query: What was Maria Sibylla Merian's first publication?

title: Maria Sibylla Merian

text: Merian first made a name for herself as an botanical artist. In 1675 she started to publish a three volume series, each with 12 plates depicting flowers.[22] In 1680 she published Neues Blumenbuch, combining the series.[23]

title: Merian family

text: The younger Basel line includes a Frankfurt sub-branch founded by the engraver Matthäus Merian the Elder (1593-1650), whose descendants became artists during the Baroque period and ran what became one of Europe's largest publishers in the 17th century. Matthäus Merian's daughter was the naturalist and artist Maria Sibylla Merian.

title: Maria Sibylla Merian

text: Merian was the first European women to independently go on a scientific expedition in South America. In the 19th century Ida Pfeiffer, Alexandrine Tinne, Florence Baker, Mary French Sheldon, Mary Henrietta Kingsley and Marianne North followed in her footsteps and explore the natural world of Africa. Margaret Fountaine studied butterflies on five continents.[48] Merian's scientific expedition of Surinam predated Alexander von Humboldt's famous South America expedition by 100 years, and that of Princess Theresa of Bavaria by 200 years.[49] Merian's publication on her expedition was later identified as a key exponent of illustrated geographical publications originating in Holland in the late 17th century, which marketed an exotic but accessible new world to Europeans.[50]

title: Maria Sibylla Merian

text: In 1690, Merian's mother had died. A year later, she moved with her daughters to Amsterdam. In 1692, her husband divorced her. In Amsterdam the same year, her daughter Johanna married Jakob Hendrik Herolt, a successful merchant on Surinam, originally from Bacharach. The flower painter Rachel Ruysch became Merian's pupil.[14] Merian made a living selling her paintings.[7] She and her daughter Johanna sold flower pictures to art collector Agnes Block. By 1698 Merian lived in a well-furnished house on Kerkstraat.[15]

title: Maria Sibylla Merian

text: Merian was one of the first naturalists to observe insects directly.[4] Merian collected and observed live insects and created detailed drawings. In her time insects still had a reputation as "beasts of the devil" and the process of metamorphosis was largely unknown. While a handful of scholars had published empirical information on the insect, moth and butterfly life cycle, the widespread contemporary believe was that they were "born of mud" by spontaneous generation. Merian documented evidence to the contrary and described the life cycles of 186 insect species.[14]

title: Maria Sibylla Merian

text: Merian also sold hand coloured editions of the Blumenbuch series.[28] Merian's process of creating her art used vellum which she primed with a white coat.[29] Because of the guild system women were not allowed to paint in oil.[16] Merian painted with watercolors and gouache, instead.[29]

title: Matthäus Merian

text: In 1617, Merian married Maria Magdalena de Bry, daughter of the publisher, and was for a time associated with the de Bry publishing house. In 1620, when Oppenheim was destroyed by fire during the Spanish occupation, they moved back to Basel, but three years later returned to Germany, this time to Frankfurt. They had four daughters and three sons, including Matthäus Merian the Younger. Maria Magdalena de Bry died in 1645 and the following year Matthäus married Johanna Catharina Hein. Five years later, Matthäus died, leaving his wife with two small children, Anna Maria Sibylla Merian (born 1647) who later became a pioneering naturalist and illustrator and a son, Maximilian, who died before his third birthday.

title: Maria Sibylla Merian

text: In 1679 Merian published the first volume of a two-volume series on caterpillars, the second volume followed in 1683. Each volume contained 50 plates engraved and etched by Merian. Along the illustrations Merian included a description of the insects, moths, butterflies and their larvae she had observed.[30] Der Raupen wunderbare Verwandlung und sonderbare Blumennahrung– The Caterpillars' Marvelous Transformation and Strange Floral Food, was very popular in certain segments of high society as a result of being published in the vernacular. However, her work was largely ignored by scientists of the time because the official language of science was still Latin.

title: Maria Sibylla Merian

text: Library resources about Main Page By Main Page

title: Maria Sibylla Merian

text: Merian received her artistic training from her stepfather, Jacob Marrel, a student of the still life painter Georg Flegel. Merian published her first book of natural illustrations in 1675. She had started to collect insects as an adolescent and at age thirteen she raised silk worms. In 1679 Merian published the first volume of a two-volume series on caterpillars, the second volume followed in 1683. Each volume contained 50 plates engraved and etched by Merian. Merian documented evidence on the process of metamorphosis and the plant hosts of 186 European insect species. Along with the illustrations Merian included a descriptions of their life cycles.

title: Maria Sibylla Merian

text: Other women still-life painters, such as Merian's contemporary Margaretha de Heer, included insects in their floral pictures, but did not breed or study them. While women of Merian's day did collect butterflies, the amateur science of naturalism was practised by men.[9] In 1679 she published her first work on insects, the first of a two-volume illustrated book focusing on insect metamorphosis.[4]

title: Catasticta sibyllae

text: The name honors Maria Sibylla Merian, a 17th century European naturalist and entomologist who studied butterflies in South America.

title: Maria Sibylla Merian

text: Maria Sibylla Merian's father, the Swiss engraver and publisher Matthäus Merian the Elder, married her mother, his second wife, Johanna Sybilla Heyne, in 1646. Maria was born within the next year in 1647, making her his 9th child. Her father died in 1650, and in 1651 her mother remarried Jacob Marrel, the flower and still life painter. Marrel encouraged Merian to draw and paint. While he lived mostly in Holland, his pupil Abraham Mignon trained her. At the age of thirteen she painted her first images of insects and plants from specimens she had captured.[4] Early on, she had access to many books about natural history.[5] Regarding her youth, in the foreword to Metamorphosis insectorum Surinamensium, Merian wrote:[6]

title: Maria Sibylla Merian

text: The renewed scientific and artistic interest in her work was triggered in part by a number of scholars who examined collection of her works, such as the one in Rosenborg Castle, Copenhagen.[66] In 2005, a modern research vessel named Maria S. Merian was launched at Warnemünde, Germany. In 2016, Merian's Metamorphosis insectorum Surinamensium was re-published with updated scientific descriptions and, in June 2017, a symposium was held in her honour in Amsterdam.[67][68][69] In March 2017, the Lloyd Library and Museum hosted a "Off the Page", an exhibit rendering many of Merian's illustrations as 3D sculptures with preserved insects, plants, and taxidermy specimens.[70][71]

title: Maria Sibylla Merian

text: Maria Sibylla Merian (2 April 1647–13 January 1717[1]) was a German-born naturalist and scientific illustrator, a descendant of the Frankfurt branch of the Swiss Merian family. Merian was one of the first naturalists to observe insects directly.

title: Maria Sibylla Merian

text: Metamorphosis Insectorum Surinamensium: images at website sponsored by Johns Hopkins University (1705) - full digital facsimile from the Linda Hall Library from the Digital Library of the Caribbean Ingrid Rowland on Merian from The New York Review of Books , images from collection at the University of Wisconsin-Madison with links to digitized works from Maria Sibylla Merian and digital sources

title: Steven Blankaart

text: Blankaart corresponded with the mystical writer Antoinette Bourignon. He argued in one letter that an earthly paradise would be created if there were a prohibition of alcohol. He collaborated with Maria Sibylla Merian on the publication of her work.

title: Maria Sibylla Merian

text: Unlike other Dutch naturalists, Merian was not employed by a commercial enterprise or corporation. But her journey was partly financed by the directors of the Dutch West India Company.[18] In her subsequent publication on the expedition Merian criticised the actions of the colonial merchants, saying that "the people there have no desire to investigate anything like that; indeed they mocked me for seeking anything other than sugar in the country." Merian also condemned the merchants’ treatment of slaves. She was given a slave helper for her research and the interaction she could thus have with the Amerindian and African slaves in the colony assisted her in researching the plants and animals of Surinam. Merian also took an interest in agriculture and lamented the colonial merchants' resistance to plant or export anything other than sugar. She later showcased the vegetables and fruits that could be found in Surinam, including the pineapple.[19]

title: Georg Gsell

text: Gsell was born in St. Gallen where he married his first wife in 1697, Marie Gertrud von Loen of Frankfurt am Main. They moved to Amsterdam in 1704 where their fifth daughter Katharina was born in 1707. His wife died and he remarried Anna Horstmans, but divorced her in 1715, when he married a third time to Dorothea Maria Merian, the daughter of Maria Sibylla Merian. The couple was recruited by Peter the Great in 1716 and went to Russia, where he became first curator of the Imperial art gallery founded in 1720. His wife, Maria-Dorothea, became the curator of the Kunstkamera. Their daughter Katharina married mathematician Leonhard Euler in 1733.

title: Abraham Mignon

text: Marrel's stepdaughter Maria Sibylla Merian (1647–1717), daughter of the engraver Matthew Merian, who lived with Marrel and thus studied with Mignon, achieved distinction as a flower painter. Besides Merian, his other pupil was Ernst Stuven. He left two daughters when he died; Catharina and Anna.

title: Maria Sibylla Merian

text: In 2018 a rare butterfly, Catasticta sibyllae was named after her.[62][63]

title: Caterpillar

text: The role of caterpillars in the life stages of butterflies was badly understood. In 1679 Maria Sibylla Merian published the first volume of "The Caterpillars' Marvelous Transformation and Strange Floral Food", which contained 50 illustrations and a description of insects, moths, butterflies and their larvae. An earlier popular publication on moths and butterflies, and their caterpillars, by Jan Goedart had not included eggs in the life stages of European moths and butterflies, because he had believed that caterpillars were generated from water. When Merian published her study of caterpillars it was still widely believed that insects were spontaneously generated. Merian's illustrations supported the findings of Francesco Redi, Marcello Malpighi and Jan Swammerdam.

title: Maria Sibylla Merian

text: Timeline of women in science

title: Maria Sibylla Merian

text: From 1685 onwards Merian, her daughters and her mother lived with the Labadist community, who had settled on the grounds of a stately home – Walt(h)a Castle – at Wieuwerd in Friesland. They stayed there for three years and Merian found the time to study natural history and Latin, the language in which scientific books were written.[7] In the moors of Friesland she observed the birth and development of frogs, and collected them to dissect them.[10] Merian stayed with the community until 1691.[7]

title: Maria Sibylla Merian

text: In 1715, Merian suffered a stroke. Despite being partially paralysed she continued her work.[14] Maria Sibylla Merian died in Amsterdam on 13 January 1717 and was buried four days later at Leidse kerkhof.[20] The death register lists her as a pauper.[21] Her daughter Dorothea published Erucarum Ortus Alimentum et Paradoxa Metamorphosis, a collection of her mother's work, posthumously.

title: Maria Sibylla Merian

text: Merian's drawings of plants, frogs,[35] snakes, spiders, iguanas, and tropical beetles are still collected today by amateurs all over the world. The German word Vogelspinne—(a spider of the infraorder Mygalomorphae), translated literally as bird spider—probably has its origins in an engraving by Merian. The engraving, created from sketches drawn in Surinam, shows a large spider who had just captured a bird. In the same engraving and accompanying text Merian was the first European to describe both army ants and leaf cutter ants as well as their effect on other organisms.[36] Merian's depictions of tropical ants were subsequently cited and copied by other artists. Her depictions of the struggle among organisms predates Charles Darwin and Lord Tennyson theories on the struggle for survival and evolution.[37]

title: Maria Sibylla Merian

text: In 1699, the city of Amsterdam granted Merian permission to travel to Suriname in South America, along with her younger daughter Dorothea Maria. On 10 July, the fifty-two year old Merian and her daughter set sail. The goal of the mission was to spend five years illustrating new species of insects.[4] In order to finance the mission, Maria Sibylla sold 255 of her own paintings.[16] Before departing, she wrote:

title: Maria Sibylla Merian

text: Merian had started to collect insects as an adolescent and kept a study journal. Aged 13 she raised silk worms and other insects. Her interest turned to moths and butterflies, which she collected and studied. While living in Nuremberg and Frankfurt Merian would travel to the surrounding countryside to search for caterpillar larvae. She recorded their food plants, the timing of their metamorphoses, and noted the behaviour she observed.[30] It was not unusual for naturalists to illustrate their own research, but Merian was among the first professionally trained artists to illustrate her lifelong studies and observations.

title: Maria Sibylla Merian

text: In 1678, the family had moved to Frankfurt am Main, but her marriage was an unhappy one.[4] She moved in with her mother, after her stepfather died in 1681. In 1683 she travelled to Gottorp and was attracted to the Labadists community in Holstein. In 1685 Merian travelled with her mother, husband and children to Friesland where her half-brother Caspar Merian had lived since 1677.

title: Maria Sibylla Merian

text: The universal classification system for all organisms was started by Carl Linnaeus about 30 years after Merian had published her research on Suriname. It is organised in five levels of kingdom, class, order, genus and species.[47] After her death Merian became so renowned among biologists that number of taxa, and two genera, were named after her. Two butterflies have been named after her, the common postman butterfly Heliconius melpomene meriana and a split-banded owlet butterfly Opsiphanes cassina merianae. The Cuban sphinx moth has been named Erinnyis merianae. A bug with no common name has been named Plisthenes merianae. A genus of mantises has been named Sibylla.[61]


query: How long is the Po river in Italy?

title: Po (river)

text: The Po (/poʊ/, Italian:[ˈpɔ]; Latin: Padus or Ēridanus; Ancient Greek: Πάδος, romanized:Pádos or Ἠριδανός, Ēridanós; Ancient Ligurian: Bodincus or Bodencus) is a river that flows eastward across northern Italy. The Po flows either 652km (405mi) or 682km (424mi) – considering the length of the Maira, a right bank tributary. The headwaters of the Po are a spring seeping from a stony hillside at Pian del Re, a flat place at the head of the Val Po under the northwest face of Monviso (in the Cottian Alps). The Po ends at a delta projecting into the Adriatic Sea near Venice. It has a drainage area of 74,000km² in all, 70,000 in Italy, of which 41,000 is in montane environments and 29,000 on the plain.[2] The Po is the longest river in Italy; at its widest point its width is 503m (1,650ft).[1] The Po extends along the 45th parallel north.

title: Stura di Lanzo

text: Stura di Lanzo () is a long river in north-western Italy (Piedmont), in the Metropolitan City of Turin. It is formed from several tributaries near Lanzo Torinese. It flows into the river Po in Turin.

title: Geography of Piedmont

text: Piedmont is the second largest of the 20 administrative regions of Italy, after Sicily. It is broadly contiguous with the upper part of the drainage basin of the river Po which rises from the slopes of Monviso in the west of the region and is Italy’s largest river. The Po collects all the waters provided within the semicircle of mountains (Alps and Apennines) which surround the region on three sides.

title: Oglio

text: The Oglio (; Latin "Ollius", or "Olius"; Lombard "Òi") is a left-side tributary of the Po River in Lombardy, Italy. It is long.

title: Adda (river)

text: The Adda (Latin "Abdua", or "Addua"; in Lombard "Ada" or, again, "Adda" in local dialects where the double consonants are marked) is a river in North Italy, a tributary of the Po. It rises in the Alps near the border with Switzerland and flows through Lake Como. The Adda joins the Po a few kilometres upstream of Cremona. It is long. The highest point of the drainage basin is the summit of la Spedla (a subpeak of Piz Bernina), at .

title: List of rivers of Italy

text:
This is a list of rivers which are at least partially located in Italy. They are organized according to what body of water they drain into, with the exceptions of Sicily and Sardinia, which are listed separately. At the bottom all of the rivers are listed alphabetically.
For the purposes of this list, the Italian rivers draining into the Adriatic Sea will begin at the coastal border between Italy and Slovenia and will follow the Adriatic coast of Italy until it reaches Santa Maria di Leuca. Beyond this point, rivers empty into the Ionian Sea rather than the Adriatic. The rivers are ordered according to how far along the coast the river mouth is from the Italian/Slovenian border, the first river having its mouth the closest to the border and the last being closest to Santa Maria di Leuca.
The tributaries of the Po are organized into right- and left-hand tributaries. The lists are ordered from the river closest to the source of the Po to the river closest to the mouth of the Po.
For the purposes of this list, the Italian rivers draining into the Ionian Sea will begin at Santa Maria di Leuca in the east and will extend to the Strait of Messina in the west. Sicilian rivers are excluded because they are listed in their own section below. The rivers are ordered according to how far east their mouth is, the first river having the easternmost mouth and the last having the westernmost mouth.For the purposes of this list, the Italian rivers draining into the Tyrrhenian Sea will begin at the Strait of Messina in the south and extend north up to San Pietro Point near Portovenere. Sicilian and Sardinian rivers are excluded from this list because those rivers are in their own sections below. The rivers are ordered according to how far south their mouth is, the first river having the southernmost mouth and the last having the northernmost mouth.
For the purposes of this list, the Italian rivers draining into the Ligurian Sea will begin at San Pietro Point near Portovenere in the east and will extend to the border with France near Monaco. Sardinian rivers are excluded from this list because those rivers are in their own section below. The rivers are ordered according to how close their mouth is to San Pietro Point. The river with its mouth closest to this geographic point is listed first and rivers further away from this point are listed in the order in which their mouth empties into the sea as one proceeds along the coast up to the border with France.

title: Tidone

text: The Tidone is a river in the Region of Emilia Romagna in northern Italy. It is a right-bank tributary of the Po River. The stream rises in the Apennine Mountains near Monte Penice and flows in a northerly direction into the Po.

title: Malone (river)

text: Malone is a long stream () of the Metropolitan City of Turin in Piedmont, north-western Italy. It is a left side tributary of the river Po which flows through the Canavese.

title: Tanaro

text: The Tanaro (), known as Tanarus in ancient times and "Tane" or "Tani" in piedmontese language, is a long river in northwestern Italy. The river begins in the Ligurian Alps, near the border with France, and is the most significant right-side tributary to the Po in terms of length, size of drainage basin (partly Alpine, partly Apennine), and discharge.

title: Cimbri

text: The Cimbri had penetrated through the Alps into northern Italy. The consul Quintus Lutatius Catulus had not dared to fortify the passes, but instead he had retreated behind the river Po, and so the land was open to the invaders. The Cimbri did not hurry, and the victors of Aquae Sextiae had the time to arrive with reinforcements. At the Battle of Vercellae, at the confluence of the river Sesia with the Po, in 101 BC, the long voyage of the Cimbri also came to an end.

title: Po Valley

text: The Po Valley, Po Plain, Plain of the Po, or Padan Plain ( , or "Val Padana") is a major geographical feature of Northern Italy. It extends approximately in an east-west direction, with an area of including its Venetic extension not actually related to the Po river basin; it runs from the Western Alps to the Adriatic Sea. The flatlands of Veneto and Friuli are often considered apart since they do not drain into the Po, but they effectively combine into an unbroken plain.

title: Geography of Italy

text: Almost 40% of the Italian territory is mountainous, with the Alps as the northern boundary and the Apennine Mountains forming the backbone of the peninsula and extending for . In between the two lies a large plain in the valley of the Po, the largest river in Italy, which flows eastward from the Cottian Alps to the Adriatic. The Po Valley is the largest plain in Italy, with , and it represents over 70% of the total plain area in the country.

title: Caviar

text:
Cristoforo da Messisbugo in his book "Libro novo nel qual si insegna a far d'ogni sorte di vivanda", Venice, 1564, at page 110, gave the first recorded recipe in Italy about extraction of the eggs from the roe and caviar preparation "to be consumed fresh or to preserve".
The writer and voyager Jérôme Lalande in his book ""Voyage en Italie"", Paris, 1771, vol. 8 page 269, noted that many sturgeon were caught in the Po delta area in the territory of Ferrara.
In 1753 a diplomatic war broke out between the Papal States, governing the Ferrara territory, and the Venetian Republic about sturgeon fishing rights in the Po river, the border between the two states. From about 1920 and until 1942 there was a shop in Ferrara, named "Nuta" from the nickname of the owner Benvenuta Ascoli, that processed all the sturgeons caught in the Po river for caviar extraction, using an elaboration of the original Messisbugo recipe, and shipped it to Italy and Europe. Production was sporadically continued by a new owner until 1972, when sturgeon stopped swimming up the Po river. Since 2015, some sturgeon have reappeared in the Po.
Currently, Italian caviar is obtained almost entirely from bred sturgeons. The caviar production is concentrated predominantly in Brescia, which is considered the capital of Italian caviar: in this area, in Calvisano, is located the world's largest sturgeons farm that produces annually 25 tonnes of caviar. Italian caviar is generally the most sold and appreciated in the world: Italy is the world's first producer.

title: Po (river)

text: The vast valley around the Po is called the Po Basin or Po Valley (Italian Pianura Padana or Val Padana); in time it became the main industrial area of the country. In 2002, more than 16 million people lived there, at the time nearly ⅓ of the population of Italy.[1]

title: Stura di Demonte

text:
Stura di Demonte () is a long river in northwestern Italy (Piedmont).
The river is a tributary to the river Tanaro, which is a tributary of the river Po. Its source is in the Alps, near the border with France. It flows through Demonte and Cuneo before joining the Tanaro just east of Cherasco.

title: Reno (river)

text: The Reno () is a river of Emilia-Romagna, northern Italy. It is the tenth longest river in Italy (the sixth longest of those that flow directly into the sea) and the most important of the region apart from the Po.

title: Scardinius hesperidicus

text:
Scardinius hesperidicus is a species of ray-finned fish in the family Cyprinidae.
It is native to Po and Adriatic drainages east of the Po in Italy, San Marino, and Switzerland, and has been introduced into other area watersheds, especially in Italy. Its natural habitats are rivers and freshwater lakes.

title: Tartaro-Canalbianco-Po di Levante

text: Tartaro-Canalbianco-Po di Levante (Latin: Tartarus) is a river of north-east Italy. It is the only river whose course runs between the Adige river and the Po river and flows into the Adriatic Sea.

title: Valle Po

text: The valley gives rise to the longest river in Italy, the Po, before it enters the Pianura Padana (or Plain of the Po). It has a length of some 32 km, from Saluzzo to Crissolo, and is home to the Monviso mountain. It is bounded by the Val Pellice, Valle Varaita and the Valle del Guil. The head of the valley is located at the Traversette pass ("Colle delle Traversette") (2950 m above sea level). The valley descends through the King's plain ("Pian del Re") (2020 m), where the Po river has its source.

title: Cristoforo di Messisbugo

text: Beluga sturgeon abounded in the Po River in the 16th century and they were a frequent capture. The first known reference to the preparation of sturgeon caviar in Italy is in Messisbugo's books. He described how to prepare the caviar both to be consumed fresh and to be preserved.

title: Dora Baltea

text: Dora Baltea () or Doire Baltée () ( or "Duria Bautica"; (Valdôtain); , ), is a river in northern Italy. It is a left-hand tributary of the Po River and is about long.

title: Scrivia

text: The Scrivia, long, is a right tributary of the Po River, in northern Italy. It runs through Liguria, Piedmont, and Lombardy.

title: Northern Italy

text: The coldest month is January: the Po valley's mean temperature is between −1–1 °C. Winter morning lows can occasionally reach −30 to −20 °C in the Alps and −14 to −8 °C in the Po valley. Summer is usually more stable with July temperatures are 22–24 °C north of river Po, like in Milan or Venice, and south of river Po can reach 24–25 °C like in Bologna.

title: Northern Italy

text:
Northern Italy is made of the basin of the River Po, which comprises the whole of the broad plain extending from the foot of the Apennines to that of the Alps, together with the valleys and slopes on both sides of it, the Venetian Plain and the Ligurian coast.
Northern Italy has the Alps as northern and western boundary and the Apennine Mountains as the southern one. In between the two mountain ranges lies a large plain made of the Venetian Plain and the valley of the Po, the largest river in Italy, which flows 652 km eastward from the Cottian Alps to the Adriatic Sea and receives all the waters that flow from the Apennines northwards, and all those that descend from the Alps towards the south. The Po Valley is the largest plain in Italy and held the vast majority of North Italian population.

title: Province of Pavia

text: The Province of Pavia is in the region of Lombardy in northwestern Italy. It is bounded to the north by the provinces of Milan and the Lodi, to the southeast by the Province of Piacenza (Emilia-Romagna), and to the southwest it is bounded by the Province of Alessandria (Piedmont). The province is crossed by the rivers Ticino and Po, which meet four kilometres south of the capital, Pavia. The province contains 190 communes and the River Po is navigable up to its confluence with the Ticino. There are three regions of the province, the Pavese, which is entirely in the Po Valley, the Lomellina, which is also completely in the Po Valley but between the Ticino and the Po, and Oltrepò, to the south of the Po and which includes Monte Lesima (1,724 m (5,656 ft)), a mountain in the Apennine Mountains which is the highest point in the province. The territory of Siccomario, at the confluence of the two great rivers, should properly be included in Lomellina, but for historical reasons it is considered part of Pavese. Another large river flowing through the province is the Olona.

title: Taro (river)

text: The Taro (Latin "Tarus") is a river in Emilia-Romagna, in northern Italy. It is a tributary of the Po and is long. It flows almost entirely in the province of Parma, west of the city Parma. The Taro flows into the Po near Gramignazzo, a frazione of the comune of Sissa, north of Parma.

title: Versa (Po)

text: The Versa is a tributary of the Po River which runs through the Province of Pavia in northern Italy.

title: Venetian Plain

text: The Venetian Plain, or Venetian-Friulan Plain ( or ) is a major geographical feature of Italy. It extends approximately from the River Adige to the River Isonzo, in a southwest-to-northeast direction, including almost all the flatlands of Veneto and Friuli. It is not properly related to the Po River basin, but it is often considered as part of the Po Valley since the flatlands of Veneto and Friuli do not drain into the Po, but they effectively combine into an unbroken plain. Sometimes, instead of the River Adige, the Euganei Hills and Berici Hills are considered to be its western border.

title: Piedmont

text: Piedmont is the second largest of Italy's 20 regions, after Sicily. It is broadly coincident with the upper part of the drainage basin of the river Po, which rises from the slopes of Monviso in the west of the region and is Italy's largest river. The Po collects all the waters provided within the semicircle of mountains (Alps and Apennines) which surround the region on three sides.

title: Po (river)

text: The river flows through many important Italian cities, including Turin (Torino), Piacenza and Ferrara. It is connected to Milan through a net of channels called navigli, which Leonardo da Vinci helped design. Near the end of its course, it creates a wide delta (with hundreds of small channels and five main ones, called Po di Maestra, Po della Pila, Po delle Tolle, Po di Gnocca and Po di Goro) at the southern part of which is Comacchio, an area famous for eels. The Po valley was the territory of the Roman Cisalpine Gaul, divided into Cispadane Gaul (South of the Po) and Transpadane Gaul (North of the Po). The Po begins in the Alps, and is in Italy, and flows eastward.


query: Who discovered special relativity?

title: Theory of relativity

text: Albert Einstein published the theory of special relativity in 1905, building on many theoretical results and empirical findings obtained by Albert A. Michelson, Hendrik Lorentz, Henri Poincaré and others. Max Planck, Hermann Minkowski and others did subsequent work.

title: Special relativity (alternative formulations)

text: Minkowski space (or Minkowski spacetime) is a mathematical setting in which special relativity is conveniently formulated. Minkowski space is named for the German mathematician Hermann Minkowski, who around 1907 realized that the theory of special relativity (previously developed by Poincaré and Einstein) could be elegantly described using a four-dimensional spacetime, which combines the dimension of time with the three dimensions of space.

title: Criticism of the theory of relativity

text: It was also claimed that special relativity cannot handle acceleration, which would lead to contradictions in some situations. However, this assessment is not correct, since acceleration actually can be described in the framework of special relativity (see Acceleration (special relativity), Proper reference frame (flat spacetime), Hyperbolic motion, Rindler coordinates, Born coordinates). Paradoxes relying on insufficient understanding of these facts were discovered in the early years of relativity. For example, Max Born (1909) tried to combine the concept of rigid bodies with special relativity. That this model was insufficient was shown by Paul Ehrenfest (1909), who demonstrated that a rotating rigid body would, according to Born's definition, undergo a contraction of the circumference without contraction of the radius, which is impossible (Ehrenfest paradox). Max von Laue (1911) showed that rigid bodies cannot exist in special relativity, since the propagation of signals cannot exceed the speed of light, so an accelerating and rotating body will undergo deformations.

title: Test theories of special relativity

text: Test theories of special relativity give a mathematical framework for analyzing results of experiments to verify special relativity.

title: Vladimir Ignatowski

text: Ignatowski wrote some papers on special relativity. In 1910 he was to first who tried to derive the Lorentz transformation by group theory only using the relativity principle, and without the postulate of the constancy of the speed of light (1910b, 1911b, 1911c, 1911h). Although he derived the correct transformation, the invariant limiting speed remained undefined. Ignatowski had to resort to length contraction of moving electrostatic fields in order to identify this limiting velocity with the velocity of light in vacuum. While some said that this approach was insufficient and the second postulate is still needed, others continued the attempts to derive special relativity without the light postulate (see Postulates of special relativity). Ignatowski also investigated the status of rigid bodies within special relativity (1910a, 1911a). He concluded that velocities greater than the speed of light are possible, even though he showed that those are not signal velocities and therefore are not in conflict with relativity (1910b, 1911g). He also formulated a relativistic theory of hydrodynamics (1911f).

title: History of special relativity

text: Planck, in 1909, compared the implications of the modern relativity principle— he particularly referred to the relativity of time– with the revolution by the Copernican system.[106] An important factor in the adoption of special relativity by physicists was its development by Minkowski into a spacetime theory.[86] Consequently, by about 1911, most theoretical physicists accepted special relativity.[107][86] In 1912 Wilhelm Wien recommended both Lorentz (for the mathematical framework) and Einstein (for reducing it to a simple principle) for the Nobel Prize in Physics– although it was decided by the Nobel committee not to award the prize for special relativity.[108] Only a minority of theoretical physicists such as Abraham, Lorentz, Poincaré, or Langevin still believed in the existence of an aether.[107] Einstein later (1918–1920) qualified his position by arguing that one can speak about a relativistic aether, but the "idea of motion" cannot be applied to it.[109] Lorentz and Poincaré had always argued that motion through the aether was undetectable. Einstein used the expression "special theory of relativity" in 1915, to distinguish it from general relativity.

title: Theory of relativity

text: Special relativity is a theory of the structure of spacetime. It was introduced in Einstein's 1905 paper "On the Electrodynamics of Moving Bodies" (for the contributions of many other physicists see History of special relativity). Special relativity is based on two postulates which are contradictory in classical mechanics:

title: Relativity priority dispute

text: In several papers, Elie Zahar (1983, 2000) argued that both Einstein (in his June paper) and Poincaré (in his July paper) independently discovered special relativity. He said that ""though Whittaker was unjust towards Einstein, his positive account of Poincaré's actual achievement contains much more than a simple grain of truth"". According to him, it was Poincaré's unsystematic and sometimes erroneous statements regarding his philosophical papers (often connected with conventionalism), which hindered many to give him due credit. In his opinion, Poincaré was rather a "structural realist" and from that he concludes, that Poincaré actually adhered to the relativity of time and space, while his allusions to the aether are of secondary importance. He continues, that due to his treatment of gravitation and four-dimensional space, Poincaré's 1905/6-paper was superior to Einstein's 1905-paper. Yet Zahar gives also credit to Einstein, who introduced Mass–Energy equivalence, and also transcended special relativity by taking a path leading to the development of general relativity.

title: De Sitter invariant special relativity

text: Since the de Sitter group naturally incorporates an invariant length parameter, de Sitter relativity can be interpreted as an example of the so-called doubly special relativity. There is a fundamental difference, though: whereas in all doubly special relativity models the Lorentz symmetry is violated, in de Sitter relativity it remains as a physical symmetry. A drawback of the usual doubly special relativity models is that they are valid only at the energy scales where ordinary special relativity is supposed to break down, giving rise to a patchwork relativity. On the other hand, de Sitter relativity is found to be invariant under a simultaneous re-scaling of mass, energy and momentum, and is consequently valid at all energy scales. A relationship between doubly special relativity, de Sitter space and general relativity is described by Derek Wise. See also MacDowell–Mansouri action.

title: Postulates of special relativity

text: The physical theory given by classical mechanics, and Newtonian gravity is consistent with Galilean relativity, but not special relativity. Conversely, Maxwell's equations are not consistent with Galilean relativity unless one postulates the existence of a physical aether. In a surprising number of cases, the laws of physics in special relativity (such as the famous equation formula_28) can be deduced by combining the postulates of special relativity with the hypothesis that the laws of special relativity approach the laws of classical mechanics in the non-relativistic limit.

title: Special relativity

text: Not until Einstein developed general relativity, introducing a curved spacetime to incorporate gravity, was the phrase "special relativity" employed. A translation that has often been used is "restricted relativity"; "special" really means "special case".

title: Relativity priority dispute

text: In his Einstein biography "Subtle is the Lord" (1982), Abraham Pais argued that Poincaré "comes near" to discovering special relativity (in his St. Louis lecture of September 1904, and the June 1905 paper), but eventually he failed, because in 1904 and also later in 1909, Poincaré treated length contraction as a third independent hypothesis besides the relativity principle and the constancy of the speed of light. According to Pais, Poincaré thus never understood (or at least he never accepted) special relativity, in which the whole theory including length contraction can simply be derived from two postulates. Consequently, he sharply criticized Whittaker's chapter on the "Relativity theory of Poincaré and Lorentz", saying ""how well the author's lack of physical insight matches his ignorance of the literature"", although Pais admitted that the first book of Whittaker's "History of Aether and Electricity" is a masterpiece.

title: History of special relativity

text: . Mathpages: , , , Berger, Andy "" June 2016, Discover magazine, explanations of Einstein's though experiments

title: Philosophical interpretation of classical physics

text: Both quantum mechanics and special relativity begin their divergence from classical mechanics by insisting on the primacy of observations and a refusal to admit unobservable entities. Thus special relativity rejects the absolute simultaneity assumed by classical mechanics; and quantum mechanics does not permit one to speak of properties of the system (exact position, say) other than those that can be connected to macro scale observations. Position and momentum are not things waiting for us to discover; rather, they are the results that are obtained by performing certain procedures.

title: Doubly special relativity

text: Since the de Sitter group naturally incorporates an invariant length parameter, de Sitter relativity can be interpreted as an example of doubly special relativity, because de Sitter spacetime incorporates invariant velocity, as well as length parameter. There is a fundamental difference, though: whereas in all doubly special relativity models the Lorentz symmetry is violated, in de Sitter relativity it remains as a physical symmetry. A drawback of the usual doubly special relativity models is that they are valid only at the energy scales where ordinary special relativity is supposed to break down, giving rise to a patchwork relativity. On the other hand, de Sitter relativity is found to be invariant under a simultaneous re-scaling of mass, energy and momentum, and is consequently valid at all energy scales.

title: Relativistic wave equations

text: A description of quantum mechanical systems which could account for "relativistic" effects was sought for by many theoretical physicists; from the late 1920s to the mid-1940s. The first basis for relativistic quantum mechanics, i.e. special relativity applied with quantum mechanics together, was found by all those who discovered what is frequently called the Klein–Gordon equation:

title: Special relativity

text: As Galilean relativity is now considered an approximation of special relativity that is valid for low speeds, special relativity is considered an approximation of general relativity that is valid for weak gravitational fields, i.e. at a sufficiently small scale (for tidal forces) and in conditions of free fall. Whereas general relativity incorporates noneuclidean geometry in order to represent gravitational effects as the geometric curvature of spacetime, special relativity is restricted to the flat spacetime known as Minkowski space. As long as the universe can be modeled as a pseudo-Riemannian manifold, a Lorentz-invariant frame that abides by special relativity can be defined for a sufficiently small neighborhood of each point in this curved spacetime.

title: De Sitter invariant special relativity

text: First proposed by Luigi Fantappiè in 1954, the theory remained obscure until it was rediscovered in 1968 by Henri Bacry and Jean-Marc Lévy-Leblond. In 1972, Freeman Dyson popularized it as a hypothetical road by which mathematicians could have guessed part of the structure of general relativity before it was discovered. The discovery of the accelerating expansion of the universe has led to a revival of interest in de Sitter invariant theories, in conjunction with other speculative proposals for new physics, like doubly special relativity.

title: The Master Puppeteer

text:
Worried about his father, who is said to be ill, Jiro briefly returns home to discover that Isako has taken his father to recuperate at a relative’s farm in Kyoto. When Jiro again returns home on New Year’s Day, he discovers that his mother is near starvation. One evening, Saburo, the mysterious bandit who steals from the rich to help the poor, leaves a notice on the door of the theater demanding a special performance of the current play, “The Thief of the Tokaido.”
Jiro later finds the sword that Saburo used for the performance day special in the second floor of the storage room, a shed-like room with walls lined with puppets which is off limits. He asks Okada for advise to use the sword to give Kinshi the opportunity to talk to Saburo, who was believed to be Yoshida. Okada later tells Jiro that he is Saburo. Okada and Isako soon trade the two boys and live a happy life.

title: Ha'Nephilim

text: Zuri afterwards discovers that some NRV residents had a relative, who died two months before they moved in. Afterwards, he and his friends discover it was Noah who killed these people, in order to bring them to the NRV. Some time later, Zuri arrives to the "-5" floor, where he finds the portal, enters it, and discovers the spaceship (Gachnect Americofabish). The spaceship contains a dangerous combination of various gases, which cause people to go insane and lose control of their actions, but it somehow has no effect on Zuri. Later on, he discovers that the alien owners of that spaceship, used to throw their criminals onto our "jail" planet using the portal. However, the special alignment and ingredients of the atmosphere, caused the criminals to obtain "super-powers". Therefore the locals called them "Ha'Nephilim" – "The Outsiders".

title: Relative clause

text: In many European languages, relative clauses are introduced by a special class of pronouns called "relative pronouns", such as "who" in the example just given. In other languages, relative clauses may be marked in different ways: they may be introduced by a special class of conjunctions called "relativizers"; the main verb of the relative clause may appear in a special morphological variant; or a relative clause may be indicated by word order alone. In some languages, more than one of these mechanisms may be possible.

title: Doubly special relativity

text:
First attempts to modify special relativity by introducing an observer-independent length were made by Pavlopoulos (1967), who estimated this length at about .
In the context of quantum gravity, Giovanni Amelino-Camelia (2000) introduced what now is called doubly special relativity, by proposing a specific realization of preserving invariance of the Planck length .
This was reformulated by Kowalski-Glikman (2001) in terms of an observer-independent Planck mass.
A different model, inspired by that of Amelino-Camelia, was proposed in 2001 by João Magueijo and Lee Smolin, who also focused on the invariance of Planck energy.

title: Doubly special relativity

text: Doubly special relativity (DSR) – also called deformed special relativity or, by some, extra-special relativity – is a modified theory of special relativity in which there is not only an observer-independent maximum velocity (the speed of light), but an observer-independent maximum energy scale and minimum length scale (the Planck energy and Planck length).

text: Test theories of special relativity are flat space-time theories which differ from special relativity by having a different postulate about light concerning one-way speed of light vs two-way speed of light. Different postulates on light result in different notions of time simultaneity. There is Robertson's test theory (1949) which predicts different experimental results from Einstein's special relativity, and then there is Edward's theory (1963) which cannot be called a test theory because it is physically equivalent to special relativity, and then there is the Mansouri-Sexl theory (1977) which is equivalent to Robertson's theory.

title: Theory of relativity

text: Doubly special relativity Galilean invariance General relativity references Scale relativity Special relativity references

title: Special relativity

text: The time lapse between two events is not invariant from one observer to another, but is dependent on the relative speeds of the observers' reference frames (e.g., the twin paradox which concerns a twin who flies off in a spaceship traveling near the speed of light and returns to discover that the non-traveling twin sibling has aged much more).

title: Observer (special relativity)

text: Physicists use the term "observer" as shorthand for a specific reference frame from which a set of objects or events is being measured. Speaking of an observer in special relativity is not specifically hypothesizing an individual person who is experiencing events, but rather it is a particular mathematical context which objects and events are to be evaluated from. The effects of special relativity occur whether or not there is a sentient being within the inertial reference frame to witness them.

title: Tests of general relativity

text: The general theory of relativity incorporates Einstein's special theory of relativity, and hence test of special relativity are also testing aspects of general relativity. As a consequence of the equivalence principle, Lorentz invariance holds locally in non-rotating, freely falling reference frames. Experiments related to Lorentz invariance special relativity (that is, when gravitational effects can be neglected) are described in tests of special relativity.

title: Max Born

text: In 1905, Albert Einstein published his paper "On the Electrodynamics of Moving Bodies" about special relativity. Born was intrigued, and began researching the subject. He was devastated to discover that Minkowski was also researching special relativity along the same lines, but when he wrote to Minkowski about his results, Minkowski asked him to return to Göttingen and do his habilitation there. Born accepted. Toeplitz helped Born brush up on his matrix algebra so he could work with the four-dimensional Minkowski space matrices used in the latter's project to reconcile relativity with electrodynamics. Born and Minkowski got along well, and their work made good progress, but Minkowski died suddenly of appendicitis on 12 January 1909. The mathematics students had Born speak on their behalf at the funeral.

title: Bloodlines of Salem

text: Group researchers investigate and publish evidence of notable descendants and relatives of trials participants. Its 2007 investigation discovered that "Harry Potter" film actor Tom Felton is a relative of several participants including Lt. Nathaniel Felton and John Proctor, who was hanged during the trials. Its 2008 investigation discovered that U.S. President George W. Bush is a descendant or relative of up to 217 participants including as an 8th great-grandson of Mary Parker who was hanged during the trials.

text: Special relativity cannot be used to describe a global frame for non-inertial i.e. accelerating frames. However general relativity implies that special relativity "can" be applied locally where the observer is confined to making local measurements. For example, an analysis of Bremsstrahlung does not require general relativity, SR is sufficient.


query: What is a metabolite

title: Metabolite

text: A metabolite is the intermediate end product of metabolism. The term metabolite is usually restricted to small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones). A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene is an example of a primary metabolite produced in large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin which is created from the primary metabolite, tryptophan. Some sugars are metabolites, such as fructose or glucose, which are both present in the metabolic pathways.

title: Trimipramine

text: Trimipramine is extensively metabolized, so its metabolites may contribute to its pharmacology, including potentially to monoamine reuptake inhibition. In what was the only study to date to have assessed the activity profiles of the metabolites of trimipramine, Haenisch et al. (2011) assayed desmethyltrimipramine, 2-hydroxytrimipramine, and trimipramine-N-oxide in addition to trimipramine and found that these metabolites showed IC values for the SERT, NET, and DAT similar to those of trimipramine (see table to the right). Like other secondary amine TCAs, desmethyltrimipramine was slightly more potent than trimipramine in its norepinephrine reuptake inhibition but less potent in its inhibition of serotonin reuptake. However, desmethyltrimipramine still showed only very weak inhibition of the NET.

title: Adenosine diphosphate receptor inhibitor

text:
The molecular target of the active metabolite of ADP receptor inhibitors is the P2Y receptor. P2Y receptor is a G-coupled receptor and is activated by adenosine diphosphate. ADP binds to the P2Y receptor that leads to inhibition of adenyl cyclase and thereby decreases the intracellular levels of cAMP. This reduction of cAMP reduces phosphorylation of vasodilator stimulated phosphoprotein that leads to the activation of the glycoprotein IIb/IIIa receptors. Activation of the glycoprotein IIb/IIIa receptors increases thromboxane production and prolonged platelet aggregation. Ticlopidine, clopidogrel and prasugrel are thienopyridine prodrugs that are irreversible platelet inhibitors of the P2Y receptor. Cangrelor and ticagrelor are direct –acting P2Y inhibitors that change the conformation of the P2Y receptor and therefore, results in reversible platelet inhibition of the receptor. Thienopyridines are metabolized in the liver and the intestinal to active metabolites.
Ticlopidine is a prodrug and is metabolized by at least five main pathways. There is one active metabolite that has been identified and shown to have antiplatelet activity. This active metabolite is formed by a CYP-dependent pathway. CYP2C19 and CYP2B6 are enzymes suggested to contribute to the metabolic transformation of ticlopidine to the thiolactone intermediate, 2-oxo-ticlopidine in the liver. The thiolactone intermediate is then converted to ticlopidine active metabolite via CYP oxidation where oxidation activation occurs. However the CYP enzymes that are involved in this pathway are unknown. In the formation of the active metabolite additional metabolites have been identified and they are dihydrothienopyridinium (M5) and thienodihydropyridinium metabolites (M6). These metabolites may be responsible for the toxic side effects of ticlopidine.

title: Norgestimate

text: Norgestimate is extensively metabolized into its active metabolites during first-pass metabolism in the liver and intestines. The major metabolite of norgestimate is norelgestromin and is formed from norgestimate via deacetylation in the liver and intestines. A more minor metabolite of norgestimate is levonorgestrel, which accounts for 20 to 25% (22 ± 6%) of an administered dose or about 40 to 70 µg norgestimate, and a very minor metabolite of norgestimate is levonorgestrel 17β-acetate. Both of these metabolites are active similarly to norgelstromin. With a typical oral contraceptive dosage of norgestimate of 200 to 250 µg/day, an amount of 50 to 60 µg/day levonorgestrel may be produced. This is similar to the ovulation-inhibiting dosage of levonorgestrel, and suggests that norgestimate may act in considerable part as a prodrug specifically of levonorgestrel. Following their formation, the active metabolites of norgestimate are inactivated via reduction, hydroxylation, and conjugation into levonorgestrel metabolites. The terminal half-life of norelgestromin is between 17 and 37 hours and of levonorgestrel is between 24 to 32 hours. The metabolites of norgestimate are eliminated 47% in urine and 37% in feces. Unchanged norgestimate is undetectable in urine.

title: Metabolite damage

text: Metabolite damage can occur through enzyme promiscuity or spontaneous chemical reactions. Many metabolites are chemically reactive and unstable and can react with other cell components or undergo unwanted modifications. Enzymatically or chemically damaged metabolites are always useless and often toxic. To prevent toxicity that can occur from the accumulation of damaged metabolites, organisms have damage-control systems that:Damage-control systems can involve one or more specific enzymes.

title: Duarte galactosemia

text: What is a galactose challenge? The goal of a galactose challenge is to learn whether a child is able to metabolize dietary galactose sufficiently to prevent the abnormal accumulation of galactose metabolites, generally measured as Gal-1P in the blood or galactitol in the urine. For infants with DG who showed elevated galactose metabolites at diagnosis, this test can be used to see if the child's ability to process galactose has improved.

title: Rabeprazole

text: Rabeprazole is extensively metabolized by the liver. 90% of the drug is rendered into metabolites by the liver, which are then excreted by the kidneys. 10% of the dose is excreted in the feces. The drug metabolizing enzymes primarily responsible for rabeprazole's metabolism are CYP2C19 and CYP3A4. However, rabeprazole is mainly metabolized through non-enzymatic reduction to a thioether metabolite. Some of rabeprazole's metabolites include the following: a thioether carboxylic acid metabolite, a thioether glucuronide metabolite, and a sulfone metabolite. The most common metabolites excreted in the urine are the mercapturic acid conjugate and carboxylic acid. A diagram of rabeprazole's phase I metabolism is shown below.

title: Mometasone furoate

text: Extensive metabolic hepatic metabolism of mometasone furoate to multiple metabolites occurs. No principal metabolites are detectable in plasma. After "in vitro" incubation, one of the minor metabolites formed is furoate 6β-hydroxymometasone. In human hepatic microsomes, the formation of these metabolites is regulated by CYP3A4.

title: Aquaculture of sea sponges

text: Understanding the environmental factors that affect metabolite biosynthesis or the ecological role of the metabolite, can be used as a competitive advantage to maximise metabolite production and total yield. For example, if the ecological role of the secondary target metabolite was to deter predators, mimicking predation via wounding the sponge before harvesting may be an efficient technique to maximise metabolite production.

title: 3-dehydroquinate dehydratase

text: The aromatic amino acids produced by the shikimate acid pathway are used by higher plants as protein building blocks and as precursors for several secondary metabolites. Examples of such secondary metabolites are plant pigments and compounds to defend against herbivores, insects, and UV light. The specific aromatic secondary metabolites produced, as well as when and in what quantities they are produced in, varies across different types of plants. Mammals consume essential amino acids in their diets, converting them to precursors for important substances such as neurotransmitters.

title: Methamphetamine

text: CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize methamphetamine or its metabolites in humans. The primary metabolites are amphetamine and 4-hydroxymethamphetamine; other minor metabolites include: , , , benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of amphetamine. Among these metabolites, the active sympathomimetics are amphetamine, , , , and norephedrine.

title: Plant secondary metabolism

text: Primary metabolism in a plant comprises all metabolic pathways that are essential to the plant's survival. Primary metabolites are compounds that are directly involved in the growth and development of a plant whereas secondary metabolites are compounds produced in other metabolic pathways that, although important, are not essential to the functioning of the plant. However, secondary plant metabolites are useful in the long term, often for defense purposes, and give plants characteristics such as color. Secondary plant metabolites are also used in signalling and regulation of primary metabolic pathways. Plant hormones, which are secondary metabolites, are often used to regulate the metabolic activity within cells and oversee the overall development of the plant. As mentioned above in the History tab, secondary plant metabolites help the plant maintain an intricate balance with the environment, often adapting to match the environmental needs. Plant metabolites that color the plant are a good example of this, as the coloring of a plant can attract pollinators and also defend against attack by animals.

title: Secondary metabolite

text: Most of the secondary metabolites of interest to humankind fit into categories which classify secondary metabolites based on their biosynthetic origin. Since secondary metabolites are often created by modified primary metabolite synthases, or "borrow" substrates of primary metabolite origin, these categories should not be interpreted as saying that all molecules in the category are secondary metabolites (for example the steroid category), but rather that there are secondary metabolites in these categories.

title: Diazepam

text: Diazepam undergoes oxidative metabolism by demethylation (CYP 2C9, 2C19, 2B6, 3A4, and 3A5), hydroxylation (CYP 3A4 and 2C19) and glucuronidation in the liver as part of the cytochrome P450 enzyme system. It has several pharmacologically active metabolites. The main active metabolite of diazepam is desmethyldiazepam (also known as nordazepam or nordiazepam). Its other active metabolites include the minor active metabolites temazepam and oxazepam. These metabolites are conjugated with glucuronide, and are excreted primarily in the urine. Because of these active metabolites, the serum values of diazepam alone are not useful in predicting the effects of the drug. Diazepam has a biphasic half-life of about one to three days, and two to seven days for the active metabolite desmethyldiazepam. Most of the drug is metabolised; very little diazepam is excreted unchanged. The elimination half-life of diazepam and also the active metabolite desmethyldiazepam increases significantly in the elderly, which may result in prolonged action, as well as accumulation of the drug during repeated administration.

title: Secondary metabolite

text: Secondary metabolites are organic compounds produced by bacteria, fungi, or plants which are not directly involved in the normal growth, development, or reproduction of the organism. Unlike primary metabolites, absence of secondary metabolites does not result in immediate death, but rather in long-term impairment of the organism's survivability, fecundity, or aesthetics, or perhaps in no significant change at all. Specific secondary metabolites are often restricted to a narrow set of species within a phylogenetic group. Secondary metabolites often play an important role in plant defense against herbivory and other interspecies defenses. Humans use secondary metabolites as medicines, flavorings, pigments, and recreational drugs.

title: Citrinin

text: At 1 hour after dosing, one metabolite (A) was found in plasma using HPLC. The retention times of parent compound citrinin (C) and this metabolite (A) were 270 and 176 seconds, respectively. The metabolite was more polar than citrinin. Urine samples at different times yielded two metabolites at 180 (A) and 140 (B) seconds, which were both more polar than CTN. Bile samples taken 3 hours after dosing yielded a retention time of 140 seconds, indicating metabolite B. Uterus extracts yielded metabolite A (retention time: 180 seconds) and fetus yielded no metabolite, only the parent compound citrinin. These results suggest that only the parent compound, which is found in plasma and uterus, can enter the fetus and the metabolite (A), also present in plasma and uterus, does not. This can be because the metabolite was more polar and can thereby not cross the placental barrier.

title: Epoxygenase

text: Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 (CYP P450 or just CYP) enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids (e.g. 5-Hydroxyeicosatetraenoic acid, 12-Hydroxyeicosatetraenoic acid, 15-hydroxyicosatetraenoic acid) and leukotrienes (e.g. leukotriene B4, leukotriene C4) in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eicosanoid production, this third pathway acts as a signaling pathway wherein a set of enzymes (the epoxygenases) metabolize arachidonic acid to a set of products (the eicosatrienoic acid epoxides, abbreviated as EETs, which are classified as nonclassic eicosanoids) that act as secondary signals to work in activating their parent or nearby cells and thereby orchestrate functional responses. However, none of these three pathways is limited to metabolizing arachidonic acid to eicosanoids. Rather, they also metabolize other polyunsaturated fatty acids to products that are structurally analogous to the eicosanoids but often have different bioactivity profiles. This is particularly true for the CYP epoxygenases which in general act on a broader range of polyunsaturated fatty acids to form a broader range of metabolites than the first and second pathways of eicosanoid production. Furthermore, the latter pathways form metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins; no such receptors have been fully characterized for the epoxide metabolites. Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and these oxygenase enzymes share similarity between humans and other mammalian animal models. The third pathway consists of a large number of metabolite-forming CYP epoxygenases and the human epoxygenases have important differences from those of animal models. Partly because of these differences, it has been difficult to define clear roles for the epoxygenase-epoxide pathways in human physiology and pathology.

title: Metabolomics

text: Metabolites are the intermediates and products of metabolism. Within the context of metabolomics, a metabolite is usually defined as any molecule less than 1 kDa in size. However, there are exceptions to this depending on the sample and detection method. For example, macromolecules such as lipoproteins and albumin are reliably detected in NMR-based metabolomics studies of blood plasma. In plant-based metabolomics, it is common to refer to "primary" and "secondary" metabolites. A primary metabolite is directly involved in the normal growth, development, and reproduction. A secondary metabolite is not directly involved in those processes, but usually has important ecological function. Examples include antibiotics and pigments. By contrast, in human-based metabolomics, it is more common to describe metabolites as being either endogenous (produced by the host organism) or exogenous. Metabolites of foreign substances such as drugs are termed xenometabolites.

title: Secondary metabolite

text: Secondary metabolites aid a host in important functions such as protection, competition, and species interactions, but are not necessary for survival. One important defining quality of secondary metabolites is their specificity. Usually, secondary metabolites are specific to an individual species, though there is considerable evidence that horizontal transfer across species or genera of entire pathways plays an important role in bacterial (and, likely, fungal) evolution. Research also shows that secondary metabolic can affect different species in varying ways. In the same forest, four separate species of arboreal marsupial folivores reacted differently to a secondary metabolite in eucalypts. This shows that differing types of secondary metabolites can be the split between two herbivore ecological niches. Additionally, certain species evolve to resist secondary metabolites and even use them for their own benefit. For example, monarch butterflies have evolved to be able to eat milkweed (Asclepias) despite the toxic secondary metabolite it contains. This ability additionally allows the butterfly and caterpillar to be toxic to other predators due to the high concentration of secondary metabolites consumed.

title: Plant secondary metabolism

text: Research into secondary plant metabolism primarily took off in the later half of the 19th century, however, there was still much confusion over what the exact function and usefulness of these compounds were. All that was known was that secondary plant metabolites were "by-products" of the primary metabolism and were not crucial to the plant's survival. Early research only succeeded as far as categorizing the secondary plant metabolites but did not give real insight into the actual function of the secondary plant metabolites. The study of plant metabolites is thought to have started in the early 1800s when Friedrich Willhelm Serturner isolated morphine from opium poppy, and after that new discoveries were made rapidly. In the early half of the 1900s, the main research around secondary plant metabolism was dedicated to the formation of secondary metabolites in plants, and this research was compounded by the use of tracer techniques which made deducing metabolic pathways much easier. However, there was still not much research being conducted into the functions of secondary plant metabolites until around the 1980s. Before then, secondary plant metabolites were thought of as simply waste products. In the 1970s, however, new research showed that secondary plant metabolites play an indispensable role in the survival of the plant in its environment. One of the most ground breaking ideas of this time argued that plant secondary metabolites evolved in relation to environmental conditions, and this indicated the high gene plasticity of secondary metabolites, but this theory was ignored for about half a century before gaining acceptance. Recently, the research around secondary plant metabolites is focused around the gene level and the genetic diversity of plant metabolites. Biologists are now trying to trace back genes to their origin and re-construct evolutionary pathways.

title: Norbormide

text:
A compound's toxicological property has been linked to metabolic pathways, which often differ in various species. For that reason the correlation between toxicity and metabolism has been observed to obtain a clear insight into cellular metabolism, both in vitro and in vivo conditions.
In vitro studies on liver preparations from rats and other rodents revealed that hydroxylation is the major process during the metabolism of NRB. Furthermore, the metabolites between the sexes of the rat seemed to deviate from one another. First and foremost when NRB had been incubated with the liver S9 fraction, a few metabolic products were observed. The S9 fraction has been defined as "Supernatant fraction obtained from an organ (usually liver) homogenate by centrifuging at 9000 g for 20 minutes in a suitable medium; this fraction contains cytosol and microsomes." The S9 fraction consists of two components: the microsomes component which incorporates cytochrome P450 isoforms (phase I metabolism) and the cytosolic component which contains transferases (phase II metabolism).
A mixture of four active endo-isomers of NRB (U, V, W en Y) formed four major metabolites in rat liver S9 and cytosolic preparations after incubation. The isomers are separately not pure compounds, but research with pure V isomer and a mixture of U and V isomers pointed out that each isomer undergoes metabolism to be formed into a single product in rat. Mass spectrometry confirmed that all metabolites had a mass consistent with a hydroxylated metabolite of NRB. Because female rats are more sensitive to NRB than the male species, the level of metabolites are higher in females than in males.
The same metabolites were found in guinea pigs, although the levels of metabolism in these rodents are considerately lower compared to those in rats. In mice two metabolites were detected: one metabolite of the V isomer (V1) which was also found in the rat preparations and another, new metabolite of the V isomer (V2). (Figure 7.1) These data acknowledge the link between the susceptibility to NRB and the production of different types and different levels of metabolites.
After collecting blood from rats 10 and 30 minutes after oral administration, plasma and red blood cell fractions were analyzed in search for either parent compounds or hydroxylated metabolites. However, neither were found, which either means that the absorption did not take place or the compounds underwent a quick clearance from the body. Whole blood samples certainly showed traces of the parent compound and a metabolite (M3) with molecular mass of 226, in samples from both female and male rats. The level in which this metabolite occurred, appeared to be once again higher in the female rats than in the male species. M3 was not found in any other rat or mouse tissue. This suggests that M3 may be formed by gut microflora in rats.
After NRB had orally been administered, an examination of both rat and mouse liver revealed traces of the parent compound. Comparing the metabolite levels in both sexes and species, a significantly higher amount was discovered in the female rats than in the male rats or the mice. HPLC chromatograms liver preparations from female of and male rats, display the detection of four metabolites (U1, V1, M1, M2). (Figure 7.2) Mass spectrometry had been used to identify these and easily so, because the hydroxylated metabolites were +16 amu higher than NRB. These studies confirmed that the metabolites were identical to those found in the in vitro preparations.
The metabolites were not found in mouse liver preparations. Moreover, neither NRB parent compound nor its metabolites were discovered in the heart after oral administration in rats as well as mice. This lack of detectable metabolites implies that NRB is able to induce a lethal effect at extremely low levels.

title: Robert L. Last

text: Robert L. Last is a plant biochemical genomicist who studies metabolic processes that protect plants from the environment and produce products important for animal and human nutrition. His research has covered (1) production and breakdown of essential amino acids, (2) the synthesis and protective roles of Vitamin C (ascorbic acid) and Vitamin E (tocopherols) as well as identification of mechanisms that protect photosystem II from damage, and (3) synthesis and biological functions of plant protective specialized metabolites (plant secondary metabolites). Four central questions are: (i) how are leaf and seed amino acids levels regulated, (ii.) what mechanisms protect and repair photosystem II from stress-induced damage, (iii.) how do plants produce protective metabolites in their glandular secreting trichomes (iv.) and what are the evolutionary mechanisms that contribute to the tremendous diversity of specialized metabolites that protect plants from insects and pathogens and are used as therapeutic agents.

title: METLIN

text: METLIN is a metabolomics database and, , contains over 64,727 structures. It serves as a data management system to assist in metabolite research and metabolite identification by providing public access to its repository of comprehensive MS/MS metabolite data. An annotated list of known metabolites and their mass, chemical formula, and structure are available on the METLIN website. Each metabolite is linked to outside resources such as the "Kyoto Encyclopedia of Genes and Genomes" (KEGG) for further reference and inquiry. Available MS/MS data are expanding continuously as more metabolite information is being deposited and discovered. The METLIN database was developed and is maintained by the Siuzdak laboratory at The Scripps Research Institute.

title: Spironolactone

text: Spironolactone is rapidly and extensively metabolized in the liver upon oral administration and has a very short terminal half-life of 1.4 hours. The major metabolites of spironolactone are 7α-thiomethylspironolactone (7α-TMS), 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (7α-desthioacetyl-δ-spironolactone). These metabolites have much longer elimination half-lives than spironolactone of 13.8 hours, 15.0 hours, and 16.5 hours, respectively, and are responsible for the therapeutic effects of the medication. As such, spironolactone is a prodrug. The 7α-thiomethylated metabolites of spironolactone were not known for many years and it was originally thought that canrenone was the major active metabolite of the medication, but subsequent research identified 7α-TMS as the major metabolite. Other known but more minor metabolites of spironolactone include 7α-thiospironolactone (7α-TS), which is an important intermediate to the major metabolites of spironolactone, as well as the 7α-methyl ethyl ester of spironolactone and the 6β-hydroxy-7α-methyl ethyl ester of spironolactone.

title: Industrial fermentation

text: Metabolites can be divided into two groups: those produced during the growth phase of the organism, called primary metabolites and those produced during the stationary phase, called secondary metabolites. Some examples of primary metabolites are ethanol, citric acid, glutamic acid, lysine, vitamins and polysaccharides. Some examples of secondary metabolites are penicillin, cyclosporin A, gibberellin, and lovastatin.

title: Isotopic labeling

text: The figure demonstrates the ability to use different labels to determine the flux through a certain reaction. Assume the original metabolite, a three carbon compound, has the ability to either split into a two carbon metabolite and one carbon metabolite in one reaction then recombine or remain a three carbon metabolite. If the reaction is provided with two isotopes of the metabolite in equal proportion, one completely labeled (blue circles), commonly known as uniformly labeled, and one completely unlabeled (white circles). The pathway down the left side of the diagram does not display any change in the metabolites, while the right side shows the split and recombination. As shown, if the metabolite only takes the pathway down the left side, it remains in a 50–50 ratio of uniformly labeled to unlabeled metabolite. If the metabolite only takes the right side new labeling patterns can occur, all in equal proportion. Other proportions can occur depending on how much of the original metabolite follows the left side of the pathway versus the right side of the pathway. Here the proportions are shown for a situation in which half of the metabolites take the left side and half the right, but other proportions can occur. These patterns of labeled atoms and unlabeled atoms in one compound represent isotopomers. By measuring the isotopomer distribution of the differently labeled metabolites, the flux through each reaction can be determined.

title: Dextromethorphan

text: Dextromethorphan has been found to possess the following actions (<1 μM) using rat tissues:Rather than acting as a direct NMDA receptor antagonist itself, dextromethorphan acts as a prodrug of its much more potent metabolite dextrorphan, and this is the actual mediator of its dissociative effects. What role, if any, (+)-3-methoxymorphinan, dextromethorphan's other major metabolite, plays in its effects is not entirely clear.

title: Primary metabolite

text:
A primary metabolite is a kind of metabolite that is directly involved in normal growth, development, and reproduction. It usually performs a physiological function in the organism (i.e. an intrinsic function). A primary metabolite is typically present in many organisms or cells. It is also referred to as a central metabolite, which has an even more restricted meaning (present in any autonomously growing cell or organism). Some common examples of primary metabolites include: lactic acid, and certain amino acids.
Note: Primary metabolites do not show any pharmacological actions or effects.

title: Metabolome

text: The Human Metabolome Database is a freely available, open-access database containing detailed data on more than 40,000 metabolites that have already been identified or are likely to be found in the human body. The HMDB contains three kinds of information: 1) chemical information, 2) clinical information, and 3) biochemical information. The chemical data includes >40,000 metabolite structures with detailed descriptions, extensive chemical classifications, synthesis information and observed/calculated chemical properties. It also contains nearly 10,000 experimentally measured NMR, GC-MS and LC/MS spectra from more than 1100 different metabolites. The clinical information includes data on >10,000 metabolite-biofluid concentrations, metabolite concentration information on more than 600 different human diseases and pathway data for more than 200 different inborn errors of metabolism. The biochemical information includes nearly 6000 protein (and DNA) sequences and more than 5000 biochemical reactions that are linked to these metabolite entries. The HMDB supports a wide variety of online queries including text searches, chemical structure searches, sequence similarity searches and spectral similarity searches. This makes it particularly useful for metabolomic researchers who are attempting to identify or understand metabolites in clinical metabolomic studies. The first version of the HMDB was released in Jan. 1 2007 and was compiled by scientists at the University of Alberta and the University of Calgary. At that time they reported data on 2,500 metabolites, 1,200 drugs and 3,500 food components. Since then these scientists have greatly expanded the collection. The latest version of the HMDB (version 3.5) contains >16,000 endogenous metabolites, >1500 drugs and >22,000 food constituents or food metabolites.

title: Metabolite damage

text:
Similarly to DNA and proteins, metabolites are prone to damage, which can occur chemically or through enzyme promiscuity. Much less is known about metabolite damage than about DNA and protein damage, in part due to the huge variety and number of damage-prone metabolites.
Many metabolites are chemically reactive and unstable, and thus prone to chemical damage. In general, any reaction that occurs "in vitro" under physiological conditions can also occur "in vivo". Some metabolites are so reactive that their half-life in a cell is measured in minutes. For example, the glycolytic intermediate 1,3-bisphosphoglyceric acid has a half-life of 27 minutes "in vivo". Typical types of chemical damage reactions that can occur to metabolites are racemization, rearrangement, elimination, photodissociation, addition, and condensation.