RNA interference

Cells have many ways of regulating gene expression, and one of the most efficient of them would be RNA interference (RNAi). This method allows the cell to effectively silence, or repress, expression of genes by using different types of short RNAs that binds to homologous sequences in order to inhibit translation, to degrade or/and, sometimes, to silence the promoter of the target gene mRNA. This method is so effective that it is now widely used in laboratories for in vivo experiments and, thus, I thought I should say a few words about it before introducing the video made by Nature about this technique:

Neurotrophins

Cells of multi-cellular organisms not only require oxygen and nutrients to survive, they also need survival signals called trophic factors. In the absence of such signals, signaling pathways that prevent the cell to undergo a “suicide” program are not activated and, thus, result in cell death.

Analysis of the development of the nervous system demonstrated the essentiality of trophic factors in cellular development. Indeed, it was shown that more cells grew than actually survived when neurons developed to connect to other neurons (or muscles), even over long distances. It was further demonstrated that only those cells that succeeded in making connections survived while the others died.

An example of such trophic factors was discovered through the study of innervation of developing limbs in chick embryos and was simply known as nerve growth factor (NGF). It was then identified to belong to the neurotrophins, which binds to and activate a family of receptor tyrosine kinases called Trk. NGF binds with high affinity to TrkA and, through this binding, provides the necessary surviving signal to avoid “suicide” for different classes of neurons that successfully made connections. Indeed, only Trk receptors produced on the growth cones of the extending axons of neurons trying to make connections bind neurotrophins produced by target tissues.

This process is key during developmental processes as it ensures that the right neurons survive and in the required amount for proper target innervation. Furthermore, neurotrophins allow for cell fate decision, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. Neurotrophins were also found to regulate many aspects of neural function, e.g. in the mature nervous system, they were demonstrated to control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

Y.S.H.

 

References:

  • Lodish et al., Molecular Cell Biology, Sixth Edition, 2008, pp. 936-938
  • Neurotrophins: roles in neuronal development and function, Huang EJ, Reichardt LF., Annu Rev Neurosci. 2001;24:677-736. Review.

Moment of Clarity

It was the first Monday of the month of November, and Kenro was having a bad day at the downtown Vancouver trading company where he worked.  His results had been sliding downwards for the last twelve weeks. Given the present state of the market, though, it wasn’t his fault: everybody was losing money, and the new regulations that kept popping out of Washington didn’t help. Of course he wanted to build a better future—who didn’t?—but he still had a mortgage to pay and a family to feed.

Kenro was the proud father of two beautiful daughters and husband to his beloved Christine. They lived in a beautiful apartment in False Creek with no worries in the world…until three months ago, that is. It had all started with a bad gamble on the expected quarterly earnings of a Canadian telecommunications company. The company had made headlines when they had claimed to have developed the next generation of communication technology. That claim turned out to be unfounded. Instead of earning money, the company was forced to return to the drawing boards, plunging its stocks from a high of $18 to a dreadful low of $2 a share.

Kenro’s clients lost a lot of money, and the trading company he was working for decided to put him on review. Kenro had been working twelve hours a day ever since then, desperately trying to make up for his losses. He didn’t have any luck, though—each new investment he made turned out to be a worse performer than the previous one. His review was in less than a week, and unless he could come up with a golden stock, he was sure to lose his job, his reputation. Even worse, he could lose the life he had spent the last ten years building with his family. Yes, Kenro was having a really bad day on that first Monday of the month of November.

Tuesday: -5 until D-Day

Kenro was frantically working the phones and computers, looking desperately for leads on any stocks that could buy him a little more time before he was fired. (Which he was sure was coming.) He called everyone he’d ever met, everyone he’d ever laid his eyes on, even random people from the yellow pages who seemed like they might aid him in his search. He prayed to all the gods he knew of and all the demons he’d ever heard of. He’d never been a man of faith—he considered it a weakness of the human spirit to find comfort where there was none—but for the past few days, he’d been praying more than a Muslim making his pilgrimage to Mecca.

Kenro was desperate and flat out of ideas. The vision of losing everything he had worked for so long became bigger and bigger in his mind; with that vision came the sense of unavoidable fatality. Kenro had little hope left and knew that he was but a step away from what he understood would be eternal damnation. The more he pondered his terrible situation, the sicker and weaker he got. Images of his family living on the streets flashed through his thoughts, images of his daughters crying in hunger and trembling in fear.  He sank into a deep despair, his soul plunged into a bottomless abyss that offered no possible return. Light had gone forever from his heart, to be replaced by inescapable doom.

Wednesday: -4 until D-Day

Kenro arrived at the office at 8 a.m. knowing that Wednesday was going to be his last day if he didn’t find a profitable stock. He had spent most of the previous night thinking about alternate solutions to his awful situation and had only been able to come up with one option: he would orchestrate his own death so that his family could collect the insurance money.  Then they would never have to experience the harshness of a penniless life.

It was a simple act, really—all he had to do was drive his car off the side of a nearby ravine while making sure to leave evidence on the road that would point to a mechanical failure in the vehicle. The insurance company would be forced to pay out the million-dollar policy he’d been paying into the past five years. That money—along with his family’s other assets—would be more than sufficient to pay off his debts and give his beloved family plenty of time to grieve and move on. He was sure that they would be better off without him, away from his failures and incapacity to provide them with the life they deserved…the life he’d been promising Christine ever since he’d met her.

His decision was final. If he couldn’t find a profitable stock, he would accidentally kill himself the next morning as he drove his usual route to the opposite shore of Vancouver. That decision made, he sat comfortably on his chair in front of his computer and got back to work, searching for the elusive stock that would save him from the desolated world he found himself in.

Kenro worked nonstop for twelve hours, looking for anything that would allow him to escape his impending death…but his efforts yielded nothing. He turned off his computer at 10 p.m., knowing that his life was coming to an end. He decided that he wasn’t going to go straight home to spend time with his family the way he usually did—he simply couldn’t face them. Instead, he would go have a drink or two in a nearby pub and smoke a few cigarettes. He had stopped smoking more than five years ago, but tonight that didn’t matter. He was going to have the condemned man’s last cigarette and he was going to enjoy it.

He entered Smiley’s pub unnoticed by anyone and went straight to the counter. He ordered a Guinness and slowly savored it, enjoying every sip of and making it last for hours. He looked at all the people around him and reminisced about the most enjoyable moments of his life. Most of them involved his wife Christine and their two daughters, Kim and Lilly. Each time he thought about the sadness his death would bring them, he took another sip of his beer and forced himself to remember the million-dollar insurance policy.

He’d been at the counter for almost an hour before a man of medium build who looked to be in his mid-thirties walked up to the bar and sat down next to Kenro. The man was just over six feet tall and had a receding hairline. His wide shoulders towered over a belly that was testament to his fondness for food; his smile could’ve charmed snakes.
He nodded his head in Kenro’s direction and then ordered a Guinness. Kenro paid the man no heed—he had no time to waste on silly pub conversations. He shifted to his left, putting his back towards the man as he took another sip of his beer.

The man just smiled and put his own glass to his lips. He gulped his stout, put his glass back on the counter, and tapped Kenro’s shoulder.

“Hey, my friend, you look like you need the company of an angel!”

Kenro turned, startled by the man’s words. He had never heard anyone speak of angels, but what shocked him even more was that when he meant to respond in a way that would brush the man off, he was caught and held by the intensity of the other’s gaze. The man wasn’t threatening; he just exuded an intense charisma that left Kenro speechless.

Kenro remained staring and mute, incapable of uttering a single word or moving a finger.

“What? You need more time to think that being left alone right now is not the best thing for you?” the man said jovially.

“Uh…I…I am Kenro… Nice to meet you… You are?” Kenro found himself saying.

“I am Rehael,” the man answered, and reached out to shake Kenro’s hand. “So…what troubles you so much?”

Kenro was once more dumbfounded by the intensity of the man’s words and gestures. He found himself unable to hide any of his emotions. Even more important, he found himself unable to lie. Once he’d spilled his guts to the stranger—omitting the part about the orchestrated suicide—he held himself stiffly, staring at Rehael with a blank look.
Rehael looked at Kenro and began laughing. “I can’t believe this small affair is the source of so much misery for you!”

Kenro was insulted by the comment and tried to turn his back on the man again. Before he could do so, however, he was halted by Rehael’s hand on his right shoulder.

“Don’t take offense, my friend. I was never known for my tact. Actually, I am more famous for my brutality than anything else!” he explained before laughing again. This time, Kenro did not feel insulted—he actually felt relieved by the friendly fellow’s self-derision.

“It’s your lucky day, Kenro,” the man continued. “Transfer everything you have into Siman’s American stocks. Your financial troubles will be forever behind you, I assure you…”

Kenro, feeling the man was making fun of him again, flagged down the bartender for his bill.

“Come now, Kenro—what do you have to lose? What is one more day?” Rehael said with true compassion in his voice.

Kenro stopped counting out his money and looked at the man, finally feeling warmth return to his heart.

“Invest in the morning—you will have a good surprise before the end of the day! What is another day?” Rehael insisted again before taking his leave.

Kenro paid his bill and went home. I can deal with one more day, was his last thought before entering a deep slumber.

Thursday: -3 until D-Day

To the surprise of his colleagues, Kenro was at the office by 8 a.m. the next day even though it was the anniversary of his father’s passing. He had never before missed honoring the tomb of his father first thing in the morning on that morning every year, yet he was in front of his computer instead of in the graveyard.

As soon as the markets opened, he invested all his capital in Siman. As Rahael had said, he had nothing to lose anymore. He spent the next five hours drinking coffee and fidgeting in his chair.

At 2:01 p.m., Siman’s stocks began to go up. The CEO of the company had made an announcement that shocked everyone: the company had been working secretly on a merger with Google for the past three months, and the deal had been confirmed just a few hours earlier. In less than two hours, Siman’s shares went from $18 a share to $67.

Kenro had reversed all of his losses and even made money in a single shot. His career was saved, his reputation was saved, his life was saved. He thanked whatever gods he knew of for having sent Rehael onto his path.

Friday: D-Day Infinity

Kenro left the office at 5 p.m. His boss had come by that morning to congratulate him on having been able to make up for his past mistakes and to praise him on his incredible sense for capturing exceptional opportunities. His job was no longer in jeopardy; his life was officially saved.

Kenro went straight to Smiley’s pub in the hopes of seeing Rehael once more. He entered the establishment and saw the good man sitting alone at a table in the back.

He ran to him. “Rehael!” he exclaimed.

Rehael looked at him and smiled. “Kenro! I guess you heard the good news, didn’t you?” he said with a wink.

“How did you know? Who are you?”

Rehael laughed. “An angel, of course!”

Kenro looked at him, perplexed. It must be another of Rehael’s jokes, he told himself. “No, seriously…”

“I’m an Angel of God! You know what angels are, don’t you?” Rehael replied in a voice of complete sincerity.

“Wha—“

“An angel of God. You know, Adam and Eve…Abraham…you must know about Jesus!”

Kenro was incapable of saying anything.

“Let me guess—you need proof!” Rehael said, then laughed out loud.

“I—“

Rehael just looked at Kenro, enveloping him in an aura of undeniable mercy.

Kenro lowered his head and pleaded for forgiveness. “I shall be forever in your debt and forever adore you!” he said to Rehael, his heart full to bursting.

The angel looked at him, clearly displeased, and said, “Adore me? No, you have mistaken for someone else. Be grateful for the Creator and use what He has given you in His way. That is all that He truly asks of you, you know.”

Kenro’s eyes welled with gratitude. “I will do so forever!”

Rehael smiled. “You can go now. Return to your family and lead your life as it ought to be.”

Kenro nodded and left to be in his family’s company, his heart filled with joy and strength. He finally knew what faith was; for the first time in his life, he felt complete.

Saturday: D-Day -298

Kenro woke up the next day with a strange feeling in his heart. He got up from his bed and went to make himself some coffee. As he was waiting for the coffee machine to finish its routine, images of his encounter with Rehael invaded his mind. He kept thinking about everything that he had said and done and could not help himself from smiling at the sneakiness of the self-proclaimed angel.

Obviously, Rehael—if that was even his real name—had given him an insider tip to cover his own illegal investments. Kenro would have reported the man on the spot if the tip hadn’t saved his career and his life. Rehael—or the organization he was working for—must have been watching for potential candidates who would be desperate enough to play their game.

That was the only logical explanation, and the only one that made any sense at all. Kenro poured himself a cup of coffee and went about his usual day, enjoying his newfound success and forgetting all that rubbish about gods and angels.

Y.S.H.

Brethren of Purity

Image

The Brethren of Purity and the Friends of Loyalty (Ikhwan al-Safa wa-Khillan al-Wafa in Arabic) was a secret, esoteric society believed to have existed in the mid-10th century. The Brethren were principally located in Basra, Iraq, but the society had ties with the neighboring countries. The identities of the Brethren’s members are still unknown to today’s scholars and are the subject of much research and vivid speculation.

This coterie of mystics put together their famed Encyclopedia of the Brethren of Purity, composed of 52 Epistles arranged into four groups. These Epistles covered a vast array of subjects, ranging from mathematics, philosophy, music, logic, astronomy, the physical and natural sciences, mineralogy, and botany to the nature of the soul, ethics, metaphysics, revelation, spirituality, theology, prophecy, spiritual entities, providence, magic, and talismans. This massive compendium was inspired in part by scholars of ancient Greek, Indian, and Persian thought; the scholars also incorporated scriptures from the Abrahamic tradition, the Torah of Judaism, and the Canonical Gospels of Christianity…all under the umbrellaof the Islamic Qur’an.

This open-mindedand eclectic endeavor was very unusual for the time. The Brethren of Purity justified its unusual undertaking by pointing out the necessity of seeking truth wherever it was to be found, without prejudice and with the intent to establish harmony between faith and reason. Religious divergences, the Brethren maintained, were born of accidental factors such as race, habitat, and time—in no way do these accidental factors affect the essential unity and universality of truth:

“…to shun no science, scorn any book, or to cling fanatically to no single creed. For [their] own creed encompasses all the others and comprehends all the sciences generally. This creed is the consideration of all existing things, both sensible and intelligible, from beginning to end, whether hidden or overt, manifest or obscure . . . in so far as they all derive from a single principle, a single cause, a single world, and a single Soul.”[1]

For the Brethren of Purity, the subjects covered in the Encyclopedia were subjects that an educated person was expected to understand in order to acquire the proper knowledge needed to improve both one’s physical lot in the material world and the fate of one’s soul in the hereafter. Knowledge was accumulated in order to bring one closer to the sublime goal of salvation. To use the Brethren’s own imagery, they perceived their Brotherhood—which they invited others to join—as being a “Ship of Salvation that would float free from the sea of matter in which the Brethren, with their doctrines of mutual cooperation, asceticism, and righteous living, would reach the gates of Paradise in its care.”[2]

Even the very name of the fraternity is representative of the doctrines the Brethren preached. Indeed, there is a common consensus among scholars that “The appellation is presumably taken from the story of the ring-dove in the classic fable Kalila wa-Dimna[3] in which a ring-dove and its companions get entangled in the net of a hunter seeking birds. Together, they leave themselves and the ensnaring net to a nearby rat, which is gracious enough to gnaw the birds free of the net; impressed by the rat’s altruistic deed, a crow becomes the rat’s friend. Soon a tortoise and gazelle also join the company of animals. After some time, the gazelle is trapped by another net; with the aid of the others and the good rat, the gazelle is soon freed, but the tortoise fails to leave swiftly enough and is itself captured by the hunter. In the final turn of events, the gazelle repays the tortoise by serving as a decoy and distracting the hunter while the rat and the others free the tortoise. After this, the animals are designated as belonging to the Brethren of Purity”.[4]

This fable is cited as a moral anecdote when the Brethren address the topic of mutual aid—a crucial part of their system of ethics—in one of their epistles:

“And know, O Brother, may God assist you and us with a spirit of His, that you ought to know for certain that you alone cannot redeem yourself from the affliction of this world into which you have fallen because of the [sin] committed by our [fore] father Adam. You need for your redemption and liberation of generation and corruption—and ascension to the world of celestial spheres—and proximity to God’s close angels, the assistance of brethren who are sincere advisers and associated with you by bonds of friendship, who are virtuous and have insight into affairs of religion, so that they can apprise you of the path of the hereafter and how to attain it. So, take an example from the story of the ring-dove mentioned in the book of Kalila wa-Dimna and how it freed itself from the snare.”[5]

The Encyclopedia of the Brethren of Purity included the philosophical sciences that were current among Arab Muslims and others living in the Middle East at that time.  What differentiated it from other contemporary texts, however, was not just the variety of sources the authors drew on (or the fact that all these sciences were compiled in one encyclopedia) but also—and most importantly—that in the Encyclopedia they managed to achieve such a remarkable overall synthesis. Indeed, given the very diverse sources of the Epistles, it would have been fortunate just to have been able to read some of the texts in the current language of the time; to have an adequate and modern synthesis would have seemed to be out of reach. The latter is what made the secret coterie and itsEncyclopedia famous among Muslims and non-Muslims alike, for the Brethren made knowledge that was usually reserved for the governing elite available to educated people of all races and professions.

Simply put, the Brethren popularized learning and philosophy without placing any limitations on the origin of truth. Consequently, their Encyclopedia was widely received and assimilated; it played a prominent role in shaping medieval Islamic beliefs. Indeed, the Encyclopedia was disseminated from the heart of the Islamic world all the way to Andalusia, Spain. It had a great influence on later intellectual leading lights of the Muslim world, such as Ibn-al-Arabi, Avicenna, and al-Ghazzali. And as the Brethren’s work contributed to the popularization, legitimization, and harmonization of Greek philosophy, it also passed along knowledge of Babylonian, Indian, Persian, Zoroastrian, Buddhist, Manichaean, Jewish and Christian principles to medieval Islamic scholars.
The Encyclopedia’s influence did not stop there, however: it spread beyond the borders of the Islamic empire into the Western one as early as the 11th century. For the most part, this was due to the Jewish scholars in Spain. The Epistles of the Brethren of Purity played an important part—although one that is not usually studied—in forming medieval Judaic thought throughout the 11th to 15th centuries in Spain, Provence, and Yemen. Many scholars believe that the Brethren of Purity were referenced by many of the Jewish intellectuals as they developed their philosophies and sciences. (The Encyclopedia may have even been the basis for those endeavors.) According to various sources, such was the case for Ibn Gabirol[6], Joseph Ibn Zaddiq[7], Moses Ibn Ezra[8], and many others. They were also referenced by Abraham Ibn Ezra[9], the well-known Spanish Jewish author and scientist who was active in Italy, France, and England during the years 1140-1160.

The Encyclopedia’s influence on Western thinking was not limited to the spread of knowledge from the Jewish scholars of Spain to those in the rest of mainland Europe. Christian Rosenkreuz, the founder of the legendary Order Rose-Croix, may have coaxed his secrets from the Brethren of Purity’s writings,[10] and rumors even say that exchanges were made between the Templars and the Brethren of Purity during the first Crusade (which took place at the end of the 11th century). Western scholars have even described the secret coterie as being an early form of Freemasonry[11].

The influence of the Brethren’s Epistles did not end in medieval times, either. One of the greatest thinkers of the 19th century, Charles Darwin, is believed to have been influenced by the Encyclopedia as he developed his theory on evolution—there are many similarities between Darwinism and the Brethren’s thoughts on evolution, and English translations of the Brethren’s epistles would have been available beginning in 1812:

“[These books] state that God first created matter and invested it with energy for development. Matter, therefore, adopted the form of vapour which assumed the shape of water in due time. The next stage of development was mineral life. Different kinds of stones developed in course of time. Their highest form being mirjan (coral). It is a stone which has in it branches like those of a tree. After mineral life evolves vegetation. The evolution of vegetation culminates with a tree which bears the qualities of an animal. This is the date-palm. It has male and female genders. It does not wither if all its branches are chopped but it dies when the head is cut off. The date-palm is therefore considered the highest among the trees and resembles the lowest among animals. Then is born the lowest of animals. It evolves into an ape. This is not the statement of Darwin, this is precisely what is written in the Epistles of the Brethren of Purity. Ape then evolved into a lower kind of a barbarian man. He then became a superior human being. Man then becomes a saint, a prophet. He then evolves into a higher stage and becomes an angel. The one higher to angels is indeed none but God. Everything begins from Him and everything returns to Him.”[12]

Even today the Brethren of Purity and their Encyclopedia do not cease to intrigue scholars all over the world. Indeed, Oxford University is collaborating with the Institute of Ismaili Studies to publish “an Arabic Critical Edition with an Annotated English Translation of the Rasa’il Ikhwan al-Safa (Epistles of the Brethren of Purity) in order to reveal the extent of interpolation and tampering with the original text to determine their [The Brethren of Purity] affiliation to a particular ideological or sectarian group within Islam… and because it has never been translated in its entirety into any Western language.”[13]

Y. S. H.

References:
1 From Encyclopedia of the Brethren of Purity, 4 volumes (Beirut, Dar Sadir, 1957). A complete untranslated edition of the 52 rasa’il.
2 Volume 4, pg 685-688 of the 1998 edition of The Routledge Encyclopedia of Philosophy; ed. Edward Craig.
3 Arabic translation of the The Panchatantra (Sanskrit: ‘Five Principles’), which is a collection of animal fables in verse and prose believed to have been composed in the 3rd century BCE in India.
4 A suggestion made by Goldziher and later written about by Philip K. Hitti in his History of the Arabs.
5 Epistle (Rasa’il), vol. 1, p. 100 (Beirut, Dar Sadir, 1957).
6 Jacques Schlanger (Schlanger 1968, 94-97)
7 Vajda 1949
8 Horovitz 1903, 3
9 Jospe 1994, 46-48
10 Christopher McIntosh, The Rosicrucians: The History, Mythology, and Rituals of an Esoteric Order, p. 25.
11 Masonic Encyclopedia II Mackey 601a-b
12 Muhammad Hamidullah and Afzal Iqbal (1993), The Emergence of Islam: Lectures on the Development of Islamic World-view, Intellectual Tradition and Polity, p. 143-144. Islamic Research Institute, Islamabad.
13 Nader El-Bizri, The Epistles of the Brethren of Purity. Ikhwan al-Safa’ and their Rasa’il: An Introduction.