Mao Zedong: a brief history.

 Mao Zedong (December 26, 1893 – September 9, 1976), also known as Chairman Mao and popularly rendered as Mao Tse-tung, was a Chinese communist revolutionary who was the founding father of the People's Republic of China (PRC), which he ruled as the chairman of the Chinese Communist Party from the establishment of the PRC in 1949 until his death in 1976. Ideologically a Marxist–Leninist, his theories, military strategies, and political policies are collectively known as Maoism.

Mao was the son of a prosperous peasant in Shaoshan, Hunan. He supported Chinese nationalism and had an anti-imperialist outlook early in his life, and was particularly influenced by the events of the Xinhai Revolution of 1911 and May Fourth Movement of 1919. He later adopted Marxism–Leninism while working at Peking University, and became a founding member of the Chinese Communist Party (CCP), leading the Autumn Harvest Uprising in 1927. During the Chinese Civil War between the Kuomintang (KMT) and the CCP, Mao helped to found the Chinese Workers' and Peasants' Red Army, led the Jiangxi Soviet's radical land policies, and ultimately became head of the CCP during the Long March. Although the CCP temporarily allied with the KMT under the Second United Front during the Second Sino-Japanese War (1937–1945), China's civil war resumed after Japan's surrender, and Mao's forces defeated the Nationalist government, which withdrew to Taiwan in 1949.

On October 1, 1949, Mao proclaimed the foundation of the PRC, a Marxist–Leninist single-party state controlled by the CCP. In the following years he solidified his control through the Chinese Land Reform against landlords, the Campaign to Suppress Counterrevolutionaries, the "Three-anti and Five-anti Campaigns", and through a psychological victory in the Korean War, which altogether resulted in the deaths of several million Chinese. From 1953 to 1958, Mao played an important role in enforcing planned economy in China, constructing the first Constitution of the PRC, launching the industrialisation program, and initiating the "Two Bombs, One Satellite" project. In 1955–1957, Mao launched the Sufan movement and the Anti-Rightist Campaign, with at least 550,000 people persecuted in the latter, most of whom were intellectuals and dissidents. In 1958, he launched the Great Leap Forward that aimed to rapidly transform China's economy from agrarian to industrial, which led to the deadliest famine in history and the deaths of 15–55 million people between 1958 and 1962. In 1963, Mao launched the Socialist Education Movement, and in 1966 he initiated the Cultural Revolution, a program to remove "counter-revolutionary" elements in Chinese society which lasted 10 years and was marked by violent class struggle, widespread destruction of cultural artifacts, and an unprecedented elevation of Mao's cult of personality. Tens of millions of people were persecuted during the Revolution, while the estimated number of deaths ranges from hundreds of thousands to millions, including Liu Shaoqi, the 2nd Chairman of the PRC. After years of ill health, Mao suffered a series of heart attacks in 1976 and died at the age of 82. During Mao's era, China's population grew from around 550 million to over 900 million while the government did not strictly enforce its family planning policy.

A controversial figure, Mao is regarded as one of the most important individuals in the twentieth century. He is also known as a political intellect, theorist, military strategist, and poet. During Mao's era, China was involved in the Korean War, the Sino-Soviet split, the Vietnam War, and the rise of Khmer Rouge. He ruled China as an autocratic and totalitarian regime responsible for mass repression as well as destruction of religious and cultural artifacts and sites. The government was responsible for vast numbers of deaths with estimates ranging from 40 to 80 million victims through starvation, persecution, prison labour, and mass executions. Supporters of Mao have credited him with transforming China from a semicolony to a powerful sovereign state, with increased literacy and life expectancy.

A stake through heart for the junk DNA zombie?

Oxford Journal: “The Days of ‘Junk DNA’ Are Over ”

Evolution News @DiscoveryCSC 

Thanks to a friend for passing along a new article at the Oxford University Press journal Genome Biology & Evolution (GBE), by several authors (from German and French universities), which opened its discussion section with the sentence “The days of junk DNA are over.” 

That by itself would be significant. Equally noteworthy, however, is the fact that GBE social media editor Casey McGrath — an evolutionary biologist employed by the Society for Molecular Biology and Evolution (SMBE), the academic sponsor of GBE and its sister journal Molecular Biology and Evolution — wrote a Highlight article calling attention to the observation that “Junk DNA” is “No More.” McGrath’s article, “‘Junk DNA’ No More: Repetitive Elements as Vital Sources of Flatworm Variation,” is open access.

None of this is accidental. Since project ENCODE provoked outrage among evolutionary biologists such as Dan Graur over a decade ago, there has been a concerted campaign to defend the notion of junk DNA, often explicitly in the context of anti-intelligent design sentiments. Graur, at the University of Houston, famously argued in 2013, in a major speech in Chicago to the SMBE, that “if ENCODE is right, then evolution is wrong.” 

Younger evolutionary biologists such as Casey McGrath are watching all this. We should not assume McGrath has any ID sympathies; almost certainly, she does not. But questions about the possible functional roles of apparent “junk” DNA are just too interesting to allow oneself to be intimidated into silence by academic bullies such as Graur.

Karl Marx: a brief hhistory.

 Karl Heinrich Marx was a German philosopher, economist, historian, sociologist, political theorist, journalist and socialist revolutionary. Born in Trier, Germany, Marx studied law and philosophy at university. He married Jenny von Westphalen in 1843. Due to his political publications, Marx became stateless and lived in exile with his wife and children in London for decades, where he continued to develop his thought in collaboration with German thinker Friedrich Engels and publish his writings, researching in the British Museum Reading Room. His best-known titles are the 1848 pamphlet The Communist Manifesto and the three-volume Das Kapital (1867–1883). Marx's political and philosophical thought had enormous influence on subsequent intellectual, economic and political history. His name has been used as an adjective, a noun, and a school of social theory.

Marx's critical theories about society, economics, and politics, collectively understood as Marxism, hold that human societies develop through class conflict. In the capitalist mode of production, this manifests itself in the conflict between the ruling classes (known as the bourgeoisie) that control the means of production and the working classes (known as the proletariat) that enable these means by selling their labour-power in return for wages. Employing a critical approach known as historical materialism, Marx predicted that capitalism produced internal tensions like previous socioeconomic systems and that those would lead to its self-destruction and replacement by a new system known as the socialist mode of production. For Marx, class antagonisms under capitalism—owing in part to its instability and crisis-prone nature—would eventuate the working class's development of class consciousness, leading to their conquest of political power and eventually the establishment of a classless, communist society constituted by a free association of producers. Marx actively pressed for its implementation, arguing that the working class should carry out organised proletarian revolutionary action to topple capitalism and bring about socio-economic emancipation.

Marx has been described as one of the most influential figures in human history, and his work has been both lauded and criticised. His work in economics laid the basis for some current theories about labour and its relation to capital. Many intellectuals, labour unions, artists, and political parties worldwide have been influenced by Marx's work, with many modifying or adapting his ideas. Marx is typically cited as one of the principal architects of modern social science.

Adam Smith: a brief history.

 Adam Smith FRSA (baptized 16 June [O.S. 5 June] 1723 – 17 July 1790) was a Scottish economist, philosopher, pioneer of political economy, and a key figure during the Scottish Enlightenment. Also known as ''The Father of Economics'' or ''The Father of Capitalism,'' Smith wrote two classic works, The Theory of Moral Sentiments (1759) and An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The latter, often abbreviated as The Wealth of Nations, is considered his magnum opus and the first modern work of economics. In his work, Adam Smith introduced his theory of absolute advantage.

Smith studied social philosophy at the University of Glasgow and at Balliol College, Oxford, where he was one of the first students to benefit from scholarships set up by fellow Scot John Snell. After graduating, he delivered a successful series of public lectures at the University of Edinburgh, leading him to collaborate with David Hume during the Scottish Enlightenment. Smith obtained a professorship at Glasgow, teaching moral philosophy and during this time, wrote and published The Theory of Moral Sentiments. In his later life, he took a tutoring position that allowed him to travel throughout Europe, where he met other intellectual leaders of his day.

Smith laid the foundations of classical free market economic theory. The Wealth of Nations was a precursor to the modern academic discipline of economics. In this and other works, he developed the concept of division of labour and expounded upon how rational self-interest and competition can lead to economic prosperity. Smith was controversial in his own day and his general approach and writing style were often satirised by writers such as Horace Walpole.

Judaism: a brief history.

 Judaism (Hebrew: יַהֲדוּת‎, Yahadut; originally from Hebrew יְהוּדָה, Yehudah, "Judah", via Greek Ἰουδαϊσμός Ioudaismos; the term itself is of Anglo-Latin origin c. 1400 ) is an Abrahamic, monotheistic, and ethnic religion comprising the collective religious, cultural, and legal tradition and civilization of the Jewish people, also sometimes called Israelites. Judaism is considered by religious Jews to be the expression of the covenant that God established with the Children of Israel. It encompasses a wide body of texts, practices, theological positions, and forms of organization. The Torah is part of the larger text known as the Tanakh or the Hebrew Bible, and supplemental oral tradition represented by later texts such as the Midrash and the Talmud. With between 14.5 and 17.4 million adherents worldwide, Judaism is the tenth largest religion in the world.

Within Judaism there are a variety of religious movements, most of which emerged from Rabbinic Judaism, which holds that God revealed his laws and commandments to Moses on Mount Sinai in the form of both the Written and Oral Torah. Historically, all or part of this assertion was challenged by various groups such as the Sadducees and Hellenistic Judaism during the Second Temple period; the Karaites during the early and later medieval period; and among segments of the modern non-Orthodox denominations. Some modern branches of Judaism such as Humanistic Judaism may be considered secular or nontheistic. Today, the largest Jewish religious movements are Orthodox Judaism (Haredi Judaism and Modern Orthodox Judaism), Conservative Judaism, and Reform Judaism. Major sources of difference between these groups are their approaches to Jewish law, the authority of the Rabbinic tradition, and the significance of the State of Israel. Orthodox Judaism maintains that the Torah and Jewish law are divine in origin, eternal and unalterable, and that they should be strictly followed. Conservative and Reform Judaism are more liberal, with Conservative Judaism generally promoting a more traditionalist interpretation of Judaism's requirements than Reform Judaism. A typical Reform position is that Jewish law should be viewed as a set of general guidelines rather than as a set of restrictions and obligations whose observance is required of all Jews. Historically, special courts enforced Jewish law; today, these courts still exist but the practice of Judaism is mostly voluntary. Authority on theological and legal matters is not vested in any one person or organization, but in the sacred texts and the rabbis and scholars who interpret them.

Judaism has its roots as an organized religion in the Middle East during the Bronze Age. Modern Judaism evolved from ancient Israelite religion around 500 BCE, and is considered one of the oldest monotheistic religions. The Hebrews and Israelites were already referred to as "Jews" in later books of the Tanakh such as the Book of Esther, with the term Jews replacing the title "Children of Israel". Judaism's texts, traditions and values strongly influenced later Abrahamic religions, including Christianity and Islam. Hebraism, like Hellenism, played a seminal role in the formation of Western civilization through its impact as a core background element of Early Christianity.

Jews are an ethnoreligious group including those born Jewish, in addition to converts to Judaism. In 2019, the world Jewish population was estimated at about 14.7 million, or roughly 0.25% of the total world population. About 46.9% of all Jews reside in Israel and another 38.8% reside in the United States and Canada, with most of the remainder living in Europe, and other minority groups spread throughout Latin America, Asia, Africa, and Australia.

Law and order by design.

 

The Stop Lights in the Cell

Evolution News @DiscoveryCSC

Road traffic usually works because most people obey the laws. The laws don’t need to be stated on every occasion, because we have shortcuts to remember them: symbols in the form of signs, lane markers, and lights. People drive on the agreed-on side of the street (right in the U.S., left in the UK). They stop at red and go on green. An eight-sided red stop sign is a familiar indicator for drivers who don’t know English. When everyone obeys the laws, the choreography is stunning when seen from above in time-lapse.

Some who have driven abroad know the anxiety of unfamiliar customs: steering wheels on the wrong side of the car, different expectations about right of way, when or not to beep, and so forth. Fortunately, all eukaryotic cells use a universal set of signals, which work well unless they are disobeyed. Those include stop codes in DNA.

Forensic Investigators

In Science,  Michael R. Lawson and six colleagues play the role of forensic investigators, figuring out what goes wrong when mRNA transcripts run a red light, so to speak. Their paper, “Mechanisms that ensure speed and fidelity in eukaryotic translation termination,” begins with a statement of the law: “How Translation Stops.” It includes a shocking statistic:

Protein synthesis concludes when a ribosome encounters a stop codon in a transcript, which triggers the recruitment of highly conserved release factors to liberate the protein product. Lawson et al. used traditional biochemical methods and single-molecule fluorescence assays to track the interplay of release factors with ribosomes and reveal the molecular choreography of termination. They identified two distinct classes of effectors, small molecules and mRNA sequences, that directly inhibited the release factors and promoted stop codon readthrough. These findings may buttress ongoing efforts to treat diseases caused by premature stop codons, which cause 11% of all heritable human diseases. [Emphasis added.]

The diseases include “cystic fibrosis, muscular dystrophy, and hereditary cancers.” Correct translation termination is a vital process, therefore, occurring constantly in every cell; it “must occur rapidly and accurately.” 

Since translation is a single-file process, a better analogy than road traffic might be a paper tape reader connected to a 3-D printer. It can read and translate any tape to build any part, but by convention, a particular set of dots means stop, cut, and eject. Then the reader lets in the next paper tape to translate. The incoming paper tapes in cells are the messenger-RNA (mRNA) transcripts from DNA in the nucleus. The readers and translators are ribosomes. The translated tapes are the polypeptides that will become proteins. 

A stop codon (typically UAA, but sometimes UAG or UGA) is not translated; it summons additional molecular machines to release the polypeptide and start translating the next one. When the ribosome correctly reads the stop codon, here’s what happens:

Protein synthesis concludes when a translating ribosome encounters a stop codon at the end of an open reading frame, triggering recruitment of two factors to liberate the nascent polypeptide: eukaryotic release factor 1 (eRF1), a tRNA-shaped protein that decodes the stop codon in the ribosomal aminoacyl-tRNA site (A site) and cleaves the peptidyl-tRNA bond, and eukaryotic release factor 3 (eRF3), a GTPase that promotes eRF1 action. After translation termination, the ribosome, peptidyl-tRNA site (P site) tRNA, and mRNA are released by recycling.

Zooming in on the Process 

These factors were known to play roles in termination, but the details were unclear. This team zoomed in on the process by labeling eRF1 and eRF3 molecules with green fluorescent dyes so that they could observe the details when the ribosome reads the stop codon:

We found that the two eukaryotic release factors bound together to recognize stop codons rapidly and elicit termination through a tightly regulated, multistep process that resembles transfer RNA selection during translation elongation. Because the release factors are conserved from yeast to humans, the molecular events that underlie yeast translation termination are likely broadly fundamental to eukaryotic protein synthesis.

They also found that binding of eRF1 is fast in the presence of eRF3, but slow without it. It needs to be fast; otherwise, inappropriate transfer RNAs (tRNA) might compete for occupancy of the A site. The interaction dynamics imply that adequate concentrations of eRF3 must be present at all times to prevent stop codon readthrough.

Further monitoring showed that the two factors bind together before entering the ribosome. “Thus,” they conclude, “eRF3 is a chaperone that delivers eRF1 to ribosomes halted at stop codons, and eRF3 departure from the ribosome is partly governed by its GTPase activity.” GTPase refers to the factor that pays the energy currency for the operation. The entire binding, cleavage and release sequence normally takes about 3 seconds. Here’s a summary of the process:

First, a prebound ternary complex of eRF1, eRF3, and GTP rapidly binds to a ribosome halted at a stop codon. eRF3 appears to unlock eRF1 conformation to facilitate fast ribosomal binding, because the association of eRF1 alone is slow and governed by an eRF1 concentration–independent event…. Next, eRF3 hydrolyzes GTP to promote its own release, which permits the rearrangement of eRF1 to an active conformation. Accommodated eRF1 then rapidly cleaves the peptidyl-tRNA bond, triggering ribosomal intersubunit rotation, movement of the deacylated P-site tRNA to a P/E hybrid state, and ejection of both eRF1 and the liberated peptide.

The termination process resembles translation elongation (the insertion of a cognate tRNA in the A site during translation), except that the GTP-bound eRF3, bound to eRF1, acts like a switch. The complex binds to the stop codon in the A site like a cognate tRNA would, but then eRF3 hydrolyzes its GTP which makes it self-eject. This, in turn, unlocks a conformational change in eRF1 that cleaves the polypeptide. The conformational change also rotates the ribosome, leading to ejection of eRF1 and the liberated polypeptide, soon to become a protein. That’s the short story. There may be more going on:

With the critical caveat that termination may also be influenced by unidentified nascent chain dynamics and other trans-acting factors, we propose that the termination mechanisms described here are fundamental to eukaryotic translation, because the release factors are widely conserved from yeast to humans.

Choreography Essential in All Life

This “essential process,” they note, requires the functioning of interdependent events. The “e” in eRF1 and eRF3 means “eukaryotic” because bacteria, too, have homologous factors (RF1/2, RF3) that perform corresponding functions. Translation termination is therefore essential for all living things. 

Additionally, safety at these cellular stop signs is partly ensured by the “choreography” of ribosome activity, the length of transcripts entering the ribosome, and controls over the availability of assisting molecular machines. They only experimented with short sequences which may not adequately mirror what happens in vivo.

The finding that termination (~4 s) is fast relative to initiation [~20 to 60 s] but somewhat slower than elongation [0.05 to 1.4 s per codon] suggests the existence of an intricate choreography that prevents the accumulation of ribosomes at stop codons. Consistent with this, ribosomal profiling in eRF1-depleted cells revealed a marked increase in queueing of ribosomes at stop codons.

Mistakes, in other words, may be rarer than what they encountered in vitro, because long transcripts “substantially outnumber” short transcripts and may act to prevent delays of the termination factors. Returning to our traffic analogy, a lawbreaker may have less opportunity to run a red light if the lanes are all full and moving smoothly.

Kinetic Proofreading

The scientists call this another aspect of what is known as “kinetic proofreading” — the prevention of mistakes by motion.

The fidelity of translation elongation is driven in part by kinetic proofreading, in which EF-Tu/eEF1Apreferentially rejects noncognate tRNAs in two sequential steps to boost overall accuracy. Although the basis of termination fidelity is unknown, we consider kinetic proofreading a plausible model. eRF3 is essential for termination fidelity, because its inclusion boosts specificity by 2600-fold. Here, we show that eRF3 conformationally unlocks and delivers eRF1 to ribosomes (Figs. 2 and 4) and facilitates eRF1 accommodationin an eRF3 GTPase–dependent manner (Fig. 4), thus providing eRF3 with multiple opportunities to favor genuine stop codons.

It’s no wonder that they call this a “tightly regulated, multistep process.”

What Causes Stop Codon Readthrough?

The team found that certain cis-acting mRNAs of untranslated regions promote harmful stop codon readthrough. They do it by hindering the cleavage activity of eRF1, lengthening the time of binding from 3s to 7s. The delay allows other substances to stabilize inappropriate tRNAs at the A site in the ribosome, preventing entry of the eRF1-eRF3-GTP complex. “Together,” they conclude, “these studies demonstrate that stop codon readthrough effectors hinder numerous facets of termination, thus uncovering additional nodes to target with potential therapeutics.”

In some cases of inherited diseases, doctors would like to promote readthrough. For instance, mutations that introduce premature stop codons are hard to treat. They result in unfinished polypeptides ejecting from the ribosome, unable to form essential proteins. They are intercepted as trash by other molecular machines that perform nonsense-mediated decay (NMD). 

To achieve effective therapeutic readthrough of premature stop codons, elongation, termination, and NMD must all be carefully tuned to avoid widespread misregulation of gene expression while still eliciting enough readthrough to alleviate disease. Thus, termination and NMD inhibitors may prove most useful as adjuvants, lengthening the kinetic window for drug-mediated readthrough of premature stop codons.

Another Irreducibly Complex System

This short look at stop codons and how they trigger a coordinated series of actions in ribosomes reveals another irreducibly complex (IC) system at work. Stop codons keep us alive and healthy unless mutations, like lawbreakers, “run the red light” and violate the rules. What molecular biologists have uncovered since Darwin’s Black Box introduced the concept of irreducible complexity is not just an IC system here or there, but an IC set of IC systems at work. If one IC system defeats evolution, how much more a superset of IC systems? It’s important that people learn about the details of some of these systems to avoid being fooled by simplistic visions of cells emerging from primordial goo. Confidence in intelligent design comes when they say, “I see IC in the details.”