The Binding Of Isaac Cain
Alyson Hoffses
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Cain/cabin1 is an endogenous inhibitor of calcineurin (Cn), a calcium-dependent serine/threonine phosphatase involved in various cellular functions including apoptosis. We show here that during apoptosis cain/cabin1 is cleaved by calpain at the carboxyl terminus to generate a cleavage product with a molecular mass of 32 kDa as a necessary step leading to Cn-mediated cell death. Mouse cain/cabin1 was identified from a thymus cDNA library by an in vitro substrate-screening assay with calpain. Exposure of Jurkat cells to the calcium ionophore, induced cain/cabin1 cleavage and cell death, accompanied by activation of calpain and Cn. The calpain inhibitors, calpeptin and zLLY, suppressed both -induced cain/cabin1 cleavage and Cn activation, indicating that Cn activation and cain/cabin1 cleavage are calpain-dependent. Expression of cain/cabin1 or a catalytically inactive Cn mutant [CnA beta(2)(1-401/H160N)] and treatment with FK506 reduced -induced cell death. In vitro calpain cleavage and immunoprecipitation assays with deletion mutants of cain/cabin1 showed that cleavage occurred in the Cn-binding domain of cain/cabin1, indicating that the cleavage at its C terminus by calpain prevented cain/cabin1 from binding to Cn. In addition, in vitro binding assays showed that cain/cabin1 bound to the Cn B-binding domain of Cn A. Taken together, these results indicate that calpain cleaves the calcineurin-binding domain of cain/cabin1 to activate Cn and elicit calcium-triggered cell death.
WELCOME to the first* Web site that offers a full English version ofthe Jashar Apocryphon. From the ancient tradition of retelling thecreation stories which appear in the Bible, this short idiosyncratic document may still beworthy of some interest today. A longer commentary and a shorter apology are also included here.
*The Internet now includes other sites on this rich literary tradition [1] [2], and readers who seek the best currentscholarship are urged to consult them. (The version here is based on early texts found on5.25" floppy disks, written in WordPerfect 4.0.)
1. At God's first word, apoint burst into flames. From the chaos of the heat came patterns that lived, and theystrove to grow and consume each other. Then God spoke again. The patterns spread andcooled and, in time, they could flow together and yet remain distinct from each other. Sothey formed a song of love that echoed throughout the universe, and they found peace.
The world was warm and wet and nourishing for living things, and sothey formed and grew on its surface. New life came from old, which died and gave itsplace. Plants turned their leaves to the sun, and animals grew eyes to see. And yet theireyes could see neither good nor evil in the world.
Such was the world, when God led Flo and Faben and Human and Evewandering northwards in Africa, along the great river. By day, Faben and Human huntedtogether, while Eve swam for fish and Flo gathered fruit. In the evening, Human sang andEve shaped rocks into tools, while Flo and Faben slept together under a tree.
Then God said, "See now what I can do with a spark." And thusfire was given into the hand of Eve. She nourished the spark with dry leaves, and Humanbrought her sticks, and they felt the warmth of their fire. Faben and Flo awoke to avision of angels with flaming swords, and they fled into the wilderness. So Human and Evesat alone by their fire, and its light shone up into heaven, past the moon and the stars,but there was no one else watching.
Then Human delved and Eve spanned, and they followed the river to thesea, where Eve gave birth to Cain. "Look," she said, "I have made anotherhuman!" Then God smiled on their family. And Eve gave birth to Abel, and later toSeth.
2. Cain gathered the fruits ofall seed-bearing plants. But Abel made spears for hunting and brought meat to Eve andyoung Seth. And the sons quarreled over the leadership of the clan, after Human lost theuse of one arm. Then Cain lived in great fear, for Abel was a stealthy hunter who couldkill without warning in the wilderness. So Cain killed Abel with his own spear as herested in the camp.
They buried Abel, and Human found support from Eve beside him. So Evebrought Human a flaming branch, to wield in his good hand, and they approached Caintogether. Now Cain started away towards the wilderness, but Human commanded him to returnafter twenty years, so that they should not lose another son forever. Cain cried that theywould not remember him, but Eve said, "We will remember our son, for we are notanimals." And Cain touched a burning stick to his forehead, so that they would knowhim by its mark.
Cain was strong and swift, and he fled from the river, into the east.He ran for six days, pausing only to eat or rest. On the seventh day, he ascended to thetop of a mountain. There God showed him a vision of a great city of peace, surrounded byfields and orchards, which the children of Abel would have made. Cain looked in wonder athis vision until it faded with the setting sun, for there were then no other peopleoutside of Africa.
And Cain continued thus in his exile. Six days he walked and gatheredfood, but every seventh day he had visions of cities which God had planned for thechildren of Abel. Cain wandered for twenty years, and then he knew the whole vastness ofthe world.
Seth found Rama, Flo's daughter, alone along the river, and togetherthey had a daughter named Jashar. When Jashar had grown into womanhood, she met Cainreturning home. On that day, Seth had killed a great beast, and so they celebrated at thereturn of Cain. Eve made a fire, and Human sang, and Rama and Jashar danced.
And God married Cain and Jashar that night, under the stars. "Inthis way," Human said, "we shall always rejoice when two branches of my familyare rejoined." Then they feasted late into the night, while Human foretold joys andsorrows, and Cain described his visions. Everything that Human said was true, but Cainspoke only of the world of the children of Abel. So Human was the first true prophet, andCain the first false prophet, but they dwelt together as kinsmen for all the rest of theirdays.
3. At that time, giant beastslived in every part of the world, and they consumed trees and made a devastationthroughout the wilderness. But Seth taught his sons to hunt as he had learned from Abel,because God told them that children must learn from their elders' wisdom. Then thedaughters of Cain married the sons of Seth and, after the death of Eve, they scattered tofind the lands that Cain had seen. So the human children killed the giant beasts, and thetrees spread over all the lands, until a squirrel could run from sea to sea withouttouching the ground. Then the whole world was like a garden in the sight of God.
The cold years came, and ice flowed over the North. God watched as thegreat glaciers slowly melted back, and then looked again for the Humanites under thetrees. And God was angered, for they were still hunting and gathering just as they had inthe time of Seth. Then God found Noah, in the land between the two rivers.
4. Noah was the daughter ofZelophehad, the wife of Tubalcain, and the mother of Shem, Ham, and Jafet. At night, whileher family slept, Noah talked to God. Then God told Noah to leave the forest and go upinto the mountains. "Make disks of wood, two by two, and set rods through theircenters. Lay a sled four cubits long across the rods, and put all that you possess on thesled. Then go with your family up to the high slopes of Mount Ararat. For the forestsbelow are to be destroyed by a great flood which will cover all the lands of theworld."
To raise the sea level over all land would require more water than thenexisted in the oceans of the world. Noah knew that her family would wonder how more watercould be made. So she asked whether God's plan would deviate from the natural laws, whichhad guided the universe since the beginning, and she got no answer.
But Tubalcain faithfully made the cart to carry their tents and theyounger children. No one knew the way to Mount Ararat, and so they followed a dove forforty days and forty nights, until it came to rest on an olive tree in a field of wheat,high above the valley. And there they stayed, waiting for the flood.
In their first winter on the mountain, they had no food, except for thewheat. But God put a blessing on Noah's porridge, and Tubalcain set out to enlarge thefield. With torch and axe he cut the brush, and in the spring they scattered their lastgrains over the clearing. By autumn, the rain and sun had brought them a rich harvest.
When Noah's sons grew up, they found wives from the surrounding forestand moved down the mountain. Shem left with Ishtar and cleared the bottom land to thesouth. Then Ham and Dravidia cleared a farm to the east, and Jafet and Juropa settled landto the west. They raised many children on the bounty of their fields, while Noah prayedeach day for the safekeeping of the world.
Noah lived long into the years of her great-grandchildren. Once, aftera day of rain, she walked up her mountain and surveyed the green fields which stretched inall directions. Then she understood that the laws that God gave at the beginning wouldnever be forsaken. For Noah saw, under the rainbow, that the forest was being destroyed byher own family, which was spreading as a flood over the land.
5. Nimrod was the mightiesthunter in the age after Noah. He shared his booty with other landless men, and he taughtthem loyalty by his stories of the jinn, who strove before the world was made. Then Nimrodtriumphed, and with his two hands he settled all disputes among the Noahites. For Nimrodknew that a united people could do great deeds before God.
But when Nimrod grew old, he heard young men grumbling, and he feltevil eyes from the children of those whom he had slain. So he spoke to the people."You cannot see the peace that I have given you, so let us build a tower for God. Youhave forgotten the warfare that I ended, so let us make blood sacrifices at the new moon.Then you will see and remember, and you will know that God still inhabits ourkingdom." Thus Nimrod reigned until his death, and he was entombed in the high tower,and everyone mourned how the mighty had fallen.
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