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Lipid bilayer fusion It has been proposed that this discrepancy is due to a difference in extent of dehydration. Under this theory, calcium ions bind more strongly to charged lipids, but less strongly to water. The resulting displacement of calcium for water destabilizes the lipid-water interface and promotes intimate interbilayer contact. A recently proposed alternative hypothesis is that the binding of calcium induces a destabilizing lateral tension. Whatever the mechanism of calcium-induced fusion, the initial interaction is clearly electrostatic, since zwitterionic lipids are not susceptible to this effect. In the fusion process, the lipid head group is not only involved in charge density, but can affect dehydration and defect nucleation. These effects are independent of the effects of ions. The presence of the uncharged headgroup phosphatidylethanolamine (PE) increases fusion when incorporated into a phosphatidylcholine bilayer. This phenomenon has been explained by some as a dehydration effect similar to the influence of calcium. The PE headgroup binds water less tightly than PC and therefore may allow close apposition more easily. An alternate explanation is that the physical rather than chemical nature of PE may help induce fusion. According to the stalk hypothesis of fusion, a highly curved bridge must form between the two bilayers for fusion to occur. Since PE has a small headgroup and readily forms inverted micelle phases it should, according to the stalk model, promote the formation of these stalks | Biology | https://en.wikipedia.org/wiki?curid=21510483 | Lipid bilayer fusion | 140,863 |
Lipid bilayer fusion Further evidence cited in favor of this theory is the fact that certain lipid mixtures have been shown to only support fusion when raised above the transition temperature of these inverted phases. This topic also remains controversial, and even if there is a curved structure present in the fusion process, there is debate in the literature over whether it is a cubic, hexagonal or more exotic extended phase. The situation is further complicated when considering fusion "in vivo" since biological fusion is almost always regulated by the action of membrane-associated proteins. The first of these proteins to be studied were the viral fusion proteins, which allow an enveloped virus to insert its genetic material into the host cell (enveloped viruses are those surrounded by a lipid bilayer; some others have only a protein coat). Broadly, there are two classes of viral fusion proteins: acidic and pH-independent. pH independent fusion proteins can function under neutral conditions and fuse with the plasma membrane, allowing viral entry into the cell. Viruses utilizing this scheme included HIV, measles and herpes. Acidic fusion proteins such as those found on influenza are only activated when in the low pH of acidic endosomes and must first be endocytosed to gain entry into the cell. Eukaryotic cells use entirely different classes of fusion proteins, the best studied of which are the SNAREs. SNARE proteins are used to direct all vesicular intracellular trafficking | Biology | https://en.wikipedia.org/wiki?curid=21510483 | Lipid bilayer fusion | 140,864 |
Lipid bilayer fusion Despite years of study, much is still unknown about the function of this protein class. In fact, there is still an active debate regarding whether SNAREs are linked to early docking or participate later in the fusion process by facilitating hemifusion. Even once the role of SNAREs or other specific proteins is illuminated, a unified understanding of fusion proteins is unlikely as there is an enormous diversity of structure and function within these classes, and very few themes are conserved. In studies of molecular and cellular biology it is often desirable to artificially induce fusion. Although this can be accomplished with the addition of calcium as discussed earlier, this procedure is often not feasible because calcium regulates many other biochemical processes and its addition would be a strong confound. Also, as mentioned, calcium induces massive aggregation as well as fusion. The addition of polyethylene glycol (PEG) causes fusion without significant aggregation or biochemical disruption. This procedure is now used extensively, for example by fusing B-cells with myeloma cells. The resulting “hybridoma” from this combination expresses a desired antibody as determined by the B-cell involved, but is immortalized due to the myeloma component. The mechanism of PEG fusion has not been definitively identified, but some researchers believe that the PEG, by binding a large number of water molecules, effectively decreases the chemical activity of the water and thus dehydrates the lipid headgroups | Biology | https://en.wikipedia.org/wiki?curid=21510483 | Lipid bilayer fusion | 140,865 |
Lipid bilayer fusion Fusion can also be artificially induced through electroporation in a process known as electrofusion. It is believed that this phenomenon results from the energetically active edges formed during electroporation, which can act as the local defect point to nucleate stalk growth between two bilayers. There are two levels of fusion: mixing of membrane lipids and mixing of contents. Assays of membrane fusion report either the mixing of membrane lipids or the mixing of the aqueous contents of the fused entities. Assays evaluating lipid mixing make use of concentration dependent effects such as nonradiative energy transfer, fluorescence quenching and pyrene eximer formation. Mixing of aqueous contents from vesicles as a result of lysis, fusion or physiological permeability can be detected fluorometrically using low molecular weight soluble tracers. | Biology | https://en.wikipedia.org/wiki?curid=21510483 | Lipid bilayer fusion | 140,866 |
Syntelic attachment occurs when both sister chromosomes are attached to a single spindle pole. Normal cell division distributes the genome equally between two daughter cells, with each chromosome attaching to an ovoid structure called the spindle. During the division process, errors commonly occur in attaching the chromosomes to the spindle, estimated to affect 86 to 90 percent of chromosomes. Such attachment errors are common during the early stages of spindle formation, but they are mostly corrected before the start of anaphase. Successful cell division requires identification and correction of any dangerous errors before the cell splits in two. If the syntelic attachment continues, it causes both sister chromatids to be segregated to a single daughter cell. | Biology | https://en.wikipedia.org/wiki?curid=21526715 | Syntelic | 140,867 |
Crackdown 2 is an open world action-adventure video game developed by Ruffian Games and published by Microsoft Game Studios. It was released on Xbox 360 in July 2010 and is a direct sequel to the 2007 video game "Crackdown". A sequel, "Crackdown 3", was released for Xbox One and Microsoft Windows in February 2019. "Crackdown 2" is modeled similarly to its predecessor "Crackdown", a third-person shooter in open world game play. The player character is an advanced super-powered officer for the city-funded "Agency", known simply as the "Agent". This time around, players choose one of four faces and armor colours (eight colours if they pre-ordered it), instead of just the preset heads offered before. Along with that, the orbs have been carried on from the first game, and the Agent's powers are expanded and enhanced such as the Agility Skill which now allows the Agent to jump higher than in "Crackdown", glide, and gain access to the helicopter landing pad at the Agency Tower. The player is able to commandeer any number of vehicles in the game, including Agency vehicles, Peacekeeper Cruisers and a large number of civilian vehicles that the Cell have armor plated. Checkpoint races are back, both Road and Rooftop versions. Like "Crackdown", the game allows for on-line co-operative play in the main game, but now supports up to four players. The game also features competitive multiplayer modes for up to sixteen players. While the "Crackdown" supported System Link playing for co-op, "Crackdown 2" does not feature the same option | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,868 |
Crackdown 2 Microsoft Producer Peter Connelly stated: "It would've taken a half-day of work, for something that only a tiny percentage of gamers will ever use." In "Crackdown 2", the player fights both the Cell, a terrorist organization, and "Freaks," strange infected mutants. Both organizations' members can be killed with melee attacks, explosions, and bullets but there are special UV weapons made for the Freaks, who cannot survive in sunlight. There are five skills to be leveled up: Agility, which the player increases by collecting Agility Orbs and Renegade Agility Orbs, by doing Rooftop Races, or by killing enemies from a highly elevated location; Firearms, which is increased by shooting both handheld and mounted guns; Driving, which is increased by running enemies over, power slides, handbrake turns, completing Road Races, jumping through Stunt Rings and collecting Renegade Driving Orbs; Explosives, which is increased by using explosives, both Launchers and thrown Grenades; and Strength, which is increased by using hand-to-hand attacks, throwing objects, beating people with those objects, or using the moves you unlock as your Strength increases, such as the Charge or Ground Slam. Multiplayer playlists include game modes such as Rocket Tag, Vehicle Tag, Capture the Orb, Deathmatch and Team Deathmatch. A Co-op game type allows you to party up with up to 4 friends. In co-op, you can obtain special orbs known as "Online Orbs" or "Xbox Live Orbs" which give an overall bonus to all your skills | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,869 |
Crackdown 2 Co-op mode is similar to single player except the campaign missions will only advance for the player that hosts the game. "Crackdown 2" takes place 10 years after the events of "Crackdown". After "saving" Pacific City, there was a short time of peace. Then, according to the Agency, a new medical student named Catalina Thorne was accepted into the Agency as a scientist. However she was found to have been performing her own unauthorized experiments and was kicked out. Afterwards, her life was ruined, with her blaming the Agency. Later, she broke into the Agency cloning facility which housed the original agents, and introduced a virus into them which mutated the already genetically modified Agents, who became mindless and enraged, going on a killing spree before dying hours later. She then went on to destroy the research labs, sending the project back to square one and single-handedly destroying the Agent program. Soon after, Catalina unleashed the "Freak" virus into the populace of Pacific City, turning the infected into mindless mutated monstrosities that kill anything they find. With no agents to combat them, the Agency and the city were left helpless as criminals also began to resurface in the absence of the agents and the weakness of the Agency. While the people were weaker and more desperate than ever, Catalina rallied their support, claiming the Agency has a cure for the virus but is keeping it secret | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,870 |
Crackdown 2 Desperate for hope, they formed the "Cell", a terrorist group devoted to destroying the Agency and making them give up the cure. That's when the Agency unveiled Project Sunburst, in which a large bomb of direct sunlight is planted and detonated inside "Freak" lairs. The light is perfectly harmless to normal people, but the sunlight burns and destroys the Freaks. These bombs are dependent on generators to gather sunlight. Upon hearing of these generators and Project Sunburst, the Cell took over and stole the generators. The Agent must reactivate all of the absorption units, three per beacon for a total of twenty-seven. The Agent must visit each freak lair, summon air support with the beacon, and defend it against the freaks until it detonates. During the final few beacons, Catalina Thorne hacks into the Agent's comm system and pleads with him to cease the beacon re-activations, but eventually is silenced by the Voice of the Agency. After the last beacon is detonated, the Agent must return to the Tower and activate the final beacon: the Tower itself. During the process, ex-agents turned into freaks, which were kept for research, break free and attack the three cores which must be defended by the Agent. After the beacon charges, Catalina herself attacks in a stolen and repainted Agency helicopter, firing at the core. Ordered to stop her, the Agent, though damaged and bruised, leaps from the tower, firing at the helicopter as he falls | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,871 |
Crackdown 2 Catalina turns the helicopter when it is fired upon, causing the agent to hit the rotor blades rather than the cockpit. He is torn apart, sacrificing himself, succeeds in stopping Thorne. His hand lands in the helicopter as Thorne spins out of control away from the tower. The beacon fires and kills all remaining freaks in Pacific City, with the Voice of the Agency admitting he feels sorry for anyone who tries to stand in the Agency's way now. After the credits, a short video shows Thorne performing research, with the hand of the Agent in a test tube on the table in front of her. The plot, as given above, is not necessarily the true story in the game. Audio Log collectibles found in the game give a different story, which paints the Agency as evil and manipulating, having engaged in a multi-step program to once again give the public a reason to accept unconditional control by their forces and cover up their own involvement in the events of the first game. This alternate story matches the twist at the end of the first "Crackdown" game. Prior to the events of the game, the Agency, after taking control of Pacific City after the events of "Crackdown", invites a group of Pacific City journalists and Agency whistleblowers to a press conference and destroys it, blaming it on terrorists | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,872 |
Crackdown 2 Thorne, a doctor who actually wants to help the Pacific City populace, attempts to open a clinic to give free medical care to the homeless, but "freaks" left over from a Pacific City supergang (funded by the Agency, as revealed in "Crackdown") invade the clinic and kill almost everyone; the Agency blames this on wild animals. Following this incident, Thorne attempts to lead protests against the Agency and call for an antidote to the freak virus, leading the Agency to blame Thorne for creating the freaks in the first place by infecting the homeless she claimed to treat at her clinic. The Agency then walls off the infected area of Pacific City and secretly creates an antidote, but only uses it on their own agents; as a side effect, the agents lose their superhuman abilities, which the Agency again blames on Thorne. They then send undercover police to instigate violence at Thorne's peaceful protests, turning the public against her entirely. The Sunburst weapon is built to supposedly deal with the freaks, but is actually built as an antipersonnel weapon, meant to kill anyone who might oppose the Agency. Thorne, in an attempt to stop the Agency's plan, leads attacks by the Cell on the Sunburst bombs, giving the Agency a reason to send their Agents back into the field | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,873 |
Crackdown 2 Phil Wilson and Billy Thomson, respectively Producer and Lead Design of "Crackdown" had previously confirmed that the game was designed from the outset to be a long-running series, stating that sequels for the game are very likely to be produced, especially if "Crackdown" performed well commercially. However, during the Industry All Stars event in September 2007, Wilson confirmed that Realtime Worlds was not working on a sequel to the game, saying "Microsoft [was] a little late in stepping up to the plate to ask for "Crackdown 2", and by then we had already started working on bigger, better things." However, then-Microsoft Game Studios corporate vice president, Shane Kim, stated that Microsoft still holds the intellectual property rights for "Crackdown" and that a "Crackdown" sequel was still a possibility. Realtime's Studio Manager Colin MacDonald clarified that if they have the resources after completion of "APB", they could approach Microsoft to discuss a sequel. Prior to its announcement, industry rumors stated that the new start-up company, Ruffian Games, a Scottish studio formed from members from the Realtime Worlds team, may be involved in the development of a "Crackdown" sequel. This was confirmed when the game was announced during the 2009 Electronic Entertainment Expo Conference | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,874 |
Crackdown 2 The rumors of Ruffian's involvement with the sequel were initially dismissed by McDonald, saying he doubted "Microsoft would harm an otherwise fruitful existing development relationship by gambling on funding "Crackdown 2" with a startup on RTW's doorstep, for obvious reasons." Following the announcement, David Jones, founder of Realtime Worlds, stated he was "a bit miffed" with Microsoft's decision, believing that Microsoft may have been looking at an internal development studio instead of the new start-up located in the same geographical area as his company and formed of many of his team's former members. Ruffian's executive producer, Peter Connelly, agreed that the situation that caused Realtime Worlds to move onto "APB" was unfortunate, but hold no animosity towards the company. Ruffian's Thomson noted that about half of their team formerly worked on "Crackdown" across all areas of game development, and felt their studio was the best choice to make the game's sequel. The team chose to keep the sequel located in Pacific City as they considered that setting had a character of its own in the first game and wanted to preserve that for the sequel to keep up its familiarity with players, while still making it "bigger and better". The team also sought to preserve the same free-form gaming experience from "Crackdown" and opted to avoid any significant dialog-driven cutscenes, while improving on parts of the gameplay from the first game that were seen as weaker aspects | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,875 |
Crackdown 2 There are no significant mechanical changes to the game, though Ruffian continues to improve on the rendering engine to allow the display of the large vista of Pacific City. "Crackdown 2" received "mixed or average reviews" according to the review aggregation website Metacritic. GameSpot praised the game's exploration, orb collecting and four-player co-op, while criticizing its similarities to its predecessor. IGN also faulted it for similarities to its predecessor and its absence of a true story, but complimented its orb collecting and cooperative campaign. Giant Bomb said that while the game was enjoyable, too much was lifted from the first game and little new was added. "Destructoid" gave the game a negative review, criticizing its similarities to the previous game, while also noting new issues not present in the original. The writer said that the game "has no real reason to exist." GameTrailers praised the game's addictive Orb collecting, but criticized its lack of story or structure. "Official Xbox Magazine UK" praised its four-player co-op, combat system, but criticized the layout of Pacific City for being too similar to its predecessor, as well as lack of transforming vehicle, but the author, Ben Talbot, still described the game "an addictive experience, and one that offers the best sandbox co-op this side of "Saints Row 2"" | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,876 |
Crackdown 2 Ben Reeves from "Game Informer" criticised the game for being too similar to the original "Crackdown", as well as unfinished texture work, unimpressive score, mindless enemy AI, as well as low replay value. He stated that the game is almost indistinguishable from the first "Crackdown". In Japan, where the game was released under the name on 8 July 2010 (the same release date as Australia's), "Famitsu" gave it a score of 30 out of 40. "The Escapist" gave the game four stars out of five and said that it "offers hours of satisfying, brainless fun for those who enjoy that sort of thing. Newcomers to the series and die-hard fans alike will find plenty to obsess over." "The A.V. Club" gave it a B and said, "Dissing "Crackdown 2" for its lack of narrative is too easy. A videogame shouldn't articulate everything. Games should be mysterious; something should always be left to the imagination." "The Daily Telegraph" gave it seven out of ten and said it was "immense fun, but this is thanks to the fact that its core gameplay remains largely unchanged from its predecessor. In a way, the game feels more like a slightly more evolved version of the original "Crackdown" than a true sequel." "Metro UK" gave it six out of ten and said it was "Rushed, repetitive and a huge waste of potential. More expansion pack than sequel - and not even a good one." However, 411Mania gave it a score of five out of ten and said it was "quite a fun game, and for gamers who love collecting things this is the way to go | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,877 |
Crackdown 2 But if you're not into that, or [you] already beat the original, there's nothing new worth seeing here." "Wired" similarly gave it five stars out of ten and said, "An interesting experiment? Sure. But the changes to the game design have all but removed the most-fun parts while emphasizing the game's weaknesses. Whoops." | Biology | https://en.wikipedia.org/wiki?curid=21527716 | Crackdown 2 | 140,878 |
Drought rhizogenesis is an adaptive root response to drought stress. New emerging roots are short, swollen, and hairless, capable of retaining turgor pressure and resistant to prolonged desiccation. Upon rewatering, they are capable of quickly forming an absorbing root surface and hair growth. This rhizogenesis has been called a drought tolerance strategy for after-stress recovery. These drought induced short roots can be found on either both the tap root and lateral roots or on lateral roots only. These patterns are mostly likely a reflection of the plants' individual ability to maintain meristematic activity under low water potential. This morphological phenomenon was found in some families of Angiosperm dicot perennials and has been documented in Arabidopsis thaliana. | Biology | https://en.wikipedia.org/wiki?curid=21529867 | Drought rhizogenesis | 140,879 |
Synovial sarcoma, X breakpoint (SSX) refers to a group of genes rearranged in synovial sarcoma. They include: The group also has several associated pseudogenes, and the interacting protein SSX2IP. The translocation t(X;18) creates a fusion of the SYT gene(at 18q11) with either SSX1 or SSX2 (both at Xp11). Neither SYT, nor the SSX proteins contain DNA-binding domains. Instead, they appear to be transcriptional regulators whose actions are mediated primarily through protein–protein interactions, with BRM in the case of SYT, and with Polycomb group repressors in the case of SSX. | Biology | https://en.wikipedia.org/wiki?curid=21530931 | Synovial sarcoma, X breakpoint | 140,880 |
BMC Evolutionary Biology is a peer-reviewed open access scientific journal covering all fields of evolutionary biology, including phylogenetics and palaeontology. It was established in 2001 and is part of a series of BMC journals published by BioMed Central. The journal is abstracted and indexed in: According to the "Journal Citation Reports", the journal has a 2017 impact factor of 3.027. | Biology | https://en.wikipedia.org/wiki?curid=21537272 | BMC Evolutionary Biology | 140,881 |
BMC Genomics is an open-access scientific journal covering all areas of genomics and proteomics. The journal was established in 2000 and is published by BioMed Central. The Editor-In-Chief is Matteo Pasini. Its 2017 impact factor is 3.730. The journal is indexed in PubMed, PubMed Central, MEDLINE, BIOSIS Previews, EMBASE, Scopus, Zoological Record, and other indexing services. The journal has a 2017 impact factor of 3.730. | Biology | https://en.wikipedia.org/wiki?curid=21537282 | BMC Genomics | 140,882 |
B-cell CLL/lymphoma refers to a family of genes associated with certain types of lymphoma and leukemia. Although named for B-cell chronic lymphocytic leukemia, they can be associated with other malignancies. Members include: | Biology | https://en.wikipedia.org/wiki?curid=21537539 | B-cell CLL/lymphoma | 140,883 |
Photoprotein Photoproteins are a type of enzyme, made of protein, from bioluminescent organisms. They add to the function of the luciferins whose usual light-producing reaction is catalyzed by the enzyme luciferase. The term photoprotein was first used to describe the unusual chemistry of the luminescent system of "Chaetopterus" (a marine Polychaete worm). This was meant to distinguish them from other light-producing proteins because these do not exhibit the usual luciferin-luciferase reaction. Photoproteins do not display typical enzyme kinetics as seen in luciferases. Instead, when mixed with luciferin, they display luminescence proportional to the amount of the photoprotein. For example, the photoprotein aequorin produces a flash of light when luciferin and calcium are added, rather than the prolonged glow that is seen for luciferases when luciferin is added. In this respect, it may appear that photoproteins are not enzymes, when in fact they do catalyze their bioluminescence reactions. This is due to a fast catalytic step, which produces the light, and a slow regeneration step, where the oxyluciferin is freed and another molecule of luciferin is then enabled to bind to the enzyme. Because of the kinetically slow step, each aequorin molecule must "recharge" with another molecule of luciferin before it can emit light again, and this makes it appear as though it is not behaving as a typical enzyme | Biology | https://en.wikipedia.org/wiki?curid=21541014 | Photoprotein | 140,884 |
Photoprotein Photoproteins form a stable luciferin-photoprotein complex, often until the addition of another required factor such as Ca in the case of aequorin. | Biology | https://en.wikipedia.org/wiki?curid=21541014 | Photoprotein | 140,885 |
Aestivation (botany) Aestivation or estivation is the positional arrangement of the parts of a flower within a flower bud before it has opened. Aestivation is also sometimes referred to as praefoliation or prefoliation, but these terms may also mean vernation: the arrangement of leaves within a vegetative bud. Aestivation can be an important taxonomic diagnostic; for example Malvaceae flower buds have valvate sepals, with the exception of the genera "Fremontodendron" and "Chiranthodendron", which have sometimes been misplaced as a result. The terms used to describe aestivation are the same as those used to describe leaf vernation. Classes of aestivation include: Vexillary aestivation is a special type of aestivation occurring in plants like pea. In this type of aestivation a large petal called standard encloses two smaller petals called | Biology | https://en.wikipedia.org/wiki?curid=21543302 | Aestivation (botany) | 140,886 |
Felidae Conservation Fund (FCF) is a California-based non-profit organization dedicated to preserving wild cats and their habitats. The organization supports and promotes international wild cat research and conservation by collaborating on field research projects, partnering with other environmental organizations, and developing community outreach and education programs. FCF was founded in 2006 by conservationist and entrepreneur Zara McDonald. As a competitive marathon runner, McDonald twice encountered mountain lions during solitary runs in the Marin Headlands in Northern California. These encounters led her to become involved in California mountain lion research in 2002, and she soon expanded her research work to include other wild cat species. In the fall of 2004, after returning from extended capture work with mountain lions, she began developing a conservation model that combined scientific research with education and outreach programs. This led her to found the (501(c)(3)) in April 2006. Today Felidae supports and collaborates in scientific research projects in nine countries, promotes community-level education and outreach programs, and fosters international cooperation among scientists, conservationists, governments, and environmental NGOs. Felidae is based in Sausalito, California, and raises money through donations, grants, fundraising events and online social networks. FCF's mission is to advance the conservation of the planet's wild cat species and their habitats through partnerships in research, education and technology | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,887 |
Felidae Conservation Fund Its model is to collaborate on research studies that examine human impact on wild cats and their habitats, then disseminate the results in outreach and education programs designed to convince people of the importance of preserving the natural environment. Felidae collaborates with scientists, educators, communities and lawmakers with the goal of protecting ecosystems, staving off further extinctions, and promoting healthy ways for humans to coexist with wild cats and their habitats. Felidae's focus on wild cat conservation is motivated by the belief that the study of wild cats can serve as a leverage point for addressing the broader environmental issues of habitat loss, human-nature interactions, and wildlife sustainability. This belief is based on the idea that because cats are often the top predators in the ecosystems they inhabit, understanding and solving the problems they face can inform and guide the conservation and preservation of wild animals and wild habitats of all kinds. Felidae currently collaborates on research projects in field locations around the globe, including the United States, Malaysia, Mongolia, Chile, Peru, Iran, Namibia and Pakistan. Felidae provides strategic guidance, funding, field support, supplies and equipment to its project partners to help them achieve their research goals. To link this scientific research to conservation efforts, Felidae incorporates the results of field studies into its outreach and education programs | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,888 |
Felidae Conservation Fund These include talks and presentations throughout the US, collaborations with artists and video producers to convey the conservation message through visual media, and online projects aimed at educating young people through an interactive portal, an online and mobile phone game, and social network activities. In its field work and conservation efforts FCF collaborates with the following organizations: National Park Service, California State Parks, California Department of Fish and Game, UC Santa Cruz, UC Davis, Wildlife Conservation Society, Wildlife Conservation Research Unit, Snow Leopard Trust, Snow Leopard Conservancy, International Wildlife Film Festival, Craighead Beringa South, Cheetah Conservation Fund and the International League of Conservation Photographers, among many other organizations. Felidae's scientific research projects are based in field locations around the globe. The Bay Area Puma Project in Northern California is the first comprehensive study of mountain lions in the San Francisco Bay Area. A primary goal of this study is to determine priority locations for wildlife overpasses and underpasses to maintain connectivity for the region's wildlife populations. In addition, the study uses GPS collars equipped with accelerometers to record detailed information on mountain lion movements that will reveal new insights into their behavior and physiology. Felidae is working with Dr. Chris Wilmers of UC Santa Cruz, along with the California Department of Fish and Game and California State Parks | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,889 |
Felidae Conservation Fund The Patagonia Puma Project in Chile is a long-term ecological study by Dr. Heiko Wittmer of UC Davis which examines the dynamics relating to the puma’s role in the decline of the huemul deer. The researchers hope to exonerate the puma from major blame in the huemul's decline. The Bornean Wild Cat and Clouded Leopard Project in Malaysia investigates the conservation needs of five species of Bornean wild cats (Bornean clouded leopard, bay cat, flat-headed cat, marbled cat, and leopard cat). The study will use GPS collars and radio tracking to document spatial patterns, ranging behavior, activity patterns, and habitat use. Felidae is working in partnership with the Global Canopy Programme (UK), the Institute for Tropical Biology and Conservation at the University of Malaysia, and Oxford graduate students Andrew Hearn and Joanna Ross. The Study on Endangered Snow Leopards in Mongolia is a long-term research project that will answer basic ecological and behavioral questions about the mysterious and elusive snow leopard. The study will be conducted using GPS collars, non-invasive genetics, and camera trapping with advanced mark-recapture modeling. It will attempt to answer basic questions about snow leopards (birth and mortality rates, cub survival, dispersal rates, habitat use, and home range size) that are currently unknown due to their cryptic nature and inaccessible habitat. Felidae's partners in the project are the Snow Leopard Trust and the Wildlife Conservation Society | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,890 |
Felidae Conservation Fund The Teton Cougar Project in Wyoming studies the population dynamics of mountain lions in the Greater Yellowstone ecosystem by examining predation, behavior associated with human development, and interactions with wolves, grizzly bears and black bears. The project is operated by Craighead Beringia South with support from Felidae. The Southern California Puma Project examines the progress and implications of habitat fragmentation as puma populations in Southern California become more isolated. Felidae is collaborating with UC Davis Wildlife Health Center on this study, which has radio-collared more than 50 pumas over 7 years. The Asiatic Cheetah Project in Iran is the first detailed ecological study of the critically endangered Asiatic cheetah. Researchers in Northern Iran work to gain insight into the cheetahs’ movements within and between reserves, information that can help scientists to protect the cats' habitat and stave off extinction. The Snow Leopard Conservation Project in Pakistan is a high-profile study in the North Western Frontier Province of Pakistan in which the first ever GPS collar was placed on a snow leopard, as seen in the BBC documentary "Snow Leopard: Beyond the Myth". The study is a partnership between Snow Leopard Trust, WWF-Pakistan, NWFP Wildlife Department, and Felidae Conservation Fund. The African Cheetah Project in Namibia is an ongoing study of the African cheetah that includes camera-trapping, spoor tracking, and DNA research | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,891 |
Felidae Conservation Fund The study is led by the Cheetah Conservation Fund and Dr. Laurie Marker with support from Felidae. | Biology | https://en.wikipedia.org/wiki?curid=21548666 | Felidae Conservation Fund | 140,892 |
Hamiltonian spite Within the field of social evolution, is a term for behaviours occurring among conspecifics that have a cost for the actor and a negative impact upon the recipient. W. D. Hamilton published an influential paper on altruism in 1964 to explain why genetic kin tend to help each other. He argued that genetically related individuals are likely to carry the copies of the same alleles; thus, helping kin may ensure that copies of the actors' alleles pass onto next generations of both the recipient and the actor. While this became a widely accepted idea, it was less noted that Hamilton published a later paper that modified this view. This paper argues that by measuring the genetic relatedness between any two (randomly chosen) individuals of a population several times, we can identify an average level of relatedness. Theoretical models predict that (1) it is adaptive for an individual to be altruistic to any other individuals that are more closely related to it than this average level, and also that (2) it is adaptive for an individual to be spiteful against any other individuals that are less closely related to it than this average level. The indirect adaptive benefits of such acts can surpass certain costs of the act (either helpful or harmful) itself. Hamilton mentioned birds and fishes exhibiting infanticide (more specifically: ovicide) as examples for such behaviours | Biology | https://en.wikipedia.org/wiki?curid=21549439 | Hamiltonian spite | 140,893 |
Hamiltonian spite Briefly, an individual can increase the chance of its genetic alleles to be passed to the next generations either by helping those that are more closely related, or by harming those that are less closely related than relationship by chance. Though altruism and spitefulness appear to be two sides of the same coin, the latter is less accepted among evolutionary biologists. First, unlike the case with the beneficiary of an altruistic act, targets of aggression are likely to act in revenge: bites will provoke bites. Thus harming non-kin may be more costly than helping kins. Second, presuming a panmictic population, the vast majority of pairs of individuals exhibit a roughly average level of relatedness. For a given individual, the majority of others are not worth helping or harming. While it is easy to identify the few most closely related ones (see: kin recognition), it is hard to identify the most genetically distant ones. Most terrestrial vertebrates exhibit a certain degree of site fidelity, so levels of kinship tend to correlate negatively with spatial distance. While this may provide some cues to identify the least related individuals, it may also ensure that non-kin rarely if ever meet each other. Many animal species exhibit infanticide, i.e. adults tend to kill the eggs or the offspring of conspecifics, even if they do not feed on them (in the absence of cannibalism) | Biology | https://en.wikipedia.org/wiki?curid=21549439 | Hamiltonian spite | 140,894 |
Hamiltonian spite This form of spitefulness is relatively free from the threat of revenge – provided that the parents and relatives of the target are either weak or far away. Infanticide may not be a form of spite as in many cases the loss of offspring to the female brings it back into estrous providing a mating advantage to an infanticidal male. This is seen in lions. An individual carrying a long-lasting infection of virulent pathogens may benefit from (1) channelling the flow of pathogens from its own body away from its kin and (2) directing them toward non-kin conspecifics. The adaptive nature of this behaviour has been supported by the analysis of theoretical models and also by the analyses of the behavioural repertoire of different animal species. Thus, tuberculosis-infected European badgers and rabies-infected dogs equally tend to emigrate from their natal ranges before starting to distribute the pathogens. Similarly, wild herds of Asian elephants tend to defecate into drinkwater holes apparently to keep rival herds away. Throughout human history, war often emerges as a costly form of aggression typically targeting the non-kin enemy. Naturally, most wars appear to be motivated by potential benefits other than the genetic. Nevertheless, the widespread occurrence of rape and infanticide during periods of war indicates Hamiltonian elements as well. Infanticide is a biologically spiteful action in that it costs the killer time and energy, and opens the killer to the threat of revenge, without any direct compensating benefits | Biology | https://en.wikipedia.org/wiki?curid=21549439 | Hamiltonian spite | 140,895 |
Hamiltonian spite Rape, by contrast, is not, in the strict definition of the word, biologically spiteful as it is likely to have a direct fitness increase on the rapist (by increasing his number of direct descendants in the next generation, should the victim fall pregnant). It was recently suggested that spiteful motivations may also play a role in economic decisions. | Biology | https://en.wikipedia.org/wiki?curid=21549439 | Hamiltonian spite | 140,896 |
Future of Marine Animal Populations The (FMAP) project was one of the core projects of the international Census of Marine Life (2000–2010). FMAP's mission was to describe and synthesize globally changing patterns of species abundance, distribution, and diversity, and to model the effects of fishing, climate change and other key variables on those patterns. This work was done across ocean realms and with an emphasis on understanding past changes and predicting future scenarios. FMAP emerged from a workshop held at Dalhousie University in 2002 and was funded from 2003 to 2010 by the Alfred P. Sloan Foundation. The project was led by Ransom A. Myers from 2002 to 2007 and from 2007 to 2010 was under the direction of Boris Worm, Heike Lotze and Ian Jonsen in the Biology Department at Dalhousie University. The FMAP project coordinated major data synthesis efforts to derive global trends and patterns in marine biodiversity. From 2003 to 2011, FMAP team members have contributed over 110 scientific articles to peer review journals, including numerous publications in top-tier journals such as "Science" and "Nature". Publications by FMAP scientists have also included many book chapters, policy publications and outreach articles. Topics of research have included patterns of species abundance, distribution and diversity, and the effects of climate change, overfishing and other key human threats on these patterns. FMAP has performed analyses on a variety of organisms, including coral reefs, large pelagic fish, marine mammals, sea turtles and invertebrates | Biology | https://en.wikipedia.org/wiki?curid=21549683 | Future of Marine Animal Populations | 140,897 |
Future of Marine Animal Populations A major output of the project was the development of advanced statistical tools for analyzing observational data to study how marine biodiversity is distributed and changing over time, and to better understand the movements and distribution of marine predators. FMAP's research was presented as part of the culmination of The Census of Marine Life, which was celebrated in October 2010 in London, England. FMAP research formed an integral part of the overall findings of the program, which were disseminated through major media outlets around the globe. | Biology | https://en.wikipedia.org/wiki?curid=21549683 | Future of Marine Animal Populations | 140,898 |
TB3Cs2H1 snoRNA TB3Cs2H1 is a member of the H/ACA-like class of non-coding RNA (ncRNA) molecule that guide the sites of modification of uridines to pseudouridines of substrate RNAs. It is known as a small nucleolar RNA (snoRNA) thus named because of its cellular localization in the nucleolus of the eukaryotic cell. TB3Cs2H1 is predicted to guide the pseudouridylation of LSU5 ribosomal RNA (rRNA) at residue Ψ308. | Biology | https://en.wikipedia.org/wiki?curid=21560109 | TB3Cs2H1 snoRNA | 140,899 |
HyperNEAT Hypercube-based NEAT, or HyperNEAT, is a generative encoding that evolves artificial neural networks (ANNs) with the principles of the widely used NeuroEvolution of Augmented Topologies (NEAT) algorithm. It is a novel technique for evolving large-scale neural networks using the geometric regularities of the task domain. It uses Compositional Pattern Producing Networks (CPPNs), which are used to generate the images for Picbreeder.org and shapes for EndlessForms.com. has recently been extended to also evolve plastic ANNs and to evolve the location of every neuron in the network. | Biology | https://en.wikipedia.org/wiki?curid=21573718 | HyperNEAT | 140,900 |
GYKI-52,466 GYKI-52466 is a 2,3-benzodiazepine that acts as an ionotropic glutamate receptor antagonist, which is a non-competitive AMPA receptor antagonist (IC50 values are 10-20, ~ 450 and » 50 μM for AMPA-, kainate- and NMDA-induced responses respectively), orally-active anticonvulsant, and skeletal muscle relaxant. Unlike conventional 1,4-benzodiazepines, GYKI-52466 and related 2,3-benzodiazepines do not act on GABA receptors. Like other AMPA receptor antagonists, GYKI-52466 has anticonvulsant and neuroprotective properties. | Biology | https://en.wikipedia.org/wiki?curid=21577748 | GYKI-52,466 | 140,901 |
Potocytosis is a type of receptor-mediated endocytosis in which small molecules are transported across the plasma membrane of a cell. The molecules are transported by caveolae (rather than clathrin-coated vesicles) and are deposited directly into the cytosol. Like other types of receptor-mediated endocytosis, potocytosis typically begins when an extracellular ligand binds to a receptor protein on the surface of a cell, thus beginning the formation of an endocytotic vesicle. The ligand is usually of low molecular mass (e.g. vitamins), but some larger molecules (such as lipids) can also act as ligands. Lipid rafts in the plasma membrane act as membrane microdomains. They are enriched in cholesterol and sphingolipids and are involved potocytosis as the lateral compartmentalization of molecules. Caveolae are caveolin-1-enriched smooth invaginations found on these lipid rafts that contribute to transportation of molecules. works by taking up material into caveolae at the surface of the cell. Glycosylphosphatidylinositol-anchored class of membrane proteins generate high concentrations of molecules. This may either be by releasing a receptor bound molecule, by converting molecules enzymatically or by releasing them from a carrier protein. | Biology | https://en.wikipedia.org/wiki?curid=21588604 | Potocytosis | 140,902 |
Ureohydrolase A ureohydrolase is a type of hydrolase enzyme. The ureohydrolase superfamily includes arginase (), agmatinase (), formiminoglutamase () and proclavaminate amidinohydrolase (). These enzymes share a 3-layer alpha-beta-alpha structure, and play important roles in arginine/agmatine metabolism, the urea cycle, histidine degradation, and other pathways. Arginase, which catalyses the conversion of arginine to urea and ornithine, is one of the five members of the urea cycle enzymes that convert ammonia to urea as the principal product of nitrogen excretion. There are several arginase isozymes that differ in catalytic, molecular and immunological properties. Deficiency in the liver isozyme leads to argininemia, which is usually associated with hyperammonemia. Agmatinase hydrolyses agmatine to putrescine, the precursor for the biosynthesis of higher polyamines, spermidine and spermine. In addition, agmatine may play an important regulatory role in mammals. Formiminoglutamase catalyses the fourth step in histidine degradation, acting to hydrolyse N-formimidoyl-L-glutamate to L-glutamate and formamide. Proclavaminate amidinohydrolase is involved in clavulanic acid biosynthesis. Clavulanic acid acts as an inhibitor of a wide range of beta-lactamase enzymes that are used by various microorganisms to resist beta-lactam antibiotics. As a result, this enzyme improves the effectiveness of beta-lactamase antibiotics. | Biology | https://en.wikipedia.org/wiki?curid=21588687 | Ureohydrolase | 140,903 |
Cytosis is a transport mechanism for the movement of large quantities of molecules into and out of cells. There are three main types of cytosis: endocytosis (into the cell), exocytosis (out of the cell), and transcytosis (through the cell, in and out). The word "cytosis" () uses combining forms of "cyto-" and "-osis", reflecting a cellular process. The term was coined by Novikoff in 1961. Endocytosis is when a cell absorbs a molecule, such as a protein, from outside the cell by engulfing it with the cell membrane. It is used by most cells, because many critical substances are large polar molecules that cannot pass through the cell membrane. The two major types of endocytosis are pinocytosis and phagocytosis. Exocytosis is when a cell directs the contents of secretory vesicles out of the cell membrane. The vesicles fuse with the cell membrane and their content, usually protein, is released out of the cell. There are two types of exocytosis: Constitutive secretion and Regulated secretion. In both of these types, a vesicle buds from the Golgi Apparatus and is shuttled to the plasma membrane, to be exocytosed from the cell. Exocytosis of lysosomes commonly serves to repair damaged areas of the plasma membrane by replenishing the lipid bilayer. Transcytosis is a type of cytosis that allows particles to be shuttled from one membrane to another. An example of this would be when a receptor normally lies on the basal or lateral membrane of an epithelial cell, but needs to be trafficked to the apical side | Biology | https://en.wikipedia.org/wiki?curid=21590012 | Cytosis | 140,904 |
Cytosis This can only be done through transcytosis due to tight junctions, which prevent movement from one plasma membrane domain to another. This type of cytosis occurs commonly in epithelium, intestinal cells, and blood capillaries. Transcytosis can also be taken advantage of by pathogenic molecules and organisms. Several studies have shown that bacterium can easily enter intestinal lumen through transcytosis of goblet cells. Other studies, however, are exploring the idea that transcytosis may play a role in allowing medications to cross the blood-brain barrier. Exploiting this fact may allow certain drug therapies to be better utilized by the brain. Methods of cytosis not only move substances in, out of, and through cells, but also add and subtract membrane from the cell's plasma membrane. The surface area of the membrane is determined by the balance of the two mechanisms and contributes to the homeostatic environment of the cell. | Biology | https://en.wikipedia.org/wiki?curid=21590012 | Cytosis | 140,905 |
Dystrophin-associated protein A dystrophin-associated protein is a protein that helps to form the connection between intracellular dystrophin and the extracellular basal lamina. Examples include sarcoglycan and dystroglycan. | Biology | https://en.wikipedia.org/wiki?curid=21596932 | Dystrophin-associated protein | 140,906 |
Laminin, beta 4 LAMB4 is a laminin gene. | Biology | https://en.wikipedia.org/wiki?curid=21598742 | Laminin, beta 4 | 140,907 |
Medea hypothesis The is a term coined by paleontologist Peter Ward for the anti-Gaian hypothesis that multicellular life, understood as a superorganism, is suicidal. In this view, microbial-triggered mass extinctions are attempts to return the Earth to the microbial-dominated state it has been for most of its history. The metaphor refers to the mythological Medea (representing the Earth), who kills her own children (multicellular life). Past "suicide attempts" include: The list does not include the Cretaceous–Paleogene extinction event, since this was, at least partially, externally induced by a meteor impact. Peter Ward also believes that the current man-made climate change and mass extinction event may be considered to be the most recent Medean event. As these events are anthropogenic, he postulates that Medean events are not necessarily caused by microbes, but by intelligent life as well. He believes that the final mass extinction of complex life, roughly about 500 million years in the future, will also be considered a Medean event. Plant life that still exists by then will be forced to adapt to a warming and expanding Sun, causing them to remove even more carbon dioxide from the atmosphere (which in turn will have already be due to the increasing heat from the Sun gradually speeding up the weathering process that removes them from the atmosphere), and ultimately accelerating the complete extinction of complex life by making carbon dioxide levels drop down to just 10 ppm, below which plants can no longer survive | Biology | https://en.wikipedia.org/wiki?curid=21599341 | Medea hypothesis | 140,908 |
Medea hypothesis However, Ward simultaneously argues that intelligent life such as humans may not necessarily just trigger future Medean events, but may eventually prevent them from occurring. | Biology | https://en.wikipedia.org/wiki?curid=21599341 | Medea hypothesis | 140,909 |
Recognition signal A recognition signal is a signal whereby a person, a ship, an airplane or something else is recognized. They can be used during war or can be used to help the police recognize each other during undercover operations. It can also be used in biology to signal that a molecule or chemical is to be bound to another molecule. These signals are often used to recognize friends and enemies in a war. For military use these signals often use colored lights or the International marine signal flags Other uses of the signal include the police who sometimes use a recognition signal so that officers in uniform can recognize officers in normal clothing (undercover). The NYPD often use headbands, wristbands or colored clothing as recognition signals which are known as the "color of the day". A recognition signal is also a chemical signal used in biology to signal the end of a section of DNA or RNA during gene duplication in cells. | Biology | https://en.wikipedia.org/wiki?curid=21599910 | Recognition signal | 140,910 |
OPN1MW2 is an opsin similar to OPN1MW. It is thought that about 12 percent of women have both forms, which gives them the potential to be tetrachromats. | Biology | https://en.wikipedia.org/wiki?curid=21603736 | OPN1MW2 | 140,911 |
Ribbon synapse The ribbon synapse is a type of neuronal synapse characterized by the presence of an electron-dense structure, the synaptic ribbon, that holds vesicles close to the active zone. It is characterized by a tight vesicle-calcium channel coupling that promotes rapid neurotransmitter release and sustained signal transmission. Ribbon synapses undergo a cycle of exocytosis and endocytosis in response to graded changes of membrane potential. It has been proposed that most ribbon synapses undergo a special type of exocytosis based on coordinated multivesicular release. This interpretation has recently been questioned at the inner hair cell ribbon synapse, where it has been instead proposed that exocytosis is described by uniquantal (i.e., univesicular) release shaped by a flickering vesicle fusion pore. These unique features specialize the ribbon synapse to enable extremely fast, precise and sustained neurotransmission, which is critical for the perception of complex senses such as vision and hearing. Ribbon synapses are found in retinal photoreceptor cells, vestibular organ receptors, cochlear hair cells, retinal bipolar cells, and pinealocytes. The synaptic ribbon is a unique structure at the active zone of the synapse. It is positioned several nanometers away from the pre-synaptic membrane and tethers 100 or more synaptic vesicles. Each pre-synaptic cell can have from 10 to 100 ribbons tethered at the membrane, or a total number of 1000–10000 vesicles in close proximity to active zones | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,912 |
Ribbon synapse The ribbon synapse was first identified in the retina as a thin, ribbon-like presynaptic projection surrounded by a halo of vesicles using transmission electron microscopy in the 1950s, as the technique was gaining mainstream usage. The photoreceptor ribbon synapse is around 30 nm in thickness. It sticks out into the cytoplasm around 200-1000 nm and anchors along its base to the arciform density which is an electron dense structure that is anchored to the presynaptic membrane. The arciform density is located within the synaptic ridge, a small evagination of the presynaptic membrane. Hair cells lack an arciform density so the anchor of this ribbon is considered to be invisible by electron microscope. The ribbon's surface has small particles that are around 5 nm wide where the synaptic vesicles tether densely via fine protein filaments. There are multiple filaments per vesicle. There are also voltage gated L-type calcium channels on the docking sites of the ribbon synapse which trigger neurotransmitter release. Specifically, ribbon synapses contain specialized organelles called synaptic ribbons, which are large presynaptic structures associated in the active zone. They are thought to fine-tune the synaptic vesicle cycle. Synaptic ribbons are in close proximity to synaptic vesicles, which, in turn, are close to the presynaptic neurotransmitter release site via the ribbon. Postsynaptic structures differ for cochlear cells and photoreceptor cells | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,913 |
Ribbon synapse Hair cells is capable of one action potential propagation for one vesicle release. One vesicle release from the presynaptic hair cell onto the postsynaptic bouton is enough to create an action potential in the auditory afferent cells. Photoreceptors allow one vesicle release for many action potential propagation. The rod terminal and cone ribbon synapse of the photoreceptors have horizontal synaptic spines expressing AMPA receptors with additional bipolar dendrites exhibiting the mGluR6 receptors. These structures allow for the binding of multiple molecules of glutamate, allowing for the propagation of many action potentials. The molecular composition between conventional neuronal synapse and ribbon synapse is surprisingly dissimilar. At the core of synaptic vesicle exocytosis machinery in vertebrate neuronal synapses is the SNARE complex. The minimally functional SNARE complex includes syntaxin 1, VAMP 1 and 2, and SNAP-25. In contrast, genetic ablation or application of botulinum, targeting SNAP-25, syntaxin 1-3, and VAMP 1-3, did not affect inner hair cell ribbon synapse exocytosis in mice. Additionally, no neuronal SNAREs were observed in hair cells using immunostaining, pointing to the possibility of a different exocytosis mechanism. However, several studies found SNARE mRNA and protein expressed in hair cell, perhaps indicating presence of a neuronal SNARE complex in ribbon synapse that is present in low levels and with very redundant components | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,914 |
Ribbon synapse Several proteins of the synaptic ribbon have also been found to be associated with conventional synapses. RIM (Rab3-interacting proteins) is a GTPase expressed on synaptic vesicles that is important in priming synaptic vesicles. Immunostaining has revealed the presence of KIF3A, a component of the kinesin II motor complex whose function is still unknown. The presynaptic cytomatrix proteins Bassoon and Piccolo are both expressed at photoreceptor ribbons, but Piccolo is only expressed at retinal bipolar synaptic ribbons. Bassoon is responsible for attaching itself to the base of the synaptic ribbons and subsequently anchoring the synaptic ribbons. The function of Piccolo is unknown. Also important is the filaments that tether the vesicles to the ribbon synapse. These are shed during high rates of exocytosis. The only unique protein associated with the synaptic ribbon is RIBEYE, first identified in purified synaptic ribbon from bovine retina. It is found to be a part of all vertebrate synaptic ribbons in ribbon synapses and is the central portion of ribbon synapses. RIBEYE interactions are required to form a scaffold formation protein of the synaptic ribbon. There has been a significant amount of research into the pre-synaptic cytomatrix protein Bassoon, which is a multi-domain scaffolding protein universally expressed at synapses in the central nervous system. Mutations in Bassoon have been shown to result in decreased synaptic transmission | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,915 |
Ribbon synapse However, the underlying mechanisms behind this observed phenomenon are not fully understood and are currently being investigated. It has been observed that in the retina of Bassoon-mutant mice, photoreceptor ribbon synapses are not anchored to pre-synaptic active zones during photoreceptor synaptogenesis. The photoreceptor ribbon synapses are observed to be free floating in the cytoplasm of the photoreceptor terminals. These observations have led to the conclusion that Bassoon plays a critical role in the formation of the photoreceptor ribbon synapse. In correspondence to its activity, ribbon synapses can have synaptic ribbons that vary in size. In mouse photoreceptor synapses when the neurotransmitter release rate is high and exocytosis is high, the synaptic ribbons are long. When neurotransmitter release rate is low and exocytosis is low, the synaptic ribbons are short. A current hypothesis is that synaptic ribbons can enlarge by the addition of more RIBEYE subunit. Features of the ribbon synapse enable it to process information extremely quickly. Bipolar neurons present a good model for how ribbon synapses function. Information is conveyed from photoreceptor cells to bipolar cells via the release of the neurotransmitter glutamate at the ribbon synapse. Conventional neurons encode information by changes in the rate of action potentials, but for complex senses like vision, this is not sufficient | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,916 |
Ribbon synapse Ribbon synapses enable neurons to transmit light signals over a dynamic range of several orders of magnitude in intensity. This is achieved by encoding intensity changes in tonic rate of transmitter release which requires the release of several hundred to several thousand synaptic vesicles per second. To accomplish this level of performance, the sensory neurons of the eye maintain large pools of fast releasable vesicles that are equipped with ribbon synapses. This enables the cell to exocytose hundreds of vesicles per second, greatly exceeding the rate of neurons without the specialized ribbon synapse. The current hypothesis of calcium-dependent exocytosis at retinal ribbon synapses suggests that the ribbon accommodates a reservoir of primed releasable vesicles. The vesicles that are in closest contact with the presynaptic plasma membrane at the base of the ribbon constitute the small, rapidly releasable pool of vesicles, whereas the remaining vesicles tethered to the ribbon constitute the large, readily (slower) releasable pool. These regularly aligned rows of synaptic vesicles tethered to either side of the ribbon along with the expression of the kinesin motor protein KIF3A at retinal ribbon synapses can move vesicles like a conveyor belt to the docking/release site at the ribbon base. During exocytosis at the bipolar ribbon synapse, vesicles are seen to pause at the membrane and then upon opening of the calcium channels to promptly release their contents within milliseconds | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,917 |
Ribbon synapse Like most exocytosis, Ca regulates the release of vesicles from the presynaptic membrane. Different types of ribbon synapses have different dependence on Ca releases. The hair cell ribbon synapses exhibit a steep dependence on Ca concentration, while the photoreceptor synapses is less steeply dependent on Ca and is stimulated by much lower levels of free Ca. The hair cell ribbon synapse experiences spontaneous activity in the absence of stimuli, under conditions of a constant hair cell membrane potential. Voltage clamp at the postsynaptic bouton showed that the bouton experiences a wide range of excitatory postsynaptic current amplitudes. The current amplitude distribution is a positive-skew, with a range of larger amplitudes for both spontaneous and stimulus evoked release. It was thought that this current distribution was not explainable with single vesicle release, and other scenarios of release have been proposed: coordinated multivesicular release, kiss-and-run, or compound fusion of vesicles prior to exocytosis. However it has been recently proposed that uniquantal release with fusion pore flickering is the most plausible interpretation of the found current distribution. In fact, the charge distribution of currents is actually normally distributed, supporting the uniquantal release scenario. It has been shown that the skewness of the current amplitude distribution is well explained by different time courses of neurotransmitter release of a single vesicles with a flickering fusion pore | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,918 |
Ribbon synapse The bipolar cell active zone of the ribbon synapse can release neurotransmitter continuously for hundreds of milliseconds during strong stimulation. This release of neurotransmitters occurs in two kinetically distinct phases: a small fast pool where about twenty percent of the total is released in about 1 millisecond, and a large sustained pool where the remaining components are released over hundreds of milliseconds. The existence of correspondence between the pool of tethered vesicles and the pool for sustained release in the rods and bipolar cells of the ribbon reveals that the ribbon may serve as a platform where the vesicles can be primed to allow sustained release of neurotransmitters. This large size of the sustained large component is what separates the ribbon synapse active zones from those of conventional neurons where sustained release is small in comparison. Once the presynaptic vesicles have been depleted, the bipolar cell's releasable pool requires several seconds to refill with the help of ATP hydrolysis. A high rate of endocytosis is necessary to counter the high rate of exocytosis during sustained neurotransmitter release at ribbon synapses. Synaptic vesicles need to be recycled for further transmission to occur. These vesicles are directly recycled and because of their mobility, quickly replenish the neurotransmitters required for continued release. In cone photoreceptors, the fused membrane is recycled into the synaptic vesicle without pooling of the membrane into the endosomes | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,919 |
Ribbon synapse Bipolar cells rely on a different mechanism. It involves taking a large portion of the membrane which is endocytosed and gives rise to synaptic vesicles. This mechanism is conserved in hair cells as well. Research has shown that abnormal expression of otoferlin, a ribbon synapse associated protein, impairs exocytosis of ribbon-bound vesicles in auditory inner hair cells. Otoferlin displays similar functional characteristics to synaptotagmin, a synapse associated protein important for mediating exocytosis in many other synapses (such as those in the central nervous system). Impaired hearing in mice has been shown to be associated with disrupted expression of otoferlin. In studies of retinal genetic coding of laboratory mice, several mutated ribbon synapse associated voltage-gated L-type calcium channel auxiliary subunits were shown to be associated with dysfunctional rod and cone activity and information transmission. Mice were shown to express significantly reduced scotopic vision, and further research has shown the dysregulation of calcium homeostasis may have a significant role in rod photoreceptor degradation and death. Much of the genetic information associated with the proteins observed in laboratory mice are shared with humans. The protein otoferlin is observed phenotypically in human auditory inner hair cells, and abnormal expression has been linked with deafness | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,920 |
Ribbon synapse In humans, cochlear implants have shown to reduce the debilitating effects of abnormal otoferlin expression by surpassing the synapse associated with the auditory inner hair cells. The genetic code for retinal subunits associated with impaired scotopic vision and rod photoreceptor degradation are conserved at approximately 93% between mice and humans. Further research into the abnormal functioning of these mechanisms could open the door to therapeutic techniques to relieve auditory and visual impairments. Several recent studies have provided evidence that loss-of-function mutations in pre-synaptic proteins of the photoreceptor cells ribbon synapse can cause X-linked congenital stationary night blindness (CSNB) through mutations in the CACNA1F gene, which codes for the αF1-subunit of the L-type calcium channel Ca1.4. The gene is expressed at the active zone of photoreceptor ribbon synapses. The mutation is characterized by a significant reduction in both night and variable perturbation of daylight vision. The mutations in CACNA1F and Ca1.4 have also been observed to co-localize with CaBP4, a photoreceptor-specific calcium-binding protein. CaBP4 has been theorized to modulate the activity of the Ca1.4 channel. It has been theorized to be associated with the proper establishment and maintenance of photoreceptor ribbon synapses. While no evidence has been published, the association between CaBP4 and Ca1.4 is an area of continued research. | Biology | https://en.wikipedia.org/wiki?curid=21610244 | Ribbon synapse | 140,921 |
China Health and Retirement Longitudinal Study The (CHARLS) is a longitudinal survey being conducted by the China Center for Economic Research at Peking University with Professor Yaohui Zhao of Peking University serving as Principal Investigator and Professors John Strauss of the University of Southern California and Albert Park of HKUST Institute for Emerging Market Studies serving as co-Principal Investigators. The survey will collect a representative sample of Chinese 45 and older every two years to enable multidisciplinary studies on issues related to population ageing. China is one of the fastest ageing countries in the world and accounts for a large fraction of the growth in the world's old. By 2050, China's elderly (65 and older) population share is expected to reach 30%. The pilot survey is funded by the National Institute on Aging, the World Bank, and Natural Science Foundation of China. The questionnaire contains information on household demographics, transfers among family members, health status, health care, employment, income, consumption and assets, as well as information on health facilities of the community and government policies in local areas. The CHARLS is designed on the models of health and retirement studies originated from the Health and Retirement Study (HRS) in the U.S., but has the advantage of including information on the community the respondent resides and local policies. Due to large internal variations of government policies, the data will enable analyses of policy impacts in the process of population ageing | Biology | https://en.wikipedia.org/wiki?curid=21611124 | China Health and Retirement Longitudinal Study | 140,922 |
China Health and Retirement Longitudinal Study Other countries participating in this international network of ageing studies include England, fifteen countries in continental Europe, Israel, India, Korea, and Japan. The pilot survey was conducted in two provinces (Zhejiang and Gansu) in 2008 and collected data on roughly 1,600 households. The pilot data of 2008 has been released to the research community since April 30, 2009. The national baseline survey is being planned for 2011. CHARLS data will be available for download by researchers at no cost. | Biology | https://en.wikipedia.org/wiki?curid=21611124 | China Health and Retirement Longitudinal Study | 140,923 |
Ocelliless (oc) or Orthodenticle is a homeobox gene involved in "Drosophila" head development. It produces a homeodomain protein which controls the development of cells in the developing head of embryos. It defines the midline of the head, and is involved in the formation of the top side of the head, including the eyes. The gene breaks the head down into subdomains; the medial subdomain (contains the ocelli); the mediolaterial ; and the lateral (just above the compound eyes). If "orthodenticle" is not expressed, structures from the lateral subdomain will be expressed all the way over the head - meaning that ocelli are not produced, i.e. "ocelliless". | Biology | https://en.wikipedia.org/wiki?curid=21611215 | Ocelliless | 140,924 |
Affinity electrophoresis is a general name for many analytical methods used in biochemistry and biotechnology. Both qualitative and quantitative information may be obtained through affinity electrophoresis. The methods include the so-called electrophoretic mobility shift assay, charge shift electrophoresis and affinity capillary electrophoresis. The methods are based on changes in the electrophoretic pattern of molecules (mainly macromolecules) through biospecific interaction or complex formation. The interaction or binding of a molecule, charged or uncharged, will normally change the electrophoretic properties of a molecule. Membrane proteins may be identified by a shift in mobility induced by a charged detergent. Nucleic acids or nucleic acid fragments may be characterized by their affinity to other molecules. The methods have been used for estimation of binding constants, as for instance in lectin affinity electrophoresis or characterization of molecules with specific features like glycan content or ligand binding. For enzymes and other ligand-binding proteins, one-dimensional electrophoresis similar to counter electrophoresis or to "rocket immunoelectrophoresis", affinity electrophoresis may be used as an alternative quantification of the protein. Some of the methods are similar to affinity chromatography by use of immobilized ligands | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,925 |
Affinity electrophoresis Currently, there is ongoing research in developing new ways of utilizing the knowledge already associated with affinity electrophoresis to improve its functionality and speed, as well as attempts to improve already established methods and tailor them towards performing specific tasks. A type of electrophoretic mobility shift assay (AMSA), agarose gel electrophoresis is used to separate protein-bound amino acid complexes from free amino acids. Using a low voltage (~10 V/cm) to minimize the risk for heat damage, electricity is run across an agarose gel. This technique utilizes a high voltage () with a 0.5× Tris-borate buffer run across an agarose gel. This method differs from the traditional agarose gel electrophoresis by utilizing a higher voltage to facilitate a shorter run time as well as yield a higher band resolution. Other factors included in developing the technique of rapid agarose gel electrophoresis are gel thickness, and the percentage of agarose within the gel. Boronate affinity electrophoresis utilizes boronic acid infused acrylimide gels to purify NAD-RNA. This purification allows for researchers to easily measure the kinetic activity of NAD-RNA decapping enzymes. Affinity capillary electrophoresis (ACE) refers to a number of techniques which rely on specific and nonspecific binding interactions to facilitate separation and detection through a formulary approach in accordance with the theory of electromigration | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,926 |
Affinity electrophoresis Using the intermolecular interactions between molecules occurring in free solution or mobilized onto a solid support, ACE allows for the separation and quantitation of analyte concentrations and binding and dissociation constants between molecules. With ACE, scientists hope to develop strong binding drug candidates, understand and measure enzymatic activity, and characterize the charges on proteins. Affinity capillary electrophoresis can be divided into three distinct techniques: non-equilibrium electrophoresis of equilibrated sample mixtures, dynamic equilibrium ACE, and affinity-based ACE. Nonequilibrium electrophoresis of equilibrated sample mixtures is generally used in the separation and study of binding interactions of large proteins and involves combining both the analyte and its receptor molecule in a premixed sample. These receptor molecules often take the form of affinity probes consisting of fluorophore-labeled molecules that will bind to target molecules that are mixed with the sample being tested. This mixture, and its subsequent complexes, are then separated through capillary electrophoresis. Because the original mixture of analyte and receptor molecule were bound together in an equilibrium, the slow dissociation of these two bound molecules during the electrophoretic experiment will result in their separation and a subsequent shift in equilibrium towards further dissociation | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,927 |
Affinity electrophoresis The characteristic smear pattern produced by the slow release of the analyte from the complex during the experiment can be used to calculate the dissociation constant of the complex. Dynamic equilibrium ACE involves the combination of the analyte found in the sample and its receptor molecule found in the buffered solution in the capillary tube so that binding and separation only occur in the instrument. It is assumed for dynamic equilibrium affinity capillary electrophoresis that ligand-receptor binding occurs rapidly when the analyte and buffer are mixed. Binding constants are generally derived from this technique based upon the peak migration shift of the receptor which is dependent upon the concentration of the analyte in the sample. Affinity-based capillary electrophoresis, also known as capillary electroaffinity chromatography (CEC), involves the binding of analyte in sample to an immobilized receptor molecule on the capillary wall, microbeads, or microchannels. CEC offers the highest separation efficacy of all three ACE techniques as non-matrixed sample components are washed away and the ligand then be released and analyzed. Affinity capillary electrophoresis takes the advantages of capillary electrophoresis and applies them to the study of protein interactions. ACE is advantageous because it has a high separation efficiency, has a shorter analysis time, can be run at physiological pH, and involves low consumption of ligand/molecules | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,928 |
Affinity electrophoresis In addition, the composition of the protein of interest does not have to be known in order to run ACE studies. The main disadvantage, though, is that it does not give much stoichiometric information about the reaction being studied. Affinity-trap polyacrylamide gel electrophoresis (PAGE) has become one of the most popular methods of protein separation. This is not only due to its separation qualities, but also because it can be used in conjunction with a variety of other analytic methods, such as mass spectrometry, and western blotting. This method utilizes a two-step approach. First, a protein sample is run through a polyacrylamide gel using electrophoresis. Then, the sample is transferred to a different polyacrylamide gel (the affinity-trap gel) where affinity probes are immobilized. The proteins that do not have affinity for the affinity probes pass through the affinity-trap gel, and proteins with affinity for the probes will be "trapped" by the immobile affinity probes. These trapped proteins are then visualized and identified using mass spectrometry after in-gel digestion. Phosphate affinity electrophoresis utilizes an affinity probe which consists of a molecule that binds specifically to divalent phosphate ions in neutral aqueous solution, known as a "Phos-Tag". This methods also utilizes a separation gel made of an acrylamide-pendent Phos-Tag monomer that is copolymerized. Phosphorylated proteins migrate slowly in the gel compared to non-phosphorylated proteins | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,929 |
Affinity electrophoresis This technique gives the researcher the ability to observe the differences in the phosphorylation states of any given protein. | Biology | https://en.wikipedia.org/wiki?curid=21620243 | Affinity electrophoresis | 140,930 |
Arsenamide or thiacetarsamide (trade name Caparsolate) is an arsenical. It is a proposed chemotherapeutic agent against canine filaria and trichomonas. | Biology | https://en.wikipedia.org/wiki?curid=21627505 | Arsenamide | 140,931 |
Ribosome-inactivating protein A ribosome-inactivating protein (RIP) is a protein synthesis inhibitor that acts at the ribosome. A number of bacterial and plant toxins act by inhibiting protein synthesis in eukaryotic cells. The toxins of the Shiga and ricin family inactivate 60S ribosomal subunits by an N-glycosidic cleavage, which releases a specific adenine base from the sugar-phosphate backbone of 28S rRNA. Members of the family include shiga and shiga-like toxins, and type I (e.g. trichosanthin and luffin) and type II (e.g. ricin, agglutinin, and abrin) ribosome inactivating proteins (RIPs). All these toxins are structurally related. RIPs have been of considerable interest because of their potential use, conjugated with monoclonal antibodies, as immunotoxins to treat cancers. Further, trichosanthin has been shown to have potent activity against HIV-1-infected T cells and macrophages. Elucidation of the structure-function relationships of RIPs has therefore become a major research effort. It is now known that RIPs are structurally related. A conserved glutamic residue has been implicated in the catalytic mechanism; this lies near a conserved arginine, which also plays a role in catalysis. Examples include: Ribosome-inactivating proteins (RIPs) are separated into three types based on protein domain composition: They exist in bacteria and plants. Only a minority of RIPs are toxic to humans when consumed, and proteins of this family are found in the vast majority of plants used for human consumption, such as Rice, Maize and Barley. | Biology | https://en.wikipedia.org/wiki?curid=21632953 | Ribosome-inactivating protein | 140,932 |
Alisporivir (INN), or Debio 025, DEB025, (or UNIL-025) is a cyclophilin inhibitor. Its structure is reminiscent of, and synthesized from ciclosporin. It inhibits cyclophilin A. is not immunosuppressive. It is being researched for potential use in the treatment of hepatitis C. It has also been investigated for Duchenne muscular dystrophy. is under development by Debiopharm for Japan and by Novartis for the rest of the world (licence granted by Debiopharm) since February 2010. | Biology | https://en.wikipedia.org/wiki?curid=21633417 | Alisporivir | 140,933 |
Whole genome sequencing is ostensibly the process of determining the complete DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria and, for plants, in the chloroplast. In practice, genome sequences that are nearly complete are also called whole genome sequences. has largely been used as a research tool, but was being introduced to clinics in 2014. In the future of personalized medicine, whole genome sequence data may be an important tool to guide therapeutic intervention. The tool of gene sequencing at SNP level is also used to pinpoint functional variants from association studies and improve the knowledge available to researchers interested in evolutionary biology, and hence may lay the foundation for predicting disease susceptibility and drug response. should not be confused with DNA profiling, which only determines the likelihood that genetic material came from a particular individual or group, and does not contain additional information on genetic relationships, origin or susceptibility to specific diseases. In addition, whole genome sequencing should not be confused with methods that sequence specific subsets of the genome - such methods include whole exome sequencing (1-2% of the genome) or SNP genotyping (<0.1% of the genome). As of 2017 there were no complete genomes for any mammals, including humans. Between 4% to 9% of the human genome, mostly satellite DNA, had not been sequenced | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,934 |
Whole genome sequencing It is also known as WGS, full genome sequencing, complete genome sequencing, or entire genome sequencing. The DNA sequencing methods used in the 1970s and 1980s were manual, for example Maxam-Gilbert sequencing and Sanger sequencing. The shift to more rapid, automated sequencing methods in the 1990s finally allowed for sequencing of whole genomes. The first organism to have its entire genome sequenced was "Haemophilus influenzae" in 1995. After it, the genomes of other bacteria and some archaea were first sequenced, largely due to their small genome size. "H. influenzae" has a genome of 1,830,140 base pairs of DNA. In contrast, eukaryotes, both unicellular and multicellular such as "Amoeba dubia" and humans ("Homo sapiens") respectively, have much larger genomes (see C-value paradox). "Amoeba dubia" has a genome of 700 billion nucleotide pairs spread across thousands of chromosomes. Humans contain fewer nucleotide pairs (about 3.2 billion in each germ cell - note the exact size of the human genome is still being revised) than "A. dubia" however their genome size far outweighs the genome size of individual bacteria. The first bacterial and archaeal genomes, including that of "H. influenzae", were sequenced by Shotgun sequencing. In 1996 the first eukaryotic genome ("Saccharomyces cerevisiae") was sequenced. "S. cerevisiae", a model organism in biology has a genome of only around 12 million nucleotide pairs, and was the first "unicellular" eukaryote to have its whole genome sequenced | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,935 |
Whole genome sequencing The first "multicellular" eukaryote, and animal, to have its whole genome sequenced was the nematode worm: "Caenorhabditis elegans" in 1998. Eukaryotic genomes are sequenced by several methods including Shotgun sequencing of short DNA fragments and sequencing of larger DNA clones from DNA libraries such as bacterial artificial chromosomes (BACs) and yeast artificial chromosomes (YACs). In 1999, the entire DNA sequence of human chromosome 22, the shortest human autosome, was published. By the year 2000, the second animal and second invertebrate (yet first insect) genome was sequenced - that of the fruit fly "Drosophila melanogaster" - a popular choice of model organism in experimental research. The first plant genome - that of the model organism "Arabidopsis thaliana" - was also fully sequenced by 2000. By 2001, a draft of the entire human genome sequence was published. The genome of the laboratory mouse "Mus musculus" was completed in 2002. In 2004, the Human Genome Project published an incomplete version of the human genome. In 2008, a group from Leiden, The Netherlands, reported the sequencing of the first female human genome (Marjolein Kriek). Currently thousands of genomes have been wholly or partially sequenced. Almost any biological sample containing a full copy of the DNA—even a very small amount of DNA or ancient DNA—can provide the genetic material necessary for full genome sequencing | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,936 |
Whole genome sequencing Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, plant leaves, or anything else that has DNA-containing cells. The genome sequence of a single cell selected from a mixed population of cells can be determined using techniques of "single cell genome sequencing". This has important advantages in environmental microbiology in cases where a single cell of a particular microorganism species can be isolated from a mixed population by microscopy on the basis of its morphological or other distinguishing characteristics. In such cases the normally necessary steps of isolation and growth of the organism in culture may be omitted, thus allowing the sequencing of a much greater spectrum of organism genomes. Single cell genome sequencing is being tested as a method of preimplantation genetic diagnosis, wherein a cell from the embryo created by in vitro fertilization is taken and analyzed before embryo transfer into the uterus. After implantation, cell-free fetal DNA can be taken by simple venipuncture from the mother and used for whole genome sequencing of the fetus. Sequencing of nearly an entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing technology. While full genome shotgun sequencing for small (4000–7000 base pair) genomes was already in use in 1979, broader application benefited from pairwise end sequencing, known colloquially as "double-barrel shotgun sequencing" | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,937 |
Whole genome sequencing As sequencing projects began to take on longer and more complicated genomes, multiple groups began to realize that useful information could be obtained by sequencing both ends of a fragment of DNA. Although sequencing both ends of the same fragment and keeping track of the paired data was more cumbersome than sequencing a single end of two distinct fragments, the knowledge that the two sequences were oriented in opposite directions and were about the length of a fragment apart from each other was valuable in reconstructing the sequence of the original target fragment. The first published description of the use of paired ends was in 1990 as part of the sequencing of the human HPRT locus, although the use of paired ends was limited to closing gaps after the application of a traditional shotgun sequencing approach. The first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991. In 1995 the innovation of using fragments of varying sizes was introduced, and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. The strategy was subsequently adopted by The Institute for Genomic Research (TIGR) to sequence the entire genome of the bacterium "Haemophilus influenzae" in 1995, and then by Celera Genomics to sequence the entire fruit fly genome in 2000, and subsequently the entire human genome | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,938 |
Whole genome sequencing Applied Biosystems, now called Life Technologies, manufactured the automated capillary sequencers utilized by both Celera Genomics and The Human Genome Project. While capillary sequencing was the first approach to successfully sequence a nearly full human genome, it is still too expensive and takes too long for commercial purposes. Since 2005 capillary sequencing has been progressively displaced by high-throughput (formerly "next-generation") sequencing technologies such as Illumina dye sequencing, pyrosequencing, and SMRT sequencing. All of these technologies continue to employ the basic shotgun strategy, namely, parallelization and template generation via genome fragmentation. Other technologies are emerging, including nanopore technology. Though nanopore sequencing technology is still being refined, its portability and potential capability of generating long reads are of relevance to whole-genome sequencing applications. In principle, full genome sequencing can provide the raw nucleotide sequence of an individual organism's DNA. However, further analysis must be performed to provide the biological or medical meaning of this sequence, such as how this knowledge can be used to help prevent disease. Methods for analysing sequencing data are being developed and refined. Because sequencing generates a lot of data (for example, there are approximately six billion base pairs in each human diploid genome), its output is stored electronically and requires a large amount of computing power and storage capacity | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,939 |
Whole genome sequencing While analysis of WGS data can be slow, it is possible to speed up this step by using dedicated hardware. A number of public and private companies are competing to develop a full genome sequencing platform that is commercially robust for both research and clinical use, including Illumina, Knome, Sequenom, 454 Life Sciences, Pacific Biosciences, Complete Genomics, Helicos Biosciences, GE Global Research (General Electric), Affymetrix, IBM, Intelligent Bio-Systems, Life Technologies, Oxford Nanopore Technologies, and the Beijing Genomics Institute. These companies are heavily financed and backed by venture capitalists, hedge funds, and investment banks. A commonly-referenced commercial target for sequencing cost until the late 2010s was $1,000, however, the private companies are working to reach a new target of only $100. In October 2006, the X Prize Foundation, working in collaboration with the J. Craig Venter Science Foundation, established the Archon X Prize for Genomics, intending to award $10 million to "the first team that can build a device and use it to sequence 100 human genomes within 10 days or less, with an accuracy of no more than one error in every 1,000,000 bases sequenced, with sequences accurately covering at least 98% of the genome, and at a recurring cost of no more than $1,000 per genome". The Archon X Prize for Genomics was cancelled in 2013, before its official start date. In 2007, Applied Biosystems started selling a new type of sequencer called SOLiD System | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,940 |
Whole genome sequencing The technology allowed users to sequence 60 gigabases per run. In June 2009, Illumina announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30× for $48,000 per genome. In August, the founder of Helicos Biosciences, Stephen Quake, stated that using the company's Single Molecule Sequencer he sequenced his own full genome for less than $50,000. In November, Complete Genomics published a peer-reviewed paper in "Science" demonstrating its ability to sequence a complete human genome for $1,700. In May 2011, Illumina lowered its Full Genome Sequencing service to $5,000 per human genome, or $4,000 if ordering 50 or more. Helicos Biosciences, Pacific Biosciences, Complete Genomics, Illumina, Sequenom, ION Torrent Systems, Halcyon Molecular, NABsys, IBM, and GE Global appear to all be going head to head in the race to commercialize full genome sequencing. With sequencing costs declining, a number of companies began claiming that their equipment would soon achieve the $1,000 genome: these companies included Life Technologies in January 2012, Oxford Nanopore Technologies in February 2012, and Illumina in February 2014. In 2015, the NHGRI estimated the cost of obtaining a whole-genome sequence at around $1,500. In 2016, Veritas Genetics began selling whole genome sequencing, including a report as to some of the information in the sequencing for $999. In summer 2019 Veritas Genetics cut the cost for WGS to $599. In 2017, BGI began offering WGS for $600 | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,941 |
Whole genome sequencing However, in 2015 some noted that effective use of whole gene sequencing can cost considerably more than $1000. Also, reportedly there remain parts of the human genome that have not been fully sequenced by 2017. Full genome sequencing provides information on a genome that is orders of magnitude larger than by DNA arrays, the previous leader in genotyping technology. For humans, DNA arrays currently provide genotypic information on up to one million genetic variants, while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000 times more data. Because of this, full genome sequencing is considered a disruptive innovation to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their consumables cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500 per 1 million basepairs). has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation. An even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical twins) 100-year-old centenarians. Only 8 somatic differences were found, though somatic variation occurring in less than 20% of blood cells would be undetected. In the specifically protein coding regions of the human genome, it is estimated that there are about 0 | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,942 |
Whole genome sequencing 35 mutations that would change the protein sequence between parent/child generations (less than one mutated protein per generation). In cancer, mutation frequencies are much higher, due to genome instability. This frequency can further depend on patient age, exposure to DNA damaging agents (such as UV-irradiation or components of tobacco smoke) and the activity/inactivity of DNA repair mechanisms. Furthermore, mutation frequency can vary between cancer types: in germline cells, mutation rates occur at approximately 0.023 mutations per megabase, but this number is much higher in breast cancer (1.18-1.66 somatic mutations per Mb), in lung cancer (17.7) or in melanomas (≈33). Since the haploid human genome consists of approximately 3,200 megabases, this translates into about 74 mutations (mostly in noncoding regions) in germline DNA per generation, but 3,776-5,312 somatic mutations per haploid genome in breast cancer, 56,640 in lung cancer and 105,600 in melanomas. The distribution of somatic mutations across the human genome is very uneven, such that the gene-rich, early-replicating regions receive fewer mutations than gene-poor, late-replicating heterochromatin, likely due to differential DNA repair activity. In particular, the histone modification H3K9me3 is associated with high, and H3K36me3 with low mutation frequencies | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,943 |
Whole genome sequencing In research, whole-genome sequencing can be used in a Genome-Wide Association Study (GWAS) - a project aiming to determine the genetic variant or variants associated with a disease or some other phenotype. In 2009, Illumina released its first whole genome sequencers that were approved for clinical as opposed to research-only use and doctors at academic medical centers began quietly using them to try to diagnose what was wrong with people whom standard approaches had failed to help. The price to sequence a genome at that time was US$19,500, which was billed to the patient but usually paid for out of a research grant; one person at that time had applied for reimbursement from their insurance company. For example, one child had needed around 100 surgeries by the time he was three years old, and his doctor turned to whole genome sequencing to determine the problem; it took a team of around 30 people that included 12 bioinformatics experts, three sequencing technicians, five physicians, two genetic counsellors and two ethicists to identify a rare mutation in the XIAP that was causing widespread problems. Due to recent cost reductions (see above) whole genome sequencing has become a realistic application in DNA diagnostics. In 2013, the 3Gb-TEST consortium obtained funding from the European Union to prepare the health care system for these innovations in DNA diagnostics. Quality assessment schemes, Health technology assessment and guidelines have to be in place | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,944 |
Whole genome sequencing The 3Gb-TEST consortium has identified the analysis and interpretation of sequence data as the most complicated step in the diagnostic process. At the Consortium meeting in Athens in September 2014, the Consortium coined the word "genotranslation" for this crucial step. This step leads to a so-called "genoreport". Guidelines are needed to determine the required content of these reports. Currently available newborn screening for childhood diseases allows detection of rare disorders that can be prevented or better treated by early detection and intervention. Specific genetic tests are also available to determine an etiology when a child's symptoms appear to have a genetic basis. Full genome sequencing, in addition has the potential to reveal a large amount of information (such as carrier status for autosomal recessive disorders, genetic risk factors for complex adult-onset diseases, and other predictive medical and non-medical information) that is currently not completely understood, may not be clinically useful to the child during childhood, and may not necessarily be wanted by the individual upon reaching adulthood. Genomes2People (G2P), an initiative of Brigham and Women's Hospital and Harvard Medical School was created in 2011 to examine the integration of genomic sequencing into clinical care of adults and children. G2P's director, Robert C | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,945 |
Whole genome sequencing Green, had previously led the REVEAL study — Risk Evaluation and Education for Alzheimer's Disease – a series of clinical trials exploring patient reactions to the knowledge of their genetic risk for Alzheimer's. In 2018, researchers at Rady Children's Institute for Genomic Medicine in San Diego, CA determined that rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. The researchers reported a retrospective cohort study of acutely ill inpatient infants in a regional children's hospital from July 2016-March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. These findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,946 |
Whole genome sequencing The introduction of whole genome sequencing may have ethical implications. On one hand, genetic testing can potentially diagnose preventable diseases, both in the individual undergoing genetic testing and in their relatives. On the other hand, genetic testing has potential downsides such as genetic discrimination, loss of anonymity, and psychological impacts such as discovery of non-paternity. Some ethicists insist that the privacy of individuals undergoing genetic testing must be protected. Indeed, privacy issues can be of particular concern when minors undergo genetic testing. Illumina's CEO, Jay Flatley, claimed in February 2009 that "by 2019 it will have become routine to map infants' genes when they are born". This potential use of genome sequencing is highly controversial, as it runs counter to established ethical norms for predictive genetic testing of asymptomatic minors that have been well established in the fields of medical genetics and genetic counseling. The traditional guidelines for genetic testing have been developed over the course of several decades since it first became possible to test for genetic markers associated with disease, prior to the advent of cost-effective, comprehensive genetic screening. When an individual undergoes whole genome sequencing, they reveal information about not only their own DNA sequences, but also about probable DNA sequences of their close genetic relatives | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,947 |
Whole genome sequencing This information can further reveal useful predictive information about relatives' present and future health risks. Hence, there are important questions about what obligations, if any, are owed to the family members of the individuals who are undergoing genetic testing. In Western/European society, tested individuals are usually encouraged to share important information on any genetic diagnoses with their close relatives, since the importance of the genetic diagnosis for offspring and other close relatives is usually one of the reasons for seeking a genetic testing in the first place. Nevertheless, a major ethical dilemma can develop when the patients refuse to share information on a diagnosis that is made for serious genetic disorder that is highly preventable and where there is a high risk to relatives carrying the same disease mutation. Under such circumstances, the clinician may suspect that the relatives would rather know of the diagnosis and hence the clinician can face a conflict of interest with respect to patient-doctor confidentiality. Privacy concerns can also arise when whole genome sequencing is used in scientific research studies. Researchers often need to put information on patient's genotypes and phenotypes into public scientific databases, such as locus specific databases. Although only anonymous patient data are submitted to locus specific databases, patients might still be identifiable by their relatives in the case of finding a rare disease or a rare missense mutation | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,948 |
Whole genome sequencing Public discussion around the introduction of advanced forensic techniques (such as advanced familial searching using public DNA ancestry websites and DNA phenotyping approaches) has been limited, disjointed, and unfocused. As forensic genetics and medical genetics converge toward genome sequencing, issues surrounding genetic data become increasingly connected, and additional legal protections may need to be established. The first nearly complete human genomes sequenced were two Americans of predominantly Northwestern European ancestry in 2007 (J. Craig Venter at 7.5-fold coverage, and James Watson at 7.4-fold). This was followed in 2008 by sequencing of an anonymous Han Chinese man (at 36-fold), a Yoruban man from Nigeria (at 30-fold), a female clinical geneticist (Marjolein Kriek) from the Netherlands (at 7 to 8-fold), and a female caucasian Leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues). Steve Jobs was among the first 20 people to have their whole genome sequenced, reportedly for the cost of $100,000. , there were 69 nearly complete human genomes publicly available. In November 2013, a Spanish family made their personal genomics data publicly available under a Creative Commons public domain license. The work was led by Manuel Corpas and the data obtained by direct-to-consumer genetic testing with 23andMe and the Beijing Genomics Institute). This is believed to be the first such Public Genomics dataset for a whole family. | Biology | https://en.wikipedia.org/wiki?curid=21647820 | Whole genome sequencing | 140,949 |
Conservation-reliant species are animal or plant species that require continuing species-specific wildlife management intervention such as predator control, habitat management and parasite control to survive, even when a self-sustainable recovery in population is achieved. The term "conservation-reliant species" grew out of the conservation biology undertaken by "The Endangered Species Act at Thirty Project" (launched 2001) and its popularization by project leader J. Michael Scott. Its first use in a formal publication was in "Frontiers in Ecology and the Environment" in 2005. Worldwide use of the term has not yet developed and it has not yet appeared in a publication compiled outside North America. Passages of the 1973 Endangered Species Act (ESA) carried with it the assumption that endangered species would be delisted as their populations recovered. It assumed they would then thrive under existing regulations and the protections afforded under the ESA would no longer be needed. However, eighty percent of species currently listed under the ESA fail to meet that assumption. To survive, they require species-specific conservation interventions (e.g. control of predators, competitors, nest parasites, prescribed burns, altered hydrological processes, etc.) and thus they are conservation-reliant | Biology | https://en.wikipedia.org/wiki?curid=21650435 | Conservation-reliant species | 140,950 |
Conservation-reliant species The criteria for assessing whether a species is conservation-reliant are: There are five major areas of management action for conservation of vulnerable species: A prominent example is in India, where tigers, an apex predator and the national animal, are considered a conservation-reliant species. This keystone species can maintain self-sustaining wild populations; however, they require ongoing management actions because threats are pervasive, recurrent and put them at risk of extinction. The origin of these threats are rooted in the changing socio-economic, political and spatial organization of society in India. Tigers have become extinct in some areas because of extrinsic factors such as habitat destruction, poaching, disease, floods, fires and drought, decline of prey species for the same reasons, as well as intrinsic factors such as demographic stochasticity and genetic deterioration. Recognizing the conservation reliance of tigers, Project Tiger is establishing a national science-based framework for monitoring tiger population trends in order to manage the species more effectively. India now has 28 tiger reserves, located in 17 states. These reserves cover including 1.14% of the total land area of the country. These reserves are kept free of biotic disturbances, forestry operations, collection of minor forest products, grazing and human disturbance. The populations of tigers in these reserves now constitute some of the most important tiger source populations in the country | Biology | https://en.wikipedia.org/wiki?curid=21650435 | Conservation-reliant species | 140,951 |
Conservation-reliant species The magnitude and pace of human impacts on the environment make it unlikely that substantial progress will be made in delisting many species unless the definition of "recovery" includes some form of active management. Preventing delisted species from again being at risk of extinction may require continuing, species-specific management actions. Viewing "recovery" of "conservation-reliant species" as a continuum of phases rather a simple "recovered/not recovered" status may enhance the ability to manage such species within the framework of the Endangered Species Act. With ongoing loss of habitat, disruption of natural cycles, increasing impacts of non-native invasive species, it is probable that the number of conservation-reliant species will increase. It has been proposed that development of "recovery management agreements", with legally and biologically defensible contracts would provide for continuing conservation management following delisting. The use of such formalized agreements will facilitate shared management responsibilities between federal wildlife agencies and other federal agencies, and with state, local, and tribal governments, as well as with private entities that have demonstrated the capability to meet the needs of conservation-reliant species. | Biology | https://en.wikipedia.org/wiki?curid=21650435 | Conservation-reliant species | 140,952 |
Sequenom () is an American company based in San Diego, California. It develops enabling molecular technologies, and highly sensitive laboratory genetic tests for NIPT. Sequenom's wholly owned subsidiarity, Center for Molecular Medicine (SCMM), offers multiple clinical molecular genetics tests to patients, including MaterniT21, plus a noninvasive prenatal test for trisomy 21, trisomy 18, and trisomy 13, and the SensiGene RHD Fetal RHD genotyping test. In June 2014 the company sold its biosciences unit to Agena Bioscience for up to $35.8 million. In July 2016, it was announced that diagnostic and testing giant LabCorp will acquire Sequenom, paying $2.40 for every outstanding share of stock. The acquisition was completed in September 2016. Companies also offering non-invasive prenatal genetic testing include Ariosa, Ravgen, Illumina (Verinata Health), PerkinElmer and Natera (The Panorama Prenatal Test). Other companies and universities that are working towards developing non-invasive prenatal testing include Stanford University. In January 2012, entered a patent battle with competing companies, Ariosa and Natera, accusing them of infringing the "540 patent" (). The cases are Inc. v. Natera Inc. 12-cv-0184, v. Ariosa Diagnostics Inc., 12-cv-0189, U.S. District Court, Southern District of California (San Diego), and Ariosa v. Sequenom. Verinatal Health and Stanford University later filed suit against in a dispute over the 'Quake patent' | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,953 |
Sequenom Verinata claims that Sequenom's lawyers sent it a letter in 2010 alleging that "'the practice of non-invasive prenatal diagnostics, including diagnosis of the Down Syndrome and other genetic disorders, using cell-free nucleic acids in a sample of maternal blood infringes' the '540 patent, as well as the claims of a pending United States Patent Application." The '540 patent was invented by Isis Ltd. and expires in 2017. Stanford University owns the Quake patents and licensing rights; Verinata is its exclusive licensee. In April 2012, acquired two pending patents from Helicos Biosciences. In consideration for the sale and transfer of the purchased assets, paid Helicos $1.3 million. The Helicos patent applications (US Patent application 12/709,057 and 12/727,824) cover methods for detecting fetal nucleic acids and diagnosing fetal abnormalities. In July 2012, The United States District Court denied Sequenom's motion for a preliminary injunction motion against Ariosa Diagnostics. In August 2013, The Court of Appeals for the Federal Circuit vacated the District Court decision and remanded that case to the District Court. In the "Ariosa" litigation, the District Court (N.D.Cal.) held that the '540 patent was invalid because it claimed a natural phenomenon, the presence of cell-free fetal DNA fragments in maternal blood. On June 13, 2015, the CAFC affirmed the District Court's judgment. Finally on December 2, 2015, the Federal Circuit declined to rehear "en banc" | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,954 |
Sequenom In 2009, Center for Molecular Medicine (SCMM) was expected to launch the SEQureDx prenatal screening tests for Down syndrome and Rhesus D. Subsequent investigation revealed significant flaws in the studies of the test's effectiveness. As a result, the board of directors of fired CEO Harry Stylli, senior vice president of research and development Elizabeth Dragon and three other employees after a probe discovered that the company had failed to adequately supervise its Down syndrome test. CFO Paul Hawran also resigned. Board chairman Harry F. Hixson Jr. was named interim CEO and director Ronald M. Lindsay was appointed to replace Dragon. Dragon has since been charged by the Securities and Exchange Commission (SEC) because she "lied to the public about the accuracy of Sequenom's prenatal screening test for Down syndrome". She died on February 26, 2011. In 2010, paid $14 million to settle a shareholder class-action lawsuit that arose from the errors in the development of the Down syndrome test. executives are under investigation by the SEC for insider trading before announcement of problems with the test. On September 1, 2011 entered into a cease-and-desist order with SEC. MaterniT21 PLUS is Center for Molecular Medicine's prenatal test for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). The test operates by sampling cell-free DNA in the mother's blood, which contains some DNA from the fetus | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,955 |
Sequenom The proportions of DNA from sequences from chromosome 21, 18, or 13 can indicate whether the fetus has trisomy in that chromosome. In a randomized controlled trial of 1,696 pregnancies at high risk for Down syndrome, the test correctly identified 98.6% of the actual cases of Down syndrome (209 out of 212), with a false positive rate of 0.2% (3 of 1471 pregnancies without Down); the test gave no result in 0.8% of the cases tested (13 of 1696). The primary advantage of MaterniT21 PLUS over the other major high accuracy tests for Down syndrome, Amniocentesis and Chorionic villus sampling, is that MaterniT21 PLUS is noninvasive. Because amniocentesis and chorionic villus sampling are invasive, they have a chance of causing miscarriage. On August 4, 2011, said it would call its new blood test for Down syndrome in pregnancy MaterniT21 when the product went on sale in the United States. On August 11, 2011, announced European licensing agreement with LifeCodexx. The companies agreed to collaborate in the development and launch of a trisomy 21 laboratory-developed test and other aneuploidies testing in Germany, Austria, Switzerland, and Liechtenstein, with the potential for additional launches in other countries | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,956 |
Sequenom Under the initial five year licensing agreement, granted LifeCodexx licenses to key patent rights, including European Patent EP0994963B1 and pending application EP2183693A1 that enable the development and commercialization of a non-invasive aneuploidy test utilizing circulating cell-free fetal DNA in maternal plasma. On October 24, 2011 International Society of Prenatal Diagnostics (ISPD) issued a rapid response statement in response to the launch of non-invasive Trisomy 21 (MaterniT21) test. On October 17, 2011 announced that a clinical validation study leading to the introduction of the MaterniT21 LDT had been published in the journal Genetics in Medicine. On October 17, 2011 Center for Molecular Medicine announced the launch of MaterniT21 Noninvasive Prenatal Test for Down Syndrome. Oncomap Version 3 – "core" set interrogates ~450 mutations in 35 genes. An "extended" set interrogates ~700 mutations in 113 genes. OncoCarta(OncoMap) identifies 396 unique "druggable" or "actionable" mutations in 33 cancer genes. In total, 417 mutations are identified. MassARRAY spectrometry is more sensitive than PreTect HPV-Proofer and Consensus PCR for type-specific detection of high-risk oncogenic human papillomavirus genotypes in cervical cancer. On October 4, 2011 introduced iPLEX ADME PGx Panel on MassARRAY System, developed to genotype polymorphisms in genes associated with drug absorption, distribution, metabolism, and excretion (ADME) | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,957 |
Sequenom This Research Use Only (RUO) panel contains a set of pre-designed single nucleotide polymorphisms (SNP), insertions and deletions (INDELS) and copy number variation (CNV) assays for use in the investigation of variants with demonstrated relevance to drug metabolism. After detection on the MassARRAY (RUO) system, a proprietary software solution is then used to score and qualify polymorphisms to create a unique haplotype report. | Biology | https://en.wikipedia.org/wiki?curid=21659403 | Sequenom | 140,958 |
Ideal observer analysis is a method for investigating how information is processed in a perceptual system. It is also a basic principle that guides modern research in perception. The "ideal observer" is a theoretical system that performs a specific task in an optimal way. If there is uncertainty in the task, then perfect performance is impossible and the ideal observer will make errors. "Ideal performance" is the theoretical upper limit of performance. It is theoretically impossible for a real system to perform better than ideal. Typically, real systems are only capable of sub-ideal performance. This technique is useful for analyzing psychophysical data (see psychophysics). Many definitions of this term have been offered. Geisler (2003) (slightly reworded): The central concept in ideal observer analysis is the "ideal observer", a theoretical device that performs a given task in an optimal fashion given the available information and some specified constraints. This is not to say that ideal observers perform without error, but rather that they perform at the physical limit of what is possible in the situation. The fundamental role of uncertainty and noise implies that ideal observers must be defined in probabilistic (statistical) terms. "Ideal observer analysis" involves determining the performance of the ideal observer in a given task and then comparing its performance to that of a real perceptual system, which (depending on the application) might be the system as a whole, a subsystem, or an elementary component of the system (e.g | Biology | https://en.wikipedia.org/wiki?curid=21659985 | Ideal observer analysis | 140,959 |
Ideal observer analysis a neuron). In sequential ideal observer analysis, the goal is to measure a real system's performance deficit (relative to ideal) at different processing stages. Such an approach is useful when studying systems that process information in discrete (or semi-discrete) stages or modules. To facilitate experimental design in the laboratory, an artificial task may be designed so that the system's performance in the task may be studied. If the task is too artificial, the system may be pushed away from a natural mode of operation. Depending on the goals of the experiment, this may diminish its external validity. In such cases, it may be important to keep the system operating naturally (or almost naturally) by designing a pseudo-natural task. Such tasks are still artificial, but they attempt to mimic the natural demands placed on a system. For example, the task might employ stimuli that resemble natural scenes and might test the system's ability to make potentially useful judgments about these stimuli. Natural scene statistics are the basis for calculating ideal performance in natural and pseudo-natural tasks. This calculation tends to incorporate elements of signal detection theory, information theory, or estimation theory. | Biology | https://en.wikipedia.org/wiki?curid=21659985 | Ideal observer analysis | 140,960 |
Cisgenesis is a product designation for a category of genetically engineered plants. A variety of classification schemes have been proposed that order genetically modified organisms based on the nature of introduced genotypical changes, rather than the process of genetic engineering. (from "same" and "beginning") is one term for organisms that have been engineered using a process in which genes are artificially transferred between organisms that could otherwise be conventionally bred. Genes are only transferred between closely related organisms. Nucleic acid sequences must be isolated and introduced using the same technologies that are used to produce transgenic organisms, making cisgenesis similar in nature to transgenesis. The term was first introduced in 2000 by Henk J. Schouten and Henk Jochemsen, and in 2004 a PhD thesis by Jan Schaart of Wageningen University in 2004, discussing making strawberries less susceptible to "Botrytis cinerea". In Europe, currently, this process is governed by the same laws as transgenesis. While researchers at Wageningen University in the Netherlands feel that this should be changed and regulated in the same way as conventionally bred plants, other scientists, writing in Nature Biotechnology, have disagreed. In 2012 the European Food Safety Authority (EFSA) issued a report with their risk assessment of cisgenic and intragenic plants | Biology | https://en.wikipedia.org/wiki?curid=21660626 | Cisgenesis | 140,961 |
Cisgenesis They compared the hazards associated with plants produced by cisgenesis and intragenesis with those obtained either by conventional plant breeding techniques or transgenesis. The EFSA concluded that "similar hazards can be associated with cisgenic and conventionally bred plants, while novel hazards can be associated with intragenic and transgenic plants." has been applied to transfer of natural resistance genes to the devastating disease "Phytophthora infestans" in potato and scab ("Venturia inaequalis") in apple. and transgenesis use artificial gene transfer, which results in less extensive change to an organism's genome than mutagenesis, which was widely used before genetic engineering was developed. Some people believe that cisgenesis should not face as much regulatory oversight as genetic modification created through transgenesis as it is possible, if not practical, to transfer alleles among closely related species even by traditional crossing. The primary biological advantage of cisgenesis is that it does not disrupt favorable heterozygous states, particularly in asexually propagated crops such as potato, which do not breed true to seed. One application of cisgenesis is to create blight resistant potato plants by transferring known resistance loci wild genotypes into modern, high yielding varieties | Biology | https://en.wikipedia.org/wiki?curid=21660626 | Cisgenesis | 140,962 |