Friday, July 29, 2022

The ecology of influenza - role of gene loss in natural disease reservoirs

The CDC defines a reservoir of an infectious agent "as the habitat in which the agent normally lives, grows, and multiplies." When the infectious agent spills over from such a reservoir species into other susceptible species, the pathogen experiences strong selective constraints in the new host. This new environment may then select for a more potent pathogen that can spread in the new host or even across other vertebrate species. The brilliant Robert G Webster describes a lifetime of knowledge he has accumulated on this spill-over process in his talk "Influenza: Lessons learned from Pandemic H1N1" at Columbia University. This talk, now more than a decade old, has some interesting discussion at the end that, in hindsight, now after the covid pandemic looks intriguing. 

The most interesting part of the talk for me is when he talks about birds. First, he mentions that shorebirds (Charadriiformes) such as the Ruddy Turnstone (Arenaria interpres), Semipalmated Sandpiper (Calidris pusilla), Sanderling (Calidris alba), European herring gull (Larus argentatus), laughing gull (Leucophaeus atricilla), and Red knot (Calidris canutus) and waterfowl (Anseriformes) species such as mallard or wild duck (Anas platyrhynchos) and pintail or northern pintail (Anas acuta) are some of the migratory birds that are monitored for influenza in North America. The second time he mentions birds is when he explains the difference between Ducks and Chicken and how the RIG-I gene is lost in chickens. RIG-I is an immune sensor that activates the production of interferon-Beta. A more detailed talk that focuses on the loss of this gene and how the discovery was made is explained by Katherine Magor of the University of Alberta in her talk titled "How ducks survive the flu; the secrets of the reservoir host." 

It has been more than a decade since the paper describing the lack of RIG-I in chicken and "Association of RIG-I with innate immunity of ducks to influenza" has been published. In this decade, it has been established that the "Loss of RIG-I leads to a functional replacement with MDA5 in the Chinese tree shrew". Although a paper (from fish immunologist Chris Secombes) looking at the "Origin and evolution of the RIG-I like RNA helicase gene family" claimed that "Unlike RIG-I, whose presence in chicken and some fish species is uncertain..", it did not conclusively establish the lack of RIG-I in chicken. Limitations in genome assembly quality and availability of large genomic datasets can be blamed for these uncertainties. Notably, the paper by Secombes also investigates the origin of RIG-I and related genes through gene fusion, domain duplication, and deletion and follows in the line of a previous paper titled "Evolution of MDA-5/RIG-I-dependent innate immunity: Independent evolution by domain grafting".

The birth and death of the genes from the terminal complement pathway are surprisingly similar to the history of the RIG-I-like RNA helicase gene family. Domain fusion events are involved in the birth of both gene families at the boundary of invertebrates and vertebrates, both RIG-I and C9 are lost in Galliform birds but are present in Anseriform birds and both are involved in the immune response. Finally, our manuscript dealing with the Birth and Death in the Terminal Complement Pathway is published.



 








Sunday, July 17, 2022

Dhyān Yog: The Yog of Meditation also known as the Atma-Samyama Yoga

Chapter 6: With 47 verses or shlokas, the sixth chapter is of the same length as the first chapter. 

Arjuna (Shloka 33-34, 37-39): 5 shlokas

Krishna, the Supreme Personality of Godhead (Shloka 1-32, 35-36, 40-47): 42 shlokas

Brief Summary: In this chapter, the lord explains the Dhyan Yog aspect as a continuation of his answer to prince Arjuna in the previous chapter.

Sanyāsīs=yogis=who perform prescribed duties without desiring the results of their actions, is free from feelings of possessiveness, lives in seclusion, and engage the body, mind, and self in a relationship with the supreme.

Shloka 5-6: The mind can be your friend if you have conquered it, but it can also be your worst enemy if you have failed to conquer your mind. 

Free from Dualities: Cold and heat, Joy and sorrow, honor and dishonor, happiness and distress

For the satisfied yogi who is in KC, 

  • Shloka 8: Dirt=stones=gold
  • Shloka 9: Well-wishers=friends=foe=pious=sinners=affectionate=benefactors=envious=neutral =mediators. Notably, this shloka lacks a purport. 
Shloka 11-12 are very specific in detail regarding the pre-requisites for meditation. The specifics are:
  1. Should be performed in a sacred/secluded place. A list of sacred places is mentioned in the purport and includes Prayag, Mathura, Brindavan, Rishikesh, and Haridwar.
  2. Kusha/Kusa grass (Desmostachya bipinnata) should be covered with deerskin and a soft cloth to prepare a seat.
  3. The seat should be at optimum height, i.e., neither too high nor too low.

Shloka 13-14: The sitting position requires the alignment of the body, neck, and head in a straight line. One should focus on the tip of the nose and meditate upon the divine within the heart.

Yoga is not a mere physical exercise, rather it is a means to attain the abode of the lord (AOL). The importance of proper sleep and a healthy diet are explained concerning becoming a perfect yogi. Discipline in the lifestyle can mitigate all material pains, one has to follow the correct schedule for habits of eating, sleeping, recreation, and work in day-to-day life.

The flickering nature of the mind can be controlled by the practice of yoga which can lead to the attainment of trance or "samadhi.". In the stage of samadhi, the person is engrossed in self and attains the highest form of happiness, and is unaffected by the miseries of the material world. 

Arjuna questions the knowledge imparted by Lord Krishna regarding yoga as impractical and unendurable. Characters of the mind described by the prince Arjuna:
  • Restless
  • Turbulent
  • Strong
  • Obstinate
  • More difficult to control than the wind
Lord: practice & detachment. Possible for those who have learned to control the mind.

Arjuna further enquires what happens to the unsuccessful yogi who cannot reach his goal due to an unsteady mind. Would such a person miss out on both material enjoyment and spiritual success? 

The lord reassures Arjuna as follows:
  • Those who strive for KC are never overcome by evil.
  • Unsuccessful yogi attains the abode of the virtuous (AOV) upon death. After dwelling in AOV for many ages, such a yogi is reborn in the family of pious and prosperous people.
  • Else, if a yogi has developed dispassion through long practice of yoga, such a yogi is reborn in the family endowed with divine wisdom.
  • Following rebirth, the yogi strives for liberation with even greater earnestness by reawakening the wisdom of past lives. 

Shloka 46: yogi > tapasvī (ascetic) ; yogi > jñānī (a person of learning); yogi > karmī (ritualistic performer)

The results of spiritual practices are accumulated and passed to the next birth. Hence, even the unsuccessful yogi is making progress and eventually attains liberation. In the last shloka, lord Krishna highlighted the importance of surrendering oneself to the divine with utmost faith and love becoming the highest yogi.

Favorite Shlokas:

Shloka 5:

uddhared ātmanātmānaṁ nātmānam avasādayet

ātmaiva hyātmano bandhur ātmaiva ripur ātmanaḥ

Shloka 16:

nātyaśhnatastu yogo ’sti na chaikāntam anaśhnataḥ

na chāti-svapna-śhīlasya jāgrato naiva chārjuna