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84-555: The Blue Lakes are in the Cache Creek watershed in northwestern Lake County, about 7 miles (11 km) west of Upper Lake . Their drainage basin comprises the upper northwest section of the Cache Creek basin. They are at an elevation of 1,358 feet (414 m). Upper Blue Lake is about 1,361 feet (415 m) above sea level, covers about 55 acres (22 ha) and contains about 3,960 acre-feet (4,880,000 m) of water. Lower Blue Lake

168-526: A 100 fold lesser selectivity for these types of receptors than it has for nAchRs. Anatoxin-a also shows much less potency in the CNS than in neuromuscular junctions. In hippocampal and brain stem neurons, a 5 to 10 times greater concentration of anatoxin-a was necessary to activate nAchRs than what was required in the PNS. In normal circumstances, acetylcholine binds to nAchRs in the post-synaptic neuronal membrane, causing

252-623: A 175-mile (280 km) network of canals . At the end of the Capay Valley near Esparto Cache Creek runs east into Sacramento Valley , ending in a settling basin east of Woodland . If the Sacramento river is not in flood then any overflow runs into the Tule Canal , continues as Prospect Slough and finally enters the Sacramento River at Cache Slough . If the Sacramento is in flood, then

336-583: A balance between the needs of the two counties, although high-water conditions can cause temporary disagreements. Under the Solano Decree Yolo currently holds appropriative rights for up to 150,000 acre-feet (190,000,000 m ) per year from Clear Lake, and all the water from the Indian Valley dam. The Cache Creek Dam on the South Fork of Cache Creek, five miles (8 km) downstream from Clear Lake ,

420-769: A certified scale. Cache Creek (Sacramento River tributary) Cache Creek is an 87-mile-long (140 km) stream in Lake , Colusa and Yolo counties, California . Cache Creek starts at the outlet of Clear Lake . It has two main tributaries: North Fork (starting in the Mendocino National Forest north of Clear Lake, and dammed by the Indian Valley Reservoir ); and Bear Creek (starting in Bear Valley ). The Capay Diversion Dam, west of Capay , diverts water for distribution throughout Yolo County using

504-476: A conformational change in the extracellular domain of the receptor which in turn opens the channel pore. This allows Na and Ca ions to move into the neuron, causing cell depolarization and inducing the generation of action potentials , which allows for muscle contraction. The acetylcholine neurotransmitter then dissociates from the nAchR, where it is rapidly cleaved into acetate and choline by acetylcholinesterase . Anatoxin-a binding to these nAchRs cause

588-633: A few miles, and turns south, again cutting through a canyon following State Route 16 in Colusa and Yolo Counties. Meanwhile, Cache Creek cuts south-east between Cache Creek Ridge (on its north bank) and Little Blue Ridge (south bank), joining Bear Creek at Route 16 near the junction of Lake, Colusa and Yolo counties. The combined Cache Creek continues in the canyon until it emerges north of Rumsey in Capay Valley . The Capay Diversion Dam, west of Capay , diverts water for distribution throughout Yolo County using

672-458: A final product. The first and most extensively explored approach used to synthesize anatoxin-a in vitro, cyclooctene cyclization involves 1,5-cyclooctadiene as its initial source. This starting substance is reacted to form methyl amine and combined with hypobromous acid to form anatoxin-a. Another method developed in the same laboratory uses aminoalcohol in conjunction with mercuric (II) acetate and sodium borohydride. The product of this reaction

756-648: A greater frequency and prevalence of cyanobacterial blooms. The World Health Organization in 1999 and EPA in 2006 both came to the conclusion that there was not enough toxicity data for anatoxin-a to establish a formal tolerable daily intake (TDI) level, though some places have implemented levels of their own. Anatoxin-a is not regulated under the Safe Drinking Water Act , but states are allowed to create their own standards for contaminants that are unregulated. Currently there are four states that have set drinking water advisory levels for anatoxin-a as seen in

840-468: A growing population of the rare tule elk , plus winter populations of bald eagles . The ruggedness of the area tends to ensure its isolation from human activity. In 2006 the United States Congress designated 27,245 acres (110 km ) of the area as the federally protected Cache Creek Wilderness . Cache Creek Conservancy has restored a 130-acre Cache Creek Nature Preserve area downstream in

924-421: A ketone intermediate. Addition of an organocuprate to the ketone produces an enol triflate derivative, which is then lysed hydrogenously and treated with a deprotecting agent in order to produce anatoxin-a. Similar strategies have also been developed and utilized by other laboratories. Iminium ion cyclization utilizes several different pathways to create anatoxin-a, but each of these produces and progresses with

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1008-468: A maximum width of perhaps a quarter of a mile. The two upper lakes are probably each of them from half to three quarters of a mile in length, and as already stated, are connected so as to form in reality a single sheet of water. An 1891 description said, The Blue Lakes are two of the most charming lakes in the State. They lie at the bottom of a long, deep valley which rises with almost precipitous sides from

1092-737: A monster fish, or water dragon, lived in the Upper Blue Lake, and therefore never camped close to the lake. In the 1870s the newspapers reported various sightings of this monster. Clear Lake prickly sculpin are only found in Clear Lake and in Upper and Lower Blue lakes. Clear Lake tule perch are endemic to Clear Lake, Lower Blue Lake and Upper Blue Lake. Its populations seem to have dropped to very low levels in Clear Lake and they are probably absent from Lower Blue Lake, but they are still common in Upper Blue Lake. The inland silverside ( Menidia beryllina )

1176-400: A network of canals . At the end of the Capay Valley , near Esparto , Cache Creek runs east into Sacramento Valley , ending in a settling basin east of Woodland , the overflow of which runs into the Sacramento River through a flood control canal. In addition to the recreational use of Clear Lake and Indian Valley Reservoir there are numerous trail-heads, parks and campgrounds, including

1260-494: A pyrrolidine iminium ion. The major differences in each pathway relate to the precursors used to produce the imium ion and the total yield of anatoxin-a at the end of the process. These separate pathways include production of alkyl iminium salts, acyl iminium salts and tosyl iminium salts. Enyne metathesis of anatoxin-a involves the use of a ring closing mechanism and is one of the more recent advances in anatoxin-a synthesis. In all methods involving this pathway, pyroglutamic acid

1344-437: A reservoir near Winters. This feeds into Willows Canal, which runs east for miles alongside Putah Creek —the water of which is used primarily by Solano County . The 474 foot long, 15 foot high concrete dam was constructed in 1914. In 1994 its apron was raised with a 5-foot high inflatable bladder (the "longest in the world"), which can be raised or lowered in 30 minutes. It underwent substantial repairs starting in 2009. From

1428-511: A short drive away. There are campsites and more upscale lodgings for longer stays.. There is a speed limit of 5 miles per hour (8.0 km/h) on the lakes. Visitors can swim or fish in the lakes, or use kayaks, canoes or paddle boards. Apart from bass and bluegill, the waters are regularly stocked with rainbow trout. Upper Blue Lake is the more popular, since the colder water supports excellent trout and bass fishing, but both lakes hold very large bass. A 12 pounds (5.4 kg) bass has been weighed on

1512-871: A species of Pseudomonas , capable of biodegrading anatoxin-a at a rate of 2–10 μg ml d , has been identified. Biological (granular) activated carbon (BAC) has also been tested as a method of biodegradation, but it is inconclusive whether biodegradation occurred or if anatoxin-a was simply adsorbing the activated carbon. Others have called for additional studies to determine more about how to use activated carbon effectively. Chemical treatment methods are more common in drinking water treatment compared to biological treatment, and numerous processes have been suggested for anatoxin-a. Oxidants such as potassium permanganate , ozone , and advanced oxidation processes ( AOPs ) have worked in lowering levels of anatoxin-a, but others, including photocatalysis, UV photolysis , and chlorination , have not shown great efficacy. Directly removing

1596-430: A weak toxic effect at 10 μg/mL only after an extended period of contact (48 hours). No data on inhalation toxicity of anatoxin-a is currently available, though severe respiratory distress occurred in a water skier after they inhaled water spray containing a fellow cyanobacterial neurotoxin, saxitoxin . It is possible that inhalation of water spray containing anatoxin-a could pose similar consequences. Anatoxin-a

1680-495: A wide channel, and are known collectively as Blue Lake or Upper Blue Lake. The settlement of Midlakes lies between Blue Lake and Lower Blue Lake, which is connected by a short channel to Scotts Creek. California State Route 20 runs along the northeast shore of the lakes. The Clear Lake basin lies between the watersheds of the Sacramento River and the Russian River . When it was formed about 600,000 years ago it drained east into

1764-424: Is an agonist of both neuronal α 4 β 2 and α 4 nicotinic acetylcholine receptors present in the CNS as well as the (α 1 ) 2 βγδ muscle-type nAchRs that are present at the neuromuscular junction . (Anatoxin-a has an affinity for these muscle-type receptors that is about 20 times greater than that of acetylcholine . ) However, the cyanotoxin has little effect on muscarinic acetylcholine receptors ; it has

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1848-478: Is anatoxin-a or another neurotoxin that causes the resulting deaths. Large amounts of sample material are also needed for such testing. In addition to the biological methods, scientists have used chromatography to detect anatoxin-a. This is complicated by the rapid degradation of the toxin and the lack of commercially available standards for anatoxin-a. Despite the relatively low frequency of anatoxin-a relative to other cyanotoxins, its high toxicity (the lethal dose

1932-477: Is because (+)-anatoxin-a, the s- cis enone conformation, has a distance a 6.0 Å between its nitrogen and carbonyl group, which corresponds well to the 5.9 Å distance that separate the nitrogen and oxygen in acetylcholine. Respiratory arrest , which results in a lack of an oxygen supply to the brain, is the most evident and lethal effect of anatoxin-a. Injections of mice, rats, birds, dogs, and calves with lethal doses of anatoxin-a have demonstrated that death

2016-529: Is called Da-no lokj'tam , or "mountain fell-in", by the Northern Pomo . They have a legend that water from Clear Lake once drained west through the Blue Lakes, then through Cold Creek into Coyote Valley and the Russian River . Then there was a great earthquake and a huge landslide blocked the flow out of Clear Lake. The land was forced up, and Clear Lake began to drain to the east through Cache Creek . This

2100-463: Is enough water. Consequently, there are no longer any anadromous fish species in Cache Creek. Cache Creek was added to California's Wild and Scenic Rivers System in October 2005 which protects 31 miles (50 km) of the river from construction of new dams or diversions. Assembly member Lois Wolk introduced AB 1328 in 2005 which received support as well as opposition. New dam construction on Cache Creek

2184-404: Is furthermore very narrow. The Blue Lakes themselves are usually called three in number, although the two upper ones are connected by a narrow strait. They are beautiful little sheets of water lying in the bottom of the narrow canyon, whose sides come down almost precipitously to the water's edge. They are said to be very deep. I estimated the lower one to be a little less than a mile in length, with

2268-454: Is introduced into the birds via water contaminated with cyanobacterial mat communities that arise from the hot springs in the lake bed. The first biologically occurring initial substance for tropane expansion into anatoxin-a was cocaine , which has similar stereochemistry to anatoxin-a. Cocaine is first converted into the endo isomer of a cyclopropane, which is then photolytically cleaved to obtain an alpha, beta unsaturated ketone. Through

2352-526: Is no official guideline level for anatoxin-a, although scientists estimate that a level of 1 μg l would be sufficiently low. Likewise, there are no official guidelines regarding testing for anatoxin-a. Among methods of reducing the risk for cyanotoxins, including anatoxin-a, scientists look favorably on biological treatment methods because they do not require complicated technology, are low maintenance, and have low running costs. Few biological treatment options have been tested for anatoxin-a specifically, although

2436-495: Is not known for humans, but is estimated to be less than 5 mg for an adult male ) means that it is still considered a serious threat to terrestrial and aquatic organisms, most significantly to livestock and to humans. Anatoxin-a is suspected to have been involved in the death of at least one person. The threat posed by anatoxin-a and other cyanotoxins is increasing as both fertilizer runoff, leading to eutrophication in lakes and rivers, and higher global temperatures contribute to

2520-512: Is not to be confused with guanitoxin (formerly anatoxin-a(S)), another potent cyanotoxin that has a similar mechanism of action to that of anatoxin-a and is produced by many of the same cyanobacteria genera, but is structurally unrelated. Anatoxin-a was first discovered by P.R. Gorham in the early 1960s, after several herds of cattle died as a result of drinking water from Saskatchewan Lake in Ontario, Canada, which contained toxic algal blooms . It

2604-564: Is plausible, since there have been tectonic events in the region and Clear Lake is 600 feet (180 m) higher than the Ukiah Valley. An 1891 account gave more detail: "At the head of the upper lake, just on the western line of the county, is a break in the mountain line which encloses Lake County like the rim of a basin. On the west of this gap Cold Creek heads, and flows down to Russian River, which comes from Potter Valley, twenty miles farther north, and goes on south into Sonoma, turning west to

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2688-469: Is preceded by a sequence of muscle fasciculations , decreased movement, collapse, exaggerated abdominal breathing, cyanosis and convulsions . In mice, anatoxin-a also seriously impacted blood pressure and heart rate, and caused severe acidosis . Many cases of wildlife and livestock deaths due to anatoxin-a have been reported since its discovery. Domestic dog deaths due to the cyanotoxin, as determined by analysis of stomach contents, have been observed at

2772-465: Is produced by multiple genera of cyanobacteria and has been reported in North America, South America, Central America, Europe, Africa, Asia, and Oceania. Symptoms of anatoxin-a toxicity include loss of coordination , muscular fasciculations , convulsions and death by respiratory paralysis . Its mode of action is through the nicotinic acetylcholine receptor (nAchR) where it mimics the binding of

2856-401: Is shallower and covers 53 acres (21 ha). The Köppen climate classification is Csb : Warm-summer Mediterranean climate. The Blue Lakes as a whole have a length of about 3 miles (4.8 km) and a breadth of 1 ⁄ 2 mile (0.80 km). They form a line running in a northeast direction down to Scotts Creek , which drains into Clear Lake . The upper two lakes are connected by

2940-671: Is suspected to have also been the cause of death of one human. One study found that anatoxin-a is capable of binding to acetylcholine receptors and inducing toxic effects with concentrations in the nano-molar (nM) range if ingested. Dermal exposure is the most likely form of contact with cyanotoxins in the environment. Recreational exposure to river, stream, and lake waters contaminated with algal blooms has been known to cause skin irritation and rashes. The first study that looked at in vitro cytotoxic effects of anatoxin-a on human skin cell proliferation and migration found that anatoxin-a exerted no effect at 0.1 μg/mL or 1 μg/mL, and

3024-540: Is unstable in water and other natural conditions, and in the presence of UV light undergoes photodegradation , being converted to the less toxic products dihydroanatoxin-a and epoxyanatoxin-a. The photodegradation of anatoxin-a is dependent on pH and sunlight intensity but independent of oxygen, indicating that the degradation by light is not achieved through the process of photo-oxidation. Studies have shown that some microorganisms are capable of degrading anatoxin-a. A study done by Kiviranta and colleagues in 1991 showed that

3108-487: Is used as a starting material in conjunction with a Grubb's catalyst. Similar to iminium cyclization, the first attempted synthesis of anatoxin-a using this pathway used a 2,5-cis-pyrrolidine as an intermediate. Anatoxin-a is synthesized in vivo in the species Anabaena flos-aquae , as well as several other genera of cyanobacteria. Anatoxin-a and related chemical structures are produced using acetate and glutamate. Further enzymatic reduction of these precursors results in

3192-525: The Cache Creek Recreation Area . Cache Creek runs north-east from the dam, behind Perkins Creek Ridge and over The Jams Waterfall before joining the North Fork about 2 miles east of the bridge over Route 20. Bear Creek starts in Bear Valley and runs south through a canyon (joining Sulphur Creek near Wilbur Springs ) until it meets Route 20. It then runs east in parallel with Route 20 for

3276-570: The Bear Valley wildflower hotspot. Bear Creek and Cache Creek run in a scenic canyon along State Route 16 in Colusa and Yolo county, including the Cache Creek Regional Park . Cache Creek provides white-water rafting, both in the spring when it is flooded, and through the summer using the agricultural water flow. The entire area south of Route 20 and west of Route 16 is a wildlife preserve, hosting two herds of Tule Elk . The name of

3360-530: The California Environmental Protection Agency published a staff report that acknowledged the continued increase of mercury in Cache Creek, and determined that 12 percent of the source were old mercury mines located near major tributaries such as: North Fork Cache Creek, Clear Lake outflow, Bear Creek , Harley Gulch, and Davis Creek. Reports like this led to protocols set in place to monitor the mercury levels within Cache Creek and warn

3444-555: The Central Valley Regional Water Quality Control Board and the U.S. Geological Survey from 1994-2001 confirmed Cache Creek as a major source contributing to mercury level spikes in the Sacramento River. Since then, multiple studies have been conducted to pinpoint the mines that are still releasing quicksilver, and the course the element has traveled to measure the extent of the issue. In 2004,

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3528-835: The Department of Fish and Game, illegal introductions by bait fishermen and dispersal via man-made waterways. A general survey of fish along the shoreline of Upper Blue Lake was conducted in June 2014. Fish collected included common carp ( Cyprinus carpio ), bluegill ( Lepomis macrochirus ), largemouth bass ( Micropterus salmoides ), rainbow trout ( Oncorhynchus mykiss ), green sunfish ( Lepomis cyanellus ), prickly sculpin ( Cottus asper ) and brown bullhead ( Ameiurus nebulosus ). Of 376 fish caught, 342 were largemouth bass, followed by bluegill (12), common carp (11), green sunfish (9), and one specimen each of brown bullhead, prickly sculpin and rainbow trout. Residents of Upper Lake or Lakeport are

3612-461: The Hudson's Bay Company trappers as Rivière la Cache . Cache Creek was temporarily blocked north of Rumsey by a landslide caused by the 1906 San Francisco earthquake  : Our Rumsey correspondent mentions the fall of Cache Creek as a result of an earthquake shock Tuesday night. The water has continued to fall some since that date and in some places it is dry. Upon investigation by the officials of

3696-495: The North Fork of Cache Creek forms Indian Valley Reservoir . The dam's primary purpose is water storage for irrigation , but a 3.3 MW hydroelectric plant was built to take advantage of the falling water. The Capay Diversion Dam, west of Capay , diverts water for distribution throughout Yolo County using a 175-mile (280 km) network of canals . For example, water is pumped into the Winters Canal, which runs south and ends in

3780-573: The Pacific. The older Indians tell of a time in the days that were, when the waters of the Blue Lakes, and probably of Clear lake also, pursued this path to the ocean. At present the drainage line is almost due east, by way of Cache Creek and the Sacramento River. The Indians say that the ridge was raised after three days of earthquake. The whole district shows evidences of volcanic action, and has many singular geological features and numerous mineral springs." According to Professor Ruliff Stephen Holway (1907)

3864-675: The Sacramento Valley. About 200,000 years ago the Clear Lake Volcanic Field blocked its outlet. The lake rose until it found a new outlet, draining west through the Blue Lakes into Cold Creek and the Russian River. At some time in the last 10,000 years a landslide at the west end of the Blue Lakes blocked this outlet, the lake rose again, and created its present outlet via Cache Creek to the Sacramento River. The gradual mountain pass between Cold Creek basin and Upper Blue Lake

3948-531: The United States, Canada, and Finland between 1980 and the present. A particularly interesting case of anatoxin-a poisoning is that of lesser flamingos at Lake Bogoria in Kenya . The cyanotoxin, which was identified in the stomachs and fecal pellets of the birds, killed roughly 30,000 flamingos in the second half of 1999, and continues to cause mass fatalities annually, devastating the flamingo population. The toxin

4032-700: The Water Company it was found that a landslide had dammed the Creek near the Leonard ranch in Lake county.... The creek subsequently broke through, causing severe flooding in Rumsey. From 1800s to the mid 1900s, mercury was mined free of environmental regulation causing an influx of the element within Cache Creek. In 2001, the Central Valley Regional Water Quality Control Board and the U.S. Geological Survey confirmed that Cache Creek

4116-933: The action potential. Later, Thomas et al., (1993) through his work with chicken α 4 β 2 nAChR subunits expressed on mouse M 10 cells and chicken α 7 nAChR expressed in oocytes from Xenopus laevis , showed that anatoxin-a is also a potent agonist of neuronal nAChR. Laboratory studies using mice showed that characteristic effects of acute anatoxin-a poisoning via intraperitoneal injection include muscle fasciculations , tremors, staggering, gasping, respiratory paralysis, and death within minutes. Zebrafish exposed to anatoxin-a contaminated water had altered heart rates. There have been cases of non-lethal poisoning in humans who have ingested water from streams and lakes that contain various genera of cyanobacteria that are capable of producing anatoxin-a. The effects of non-lethal poisoning were primarily gastrointestinal: nausea, vomiting, diarrhea, and abdominal pain. A case of lethal poisoning

4200-878: The amount of cyanotoxins in the surrounding water, threatening the health of both aquatic and terrestrial organisms. Some species of cyanobacteria that produce anatoxin-a don't produce surface water blooms but instead form benthic mats. Many cases of anatoxin-a related animal deaths have occurred due to ingestion of detached benthic cyanobacterial mats that have washed ashore. Anatoxin-a producing cyanobacteria have also been found in soils and aquatic plants. Anatoxin-a sorbs well to negatively charged sites in clay-like, organic-rich soils and weakly to sandy soils. One study found both bound and free anatoxin-a in 38% of aquatic plants sampled across 12 Nebraskan reservoirs, with much higher incidence of bound anatoxin-a than free. In 1977, Carmichael, Gorham, and Biggs experimented with anatoxin-a. They introduced toxic cultures of A. flos-aquae into

4284-475: The amount of water that can flow through at that point. The limited capacity of the stream means that it takes a very long time to drain excess flow from Clear Lake, increasing the chance of flooding around the lake. The bottleneck is seen as a backup to prevent flooding downstream and Yolo County is prohibited from increasing the capacity of the channel by the Gopcevic and Bemmerly Decrees. The Indian Valley dam on

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4368-417: The bacterial genus Pseudomonas was capable of degrading anatoxin-a at a rate of 2–10 μg/ml per day. Later experiments done by Rapala and colleagues (1994) supported these results. They compared the effects of sterilized and non-sterilized sediments on anatoxin-a degradation over the course of 22 days, and found that after that time vials with the sterilized sediments showed similar levels of anatoxin-a as at

4452-510: The commencement of the experiment, while vials with non-sterilized sediment showed a 25-48% decrease. There are two categories of anatoxin-a detection methods. Biological methods have involved administration of samples to mice and other organisms more commonly used in ecotoxicological testing, such as brine shrimp ( Artemia salina ), larvae of the freshwater crustacean Thamnocephalus platyurus , and various insect larvae. Problems with this methodology include an inability to determine whether it

4536-454: The creek. As well as a monitoring of these pits every other year for 10 years once the reclamation process is completed A large part of the creek within Lake County is designated a Wildlife Area by the state of California and the federal Bureau of Land Management , on which vehicles are prohibited but hiking, primitive camping, and hunting are allowed. The North Fork and Bear Creek each host

4620-500: The cyanobacteria in the water treatment process through physical treatment (e.g., membrane filtration ) is another option because most of the anatoxin-a is contained within the cells when the bloom is growing. However, anatoxin-a is released from cyanobacteria into water when they senesce and lyse, so physical treatment may not remove all of the anatoxin-a present. Additional research needs to be done to find more reliable and efficient methods of both detection and treatment. Anatoxin-a

4704-455: The early 1800s to much of the 1900s, mining for elemental mercury, also known as quicksilver , was widely popular in Cache Creek's upper watershed, given its gold recovering properties. At the peak of mercury production, over 6 million pounds (2.7 million kg) of mercury were mined, creating large mining caverns across the entirety of California. Throughout this period, little to no environmental regulations had been established causing mercury, in

4788-467: The form of mining waste from retorting , to infiltrate water systems and make its way into Cache Creek . Through a process known as bio-accumulation , the integration of mercury into the creek caused increased levels of the element in organisms within the creek. If consumed, accumulation of high mercury levels within organisms, particularity fish, may induce harm to the nervous systems of unborn babies and young children. Water quality studies conducted by

4872-402: The formation of anatoxin-a. Homoanatoxin, a similar chemical, is produced by Oscillatoria formosa and utilizes the same precursor. However, homoanatoxin undergoes a methyl addition by S-adenosyl-L-methionine instead of an addition of electrons, resulting in a similar analogue. The biosynthetic gene cluster (BGC) for anatoxin-a was described from Oscillatoria PCC 6506 in 2009. Anatoxin-a

4956-725: The lower North Island in New Zealand in 2005, in eastern France in 2003, in California of the United States in 2002 and 2006, in Scotland in 1992, in Ireland in 1997 and 2005, in Germany in 2017 and 2020. In each case, the dogs began showing muscle convulsions within minutes, and were dead within a matter of hours. Numerous cattle fatalities arising from the consumption of water contaminated with cyanobacteria that produce anatoxin-a have been reported in

5040-579: The lower lake with smaller corrages around it, the Blue Lakes Hotel, with a hotel and several pretty cottages, where the upper lake flowed into the lower in a lawn-like expanse of grassland with clumps of gnarled and moss-covered oak, and Le Trianon, a very prettily situated hotel at the upper end of the upper lake. The Blue Lakes today are highly altered and have lost the majority of their native fishes. They are surrounded by housing which reduces shoreline habitat and contributes pollutants. In 2019 anatoxin

5124-496: The name Very Fast Death Factor. They determined the LD50 for mice to be 250 μg/kg body weight. Electrophysiological experiments done by Spivak et al. (1980) on frogs showed that anatoxin-a is a potent agonist of the muscle-type (α 1 ) 2 βγδ nAChR. Anatoxin-a induced depolarizing neuromuscular blockade, contracture of the frog's rectus abdominis muscle, depolarization of the frog sartorius muscle, desensitization, and alteration of

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5208-476: The oral minimum lethal dose (MLD) (of the algae, not the anatoxin molecule), for calves is roughly 420 mg/kg body weight. In the same year, Devlin and colleagues discovered the bicyclic secondary amine structure of anatoxin-a. They also performed experiments similar to those of Carmichael et al. on mice. They found that anatoxin-a kills mice 2–5 minutes after intraperitoneal injection preceded by twitching, muscle spasms, paralysis and respiratory arrest, hence

5292-634: The overflow from the settling basin is swept into the Yolo Bypass and Sacramento Bypass flood control system, emerging directly at Cache Slough . Water rights and flooding protection have been in dispute between Yolo and Lake Counties since the late 19th century. The Yolo County Flood Control & Water Conservation District ("Yolo") has "an 1855 priority right to divert the natural flow of Cache Creek, and 1912 priority right to store waters in Clear Lake to elevation 7.56 feet Rumsey Gauge for later release and beneficial use." Various decrees attempt to ensure

5376-414: The public of possible health concerns from fish consumption. In 2017, The Department of Environmental Science and Policy from UC Davis, in consultation with The Yolo County Cache Creek Technical Advisory Committee, proposed revisions to the existing protocols. The revision proposal called for yearly monitoring of off channel wet pits for five years, given they may explain additional sources of mercury within

5460-440: The receptor's natural ligand , acetylcholine . As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to animals, including humans. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy. Anatoxin-a

5544-449: The same effects in neurons. However, anatoxin-a binding is irreversible , and the anatoxin-a nAchR complex cannot be broken down by acetylcholinesterase . Thus, the nAchR is temporarily locked open, which leads to overstimulation due to the constant generation of action potentials. Two enantiomers of anatoxin-a, the positive enantiomer , (+)-anatoxin-a, is 150 fold more potent than the synthetic negative enantiomer, (−)-anatoxin-a. This

5628-498: The south-east end of Clear Lake (for which it is the outlet), flowing east to the dam which now controls the level of Clear Lake. The North Fork begins in Lake County in the Mendocino National Forest north of Upper Lake. It flows east, where it is joined by Bartlett Creek , and is then dammed by the Indian Valley Reservoir . It then flows south along New Long Valley Road, and turns east along State Route 20 , which it crosses at

5712-412: The state of Washington implemented a recreational advisory level for anatoxin-a of 1 μg/L in order to better manage algal blooms in lakes and protect users from exposure to the blooms. The Canadian province of Québec has a drinking water Maximum Accepted Value for anatoxin-a of 3.7 μg/L. New Zealand has a drinking water Maximum Accepted Value for anatoxin-a of 6 μg/L. As of now, there

5796-445: The stomachs of two young male calves, and observed that muscular fasciculations and loss of coordination occurred in a matter of minutes, while death due to respiratory failure occurred anywhere between several minutes and a few hours. They also established that extensive periods of artificial respiration did not allow for detoxification to occur and natural neuromuscular functioning to resume. From these experiments, they calculated that

5880-529: The table below. On October 8, 2009 the EPA published the third Drinking Water Contaminant Candidate List (CCL) which included anatoxin-a (among other cyanotoxins), indicating that anatoxin-a may be present in public water systems but is not regulated by the EPA. Anatoxin-a's presence on the CCL means that it may need to be regulated by the EPA in the future, pending further information on its health effects in humans. In 2008

5964-494: The use of diethyl azodicarboxylate, the ketone is demethylated and anatoxin-a is formed. A similar, more recent synthesis pathway involves producing 2-tropinone from cocaine and treating the product with ethyl chloroformate producing a bicyclic ketone. This product is combined with trimethylsilyldiazylmethane, an organoaluminum Lewis acid and trimethylsinyl enol ether to produce tropinone. This method undergoes several more steps, producing useful intermediates as well as anatoxin-a as

6048-418: The water body comes from Hudson's Bay Company trappers who cached their furs along the Sacramento River and smaller tributaries, one of which became known to them as Cache Creek. One of their camps, recognized by early settlers as French Camp, was situated in a grove of oaks on the north bank of Cache Creek one mile (1.6 km) east of the present town of Yolo, California . Cache Creek was originally known to

6132-509: The water; intense blue is surrounded by the perpetual green of the dark coniferous forest about them. No streams flow into these lakes, nor is there any outlet except in the rainy season, when the short mountain torrents cause them to overflow, across a low neck of land, into a small lake, Tulé, and so on into Clear Lake. Springs in the bottom of the lakes doubtless supply them, and they are heavily stocked with speckled trout, perch, "silver-sides," and other species of fish. A mineral springs resort

6216-498: The waters of Blue Lakes and Scotts Creek once drained into Russian River by way of Cold Creek, but in recent prehistorical times a large landslide formed a ridge that diverted these waters to Clear Lake. This could account for the relatively mature profile of Cold Creek. An 1890 account by the State Mineralogist said, I observe first, that the canyon itself [Blue Lakes Canyon] is very deep, its sides also being very steep; it

6300-592: The watershed. Whitewater boating on Cache Creek includes kayaking , rafting, canoeing and innertubing which are popular in the summer using the water released from the dams for downstream agriculture. Nominally a tributary of the Sacramento River , Cache Creek now only reaches it during extremely wet years due to damming and diversion of the stream's water. Degradation of the channel caused by invasive plants , such as Arundo donax and Tamarix spp., as well as gravel mining has left no suitable habitat for Chinook salmon and steelhead to spawn , even if there

6384-512: Was a contributor to the increase of mercury levels within the Sacramento River . Since then, various regulations have been enacted to monitor the mercury levels in Cache Creek, and multiple studies have been conducted to find the site of contamination. The California Office of Environmental Health Hazard Assessment released an advisory regarding eating fish caught from this creek based on the mercury level. Cache Creek has two main tributaries: North Fork, and Bear Creek . Cache Creek begins at

6468-494: Was built to increase Clear Lake's capacity and to regulate outflow for downstream users of Cache Creek water. The dam was later modified to include a 3 MW hydroelectric plant. The stream has a relatively small capacity, less than a quarter of the amount the dam is able to release. There is a rock ledge a mile and a half downstream of Clear Lake, called the Grigsby Riffle, near the bridge on State Route 53 . This ledge restricts

6552-460: Was detected in the Blue Lakes, but later tests showed no sign of the toxin, so warning signs were removed in January 2020. Lower Blue Lake, like Clear Lake, is eutrophic , alkaline with a pH of c.  8 , and fairly turbid with a Secchi depth less than 2 metres (6 ft 7 in). Upper Blue Lake, in contrast, is clear and cool. The original Pomo people of the region know of a legend that

6636-401: Was founded at Blue Lakes, visited both by the sick for cures and by the wealthy and fashionable as summer resorts. The Blue Lakes Hotel could accommodate 40-50 guests, and had a white sulphur spring on its 320 acres (130 ha) grounds. The neighboring forests had plentiful game, including deer, rabbits, quail and pigeons. Resorts in 1892 included Laurel Dell, a Swiss cottage on a grassy flat on

6720-496: Was introduced from Lake Texoma , Oklahoma, into the Blue Lakes and Clear Lake in 1967 to test its effectiveness in controlling the Clear Lake gnat and chironomid midges. About 6,000 fish were released in Upper Blue Lake and 3,000 in Lower Blue Lake and Clear Lake. Within a year the silversides were abundant in Lower Blue Lake and Clear Lake. They have since been widely distributed in California through experimental introductions by

6804-646: Was isolated in 1972 by J.P. Devlin from the cyanobacteria Anabaena flos-aquae . Anatoxin-a is a neurotoxin produced by multiple genera of freshwater cyanobacteria that are found in water bodies globally. Some freshwater cyanobacteria are known to be salt tolerant and thus it is possible for anatoxin-a to be found in estuarine or other saline environments. Blooms of cyanobacteria that produce anatoxin-a among other cyanotoxins are increasing in frequency due to increasing temperatures, stratification , and eutrophication due to nutrient runoff. These expansive cyanobacterial harmful algal blooms , known as cyanoHABs, increase

6888-496: Was reported in Wisconsin after a teen jumped into a pond contaminated with cyanobacteria. Ingestion of drinking water or recreational water that is contaminated with anatoxin-a can pose fatal consequences since anatoxin-a was found to be quickly absorbed through the gastrointestinal tract in animal studies. Dozens of cases of animal deaths due to ingestion of anatoxin-a contaminated water from lakes or rivers have been recorded, and it

6972-402: Was transformed into an alpha, beta ketone and oxidized by ethyl azodicarboxylate to form anatoxin-a. This method for anatoxin-a production was one of the first used that does not utilize a chimerically analogous starting substance for anatoxin formation. Instead, a racemic mixture of 3-tropinone is used with a chiral lithium amide base and additional ring expansion reactions in order to produce

7056-596: Was under consideration in 2002 by the Yolo County Water District, the agency that had built the Indian Valley Dam and the present dam on Cache Creek. Anatoxin-a Anatoxin-a , also known as Very Fast Death Factor ( VFDF ), is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity . It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin

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