Jervine
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Jervine
Jervine is a steroidal alkaloid with molecular formula C27H39NO3 which is derived from the plant genus ''Veratrum''. Similar to cyclopamine, which also occurs in the genus ''Veratrum'', it is a teratogen implicated in birth defects when consumed by animals during a certain period of their gestation. Physiological effects Jervine is a potent teratogen causing birth defects in vertebrates. In severe cases it can cause cyclopia and holoprosencephaly. Mechanism of action Jervine's biological activity is mediated via its interaction with the 7 pass trans membrane protein smoothened. Jervine binds with and inhibits smoothened, which is an integral part of the hedgehog signaling pathways. With smoothened inhibited, the GLI1 Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells. Function The Gli proteins are the effectors of Hedgehog (Hh) ... transcrip ...
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Cyclopamine
Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily (''Veratrum californicum'') that causes fatal birth defects. It prevents the embryonic brain from separating into two lobes (an extreme form of holoprosencephaly), which in turn causes the development of a single eye (cyclopia). The chemical was named after this effect, as it was originally noted by Idaho lamb farmers who contacted the US Department of Agriculture after their herds gave birth to cycloptic lambs in 1957. It then took more than a decade to identify the corn lily as the culprit. Later work suggested that different rain patterns caused the sheep to graze differently, impacting the amount of corn lily ingested by pregnant sheep. The poison interrupts the sonic hedgehog signaling pathway during development, thus causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Departm ...
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Steroidal Alkaloid
Steroidal alkaloids have organic ring backbones which feature nitrogen-based functional groups. More specifically, they are distinguished by their tetracyclic cyclopentanophenanthrene backbone that marks their close relationship with sterols. They fall in two major categories: Solanum alkaloids and Veratrum alkaloids. A Steroidal alkaloid has also been found in ''Chonemorpha fragrans'' (Frangipani vine), 'chonemorphine' was used to treat intestinal infections in Wistar rats. (Chatterjee DK et al (1987) Parasitol Res 74, 1, 30-33). ''Solanum'' alkaloids These compounds generally appear as their corresponding glycoside in plants of the genus ''Solanum''. ''Solanum'' includes plants like potatoes, tomatoes, and various nightshades Starting with cholesterol, the biosynthesis of these compounds follow a similar general mechanism including hydroxylation, oxidation, and transamination before differentiating. Alkaloids found in these plants include chaconine, solanine, solasodine, tom ...
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Cyclopia
Cyclopia (named after the Greek mythology character cyclopes) is the most extreme form of holoprosencephaly and is a congenital disorder (birth defect) characterized by the failure of the embryonic prosencephalon to properly divide the orbits of the eye into two cavities. Its incidence is 1 in 16,000 in born animals and 1 in 200 in miscarried fetuses. Signs and symptoms Typically, the nose is either missing or not functional. This deformity (called proboscis) forms above the center eye and is characteristic of a form of cyclopia called rhinencephaly or rhinocephaly. Most such embryos are either naturally aborted or are stillborn upon delivery. Although cyclopia is rare, several cyclopic human babies are preserved in medical museums (e.g. The Vrolik Museum, Amsterdam, Trivandrum Medical College). Some extreme cases of cyclopia have been documented in farm animals (horses, sheep, pigs, and sometimes chickens). In such cases, the nose and mouth fail to form, or the nose grows ...
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Veratrum
''Veratrum'' is a genus of flowering plants in the family Melanthiaceae. It occurs in damp habitats across much of temperate and subarctic Europe, Asia, and North America. ''Veratrum'' species are vigorous herbaceous perennials with highly poisonous black rhizomes, and panicles of white or brown flowers on erect stems. In English they are known as false hellebores, false helleborines, and corn lilies. However, ''Veratrum'' is not closely related to hellebores, helleborines, corn, or lilies. File:Veratrum nigrum Ciemiężyca czarna flowers 01.jpg, '' Veratrum nigrum'' flowers, Poland File:Veratrum album subsp. oxysepalum 0807.JPG, ''Veratrum album'' subsp. ''oxysepalum'', Fukushima Prefecture, Japan File:VeratrumViride-pousses-1.jpg, ''Veratrum viride'' shoot emerging, Quebec, Canada File:Veratrum stamineum 06.jpg, ''Veratrum stamineum'' in the mountains of Japan Ecology ''Veratrum'' species are used as food plants by the larvae of some Lepidoptera species including Setaceous ...
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Teratogens
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. These may include growth retardation, delayed mental development or other congenital disorders without any structural malformations. Teratogens are substances that may cause birth defects via a toxic effect on an embryo or fetus. Known teratogens include: retinol, thalidomide, mercury, alcohol, lead, polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlorodibenzodioxin. Etymology The term was borrowed in 1842 from the French , where it was formed in 1830 from the Greek (word stem ), meaning "sign sent by the gods, portent, marvel, monster", and ('' -ology''), used to designate a discourse, treaty, science, theory, ...
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Oxygen Heterocycles
Oxygen is the chemical element with the chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen Group (periodic table), group in the periodic table, a highly Chemical reaction, reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as well as with other chemical compound, compounds. Oxygen is Earth's Abundance of the chemical elements, most abundant element, and after hydrogen and helium, it is the third-most abundant element in the universe. At standard temperature and pressure, two atoms of the element chemical bond, bind to form Allotropes of oxygen#Dioxygen, dioxygen, a colorless and odorless diatomic molecule, diatomic gas with the formula . Diatomic oxygen gas currently constitutes 20.95% of the Earth's atmosphere, though this has Geological history of oxygen, changed considerably over long periods of time. Oxygen makes up almost half of the Earth's crust in the form of oxides.Atkins, P.; Jones, L.; Laverman, L. ...
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Ketones
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bond C=O). The simplest ketone is acetone (where R and R' is methyl), with the formula . Many ketones are of great importance in biology and in industry. Examples include many sugars (ketoses), many steroids (e.g., testosterone), and the solvent acetone. Nomenclature and etymology The word ''ketone'' is derived from ''Aketon'', an old German word for ''acetone''. According to the rules of IUPAC nomenclature, ketone names are derived by changing the suffix ''-ane'' of the parent alkane to ''-anone''. Typically, the position of the carbonyl group is denoted by a number, but traditional nonsystematic names are still generally used for the most important ketones, for example acetone and benzophenone. These nonsystematic names are considered ret ...
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Secondary Alcohols
In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl () functional group bound to a saturated carbon atom. The term ''alcohol'' originally referred to the primary alcohol ethanol (ethyl alcohol), which is used as a drug and is the main alcohol present in alcoholic drinks. An important class of alcohols, of which methanol and ethanol are the simplest examples, includes all compounds which conform to the general formula . Simple monoalcohols that are the subject of this article include primary (), secondary () and tertiary () alcohols. The suffix ''-ol'' appears in the IUPAC chemical name of all substances where the hydroxyl group is the functional group with the highest priority. When a higher priority group is present in the compound, the prefix ''hydroxy-'' is used in its IUPAC name. The suffix ''-ol'' in non-IUPAC names (such as paracetamol or cholesterol) also typically indicates that the substance is an alcohol. However, some compound ...
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Spiro Compounds
In organic chemistry, spiro compounds are compounds that have at least two molecular rings with only one common atom. The simplest spiro compounds are bicyclic (having just two rings), or have a bicyclic portion as part of the larger ring system, in either case with the two rings connected through the defining single common atom. The one common atom connecting the participating rings distinguishes spiro compounds from other bicyclics: from ''isolated ring compounds'' like biphenyl that have no connecting atoms, from ''fused ring compounds'' like decalin having two rings linked by two adjacent atoms, and from ''bridged ring compounds'' like norbornane with two rings linked by two non-adjacent atoms.For all four categories, see The specific chapters can be found aan respectively, same access date. For the description featuring adjacent atoms for all but the isolated category, see Clayden, op. cit. Spiro compounds may be fully carbocyclic (all carbon) or heterocyclic (havi ...
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Hedgehog Signaling Pathway
The Hedgehog signaling pathway is a signaling pathway that transmits information to embryonic cells required for proper cell differentiation. Different parts of the embryo have different concentrations of hedgehog signaling proteins. The pathway also has roles in the adult. Diseases associated with the malfunction of this pathway include cancer. The Hedgehog signaling pathway is one of the key regulators of animal development and is present in all bilaterians. The pathway takes its name from its polypeptide ligand, an intracellular signaling molecule called Hedgehog (''Hh'') found in fruit flies of the genus ''Drosophila''; fruit fly larva lacking the ''Hh'' gene are said to resemble hedgehogs. ''Hh'' is one of Drosophila's segment polarity gene products, involved in establishing the basis of the fly body plan. Larvae without ''Hh'' are short and spiny, resembling the hedgehog animal. The molecule remains important during later stages of embryogenesis and metamorphosis. Mamma ...
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GLI1
Zinc finger protein GLI1 also known as glioma-associated oncogene is a protein that in humans is encoded by the GLI1 gene. It was originally isolated from human glioblastoma cells. Function The Gli proteins are the effectors of Hedgehog (Hh) signaling and have been shown to be involved in cell fate determination, proliferation and patterning in many cell types and most organs during embryo development. In the developing spinal cord the target genes of Gli proteins, that are themselves transcription factors, are arranged into a complex gene regulatory network that translates the extracellular concentration gradient of Sonic hedgehog into different cell fates along the dorsoventral axis. The Gli transcription factors activate/inhibit transcription by binding to Gli responsive genes and by interacting with the transcription complex. The Gli transcription factors have DNA binding zinc finger domains which bind to consensus sequences on their target genes to initiate or suppress ...
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