rabid dog bite would be fatal those days (the killer being RNA Lyssavirus in this case which is both neuroinvasive and neurovirulent).

For the sake of better understanding therefore meiosis has been classified into stages which we need not go into since it is available at the tip of your fingers quite literally.

Minute details of this fundamental biological mechanism are also invariably tested in all the competitive exams that serve as an entrance portal to any profession remotely connected with biology.   

The crossing-over was first discovered by a Belgian priest and cytologist by the name of Frans A. Janssens who published his finding in a paper in the year of 1909 in the first journal of cytology called La Cellule.

(You would recall that it was yet another Belgian priest by the name of Georges Lemaître who had first proposed on theoretical grounds that our universe must be expanding). 

He called crossing-over “chiasmatypie” and his 1909 paper was titled “The theory of the Chiasmatypie”.

Stay tuned to the voice of an average story storytelling chimpanzee or login at http://panarrans.blogspot.com

                              

Good night Mon Ami and my fellow cousin ape.

                           

  

                

             

Advertisements

Another great educator and a teacher that I am aware of is Professor Subhashish Chattopadhyay in Bangalore, India.

While I narrate stories, Professor Subhashish an electronic engineer and a former professor at BARC, does and teaches real mathematics and physics.

He started the participation of Indian students at the International Physics Olympiad.

Do visit him here:

http://skmclasses.weebly.com/

All his books can be downloaded for free through this link:

https://zookeepersblog.wordpress.com/science-tuition-chemistry-physics-mathematics-for-iit-jee-aieee-std-11-12-pu-isc-cbse/

For edutainment and English education of your children, I recommend this large collection of Halloween Songs for Kids:

https://www.youtube.com/channel/UCd14DRdYKj454znayUIfcAg