document_title: British colonization of the Americas

question_text: who were the first british settlers in america

text: British colonization of the Americas

text: North America[edit]

text: Pre-British colonization of North America[edit]

text: English colonies in North America[edit]

text: A number of English colonies were established under a system of Proprietary Governors, who were appointed under mercantile charters to English joint stock companies to found and run settlements.

text:
In 1607, Jamestown, Virginia was founded by the London Company (also known as the Virginia Company).
In Newfoundland, a chartered company known as the Society of Merchant Venturers established a permanent settlement at Cuper's Cove, from 1610.
St. George's, Bermuda was founded by the Virginia Company, in 1612.

text: In 1664, England took over the Dutch colony of New Netherland (including its capital of New Amsterdam) which England renamed the Province of New York. With New Netherland, the English also came to control the former New Sweden (in what is now Delaware), which the Dutch had conquered earlier. This later became part of Pennsylvania after that was established in 1680.

text: Scottish colonies in North America[edit]

text: The Kingdom of Scotland tried unsuccessfully to establish a colony at Darién, and the Scottish colonization of Nova Scotia (New Scotland) lasted from 1629 to 1632. Thousands of Scotsmen also participated in English colonization before the two countries were united in 1707.

text: British colonies in North America[edit]

text: The Kingdom of Great Britain acquired the French colony of Acadia in 1713 and then Canada and the Spanish colony of Florida in 1763. After being renamed the Province of Quebec, the former French Canada was divided into two Provinces, the Canadas, consisting of the old settled country of Lower Canada (today Quebec) and the newly settled Upper Canada (today Ontario).

text: In the north, the Hudson's Bay Company actively traded for fur with the indigenous peoples, and had competed with French, Aboriginal, and Métis fur traders. The company came to control the entire drainage basin of Hudson Bay, called Rupert's Land. The small part of the Hudson Bay drainage south of the 49th parallel went to the United States in the Anglo-American Convention of 1818.

text: Thirteen of Great Britain's colonies rebelled in the American Revolutionary War, beginning in 1775, primarily over representation, local laws and tax issues, and established the United States of America, which was recognised internationally with the signing of the Treaty of Paris on 3 September 1783.

text: Great Britain also colonised the west coast of North America, indirectly via the Hudson's Bay Company licenses west of the Rocky Mountains: the Columbia District and New Caledonia fur district. Most of these were jointly claimed as the Oregon Country by the United States from 1818 until the 49th parallel was established as the international boundary west of the Rockies by the Oregon Treaty of 1846. The Colony of Vancouver Island, founded in 1849, and the Colony of British Columbia, founded in 1858, were combined in 1866 under the name Colony of British Columbia, and joined the Confederation in 1871. British Columbia was expanded with the inclusion of the Stikine Territory in 1863; and upon joining Confederation the Peace River Block, formerly part of Rupert's Land, was added.

text: In 1867, the colonies of New Brunswick, Nova Scotia, and the Province of Canada (the southern portion of modern-day Ontario and Quebec) combined to form a self-governing dominion, named Canada, within the British Empire (the term "kingdom" was avoided so as to not provoke the United States). Quebec (including what is now the southern portion of Ontario) and Nova Scotia (including what is now New Brunswick and Prince Edward Island) had been ceded to Britain by the French. The colonies of Prince Edward Island and British Columbia joined over the next six years, and Newfoundland joined in 1949. Rupert's Land and the North-Western Territory were ceded to Canada in 1870. This area now consists of the provinces of Manitoba (admitted after negotiation between Canada and a Métis provisional government in 1870), Saskatchewan, and Alberta (both created in 1905), as well as the Northwest Territories, the Yukon Territory (created 1898, following the start of the Klondike Gold Rush), and Nunavut (created in 1999).

text: List of English and British colonies in North America (in rough chronological order)[edit]

text:
Roanoke Colony, founded 1586, abandoned the next year. Second attempt in 1587 disappeared (also called the Lost Colony).
Cuttyhunk Island, established as a small fort and trading post by Bartholomew Gosnold in 1602, abandoned after one month.
Virginia Company, chartered 1606 and became the Virginia Colony in 1624

London Company

Jamestown, Virginia, founded 1607 (briefly abandoned in 1610)
Bermuda, islands located in the North Atlantic, first settled in 1609 by the London Virginia Company; administration passed in 1615 to the Somers Isles Company, formed by the same shareholders. Known officially as the Somers Isles, they remain today a British overseas territory.
Citie of Henricopolis, founded in 1611 as an alternative to the swampy Jamestown site and destroyed in the Indian massacre of 1622.

Plymouth Company

Popham Colony, founded 1607, abandoned 1608

Society of Merchant Venturers (Newfoundland)

Cuper's Cove, founded 1610, abandoned in the 1620s
Bristol's Hope, founded 1618, abandoned in the 1630s

London and Bristol Company (Newfoundland)

The massacre of Jamestown settlers in 1622. Soon the colonists in the South feared all natives as enemies.

New Cambriol, founded 1617, abandoned before 1637
Renews, founded 1615, abandoned in 1619[1]

St. John's, Newfoundland, chartered by Sir Humphrey Gilbert in 1583; seasonal settlements ca. 1520;[2] informal year-round settlers before 1620.[3][4]
Plymouth Council for New England

Plymouth Colony, founded 1620, merged with Massachusetts Bay Colony in 1691

Ferryland, Newfoundland, granted to George Calvert, 1st Baron Baltimore in 1620, first settlers in August 1621[5]
Province of Maine, granted 1622, sold to Massachusetts Bay Colony in 1677
South Falkland, Newfoundland, founded 1623 by Henry Cary, 1st Viscount Falkland
Province of New Hampshire, later New Hampshire settled in 1623, see also New Hampshire Grants
Dorchester Company Colony, (Dorchester Company planted an unsuccessful fishing colony on Cape Ann at modern Gloucester, Massachusetts in 1624)
Salem Colony, later Salem, Massachusetts, settled in 1628, merged with Massachusetts Bay Colony the next year
Massachusetts Bay Colony, later part of Massachusetts, founded 1629
New Scotland, in present Nova Scotia, 1629–1632
Connecticut Colony, later part of Connecticut founded 1633
Province of Maryland, later Maryland, founded in 1634

The Treaty of William Penn with the Indians. Penn's Treaty was never violated.

New Albion, chartered in 1634, failed by 1649–50, not to be confused with Nova Albion on the Pacific coast (see next section)
Saybrook Colony, founded 1635, merged with Connecticut in 1644
Rhode Island and Providence Plantations, first settled in 1636
New Haven Colony, founded 1638, merged with Connecticut in 1665
Gardiners Island, founded 1639, now part of East Hampton, New York
Province of New York, captured 1664
Province of New Jersey, captured in 1664

divided into West Jersey and East Jersey after 1674, each held by its own company of Proprietors.

Province of Pennsylvania, later Pennsylvania, founded 1681 as an English colony, although first settled by Dutch and Swedes
Delaware Colony, later Delaware, separated from Pennsylvania in 1704
Province of Carolina

Province of North Carolina, first permanent English settlements in the late 1600s (nearly a century after the failed Roanoke Colony; see Albemarle Settlements), became a separate colony in 1710-12.
Province of South Carolina, first permanent English settlement in 1670, became a separate colony in 1710-12.

Province of Georgia, later Georgia; first settled in about 1670, formal colony in 1732
Nova Scotia, site of abortive Scottish colony in 1629; British colony 1713, but this did not permanently include Cape Breton Island until 1758.
Province of Quebec, which had been called Canada under French rule. Canada was by far the most settled portion of New France. Britain gained complete control of French Canada in 1759–1761, from the events within the North American theater of the Seven Years' War; France ceded title with the Treaty of Paris in 1763. Became Canada East in the Province of Canada, which also included Ontario (Upper Canada) as Canada West, from 1841 to 1867.
East Florida and West Florida, acquired from Spain in 1763 in exchange for returning Cuba, taken from Spain in 1761; the Floridas were recovered by Spain in 1783. Backwoods areas almost unaffected by the Stamp Act Crisis of 1765, which unified the thirteen colonies that formed the United States, not much for abstract principles, and grateful to the crown, they declined to send representatives to the Continental Congress or to participate in any way in the independence movement. After the Second Spanish period, they were acquired by the United States in 1821.
Island of St. John, separated from Nova Scotia 1769, renamed Prince Edward Island in 1798
New Brunswick, separated from Nova Scotia in 1784

text:
Ontario, separated from Quebec in 1791 as the Province of Upper Canada until 1841, when it became Canada West in the Province of Canada.
Province of Canada combined the colonies of Quebec (Lower Canada) and Ontario (Upper Canada) from 1841 to 1867.
Colony of Vancouver Island, founded by the Hudson's Bay Company at Fort Victoria in 1843. Received royal charter for the Island as a colony in 1849, and merged with the colony of British Columbia in 1866.
Colony of the Queen Charlotte Islands, founded in 1852, merged with the Colony of Vancouver Island in 1863.
Colony of British Columbia, also called the Mainland Colony or the Gold Colony, founded in 1858 from the New Caledonia fur district and the remnant of the Columbia fur district north of the 49th parallel (see below). The colony was expanded with the addition of most of the Stikine Territory (also called Stickeen Territory) and the Colony of the Queen Charlotte Islands in 1863.
Colony of British Columbia, formed in 1866 from a merger of the Vancouver Island and Mainland Colonies. The name British Columbia was chosen for the newly merged colony despite the opposition from Vancouver Island colonists.

text: Non-colonial British territories in North America[edit]

text:
Rupert's Land, territory of the Hudson's Bay Company, founded in 1670 and transferred to the new Dominion of Canada in 1867 as the Northwest Territories
Columbia District, the trading district of the Columbia Department of the Hudson's Bay Company from 1821 to the Oregon Treaty of 1846, by which most of the Columbia District was formally annexed to the United States. HBC lands south of the 49th parallel were guaranteed by the Oregon Treaty but ownership and compensation issues were not fully resolved until 1861.
New Caledonia, fur district. First created in 1805 as part of North West Company for operations, administered by Hudson's Bay Company following the two companies' forced merger in 1821, until incorporated as the part of the Colony of British Columbia in 1858, by which time the term "New Caledonia" had come to refer to the whole of the British Columbia mainland, not just the original fur district in what is now its Central Interior.
Stikine Territory, also called Stickeen Territories, founded in 1862 in response to the Stikine Gold Rush to prevent an American takeover.
North-Western Territory, a Hudson's Bay Company trading area covering lands north and northwest of Rupert's Land and, after 1863, north of the Stikine Territory's original boundary at the 62nd parallel. Its remnant was incorporated at the Yukon Territory after the part of it south of the 60th parallel was amalgamated to British Columbia.
Nova Albion, never incorporated or settled, exact location unknown, claimed by Sir Francis Drake and one of the precedents for the British claims to the Pacific Northwest during the Oregon boundary dispute.
the southeastern Alaska Panhandle was leased from the Russian Empire, from 1839 to 1867, until the lease was ignored by both the Russians and Americans and, subsequently, by the Canadian and the British imperial governments, despite British Columbia's protests.

text: Central and South America, Caribbean[edit]

text: English and later British Caribbean colonies[edit]

text: In order of settlement or founding:

text:
Saint Kitts – The island was settled by Sir Thomas Warner in 1623. The following year the French also settled part of St Kitts. After they massacred the Caribs, the British and French turned on each other and St Kitts changed hands between the two several times before the Treaty of Paris (1783) gave the island to Britain. It became independent as part of Saint Kitts and Nevis in 1983.
Barbados – The island was claimed for the British Empire in 1625, and later settled in 1627 as a proprietary colony of Anglo-Dutchman William Courten. It became an independent nation in 1966.
Nevis – The island was permanently settled in 1628. It became independent as part of Saint Kitts and Nevis in 1983.
Providencia Island – part of an archipelago off the coast of Nicaragua, this island was settled in 1630 by English Puritans. The colony was conquered by the Spanish and became extinct in 1641. The island is today administered by Colombia. Providence Island colony was a sister colony to the more well known Massachusetts Bay Colony.
Antigua – The island was settled in 1632. It became independent as part of Antigua and Barbuda in 1981.
Barbuda – The island was settled about 1632. It became independent as part of Antigua and Barbuda in 1981.
Montserrat – The island was settled in 1632. It was occupied by the French in 1664–68 and 1782–84. It remains a British territory.
Bahamas – The islands were settled from 1647. They became independent in 1973.
Anguilla – The island was settled in 1650. Its government was united with St Christopher (St Kitts) from 1882 until 1967, when it declared its separation. It was brought back under British administration in 1969. It remains a British territory.
Jamaica – The island was conquered from Spain in 1655. It became independent in 1962.
British Virgin Islands – The islands were settled from 1666. They remain a British territory.
Cayman Islands – The islands were acquired from Spain in 1670. They remain a British territory.
Turks and Caicos Islands – The islands were first permanently settled in the 1750s. They remain a British territory.

A linen market in the West Indies, circa 1780

Dominica – The island was captured from the French in 1761. The French occupied it again from 1778 to 1783. Dominica became independent in 1978.
Trinidad and Tobago – The island of Tobago was captured in 1762. The island of Trinidad was captured from the Spanish in 1797. The two governments were joined in 1888. They became independent in 1962.
Saint Vincent and the Grenadines – Saint Vincent was colonised in 1762. France captured it in 1779 but returned it to Britain in 1783. The islands were part of the British colony of the British Windward Islands from 1871 to 1958. The nation gained full independence in 1979.
Grenada – The island was conquered from France in 1762. The French reoccupied it from 1779 to 1783. It became independent in 1974.
Saint Lucia – The island was captured from the French in 1778, but returned in 1783. In 1796 and in 1803 it was captured again, but permanently annexed by Britain in 1814. Saint Lucia became independent in 1979.

text: English and later British Central and South American colonies[edit]

text:
Belize – from 1638 English adventurers used Belize as a source of logwood, a tree used to make a wool dye. The area was claimed by Spain but they had not settled it or been able to control the natives. The Spanish destroyed the British colony in 1717, 1730, 1754 and 1779. The Spanish attacked a final time in 1798, but were defeated. The colony was known as British Honduras from the 19th century until 1973, when its name changed to Belize. Guatemalan claims to Belize delayed independence, but full independence was granted in 1981.[6]
Mosquito Coast (Nicaragua's Caribbean coast) – This area was first settled by the English in 1630. It was briefly assigned to Honduras in 1859, along with the Bay Islands north of the country, then ceded to Nicaragua in 1860; the area was disputed until a treaty of 1965 divided the Mosquito Coast for each country.[clarification needed][citation needed]
British Guiana – The English began colonies in the Guiana area in the early 17th century. In the Treaty of Breda, the Dutch gained control of these colonies. Britain later controlled various colonies in the area. Britain ceded Suriname in exchange for New Amsterdam. The Congress of Vienna (1815) awarded the settlements of Berbice, Demerara, and Essequibo in the Guiana region to Great Britain; they were united as British Guiana in 1831. It became independent as Guyana in 1966. Currently, Venezuela claims sovereignty over half of Guyana's territory.
Falkland Islands – The British first established a presence on the Falkland Islands in 1765 but were compelled to withdraw for economic reasons related to the American War of Independence in 1774.[7] The islands continued to be used by British sealers and whalers, although the settlement of Port Egmont was destroyed by the Spanish in 1780. Argentina attempted to establish a colony in the ruins of the former Spanish settlement of Puerto Soledad, which ended with the British return in 1833. The islands have been under British control ever since, save for a brief Argentine occupation during the Falklands War of 1982.


document_title: Collagen

question_text: where is collagen found in the human body

root

text: Collagen

text: Types[edit]

text: Collagen occurs in many places throughout the body. Over 90% of the collagen in the human body, however, is type I.[8]

tag: p

text: So far, 28 types of collagen have been identified and described. They can be divided into several groups according to the structure they form:

text:
Fibrillar (Type I, II, III, V, XI)
Non-fibrillar
FACIT (Fibril Associated Collagens with Interrupted Triple Helices) (Type IX, XII, XIV, XIX, XXI)
Short chain (Type VIII, X)
Basement membrane (Type IV)
Multiplexin (Multiple Triple Helix domains with Interruptions) (Type XV, XVIII)
MACIT (Membrane Associated Collagens with Interrupted Triple Helices) (Type XIII, XVII)
Other (Type VI, VII)

tag: ul

text: The five most common types are:

text:
Type I: skin, tendon, vasculature, organs, bone (main component of the organic part of bone)
Type II: cartilage (main collagenous component of cartilage)
Type III: reticulate (main component of reticular fibers), commonly found alongside type I.
Type IV: forms basal lamina, the epithelium-secreted layer of the basement membrane.
Type V: cell surfaces, hair, and placenta

text: Medical uses[edit]

text: Cardiac applications[edit]

text: The collagenous cardiac skeleton which includes the four heart valve rings, is histologically, elastically and uniquely bound to cardiac muscle. The cardiac skeleton also includes the separating septa of the heart chambers – the interventricular septum and the atrioventricular septum. Collagen contribution to the measure of cardiac performance summarily represents a continuous torsional force opposed to the fluid mechanics of blood pressure emitted from the heart. The collagenous structure that divides the upper chambers of the heart from the lower chambers is an impermeable membrane that excludes both blood and electrical impulses through typical physiological means. With support from collagen, atrial fibrillation should never deteriorate to ventricular fibrillation. Collagen is layered in variable densities with cardiac muscle mass. The mass, distribution, age and density of collagen all contribute to the compliance required to move blood back and forth. Individual cardiac valvular leaflets are folded into shape by specialized collagen under variable pressure. Gradual calcium deposition within collagen occurs as a natural function of aging. Calcified points within collagen matrices show contrast in a moving display of blood and muscle, enabling methods of cardiac imaging technology to arrive at ratios essentially stating blood in (cardiac input) and blood out (cardiac output). Pathology of the collagen underpinning of the heart is understood within the category of connective tissue disease.

text: Cosmetic surgery[edit]

text: Collagen has been widely used in cosmetic surgery, as a healing aid for burn patients for reconstruction of bone and a wide variety of dental, orthopedic, and surgical purposes. Both human and bovine collagen is widely used as dermal fillers for treatment of wrinkles and skin aging.[9] Some points of interest are:

text:
When used cosmetically, there is a chance of allergic reactions causing prolonged redness; however, this can be virtually eliminated by simple and inconspicuous patch testing prior to cosmetic use.
Most medical collagen is derived from young beef cattle (bovine) from certified BSE-free animals. Most manufacturers use donor animals from either "closed herds", or from countries which have never had a reported case of BSE such as Australia, Brazil, and New Zealand.

tag: ol

text: Bone grafts[edit]

text: As the skeleton forms the structure of the body, it is vital that it maintains its strength, even after breaks and injuries. Collagen is used in bone grafting as it has a triple helical structure, making it a very strong molecule. It is ideal for use in bones, as it does not compromise the structural integrity of the skeleton. The triple helical structure of collagen prevents it from being broken down by enzymes, it enables adhesiveness of cells and it is important for the proper assembly of the extracellular matrix.[10]

text: Tissue regeneration[edit]

text: Collagen scaffolds are used in tissue regeneration, whether in sponges, thin sheets, or gels. Collagen has the correct properties for tissue regeneration such as pore structure, permeability, hydrophilicity, and being stable in vivo. Collagen scaffolds are also ideal for the deposition of cells such as osteoblasts and fibroblasts, and once inserted, growth is able to continue as normal in the tissue.[11]

text: Reconstructive surgical uses[edit]

text: Collagens are widely employed in the construction of the artificial skin substitutes used in the management of severe burns and wounds.[12][13] These collagens may be derived from bovine, equine, porcine, or even human sources; and are sometimes used in combination with silicones, glycosaminoglycans, fibroblasts, growth factors and other substances.

text: Wound care[edit]

text: Collagen is one of the body’s key natural resources and a component of skin tissue that can benefit all stages of the wound healing process.[14] When collagen is made available to the wound bed, closure can occur. Wound deterioration, followed sometimes by procedures such as amputation, can thus be avoided.

text: Collagen is a natural product and is thus used as a natural wound dressing and has properties that artificial wound dressings do not have. It is resistant against bacteria, which is of vital importance in a wound dressing. It helps to keep the wound sterile, because of its natural ability to fight infection. When collagen is used as a burn dressing, healthy granulation tissue is able to form very quickly over the burn, helping it to heal rapidly.[15]

text: Throughout the 4 phases of wound healing, collagen performs the following functions in wound healing:

text:
Guiding function: Collagen fibers serve to guide fibroblasts. Fibroblasts migrate along a connective tissue matrix.
Chemotactic properties: The large surface area available on collagen fibers can attract fibrogenic cells which help in healing.
Nucleation: Collagen, in the presence of certain neutral salt molecules can act as a nucleating agent causing formation of fibrillar structures. A collagen wound dressing might serve as a guide for orienting new collagen deposition and capillary growth.
Hemostatic properties: Blood platelets interact with the collagen to make a hemostatic plug.

text: As a supplement[edit]

text: When hydrolyzed, collagen is reduced to small peptides, which can be ingested in the form of dietary supplement or functional foods and beverages with the intent to aid joint and bone health and enhance skin health.[16][17][18][19][20][21][22] Hydrolyzed collagen has a much smaller molecular weight in comparison to native collagen or gelatin, study suggests that more than 90% of hydrolyzed collagen is digested and available as small peptides in the blood stream within one hour. From the blood, the peptides (containing hydroxyproline) are transported into the target tissues (e.g., skin, bones, and cartilage), where the peptides act as building blocks for local cells and help boost the production of new collagen fibers.[23][24][25]

text: Basic research[edit]

text: Collagen is used in laboratory studies for cell culture, studying cell behavior and cellular interactions with the extracellular environment.[26]

text: Veterinary use[edit]

text: Some studies have shown efficacy of collagen supplementation for dogs with osteoarthritis pain, alone or in combination with other nutraceuticals like glucosamine and chondroitin.[27][28]

text: Chemistry[edit]

text: The collagen protein is composed of a triple helix, which generally consists of two identical chains (α1) and an additional chain that differs slightly in its chemical composition (α2).[29] The amino acid composition of collagen is atypical for proteins, particularly with respect to its high hydroxyproline content. The most common motifs in the amino acid sequence of collagen are glycine-proline-X and glycine-X-hydroxyproline, where X is any amino acid other than glycine, proline or hydroxyproline. The average amino acid composition for fish and mammal skin is given.[29]

text:
Amino acid
Abundance in mammal skin(residues/1000)
Abundance in fish skin(residues/1000)

Glycine
329
339

Proline
126
108

Alanine
109
114

Hydroxyproline
95
67

Glutamic acid
74
76

Arginine
49
52

Aspartic acid
47
47

Serine
36
46

Lysine
29
26

Leucine
24
23

Valine
22
21

Threonine
19
26

Phenylalanine
13
14

Isoleucine
11
11

Hydroxylysine
6
8

Methionine
6
13

Histidine
5
7

Tyrosine
3
3

Cysteine
1
1

Tryptophan
0
0

tag: table

text: Synthesis[edit]

text:
First, a three-dimensional stranded structure is assembled, with the amino acids glycine and proline as its principal components. This is not yet collagen but its precursor, procollagen. Procollagen is then modified by the addition of hydroxyl groups to the amino acids proline and lysine. This step is important for later glycosylation and the formation of the triple helix structure of collagen. Because the hydroxylase enzymes that perform these reactions require vitamin C as a cofactor, a long-term deficiency in this vitamin results in impaired collagen synthesis and scurvy.[30] These hydroxylation reactions are catalyzed by two different enzymes: prolyl-4-hydroxylase[31] and lysyl-hydroxylase. Vitamin C also serves with them in inducing these reactions. In this service, one molecule of vitamin C is destroyed for each H replaced by OH.
[32]
The synthesis of collagen occurs inside and outside of the cell. The formation of collagen which results in fibrillary collagen (most common form) is discussed here. Meshwork collagen, which is often involved in the formation of filtration systems, is the other form of collagen. All types of collagens are triple helices, and the differences lie in the make-up of the alpha peptides created in step 2.

text:
Transcription of mRNA: About 34 genes are associated with collagen formation, each coding for a specific mRNA sequence, and typically have the "COL" prefix. The beginning of collagen synthesis begins with turning on genes which are associated with the formation of a particular alpha peptide (typically alpha 1, 2 or 3).
Pre-pro-peptide formation: Once the final mRNA exits from the cell nucleus and enters into the cytoplasm, it links with the ribosomal subunits and the process of translation occurs. The early/first part of the new peptide is known as the signal sequence. The signal sequence on the N-terminal of the peptide is recognized by a signal recognition particle on the endoplasmic reticulum, which will be responsible for directing the pre-pro-peptide into the endoplasmic reticulum. Therefore, once the synthesis of new peptide is finished, it goes directly into the endoplasmic reticulum for post-translational processing. It is now known as pre-pro-collagen.
Pre-pro-peptide to pro-collagen: Three modifications of the pre-pro-peptide occur leading to the formation of the alpha peptide:
The signal peptide on the N-terminal is dissolved, and the molecule is now known as propeptide (not procollagen).
Hydroxylation of lysines and prolines on propeptide by the enzymes 'prolyl hydroxylase' and 'lysyl hydroxylase' (to produce hydroxyproline and hydroxylysine) occurs to aid cross-linking of the alpha peptides. This enzymatic step requires vitamin C as a cofactor. In scurvy, the lack of hydroxylation of prolines and lysines causes a looser triple helix (which is formed by three alpha peptides).
Glycosylation occurs by adding either glucose or galactose monomers onto the hydroxyl groups that were placed onto lysines, but not on prolines.
Once these modifications have taken place, three of the hydroxylated and glycosylated propeptides twist into a triple helix forming procollagen. Procollagen still has unwound ends, which will be later trimmed. At this point, the procollagen is packaged into a transfer vesicle destined for the Golgi apparatus.
Golgi apparatus modification: In the Golgi apparatus, the procollagen goes through one last post-translational modification before being secreted out of the cell. In this step, oligosaccharides (not monosaccharides as in step 3) are added, and then the procollagen is packaged into a secretory vesicle destined for the extracellular space.
Formation of tropocollagen: Once outside the cell, membrane bound enzymes known as 'collagen peptidases', remove the "loose ends" of the procollagen molecule. What is left is known as tropocollagen. Defects in this step produce one of the many collagenopathies known as Ehlers-Danlos syndrome. This step is absent when synthesizing type III, a type of fibrilar collagen.
Formation of the collagen fibril: lysyl oxidase, an extracellular copper-dependent enzyme, produces the final step in the collagen synthesis pathway. This enzyme acts on lysines and hydroxylysines producing aldehyde groups, which will eventually undergo covalent bonding between tropocollagen molecules. This polymer of tropocollogen is known as a collagen fibril.

text: Amino acids[edit]

text: Collagen has an unusual amino acid composition and sequence:

text:
Glycine is found at almost every third residue.
Proline makes up about 17% of collagen.
Collagen contains two uncommon derivative amino acids not directly inserted during translation. These amino acids are found at specific locations relative to glycine and are modified post-translationally by different enzymes, both of which require vitamin C as a cofactor.
Hydroxyproline derived from proline
Hydroxylysine derived from lysine - depending on the type of collagen, varying numbers of hydroxylysines are glycosylated (mostly having disaccharides attached).

text: Cortisol stimulates degradation of (skin) collagen into amino acids.[33]

text: Collagen I formation[edit]

text: Most collagen forms in a similar manner, but the following process is typical for type I:

text:
Inside the cell
Two types of alpha chains are formed during translation on ribosomes along the rough endoplasmic reticulum (RER): alpha-1 and alpha-2 chains. These peptide chains (known as preprocollagen) have registration peptides on each end and a signal peptide.
Polypeptide chains are released into the lumen of the RER.
Signal peptides are cleaved inside the RER and the chains are now known as pro-alpha chains.
Hydroxylation of lysine and proline amino acids occurs inside the lumen. This process is dependent on ascorbic acid (vitamin C) as a cofactor.
Glycosylation of specific hydroxylysine residues occurs.
Triple alpha helical structure is formed inside the endoplasmic reticulum from two alpha-1 chains and one alpha-2 chain.
Procollagen is shipped to the Golgi apparatus, where it is packaged and secreted by exocytosis.
Outside the cell
Registration peptides are cleaved and tropocollagen is formed by procollagen peptidase.
Multiple tropocollagen molecules form collagen fibrils, via covalent cross-linking (aldol reaction) by lysyl oxidase which links hydroxylysine and lysine residues. Multiple collagen fibrils form into collagen fibers.
Collagen may be attached to cell membranes via several types of protein, including fibronectin, laminin, fibulin and integrin.

text: Synthetic pathogenesis[edit]

text: Vitamin C deficiency causes scurvy, a serious and painful disease in which defective collagen prevents the formation of strong connective tissue. Gums deteriorate and bleed, with loss of teeth; skin discolors, and wounds do not heal. Prior to the 18th century, this condition was notorious among long-duration military, particularly naval, expeditions during which participants were deprived of foods containing vitamin C.

text: An autoimmune disease such as lupus erythematosus or rheumatoid arthritis[34] may attack healthy collagen fibers.

text: Many bacteria and viruses secrete virulence factors, such as the enzyme collagenase, which destroys collagen or interferes with its production.

text: Molecular structure[edit]

text: A single collagen molecule, tropocollagen, is used to make up larger collagen aggregates, such as fibrils. It is approximately 300 nm long and 1.5 nm in diameter, and it is made up of three polypeptide strands (called alpha peptides, see step 2), each of which has the conformation of a left-handed helix – this should not be confused with the right-handed alpha helix. These three left-handed helices are twisted together into a right-handed triple helix or "super helix", a cooperative quaternary structure stabilized by many hydrogen bonds. With type I collagen and possibly all fibrillar collagens, if not all collagens, each triple-helix associates into a right-handed super-super-coil referred to as the collagen microfibril. Each microfibril is interdigitated with its neighboring microfibrils to a degree that might suggest they are individually unstable, although within collagen fibrils, they are so well ordered as to be crystalline.

text: A distinctive feature of collagen is the regular arrangement of amino acids in each of the three chains of these collagen subunits. The sequence often follows the pattern Gly-Pro-X or Gly-X-Hyp, where X may be any of various other amino acid residues.[29] Proline or hydroxyproline constitute about 1/6 of the total sequence. With glycine accounting for the 1/3 of the sequence, this means approximately half of the collagen sequence is not glycine, proline or hydroxyproline, a fact often missed due to the distraction of the unusual GX1X2 character of collagen alpha-peptides. The high glycine content of collagen is important with respect to stabilization of the collagen helix as this allows the very close association of the collagen fibers within the molecule, facilitating hydrogen bonding and the formation of intermolecular cross-links.[29] This kind of regular repetition and high glycine content is found in only a few other fibrous proteins, such as silk fibroin.

text: Collagen is not only a structural protein. Due to its key role in the determination of cell phenotype, cell adhesion, tissue regulation, and infrastructure, many sections of its non-proline-rich regions have cell or matrix association/regulation roles. The relatively high content of proline and hydroxyproline rings, with their geometrically constrained carboxyl and (secondary) amino groups, along with the rich abundance of glycine, accounts for the tendency of the individual polypeptide strands to form left-handed helices spontaneously, without any intrachain hydrogen bonding.

text: Because glycine is the smallest amino acid with no side chain, it plays a unique role in fibrous structural proteins. In collagen, Gly is required at every third position because the assembly of the triple helix puts this residue at the interior (axis) of the helix, where there is no space for a larger side group than glycine’s single hydrogen atom. For the same reason, the rings of the Pro and Hyp must point outward. These two amino acids help stabilize the triple helix—Hyp even more so than Pro; a lower concentration of them is required in animals such as fish, whose body temperatures are lower than most warm-blooded animals. Lower proline and hydroxyproline contents are characteristic of cold-water, but not warm-water fish; the latter tend to have similar proline and hydroxyproline contents to mammals.[29] The lower proline and hydroxproline contents of cold-water fish and other poikilotherm animals leads to their collagen having a lower thermal stability than mammalian collagen.[29] This lower thermal stability means that gelatin derived from fish collagen is not suitable for many food and industrial applications.

text: The tropocollagen subunits spontaneously self-assemble, with regularly staggered ends, into even larger arrays in the extracellular spaces of tissues.[35][36] Additional assembly of fibrils is guided by fibroblasts, which deposit fully formed fibrils from fibripositors. In the fibrillar collagens, molecules are staggered to adjacent molecules by about 67 nm (a unit that is referred to as ‘D’ and changes depending upon the hydration state of the aggregate). In each D-period repeat of the microfibril, there is a part containing five molecules in cross-section, called the “overlap”, and a part containing only four molecules, called the "gap".[37] These overlap and gap regions are retained as microfibrils assemble into fibrils, and are thus viewable using electron microscopy. The triple helical tropocollagens in the microfibrils are arranged in a quasihexagonal packing pattern.[37][38]

text: There is some covalent crosslinking within the triple helices, and a variable amount of covalent crosslinking between tropocollagen helices forming well organized aggregates (such as fibrils).[39] Larger fibrillar bundles are formed with the aid of several different classes of proteins (including different collagen types), glycoproteins, and proteoglycans to form the different types of mature tissues from alternate combinations of the same key players.[36] Collagen's insolubility was a barrier to the study of monomeric collagen until it was found that tropocollagen from young animals can be extracted because it is not yet fully crosslinked. However, advances in microscopy techniques (i.e. electron microscopy (EM) and atomic force microscopy (AFM)) and X-ray diffraction have enabled researchers to obtain increasingly detailed images of collagen structure in situ. These later advances are particularly important to better understanding the way in which collagen structure affects cell–cell and cell–matrix communication and how tissues are constructed in growth and repair and changed in development and disease.[40][41] For example, using AFM–based nanoindentation it has been shown that a single collagen fibril is a heterogeneous material along its axial direction with significantly different mechanical properties in its gap and overlap regions, correlating with its different molecular organizations in these two regions.[42]

text: Collagen fibrils/aggregates are arranged in different combinations and concentrations in various tissues to provide varying tissue properties. In bone, entire collagen triple helices lie in a parallel, staggered array. 40 nm gaps between the ends of the tropocollagen subunits (approximately equal to the gap region) probably serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component, which is hydroxylapatite (approximately) Ca10(OH)2(PO4)6.[43] Type I collagen gives bone its tensile strength.

text: Associated disorders[edit]

text: Collagen-related diseases most commonly arise from genetic defects or nutritional deficiencies that affect the biosynthesis, assembly, postranslational modification, secretion, or other processes involved in normal collagen production.

text:
Genetic Defects of Collagen Genes

Type
Notes
Gene(s)
Disorders

I
This is the most abundant collagen of the human body. It is present in scar tissue, the end product when tissue heals by repair. It is found in tendons, skin, artery walls, cornea, the endomysium surrounding muscle fibers, fibrocartilage, and the organic part of bones and teeth.
COL1A1, COL1A2
Osteogenesis imperfecta, Ehlers–Danlos syndrome, Infantile cortical hyperostosis a.k.a. Caffey's disease

II
Hyaline cartilage, makes up 50% of all cartilage protein. Vitreous humour of the eye.
COL2A1
Collagenopathy, types II and XI

III
This is the collagen of granulation tissue and is produced quickly by young fibroblasts before the tougher type I collagen is synthesized. Reticular fiber. Also found in artery walls, skin, intestines and the uterus
COL3A1
Ehlers–Danlos syndrome, Dupuytren's contracture

IV
Basal lamina; eye lens. Also serves as part of the filtration system in capillaries and the glomeruli of nephron in the kidney.
COL4A1, COL4A2, COL4A3, COL4A4, COL4A5, COL4A6
Alport syndrome, Goodpasture's syndrome

V
Most interstitial tissue, assoc. with type I, associated with placenta
COL5A1, COL5A2, COL5A3
Ehlers–Danlos syndrome (Classical)

VI
Most interstitial tissue, assoc. with type I
COL6A1, COL6A2, COL6A3, COL6A5
Ulrich myopathy, Bethlem myopathy, Atopic dermatitis[44]

VII
Forms anchoring fibrils in dermoepidermal junctions
COL7A1
Epidermolysis bullosa dystrophica

VIII
Some endothelial cells
COL8A1, COL8A2
Posterior polymorphous corneal dystrophy 2

IX
FACIT collagen, cartilage, assoc. with type II and XI fibrils
COL9A1, COL9A2, COL9A3
EDM2 and EDM3

X
Hypertrophic and mineralizing cartilage
COL10A1
Schmid metaphyseal dysplasia

XI
Cartilage
COL11A1, COL11A2
Collagenopathy, types II and XI

XII
FACIT collagen, interacts with type I containing fibrils, decorin and glycosaminoglycans
COL12A1
–

XIII
Transmembrane collagen, interacts with integrin a1b1, fibronectin and components of basement membranes like nidogen and perlecan.
COL13A1
–

XIV
FACIT collagen, also known as undulin
COL14A1
–

XV
–
COL15A1
–

XVI
–
COL16A1
–

XVII
Transmembrane collagen, also known as BP180, a 180 kDa protein
COL17A1
Bullous pemphigoid and certain forms of junctional epidermolysis bullosa

XVIII
Source of endostatin
COL18A1
–

XIX
FACIT collagen
COL19A1
–

XX
–
COL20A1
–

XXI
FACIT collagen
COL21A1
–

XXII
–
COL22A1
–

XXIII
MACIT collagen
COL23A1
–

XXIV
–
COL24A1
–

XXV
–
COL25A1
–

XXVI
–
EMID2
–

XXVII
–
COL27A1
–

XXVIII
–
COL28A1
–

XXIX
Epidermal collagen
COL29A1
Atopic Dermatitis[45]

text: In addition to the above-mentioned disorders, excessive deposition of collagen occurs in scleroderma.

text: Diseases[edit]

text: One thousand mutations have been identified in 12 out of more than 20 types of collagen. These mutations can lead to various diseases at the tissue level.[46]

text: Osteogenesis imperfecta – Caused by a mutation in type 1 collagen, dominant autosomal disorder, results in weak bones and irregular connective tissue, some cases can be mild while others can be lethal. Mild cases have lowered levels of collagen type 1 while severe cases have structural defects in collagen.[47]

text: Chondrodysplasias – Skeletal disorder believed to be caused by a mutation in type 2 collagen, further research is being conducted to confirm this.[48]

text: Ehlers-Danlos syndrome – Six different types of this disorder, which lead to deformities in connective tissue, are known. Some types can be lethal, leading to the rupture of arteries. Each syndrome is caused by a different mutation, for example type four of this disorder is caused by a mutation in collagen type 3.[49]

text: Alport syndrome – Can be passed on genetically, usually as X-linked dominant, but also as both an autosomal dominant and autosomal recessive disorder, sufferers have problems with their kidneys and eyes, loss of hearing can also develop in during the childhood or adolescent years.[50]

text: Osteoporosis – Not inherited genetically, brought on with age, associated with reduced levels of collagen in the skin and bones, growth hormone injections are being researched as a possible treatment to counteract any loss of collagen.[51]

text: Knobloch syndrome – Caused by a mutation in the COL18A1 gene that codes for the production of collagen XVIII. Patients present with protrusion of the brain tissue and degeneration of the retina; an individual who has family members suffering from the disorder is at an increased risk of developing it themselves since there is a hereditary link.[46]

text: Characteristics[edit]

text: Collagen is one of the long, fibrous structural proteins whose functions are quite different from those of globular proteins, such as enzymes. Tough bundles of collagen called collagen fibers are a major component of the extracellular matrix that supports most tissues and gives cells structure from the outside, but collagen is also found inside certain cells. Collagen has great tensile strength, and is the main component of fascia, cartilage, ligaments, tendons, bone and skin.[52][53] Along with elastin and soft keratin, it is responsible for skin strength and elasticity, and its degradation leads to wrinkles that accompany aging.[9] It strengthens blood vessels and plays a role in tissue development. It is present in the cornea and lens of the eye in crystalline form. It may be one of the most abundant proteins in the fossil record, given that it appears to fossilize frequently, even in bones from the Mesozoic and Paleozoic.[54]

text: Uses[edit]

text: Collagen has a wide variety of applications, from food to medical. For instance, it is used in cosmetic surgery and burn surgery. It is widely used in the form of collagen casings for sausages, which are also used in the manufacture of musical strings.

text: If collagen is subject to sufficient denaturation, e.g. by heating, the three tropocollagen strands separate partially or completely into globular domains, containing a different secondary structure to the normal collagen polyproline II (PPII), e.g. random coils. This process describes the formation of gelatin, which is used in many foods, including flavored gelatin desserts. Besides food, gelatin has been used in pharmaceutical, cosmetic, and photography industries.

text: From the Greek for glue, kolla, the word collagen means "glue producer" and refers to the early process of boiling the skin and sinews of horses and other animals to obtain glue. Collagen adhesive was used by Egyptians about 4,000 years ago, and Native Americans used it in bows about 1,500 years ago. The oldest glue in the world, carbon-dated as more than 8,000 years old, was found to be collagen—used as a protective lining on rope baskets and embroidered fabrics, and to hold utensils together; also in crisscross decorations on human skulls.[55] Collagen normally converts to gelatin, but survived due to dry conditions. Animal glues are thermoplastic, softening again upon reheating, so they are still used in making musical instruments such as fine violins and guitars, which may have to be reopened for repairs—an application incompatible with tough, synthetic plastic adhesives, which are permanent. Animal sinews and skins, including leather, have been used to make useful articles for millennia.

text: Gelatin-resorcinol-formaldehyde glue (and with formaldehyde replaced by less-toxic pentanedial and ethanedial) has been used to repair experimental incisions in rabbit lungs.[56]

text: History[edit]

text:
The molecular and packing structures of collagen have eluded scientists over decades of research. The first evidence that it possesses a regular structure at the molecular level was presented in the mid-1930s.[57][58] Since that time, many prominent scholars, including Nobel laureates Crick, Pauling, Rich and Yonath, and others, including Brodsky, Berman, and Ramachandran, concentrated on the conformation of the collagen monomer. Several competing models, although correctly dealing with the conformation of each individual peptide chain, gave way to the triple-helical "Madras" model of Ramachandran, which provided an essentially correct model of the molecule's quaternary structure[59][60][61] although this model still required some refinement.[62][clarification needed] [63][64][65][66] The packing structure of collagen has not been defined to the same degree outside of the fibrillar collagen types, although it has been long known to be hexagonal or quasi-hexagonal.[38][67][68] As with its monomeric structure, several conflicting models alleged that either the packing arrangement of collagen molecules is 'sheet-like' or microfibrillar.[62][69][70] The microfibrillar structure of collagen fibrils in tendon, cornea and cartilage has been directly imaged by electron microscopy.[71][72][73] The microfibrillar structure of tail tendon, as described by Fraser, Miller, and Wess (amongst others), was modeled as being closest to the observed structure,[62] although it oversimplified the topological progression of neighboring collagen molecules, and hence did not predict the correct conformation of the discontinuous D-periodic pentameric arrangement termed simply: the microfibril.[37][74][75] Various cross linking agents like L-Dopaquinone, embeline, potassium embelate and 5-O-methyl embelin could be developed as potential
cross-linking/stabilization agents of collagen preparation and its application as wound dressing sheet in clinical applications is enhanced.[76]

text: The evolution of collagens was a fundamental step in the early evolution of life, supporting the coalescence of multicellular life forms.[77]

text: D-banding[edit]

text: Collagen D-banding is viable as periodic formation of ridging on all fibrils forming collagen[78].  D-bands are created due to the semi-crystalline formation of the collagen within the fibrils.  The pattern exhibited by D-banding is consistently independent of fibril diameter[79].  When undergoing deformation, collagen fibrils may lose their D-banding, making the disappearance of the d-bands an indicator of the type of damage undergone by then tendon fibrils.


document_title: The Dauphin (Star Trek: The Next Generation)

question_text: star trek next generation season 2 episode 10

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text:
"The Dauphin"

Star Trek: The Next Generation episode

Episode no.
Season 2
Episode 10

Directed by
Rob Bowman

Written by

Scott Rubenstein
Leonard Mlodinow

Featured music
Dennis McCarthy

Production code
136

Original air date
February 20, 1989 (1989-02-20)

Guest appearance(s)

Diana Muldaur - Katherine Pulaski
Paddi Edwards - Anya
Jaime Hubbard - Salia
Whoopi Goldberg - Guinan
Colm Meaney - Miles O'Brien
Peter Neptune - Aron
Mädchen Amick - Young Anya
Cindy Sorensen - Furry Animal
Jennifer Barlow - Gibson

Episode chronology

← Previous
"The Measure of a Man"
Next →
"Contagion"

List of Star Trek: The Next Generation episodes

text: "The Dauphin" is the tenth episode of the second season of the American science fiction television series Star Trek: The Next Generation, the 36th episode overall. It was originally released on February 20, 1989 in broadcast syndication.

text: Set in the 24th century, the series follows the adventures of the crew of the Federation starship Enterprise. In this episode, the Enterprise must transport a young head of state to the planet she is to lead.

text: Plot[edit]

text: The Federation starship Enterprise, under the command of Captain Jean-Luc Picard, is assigned to transport beautiful Salia, the future ruler and dauphin of Daled IV, and her governess Anya from a planet to where she voluntarily exiled herself. Her parents, rulers of two opposing factions on Daled IV, recently died, and Salia represents a chance to bring unification to the two factions. As such, Anya is overly protective of her. On board, Salia meets young Acting Ensign Wesley Crusher, who instantly becomes smitten with her. Wesley receives courtship advice from the crew members (including from Worf, who explains that with Klingons it consists of "the male grunting and growling, followed by the female bellowing and hurling heavy objects, the males read poetry"), and the two form a bond. He introduces her to Thalian chocolate mousse, and takes her to the holodeck to show her several other worlds after she expresses an interest in exploring the galaxy.

text: When Anya, touring the ship, discovers a crew member with a virulent disease being in a containment field in Sickbay, she demands the crew member be killed to protect Salia. Chief Medical Officer Dr. Pulaski refuses and insists the disease is contained, but Anya transforms into a large monstrous form, easily matching Lt. Worf's strength when he tries to intervene. When Captain Picard arrives, Anya reverts to her petite humanoid form and defiantly explains her actions. Dr. Pulaski identifies Anya as an allasomorph, a shapeshifter, who could present a danger for the crew. Picard orders Anya to be confined to quarters, and Worf, as head of security, promises Anya he will watch over Salia. Picard, aware of Wesley's attraction to Salia, asks him to stay away from her, to which he agrees. At night however, as Anya is sleeping, Salia slips out of their quarters and visits Wesley, and the two share a kiss. However, they are interrupted when Anya bursts into his quarters and transforms into the same giant beast as before. To Wesley's horror, Salia also transforms into a similar beast, holding Anya at bay. Both revert to their human forms as security arrives. Later, Salia attempts to apologize to Wesley for her deception, but Wesley, appalled by seeing Salia's appearance was not the real her, is too upset and refuses to listen.

text: The Enterprise arrives at Daled IV with no further incidents. As Salia prepares to depart, Anya reveals she will not be going with her, instead returning to her home on an orbiting moon. Anya also warns her that she will likely be unable to leave the planet once she has taken the leadership role. Salia thanks Anya for her upbringing before Anya departs. Just before Salia is to be beamed down to the planet, Wesley arrives to say his goodbyes, bringing her one last taste of chocolate mousse. Salia thanks him, and transforms into her natural form, a luminous figure of energy, before she is beamed down to the planet.