Biology // Current

Endocannabinoids

Endocannabinoids are derivatives of arachidonic acid (and of other poly-unsaturated fatty acids), that have been discovered approximately 15 years ago. Nowadays they are recognized as a new class of lipid signaling molecules, that play several central and peripheral roles. Endocannabinoids are endogenous ligands of brain-type (CB1) and spleen-type (CB2) cannabinoid receptors, that bind also an exogenous ligand like Δ9- tetrahydrocannabinol (THC), the psychoactive component of Cannabis sativa.

CB1 receptors have been found mainly in the central nervous system, but they are also present in lymphocytes, ovary, uterine endometrium, testis, vas deferens, urinary bladder, and other peripheral endocrine and neurological tissues. CB2 receptors have been identified mainly in immune cells, but are expressed also in astrocytes and in the brain stem.The best characterized endocannabinoids are N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoylglycerol (2-AG), that are prototype members of two types of compounds: the fatty acid amides and the monoacylglycerols, respectively. These lipids are not stored in intracellular compartments, but are synthesised from membrane precursors through multiple biosynthetic pathways; therefore, they are released “on demand” by neurons and peripheral cells. AEA is produced mainly by a transacylase-phosphodiesterase-mediated pathway, starting from the precursor N-arachidonoyl-phosphatidylethanolamine through the action of N-archidonoyl-phosphatidylethanolamine (NAPE) hydrolysis, catalysed by a specific phospholipase D (NAPE-PLD). The biosynthetic pathway of 2-AG provides for rapid hydrolysis of inositol phospholipids by a specific phospholipase C; this enzyme generates diacylglycerol (DAG), which is subsequentially converted to 2-AG by a sn-1-DAG lipase. The biological effects of AEA and 2-AG depend on their life span in the extracellular space, which is limited by a rapid transport through the plasma membrane. Both compounds have been proposed to be taken up by cells through a specific carrier, but the identity of this putative entity is still a controversal issue. Once inside the cells, endocannabinoids can be metabolized by multiple pathways; AEA is a substrate for fatty acid amide hydrolase (FAAH), that breaks the amide bond and releases arachidonic acid and ethanolamine, whereas 2-AG is degraded to arachidonic acid and glycerol mainly by a specific monoacylglycerol lipase (MAGL). As mentioned above, AEA and 2-AG act primarily at cannabinoid receptors. These are seven trans-membrane spanning receptors that belong to the rhodopsin family of G protein-coupled receptors, particularly those of the Gi/o group. The binding of endocannabinoids to CB receptors triggers various signaling pathways, such as the inhibition of adenylyl cyclase, the regulation of ionic currents (inhibition of voltage-gated L, N and P/Q-type Ca2+ channels, activation of K+ channels), the activation of focal adhesion kinase, of mitogen-activated protein kinase (MAPK), and of cytosolic phospholipase A2, and the activation (CB1) or the inhibition (CB2) of nitric oxide synthetase. In addition, recently an unprecedented coupling of CB1 to Gq/11 proteins has been shown, suggesting further diversity of CB1 signaling. Furthermore, there is some evidence that endocannabinoids induce a biological activity via other CB receptors, like a purported CB3 (GPR55) receptor, via non-CB1/non-CB2 receptors, and via non-cannabinoid receptors. In the latter group, type-1 vanilloid receptor (now called transient receptor potential vanilloid 1, TRPV1) has emerged as an important target of AEA, but remarkably not of 2-AG. TRPV1 is a six trans-membrane spanning protein with intracellular N - and C - terminals; this ligand-gated and non-selective cationic c-terminals; this ligand-gated and non-selective cationic channel is activated by molecules derived from plants, such as the pungent component of “hot” red peppers capsaicin, by noxious stimuli like heat and protons, and by peptides contained in spider toxins. AEA is so far the only “endovanilloid” known, behaving as an authentic (though weak) endogenous ligand of TRPV1. In the last 5 years endocannabinoids have emerged as key-mediators of several central and peripheral pathophysiological processes. In fact they act as retrograde neurotransmitters, and as neuroprotective and anti-inflammatory substances, taking part in neuronal circuitries that include dopaminergic, glutamatergic and GABAergic transmission. In addition, they participate in signaling networks that include cytokines (e.g., interleukins, growth factors, interferon-γ and tumor necrosis factor-α), and steroid hormones (e.g., progesterone, 17-β-estradiol and glucocorticoids). Furthermore, only recently new endocannabinoids (like N-arachidonoyldopamine) have been discovered, that along with “endocannabinoid-like” molecules (e.g., N-oleoylethanolamine and N-palmitoylethanolamine) are able to activate unexpected molecular targets like TRPV1, peroxisome proliferator activator receptors (PPAR), and CB3. Against this background, it is not surprising that endocannabinoid signaling is at the basis of neuroinflammatory diseases (like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis and amyotrophic lateral sclerosis), of cancer cell survival and death, of immune response and of metabolic disease. For instance, endocannabinoids have been shown to regulate food intake, and in fact a selective CB1 antagonist is available on several markets as the first anti-obesity drug for humans. Last but not least, human reproduction is under the control of endocannabinoid signaling, that regulates oviductal transport and implantation of embryos (on the female side), as well as spermatogenic output, sperm viability and motility (on the male side).Taken together, endocannabinoids have emerged as widespread signaling molecules, which take part in neuronal circuitries and cytokine-hormone networks that impact to different extents a number of pathophysiological conditions in humans.

http://cannabisasmedicine.com/story/endocannabinoids-0Endocannabinoids are derivatives of arachidonic acid (and of other poly-unsaturated... more

copperdragon
added this
2 days ago
|
10 comments

Technology Review: Mimicking the Building Prowess of Nature

Joanna Aizenberg, a materials scientist at Harvard University, has scoured the natural world for clues to biological building codes. She aims to decipher some of Mother Nature’s unique designs, including dirt-resistant sea urchins and sea sponges made of super-strong light-conducting glass, to develop novel materials that, like these organisms, can self-assemble and sense and respond to their environment.

“We try to identify biological systems that have unusual and sophisticated properties, such as optical, structural, or magnetic properties, to make extremely sophisticated, efficient, and highly potent devices and materials,” says Aizenberg, who is also a core faculty member at the Wyss Institute for Biologically Inspired Engineering. “Then we take these principles and try to integrate them with what we already know in materials science--incorporating them into existing materials or fabricating a new generation of materials based on biological principles.” The work could result in better fiber optics, paint that changes color in response to temperature or light, and new ways of delivering drugs or clearing arterial plaques.

This collection of striking images explores some of Aizenberg’s new materials, as well as the organisms that inspired them.

Nanodreadlocks: “One specific feature that interests me more than anything else at the moment is how nature creates adaptive materials that optimize performance in response to changing environmental cues,” says Aizenberg. “The systems I am trying to replicate in my lab are the surfaces of sea urchins. They cover their bodies with an array of microflowers that constantly open and close, protecting the body from contamination.”

Taking inspiration from sea urchins, Aizenberg’s team has developed nanobristles that spontaneously curl into a precise array of helical bundles when immersed in an evaporating liquid. Aizenberg likens the phenomena to the way wet, curly hair clumps together and coils to form dreadlocks. The bristles shown here are made of an epoxy resin and are approximately 100 nanometers in diameter--about one-thousandth the width of a human hair.

http://www.technologyreview.com/biomedicine/23933/?nlid=2503Joanna Aizenberg, a materials scientist at Harvard University, has scoured the natural... more

remanns
added this
3 days ago
|
3 comments

BioPlastics Man

Biochemist Oliver Peoples explains how his polymer-producing microbes could transform... more

nikkisaintbautista
added this
4 days ago
|
1 comment

Deepest river in the world, new species

Ned Gardiner, a scientist who specializes in mapping ecosystems, is fiddling with an instrument floating over the side of our wooden pirogue when the boat emerges from an eddy into the main stream of the Congo River. The transition from the still water to the turbulent flow swings the bow downstream and nearly knocks Gardiner into the water. “Almost fell into the drink, eh?” he says with a laugh, though he knows a swim here could be dangerous, even deadly. The Congo is flowing at 1.25 million cubic feet of water per second, enough to fill 13 Olympic-size swimming pools every second. Gardiner, who works for the National Climatic Data Center, in Ashville, North Carolina, is here because he thinks the Lower Congo may contain the deepest point of any river in the world.

We’re in Central Africa, 90 miles west of the Democratic Republic of Congo’s capital of Kinshasa and about 100 miles east of where the river drains into the Atlantic Ocean, ending its 3,000-mile run across equatorial Africa. A series of grassy hills called the Crystal Mountains rise subtly behind us. Gardiner and John Shelton, a hydrologist from the United States Geologic Survey, are plotting how water moves in such a massive flow. To do this, they brought along an instrument that floats alongside a boat in an orange, plastic vessel about the size of an elementary-school desk. The instrument maps water movement and measures the river’s depth. Gardiner tried to accomplish the same thing last year with a device designed for rivers. “The signal petered out well before the bottom,” he explains, his hand skimming the river’s surface. “So we bought one for oceans.”

We’re midstream, heading from the north bank to the south, on a course directly perpendicular to the current. If we manage to keep the instrument from being swallowed by one of the 40-foot-wide whirlpools studding the flow, Shelton and Gardiner’s work will produce a digital cross section of the river’s currents and depth.

The Congo’s power—its depth, speed and turbulence—is of particular interest to ichthyologist Melanie Stiassny of the American Museum of Natural History, one of the scientists in our expedition. She studies fish on the lower Congo and over the past decade has discovered six new species (she’s working on identifying three more). The number of species known to live in the lower Congo now exceeds 300 and the river contains one of the highest concentrations of "endemism," or species found nowhere else in the world. Stiassny thinks the river’s power is shaping evolution in the Congo.

Read more: http://www.smithsonianmag.com/science-nature/Evolution-in-the-Deepest-River-in-the-World.html#ixzz0WCNmMCVZNed Gardiner, a scientist who specializes in mapping ecosystems, is fiddling with an... more

pandaman2105
added this
7 days ago
|
18 comments

100 Amazing Things You Never Knew About Your Body

Some of the facts below are trivial, some are ancient history, and some of them may... more

sunnyspeaks
added this
11 days ago
|
3 comments

Chocolate Moon - Science and Cows Sketch

There are many ways we could prevent global warming, or climate change. This sketch is... more

serenitypictures
added this
12 days ago
|
0 comments

Shrink Yourself & Explore Innerspace!

frank_runyeon
added this
12 days ago
|
0 comments

Toyota Develops New Flower Species To Reduce Pollution

Toyota has created two flower species that absorb nitrogen oxides and take heat out of... more

Tyrannous
added this
13 days ago
|
18 comments

Macro Video of a Phidippus princeps Jumping Spider

A nice little Phidippus princeps "chewing" on her (his?) feet, cleaning her eyes, and... more

GrrlScientist
added this
18 days ago
|
0 comments

Ant-Mimicking Jumping Spider [video]

Unfortunately, no species ID yet (can you ID this spider?), but the mimicry in both... more

GrrlScientist
added this
19 days ago
|
0 comments

The Solution to Our Environmental Woes is to End Prohibition

The best solution to our environmental problems is to end prohibition. There is no other viable option short of the immediate end to military conflict that will have the same positive impact on the ecosystem.

Our first step towards a sustainable existence should begin with cannabis. Its assimilation into our civilization is the safest, simplest, most efficient immediate solution that we can implement in time to prevent an ecological catastrophe.

Cannabis is a plant, and its use is as old as civilization itself. It has thousands of immediate and potential applications. Its cultivation rejuvenates the soil, it can replace wood products, it’s medicinal, and it can be used as building material, textiles, paint, plastic, fuel, paper, food and body care. It is one of the most important bounties of nature. It’s a plant that we were meant to use.

So what’s the hold up? The short answer is America’s “War on Drugs”. The United States started a legislative war on this plant genus almost a century ago and they do not want to give up the fight.

The war on drugs is not a war between nations; it’s a corporate war on people, irrelevant of their nationality or ethnicity. It is a war against citizens of the United States and those of other nations. It’s a war without borders. It has gone through multiple mutations and over the last few decades grown into the monstrosity that it is today. It is a one sided war declared by nations on their citizens. A conflict not reciprocated by the citizens. It is a war that is sustained entirely do to ignorance, fear, and greed.

If there is such a thing as a just war, then the war on drugs is on the other end of the spectrum. It is the most unjust war that has ever been. It is a war exclusively waged for money. Every other war throughout history has had at least one other fathomable pretence. The war on drugs doesn’t.

The irony is that this war and the destruction that it unleashes can be brought to an end within an instant, if it was so desired. All that is required is to end prohibition, to repeal one law.

We know that the end to prohibition will have positive effects for our society because precedent for this has already been set. When prohibition of alcohol ended, so did most of the violence associated with gang warfare, as did much of the corruption in government. When prohibition ended, precious resources were made available again and a major source of revenue and employment was established through the sale of alcohol and its associated paraphernalia.

These same results have also been observed in Portugal’s experiment with drug decriminalization. The United Nations has also confirmed these findings in its annual report on the state of global drug policy, and many countries have been paying-heed and following Portugal’s example. Decriminalization is sweeping through major parts of Latin America as well as numerous municipalities and States within the United States of America.

The only reason that America’s Federal “War on Drugs” still continues to this day is because its so-called adversaries, criminal organizations and certain sectors of government, don’t want it to end since its continuation guarantees them flow of funds.

All of the above is common knowledge to anyone who has remotely researched this topic, or for that matter, even thought about it. After all, who in their right mind would ever approve of a war on nature, a war on a plant, a war on a plant that’s not even poisonous, a war on a plant that is actually beneficial for us, our society, and the ecosystem? You would have to be deranged to do such a thing. But this is exactly what we have done. We have been waging a war on a plant for almost a century. We have been waging a war on cannabis that spans the globe, costs trillions of dollars, destroys millions of lives, and consumes precious resources.

On the behest of certain corporations and a small minority that profit from prohibition, we have been CONTINUED>>>The best solution to our environmental problems is to end prohibition. There is no... more

copperdragon
added this
21 days ago
|
37 comments

New Study Finds Men Able to Control Sexual Arousal Can Also Control Their Emotions

Is sex a state of mind? A recent study from the University of British Columbia finds that while most men can regulate their physical and mental sexual arousal to some degree, the men most able to do so are able to control their other emotions as well.

“We suspect that if an individual is good at regulating one type of emotional response, he/she is probably good at regulating other emotional responses,” says Jason Winters, the study’s research head. “This has never been shown before.”

The study employed 16 randomly ordered video clips. Eight were erotic, and eight were funny (specifically, the funny video clips featured the least sexy comedian the researchers could find: Mitch Hedberg). Participants were instructed to control their response to certain videos, and simply to watch the others. They then rated their arousal following each clip, and were hooked up to machines that measured their erections.

Researchers wanted to know: Could men control sexual arousal, fooling both themselves and others?

“I’m trained in forensic psychology, and the original plan was to do this study with sexual offenders,” Winters tells LiveScience. “However, I needed to first establish that there is range of sexual arousal regulation abilities in the general male population.”

Indeed, participants were, on average, able to regulate their physiological sexual arousal when told to do so; in fact, they showed a 25 percent reduction in erectile response. “This is consistent with success rates from previous, well-controlled [measuring-device] faking studies in which success rates range from 26 to 38 percent,” Winters writes in his study.

The range of regulation abilities had nothing to do with age, sexual experience, or sexual compulsivity. However, sexual excitation, inhibition, and desire were related to regulation success: Men who were more easily excited were, unsurprisingly, less able to regulate; guys who tended to be sexually inhibited because of performance issues were better able to stave off an erection.

Furthermore, the study found that the men who were best able to control their response to the pornographic videos were also able to control their response to Mitch Hedberg. But for those who had difficulty regulating, reverse psychology could be to blame.

“The finding that was most surprising was that some men became more sexually aroused when they tried to regulate their sexual arousal,” Winters says. “In other words, they responded more strongly (both physiologically and self-reported) during trials in which they attempted to regulate their arousal than trials during which they merely watched the stimuli. We attributed this increased response to anxiety — in this case, demand anxiety. It’s sort of like when you tell someone not to think of a white elephant; those [who] are most anxious during the task have the most trouble not thinking about the white elephant.”

The study’s findings could have significant implications.

“The next step is to do a similar study with sexual offenders,” Winters says. “I suspect that sexual offenders will generally be very poor regulators, and that poor regulation is one of the factors that contributes to their offending.”Is sex a state of mind? A recent study from the University of British Columbia finds... more

EmperorThan
added this
23 days ago
|
4 comments

New Drug Corrects Memory Problems in Sleep-Deprived Mice

Researchers have found a pharmaceutical way to clear some of the cognitive fog that... more

EmperorThan
added this
23 days ago
|
0 comments

First HIV vaccine trial success confirmed

The first HIV vaccine to be called a success has stood up to scrutiny after further analysis of the data was presented today in Paris, France.

However, the new analysis also confirms that the optimistic claims, first made in September and viewed sceptically at the time, are indeed very modest.

Last month's announcement of success (PDF) was made by researchers from the US Military HIV Research Program (MHRP). They reported that their vaccine reduced the risk of infection by about 31 per cent in a trial in Thailand.

But it was not clear that the vaccine offered any protection because the result was based on very few cases: 51 of 8197 vaccinated individuals became infected with HIV compared with 74 of 8198 unvaccinated people, a difference of just 23.
Bonus data

Today, at the AIDS Vaccine 2009 meeting in Paris, MHRP researchers presented the analysis underlying the result that they announced a month ago, plus two additional analyses of the raw data (PDF).

These new analyses included people who had been excluded from the research results, such as those who did not take the six vaccine shots in the correct order. In neither was the trend statistically significant.

After hearing the new results, Seth Berkley, chief executive of the International AIDS Vaccine Initiative, said, "Certainly, there's some kind of signal there," but added, "It's a modest effect."

He also says that the new results are interesting because they give novel insights into how the vaccine works over time.
Early effect

The risks of infection in the vaccinated group were reduced by around 60 per cent within a year, but by 30 months after vaccination the protective effect was only 36 per cent. This resulted in a 31 per cent figure overall.

"It looked like there's an early effect that wanes with time," said Berkley. "It may be that the vaccine generates only weak antibodies against HIV, and these are only effective early on."

Berkley says that further investigation of the mechanisms by which the vaccine worked would provide powerful new knowledge to guide selection of new, more potent vaccines.The first HIV vaccine to be called a success has stood up to scrutiny after further... more

EmperorThan
added this
25 days ago
|
43 comments

Genetically Engineering the "Smart Rat"

Dubbed Hobbie-J after a smart rat that stars in a Chinese cartoon book, the transgenic rat was able to remember novel objects, such as a toy she played with, three times longer than the average Long Evans female rat, which is considered the smartest rat strain. Hobbie-J was much better at more complex tasks as well, such as remembering which path she last traveled to find a chocolate treat.

The report comes about a decade after the scientists first reported in the journal Nature that they had developed "Doogie," a smart mouse that over-expresses the NR2B gene in the hippocampus, a learning and memory center affected in diseases such as Alzheimer's. Memory improvements they found in the new genetically modified Long Evans rat were very similar to Doogie's. Subsequent testing has shown that Doogie maintained superior memory as he aged.

"This adds to the notion that NR2B is a universal switch for memory formation," says Dr. Joe Z. Tsien, co-director of the MCG Brain & Behavior Discovery Institute and co-corresponding author on the paper published Oct. 19 in PLoS One.

The finding also further validates NR2B as a drug target for improving memory in healthy individuals as well as those struggling with Alzheimer's or mild dementia, the scientists says.

NR2B is a subunit of NMBA receptors, which are like small pores on brain cells that let in electrically-charged ions that increase the activity and communication of neurons. Dr. Tsien refers to NR2B as the "juvenile" form of the receptor because its levels decline after puberty and the adult counterpart, NR2A, becomes more prevalent.

While the juvenile form keeps communication between brain cells open maybe just a hundred milliseconds longer, that's enough to significantly enhance learning and memory and why young people tend to do both better, says Dr. Tsien, the Georgia Research Alliance Eminent Scholar in Cognitive and Systems Neurobiology. This trap door configuration that determines not just how much but how fast information flows is unique to NMBA receptors.

Scientists found that Hobbie-J consistently outperformed the normal Long Evans rat even in more complex situations that require association, such as working their way through a water maze after most of the designated directional cues and the landing point were removed. "It's like taking Michael Jordan and making him a super Michael Jordan," Deheng Wang, MCG graduate student and the paper's first author, says of the large black and white rats already recognized for their superior intellect.

But even a super rat has its limits. For example with one test, the rats had to learn to alternate between right and left paths to get a chocolate reward. Both did well when they only had to wait a minute to repeat the task, after three minutes only Hobbie-J could remember and after five minutes, they both forgot. "We can never turn it into a mathematician. They are rats, after all," Dr. Tsien says, noting that when it comes to truly complex thinking and memory, the size of the brain really does matter.

That's one of the reasons scientists pursue this type of research: to see if increased production of NR2B in more complex creatures, such as dogs and perhaps eventually humans, gets the same results. He also is beginning studies to explore whether magnesium – a mineral found in nuts, legumes and green vegetables such as spinach – can more naturally replicate the results researchers have obtained through genetic manipulation. Magnesium ion blocks entry to the NMDA receptor so more magnesium forces the brain cell to increase expression levels of the more efficient NR2B to compensate. This is similar to how statin drugs help reduce cholesterol levels in the blood by inhibiting its synthesis in the liver.

Scientists created Hobbie-J and Doogie by making them over-express CaMKII, an abundant protein that works as a promoter and signaling molecule for the NMDA receptor, something that likely could not be replicated in humans.Dubbed Hobbie-J after a smart rat that stars in a Chinese cartoon book, the transgenic... more