19.06.2009

Повреждения ДНК и марихуана

Однако! http://www.biologynews.net/archives/2009/06/16/cannabis_alters_human_dna_new_study.html
A new study published by University of Leicester researchers has found "convincing evidence" that cannabis smoke damages DNA in ways that could potentially increase the risk of cancer development in humans.
Using a newly developed highly sensitive liquid chromatography-tandem mass spectrometry method, the University of Leicester scientists found clear indication that cannabis smoke damages DNA, under laboratory conditions.
They have now published the findings in the journal Chemical Research in Toxicology1.
The research was carried out by Rajinder Singh, Jatinderpal Sandhu, Balvinder Kaur, Tina Juren, William P. Steward, Dan Segerback and Peter B. Farmer from the Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine and Karolinska Institute, Sweden.
Raj Singh said: "Parts of the plant Cannabis sativa, also known as marijuana, ganja, and various street names, are commonly smoked as a recreational drug, although its use for such purposes is illegal in many countries.
"There have been many studies on the toxicity of tobacco smoke. It is known that tobacco smoke contains 4000 chemicals of which 60 are classed as carcinogens. Cannabis in contrast has not been so well studied. It is less combustible than tobacco and is often mixed with tobacco in use. Cannabis smoke contains 400 compounds including 60 cannabinoids. However, because of its lower combustibility it contains 50% more carcinogenic polycyclic aromatic hydrocarbons including naphthalene, benzanthracene, and benzopyrene, than tobacco smoke."
Writing in the journal Chemical Research in Toxicology, the scientists describe the development of a mass spectrometry method that provides a clear indication that cannabis smoke damages DNA, under laboratory conditions.
The authors added: "It is well known that toxic substances in tobacco smoke can damage DNA and increase the risk of lung and other cancers. Scientists were unsure though whether cannabis smoke would have the same effect. Our research has focused on the toxicity of acetaldehyde, which is present in both tobacco and cannabis."
The researchers add that the ability of cannabis smoke to damage DNA has significant human health implications especially as users tend to inhale more deeply than cigarette smokers, which increases respiratory burden. "The smoking of 3-4 cannabis cigarettes a day is associated with the same degree of damage to bronchial mucus membranes as 20 or more tobacco cigarettes a day," the team adds.
"These results provide evidence for the DNA damaging potential of cannabis smoke," the researchers conclude, "implying that the consumption of cannabis cigarettes may be detrimental to human health with the possibility to initiate cancer development."
Source : University of Leicester

Продолжительность жизни и окислительный стресс

Такой вот спорный вопрос - этот окислительный стресс... Новая инфа на http://www.scienceblog.com/cms/how-oxidative-stress-may-help-prolong-life-21533.html
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins ? cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one ? covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 ? and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels ? and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway ? to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
###
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.

05.06.2009

О счастье и мозге

Отличная статья на http://www.scienceblog.com/cms/blog/5634-happiness-%E2%80%93-theory-how-our-brains-lie-us-21534.html

Happiness – A Theory: How our Brains Lie to Us

May 29, 2009
The dialectic between descent with modification and the expanded cortex of the mammalian brain appears to have led to a kind of “house of mirrors” in humans. The smarter we get, it seems, the more we believe in our perceptions, while our brains work overtime to concoct a version of reality divorced from the evidence.
As part of the tangle of sophisticated circuitry enabled by our expanded cortex, we are able to associate any one thing with virtually any other thing, creating for ourselves an illusion of passive observation of what is actually happening in our present-time experience. We think of our brains as truth-seeking devices, but they deceive us without respite, and in staggeringly sophisticated ways.
Vision, for instance, is a projection of our minds, rather than the passive process that our brains might have us believe. Memory is fraught with error, but we adopt a false recollection with the fervor of a loving mother toward her child. We strive to acquire multiple choices, but we thrive where there are very few choices to be made, and suffer where there is a profusion. We are willing to diminish our own resources in order to punish someone we perceive as acting unfairly. We divide our fellows into “us” and “them” with regularity, despite the evidence that, in every meaningful way, we are just the same. We fret over a perceived threat that is little more than a dissenting opinion – i.e., something that would make us wiser, if we gave it shrift. We ruminate over real and imagined negatives, traumatizing ourselves more than would ever occur if we simply dealt with adversity as it arose. We set for ourselves the impossible goal of changing another person, then fall into a funk as the futility of the venture becomes apparent. We consider ourselves to be right in demanding that the world be different than it is. We perceive ourselves as victims, where the overwhelming evidence is that we are being treated to a truly unique experience in the universe. We expend energy in loathing others, when the evidence is that doing so is like taking poison. We think we are thinking when we have the perception that we are thinking, where the evidence is that our brains are whirring away 24/7, primarily in ways to which we have no access.
Recognizing that our brains lie – that we must cultivate a healthy skepticism of our own mental processes – is an important step in the pursuit of happiness.

Оксидативный стресс - подробности влияния

Я, как обычно, отслеживаю новости об окислительном стрессе. Вот - очередная: http://www.scientificblogging.com/news_articles/oxidative_stress_linked_aging_cancer_and_now_longer_life
Oxidative stress has been linked to aging, cancer and other diseases in humans. Paradoxically, researchers have suggested that small exposure to oxidative conditions may actually offer protection from acute doses. Now, scientists at the University of California, San Diego, have discovered the gene responsible for this effect. Their study, published in PLoS Genetics on May 29, explains the underlying mechanism of the process that prevents cellular damage by reactive oxygen species (ROS).
"We may drink pomegranate juice to protect our bodies from so-called 'free radicals' or look at restricting calorie intake to extend our lifespan," said Trey Ideker, PhD, chief of the Division of Genetics in the Department of Medicine at UC San Diego's School of Medicine and professor of bioengineering at the Jacobs School of Engineering. "But our study suggests why humans may actually be able to prolong the aging process by regularly exposing our bodies to minimal amounts of oxidants."
Reactive oxygen species (ROS), ions that form as a natural byproduct of the metabolism of oxygen, play important roles in cell signaling. These very small molecules include oxygen ions, free radicals and peroxides. However, during times of environmental stress (for example, ultraviolet radiation or heat or chemical exposure), ROS levels can increase dramatically. This can result in significant damage to cellular damage to DNA, RNA and proteins – cumulating in an effect called oxidative stress.
One major contributor to oxidative stress is hydrogen peroxide, converted from a type of free radical that leaks from the mitochondria as it produces energy. While the cell has ways to help minimize the damaging effects of hydrogen peroxide by converting it to oxygen and water, this conversion isn't 100 percent successful.
Ideker and first author Ryan Kelley used the rich functional genomics toolbox of yeast to identify pathways involved in the cell's adaption to hydrogen peroxide. Adaption (or hormesis) is an effect where a toxic substance acts like a stimulant in small doses, but is an inhibitor in large doses.
To shed light on the molecular mechanisms of adaptation, Ideker and Kelley designed a way to identify genes involved in adaptation to hydrogen peroxide. They elicited adaptation by pre-treating cells with a mild dose of hydrogen peroxide, followed by a high dose. They observed that the cells undergoing this adaptation protocol exhibited a smaller reduction in viability than cells exposed to only an acute treatment protocol (in which about half of the cells died.)
To figure out which genes might control this adaptation mechanism, Kelley and Ideker ran a series of experiments in which cells were forced to adapt while each gene in the genome was removed, one by one – covering a total of nearly 5,000 genes. By systematically removing genes, they identified a novel factor called Mga2 – and discovered that this transcription factor is essential for adaptation.
"This was a surprise, because Mga2 is found at the control point of a completely different pathway than those which respond to acute exposure of oxidative agents," said Ideker. "This second pathway is only active at lower doses of oxidation."
This finding may explain recent studies suggesting that eating less may, in fact, raise ROS levels – and, in doing so, provide protection from acute doses of oxidants. This is counter to the hypothesis that caloric restriction extends lifespan in some species because it reduces ROS produced as a by-product of the energy regenerated by mitochondria.
"It may be that adaption to oxidative stress is the main factor responsible for the lifespan-expanding effects of caloric restriction," said Ideker. "Our next step is to figure out how Mga2 works to create a separate pathway – to discover the upstream mechanism that senses low doses of oxidation and triggers a protective mechanism downstream." Further efforts to understand this process may have broad implications on models of aging and disease.
This work was supported by a grant from the National Institute of Environmental Health Sciences. Ideker is a David and Lucille Packard Fellow.
Kelley R, Ideker T (2009) Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide. PLoS Genet 5(5): e1000488. doi:10.1371/journal.pgen.1000488