document_title: Birth certificate

question_text: birth certificates are most often completed by the department

text: Birth certificate

text: History and contemporary times[edit]

text: The documentation of births is a practice widely held throughout human civilization, especially in China, Egypt, Greece, Rome, and Persia. The original purpose of vital statistics was for tax purposes and for the determination of available military manpower. Births were initially registered with churches, who maintained registers of births. This practice continued into the 19th century.[1] The compulsory registration of births with governmental agencies is a practice that originated in the United Kingdom in 1853.[2] The United States did not get a standardized system until 1902.[3]

text: Most countries have statutes and laws that regulate the registration of births. In all countries, it is the responsibility of the mother's physician, midwife, hospital administrator, or the parents of the child to see that the birth is properly registered with the appropriate government agency.

text: The actual record of birth is stored with a government agency. That agency will issue certified copies or representations of the original birth record upon request, which can be used to apply for government benefits, such as passports. The certification is signed and/or sealed by the registrar or other custodian of birth records, who is commissioned by the government.

text: The right of every child to a name and nationality, and the responsibility of national governments to achieve this are contained in Articles 7 and 8 in the United Nations Convention on the Rights of the Child: "The child shall be registered immediately after birth and shall have the right from birth to a name, the right to acquire a nationality..." (CRC Article 7) and "States Parties undertake to respect the right of the child to preserve his or her identity, including nationality, name and family relations..." (CRC Article 8).[4]

text: ...it's a small paper but it actually establishes who you are and gives access to the rights and the privileges, and the obligations, of citizenship.

text: Despite 191 countries ratifying the Convention, the births of millions of children worldwide go unregistered. By their very nature, data concerning unregistered children are approximate; however, it was estimated in 2008 that 51 million babies – more than two fifths of those born worldwide – were not registered at birth.[6] This phenomenon disproportionately impacts indigenous populations and even in many developed countries, contributes to difficulties in fully accessing civic rights.[7]

text: Birth registration opens the door to rights to children and adults which many other human beings take for granted: to prove their age; to prove their nationality; to receive healthcare; to go to school; to take exams; to be adopted; to protection from under-age military service or conscription; to marry; to open a bank account; to hold a driving licence; to obtain a passport; to inherit money or property; and to vote or stand for elected office.[8]

text: There are many reasons why births go unregistered, including social and cultural beliefs and attitudes; alternative documents and naming ceremonies; remote areas, poor infrastructure; economic barriers; lack of office staff, equipment and training; legal and political restrictions; fear of discrimination and persecution; war, conflict and unrest or simply the fact that there is no system in place.[8][9][10][11][12][13]

text: Retrospective registration may be necessary where there is a backlog of children whose births have gone unregistered. In Senegal, the government is facilitating retrospective registration through free local court hearings and the number of unregistered children has fallen considerably as a result. In Sierra Leone, the government gave the National Office of Births and Deaths special permission to issue birth certificates to children over seven. In Bolivia, there was a successful three-year amnesty for the free registration of young people aged between 12 and 18.[14]

text: Statelessness, or the lack of effective nationality, impacts the daily lives of some 11-12 million people around the world. Perhaps those who suffer most are stateless infants, children, and youth. Though born and raised in their parents’ country of habitual residence, they lack formal recognition of their existence.[15]

text: Australia[edit]

text: States and territories of Australia are responsible for the issuance of birth certificates, through agencies generally titled "Registry of Births Deaths and Marriages" or similar.[16]

text: Initially registering a birth is done by a hospital through a "Birth Registration Statement" or similar, signed by appropriately licensed and authorised health professionals, and provided to the state or territory registry. Home births are permitted, but a statement is required from a registered midwife, doctor or 2 other witnesses other than the parents. Unplanned births require in some states that the baby be taken to a hospital within 24 hours.[17] Once registered, a separate application (sometimes it can be done along with the Birth Registration Statement) can be made for a birth certificate, generally at a cost. The person named or a parent can apply for a certificate at any time.[18] Generally, there is no restriction on re-applying for a certificate at a later date, so it could be possible to legally hold multiple original copies.

text: The Federal government requires that births be also registered through a "Proof of Birth Declaration" similarly signed as above by a doctor or midwife. This ensures the appropriate benefits can be paid, and the child is enrolled for Medicare.[19]

text: The state or territory issued birth certificate is a secure A4 paper document, generally listing: Full name at birth, sex at birth, parents and occupation, older siblings, addresses, date and place of birth, name of the registrar, date of registration, date of issue of certificate, a registration number, with the signature of the registrar and seal of the registry printed and or embossed. Most states allow for still births to be issued a birth certificate. Some states issue early pregnancy loss certificates (without legal significance if before 20 weeks).[20] Depending on the state, amendments are allowed to correct the certificate, add parents, recognising same sex relationships,[21] changing the sex of the holder is also permitted in some states.[22]

text: The full birth certificate in Australia is an officially recognised identity document generally in the highest category.[23] The birth certificate assists in establishing citizenship. Shorter and/or commemorative birth certificates are available, however are not generally acceptable for identification purposes.[24]

text: Birth certificates in Australia can be verified online by approved agencies through the Attorney-General's Department Document Verification Service[25] and can be used to validate identity digitally, e.g. online.

text:
[show]

v
t
e

Australian Identity Documents

Federal Government

Passport
Citizenship certificate
Certificate of Identity
Document of Identity
Convention Travel Document
Medicare card

State and Territory Governments

Birth certificate
AusPost Keypass ID
Seniors card
Photo card
Drivers licence
Marriage certificate
Change of name certificate

International

Passport

Indigenous (not recognized)

Aboriginal passport

Non physical/digital

Digital identity in Australia
Tax File Number

text: Canada[edit]

text: In Canada, the issuance of birth certificates is a function of the provinces or territories.[26]

text: Agencies or various ministers are in charge of issuing birth certificates:[27]

text:
Alberta - Department of Vital Statistics (Service Alberta)
British Columbia - Vital Statistics Agency (Ministry of Health)
Manitoba - Vital Statistics Agency (Ministry of Healthy Living, Seniors and Consumer Affairs/Consumer and Corporate Affairs)
New Brunswick - Vital Statistics (Service New Brunswick)
Newfoundland and Labrador - Vital Statistics Government Services (Service NL)
Northwest Territories - Vital Statistics (Department of Health and Social Services - Health Services Administration Division)
Nova Scotia - Registrar General Division of Vital Statistics (Service Nova Scotia and Municipal Relations)
Nunavut - Registrar General of Vital Statistics (Nunavut Health and Social Services)
Ontario - Office of Registrar General-Service Ontario (Ministry of Government Services)
Prince Edward Island - Vital Statistics (Health and Social Services)
Quebec - Director of Civil State (Minister of Justice)
Saskatchewan - Vital Statistics-Information Service Corporation (Department of Health)
Yukon - Vital Statistics (Ministry of Health and Social Services - Health Services)

text: Types of certified copies issued[edit]

text: There are three types of birth certificates issued:

text:
Copy of an act - Contains all information available on the birth of a person.
Long form - legal size or two page form with details of the person, their parents', place of birth, certification by the parents, signature and stamp of the issuing agency or department. Recent forms are in English and French.
Short form or card - provides name, birth date, place of birth, date of registration, date of issue, registration number, certificate number, and signature of registrar general

text:
[show]

v
t
e

 Canadian Identity Documents

Federal Government

Passport
Citizenship certificate
Social Insurance Card
Permanent resident Card
Certificate of Indian Status
Refugee travel document
Canadian Certificate of Identity
Firearms Possession and Acquisition Licence
Old Age Security Identification Card
Seafarer’s Identity Document
Parolee Identification Card
Armed Forces Identification Card

Provincial and Territorial

Birth certificate
Driver's licence
Health card
Provincial Photo ID Card
Provincial Liquor Card

International

Nexus Card
British emergency passport
International Driving Permit

text: England and Wales[edit]

text: In England and Wales, the description "birth certificate" is used to describe a certified copy of an entry in the birth register.[28]

text: Civil registration of births, marriages and deaths in England and Wales started on 1 July 1837.[29] Registration was not compulsory until 1875, following the Registration of Births and Deaths Act 1874, which made registration of a birth the responsibility of those present at the birth.[30]

text: When a birth is registered, the details are entered into the register book at the local register office for the district in which the birth took place and is retained permanently in the local register office. A copy of each entry in the birth register is sent to the General Register Office (GRO).[31]

text: Pre-1837 birth and baptism records[edit]

text: Before the government's registration system was created, evidence of births and/or baptisms (and also marriages and death or burials) was dependent on the events being recorded in the records of the Church of England or in those of other various churches – not all of which maintained such records or all types of those records. Copies of such records are not issued by the General Register Office; but can be obtained from these churches, or from the local or national archive, which usually now keeps the records in original or copy form.

text: Types of certified copies issued in England and Wales[edit]

text: There are two types of birth certificates:

text: A full certificate, titled 'CERTIFIED COPY OF AN ENTRY' is a copy of the original entry in the birth register, giving all the recorded details.[32] Information includes; name, sex, date and place of birth of the child, father's name, place of birth and occupation, mother's name, place of birth, maiden name and occupation. Certificates for births before 1911 do not show the mothers maiden name, before 1969 do not show the details of the parents' place of birth and registration and before 1984 do not show mothers occupation.[33]

text: The short certificate, titled 'CERTIFICATE OF BIRTH', shows the child’s full name, sex, date and place of birth. It does not give any particulars of the parents; therefore it is not proof of parentage. A short birth certificate is issued, free of charge, at the time of registration.[32]

text: Both versions of certificate can be used in the verification of identity by acting as a support to other information or documentation provided. Where proof of parentage is required only a full certificate will be accepted.[34]

text: The original registrations are required by law[35] to be issued in the form of certified copies to any person who identifies an index entry and pays the prescribed fee. They can be ordered by registered users from the General Register Office Certificate Ordering Service or by postal or telephone ordering from the General Register Office or by post or in person from local registrars. If the birth was registered within the past 50 years detailed information is required before a certificate will be issued.[36]

text: India[edit]

text: Traditionally Births were poorly recorded in India.[37]

text: For official purposes, other proofs are accepted in India in lieu of the Birth certificate, such as Matriculation certificates.[38] Facilities are available to produce a Birth certificate from a passport.[39]

text: By law since 1969, Registration of Births is compulsory as per provisions of Registration of Births & Deaths Act.[40] Birth certificates are issued by the Government of India or the municipality concerned. Specific rules vary by state, region and municipality.

text: In Delhi, for example, births must be registered within 21 days by the hospital or institution, or by a family member if the birth has taken place at home. After registration, a birth certificate can be obtained by applying to the relevant authority. Certificates can also be issued under special provisions to adopted children, and undocumented orphans. Overseas births can also be registered.[40]

text: Some municipalities, such as Greater Chennai Corporation allow for fully digital Birth certificates to be applied for printed, and verified online.[41]

text: Russia[edit]

text: Earlier testimony was a small book format-bound, now it's just a page format B5, provided with water marks. The certificate has a series and number.

text: Blank insert is made in Russian. In the case of being issued in one of the country's republics, its national language form liner can be made in Russian and in the official language of the republic on the model, approved by the Ministry of Internal Affairs of the Russian Federation.

text: Filling[edit]

text: A birth certificate can be filled with a handwritten way and with the use of technical equipment (typewriters, computers). When filling in the form is carried handwritten way, all records are made legibly in ink or paste blue or black. If you are using a computer or typewriter dye must be black. The quality of paste, ink, dye, used in completing the documents should ensure the preservation of text documents for a set retention period. When filling out the birth certificate is not allowed to have it in patches, blots and erasures, cuts.

text: Birth certificate is signed by the head of the registrar or other public authority issuing the certificate (e.g., the consulate). Signature of the registrar should have a transcript (initials and surname) and sealed with the official seal.

text: Currently, information about the nationality of the parents is mentioned in the certificate on request. By default, this column is empty

text: When making a citizenship, a special insert is issued to the birth certificate. In testimony Stamp.

text: February 6, 2007 ear of citizenship were canceled, on the reverse side of the Certificate began to put a stamp on the child's citizenship. This rule applies to newborns or those who change or restores documents.

text: Old shells are valid for achieving a child 14 years old and to change them is not necessary.

text: The procedure for obtaining[edit]

text: The birth certificate of the child's parents can get (not deprived of parental rights), itself a child of full age, guardian or caregiver. Issuance of the document is made in the offices of the registrar, ZAGS (Russian: ЗАГС).

text: With the loss of the certificate, a new document is issued by the registry office (ZAGS) in the place of the original receipt on the basis of a written application.

text: United States[edit]

text: In the U.S., the issuance of birth certificates is a function of the Vital Records Office of the states, capital district, territories[42] and former territories.[43] Birth in the U.S. establishes automatic eligibility for American citizenship, so a birth certificate from a local authority is commonly provided to the federal government to obtain a U.S. passport.[44][45] However, the U.S. State Department does issue a Consular Report of Birth Abroad for children born to U.S. citizens (who are also eligible for citizenship), including births on military bases in foreign territory.[46]

text: The federal and state governments have traditionally cooperated to some extent to improve vital statistics. From 1900 to 1946 the U.S. Census Bureau designed standard birth certificates, collected vital statistics on a national basis, and generally sought to improve the accuracy of vital statistics. In 1946 that responsibility was passed to the U.S. Public Health Service. Unlike the British system of recording all births in "registers", the states file an individual document for each and every birth.[47]

text: The U.S. National Center for Health Statistics creates standard forms that are recommended for use by the individual states to document births. However, states are free to create their own forms.[48] As a result, neither the appearance nor the information content of birth certificate forms is uniform across states. These forms are completed by the attendant at birth or a hospital administrator, which are then forwarded to a local or state registrar, who stores the record and issues certified copies upon request.[1]

text: Types of certified copies issued[edit]

text: According to the Department of Health and Human Services, Office of Inspector General, as of 2000 there were more than 6,000 entities issuing birth certificates. The Inspector General report states that according to staff at the Immigration and Naturalization Service’s Forensics Document Laboratory the number of legitimate birth certificate versions in use exceeded 14,000.[49]

text: Acceptance of short forms[edit]

text: In the case of applying for a U.S. passport, not all legitimate government-issued birth certificates are acceptable:

text: A certified birth certificate has a registrar's raised, embossed, impressed or multicolored seal, registrar's signature, and the date the certificate was filed with the registrar's office, which must be within 1 year of your birth. Please note, some short (abstract) versions of birth certificates may not be acceptable for passport purposes.

text: Beginning April 1, 2011, all birth certificates must also include the full names of the applicant's parent(s).[50]

text: The U.S. State Department has paid close attention to abstract certificates from both Texas and California. There have been reports of a high instance of midwife registration fraud along the border region between Texas and Mexico,[51][52] and the Texas abstract certificate form does not list the name or occupation of the attendant. The California Abstract of Birth did not include an embossed seal, was no longer considered a secure document, and have not been issued in California since 2001.[53]

text: Other forms[edit]

text: Most hospitals in the U.S. issue a souvenir birth certificate which may include the footprints of the newborn. However, these birth certificates are not legally accepted as proof of age or citizenship, and are frequently rejected by the Bureau of Consular Affairs during passport applications. Many Americans believe[citation needed] the souvenir records to be their official birth certificates, when in reality they hold little legal value.[54]

text: Birth certificates in cases of adoptions[edit]

text: In the United States, when an adoption is finalized, the government seals the original birth certificate and will issue a replacement birth certificate substituting the individual's birth name with the name selected by the adoptive parents, and replacing the birth parents' names with the adoptive parents. In those cases, adopted individuals are not granted access to their own original birth certificates upon request. Laws vary depending on the state where the birth was originally registered and the adoption was finalized. Some states allow adopted people unrestricted access to their own original birth certificates, while in others the certificate is available only if the biological parents have given their permission or a petition has been granted by the court of jurisdiction. Other jurisdictions do not allow adopted people access to their own original birth certificates under any circumstances.[citation needed]

text: China[edit]

text: The People's Republic of China issued its first birth certificate on January 1, 1996. Birth certificate used currently is the fifth edition, which was adopted since January 1, 2014.[55]


document_title: Valley of the Dolls

question_text: who is the valley of the dolls based on

question_tokens: who is the valley of the dolls based on

root

text: Valley of the Dolls

text: Plot summary[edit]

text: The novel tells the story of three young women who become fast friends in the turbulent post-war worlds of Broadway and Hollywood: Anne Welles, a reserved New England beauty who sees New York as the romantic city of her dreams; Neely O'Hara, an ebullient vaudevillian with a talent she doesn't fully understand; and Jennifer North, a sweet-natured showgirl who wants only to be loved. As life becomes difficult, each woman grows increasingly dependent on "dolls," the amphetamines and barbiturates which, for a time, seem to help.

tag: p

text: Crossing their paths are such people as Helen Lawson, a brilliant but ruthless Broadway legend; Lyon Burke, a magnetic but self-centered theatrical attorney; Tony Polar, a child-like but sexually aggressive pop singer; Kevin Gillmore, a powerful but lovesick cosmetics tycoon; and Ted Casablaca, a potent but opportunistic fashion designer.

text: Over the course of twenty eventful years (1945–1965), each of the women strives to ascend the Mount Everest of her dreams, only to find herself back in the valley of the dolls.

text: Background[edit]

text: Susann had apparently been thinking about the novel for some time. Some years earlier, she had begun a show business novel, Underneath the Pancake, with her friend, actress Beatrice Cole (c. 1910–1999).[4] Later, she considered writing a novel about drug usage in show business to be called The Pink Dolls.[5]

text: Valley of the Dolls is widely considered to be a roman a clef, with its characters based on such famous figures as Judy Garland, Carole Landis, Dean Martin, and Ethel Merman.[6] In 1973, after publication of her third novel, Susann said, "They can keep calling it that [roman a clef]. It'll only make my books sell, I don't care."[7] Susann insisted that she began each book with a theme: "Then I start asking, what kind of a personality? And because I have a good ear, I unconsciously pick up certain people."[7]

text: Susann dedicated the book to her poodle, Josephine, and to her husband, Irving Mansfield.[8]

text: Reception[edit]

text: The book was published by Bernard Geis Associates on February 10, 1966, and "took off like a Cape Canaveral space shot." [9]

text: Although Publishers Weekly, in an advance review, called the novel "big, brilliant and sensational" (if "poorly written"),[10] the book received largely negative reviews. Gloria Steinem panned the book in The New York Herald Tribune [11] as did the reviewer in The New York Times.[12] Time magazine called it the "Dirty Book of the Month," and said, "it might more accurately be described as a highly effective sedative, a living doll."[13]

text: Despite the poor reviews, the book was a commercial juggernaut. On May 8, 1966, in its ninth week on the list, the book reached #1 on the New York Times Best Seller List, where it remained for 28 consecutive weeks.[14] With a total of 65 weeks on the list, the book became the best selling novel of 1966.[1] By the time of Susann's death in 1974, it had entered the Guinness Book of World Records as the best selling novel in publishing history, with more than 17 million copies sold.[15] By 2016, the book had sold more than 31 million copies.[2]

text: Adaptations[edit]

text: In 1967 the book was adapted into a film of the same name, directed by Mark Robson (Peyton Place), and starring Barbara Parkins (as Anne), Patty Duke (Neely), Paul Burke (Lyon), Sharon Tate (Jennifer), and Susan Hayward (Helen). The movie was written by Helen Deutsch (National Velvet) and Dorothy Kingsley (Seven Brides for Seven Brothers), and produced by Robson and David Weisbart. Reviews were scathing,[16] but the film was an enormous box-office hit, becoming the sixth most popular of the year with $44 million at the domestic box office.[17] Susann, who had a cameo as a news reporter, hated the film, reportedly telling director Robson that it was "a piece of shit."[18]

text: The novel was adapted for television in 1981 as Jacqueline Susann's Valley of the Dolls, a mini-series executive-produced by Susann's widower Irving Mansfield and directed by Walter Grauman. This version stars Catherine Hicks, Lisa Hartman, and Veronica Hamel. In 1994 a late-night, syndicated television soap opera, Valley of the Dolls, ran for one season and 65 episodes. The premise was a loose adaptation of the novel.[19] BBC Radio 4 broadcast a 15-episode dramatisation scripted by Yvonne Antrobus over three weeks in August and September 2005. It was part of the Woman's Hour programme's ongoing fifteen-minute daily drama slot,[20] and has been rebroadcast several times on BBC Radio 4 Extra in three 70-minute omnibus episodes.[21]

text: Notes[edit]


document_title: Transfer RNA

question_text: what is the function of trnas in protein synthesis

text: Transfer RNA

text: Overview[edit]

text: While the specific nucleotide sequence of a mRNA specifies which amino acids are incorporated into the protein product of the gene from which the mRNA is transcribed, the role of tRNA is to specify which sequence from the genetic code corresponds to which amino acid.[3] The mRNA encodes a protein as a series of contiguous codons, each of which is recognized by a particular tRNA. One end of the tRNA matches the genetic code in a three-nucleotide sequence called the anticodon. The anticodon forms three base pairs with a codon in mRNA during protein biosynthesis. On the other end of the tRNA is a covalent attachment to the amino acid that corresponds to the anticodon sequence. Each type of tRNA molecule can be attached to only one type of amino acid, so each organism has many types of tRNA. Because the genetic code contains multiple codons that specify the same amino acid, there are several tRNA molecules bearing different anticodons which carry the same amino acid.

text: The covalent attachment to the tRNA 3’ end is catalyzed by enzymes called aminoacyl tRNA synthetases. During protein synthesis, tRNAs with attached amino acids are delivered to the ribosome by proteins called elongation factors, which aid in association of the tRNA with the ribosome, synthesis of the new polypeptide and translocation (movement) of the ribosome along the mRNA. If the tRNA's anticodon matches the mRNA, another tRNA already bound to the ribosome transfers the growing polypeptide chain from its 3’ end to the amino acid attached to the 3’ end of the newly delivered tRNA, a reaction catalyzed by the ribosome.

text: A large number of the individual nucleotides in a tRNA molecule may be chemically modified, often by methylation or deamidation. These unusual bases sometimes affect the tRNA's interaction with ribosomes and sometimes occur in the anticodon to alter base-pairing properties.[4]:29.1.2

text: Structure[edit]

text: The structure of tRNA can be decomposed into its primary structure, its secondary structure (usually visualized as the cloverleaf structure), and its tertiary structure[5] (all tRNAs have a similar L-shaped 3D structure that allows them to fit into the P and A sites of the ribosome). The cloverleaf structure becomes the 3D L-shaped structure through coaxial stacking of the helices, which is a common RNA tertiary structure motif.

text: The lengths of each arm, as well as the loop 'diameter', in a tRNA molecule vary from species to species.[5][6]

text: The tRNA structure consists of the following:

text:
A 5'-terminal phosphate group.
The acceptor stem is a 7- to 9-base pair (bp) stem made by the base pairing of the 5'-terminal nucleotide with the 3'-terminal nucleotide (which contains the CCA 3'-terminal group used to attach the amino acid). In general, such 3'-terminal tRNA-like structures are referred to as 'genomic tags'. The acceptor stem may contain non-Watson-Crick base pairs.[5][7]
The CCA tail is a cytosine-cytosine-adenine sequence at the 3' end of the tRNA molecule. The amino acid loaded onto the tRNA by aminoacyl tRNA synthetases, to form aminoacyl-tRNA, is covalently bonded to the 3'-hydroxyl group on the CCA tail.[8] This sequence is important for the recognition of tRNA by enzymes and critical in translation.[9][10] In prokaryotes, the CCA sequence is transcribed in some tRNA sequences. In most prokaryotic tRNAs and eukaryotic tRNAs, the CCA sequence is added during processing and therefore does not appear in the tRNA gene.[11]
The D arm is a 4- to 6-bp stem ending in a loop that often contains dihydrouridine.[5]
The anticodon arm is a 5-bp stem whose loop contains the anticodon.[5] The tRNA 5'-to-3' primary structure contains the anticodon but in reverse order, since 3'-to-5' directionality is required to read the mRNA from 5'-to-3'.
The T arm is a 4- to 5- bp stem containing the sequence TΨC where Ψ is pseudouridine, a modified uridine.[5]
Bases that have been modified, especially by methylation (e.g. tRNA (guanine-N7-)-methyltransferase), occur in several positions throughout the tRNA. The first anticodon base, or wobble-position, is sometimes modified to inosine (derived from adenine), pseudouridine or lysidine (derived from cytosine).[12]

tag: ol

text: Anticodon[edit]

text: An anticodon[13] is a unit made up of three nucleotides that correspond to the three bases of the codon on the mRNA. Each tRNA contains a distinct anticodon triplet sequence that can base-pair to one or more codons for an amino acid. Some anticodons can pair with more than one codon due to a phenomenon known as wobble base pairing. Frequently, the first nucleotide of the anticodon is one not found on mRNA: inosine, which can hydrogen bond to more than one base in the corresponding codon position.[4]:29.3.9 In the genetic code, it is common for a single amino acid to be specified by all four third-position possibilities, or at least by both pyrimidines and purines; for example, the amino acid glycine is coded for by the codon sequences GGU, GGC, GGA, and GGG. Other modified nucleotides may also appear at the first anticodon position—sometimes known as the "wobble position"—resulting in subtle changes to the genetic code, as for example in mitochondria.[14]

text: To provide a one-to-one correspondence between tRNA molecules and codons that specify amino acids, 61 types of tRNA molecules would be required per cell, as there are 61 sense codons of the standard genetic code. However, many cells contain fewer than 61 types of tRNAs because the wobble base is capable of binding to several, though not necessarily all, of the codons that specify a particular amino acid. A minimum of 31 tRNAs are required to translate, unambiguously, all 61 sense codons. The maximum observed is 41.[3][15]

text: Aminoacylation[edit]

text: Aminoacylation is the process of adding an aminoacyl group to a compound. It covalently links an amino acid to the CCA 3' end of a tRNA molecule.

text: Each tRNA is aminoacylated (or charged) with a specific amino acid by an aminoacyl tRNA synthetase. There is normally a single aminoacyl tRNA synthetase for each amino acid, despite the fact that there can be more than one tRNA, and more than one anticodon, for an amino acid. Recognition of the appropriate tRNA by the synthetases is not mediated solely by the anticodon, and the acceptor stem often plays a prominent role.[16]

text: Reaction:

text:
amino acid + ATP → aminoacyl-AMP + PPi
aminoacyl-AMP + tRNA → aminoacyl-tRNA + AMP

text: Certain organisms can have one or more aminoacyl tRNA synthetases missing. This leads to charging of the tRNA by a chemically related amino acid. An enzyme or enzymes modify the charged amino acid to the final one. For example, Helicobacter pylori has glutaminyl tRNA synthetase missing. Thus, glutamate tRNA synthetase charges tRNA-glutamine(tRNA-Gln) with glutamate. An amidotransferase then converts the acid side chain of the glutamate to the amide, forming the correctly charged gln-tRNA-Gln.

text: Binding to ribosome[edit]

text: The ribosome has three binding sites for tRNA molecules that span the space between the two ribosomal subunits: the A (aminoacyl),[18] P (peptidyl), and E (exit) sites. In addition, the ribosome has two other sites for tRNA binding that are used during mRNA decoding or during the initiation of protein synthesis. These are the T site (named elongation factor Tu) and I site (initiation).[19][20] By convention, the tRNA binding sites are denoted with the site on the small ribosomal subunit listed first and the site on the large ribosomal subunit listed second. For example, the A site is often written A/A, the P site, P/P, and the E site, E/E.[19] The binding proteins like L27, L2, L14, L15, L16 at the A- and P- sites have been determined by affinity labeling by A.P. Czernilofsky et al. (Proc. Natl. Acad. Sci, USA, pp 230–234, 1974).

text: Once translation initiation is complete, the first aminoacyl tRNA is located in the P/P site, ready for the elongation cycle described below. During translation elongation, tRNA first binds to the ribosome as part of a complex with elongation factor Tu (EF-Tu) or its eukaryotic (eEF-1) or archaeal counterpart. This initial tRNA binding site is called the A/T site. In the A/T site, the A-site half resides in the small ribosomal subunit where the mRNA decoding site is located. The mRNA decoding site is where the mRNA codon is read out during translation. The T-site half resides mainly on the large ribosomal subunit where EF-Tu or eEF-1 interacts with the ribosome. Once mRNA decoding is complete, the aminoacyl-tRNA is bound in the A/A site and is ready for the next peptide bond to be formed to its attached amino acid. The peptidyl-tRNA, which transfers the growing polypeptide to the aminoacyl-tRNA bound in the A/A site, is bound in the P/P site. Once the peptide bond is formed, the tRNA in the P/P site is deacylated, or has a free 3’ end, and the tRNA in the A/A site carries the growing polypeptide chain. To allow for the next elongation cycle, the tRNAs then move through hybrid A/P and P/E binding sites, before completing the cycle and residing in the P/P and E/E sites. Once the A/A and P/P tRNAs have moved to the P/P and E/E sites, the mRNA has also moved over by one codon and the A/T site is vacant, ready for the next round of mRNA decoding. The tRNA bound in the E/E site then leaves the ribosome.

text: The P/I site is actually the first to bind to aminoacyl tRNA, which is delivered by an initiation factor called IF2 in bacteria.[20] However, the existence of the P/I site in eukaryotic or archaeal ribosomes has not yet been confirmed. The P-site protein L27 has been determined by affinity labeling by E. Collatz and A.P. Czernilofsky (FEBS Lett., Vol. 63, pp 283–286, 1976).

text: tRNA genes[edit]

text: Organisms vary in the number of tRNA genes in their genome. The nematode worm C. elegans, a commonly used model organism in genetics studies, has 29,647 [21] genes in its nuclear genome, of which 620 code for tRNA.[22][23] The budding yeast Saccharomyces cerevisiae has 275 tRNA genes in its genome.

text: In the human genome, which, according to January 2013 estimates, has about 20,848 protein coding genes [24] in total, there are 497 nuclear genes encoding cytoplasmic tRNA molecules, and 324 tRNA-derived pseudogenes—tRNA genes thought to be no longer functional[25] (although pseudo tRNAs have been shown to be involved in antibiotic resistance in bacteria ).[26] Regions in nuclear chromosomes, very similar in sequence to mitochondrial tRNA genes, have also been identified (tRNA-lookalikes).[27] These tRNA-lookalikes are also considered part of the nuclear mitochondrial DNA (genes transferred from the mitochondria to the nucleus).[27][28]

text: As with all eukaryotes, there are 22 mitochondrial tRNA genes[29] in humans. Mutations in some of these genes have been associated with severe diseases like the MELAS syndrome.

text: Cytoplasmic tRNA genes can be grouped into 49 families according to their anticodon features. These genes are found on all chromosomes, except 22 and Y chromosome. High clustering on 6p is observed (140 tRNA genes), as well on 1 chromosome.[25]

text: The HGNC, in collaboration with the Genomic tRNA Database (GtRNAdb) and experts in the field, has approved unique names for human genes that encode tRNAs.

text: Evolution[edit]

text: The top half of tRNA (consisting of the D arm and the acceptor stem with 5'-terminal phosphate group and 3'-terminal CCA group) and the bottom half (consisting of the T arm and the anticodon arm) are independent units in structure as well as in function. The top half may have evolved first including the 3'-terminal genomic tag which originally may have marked tRNA-like molecules for replication in early RNA world. The bottom half may have evolved later as an expansion, e. g. as protein synthesis started in RNA world and turned it into a (ribonucleoprotein world (RNP world). This proposed scenario is called genomic tag hypothesis. In fact, tRNA and tRNA-like aggregates have an important catalytic influence (i. e. as ribozymes) on replication still today. These roles may be regarded as 'molecular (or chemical) fossiles' of RNA world.[30]

text: Genomic tRNA content is a differentiating feature of genomes among biological domains of life: Archaea present the simplest situation in terms of genomic tRNA content with a uniform number of gene copies, Bacteria have an intermediate situation and Eukarya present the most complex situation.[31] Eukarya present not only more tRNA gene content than the other two kingdoms but also a high variation in gene copy number among different isoacceptors, and this complexity seem to be due to duplications of tRNA genes and changes in anticodon specificity[citation needed].

text: Evolution of the tRNA gene copy number across different species has been linked to the appearance of specific tRNA modification enzymes (uridine methyltransferases in Bacteria, and adenosine deaminases in Eukarya), which increase the decoding capacity of a given tRNA.[31] As an example, tRNAAla encodes four different tRNA isoacceptors (AGC, UGC, GGC and CGC). In Eukarya, AGC isoacceptors are extremely enriched in gene copy number in comparison to the rest of isoacceptors, and this has been correlated with its A-to-I modification of its wobble base. This same trend has been shown for most amino acids of eukaryal species. Indeed, the effect of these two tRNA modifications is also seen in codon usage bias. Highly expressed genes seem to be enriched in codons that are exclusively using codons that will be decoded by these modified tRNAs, which suggests a possible role of these codons—and consequently of these tRNA modifications—in translation efficiency.[31]

text: tRNA-derived fragments[edit]

text: tRNA-derived fragments (or tRFs) are short molecules that emerge after cleavage of the mature tRNAs or the precursor transcript.[32][33][34][35] Both cytoplasmic and mitochondrial tRNAs can produce fragments.[36] There are at least four structural types of tRFs believed to originate from mature tRNAs, including the relatively long tRNA halves and short 5’-tRFs, 3’-tRFs and i-tRFs.[32][36][37] The precursor tRNA can be cleaved to produce molecules from the 5’ leader or 3’ trail sequences. Cleavage enzymes include Angiogenin, Dicer, RNase Z and RNase P.[32][33] Especially in the case of Angiogenin, the tRFs have a characteristically unusual cyclic phosphate at their 3’ end and a hydroxyl group at the 5’ end.[38]

text: tRFs have multiple dependencies and roles. They exhibit significant changes between sexes, among races and disease status.[36] Functionally, they can be loaded on Ago and act through RNAi pathways,[34][36][37][39] participate in the formation of stress granules,[40] displace mRNAs from RNA-binding proteins[41] or inhibit translation.[42] At the system or the organismal level, the four types of tRFs have a diverse spectrum of activities. Functionally, tRFs are associated with viral infection,[43] cancer,[36][37] cell proliferation [38] and also with epigenetic transgenerational regulation of metabolism.[44]

text: tRFs are not restricted to humans but have been shown to exist in multiple organisms.[37][45][46][47]

text: Two online tools are available for those wishing to learn more about tRFs: the framework for the interactive exploration of mitochondrial and nuclear tRNA fragments (MINTbase)[48] and the relational database of Transfer RNA related Fragments(tRFdb).[49] MINTbase also provides a naming scheme for the naming of tRFs called tRF-license plates that is genome independent.

text: tRNA biogenesis[edit]

text: In eukaryotic cells, tRNAs are transcribed by RNA polymerase III as pre-tRNAs in the nucleus.[50] RNA polymerase III recognizes two highly conserved downstream promoter sequences: the 5' intragenic control region (5'-ICR, D-control region, or A box), and the 3'-ICR (T-control region or B box) inside tRNA genes.[2][51][52] The first promoter begins at +8 of mature tRNAs and the second promoter is located 30-60 nucleotides downstream of the first promoter. The transcription terminates after a stretch of four or more thymidines.[2][52]

text: Pre-tRNAs undergo extensive modifications inside the nucleus. Some pre-tRNAs contain introns that are spliced, or cut, to form the functional tRNA molecule;[53] in bacteria these self-splice, whereas in eukaryotes and archaea they are removed by tRNA-splicing endonucleases.[54] Eukaryotic pre-tRNA contains bulge-helix-bulge (BHB) structure motif that is important for recognition and precise splicing of tRNA intron by endonucleases.[55] This motif position and structure are evolutionary conserved. However, some organisms, such as unicellular algae have a non-canonical position of BHB-motif as well as 5'- and 3'-ends of the spliced intron sequence.[55] The 5' sequence is removed by RNase P,[56] whereas the 3' end is removed by the tRNase Z enzyme.[57] A notable exception is in the archaeon Nanoarchaeum equitans, which does not possess an RNase P enzyme and has a promoter placed such that transcription starts at the 5' end of the mature tRNA.[58] The non-templated 3' CCA tail is added by a nucleotidyl transferase.[59] Before tRNAs are exported into the cytoplasm by Los1/Xpo-t,[60][61] tRNAs are aminoacylated.[62] The order of the processing events is not conserved. For example, in yeast, the splicing is not carried out in the nucleus but at the cytoplasmic side of mitochondrial membranes.[63]

text: History[edit]

text: The existence of tRNA was first hypothesized by Francis Crick, based on the assumption that there must exist an adapter molecule capable of mediating the translation of the RNA alphabet into the protein alphabet. Significant research on structure was conducted in the early 1960s by Alex Rich and Don Caspar, two researchers in Boston, the Jacques Fresco group in Princeton University and a United Kingdom group at King's College London.[64] In 1965, Robert W. Holley of Cornell University reported the primary structure and suggested three secondary structures.[65] tRNA was first crystallized in Madison, Wisconsin, by Robert M. Bock.[66] The cloverleaf structure was ascertained by several other studies in the following years[67] and was finally confirmed using X-ray crystallography studies in 1974. Two independent groups, Kim Sung-Hou working under Alexander Rich and a British group headed by Aaron Klug, published the same crystallography findings within a year.[68][69]


document_title: Myofascial trigger point

question_text: where are trigger points located in the body

text: Myofascial trigger point

text: Definition[edit]

text: The term "trigger point" was coined in 1942 by Dr. Janet Travell to describe a clinical finding with the following characteristics:

text:
Pain related to a discrete, irritable point in skeletal muscle or fascia, not caused by acute local trauma, inflammation, degeneration, neoplasm or infection.
The painful point can be felt as a nodule or band in the muscle, and a twitch response can be elicited on stimulation of the trigger point.
Palpation of the trigger point reproduces the patient's complaint of pain, and the pain radiates in a distribution typical of the specific muscle harboring the trigger point.
The pain cannot be explained by findings on neurological examination.

tag: ul

text: Diagnosis[edit]

text: Practitioners do not agree on what constitutes a trigger point, but the assessment typically considers symptoms, pain patterns and manual palpation. Usually there is a taut band in muscles containing trigger points, and a hard nodule can be felt. Often a twitch response can be felt in the muscle by running your finger perpendicular to the muscle's direction; this twitch response often activates the "all or nothing" response in a muscle that causes it to contract. Pressing on an affected muscle can often refer pain. Clusters of trigger points are not uncommon in some of the larger muscles, such as the gluteus group (gluteus maximus, gluteus medius, and gluteus minimus). Often there is a heat differential in the local area of a trigger point.[citation needed]

text: A 2007 review of diagnostic criteria used in studies of trigger points concluded that

text: A 2009 review of nine studies examining the reliability of trigger point diagnosis found that physical examination could not be recommended as reliable for the diagnosis of trigger points.[5]

text: Imaging[edit]

text: A 2008 review in Archives of Physical Medicine and Rehabilitation of two recent studies concludes they present findings that can reduce some of the controversy surrounding the cause and identification of myofascial trigger points (MTPs).[6] The study by Chen on the use of magnetic resonance elastography (MRE) imaging of the taut band of an MTP in an upper trapezius muscle may present a convincing demonstration of the cause of MTP symptoms. MRE is a modification of existing magnetic resonance imaging equipment to image stress produced by adjacent tissues with different degrees of tension. This report presents an MRE image of the taut band that shows the V-shaped signature of the increased tension compared with surrounding tissues.[7] Results were all consistent with the concept that taut bands are detectable and quantifiable with MRE imaging. The findings in the subjects suggest that the stiffness of the taut bands in patients with myofascial pain may be 50% greater than that of the surrounding muscle tissue. The findings suggest that MRE can quantitate asymmetries in muscle tone that could previously only be identified subjectively by examination.[8]

text: In the study by Shah and associates, they have shown the feasibility of continuous, in vivo recovery of small molecules from soft tissue without harmful effects. With this technique, they have been able to investigate the biochemistry of muscle in subjects with myofascial trigger points and to contrast this with that of the noninvolved muscle.[9]

text: Myofascial pain syndrome[edit]

text: The main innovation of Travell's work was the introduction of the myofascial pain syndrome concept (myofascial referring to the fascia that surrounds and permeates muscle). This is described as a focal hyperirritability in muscle that can strongly modulate central nervous system functions. Travell and followers distinguish this from fibromyalgia, which is characterized by widespread pain and tenderness and is described as a central augmentation of nociception giving rise to deep tissue tenderness that includes muscles. Studies estimate that in 75–95 percent of cases, myofascial pain is a primary cause of regional pain. Myofascial pain is associated with muscle tenderness that arises from trigger points, focal points of tenderness, a few millimeters in diameter, found at multiple sites in a muscle and the fascia of muscle tissue. Biopsy tests found that trigger points were hyperirritable and electrically active muscle spindles in general muscle tissue.[10]

text: Misdiagnosis of pain[edit]

text: The misdiagnosis of pain is the most important issue taken up by Travell and Simons. Referred pain from trigger points mimics the symptoms of a very long list of common maladies, but physicians, in weighing all the possible causes for a given condition, rarely consider a myofascial source. The study of trigger points has not historically been part of medical education. Travell and Simons hold that most of the common everyday pain is caused by myofascial trigger points and that ignorance of that basic concept could inevitably lead to false diagnoses and the ultimate failure to deal effectively with pain.[11]

text: Pathophysiology[edit]

text: Activation of trigger points may be caused by a number of factors, including acute or chronic muscle overload, activation by other trigger points (key/satellite, primary/secondary), disease, psychological distress (via systemic inflammation), homeostatic imbalances, direct trauma to the region, collision trauma (such as a car crash which stresses many muscles and causes instant trigger points) radiculopathy, infections and health issues such as smoking.

text: Trigger points form only in muscles. They form as a local contraction in a small number of muscle fibers in a larger muscle or muscle bundle. These in turn can pull on tendons and ligaments associated with the muscle and can cause pain deep within a joint where there are no muscles. The integrated hypothesis theory states that trigger points form from excessive release of acetylcholine which produces sustained depolarization of muscle fibers. Indeed, the trigger point has an abnormal biochemical composition with elevated concentrations of acetylcholine, noradrenaline and serotonin and a lower pH.[12] These sustained contractions of muscle sarcomeres compresses local blood supply restricting the energy needs of the local region. This crisis of energy produces sensitizing substances that interact with some nociceptive (pain) nerves traversing in the local region which in turn can produce localized pain within the muscle at the neuromuscular junction (Travell and Simons 1999). When trigger points are present in muscles there is often pain and weakness in the associated structures. These pain patterns in muscles follow specific nerve pathways and have been readily mapped to allow for identification of the causative pain factor. Many trigger points have pain patterns that overlap, and some create reciprocal cyclic relationships that need to be treated extensively to remove them.

text: Treatment[edit]

text: Physical muscle treatment[edit]

text: Therapists may use myotherapy (deep pressure as in Bonnie Prudden's approach, massage or tapotement as in Dr. Griner's approach), mechanical vibration, pulsed ultrasound, electrostimulation,[13] ischemic compression, trigger-point-injection (see below), dry-needling, "spray-and-stretch" using a cooling (vapocoolant) spray, Low Level Laser Therapy and stretching techniques that invoke reciprocal inhibition within the musculoskeletal system. Practitioners may use elbows, feet or various tools to direct pressure directly upon the trigger point, to avoid overuse of their hands.

text: A successful treatment protocol relies on identifying trigger points, resolving them and, if all trigger points have been deactivated, elongating the structures affected along their natural range of motion and length. In the case of muscles, which is where most treatment occurs, this involves stretching the muscle using combinations of passive, active, active isolated (AIS), muscle energy techniques (MET), and proprioceptive neuromuscular facilitation (PNF) stretching to be effective. Fascia surrounding muscles should also be treated to elongate and resolve strain patterns, otherwise muscles will simply be returned to positions where trigger points are likely to re-develop.

text: The results of manual therapy are related to the skill level of the therapist. If trigger points are pressed too short a time, they may activate or remain active; if pressed too long or hard, they may be irritated or the muscle may be bruised, resulting in pain in the area treated. This bruising may last for a 1–3 days after treatment, and may feel like, but is not similar to, delayed onset muscle soreness (DOMS), the pain felt days after overexerting muscles. Pain is also common after a massage if the practitioner uses pressure on unnoticed latent or active trigger points, or is not skilled in myofascial trigger point therapy.

text: Researchers of evidence-based medicine concluded as of 2001 that evidence for the usefulness of trigger points in the diagnosis of fibromyalgia is thin.[14] More recently, an association has been made between fibromyalgia tender points and active trigger points.[15][16]

text: Trigger-point-injection[edit]

text: Injections without anesthetics, or dry needling, and injections including saline, local anesthetics such as procaine hydrochloride (Novocain) or articaine without vasoconstrictors like epinephrine,[17] steroids, and botulinum toxin provide more immediate relief and can be effective when other methods fail. In regards to injections with anesthetics, a low concentration, short acting local anesthetic such as procaine 0.5% without steroids or adrenalin is recommended. High concentrations or long acting local anesthetics as well as epinephrine can cause muscle necrosis, while use of steroids can cause tissue damage.

text: Despite the concerns about long acting agents,[1] a mixture of lidocaine and marcaine is often used.[18] A mixture of 1 part 2% lidocaine with 3 parts 0.5% bupivacaine (trade name:Marcaine) provides 0.5% lidocaine and 0.375% bupivacaine. This has the advantages of immediate anesthesia with lidocaine during injection to minimize injection pain while providing a longer duration of action with a lowered concentration of bupivacaine.

text: In 1979, a study by Czech physician Karl Lewit reported that dry needling had the same success rate as anesthetic injections for the treatment of trigger points. He dubbed this the 'needle effect'.[19]

text: In the 1950s and 1960s, studies relevant to trigger points were done by J. H. Kellgren at University College Hospital, London, in the 1930s and, independently, by Michael Gutstein in Berlin and Michael Kelly in Australia. [20]

text: Health insurance companies in the US such as Blue Cross, Medica, and HealthPartners began covering trigger point injections in 2005.[citation needed]

text: Risks[edit]

text: Treatment, whether by self or by a professional, has some inherent dangers. It may lead to damage of soft tissue and other organs. The trigger points in the upper quadratus lumborum, for instance, are very close to the kidneys and poorly administered treatment (particularly injections) may lead to kidney damage. Likewise, treating the masseter muscle may damage the salivary glands superficial to this muscle. Furthermore, some experts believe trigger points may develop as a protective measure against unstable joints.[citation needed]

text: Efficacy[edit]

text: Studies to date on the efficacy of dry needling for MTrPs and pain have been too small to be conclusive.[21]

text: Overlap with acupuncture[edit]

text: In a June 2000 review, Chang-Zern Hong correlates the MTrP "tender points" to acupunctural "ah shi" ("Oh Yes!") points, and the "local twitch response" to acupuncture's "de qi" ("needle sensation"),[22] based on a 1977 paper by Melzack et al.[23] Peter Dorsher comments on a strong correlation between the locations of trigger points and classical acupuncture points, finding that 92% of the 255 trigger points correspond to acupuncture points, including 79.5% with similar pain indications.[24][25]