Why humans did not become extinct just like their Neanderthal cousins

More than 500’000 years ago, Denisovan, Neanderthal and hominin ancestors not only coexisted but bred common offspring as DNA analyses on bones discovered in the Denisova caves have proven as well as the fact that Neanderthal DNA can be found to this day in humans living outside of Africa, albeit in minuscule amounts. But as evolution progressed, hominins gained an upper edge over the Denisovans and Neanderthals, the latter two became extinct and the hominins continued to survive and ultimately prosper.

Scientists now have an explanation as to why humans acquired a distinct advantage over their extinct cousins: a genetic mutation TKTL1.

In 2014, the sequence of a complete Neanderthal genome was published. Researchers discovered that 96 amino acids differ between modern humans and Neanderthals and initiated studies to investigate if these changes gave humans a definitive edge over the Neanderthals.

Pinson et al. have now reported that that expression of a variant of human transketolase-like protein 1 (TKTL1) increases the number of bRGs in modern humans and thereby the output of upper layer projection neurons. 

Without this mutation, humans would have become extinct just like their Denisovan and Neanderthal cousins.

To quote from an article that has been published in Nature ( https://www.nature.com/articles/d41586-022-02895-2

utm_source=Nature+Briefing&utm_campaign=e25edaf388-briefing-dy-20220909&utm_medium=email&utm_term=0_c9dfd39373-e25edaf388-47096220):

“The neocortex, the outer region of the cerebral cortex, is an evolutionarily advanced brain structure that is responsible for cognitive abilities. It has expanded in size and function across the mammalian clade (1). The extraordinary cognitive abilities of humans are thought to rely on brain size (and thus the number of neurons) and the intricate cytoarchitecture of the neocortex. The expansion and folding of the neocortex have been partly attributed to the existence of basal radial glial cells (bRGs). These progenitors generate most cortical neurons, and their number increases in gyrencephalic mammals (which have neocortical folds), such as primates and ferrets. On page 1170 of this issue, Pinson et al. (2) report that expression of a variant of human transketolase-like protein 1 (TKTL1) increases the number of bRGs in modern humans and thereby the output of upper layer projection neurons. This genetic change could contribute to differences in cognition with extinct archaic humans”.

Source: Sara Reardon,  Nature | Vol 609 | 22 September 2022 | 665

Where was ZERO invented or discovered?

 An interesting article that claims that zero was not invented in India.

https://www.scientificamerican.com/article/the-elusive-origin-of-zero/

Gene-edited tomatoes may wipe out $1.6 billion Vitamin D business

 Gene-edited tomatoes could become a source of Vitamin D

Approximately 1 billion persons worldwide suffer from Vitamin D deficiency. Insufficient Vitamin D affects the immune system and inflammation and is connected to several medical conditions such as rickets in children, weak bones, diabetes, high blood pressure, cancer and autoimmune diseases such as multiple sclerosis.
The source of Vitamin D in humans is threefold:

1. Skin. Humans synthesise Vitamin D from 7-dehydrocholesterol (7-DHC, provitamin D₃) after exposure to sunlight, specifically ultraviolet B or UVB radiation emitted by the sun. Over-exposure to sunlight, however, can cause skin cancer for which reason people wear protective clothing and use sunscreens and this in turn can result in Vitamin D insufficiency. Vitamin D synthesis also decreases with age and therefore affects the elderly.

1. Foods such as fatty fish (e.g., salmon, tuna or mackerel), beef liver, dairy products (cheese, milk), mushrooms and egg yolks. With few exceptions, plants and vegetables are a very poor source of Vitamin D and this puts vegans in particular at risk of suffering from Vitamin D insufficiency.

1. Supplements. Several companies sell Vitamin D supplements to compensate for its deficiency in humans. Vitamin D sales attained $1.1 billion in 2020 and are expected to reach $1.6 billion in 2025.

All this could change after scientists have found a way of boosting the presence of provitamin B₃ in tomatoes through gene-editing using CRISPR-Cas9 technology.
Genetically modified crops are made by inserting extraneous genes into the genomes of the plants and thereby make them e.g. resistant to damage or destruction by insects or viruses and so on. Crops thus modified using extraneous genes are submitted to intense scrutiny by government regulators though in recent times the rules have been relaxed somewhat and approval is granted if the editing is relatively simple and the mutations could have occurred naturally as for example in the case of the sweet potato.
Although some plants do produce isoforms of the precursors of Vitamin D, these are subsequently converted to chemicals that regulate the plant’s growth and altering these chemicals make the plants stunted and yields decrease substantially.
7-DHC or provitamin D₃ has been identified in tomato leaves but it does not accumulate in the tomato fruit. In an article published recently, scientists working on this project (Li, J., Scarano, A., Gonzalez, N.M. et al. Biofortified tomatoes provide a new route to vitamin D sufficiency) discovered that solanaceous plants such as tomato exhibit a duplicate pathway by which specific isoforms of some enzymes responsible for the biosynthesis of phytosterol and brassinosteroid produce cholesterol for the formation of steroidal glykoalkoloid SGA. A specific form of 7-DHC reductase Sl7-DR2 then converts 7-DHC to cholesterol. The researchers turned off the activity of 
Sl7-DR2 using CRISPR-Cas9 technology, leading to an accumulation of 7-DHC in the tomato fruit. They also found that this procedure does not affect the growth, development or yield of the plant.
The next step will be to obtain regulatory approval to grow the gene-edited tomato plants outside the laboratory and test how they fare in this environment. If they perform well in field studies, they will still have to face the scrutiny of the regulatory authorities before they can be cultivated on a large scale. Keeping in mind that no extraneous genes are introduced into the tomato plant genome in the technique used and the gene-editing performed by the researchers could have occurred naturally, regulatory approvals should in theory be less stringent. But it could be years before the general public can switch from Vitamin D supplements to the gene-edited tomatoes.

Sources:

• Li, J. et al. Nature Plants https://doi.org/10.1038/s41477-022-01154-6 (2022).
• doi: https://doi.org/10.1038/d41586-022-01443-2
• https://www.nature.com/articles/d41586-022-01443-2?utm_source=Nature+Briefing&utm_campaign=9784ac12ed-briefing-dy-20220524&utm_medium=email&utm_term=0_c9dfd39373-9784ac12ed-47096220

Paperback of The Denaming of Goans now available in India

Availability in India of

The Denaming of Goans, Case Studies of Conversions in Medieval Goa

in paperback format

I am pleased to inform you that readers in India can now order this book in paperback format from Pothi.com:

https://store.pothi.com/search/?q=The+Denaming+of+Goans&sort_by=relevancy

Thank you for your interest and patience.

FOREVER YOUNG

 FOREVER YOUNG

     Alzheimer Dementia (AD), Parkinson, many forms of cancer and cardiovascular diseases are primarily age related; the older we grow, the greater the probability that we will be afflicted by one of these diseases. Even though science has discovered many novel approaches to deal with cancer and have successfully extended the lives of many cancer patients, progress in finding a cure for AD or Parkinson and many forms of cancer has been limited. 

     Scientists have, however, been working on finding ways and means to slow down, or even halt or reverse the ageing process, thereby not only extending life but keeping the diseases attributed to the ageing process at bay and making these additional years of life disease free and therefore enjoyable. If the ageing process could be delayed or even reversed, the age-related diseases would not strike the elderly.

     In a fascinating and very readable book entitled “The Melatonin Miracle, Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone”, authors Walter Pierpaoli and William Regelson proposed that Melatonin can do precisely that: slow down senescence, extend life and keep people healthy even in old age. The two doctors based their statements on extensive experiments on mice and rats and even claim in their book that by administering melatonin, they could reverse the early onset of Parkinson’s disease in a patient. They further attribute to melatonin the role of the conductor of an orchestra that coordinates the functioning of all other hormones in our bodies.

     Melatonin is a hormone produced and released primarily by the Pineal Gland. The production is connected to time of day, increasing when it is dark and decreasing when it is light. It helps with the timing of our circadian rhythm (24-hour internal clock) and is administered to individuals suffering from sleep disorders or jet lag. It has shown positive results in clinical trials on patients with cancer and is used in chemotherapy for cancer patients; as a powerful antioxidant, the hormone appears to protect the mitochondria of the cells that could be affected during chemotherapy. Many doctors prescribe melatonin to patients afflicted by Parkinson’s disease.

     Melatonin production decreases with age and Pierpaoli and Regelson suggest that it is this decrease that is responsible for senescence and the onset of age-related diseases. The authors were, however,  clearly carried away by their enthusiasm because even though many of the benefits of melatonin are undisputed and its role is greater that only regulating the circadian clock, an overarching role in regulating all the hormones in our body is improbable. Besides, the authors have not taken the role of genetics and gene mutations in the ageing process into consideration. Which brings us to the next topic.

     It is already well established that many diseases such as cancer and Alzheimer’s are the result of undesired genetic mutations. The probability of these mutations grows exponentially as we grow older bringing with them the dreaded age-related diseases mentioned above.

     In a landmark study published in April 2022 by scientists of the UK Dementia Research Institute at Cardiff University in Nature Genetics, 42 previously unknown AD-related genes have been discovered, adding to the 33 which were already known. Through these 75 genes associated with AD, the scientists have found new pathways that lead to Alzheimer, one of them associated interestingly with inflammation that is in turn associated with many other diseases. One protein associated with AD that the authors singled out is tumour necrosis factor alpha or TNF that is also involved in many autoimmune diseases such as rheumatoid and psoriatic arthritis, Crohn’s disease and type 1 diabetes. The study seems to suggest, therefore, that neurodegenerative diseases may all have a common cause even though it is well known that there are different pathways that lead to Alzheimer’s because the disease “presents differently and progresses differently in different people” as Dr. Richard Isaacson, director of the Alzheimer’s Prevention Clinic in the Center of Brain Health at Florida Atlantic University’s Schmidt College of Medicine puts it. According to the authors, 60-80% of Alzheimer disease risk is based on our genetics, the remaining 20-40% risks can be attributed to lifestyle habits such as smoking, lack of exercise or a poor diet. The question arises as to what exactly causes one or more of the 75 identified genes to mutate in such a way that they trigger Alzheimer’s, Parkinson or other neurodegenerative diseases attributed to ageing.

    The answer to that question is: Epigenetics. On 27 October 2021, I posted on this blog an article on EPIGENETICS and it would provide a  better understanding of what follows next. Epigenomes are chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it, and when to do it. Different cells have different epigenetic marks. In other words, epigenomes turn a gene on or off like a switch.

     In the year 2020, Professor Vittorio Sebastiano and his team from the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA published a breakthrough discovery that could reverse the ageing process by introducing mRNA with instructions to repair mutated epigenomes and thus reverse the undesirable changes that had been caused to the cells. The authors introduce their paper as follows:

“Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis. Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells. Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.”

     Sebastiano’s process using mRNA functions not only at the level of the cell but also at that of tissue.

     A spin-off of Stanford University, Turn Biotechnoligies or turn.bio, located in Mountain View, Silicon Valley where professor Vittorio Sebastiano is co-founder and Scientific Advisory Board Chairman is pursuing research in this exciting area. The company describes its brief as follows:

“Turn Biotechnologies develops mRNA medicines that induce the body to heal itself by instructing specific cells to fight disease or repair damaged tissue. We are focused on reprogramming the epigenome – a network of chemical compounds and proteins that control cell functions by influencing which genes are active – to restore capabilities that are often lost with age.”

     The start-up has already succeeded in repairing and rejuvenating human skin, muscle and blood cells in the laboratory. Clinical studies with volunteers are expected to initiate within the next two years. The interest is so great that the company has had to place people on waiting lists.

     There are, however, justified concerns regarding this therapeutic approach. A study conducted on mice in 2013 showed that if this therapy is prolonged for too long or is too intensive, it can lead to cancer. This is not surprising since cancer is an uncontrolled multiplication of cells that invades the whole body and turning on a gene without it being subsequently turned off will make cell multiplication uncontrollable. The challenge for turn.bio is thus to ensure that this does not occur by finding the correct dosage.

     The start-up is working at the present time on a more modest project: skin therapy that would rejuvenate the skin, accelerate healing of wounds in the elderly and restore the original colour of grey hair. The choice of skin as the first organ on which to focus epigenetic clinical trials is deliberate because it can be easily minutely observed and scrutinised unlike internal organs such as a liver or a heart.

     Yet another approach that is being tried out is blood plasma therapy. Alkahest, another Stanford spin-off, has been administering blood plasma infusions of young and healthy donors to patients inflicted with Alzheimer’s disease and the results are promising.

     The rejuvenation of human cells and tissues will not make humans eternal but it could extend life to 120 or 150 years and above all, make these additional years free of dreaded diseases such as Alzheimer’s, Parkinson, cancer or other neurodegenerative diseases and therefore make the additional years worth living.

Sources:

1. Walter Pierpaoli & William Regelson, The Melatonin Miracle, Pocket Books 1996, ISBN 978-1-4516-1312-4
2. https://www.nature.com/articles/s41588-022-01024-z
3. https://www.nature.com/articles/s41467-020-15174-3
4. https://doi.org/10.1038/s41467-020-15174-3
5. https://www.turn.bio/about
6. Gioa da Silva, Neue Zürcher Zeitung, “Im Silikon Valley arbeiten Forschende daran, das Altern rückgängig zu machen.Bei Mäusen funktioniert das schon. Nun werden Studien mit Menschen durchgeführt”. NZZ, 02.04.2022, https://www.nzz.ch/wissenschaft/im-silicon-valley-arbeiten-forschende-daran-das-altern-rueckgaengig-zu-machen-bei-maeusen-funktioniert-das-schon-nun-werden-studien-mit-menschen-durchgefuehrt-ld.1665387?mktcid=smsh&mktcval=E-mail

Autopsy Report on the body of St. Francis Xavier performed in June 1951

This report can be found in ANNEX II of "The Denaming of Goans, Case Studies of Conversions in Medieval Goa".
The autopsy was performed by Dr. Antonio Luis de Sousa Sobrinho, Director of the Services of Health and Hygiene and Professor Dr. João Manuel Pacheco de Figueiredo, Director of the Medical and Surgical School of Goa.

ANNEX 2: Autopsy report

Document of the Exam of the Venerable Body of St. Francis Xavier. (Confidential). On the 23^rd of June 1951, at 8:30, upon the invitation of His Excellency Reverend Patriarch of the Indies, D. José da Costa Nunes, in the Sacristy of the Basilica of the Bom Jesus, the doctors Antonio Luis de Sousa Sobrinho, Director of the Services of Health and Hygiene of the Estado da Índia, and João Manuel Pacheco de Figueiredo, Director of the Medical and Surgical School of Goa, met in order to proceed to examine the venerable Body of St. Francis Xavier that was closed inside the coffin of wood arranged on a table. The seals were broken and the coffin was opened by His Excellency Reverend the Patriarch, His Excellency in Charge of General Government, Dr. Manuel Marques de Abrantes Amaral and His Excellency the Reverend Archbishop Coadjutor (Assistant) D. José Vieira Alvernaz, Archbishop of Anazartha, being present also the Reverend Canon Aires Franklin de Sa, Administrator of the Basilica, who observed that the Body of the Saint was found dressed in his sacerdotal vestments with the head flexed towards the thorax and the left forearm and hand with its fingers half flexed, resting transversally across the chest. The objective of the exam was directed in first place to those accessible regions, that is, those not covered by the vestments, like the head, left hand, and the feet.

HEAD: The occipital and parietal left sides are denuded [bare] but
perfectly conserved. The parietal and frontal sides present themselves dressed in dry withered skin with some signs of destruction on them and there are seen a few rare hairs attached to the body by skin, where they appear to be encrusted. The side presents a perforation underneath the right arch. The prominence of the molar regions and that of the ocular globes is conserved, being able to distinguish the eyelids of the right eye. The small nose is well conserved, being the right nasal bone dislocated backwards and the earlobe of the same side a little worn out. The orifices of the nasal passages are visible. The relief of the mouth is conserved, the lips half open, with the musculature and skin in the direction of destruction, leaving to see the distinctiveness of the inferior incisors, small and regular, being the second left one dislocated backwards. Rare hairs of the beard on the left side being, like on the head, attached with skin to the body. The right ear is conserved. The outer lobe of the right ear doesn’t exist, noting in the temporal maxillary region, of the same side, in consequence of the destruction of skin, three large orifices, one of which the major one, corresponds to the location of the implantation of the outer lobe. Across these orifices are clearly visible the bones.

LEFT HAND: Resting with palm side on the chest, with the fingers half-flexed, muscular substances and conserved skin. Dorsal side: some flexible tendons are distinguishable, being most clear and prominent at the extension of the index finger. Only the thumb finger has a nail.

Palm Side: some flexible tendons are clearly distinguishable, with little flexibility of the veins.

LEFT FOOT: Dorsal side. Conserved masses of muscles, the tendons distinctive and the skin withered. The first and fifth toes are complete and with nails; absent are the digital bones on the second toe; the third toe is reduced to a plain morsel of cutaneous (pertaining to the skin) place; it is missing the bones and the fourth toe doesn’t have skin on the dorsal side. The sole of the foot is very well conserved, as well as the muscular masses that cover the heel that is on the path of destruction.

RIGHT FOOT: Of reformed aspect and in forced extension . The heel is dislocated inside. It does not have the last four toes. By the opening, the result is that they don’t exist, the insteps are visible, the muscle masses conserved, minus the posterior part which is destroyed in part and with faded skin. Some tendons are distinguishable, the big toe is prominent and without a nail. The major part of the skin of the sole is conserved.

Accordingly, by determination of His Excellency, the Reverend Patriarch, the vestments that covered the anterior part of the body were removed and he observed:

1. The head was disarticulated, completely free resting on a pillow cushion and the cranial cavity empty.
2. The left hand is articulated (joined) with the two bones of the forearm, maintaining the wholeness and articulation of the wrist. The bones of the forearm are losing their covered skin, of which was noted the third inferior, with small pieces of destruction.
3. Maintained whole is the tibia joint of both sides of the inferior members, like on the forearm, the bones — tibia and fibula — on both sides, are covered in skin, with zones of destruction, only on the third inferior.
4. The left tibia and fibula, in the superior extremity, are still conserved.
5. The two femurs, have regressed to some small pieces of skin, and the kneecaps are jointed with the bones of the leg for half the length.
6. Deposited in the central part of the coffin we found the following bones: a bone of the sternum, two clavicle bones, the left omoplate, the humer, 2 fragments of the ribs, 21 vertebrae (4 cervical, 12 dorsal, and 5 lombar) the sacrum, and the two ilialic bones with only 5 lumbar vertebra and the last dorsal jointed.
7. Various discoloured pieces of skin, of which 5 were large, seeing clearly that the major was of the buttocks region. In order to reconstitute the skeleton, all the existing portions and those already mentioned were collected in order on a table, being for this end to arrange a wire in the vertebrae cavities to connect them. Reconstituting the skeleton by juxtaposing the bones, it was observed that the Body of the Saint, measured from the extremity of the first toe of the left foot to the top of the head, was 171 centimetres in length, and 162 centimetres when measured from head to the heel. Finally, all the parts of the Body, in appropriate order, but not jointed, and the 5 pieces of skin, were placed in the coffin and covered by the vestments that had been removed by reason of the exam. We declare that the Body doesn’t present any sign of putrefaction, nor of a bad smell. In the duration of the exam, several photographs were taken by J.P. Guerra.

From this exam, the minutes of this present act are drawn that is signed by us. Old Goa, Basilica of Bom Jesus, on the 23^rd of June 1951. Signed: Antonio Luis de Souza Sobrinho, João Manuel Pacheco de Figueiredo and José Vieira Alvernaz, Archbishop of Anarta

The Last Prabhu reviewed in The Navhind Times

The last Prabhu: A story from Aldona

https://www.navhindtimes.in/2020/04/21/magazines/buzz/the-last-prabhu-a-story-from-aldona/