Search This Blog

Thursday, June 24, 2021

Bible

From Wikipedia, the free encyclopedia

The Gutenberg Bible, the first printed Bible (mid-15th century)

The Bible (from Koine Greek τὰ βιβλία, biblía, "the books") is a collection of religious texts, writings, or scriptures sacred to Jews, Samaritans, Christians, Muslims, and others. It appears in the form of an anthology, a compilation of texts of a variety of forms that are all linked by the belief that they are collectively revelations of God. These texts include theologically-focused historical accounts, hymns, prayers, proverbs, parables, didactic letters, admonitions, essays, poetry, and prophecies. Believers also generally consider the Bible to be a product of divine inspiration.

Those books that are included in the Bible by a tradition or group are called canonical, indicating that the tradition/group views the collection as the true representation of God's word and will. A number of biblical canons have evolved, with overlapping and diverging contents from denomination to denomination. The Hebrew Bible shares most of its content with its ancient Greek translation, the Septuagint, which in turn was the base for the Christian Old Testament. The Christian New Testament is a collection of writings by early Christians, believed to be Jewish disciples of Christ, written in first-century Koine Greek. Among Christian denominations there is some disagreement about what should be included in the canon, primarily about the biblical apocrypha, a list of works that are regarded with varying levels of respect or recognition.

Attitudes towards the Bible also differ among Christian groups. Roman Catholics, High Church Anglicans, Methodists and Eastern Orthodox Christians stress the harmony and importance of both the Bible and sacred tradition, while many Protestant churches focus on the idea of sola scriptura, or scripture alone. This concept rose to prominence during the Reformation, and many denominations today support the use of the Bible as the only infallible source of Christian teaching. Others, though, advance the concept of prima scriptura in contrast, meaning scripture primarily or scripture mainly.

The Bible has had a profound influence on literature and history, especially in the Western world, where the Gutenberg Bible was the first book printed using movable type. According to the March 2007 edition of Time, the Bible "has done more to shape literature, history, entertainment, and culture than any book ever written. Its influence on world history is unparalleled, and shows no signs of abating." With estimated total sales of over five billion copies, it is widely considered to be the best-selling book of all time. As of the 2000s, it sells approximately 100 million copies annually.

Etymology

The English word Bible is derived from Koinē Greek: τὰ βιβλία, romanized: ta biblia, meaning "the books" (singular βιβλίον, biblion). The word βιβλίον itself had the literal meaning of "scroll" and came to be used as the ordinary word for "book". It is the diminutive of βύβλος byblos, "Egyptian papyrus", possibly so called from the name of the Phoenician sea port Byblos (also known as Gebal) from whence Egyptian papyrus was exported to Greece.

By the 2nd century BCE, Jewish groups began calling the books of the Bible the "scriptures" and they referred to them as "holy", or in Hebrew כִּתְבֵי הַקֹּדֶשׁ (Kitvei hakkodesh), and Christians now commonly call the Old and New Testaments of the Christian Bible "The Holy Bible" (in Greek τὰ βιβλία τὰ ἅγια, tà biblía tà ágia) or "the Holy Scriptures" (η Αγία Γραφή, e Agía Graphḗ).

The Greek ta biblia (lit. "little papyrus books") was "an expression Hellenistic Jews used to describe their sacred books" (the Septuagint). Christian use of the term can be traced to c. 223 CE. The biblical scholar F. F. Bruce notes that Chrysostom appears to be the first writer (in his Homilies on Matthew, delivered between 386 and 388) to use the Greek phrase ta biblia ("the books") to describe both the Old and New Testaments together.

Medieval Latin biblia is short for biblia sacra "holy book", while biblia in Greek and Late Latin is neuter plural (gen. bibliorum). It gradually came to be regarded as a feminine singular noun (biblia, gen. bibliae) in medieval Latin, and so the word was loaned as singular into the vernaculars of Western Europe. Latin biblia sacra "holy books" translates Greek τὰ βιβλία τὰ ἅγια tà biblía tà hágia, "the holy books".

Development

The Bible is not a single book but a collection of books, whose complex development is not completely understood. The books began as songs and stories orally transmitted from generation to generation before being written down in a process that began sometime around the start of the first millennium BCE and continued for over a thousand years. The Bible was written and compiled by many people, from a variety of disparate cultures, most of whom are unknown. British biblical scholar John K. Riches wrote:

[T]he biblical texts were produced over a period in which the living conditions of the writers – political, cultural, economic, and ecological – varied enormously. There are texts which reflect a nomadic existence, texts from people with an established monarchy and Temple cult, texts from exile, texts born out of fierce oppression by foreign rulers, courtly texts, texts from wandering charismatic preachers, texts from those who give themselves the airs of sophisticated Hellenistic writers. It is a time-span which encompasses the compositions of Homer, Plato, Aristotle, Thucydides, Sophocles, Caesar, Cicero, and Catullus. It is a period which sees the rise and fall of the Assyrian empire (twelfth to seventh century) and of the Persian empire (sixth to fourth century), Alexander's campaigns (336–326), the rise of Rome and its domination of the Mediterranean (fourth century to the founding of the Principate, 27 BCE), the destruction of the Jerusalem Temple (70 CE), and the extension of Roman rule to parts of Scotland (84 CE).

Hebrew Bible from 1300. page 20, Genesis.
Hebrew Bible from 1300. Genesis.

Considered to be scriptures (sacred, authoritative religious texts), the books were compiled by different religious communities into various biblical canons (official collections of scriptures). The earliest compilation, containing the first five books of the Bible and called the Torah (meaning "law", "instruction", or "teaching") or Pentateuch ("five books"), was accepted as Jewish canon by the fifth century BCE. A second collection of narrative histories and prophesies, called the Nevi'im ("prophets"), was canonized in the third century BCE. A third collection called the Ketuvim ("writings"), containing psalms, proverbs, and narrative histories, was canonized sometime between the second century BCE and the second century CE. These three collections were written mostly in Hebrew, with some parts in Aramaic, and together form the Hebrew Bible or "TaNaKh" (a portmanteau of "Torah", "Nevi'im", and "Ketuvim").

Greek-speaking Jews in Alexandria and elsewhere in the Jewish diaspora considered additional scriptures, composed between 200 BCE and 100 CE and not included in the Hebrew Bible, to be canon. These additional texts were included in a translation of the Hebrew Bible into Koine Greek (common Greek spoken by ordinary people) known as the Septuagint (meaning "the work of the seventy"), which began as a translation of the Torah made around 250 BCE and continued to develop for several centuries. The Septuagint contained all of the books of the Hebrew Bible, re-organized and with some textual differences, with the additional scriptures interspersed throughout.

Saint Paul Writing His Epistles, 16th-century painting.

During the rise of Christianity in the first century CE, new scriptures were written in Greek about the life and teachings of Jesus Christ, who Christians believed was the messiah prophesized in the books of the Hebrew Bible. Two collections of these new scriptures – the Pauline epistles and the Gospels – were accepted as canon by the end of the second century CE. A third collection, the catholic epistles, were canonized over the next few centuries. Christians called these new scriptures the "New Testament", and began referring to the Septuagint as the "Old Testament".

Between 385 and 405 CE, the early Christian church translated its canon into Vulgar Latin (the common Latin spoken by ordinary people), a translation known as the Vulgate, which included in its Old Testament the books that were in the Septuagint but not in the Hebrew Bible. The Vulgate introduced stability to the Bible, but also began the East-West Schism between Latin-speaking Western Christianity (led by the Catholic Church) and multi-lingual Eastern Christianity (led by the Eastern Orthodox Church). Christian denominations' biblical canons varied not only in the language of the books, but also in their selection, organization, and text.

Jewish rabbis began developing a standard Hebrew Bible in the first century CE, maintained since the middle of the first millennium by the Masoretes, and called the Masoretic Text. Christians have held ecumenical councils to standardize their biblical canon since the fourth century CE. The Council of Trent (1545–63), held by the Catholic Church in response to the Protestant Reformation, authorized the Vulgate as its official Latin translation of the Bible. The Church deemed the additional books in its Old Testament that were interspersed among the Hebrew Bible books to be "deuterocanonical" (meaning part of a second or later canon). Protestant Bibles either separated these books into a separate section called the "Apocrypha" (meaning "hidden away") between the Old and New Testaments, or omitted them altogether. The 17th century Protestant King James Version was the most ubiquitous English Bible of all time, but it has largely been superseded by modern translations.

Textual history

The books of the Bible were written and copied by hand, initially on papyrus scrolls. No originals survive, and the oldest existing scrolls are copies that were made centuries after the books were first written. The copies contained both errors and intentional changes, resulting in different versions of the books in circulation, ultimately diverging into distinct lineages, called "text families" or "text types". Over time, the individual scrolls were gathered into collections, but these collections had different scrolls, and different versions of the same scrolls, with no standard organization. By the 3rd century CE, scrolls were supplanted by early bound books called codexes, and collections of biblical books began being copied as a set.

The Isaiah scroll, which is a part of the Dead Sea Scrolls, contains almost the whole Book of Isaiah. It dates from the 2nd century BCE.

More than 220 Dead Sea Scrolls discovered in Qumran in 1947, which date between 250 BCE and 100 CE, are the oldest existing copies of the books of the Hebrew Bible of any considerable length. The Qumran scrolls attest to many different biblical text types. In addition to the Qumran scrolls, there are three major manuscript witnesses (historical copies) of the Hebrew Bible: the Septuagint, the Masoretic Text, and the Samaritan Pentateuch. Existing complete copies of the Septuagint, a translation of the Hebrew Bible into Greek, date from the third to the fifth centuries CE, with fragments dating back to the second century BCE. The Masoretic Text is a standardized version of the Hebrew Bible that began to be developed in the first century CE and has been maintained by the Masoretes since the latter half of the first millennium CE. Its oldest complete copy in existence is the Leningrad Codex, dating to c. 1000 CE. The Samaritan Pentateuch is a version of the Torah maintained by the Samaritan community since antiquity and rediscovered by European scholars in the 17th century; the oldest existing copies date to c. 1100 CE.

There are about 3,000 existing New Testament manuscripts, copied between the 2nd and 17th centuries. The manuscripts include papyri, over a hundred of which have been discovered in Egypt since 1890; about 300 great uncial codices, which are vellum or parchment books written in block Greek letters, mostly dating between the 3rd and 9th centuries CE; and about 2,900 minuscules, written in a cursive style (using connected letters) that superseded uncials beginning in the 9th century. These manuscripts differ in varying degrees from one another and are grouped according to their similarities into textual families or lineages; the four most commonly recognized are Alexandrian, Western, Caesarean, and Byzantine.

Hebrew Bible

The Nash Papyrus (2nd century BCE) contains a portion of a pre-Masoretic Text, specifically the Ten Commandments and the Shema Yisrael prayer.

The Masoretic Text is the authoritative Hebrew text of the Hebrew Bible. It defines the books of the Jewish canon, and also the precise letter-text of these biblical books, with their vocalization and accentuation.

The oldest extant manuscripts of the Masoretic Text date from approximately the 9th century CE, and the Aleppo Codex (once the oldest complete copy of the Masoretic Text, but now missing its Torah section) dates from the 10th century. The term "Keter" (crown, from the Arabic, taj) originally referred to this particular manuscript, Over the years, the term Keter came to refer to any full text of the Hebrew Bible, or significant portion of it, bound as a codex (not a scroll) and including vowel points, cantillation marks, and Masoretic notes. Medieval handwritten manuscripts were considered extremely precise, the most authoritative documents from which to copy other texts.

The name Tanakh (Hebrew: תנ"ך‎) reflects the threefold division of the Hebrew Scriptures, Torah ("Teaching"), Nevi'im ("Prophets") and Ketuvim ("Writings").

Torah

The Torah (תּוֹרָה) is also known as the "Five Books of Moses" or the Pentateuch, meaning "five scroll-cases". Traditionally these books were considered to have been written almost entirely by Moses himself. In the 19th century, Julius Wellhausen and other scholars proposed that the Torah had been compiled from earlier written documents dating from the 9th to the 5th century BCE, the "documentary hypothesis". Scholars Hermann Gunkel and Martin Noth, building on the form criticism of Gerhard von Rad, refined this hypothesis, while other scholars have proposed other ways that the Torah might have developed over the centuries.

Samaritan Inscription containing portion of the Bible in nine lines of Hebrew text, currently housed in the British Museum

The Hebrew names of the books are derived from the first words in the respective texts. The Torah consists of the following five books:

The first eleven chapters of Genesis provide accounts of the creation (or ordering) of the world and the history of God's early relationship with humanity. The remaining thirty-nine chapters of Genesis provide an account of God's covenant with the biblical patriarchs Abraham, Isaac and Jacob (also called Israel) and Jacob's children, the "Children of Israel", especially Joseph. It tells of how God commanded Abraham to leave his family and home in the city of Ur, eventually to settle in the land of Canaan, and how the Children of Israel later moved to Egypt. The remaining four books of the Torah tell the story of Moses, who lived hundreds of years after the patriarchs. He leads the Children of Israel from slavery in ancient Egypt to the renewal of their covenant with God at biblical Mount Sinai and their wanderings in the desert until a new generation was ready to enter the land of Canaan. The Torah ends with the death of Moses.

The commandments in the Torah provide the basis for Jewish religious law. Tradition states that there are 613 commandments (taryag mitzvot).

Nevi'im

Nevi'im (Hebrew: נְבִיאִים‎, romanizedNəḇî'îm, "Prophets") is the second main division of the Tanakh, between the Torah and Ketuvim. It contains two sub-groups, the Former Prophets (Nevi'im Rishonim נביאים ראשונים‎, the narrative books of Joshua, Judges, Samuel and Kings) and the Latter Prophets (Nevi'im Aharonim נביאים אחרונים‎, the books of Isaiah, Jeremiah and Ezekiel and the Twelve Minor Prophets).

The Nevi'im tell the story of the rise of the Hebrew monarchy and its division into two kingdoms, ancient Israel and Judah, focusing on conflicts between the Israelites and other nations, and conflicts among Israelites, specifically, struggles between believers in "the LORD God" (Yahweh) and believers in foreign gods, and the criticism of unethical and unjust behaviour of Israelite elites and rulers; in which prophets played a crucial and leading role. It ends with the conquest of the Kingdom of Israel by the Assyrians followed by the conquest of the Kingdom of Judah by the Babylonians and the destruction of the Temple in Jerusalem.

Former Prophets

The Former Prophets are the books Joshua, Judges, Samuel and Kings. They contain narratives that begin immediately after the death of Moses with the divine appointment of Joshua as his successor, who then leads the people of Israel into the Promised Land, and end with the release from imprisonment of the last king of Judah. Treating Samuel and Kings as single books, they cover:

  • Joshua's conquest of the land of Canaan (in the Book of Joshua),
  • the struggle of the people to possess the land (in the Book of Judges),
  • the people's request to God to give them a king so that they can occupy the land in the face of their enemies (in the Books of Samuel)
  • the possession of the land under the divinely appointed kings of the House of David, ending in conquest and foreign exile (Books of Kings)

Latter Prophets

The Latter Prophets are divided into two groups, the "major" prophets, Isaiah, Jeremiah, Ezekiel, Daniel, and the Twelve Minor Prophets, collected into a single book. The collection is broken up to form twelve individual books in the Christian Old Testament, one for each of the prophets:

Ketuvim

Ketuvim or Kəṯûḇîm (in Biblical Hebrew: כְּתוּבִים‎ "writings") is the third and final section of the Tanakh. The Ketuvim are believed to have been written under the Ruach HaKodesh (the Holy Spirit) but with one level less authority than that of prophecy.

The poetic books

In Masoretic manuscripts (and some printed editions), Psalms, Proverbs and Job are presented in a special two-column form emphasizing the parallel stichs in the verses, which are a function of their poetry. Collectively, these three books are known as Sifrei Emet (an acronym of the titles in Hebrew, איוב, משלי, תהלים yields Emet אמ"ת, which is also the Hebrew for "truth").

These three books are also the only ones in Tanakh with a special system of cantillation notes that are designed to emphasize parallel stichs within verses. However, the beginning and end of the book of Job are in the normal prose system.

The five scrolls (Hamesh Megillot)

The five relatively short books of Song of Songs, Book of Ruth, the Book of Lamentations, Ecclesiastes and Book of Esther are collectively known as the Hamesh Megillot (Five Megillot). These are the latest books collected and designated as "authoritative" in the Jewish canon even though they were not complete until the 2nd century CE.

Other books

Besides the three poetic books and the five scrolls, the remaining books in Ketuvim are Daniel, Ezra–Nehemiah and Chronicles. Although there is no formal grouping for these books in the Jewish tradition, they nevertheless share a number of distinguishing characteristics:

  • Their narratives all openly describe relatively late events (i.e., the Babylonian captivity and the subsequent restoration of Zion).
  • The Talmudic tradition ascribes late authorship to all of them.
  • Two of them (Daniel and Ezra) are the only books in the Tanakh with significant portions in Aramaic.

Order of the books

The following list presents the books of Ketuvim in the order they appear in most printed editions. It also divides them into three subgroups based on the distinctiveness of Sifrei Emet and Hamesh Megillot.

The Three Poetic Books (Sifrei Emet)

The Five Megillot (Hamesh Megillot)

Other books

The Jewish textual tradition never finalized the order of the books in Ketuvim. The Babylonian Talmud (Bava Batra 14b–15a) gives their order as Ruth, Psalms, Job, Proverbs, Ecclesiastes, Song of Solomon, Lamentations of Jeremiah, Daniel, Scroll of Esther, Ezra, Chronicles.

In Tiberian Masoretic codices, including the Aleppo Codex and the Leningrad Codex, and often in old Spanish manuscripts as well, the order is Chronicles, Psalms, Job, Proverbs, Ruth, Song of Solomon, Ecclesiastes, Lamentations of Jeremiah, Esther, Daniel, Ezra.

Canonization

The Ketuvim is the last of the three portions of the Tanakh to have been accepted as biblical canon. While the Torah may have been considered canon by Israel as early as the 5th century BCE and the Former and Latter Prophets were canonized by the 2nd century BCE, the Ketuvim was not a fixed canon until the 2nd century of the Common Era.

Evidence suggests, however, that the people of Israel were adding what would become the Ketuvim to their holy literature shortly after the canonization of the prophets. As early as 132 BCE references suggest that the Ketuvim was starting to take shape, although it lacked a formal title. References in the four Gospels as well as other books of the New Testament indicate that many of these texts were both commonly known and counted as having some degree of religious authority early in the 1st century CE.

Many scholars believe that the limits of the Ketuvim as canonized scripture were determined by the Council of Jamnia c. 90 CE. Against Apion, the writing of Josephus in 95 CE, treated the text of the Hebrew Bible as a closed canon to which "... no one has ventured either to add, or to remove, or to alter a syllable..." For a long time following this date the divine inspiration of Esther, the Song of Songs, and Ecclesiastes was often under scrutiny.

Original languages

The Tanakh was mainly written in biblical Hebrew, with some small portions (Ezra 4:8–6:18 and 7:12–26, Jeremiah 10:11, Daniel 2:4–7:28) written in biblical Aramaic, a sister language which became the lingua franca for much of the Semitic world.

Samaritan Pentateuch

Samaritans include only the Pentateuch in their biblical canon. They do not recognize divine authorship or inspiration in any other book in the Jewish Tanakh. A Samaritan Book of Joshua partly based upon the Tanakh's Book of Joshua exists, but Samaritans regard it as a non-canonical secular historical chronicle.

Septuagint

Fragment of a Septuagint: A column of uncial book from 1 Esdras in the Codex Vaticanus c. 325–350 CE, the basis of Sir Lancelot Charles Lee Brenton's Greek edition and English translation.

The Septuagint, or the LXX, is a translation of the Hebrew Scriptures and some related texts into Koine Greek, begun in the late 3rd century BCE and completed by 132 BCE, initially in Alexandria, but in time it was completed elsewhere as well. It is not altogether clear which was translated when, or where; some may even have been translated twice, into different versions, and then revised.

As the work of translation progressed, the canon of the Septuagint expanded. The Torah always maintained its pre-eminence as the basis of the canon but the collection of prophetic writings, based on the Nevi'im, had various hagiographical works incorporated into it. In addition, some newer books were included in the Septuagint, among these are the Maccabees and the Wisdom of Sirach. However, the book of Sirach, is now known to have existed in a Hebrew version, since ancient Hebrew manuscripts of it were rediscovered in modern times. The Septuagint version of some Biblical books, like Daniel and Esther, are longer than those in the Jewish canon. Some of these deuterocanonical books (e.g. the Wisdom of Solomon, and the second book of Maccabees) were not translated, but composed directly in Greek.

Since Late Antiquity, once attributed to a hypothetical late 1st-century Council of Jamnia, mainstream Rabbinic Judaism rejected the Septuagint as valid Jewish scriptural texts. Several reasons have been given for this. First, some mistranslations were claimed. Second, the Hebrew source texts used for the Septuagint differed from the Masoretic tradition of Hebrew texts, which was chosen as canonical by the Jewish rabbis. Third, the rabbis wanted to distinguish their tradition from the newly emerging tradition of Christianity. Finally, the rabbis claimed a divine authority for the Hebrew language, in contrast to Aramaic or Greek – even though these languages were the lingua franca of Jews during this period (and Aramaic would eventually be given a holy language status comparable to Hebrew).

The Septuagint is the basis for the Old Latin, Slavonic, Syriac, Old Armenian, Old Georgian and Coptic versions of the Christian Old Testament. The Roman Catholic and Eastern Orthodox Churches use most of the books of the Septuagint, while Protestant churches usually do not. After the Protestant Reformation, many Protestant Bibles began to follow the Jewish canon and exclude the additional texts, which came to be called biblical apocrypha. The Apocrypha are included under a separate heading in the King James Version of the Bible, the basis for the Revised Standard Version.

Incorporations from Theodotion

In most ancient copies of the Bible which contain the Septuagint version of the Old Testament, the Book of Daniel is not the original Septuagint version, but instead is a copy of Theodotion's translation from the Hebrew, which more closely resembles the Masoretic Text. The original Septuagint version was discarded in favour of Theodotion's version in the 2nd to 3rd centuries CE. In Greek-speaking areas, this happened near the end of the 2nd century, and in Latin-speaking areas (at least in North Africa), it occurred in the middle of the 3rd century. History does not record the reason for this, and St. Jerome reports, in the preface to the Vulgate version of Daniel, "This thing 'just' happened." One of two Old Greek texts of the Book of Daniel has been recently rediscovered and work is ongoing in reconstructing the original form of the book.

The canonical Ezra–Nehemiah is known in the Septuagint as "Esdras B", and 1 Esdras is "Esdras A". 1 Esdras is a very similar text to the books of Ezra–Nehemiah, and the two are widely thought by scholars to be derived from the same original text. It has been proposed, and is thought highly likely by scholars, that "Esdras B" – the canonical Ezra–Nehemiah – is Theodotion's version of this material, and "Esdras A" is the version which was previously in the Septuagint on its own.

Final form

Some texts are found in the Septuagint but are not present in the Hebrew. These additional books are Tobit, Judith, Wisdom of Solomon, Wisdom of Jesus son of Sirach, Baruch, the Letter of Jeremiah (which later became chapter 6 of Baruch in the Vulgate), additions to Daniel (The Prayer of Azarias, the Song of the Three Children, Susanna and Bel and the Dragon), additions to Esther, 1 Maccabees, 2 Maccabees, 3 Maccabees, 4 Maccabees, 1 Esdras, Odes, including the Prayer of Manasseh, the Psalms of Solomon, and Psalm 151.

Some books that are set apart in the Masoretic Text are grouped together. For example, the Books of Samuel and the Books of Kings are in the LXX one book in four parts called Βασιλειῶν ("Of Reigns"). In LXX, the Books of Chronicles supplement Reigns and it is called Paralipomenon (Παραλειπομένων – things left out). The Septuagint organizes the minor prophets as twelve parts of one Book of Twelve.

The Orthodox
Old Testament
Greek-based
name
Conventional
English name
Law
Γένεσις Génesis Genesis
Ἔξοδος Éxodos Exodus
Λευϊτικόν Leuitikón Leviticus
Ἀριθμοί Arithmoí Numbers
Δευτερονόμιον Deuteronómion Deuteronomy
History
Ἰησοῦς Nαυῆ Iêsous Nauê Joshua
Κριταί Kritaí Judges
Ῥούθ Roúth Ruth
Βασιλειῶν Αʹ I Reigns I Samuel
Βασιλειῶν Βʹ II Reigns II Samuel
Βασιλειῶν Γʹ III Reigns I Kings
Βασιλειῶν Δʹ IV Reigns II Kings
Παραλειπομένων Αʹ I Paralipomenon I Chronicles
Παραλειπομένων Βʹ II Paralipomenon II Chronicles
Ἔσδρας Αʹ I Esdras 1 Esdras
Ἔσδρας Βʹ II Esdras Ezra–Nehemiah
Τωβίτ Tobit Tobit or Tobias
Ἰουδίθ Ioudith Judith
Ἐσθήρ Esther Esther with additions
Μακκαβαίων Αʹ I Makkabaioi 1 Maccabees
Μακκαβαίων Βʹ II Makkabaioi 2 Maccabees
Μακκαβαίων Γʹ III Makkabaioi 3 Maccabees
Wisdom
Ψαλμοί Psalms Psalms
Ψαλμός ΡΝΑʹ Psalm 151 Psalm 151
Προσευχὴ Μανάσση Prayer of Manasseh Prayer of Manasseh
Ἰώβ Iōb Job
Παροιμίαι Proverbs Proverbs
Ἐκκλησιαστής Ekklesiastes Ecclesiastes
Ἆσμα Ἀσμάτων Song of Songs Song of Solomon or Canticles
Σοφία Σαλoμῶντος Wisdom of Solomon Wisdom
Σοφία Ἰησοῦ Σειράχ Wisdom of Jesus the son of Seirach Sirach or Ecclesiasticus
Ψαλμοί Σαλoμῶντος Psalms of Solomon Psalms of Solomon
Prophets
Δώδεκα The Twelve Minor Prophets
Ὡσηέ Αʹ I. Osëe Hosea
Ἀμώς Βʹ II. Amōs Amos
Μιχαίας Γʹ III. Michaias Micah
Ἰωήλ Δʹ IV. Ioël Joel
Ὀβδίου Εʹ V. Obdias Obadiah
Ἰωνᾶς Ϛ' VI. Ionas Jonah
Ναούμ Ζʹ VII. Naoum Nahum
Ἀμβακούμ Ηʹ VIII. Ambakum Habakkuk
Σοφονίας Θʹ IX. Sophonias Zephaniah
Ἀγγαῖος Ιʹ X. Angaios Haggai
Ζαχαρίας ΙΑʹ XI. Zacharias Zachariah
Ἄγγελος ΙΒʹ XII. Messenger Malachi
Ἠσαΐας Hesaias Isaiah
Ἱερεμίας Hieremias Jeremiah
Βαρούχ Baruch Baruch
Θρῆνοι Lamentations Lamentations
Ἐπιστολή Ιερεμίου Epistle of Jeremiah Letter of Jeremiah
Ἰεζεκιήλ Iezekiêl Ezekiel
Δανιήλ Daniêl Daniel with additions
Appendix
Μακκαβαίων Δ' Παράρτημα IV Makkabees 4 Maccabees

Christian Bibles

A page from the Gutenberg Bible

A Christian Bible is a set of books that a Christian denomination regards as divinely inspired and thus constituting scripture. Although the Early Church primarily used the Septuagint or the Targums among Aramaic speakers, the apostles did not leave a defined set of new scriptures; instead the canon of the New Testament developed over time. Groups within Christianity include differing books as part of their sacred writings, most prominent among which are the biblical apocrypha or deuterocanonical books.

Significant versions of the Christian Bible in English include the Douay–Rheims Bible, the Authorized King James Version, the Revised Version, the American Standard Version, the Revised Standard Version, the New American Standard Version, the New King James Version, the New International Version, the New American Bible, and the English Standard Version.

Old Testament

The books which make up the Christian Old Testament differ between the Catholic (see Catholic Bible), Orthodox, and Protestant churches, with the Protestant movement accepting only those books contained in the Hebrew Bible, while Catholic and Orthodox traditions have wider canons. A few groups consider particular translations to be divinely inspired, notably the Greek Septuagint and the Aramaic Peshitta. The Old Testament consists of many distinct books produced over a period of centuries: The first five books – Genesis, Exodus, Leviticus, book of Numbers and Deuteronomy – reached their present form in the Persian period (538–332 BCE), and their authors were the elite of exilic returnees who controlled the Temple at that time. The books of Joshua, Judges, Samuel and Kings follow, forming a history of Israel from the Conquest of Canaan to the Siege of Jerusalem c. 587 BCE.

These history books make up around half the total content of the Old Testament. Of the remainder, the books of the various prophets – Isaiah, Jeremiah, Ezekiel, and the twelve "minor prophets" – were written between the 8th and 6th centuries BC, with the exceptions of Jonah and Daniel, which were written much later. The "wisdom" books – Job, Proverbs, Ecclesiastes, Psalms, Song of Solomon – have various dates: Proverbs possibly was completed by the Hellenistic time (332–198 BCE), though containing much older material as well; Job completed by the 6th century BCE; Ecclesiastes by the 3rd century BCE.

Apocryphal or deuterocanonical books

The contents page in a complete 80 book King James Bible, listing "The Books of the Old Testament", "The Books called Apocrypha", and "The Books of the New Testament".

In Eastern Christianity, translations based on the Septuagint still prevail. The Septuagint was generally abandoned in favour of the 10th-century Masoretic Text as the basis for translations of the Old Testament into Western languages. Some modern Western translations since the 14th century make use of the Septuagint to clarify passages in the Masoretic Text, where the Septuagint may preserve a variant reading of the Hebrew text. They also sometimes adopt variants that appear in other texts, e.g., those discovered among the Dead Sea Scrolls.

A number of books which are part of the Peshitta or the Greek Septuagint but are not found in the Hebrew Bible (i.e., among the protocanonical books) are often referred to as deuterocanonical books by Roman Catholics referring to a later secondary (i.e., deutero) canon, that canon as fixed definitively by the Council of Trent 1545–1563. It includes 46 books for the Old Testament (45 if Jeremiah and Lamentations are counted as one) and 27 for the New.

Eighty book Protestant Bibles have fourteen books in between the Old Testament and New Testament in a section called the Apocrypha. Protestant traditions traditionally teach that these books are useful for instruction, but are non-canonical. However, Eastern Orthodox Churches include these books as part of their Old Testament and the Roman Catholic Church most of them with the exception of three books.

The Roman Catholic Church recognizes:

In addition to those, the Greek and Russian Orthodox Churches recognize the following:

Russian and Georgian Orthodox Churches include:

  • 2 Esdras i.e., Latin Esdras in the Russian and Georgian Bibles

There is also 4 Maccabees which is only accepted as canonical in the Georgian Church, but was included by St. Jerome in an appendix to the Vulgate, and is an appendix to the Greek Orthodox Bible, and it is therefore sometimes included in collections of the Apocrypha.

The Syriac Orthodox tradition includes:

The Ethiopian Biblical canon includes:

and some other books.

The Revised Common Lectionary of the Lutheran Church, Moravian Church, Reformed Churches, Anglican Church and Methodist Church uses the Apocryphal Books liturgically, with alternative Old Testament readings available. Therefore, editions of the Bible intended for use in the Lutheran Church and Anglican Church include the fourteen books of the Protestant Apocrypha, many of which are the Deuterocanonical books accepted by the Catholic Church, plus 1 Esdras, 2 Esdras and the Prayer of Manasseh, which were in the Vulgate appendix.

Pseudepigraphal books

The term pseudepigrapha commonly describes numerous works of Jewish religious literature written from about 300 BCE to 300 CE. Not all of these works are actually pseudepigraphical. It also refers to books of the New Testament canon whose authorship is misrepresented or questionable. The Old Testament pseudepigraphal works include the following:

Book of Enoch

Notable pseudepigraphal works include the Books of Enoch (such as 1 Enoch, 2 Enoch, surviving only in Old Slavonic, and 3 Enoch, surviving in Hebrew, c. 5th to 6th century CE). These are ancient Jewish religious works, traditionally ascribed to the prophet Enoch, the great-grandfather of the patriarch Noah. They are not part of the biblical canon used by Jews, apart from Beta Israel. Most Christian denominations and traditions may accept the Books of Enoch as having some historical or theological interest or significance. It has been observed that part of the Book of Enoch is quoted in the Epistle of Jude (part of the New Testament) but Christian denominations generally regard the Books of Enoch as non-canonical or non-inspired. However, the Enoch books are treated as canonical by the Ethiopian Orthodox Tewahedo Church and Eritrean Orthodox Tewahedo Church.

The older sections (mainly in the Book of the Watchers) are estimated to date from about 300 BCE, and the latest part (Book of Parables) probably was composed at the end of the 1st century BCE.

Denominational views of pseudepigrapha

There arose in some Protestant biblical scholarship an extended use of the term pseudepigrapha for works that appeared as though they ought to be part of the biblical canon, because of the authorship ascribed to them, but which stood outside both the biblical canons recognized by Protestants and Catholics. These works were also outside the particular set of books that Roman Catholics called deuterocanonical and to which Protestants had generally applied the term Apocryphal. Accordingly, the term pseudepigraphical, as now used often among both Protestants and Roman Catholics (allegedly for the clarity it brings to the discussion), may make it difficult to discuss questions of pseudepigraphical authorship of canonical books dispassionately with a lay audience. To confuse the matter further, Eastern Orthodox Christians accept books as canonical that Roman Catholics and most Protestant denominations consider pseudepigraphical or at best of much less authority. There exist also churches that reject some of the books that Roman Catholics, Orthodox and Protestants accept. The same is true of some Jewish sects. Many works that are apocryphal are otherwise considered genuine.

Role of the Old Testament in Christian theology

The Old Testament has always been central to the life of the Christian church. Bible scholar N.T. Wright says "Jesus himself was profoundly shaped by the scriptures." He adds that the earliest Christians also searched those same Hebrew scriptures in their effort to understand the earthly life of Jesus. They regarded the "holy writings" of the Israelites as necessary and instructive for the Christian, as seen from Paul's words to Timothy (2 Timothy 3:15), and as pointing to the Messiah, and as having reached a climactic fulfilment in Jesus himself, generating the "new covenant" prophesied by Jeremiah.

New Testament

The New Testament is the name given to the second and final portion of the Christian Bible. Jesus is its central figure.

The term "New Testament" came into use in the second century during a controversy among Christians over whether the Hebrew Bible should be included with the Christian writings as sacred scripture. The New Testament presupposes the inspiration of the Old Testament. Some other works which were widely read by early churches were excluded from the New Testament and relegated to the collections known as the Apostolic Fathers (generally considered orthodox) and the New Testament Apocrypha (including both orthodox and heretical works).

The New Testament is a collection of 27 books of 4 different genres of Christian literature (Gospels, one account of the Acts of the Apostles, Epistles and an Apocalypse). These books can be grouped into:

The New Testament books are ordered differently in the Catholic/Orthodox/Protestant tradition, the Slavonic tradition, the Syriac tradition and the Ethiopian tradition.

Original language

The mainstream consensus is that the New Testament was written in a form of Koine Greek, which was the common language of the Eastern Mediterranean from the Conquests of Alexander the Great (335–323 BCE) until the evolution of Byzantine Greek (c. 600).

Historic editions

An early German translation by Martin Luther. His translation of the text into the vernacular was highly influential.

The original autographs, that is, the original Greek writings and manuscripts written by the original authors of the New Testament, have not survived. But historically copies exist of those original autographs, transmitted and preserved in a number of manuscript traditions. There have been some minor variations, additions or omissions, in some of the texts. When ancient scribes copied earlier books, they sometimes wrote notes on the margins of the page (marginal glosses) to correct their text – especially if a scribe accidentally omitted a word or line – and to comment about the text. When later scribes were copying the copy, they were sometimes uncertain if a note was intended to be included as part of the text.

The three main textual traditions of the Greek New Testament are sometimes called the Alexandrian text-type (generally minimalist), the Byzantine text-type (generally maximalist), and the Western text-type (occasionally wild). Together they comprise most of the ancient manuscripts.

Development of the Christian canons

St. Jerome in his Study, by Marinus van Reymerswaele, 1541. Jerome produced a 4th-century Latin edition of the Bible, known as the Vulgate, that became the Catholic Church's official translation.

The Old Testament canon entered into Christian use in the Greek Septuagint translations and original books, and their differing lists of texts. In addition to the Septuagint, Christianity subsequently added various writings that would become the New Testament. Somewhat different lists of accepted works continued to develop in antiquity. In the 4th century a series of synods produced a list of texts equal to the 39, 46, 51, or 54-book canon of the Old Testament and to the 27-book canon of the New Testament that would be subsequently used to today, most notably the Synod of Hippo in 393 CE. Also c. 400, Jerome produced a definitive Latin edition of the Bible (see Vulgate), the canon of which, at the insistence of the Pope, was in accord with the earlier Synods. With the benefit of hindsight, it can be said that this process effectively set the New Testament canon, although there are examples of other canonical lists in use after this time.

The Protestant Old Testament of today has a 39-book canon – the number of books (though not the content) varies from the Jewish Tanakh only because of a different method of division – while the Roman Catholic Church recognizes 46 books (51 books with some books combined into 46 books) as the canonical Old Testament. The Eastern Orthodox Churches recognize 3 Maccabees, 1 Esdras, Prayer of Manasseh and Psalm 151 in addition to the Catholic canon. Some include 2 Esdras. The term "Hebrew Scriptures" is often used as being synonymous with the Protestant Old Testament, since the surviving scriptures in Hebrew include only those books, while Catholics and Orthodox include additional texts that have not survived in Hebrew. Eighty book Protestant Bibles include 14 books called Apocrypha in between the Old Testament and the New Testament that are deemed useful for instruction but non-canonical. Both Catholics and Protestants (as well as Greek Orthodox) have the same 27-book New Testament Canon.

The New Testament writers assumed the inspiration of the Old Testament, probably earliest stated in 2 Timothy 3:16, "All scripture is given by inspiration of God".

Some denominations have additional canonical holy scriptures beyond the Bible, including the standard works of the Latter Day Saints movement and Divine Principle in the Unification Church.

Ethiopian Orthodox canon

The Canon of the Ethiopian Orthodox Tewahedo Church is wider than the canons used by most other Christian churches. There are 81 books in the Ethiopian Orthodox Bible. The Ethiopian Old Testament Canon includes the books found in the Septuagint accepted by other Orthodox Christians, in addition to Enoch and Jubilees which are ancient Jewish books that only survived in Ge'ez but are quoted in the New Testament, also Greek Ezra First and the Apocalypse of Ezra, 3 books of Meqabyan, and Psalm 151 at the end of the Psalter. The three books of Meqabyan are not to be confused with the books of Maccabees. The order of the other books is somewhat different from other groups', as well. The Old Testament follows the Septuagint order for the Minor Prophets rather than the Jewish order.

Peshitta

The Peshitta (Classical Syriac: ܦܫܺܝܛܬܳܐor ܦܫܝܼܛܬܵܐ pšīṭtā) is the standard version of the Bible for churches in the Syriac tradition. The consensus within biblical scholarship, although not universal, is that the Old Testament of the Peshitta was translated into Syriac from biblical Hebrew, probably in the 2nd century AD, and that the New Testament of the Peshitta was translated from the Greek. This New Testament, originally excluding certain disputed books (2 Peter, 2 John, 3 John, Jude, Revelation), had become a standard by the early 5th century. The five excluded books were added in the Harklean Version (616 AD) of Thomas of Harqel.

Divine inspiration

A Bible is placed centrally on a Lutheran altar, highlighting its importance

The Second Epistle to Timothy says that "all scripture is given by inspiration of God, and is profitable for doctrine, for reproof, for correction, for instruction in righteousness". (2 Timothy 3:16) Various related but distinguishable views on divine inspiration include:

  • the view of the Bible as the inspired word of God: the belief that God, through the Holy Spirit, intervened and influenced the words, message, and collation of the Bible
  • the view that the Bible is also infallible, and incapable of error in matters of faith and practice, but not necessarily in historic or scientific matters
  • the view that the Bible represents the inerrant word of God, without error in any aspect, spoken by God and written down in its perfect form by humans

Within these broad beliefs many schools of hermeneutics operate. "Bible scholars claim that discussions about the Bible must be put into its context within church history and then into the context of contemporary culture." Fundamentalist Christians are associated with the doctrine of biblical literalism, where the Bible is not only inerrant, but the meaning of the text is clear to the average reader.

Jewish antiquity attests to belief in sacred texts, and a similar belief emerges in the earliest of Christian writings. Various texts of the Bible mention divine agency in relation to its writings. In their book A General Introduction to the Bible, Norman Geisler and William Nix write: "The process of inspiration is a mystery of the providence of God, but the result of this process is a verbal, plenary, inerrant, and authoritative record." Most evangelical biblical scholars associate inspiration with only the original text; for example some American Protestants adhere to the 1978 Chicago Statement on Biblical Inerrancy which asserted that inspiration applied only to the autographic text of Scripture. Among adherents of Biblical literalism, a minority, such as followers of the King-James-Only Movement, extend the claim of inerrancy only to a particular version.

Versions and translations

Title page from the first Welsh translation of the Bible, 1588. William Morgan (1545–1604)

The original texts of the Tanakh were almost entirely written in Hebrew; about one per cent is written in Aramaic. In addition to the authoritative Masoretic Text, Jews still refer to the Septuagint, the translation of the Hebrew Bible into Greek, and the Targum Onkelos, an Aramaic version of the Bible. There are several different ancient versions of the Tanakh in Hebrew, mostly differing by spelling, and the traditional Jewish version is based on the version known as Aleppo Codex. Even in this version there are words which are traditionally read differently from written, because the oral tradition is considered more fundamental than the written one, and presumably mistakes had been made in copying the text over the generations.

The primary biblical text for early Christians was the Septuagint. In addition, they translated the Hebrew Bible into several other languages. Translations were made into Syriac, Coptic, Ethiopic, and Latin, among other languages. The Latin translations were historically the most important for the Church in the West, while the Greek-speaking East continued to use the Septuagint translations of the Old Testament and had no need to translate the New Testament.

The earliest Latin translation was the Old Latin text, or Vetus Latina, which, from internal evidence, seems to have been made by several authors over a period of time. It was based on the Septuagint, and thus included books not in the Hebrew Bible.

According to the Latin Decretum Gelasianum (also known as the Gelasian Decree), thought to be of a 6th-century document of uncertain authorship and of pseudepigraphal papal authority (variously ascribed to Pope Gelasius I, Pope Damasus I, or Pope Hormisdas) but reflecting the views of the Roman Church by that period, the Council of Rome in 382 CE under Pope Damasus I (366–383) assembled a list of books of the Bible. Damasus commissioned Saint Jerome to produce a reliable and consistent text by translating the original Greek and Hebrew texts into Latin. This translation became known as the Latin Vulgate Bible, in the fourth century CE (although Jerome expressed in his prologues to most deuterocanonical books that they were non-canonical). In 1546, at the Council of Trent, Jerome's Vulgate translation was declared by the Roman Catholic Church to be the only authentic and official Bible in the Latin Church.

Since the Protestant Reformation, Bible translations for many languages have been made. The Bible continues to be translated to new languages, largely by Christian organizations such as Wycliffe Bible Translators, New Tribes Mission and Bible societies.

Bible translations, worldwide (as of October 2020)
Number Statistic
7,360 Approximate number of languages spoken in the world today
2,731 Number of translations into new languages in progress
1,551 Number of languages with a translation of the New Testament
704 Number of languages with a translation of the Bible (Protestant Canon)

Views

John Riches, professor of Divinity and Biblical Criticism at the University of Glasgow, provides the following view of the diverse historical influences of the Bible:

It has inspired some of the great monuments of human thought, literature, and art; it has equally fuelled some of the worst excesses of human savagery, self-interest, and narrow-mindedness. It has inspired men and women to acts of great service and courage, to fight for liberation and human development; and it has provided the ideological fuel for societies which have enslaved their fellow human beings and reduced them to abject poverty. ... It has, perhaps above all, provided a source of religious and moral norms which have enabled communities to hold together, to care for, and to protect one another; yet precisely this strong sense of belonging has in turn fuelled ethnic, racial, and international tension and conflict.

Other religions

In Islam, the Bible is held to reflect true unfolding revelation from God; but revelation which had been corrupted or distorted (in Arabic: tahrif); which necessitated the giving of the Qur'an to the Islamic prophet, Muhammad, to correct this deviation.

Members of other religions may also seek inspiration from the Bible. For example, Rastafaris view the Bible as essential to their religion and Unitarian Universalists view it as "one of many important religious texts".

Biblical studies

Biblical criticism refers to the investigation of the Bible as a text, and addresses questions such as authorship, dates of composition, and authorial intention. It is not the same as criticism of the Bible, which is an assertion against the Bible being a source of information or ethical guidance, or observations that the Bible may have translation errors.

Higher criticism

In the 17th century, Thomas Hobbes collected the current evidence to conclude outright that Moses could not have written the bulk of the Torah. Shortly afterwards the philosopher Baruch Spinoza published a unified critical analysis, arguing that the problematic passages were not isolated cases that could be explained away one by one, but pervasive throughout the five books, concluding that it was "clearer than the sun at noon that the Pentateuch was not written by Moses ..."

Archaeological and historical research

Biblical archaeology is the archaeology that relates to and sheds light upon the Hebrew Scriptures and the Christian Greek Scriptures (or the New Testament). It is used to help determine the lifestyle and practices of people living in biblical times. There are a wide range of interpretations in the field of biblical archaeology. One broad division includes biblical maximalism which generally takes the view that most of the Old Testament or the Hebrew Bible is based on history although it is presented through the religious viewpoint of its time. It is considered to be the opposite of biblical minimalism which considers the Bible to be a purely post-exilic (5th century BCE and later) composition. Even among those scholars who adhere to biblical minimalism, the Bible is a historical document containing first-hand information on the Hellenistic and Roman eras, and there is universal scholarly consensus that the events of the 6th century BCE Babylonian captivity have a basis in history.

The historicity of the biblical account of the history of ancient Israel and Judah of the 10th to 7th centuries BCE is disputed in scholarship. The biblical account of the 8th to 7th centuries BCE is widely, but not universally, accepted as historical, while the verdict on the earliest period of the United Monarchy (10th century BCE) and the historicity of David is unclear. Archaeological evidence providing information on this period, such as the Tel Dan Stele, can potentially be decisive. The biblical account of events of the Exodus from Egypt in the Torah, and the migration to the Promised Land and the period of Judges are not considered historical in scholarship.

Bible museums

 

Criticism of Buddhism

From Wikipedia, the free encyclopedia

Criticism of Buddhism has taken numerous different forms, including that its practitioners act in ways contrary to Buddhist principles or that those principles systemically marginalize women. There are many sources of criticism, both ancient and modern, stemming from other religions, the non-religious, and other Buddhists.

Criticism of Buddhist practices

Women in Buddhism

Most schools of Buddhism have more rules for bhikkunis (nuns) than bhikkus (monk) lineages. Theravada Buddhists explain that in the time of the Buddha, nuns had such problems like safety if they were to be ordained the same way as monks who traveled around in the forest and between cities. Thus, more rules have to be created for nuns; for instance: nuns are forbidden to travel alone.

Alexander Berzin referred to the Dalai Lama's statement at the 2007 Hamburg congress:

Sometimes in religion there has been an emphasis on male importance. In Buddhism, however, the highest vows, namely the bhikshu and bhikshuni ones, are equal and entail the same rights. This is the case despite the fact that in some ritual areas, due to social custom, bhikshus go first. But Buddha gave the basic rights equally to both sangha groups. There is no point in discussing whether or not to revive the bhikshuni ordination; the question is merely how to do so properly within the context of the Vinaya.

The most criticised doctrine is found in Amida Buddha's vow 35: "The Buddha established the Vow of transformation [women] into men, Thereby vowing to enable women to attain Buddhahood". Earlier limitations on attainment of Buddhahood by women were abolished in the Lotus Sutra which opened the direct path to enlightenment for women equally to men. According to Nichiren "Only in the Lotus Sutra do we read that a woman who embraces this sutra not only excels all other women but surpasses all men".

Nationalism

In medieval Southeast Asia, there were a number of Buddhist states, including the Pagan Kingdom, the Sukhothai Kingdom, and the Kingdom of Polonnaruwa. In Sri Lanka especially, modern monks frequently involve themselves in nationalist politics. These Buddhist nationalists have been opposed by the Sarvodaya Shramadana Movement, a self-governance movement led by the Buddhist A. T. Ariyaratne and based in Buddhist ideals, who condemn the use of violence and the denial of human rights to Tamils and other non-Buddhists.

Maung Zarni, a Burmese democracy advocate, human rights campaigner, and a research fellow at the London School of Economics who has written on the violence in Myanmar and Sri Lanka, states that there is no room for fundamentalism in Buddhism. "No Buddhist can be nationalistic," said Zarni, "There is no country for Buddhists. I mean, no such thing as ‘me,’ ‘my’ community, ‘my’ country, ‘my’ race or even ‘my’ faith."

Accusations of violence

Violence in Buddhism refers to acts of violence and aggression committed by Buddhists with religious, political, and socio-cultural motivations. Buddhism is generally seen as among the religious traditions least associated with violence, but in the history of Buddhism there have been acts of violence directed, fomented or inspired by Buddhists.

Criticism of Buddhist doctrine

Accusations of nihilism

Friedrich Nietzsche, through Schopenhauer whose pessimism was highly influenced by Buddhist philosophy, interpreted Buddhism as a life-negating philosophy that seeks to escape an existence dominated by suffering. According to Omar Moad, Nietzsche misunderstood the meaning of Buddhist doctrine. The term Dukkha has several different meanings. Dukkha may mean disappointment, desires, cravings, bereavement, unfulfillment, or dissatisfaction. Nevertheless dukkha always has a negative connotation, with different proposed English translations merely varying in degree of negativity.

Lama Surya Das emphasizes the matter-of-fact nature of Dukkha:

Buddha Dharma does not teach that everything is suffering. What Buddhism does say is that life, by its nature, is difficult, flawed, and imperfect. [...] That's the nature of life, and that's the First Noble Truth. From the Buddhist point of view, this is not a judgement of life's joys and sorrows; this is a simple, down-to-earth, matter-of-fact description.

While the Buddha describes the flawed and imperfect nature of life in the first noble truth, he also points to the causes that underlie this imperfection and how to bring these causes to an end. Therefore Buddhism can be said to be optimistic with regard to the ability to overcome suffering even if it is pessimistic with regard to many aspects of everyday life.

Confucian criticism

Buddhism is sometimes seen as antithetical to much of Confucian philosophy. Due to the focus on social roles as the source of ethical obligation in Confucianism compared to the seemingly inherent nonconformity of Buddhism, there was a sustained ethical critique of Buddhism in early Confucianism. While Buddhism entails the belief there is nothing rightfully considered the self, Confucianism emphasized the self a great deal in their doctrines of self-development and societal roles. As a consequence Buddhism was considered by many to be nihilistic.

Arguments of secular origin

Sam Harris, a prominent proponent of New Atheism and practitioner of Buddhist meditation, claims that many practitioners of Buddhism improperly treat it as a religion, criticizes their beliefs as "naive, petitionary, and superstitious," and claims that such beliefs impede the spread of Buddhist principles. However, he has also underlined that these beliefs stem from the tendency of some Buddhists to not follow a fundamental teaching of Buddhism; namely, to believe a teaching only with sufficient evidence.

Stephen Batchelor, author of "Buddhism without Beliefs" has written about karma and rebirth, asserting that the Buddha “did not claim to have had experience that granted him privileged, esoteric knowledge of how the universe ticks”. However, his critics point out that his assertion is contrary to the earliest written records of the Buddha's teaching as well as hundreds of years of academic study on the topic. They also point to a lack of scholarly research on Batchelor's part to give credibility to his claims; and suggest that Batchelor may be attempting to reshape Buddhism due to his own discomfort with concepts such as karma and rebirth.

Criticism from Hinduism

There has been a long tradition of philosophical debate between Buddhism and Hinduism. Many ancient, mediaeval and modern Hindu philosophers have criticised various doctrines of Buddhism.

Criticism from Gaudapada

Gaudapada, a mediaeval philospher of the Advaita Vedanta tradition and a teacher of Adi Shankara, has criticised the Buddha in his Karikas on the Mandukya Upanishad. The 99th Karika of 4th chapter says -

The knowledge of the wise one, who is all-light, is ever untouched by objects. All the entities as well as knowledge (which are non-different) are also ever-untouched by any object. This is not the view of the Buddha.

Criticism from Adi Shankara

Adi Shankara, a very influential expounder of the Advaita Vedanta philosophy, has criticised many doctrines of Buddhism in many of his commentaries. However, his most direct criticism of Buddhism is found in his commentary on the Sutra 2.2.32 of the Brahma Sutras. In the commentary of this sutra, Shankara says -

किं बहुना सर्वप्रकारेण यथा यथायं वैनाशिकसमय उपपत्तिमत्त्वाय परीक्ष्यते तथा तथा सिकताकूपवद्विदीर्यत एव न कांचिदप्यत्रोपपत्तिं पश्यामः अतश्चानुपपन्नो वैनाशिकतन्त्रव्यवहारः। अपि च बाह्यार्थविज्ञानशून्यवादत्रयमितरेतरविरुद्धमुपदिशता सुगतेन स्पष्टीकृतमात्मनोऽसंबद्धप्रलापित्वम् प्रद्वेषो वा प्रजासु विरुद्धार्थप्रतिपत्त्या विमुह्येयुरिमाः प्रजा इति। सर्वथाप्यनादरणीयोऽयं सुगतसमयः श्रेयस्कामैरित्यभिप्रायः।।

In brief, whenever we examine the doctrine of the Vainashikas for its tenability, it falls apart like a pit of sand, therefore it is untenable. The Buddha taught the three contradictory doctrines of impermanence, momentary-knowledge and emptiness. He was uttering confused speech, because he either hated the people, or he intended to delude the people by teaching them contradictory docrtines. The doctrine of Buddha is not worthy of respect for those who are desirous of Moksha.

Wednesday, June 23, 2021

Anticancer gene

From Wikipedia, the free encyclopedia

Anticancer genes are genes that, when ectopically overexpressed, specifically destroy tumour cells without harming normal, untransformed cells. This cellular destruction can be due to a variety of mechanisms, such as apoptosis, mitotic catastrophe followed by apoptosis or necrosis, and autophagy. Anticancer genes emerged from studies on cancer cells in the late 1990s. Currently, there have been 291 anticancer genes discovered in the human genome. In order to be classified as an anticancer gene, the gene must have base substitutions leading to missense amino-acid changes, deletions, or insertions leading to frameshifts that alter the protein the gene codes for, increases and decreases in copy-number increases, or gene rearrangements leading to their deregulation.

Anticancer genes as therapeutics

Cancer is classified as a group of diseases, all of which are characterized by uncontrolled cell proliferation. In normal functioning cells, apoptosis is induced to avoid these proliferative events. However, these processes may continue on to become cancer in the event the processes become dysregulated. Epidemiological studies have shown cancer to be a leading cause of death worldwide  (Figure 1). Current advancements in therapeutics have led to a substantial increase in patient survival rates.

Common anticancer gene examples

APOPTIN

History

Apoptin was the first anticancer gene to be isolated. This gene comes from the single, circular minus-strand DNA found in the Chicken Anemia Virus (CAV) genome. This virus belongs to the Gyrovirus genus, and is currently being studied as a new cancer therapeutic and diagnostic tool. This protein, also known as viral protein 3 (VP3) was isolated from chickens, and has been shown to cause PCD in transformed human cells.

Action

This protein encoded for by Apoptin has the specific capability of attacking transforming cells while leaving untransformed cells unharmed. Independent of p53, Apoptin induces apoptosis through an intrinsic, mitochondrial pathway. And unlike other PCD pathways, the pathway of Apoptin is independent of death receptors. In normal functioning cells, this 13.6-kDa protein resides in the cytoplasm, yet in cancerous cells, it travels to the nucleus via phosphorylation at the Thr-108 position via the mitogenic cyclin dependent kinase (CDK2). Additionally, this protein does not act alone. Several Apoptin-interacting molecules are needed in order for Apoptin to be fully functional. These molecules include, but not limited to, DNA, clyclinA-CDK2, and fas-associated death domain protein (FADD). Current apoptin therapeutic agents have been used to treat Lewis lung carcinomas, and osteosarcomas with future implications in treating liver cancers.

Brevinin-2R

History

Figure 2 Depiction of Rana ridibunda.

Brevinin-2R is a peptide product isolated from the skin of the frog Rana ridibunda (Figure 2). This non-hemolytic defensin has been shown to have preferential cytotoxicity towards various cancer cells including B-cell lymphoma, colon carcinomas, lung carcinomas, and breast adenocarcinoma. Currently, this peptide and two of its analogs, Brevinin-2R-C and Brevinin-2R-D, are being explored for cancer drug development. A phylogenetic analysis shows that Brevinin-2 is segregated into three major clades: A, B and C, where clade A contains the Brevining-2R homolog.

Action

This 25 amino acid peptide, in contrast to the majority of peptides within the Brevinin family, has low hemolytic action. Not only does the peptide have a reduced hemolytic action, it also is semi-selective towards cancer cells and leaves non cancerous cells largely unharmed. This peptide works as to prevent the progression of cancer by arresting the cell cycle at the G2/M phase, resulting in an induction of apoptosis.

This defensin traditionally works as a part of the innate immune system, working as an antimicrobial defense. However, this peptide is currently being studied as an anticancer peptide. Brevinin-2R works to trigger cell death by reducing the mitochondrial membrane potential resulting in lower cellular ATP levels while simultaneously increasing the concentration of reactive oxygen species. Currently and somewhat unrelated, Brevinin-2R is being considered for diabetic treatments. In treating type II diabetes, or diabetes mellitus, Brevinins have been shown to promote insulin release. Finally, these peptides even have the capability to increase the rate of tissue regeneration, as seen with the frog in which Brevinin-2R was isolated from.

E4orf4

History

Early region 4 open-reading-frame 4 (E4orf4) is an adenovirus protein of 14kDa which regulates growth in all stages of the adenovirus (Ad) infection. E4orf4 partners mainly with protein phosphatase 2A (PP2A) and Src kinases to induce cell death. Modeling of this protein reveals that it is likely made up of 3 α-helices with N- and C-terminal loops. It has a small stretch of amino acids in positions 66–75, which are highly basic, and likely are a place of nuclear and nucleolar targeting, as well as a place for Src kinases to bind.

Action

E4orf4 is an important regulator of adenoviruses. Additionally, outside of the context of the virus, it causes programmed cell death both in the context of a healthy cellular environment, and cancer. E4orf4 is a key regulator of Ad by down-regulating both viral and cellular genes, which plays an important role in regulating the proliferation of the virus. In turn, the down-regulation also impacts the alternative splicing of the viral RNA and protein translation. In the absence of a viral infection, E4orf4 induces apoptosis in a p53 and caspase-independent manner; however, there is still communication between this pathway and the caspase-dependent apoptosis pathway. In the context of cancer, E4orf4 is even more efficient at inducing cell death than in healthy cells, which could be an important finding for potential cancer therapies. It has been discovered that the mechanisms behind the function of E4orf4 is closely associated with several other proteins including the B55 subunit of PP2A. E4orf4 binds to PP2A to reduce the phosphorylation of the DNA damage response (DDR) proteins. Consequently, this reduces the function of DDR and limits DNA repair. Many cancer cells have defects in the DDR pathways and targeting these cells with E4orf4 can potentially destroy the remaining DDR pathways, resulting in cancer cell death.

The main mechanism behind the specificity of cancer cell targeting by E4orf4 is unknown but there are multiple hypotheses that scientists are considering: 1) The activation of the oncogenic state causes dormant apoptotic signals to be initiated and cause cell death to be more easily achieved by different signals. 2) There has been some indication that cancer cells become addicted to oncogenic pathways. E4orf4 may inhibit these pathways, causing cell death in cancer cells, but not normal cells. 3) E4orf4 may use oncogenes that have been activated in cancer cells, including Src, to cause cell death. 4) Cancer cells have disrupted cell cycle checkpoints and E4orf4 can take advantage of this by disrupting checkpoints in mitosis. 5) A Drosophila model demonstrated that E4orf4 can inhibit classical apoptosis in healthy tissues. It has been considered that this function of E4orf4 is lost in cancer cells causing a more effective killing of cells. 6) E4orf4 has been shown to cause structural changes in mitochondria, which could impact metabolic reprogramming and may affect cancer and healthy cells differently.

Figure 3: Crystal Structure of Calcium-bound α-lactalbumin.

HAMLET

History

HAMLET is known as an anticancer protein complex found in breast milk. One of the two molecules of this complex is multimeric alpha lactalbumin (MAL) (Figure 3), which was first discovered during a study in 1995 that investigated how breast milk affects bacteria transformed with lung cancer. This study found that transformed cells were selected for apoptosis at a much higher rate than the untransformed, healthy cells. A later study in 2000, ascertained that oleic acid, a C18:1 fatty acid, is a cofactor that binds to MAL forming HAMLET. This complex, in a partially unfolded state, then displays apoptotic activity in cancer cells.

Action

Apoptosis, or programed cell death, can occur through activation of three different pathways, intrinsic, extrinsic, or tumor necrosis factor. HAMLET proceeds by both a multifaceted intrinsic pathway and the caspase cascade, a subsection of the TNF pathway, through targeting many different cell components. First, after uptake by the cell, HAMLET proceeds to the mitochondria and depolarize the membranes at cytochrome c. Consequently, mitochondria dependent apoptosis factors are released as well as the caspase cascade is activated. Second, proteasomes are targeted by HAMLET through a mechanism that is less understood. Research does suggest that HAMLET directly binds to the proteasome leading to its inhibition. Third, HAMLET has been found to target the nucleus, specifically histones. HAMLET irreversibly binds to histones leading to the inactivation of transcription and chromatin condensation, which inevitably causes apoptosis. Lastly, studies show that cells treated by HAMLET exhibit behaviors common to macroautophagy. This includes presence of cytoplasmic vacuoles, double-membrane vesicles, and a dose-dependent decrease in ATP levels.

MDA-7

History

Melanoma differentiation associated gene-7 (mda-7), and also known as IL-24, was discovered in the mid-1900s using subtraction hybridization. mda-7 is classified in the interleukin IL-10 family because of similar structure and amino acid sequence to other interleukins in that class, the chromosomal location (human chromosome 1q32-33), and the shared properties it has with cytokines. Protein structural studies reveal that it is a dimer and glycolsylated. It has been found that its expression is either not present or present at very low levels in tumor cells, including advanced stage melanoma and metastatic disease, compared to normal non-transformed cells. Multiple studies within the past 15 years have demonstrated that increasing mda-7 expression in tumor cells results in growth arrest and cell death in many different cell lines. When mda-7 is over-expressed in normal cells, no change in growth or cell viability is detected. mda-7 is also considered a radio-sensitizing cytokine because it generates a reactive oxygen species and causes stress in endoplasmic reticulum. mda-7 has been used in several clinical trials because of its ability to induce apoptosis, prevent tumor angiogenesis, cause immune-regulation, and increase radiation lethality. It was seen in one Phase I clinical trial that injecting mda-7 via an adenovirus directly into a tumor resulted in safe tumor regulation and immune activation.

Action

mda-7 interacts with two of the type II cytokine hetero-dymeric receptor complexes IL-20R1/IL-20R2 and IL-22R1/IL-20R2. It has been seen that in some contexts, mda-7 activates STAT transcription factors. However, the STAT pathway is not always activated and is not required for mda-7 cell growth arrest and cell death. mda-7 can be placed into tumor cell lines via transfection or adenovirus-transduction; it has been seen that following this, apoptosis is induced only in the tumor cells and results in no toxicity in the healthy cells. Its function as a tumor suppressor is not fully understood, but it has been observed that in the context of melanoma, mda-7 expression is drastically decreased. While there are no official studies published backing this claim, it is thought that mda-7 could potentially act as a paracrine factor, be involved in signaling short-range, and immune function in skin. mda-7 is also thought to have a pro-inflammatory purpose. It is also possible that mda-7 induces cytokine secretion, which causes antigen-presenting cells to present tumor antigens, resulting in an immune response against tumors. It has also been discovered that mda-7, and its translated protein MDA-7, interacts with kinases including serine/threonine protein kinase (PKR). Further studies will need to be performed to better understand the mechanisms of mda-7 action.

NOXA

History

Figure 4: Depiction of T-Cells, T-Helper Cells, and B-Cells (CD4+) working to illicit an immune response.

Noxa, isolated from mice, is a member of the Bcl-2 family and is able to regulate cell death through a variety of intracellular stress signals. Having been discovered nearly three decades ago in 1990 by Hijikata et al., this gene product was isolated this protein from an adult T-cell leukemia (ATL) library This gene, and its protein in which it encodes for, has been studied as a potential therapeutic in chronic lymphocytic leukemia (CLL), the most common leukemia found in adults in the Western world. In humans, the Noxa homologue is known as APR/PMAIP1.

Action

Upon receiving intrinsic death signals, the gene NOXA encodes for the protein Noxa through a three-exon transcript. This protein binds to anti-apoptotic proteins resulting in these proteins' inhibition. As a p53 inducible gene, NOXA is transcribed and translated to Noxa in response to DNA damage and hypoxia induced apoptosis. A constitutive gene found in the brain, thymus, spleen, and several other organs, it initiates apoptosis through Bax-mediated mitochondrial-dysfunction through the inhibition of the Bcl2 family's antiapoptotic members. Through gene knockout studies, it was shown that double deficient Noxa there was no spontaneous tumor development as commonly observed with knockout of p53. Noxa has been shown to be involved in the maintenance of memory CD4+ T Th1/Th2 cell homeostasis where in the absence of Noxa, Th2 memory T-cell death results.[20]

NS1

History

In the 1960s rodent parvovirus was discovered by Dr. Helene Toolan to have an oncosuppressive activity. However, the specific gene found in the parvovirus genome, which is called NS1, that causes the oncosuppressive activity was not characterized until later. NS1 is a small protein (only 672 amino acids) with 5 distinct domains that exert different functions that inevitably lead to apoptosis and cell death. NS1 activates cell death through two different pathways, apoptosis/lysosomal-like programed cell death and necrosis/cytolysis.

Action

NS1 is considered a regulatory protein due to its activity in transcription, translation, and protein-protein interactions, which allows the parvovirus to replicate unhindered. However, scientists are primarily interested in utilizing its cytolytic activity since this has been proven to be active in cancerous cells. The first way NS1 propagates cell death through cytolysis is by interrupting the cell cycle at the S/G2 junction, causing a stress response in the cell. Specifically, NS1 interacts with many molecules and compounds important in the transition and inhibits their activity. When NS1 expression reaches a certain threshold, the triggered stress response finally causes caspase 3/9-mediated programmed cell death. Another way that NS1 causes cytolysis is through degradation of the cytoskeleton of the cell. NS1 specifically targets and degrades the microfilament tropomyosin using casein kinase II, actin filaments through activation of actin-severing protein gelsolin, and vimentin through an unknown mechanism. The last NS1-mediated mechanism of cytolysis involves the depolarization of the mitochondria. This results in the release of many reactive oxygen species, causing DNA damage. When DNA is damaged, a DNA damage response occurs, which in this case results in cell death.

ORCTL3

History

Organic Cation Transporter Like-3 (ORCTL3) was first discovered as a result of a large-scale DNA sequencing project in search of genes with a tumor-specific apoptosis activity. The name ORCTL3 was decided upon because of its structural homology to proteins belonging to the family of organic cation transporters. However, the name is a misnomer as after examining the properties of ORCTL3, it was revealed that ORCTL3 is a transporter for urate. The ORCTL3 gene spans around 12 kb of genomic DNA and consists of ten exons. It was shown that the 2.4 kb transcript of this gene is universally expressed in all human tissues. Additionally, ORCTL3 transfection into numerous tumorigenic cells induced apoptosis, while normal and primary cells remained healthy.

Action

ORCTL3 is a 90 kDa protein composed of 351 amino acids. It is suggested that the protein spans the cell membrane several times, based on computational methods. Overexpressed ORCTL3 is localized to the endoplasmic reticulum (ER), Golgi and the plasma membrane but not to mitochondria. ORCTL3 was identified as the first high-affinity nicotinate exchanger in kidneys and intestine. Nicotinate is an essential vitamin (Vitamin B3) that is involved in NAD+ synthesis, which in turn is important for energetic processes, signal transduction pathways, and the activation of the NAD+ -dependent histone deacetylase SIRT1. ORCTL3 has been shown to be activated for apoptosis induction in renal cells in vitro, in vivo and ex vivo. For its apoptosis effect ORCTL3 targets stearoyl-CoA desaturase (SCD), an enzyme that introduces a double bond in the fatty acid stearic acid. The fact that SCD is commonly overexpressed in cancer and oncogene transformed cells might explain the tumor-specificity of ORCTL3 to some extent, however, the existence of other additional targets of ORCTL3 cannot formally be ruled out.

Par-4

History

Prostate apoptosis response-4 (Par-4) is a tumor suppressor protein with a pro-apoptotic function. Par-4 was first discovered in rat prostate cancer cells as part of an effort determined in discovering genes that were induced in response to increased Ca2+ in cells, although it is now known to be ubiquitously expressed in a wide variety of tissues across many different species. The Par-4 gene is located on the minus strand of chromosome 12q21.2, spanning 99.06 kb of DNA and containing seven exons and six introns. Par-4 is known to be downregulated in certain terminally differentiated cells such as neurons, specific retinal cells, and smooth muscle cells as well as in certain cancer cells such as renal cancers, neuroblastoma, and leukemia. Par-4 has also been shown to be generally higher in dying cells, consistent with its pro-apoptotic functions.

Action

Par-4 is a 38 kDa multi-domain protein composed of about 340 amino acids. Conserved domains among human, mouse, and rat homologs include the leucine zipper (LZ) domain at the C-terminal region, two nuclear localization sequences, NLS1 and NLS2, in the N-terminal region, and a nuclear export sequence within the LZ domain. Although Par-4 mutations are rare, it was identified that an A to T point mutation affecting residue 189 localized in exon 3 causes premature termination of Par-4 in human endometrial carcinoma. Knockout of Par-4 in mice leads to the development of spontaneous tumors in various tissues revealed by increased proliferative response of peripheral T cells, inhibition of apoptosis, increased NF-κB activity, and decreased JNK activity. Par-4 overexpression is sufficient to induce apoptosis in most cancer cells in the absence of a second apoptotic signal, but does not induce apoptosis in normal or immortalized cells.

The anticancer function of Par-4 is achieved by two distinct means: activating the molecular components of the cell-death machinery and inhibiting pro-survival factors. One essential apoptotic function of Par-4 is inhibiting the NF-κB pathway, which is a key contributing factor in many tumors and prevents cell death by activating the expression of pro-survival genes. Par-4 also assists in PCD by enabling the trafficking of specific ligands such and cell surface death receptors, such as FasL and Fas, respectively, to the plasma membrane thus activating the extrinsic death pathway. Overexpression of Par-4 selectively induces apoptosis in cancer cells, attributed to the selective activation via phosphorylation of the T155 residue by protein kinase A (PKA). It has been shown that two events are required for Par-4 activation: nuclear entry and phosphorylation by PKA.

Figure 5: Crystal Structure of Human TRAIL.

TRAIL

History

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (Figure 5) is a member of the tumor necrosis factor (TNF) family that also includes Fas ligands, TNFα, and TL1A. It was discovered in 1995 by Wiley et al. and then further characterized in 1996 by Pitti et al. The former study discovered that TRAIL is localized to surfaces of cells in most human tissues, excluding the brain, liver, and testes, while the latter study was able to elicit that the protein is a type II membrane protein that can also be cleaved into a soluble form.

Action

The intrigue surrounding TRAIL is all due to this protein's ability both in vivo and in vitro to specifically target tumor cells for apoptosis while leaving healthy cells intact. This activity proceeds by both the intrinsic and extrinsic pathway. First, the homotrimer of TRAIL binds three molecules of either TRAIL-receptor 1 or 2, which are transmembrane proteins that contain a cytoplasmic death domain. Once TRAIL is bound, Fas, caspase-8, and caspase-10 associate with the death domain forming death-inducing signaling complex (DISC) that proceeds through two different mechanisms depending on the cell type. In one cell type, DISC can directly activate the effector caspase leading to apoptosis, while in the other the complex activates a bcl-2-mediated pathway in a similar fashion as HAMLET that results in the release of cytochrome c from the mitochondria, which then causes the activation of effector caspase. The latter mechanism is the focus of many oncogenic therapies because p53, the tumor suppressor gene, activates the same pathway. Since cancer is commonly caused by the inactivation of p53, TRAIL could mediate this effect by still activating the apoptotic pathway.

Figure 6: Structure of TP53 bound to DNA.

TP53

History

TP-53 (Figure 6) is a gene that encodes for the protein p53; this protein is a tumor suppressor. p53 was discovered in 1979 stemming from a study involving cancer immunology and the role of viruses in some cancers. The protein was so named because it was measured to have a weight of 53 kDa. This study was conducted by David Philip Lane and technician Alan K. Roberts, in Lionel V. Crawford's lab in London. It was seen in this study that p53 could bind to viral tumor antigens. This information was corroborated during the same year when a separate study found that p53 had immunoreactivity with serum from tumors containing antibodies. This later study was run by Daniel I. H. Linzer and Arnold J. Levine out of Princeton University. Further papers came out around the same time all mentioning the discovery of a tumor suppressing protein. While p53 was first officially identified in 1979, many labs in previous years had come across the same protein, without knowing what it was. In the mid-1970s, a scientist by the name of Peter Tegtmeyer happened upon a protein with an approximate size of 50 kDa. However, because he was focusing his studies on SV40, a tumor-causing virus affecting monkeys and humans, he did not pay much attention to this protein.

Action

The p53 protein is a tumor-suppressing transcription factor (TF), which can recognize when there is an alteration in a cell's DNA caused by factors including chemical toxins, radiation, ultraviolet (UV) rays, and other damaging agents. Crucially, p53 plays a role in determining whether the damaged genetic material in the cell can be repaired, or if the cell should be destroyed through apoptosis. The individual topologically associating domains (TADs) target different genes and unique effector pathways. It has been observed that inactivating both of the TADs detrimentally affects the ability of p53 to suppress tumor growth and interact with target genes. When only one TAD is inactivated, p53 can still suppress specific tumors; however, it can no longer successfully engage in transactivation. The C-terminal domain (CTD) is an intrinsically disordered domain (IDD), which can take on different conformations depending on what it is binding with and is a location of many post-translational modifications, resulting in its ability to regulate p53 function depending on what it is bound to and what modifications are linked with the CTD. This domain also aids in the binding of the central DNA-binding domain (DBD) to specific DNA sequences; the CTD is a positive regulator of DNA binding and stabilizes the interaction of the DNA with the DBD. p53 is unique as a transcription factor in that it can recognize and bind response elements (RE) in many different environments and doesn't need other transcription factors to cooperatively bind with it like many other TFs.

Mutations in the p53 pathway have been observed in almost all cancer types including breast cancer, bladder cancer, lung cancer, ovarian cancer, cholangiocarcinoma, head and neck squamous cell carcinoma, melanoma, wilms tumor, and other cancers often due to a single point mutation in p53. Li-Fraumeni Syndrome is a condition linked to inherited mutations, at least 140 mutations, in the TP-53 gene. This condition largely increases the risk of developing cancers like breast cancer, bone cancer, and soft tissue sarcomas. Specifically, this impacts children and young adults. A majority of these mutations in the TP-53 gene are single amino acid changes, but other mutations cause a small portion of the DNA to be absent. This leads to a faulty p53 protein that fails to recognize DNA damage in cells, control cell growth, and initiate apoptosis in cells with damaged DNA. Consequently, cells containing erroneous DNA can uncontrollably divide.

Common misconceptions

Often, genes are confused with the proteins in which they code for (Figure 7). Genes are composed of nucleotides, while proteins are composed of amino acids. The genes serve as codes and blueprints to create either proteins of interest, or various non-coding ribonucleic acids (ncRNAs), which exhibit various effects, such as working to prevent cancer within cells.

Figure 7: Central Dogma schematic depicting the protein product via the transcription and translation of a gene.

 

Introduction to entropy

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Introduct...