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.”

And still yet more on the thumb print of JEHOVAH.

 

Brian Miller: The Physics of God

David Klinghoffer

The latest episode of Science Uprising, “Big Bang: Something from Nothing?,” features physicist Brian Miller, along with John Lennox and Stephen Meyer. Dr. Miller, who holds a PhD in his field from Duke University, also sat down to answer basic and advanced questions about the Big Bang. The video, a bonus feature from Science Uprising, is wonderfully concise in explaining why scientists once favored the model of an eternal universe, without a beginning, how that idea was vanquished by the advance of science, how some atheist cosmologists still resist, and why their resistance is futile 

In just 18 minutes, Miller lays to rest any reasonable doubts that our universe must have had a beginning. As in, “In the beginning.” Miller explains and detonates each major challenge to the Big Bang. There might be philosophical reasons to reject the conclusion and what it implies, or reasons of personal preference. But there are no plausible and non-desperate scientific reasons. This video is something to share with, among others, any students you know who are studying physics at the high school or college level. It would be interesting to hear what their teachers have to say in response. Also, let them know about the new Science Uprising episode.

On the prince of darkness: the Watchtower society's commentary.

 SATAN

[Resister].

In many places in the Hebrew Scriptures, the word sa·tanʹ appears without the definite article. Used in this way, it applies in its first appearance to the angel that stood in the road to resist Balaam as he set out with the objective of cursing the Israelites. (Nu 22:22, 32) In other instances it refers to individuals as resisters of other men. (1Sa 29:4; 2Sa 19:21, 22; 1Ki 5:4; 11:14, 23, 25) But it is used with the definite article ha to refer to Satan the Devil, the chief Adversary of God. (Job 1:6, ftn; 2:1-7; Zec 3:1, 2) In the Greek Scriptures the word sa·ta·nasʹ applies to Satan the Devil in nearly all of its occurrences and is usually accompanied by the definite article ho.

Origin. The Scriptures indicate that the creature known as Satan did not always have that name. Rather, this descriptive name was given to him because of his taking a course of opposition and resistance to God. The name he had before this is not given. God is the only Creator, and ‘his activity is perfect,’ with no injustice or unrighteousness. (De 32:4) Therefore, the one becoming Satan was, when created, a perfect, righteous creature of God. He is a spirit person, for he appeared in heaven in the presence of God. (Job chaps 1, 2; Re 12:9) Jesus Christ said of him: “That one was a manslayer when he began, and he did not stand fast in the truth, because truth is not in him.” (Joh 8:44; 1Jo 3:8) Jesus here shows that Satan was once in the truth, but forsook it. Beginning with his first overt act in turning Adam and Eve away from God, he was a manslayer, for he thereby brought about the death of Adam and Eve, which, in turn, brought sin and death to their offspring. (Ro 5:12) Throughout the Scriptures the qualities and actions attributed to him could be attributed only to a person, not to an abstract principle of evil. It is clear that the Jews, and Jesus and his disciples, knew that Satan existed as a person.

So, from a righteous, perfect start, this spirit person deviated into sin and degradation. The process bringing this about is described by James when he writes: “Each one is tried by being drawn out and enticed by his own desire. Then the desire, when it has become fertile, gives birth to sin; in turn, sin, when it has been accomplished, brings forth death.” (Jas 1:14, 15) In the course that Satan took, there seems to be, in some respects, a parallel with that of the king of Tyre as described in Ezekiel 28:11-19.​—See PERFECTION (The first sinner and the king of Tyre).

The Scriptural account, therefore, makes it plain that it was Satan who spoke through the medium of a serpent, seducing Eve into disobedience to God’s command. In turn, Eve induced Adam to take the same rebellious course. (Ge 3:1-7; 2Co 11:3) As a consequence of Satan’s use of the serpent, the Bible gives Satan the title “Serpent,” which came to signify “deceiver”; he also became 

“the Tempter” (Mt 4:3) and a liar, “the father of the lie.”​—Joh 8:44; Re 12:9.

Issue of Sovereignty Raised. When Satan approached Eve (through the speech of the serpent), he actually challenged the rightfulness and righteousness of Jehovah’s sovereignty. He intimated that God was unrightfully withholding something from the woman; he also declared that God was a liar in saying that she would die if she ate the forbidden fruit. Additionally, Satan made her believe she would be free and independent of God, becoming like God. By this means this wicked spirit creature raised himself higher than God in Eve’s eyes, and Satan became her god, even though Eve, at the time, apparently did not know the identity of the one misleading her. By his action he brought man and woman under his leadership and control, standing up as a rival god in opposition to Jehovah.​—Ge 3:1-7.

The Bible, in lifting the veil to give a glimpse into heavenly affairs, reveals that Satan later as a rival god appeared before Jehovah in heaven, challenging Jehovah to His face, saying that he could turn God’s servant Job, and by implication any servant of God, away from Him. He charged God, in effect, with unrighteously giving Job everything, along with full protection, so that he, Satan, could not test Job and show what was really in his heart, which, Satan intimated, was bad. He implied that Job served God primarily for selfish considerations. Satan made this point of his argument clear when he said: “Skin in behalf of skin, and everything that a man has he will give in behalf of his soul. For a change, thrust out your hand, please, and touch as far as his bone and his flesh and see whether he will not curse you to your very face.”​—Job 1:6-12; 2:1-7; see SOVEREIGNTY.

In this special case, Jehovah allowed Satan to bring calamity upon Job by not interfering when Satan brought about a raid from Sabean marauders as well as destruction of flocks and shepherds by what Job’s messenger called “the very fire of God” from the heavens; whether this was lightning or other fire is not stated. Satan also brought a raid by three bands of Chaldeans, as well as a windstorm. These things caused the death of all of Job’s children and destroyed his property. Finally, Satan inflicted a loathsome disease upon Job himself.​—Job 1:13-19; 2:7, 8.

These things reveal the might and power of the spirit creature Satan, as well as his vicious, murderous attitude.

It is important to note, however, that Satan recognized his impotence in the face of God’s express command, for he did not challenge God’s power and authority when God restricted him from taking Job’s life.​—Job 2:6.

Continued Opposition to God. By his challenge of God and his charging God’s servants with lack of integrity, Satan lived up to his title “Devil,” meaning “Slanderer,” which title he deserved for having slandered Jehovah God in the garden of Eden.

Joined by other wicked demons. Before the Flood of Noah’s day, it appears that other angels of God left their proper habitation in the heavens, as well as their assigned positions there. Materializing human bodies, they came to dwell on earth, marrying women and producing offspring called Nephilim. (Ge 6:1-4; 1Pe 3:19, 20; 2Pe 2:4; Jude 6; see NEPHILIM; SON[S] OF GOD.) These angels, having left God’s service, came under the control of Satan. Hence Satan is called “the ruler of the demons.” In one instance, when Jesus expelled demons from a man, the Pharisees accused him of doing so by the power of “Beelzebub, the ruler of the demons.” That they had reference to Satan is shown by Jesus’ answer: “If Satan expels Satan, he has become divided against himself.”​—Mt 12:22-27.

The apostle Paul associates Satan with “the wicked spirit forces in the heavenly places,” and he speaks of them as “the world rulers of this darkness.” (Eph 6:11, 12) As a governing force in the invisible realm immediately about the earth, Satan is “the ruler of the authority of the air.” (Eph 2:2) In Revelation he is shown to be the one “misleading the entire inhabited earth.” (Re 12:9) The apostle John said that “the whole world is lying in the power of the wicked one.” (1Jo 5:19) He is therefore “the ruler of this world.” (Joh 12:31) That is why James wrote that “the friendship with the world is enmity with God.”​—Jas 4:4.

His Fight to Destroy the “Seed.” Satan made early efforts to block the promise of the “seed” to come through Abraham. (Ge 12:7) He evidently tried to get Sarah contaminated so that she would be unfit to bear the seed; but God protected her. (Ge 20:1-18) He did everything possible to destroy the ones whom God chose as Abraham’s seed, the nation of Israel, by inducing them to sin and by bringing other nations against them, as Bible history shows throughout. A high point in Satan’s ambitious attempts in his fight against God, and what appeared to Satan to be success, was reached when the king of the Third World Power of Bible history, Babylon, took Jerusalem, overturning the rulership of King Zedekiah of 

the line of David, and destroyed the temple of Jehovah, desolating Jerusalem and Judah.​—Eze 21:25-27.

As an instrument of Satan, the ruling dynasty of Babylon, initially headed by Nebuchadnezzar, held Israel in exile for 68 years, until Babylon’s overthrow. Babylon had no intention of ever releasing its captives and so reflected Satan’s own boastful, ambitious attempts as a rival god opposed to the Universal Sovereign Jehovah. The Babylonian kings, worshiping their idol god Marduk, the goddess Ishtar, and a host of others, were actually worshipers of the demons and, as part of the world alienated from Jehovah, were under Satan’s domination.​—Ps 96:5; 1Co 10:20; Eph 2:12; Col 1:21.

Satan filled the king of Babylon with the ambition to have complete domination over the earth, even over “Jehovah’s throne” (1Ch 29:23) and “the stars of God,” the kings of the line of David sitting on the throne at Mount Moriah (by extension, Zion). This “king,” that is, the dynasty of Babylon, ‘lifted himself up’ in his own heart and was in his own eyes and in the eyes of his admirers a “shining one,” a “son of the dawn.” (In some translations the Latin Vulgate term “Lucifer” is retained. It is, however, merely the translation of the Hebrew word heh·lelʹ, “shining one.” Heh·lelʹ is not a name or a title but, rather, a term describing the boastful position taken by Babylon’s dynasty of kings of the line of Nebuchadnezzar.) (Isa 14:4-21) Since Babylon was a tool of Satan, its “king” reflected Satan’s own ambitious desire. Again, Jehovah came to the salvation of his people by restoring them to their land, until the real Seed of promise should come.​—Ezr 1:1-6.

Efforts to cause Jesus to stumble. Satan, no doubt identifying Jesus as the Son of God and the one who was prophesied to bruise him in the head (Ge 3:15), did everything he could to destroy Jesus. But, when announcing the conception of Jesus to Mary, the angel Gabriel told her: “Holy spirit will come upon you, and power of the Most High will overshadow you. For that reason also what is born will be called holy, God’s Son.” (Lu 1:35) Jehovah safeguarded his Son. The efforts to destroy Jesus when an infant were unsuccessful. (Mt 2:1-15) God continued to protect Jesus during his youth. After his baptism, Satan approached Jesus in the wilderness with three different strong temptations, thoroughly testing him on the issue of devotion to Jehovah. In one of his appeals Satan showed Jesus all the kingdoms of the world, claiming them to be his own. Jesus did not contradict this claim. Nonetheless, Jesus refused to contemplate even for the briefest instant of time any “shortcut” to kingship, nor did he consider for an instant the doing of anything merely to please himself. His immediate reply to Satan was, “Go away, Satan! For it is written, ‘It is Jehovah your God you must worship, and it is to him alone you must render sacred service.’” At this, “the Devil . . . retired from him until another convenient time.” (Mt 4:1-11; Lu 4:13) This illustrates the truth of James’ words later written: “Oppose the Devil, and he will flee from you.”​—Jas 4:7.

Jesus was ever alert to the danger of Satan’s machinations and to the fact that Satan desired to cause his destruction by getting him to entertain a thought contrary to Jehovah’s will. This was demonstrated when Peter, on one occasion, though with good intentions, was actually throwing temptation in his way. Jesus had spoken of the suffering and death he was to undergo. “At this Peter took him aside and commenced rebuking him, saying: ‘Be kind to yourself, Lord; you will not have this destiny at all.’ But, turning his back, he said to Peter: ‘Get behind me, Satan! You are a stumbling block to me, because you think, not God’s thoughts, but those of men.’”​—Mt 16:21-23.

Throughout Jesus’ ministry he was in danger; Satan used human agents to oppose Jesus, trying either to cause him to stumble or to kill him. At one time the people were about to seize Jesus to make him king. But he would not consider such a thing; he would accept kingship only in God’s time and way. (Joh 6:15) On another occasion those of his own hometown attempted to kill him. (Lu 4:22-30) He was constantly harassed by those whom Satan used to try to trap him. (Mt 22:15) But in all of Satan’s efforts, he failed to cause Jesus to sin in the slightest thought or deed. Satan was thoroughly proved to be a liar, and he failed in his challenge of God’s sovereignty and the integrity of God’s servants. As Jesus said, shortly before his death: “Now there is a judging of this world; now the ruler of this world will be cast out”​—completely discredited. (Joh 12:31) Satan had a grip on all mankind through sin. But, knowing that Satan would soon bring about his death, Jesus, after celebrating his last Passover with his disciples, could say: “The ruler of the world is coming. And he has no hold on me.”​—Joh 14:30.

A few hours later, Satan succeeded in having Jesus put to death, first getting control of one of Jesus’ apostles, then using the Jewish leaders and the Roman World Power to execute Jesus in a painful and ignominious manner. (Lu 22:3; Joh 13:26, 

27; chaps 18, 19) Here Satan acted as “the one having the means to cause death, that is, the Devil.” (Heb 2:14; Lu 22:53) But in this Satan failed to promote his cause; he only unwillingly fulfilled prophecy, which required that Jesus die as a sacrifice. The death of Jesus in blamelessness provided the ransom price for humankind, and by his death (and subsequent resurrection by God) Jesus could now help sinful humankind to escape from the grip of Satan, for, as it is written, Jesus became blood and flesh “that through his death he might bring to nothing the one having the means to cause death, that is, the Devil; and that he might emancipate all those who for fear of death were subject to slavery all through their lives.”​—Heb 2:14, 15.

Continues to fight Christians. After Jesus’ death and resurrection, Satan continued to wage a bitter fight against Christ’s followers. The accounts in the book of Acts and in the letters of the Christian Greek Scriptures furnish numerous proofs of this. Paul said that he had been given “a thorn in the flesh, an angel of Satan, to keep slapping” him. (2Co 12:7) And as in the case with Eve, Satan disguised his real nature and purposes by “transforming himself into an angel of light,” and he had agents, ministers who “also keep transforming themselves into ministers of righteousness.” (2Co 11:14, 15) Examples of these were the false apostles who fought against Paul (2Co 11:13) and those in Smyrna ‘who said they themselves were Jews, and yet they were not but were a synagogue of Satan.’ (Re 2:9) Satan never ceased in making accusations “day and night” against Christians, challenging their integrity, as he did Job’s. (Re 12:10; Lu 22:31) But Christians have “a helper with the Father, Jesus Christ, a righteous one,” who appears before the person of God in their behalf.​—1Jo 2:1.

His Abyssing and Final Destruction. At the time of Satan’s act in causing Eve and then Adam to rebel against God, God said to the serpent (actually speaking to Satan, since a mere beast could not understand the issues involved): “Dust is what you will eat all the days of your life. And I shall put enmity between you and the woman and between your seed and her seed. He will bruise you in the head and you will bruise him in the heel.” (Ge 3:14, 15) Here God made it known that Satan, cast outside God’s holy organization, would have no life-sustaining hope but would ‘eat dust,’ as it were, until he died. The “seed” eventually was to bruise him in the head, which would signify a death wound. When Christ was on earth, the demons identified him as the One who was to hurl them into the “abyss,” evidently a condition of restraint that in the parallel account is spoken of as “torment.”​—Mt 8:29; Lu 8:30, 31; see TORMENT.

In the book of Revelation, we find described the last days of Satan and his end. Revelation reports that at the time of Christ’s taking Kingdom power, Satan is hurled down out of heaven to the earth, no longer having access to the heavens, as he did in the days of Job and for centuries thereafter. (Re 12:7-12) After this defeat Satan has only a “short period of time,” during which he makes war with “the remaining ones of [the woman’s] seed, who observe the commandments of God and have the work of bearing witness to Jesus.” In his efforts to devour the remaining ones of the woman’s seed, he is called “the dragon,” a swallower or crusher. (Re 12:16, 17; compare Jer 51:34, where Jeremiah speaks for Jerusalem and Judah, saying: “Nebuchadrezzar the king of Babylon . . . has swallowed me down like a big snake [or, “a dragon,” ftn].”) In the earlier description of his fight against the woman and his efforts to devour her man child, he is pictured as “a great fiery-colored dragon.”​—Re 12:3.

Revelation’s 20th chapter describes Satan’s being bound and abyssed for a thousand years, at the hands of a great angel​—doubtless Jesus Christ, who has the key of the abyss and who is the “seed” to bruise Satan’s head.​—Compare Re 1:18; see ABYSS.

Satan’s final effort culminates in permanent defeat. The prophecy says that he is to be let loose for “a little while” as soon as Christ’s Thousand Year Reign is ended and that he will lead rebellious persons in another attack upon God’s sovereignty; but he is hurled (along with his demons) into the lake of fire and sulfur, everlasting destruction.​—Re 20:1-3, 7-10; compare Mt 25:41; see LAKE OF FIRE.

What is meant by ‘handing a person over to Satan for destruction of the flesh’?

In instructing the congregation at Corinth as to the action to take toward a member of the congregation who had wickedly been committing incest with the wife of his father, the apostle Paul wrote: “Hand such a man over to Satan for the destruction of the flesh.” (1Co 5:5) This was a command to expel the man from the congregation, cutting off all fellowship with him. (1Co 5:13) Turning 

him over to Satan would put him out of the congregation and into the world over which Satan is the god and ruler. Like “a little leaven” in “the whole lump” of dough, this man was “the flesh,” or fleshly element inside the congregation; and by removing this incestuous man, the spiritually minded congregation would destroy “the flesh” from the midst of it. (1Co 5:6, 7) Similarly, Paul handed Hymenaeus and Alexander over to Satan, because they had thrust aside faith and a good conscience and had experienced shipwreck concerning their faith.​—1Ti 1:20.

Later, the incestuous man in Corinth apparently repented from his wrongdoing and cleaned up, prompting the apostle Paul to recommend his being received back into the congregation. In exhorting them to forgiveness, he gave as one of the reasons, “that we may not be overreached by Satan, for we are not ignorant of his designs.” (2Co 2:11) In the first instance, Satan had brought the congregation into a bad condition in which they had to be reproved by the apostle, for they were too lenient, in fact, were letting the wicked man carry on his practice without regard for the reproach it brought, being “puffed up” in allowing it. (1Co 5:2) But on the other hand, if they now swung to the other extreme and refused forgiveness to the repentant one, Satan would be overreaching them in another direction, namely, that he could take advantage of their becoming hard and unforgiving. Through God’s Word, Christians are enlightened to realize Satan’s existence, his power, his designs and purposes, and his manner of operation, so that they can fight this spiritual foe with the spiritual weapons God provides.​—Eph 6:13-17.

Hinduism: a brief history.

 Hinduism is an Indian religion and dharma, or way of life. It is the world's third-largest religion, with over 1.2 billion followers, or 15–16% of the global population, known as Hindus. The word Hindu is an exonym, and while Hinduism has been called the oldest religion in the world, many practitioners refer to their religion as Sanātana Dharma (Sanskrit: सनातनधर्म:, lit. ''the Eternal way''), which refers to the idea that its origins lie beyond human history, as revealed in the Hindu texts. Another, though less fitting, self-designation is Vaidika dharma, the 'dharma related to the Vedas.'

Hinduism is a diverse system of thought marked by a range of philosophies and shared concepts, rituals, cosmological systems, pilgrimage sites and shared textual sources that discuss theology, metaphysics, mythology, Vedic yajna, yoga, agamic rituals, and temple building, among other topics. Prominent themes in Hindu beliefs include the four Puruṣārthas, the proper goals or aims of human life; namely, dharma (ethics/duties), artha (prosperity/work), kama (desires/passions) and moksha (liberation/freedom from the cycle of death and rebirth/salvation), as well as karma (action, intent and consequences) and saṃsāra (cycle of death and rebirth). Hinduism prescribes the eternal duties, such as honesty, refraining from injuring living beings (Ahiṃsā), patience, forbearance, self-restraint, virtue, and compassion, among others. Hindu practices include rituals such as puja (worship) and recitations, japa, meditation (dhyāna), family-oriented rites of passage, annual festivals, and occasional pilgrimages. Along with the practice of various yogas, some Hindus leave their social world and material possessions and engage in lifelong Sannyasa (monasticism) in order to achieve Moksha.

Hindu texts are classified into Śruti ("heard") and Smṛti ("remembered"), the major scriptures of which are the Vedas, the Upanishads, the Purānas, the Mahābhārata, the Rāmāyana, and the Āgamas. There are six āstika schools of Hindu philosophy, who recognise the authority of the Vedas, namely Sānkhya, Yoga, Nyāya, Vaisheshika, Mimāmsā and Vedānta. While the Puranic chronology presents a genealogy of thousands of years, starting with the Vedic rishis, scholars regard Hinduism as a fusion or synthesis of Brahmanical orthopraxy with various Indian cultures, having diverse roots and no specific founder. This Hindu synthesis emerged after the Vedic period, between c. 500 –200 BCE and c. 300 CE, in the period of the Second Urbanisation and the early classical period of Hinduism, when the Epics and the first Purānas were composed. It flourished in the medieval period, with the decline of Buddhism in India.

Currently, the four largest denominations of Hinduism are Vaishnavism, Shaivism, Shaktism and Smartism. Sources of authority and eternal truths in the Hindu texts an important role, but there is also a strong Hindu tradition of questioning authority in order to deepen the understanding of these truths and to further develop the tradition. Hinduism is the most widely professed faith in India, Nepal and Mauritius. Significant numbers of Hindu communities are found in Southeast Asia including in Bali, Indonesia, the Caribbean, North America, Europe, Oceania, Africa, and other regions. Hinduism is the second fastest-growing religion in the world, after Islam with a growth of 17%.