MOTHER OF DNA DOUBLE HELIX MODEL

 THE KB                                                                                                                        30.05.21

CURIOUS CASES BEHIND ‘ PHOTO 51’ &  BEYOND

‘ Science for me, gives a partial explanation for life. In so far as it goes, it I based on fact, experience and experiment’ – this widely known famous quote was stated by an unsung hero, often less prioritized, supreme genius yet too much underrated ‘ The dark lady of DNA’ ( by Barbara Maddox) , a British chemist ; Rosalind Franklin.

It was evident very early when she first stepped in the King’s College of London on 1951 at the age of 31. Born in 1920; A passionate, dedicated, calm and composed yet rebellious, extremely brilliant with inventory thought depicts Rosalind Franklin the best. She was an enigma at that time. She started schooling previously at St. Pauls’ and completed her study from Cambridge University in Chemistry till 1938, worked in CURA(Coal utilization Research Association) till 1947 and learned X ray crystallography from Mareel Mathieu.

 

Her times in King’s College London was the most significant chapter of her life where she worked upon one of the ground breaking discovery of all time not only in science but also for humanity that is to reveal the double helix structure of DNA which was still under the mystery. She faced many facets of challenges of being woman and also being a jew but she was determined and disciplined on her work. She used to work intensely in the lab mostly on the X ray crystallography to reveal the actual structure of DNA double helix. She along with her assistant Gosling continued to excel in their work. The guide of Franklin was Maurice Wilkins who was envious on his research scholar, never gave the credit and also used to torture mentally to Franklin and unethically wanted to reveal all of her work to his close friend JD Watson who was also working on the same purpose in another place names as Cavendish Laboratory along with his senior Francois Crick, they were trying to reveal the DNA structure in theoretically and were perplexed about the position of H-bond in double helix structure. Rosalind Franklin was spending her time and as a true perfectionist she used to take the near perfect conclusive evident on the X ray crystallographic image of DNA double helix for 50 times and took 100 hours to make famous ‘photo 51’; the most perfect image was the 51^st one. That’s why the number 51 is very significant in Franklin’s life, as a full time researcher she started her work in King’s College on 1951 too. Unfortunately her tremendous hard work had been unethically robbed by Wilkins and helped Watson and Crick to solve the puzzle of DNA double helix model. Later in life Watson became a good friend of Franklin but at that time Watson also betrayed Franklin. Watson, Crick and Wilkins awarded Nobel prize on 1962 for the discovery of DNA double helix model and the ill fortunate Franklin died in ovarian cancer on 1958 at the age of 38 only. She was fallen ill during her work according to Gosling.

 

So, this was the epitome of a tragic story of science, excellent researcher, amazing personality of Franklin. She got her credit after the death when whole scenario came in front, during her time she never got any recognition about her work. Now she is called as ‘ mother of DNA double helix model’. Very few people knows that she was very keen to study in the field of virology also, she described the 3D structure of TMV( tomato mosaic virus), depicted the structures of coal and graphite.

 

Confrontation when cornered was Rosalind’s tactic. The alternative- passive acquiescence in something she knew to be wrong – was intolerable, totally contradictory to her faith in the provable truth of science.

 

EMPTY ROAD…SPOTLESS MIND

T

he long way ; may be the longer…

Wait, wait, and further wait…

Let's see ; the unsown desires…

Like shadows are passing by…

To the empty road 

That unfinished journey, to the spotless end...

How can we stop?

There is no stop of stupidity... 

Dreadful  greed; bloody desires…

 

T

he dying mortality; degraded socialism…

Flying like shadowy imposters…

No respect, no grit, no matters to survive...

The divine images that are broken... 

Their kindlier souls of statuesque...

Breaks the soul of inspirations, soul of the greatness…

Imprisoned in the jail of evils; like a jail bird...

Way to the eternal sunshine to the spotless mind…

Still in a long…long…long…way...

The way of resurgence...

The gateway of wisdom and will power; the great pleasure.

 

THE KB

Human aDNA

 OPENSIVE MIND// THE KB

Due to the considerable anthropological, archaeological, and public interest directed toward human remains, they have received considerable attention from the DNA community. There are also more profound contamination issues, since the specimens belong to the same species as the researchers collecting and evaluating the samples.

Sources:-

Due to the morphological preservation in mummies, many studies from the 1990s and 2000s used mummified tissue as a source of ancient human DNA. Examples include both naturally preserved specimens, for example, those preserved in ice, such as the Ötzi the Iceman, or through rapid desiccation, such as high-altitude mummies from the Andes, as well as various sources of artificially preserved tissue (such as the chemically treated mummies of ancient Egypt). However, mummified remains are a limited resource. The majority of human aDNA studies have focused on extracting DNA from two sources that are much more common in the archaeological record – bone and teeth. The bone that is most often used for DNA extraction is the petrous bone, since its dense structure provides good conditions for DNA preservation. Several other sources have also yielded DNA, including paleo faeces, and hair. Contamination remains a major problem when working on ancient human material.

Ancient pathogen DNA has been successfully retrieved from samples dating to more than 5,000 years old in humans and as long as 17,000 years ago in other species. In addition to the usual sources of mummified tissue, bones and teeth, such studies have also examined a range of other tissue samples, including calcified pleura, tissue embedded in paraffin, and formalin-fixed tissue. Efficient computational tools have been developed for pathogen and microorganism aDNA analyses in a small (QIIME) and large scale (FALCON).

Results:-

Taking preventative measures in their procedure against such contamination though, a 2012 study analyses bone samples of a Neanderthal group in the El Sidon cave, finding new insights on potential kinship and genetic diversity from the aDNA. In November 2015, scientists reported finding a 110,000-year-old tooth containing DNA from the Denisovan hominin, an extinct species of human in the genus Homo.

The research has added new complexity to the peopling of Eurasia. It has also revealed new information about links between the ancestors of Central Asians and the indigenous peoples of the Americas. In Africa, older DNA degrades quickly due to the warmer tropical climate, although, in September 2017, ancient DNA samples, as old as 8,100 years old, have been reported.

Moreover, ancient DNA has helped researchers to estimate modern human divergence. By sequencing African genomes from three Stone Age hunter gatherers (2000 years old) and four Iron Age farmers (300 to 500 years old), Schlebusch and colleagues were able to push back the date of the earliest divergence between human populations to 350,000 to 260,000 years ago.

WORLD'S MOST EXPENSIVE DRUG

 OPENSIVE MIND// THE KB

Invention:- Zolgensma was developed by AveXis, a Chicago-headquartered biotech that Novartis bought in 2018 for $8.7bn. It had been manufactured in Maryland.

Zolgensma (onasemnogene abeparvovec-xioi), marketed by Novartis Gene Therapies, is an FDA-approved therapy to treat SMA. It is a type of treatment referred to as gene therapy or gene replacement therapy. More than 20 private health-insurance plans and four Medicaid plans have set up coverage policies for Zolgensma since the FDA approval, according to Novartis.

How it works ?

As a gene therapy, ZOLGENSMA^® (onasemnogene abeparvovec-xioi) is designed to target the genetic root cause of spinal muscular atrophy (SMA) by replacing the function of the missing or nonworking SMN1 gene with a new, working copy of a human SMN gene. ZOLGENSMA does not change or become a part of the child's DNA.

Pathophysiology:- Survival motor neuron (SMN) proteins facilitate proper signaling between CNS motor neurons and muscles in the body § SMA is an autosomal recessive condition caused by deletions or mutations in the SMN1 gene, resulting in a shortage of SMN protein o SMN2 gene produces a small amount of functional length SMN protein, and an increase in copy number may decrease severity of disease but cannot fully compensate for the loss-of-function of SMN1.

 

Why is it so expensive?

The reason Zolgensma is so expensive is because that is the price Novartis has decided it is worth because it “dramatically transforms the lives of families affected by this devastating disease” and the claimed cost of bringing new drugs to market. But this price is not without controversy. While a genetic test for SMA costs just under $500, more than 12,500 women would have to be screened to prevent one case of SMA, which affects only about 1 in 10,000 newborns.

Result of application

Zolgensma® data shows rapid, significant, clinically meaningful benefit in SMA including prolonged event-free survival, motor milestone achievement and durability now up to 5 years post-dosing.

Dosage:- Monitor troponin-I before ZOLGENSMA infusion and on a regular basis for at least 3 months afterwards (weekly for the first month, and then monthly for the second and third months until troponin-I level returns to baseline). Now that Zolgensma is finally approved in Europe, though, Novartis has an opportunity to steal market share from Biogen's SMA drug Spinraza. That's because the European approval allows the Zolgensma to be used in children weighing up to 21 kilograms, which basically covers any child under the age of 5.

Comparison of Zolgensma and Spinraza:-

An indirect comparison of the two treatments indicates that Zolgensma may be more effective than Spinraza among infants with symptomatic SMA type 1 in terms of overall survival, independence from permanent assisted ventilation, motor function and motor milestones.

Availability:-

Novartis Gene Therapies' Zolgensma (onasemnogene abeparvovec) will be available for use in the UK's National Health Service (NHS) following recommendations by regulators in England and Wales, as well as Scotland. Zolgensma is deemed to be the most expensive drug in the world with a list price of £1.79m per dose.

THE HEADLESS CHICKEN

 OPENSIVE MIND// THE KB

Mike the Headless Chicken (April 20, 1945 – March 17, 1947) was a Wyandotte’s chicken that lived for 18 months after his head had been cut off. After the loss of his head, Mike achieved national fame until his death in March 1947. In Fruita, Colorado, an annual "Mike the Headless Chicken Day" is held every May.

Beheading:- On September 10, 1945, farmer Lloyd Olsen of Fruita, Colorado, was planning to eat supper with his mother-in-law and was sent out to the yard by his wife to bring back a chicken. Olsen chose a five-and-a-half-month-old Wyandotte chicken named Mike. The axe removed the bulk of the head, but missed the jugular vein, leaving one ear and most of the brain stem intact.

Due to Olsen's failed attempt to behead Mike, the chicken was still able to balance on a perch and walk clumsily. He attempted to preen, peck for food, and crow, though with limited success; his "crowing" consisted of a gurgling sound made in his throat. When Mike did not die, Olsen instead decided to care for the bird. He fed it a mixture of milk and water via an eyedropper, and gave it small grains of corn and worms.

Death:- In March 1947, at a motel in Phoenix on a stopover while traveling back from tour, Mike started choking in the middle of the night. He had managed to get a kernel of corn in his throat. The Olsens had inadvertently left their feeding and cleaning syringes at the sideshow the day before, and so were unable to save Mike. Olsen claimed that he had sold the bird off, resulting in stories of Mike still touring the country as late as 1949. Other sources say that the chicken's severed trachea could not properly take in enough air to be able to breathe, and it therefore choked to death in the motel.

Explanation of death: - 

• It was determined that the axe had missed the jugular vein and a clot had prevented Mike from bleeding to death. Although most of his head was severed, most of his brain stem and one ear were left on his body. Since basic functions (breathing, heart rate, etc.) as well as most of a chicken's reflex actions are controlled by the brain stem, Mike was able to remain quite healthy. 
• This is a good example of central motor generators enabling basic homeostatic functions to be carried out in the absence of higher brain centers. 
• In addition, birds possess a secondary balance organ in the pelvic region, the lumbosacral organ, which controls walking locomotion virtually independently from the vestibular organ involved in flight. This has been used to explain how a headless chicken can walk and balance, despite the destruction of much of the cranial vestibular system.

 

Fame:- Once his fame had been established, Mike began a career of touring sideshows in the company of such other anomalies as a two-headed baby. He was also photographed for dozens of magazines and papers, and was featured in Time and Life magazines.  

Legacy:- Mike the Headless Chicken is now a cultural institution in Fruita, Colorado, with an annual "Mike the Headless Chicken Day", the third weekend of May, starting in 1999. Events held include the "5K Run Like a Headless Chicken Race", egg toss, "Pin the Head on the Chicken", the "Chicken Cluck-Off", and "Chicken Bingo", in which chicken droppings on a numbered grid choose the numbers.

Mike the Headless Chicken was an inspiration for the poultry-themed comedy punk band The Radioactive Chicken Heads, serving as the subject of their 2008 song "Headless Mike", for which a music video was filmed. The band also features a Headless Mike puppet which is frequently used in their live shows.

References:-  

BBC NEWS ONLINE

CLINICAL NEUROSCIENCE

Amy Reiter (1999). "Mike the Headless Chicken more popular than Clinton".

FAMOUS HIPPO FROM PROTEAN LAND

 HUBERT OR HUBERTA?                                                                       THE KB // OPENSIVE MIND

Huberta (initially named Hubert; the gender was discovered after death) was a hippopotamus and one of the most famous animals in South African history.

In November 1928, Huberta left her waterhole in the St. Lucia Estuary in Zululand and set off on the 1,600-kilometre (1,000 mi) journey to the Eastern Cape, a journey which took her three years. 

In that time, Huberta became a minor celebrity in South Africa and attracted crowds wherever she went. She was initially thought to be a male and was nicknamed Hubert by the press. The first report in the press was on 23 November 1928 in the Natal Mercury and reported the appearance of a hippo in Natal. The report was accompanied by the only photograph of Huberta in life.

Huberta stopped for a while at the mouth of the Mhlanga River about 15 kilometers (9 mi) north of Durban and a failed attempt was made to capture her and put her in Johannesburg Zoo. After this, she headed south to Durban where she visited a beach and a country club. Moving on to the Umgeni River, she became revered by Zulus and Xhosas alike.

Finally, Huberta arrived in East London in March 1931. Despite her having been declared royal game (and thus protected) by the Natal Provincial Council, she was shot by farmers a month later. After a public outcry, the farmers were arrested and fined £25. Huberta's body was recovered and sent to a taxidermist in London. Upon her return to South Africa in 1932, she was greeted by 20,000 people and was displayed at the Amatole Museum (previously known as the Kaffrarian Museum) in King William's Town.

Huberta is the subject of the children's book Hubert The Traveling Hippopotamus by Edmund Lindo and illustrated by Jane Carlson. The book was published in 1961 by Little, Brown and Company.

REFERENCES:- 

Witz, Leslie (2004). "The making of an animal biography: Huberta's journey into South African natural history, 1928-1932". Kronos. 30: 138–166.

Lindop, Edmund; Carlson, Jane (1961). Hubert, the Traveling Hippopotamus. Little, Brown.

FOXP2 : A master gene for language?

 

Perhaps the greatest insight into the evolution of language has come from work on the FOXP2 gene. This gene plays a key role in language and vocalization and allows us to explore the changes underpinning the evolution of complex language.
The FOXP2 gene was first discovered by Simon Fisher, Anthony Monaco and colleagues at the University of Oxford in 2001. They came across the gene through their studies of DNA samples from a family with distinctive speech and language difficulties. Around 15 members of the family, across three generations, were able to understand spoken words perfectly, but struggled to string words together in order to form a response. The pattern in which this condition was inherited, suggested that it was a dominant single-gene condition (one copy of the altered gene was enough to disrupt their overall language abilities). The researchers identified the area of the genome likely to contain the affected gene but were unable to identify the specific gene mutation within this region.
They then had a stroke of luck, in the form of another unrelated child with very similar symptoms. Looking at this child’s DNA they identified a chromosome rearrangement that sliced through a gene in the region of DNA where they suspected the mutated gene was. This gene was FOXP2.  After sequencing the FOXP2 gene in the family they found a specific mutation in the gene that was shared by all the affected family members. This confirmed the importance of FOXP2 in human language.
Simon and his colleagues went on to characterize FOXP2 as a ‘master controller’, regulating the activity of many different genes in several areas of the brain. One key role is in the growth of nerve cells and the connections they make with other nerve cells during learning and development. Mutations in the FOXP2 gene interfere with the part of the brain responsible for language development, leading to the language problems seen in this family.

The evolution of FOXP2 

The FOXP2 gene is highly conserved between species. This  means that the gene has a very similar DNA sequence in different species, suggesting it has not evolved much over time. The FOXP2 protein in the mouse only differs from the human version by three amino acids. The chimpanzee version only differs from the human version by two amino acids. These two changes in amino acids may be key steps in the evolution of language in humans.  What difference do these small changes in sequence make to the functionality of the FOXP2 protein? Studies with mice show that changing the mouse version of the FOXP2 gene to be the same sequence as the human version only has subtle effects. Remarkably, the resulting mouse pups are essentially normal but show subtle changes in the frequency of their high-pitched vocalizations. They also show distinctive changes to wiring in certain parts of their brain. From these studies scientists have concluded that FOXP2 is involved in the brain’s ability to learn sequences of movements. In humans this has translated into the complex muscle movements needed to produce the sounds for speech, whereas in other species it may have a different role, coordinating other movements.FOXP2 regulates many other genes in the body and evolution seems to have favored a subset of these as well, particularly in Europeans. FOXP2 regulated genes are important not only in brain development, but they also play important roles in human reproduction and immunity.

FOXP2 and the Neanderthals

Neanderthals have generally been characterized as a large, brutish species with little or no intellectual, social or cultural development. However, the fact that they had the same FOXP2 gene as modern humans suggests that Neanderthals may have had some capacity for speech and communication. Various strands of evidence have helped to establish a picture of how Neanderthals might have lived and communicated. Archaeological records suggest that they probably lived in small groups and due to their high energy needs, spent most of their time hunting. Neanderthals are unlikely to have developed social groups bound together by effective communication. This is probably because they lacked the key mental abilities needed to establish and maintain social groups. Recursive thinking (thinking about thinking), theory of mind (appreciating what is going on in someone else’s head) and inhibition of impulsive reactions (being able to control impulses) are all important elements to successful social interactions. Interestingly brain injury and developmental disorders, such as autism, can interfere with these abilities and social skills in humans. This evidence suggests that the Neanderthal brain may not have been wired to support effective communication and diplomatic skills. They would have been extremely difficult to get along with! The Neanderthal brain was probably better adapted to maximize their visual abilities. They would have used their oversized eyes and large brains to survive and hunt in the lower-light levels in Europe. This would limit the space available in the brain to develop the systems needed for communication and social interactions. However, their smaller social brain regions could have enabled them to establish smaller social networks which may have improved their chances of survival in the harsh European environment.