Прозак может быть лекарством от рака?

Статья с http://scienceblogs.com/bushwells/2008/12/prozac_the_anticancer_drug.phpProzac, the anti-cancer drug?
Category: The Medical Tent
Posted on: December 22, 2008 9:46 AM, by Kevin Beck

It's common for cancer patients to be prescribed antidepressants as a means of helping them cope with an obviously traumatic diagnosis. But researchers in Israel have found that the selective serotonin-reuptake inhibitor Prozac (generic name fluoxetine) can increase the effectiveness of a common anti-cancer agent, doxorubicin, by tenfold.

A study [Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University] and his colleagues recently completed validates that Prozac dramatically enhances the effectiveness of a widely used anti-cancer drug.
"The good news is that the medical community won't have to wait - Prozac can be used for this purpose right away," says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.

"Prozac is a very interesting non-specific blocker of cancer resistance," says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.

In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.

In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.

It would be interesting to have more information on the exact mechanism of action involved here. At first I assumed that fluoxetine had been found to slow hepatic metabolism of doxorubicin or something like that, but it appears that fluoxetine's "wingman" effects on the anticancer agent are indeed direct.

The study results will be published in Cancer Letters.
Ещё, об этом же - http://www.scienceblog.com/cms/prozac-not-just-depression-anymore-18039.html
Prozac is regularly prescribed to ease the emotional pain of patients who are being treated for cancer. But can this common anti-depressant help to fight cancer itself?

Dr. Dan Peer of the Department of Cell Research and Immunology at Tel Aviv University is proving that it can. A study he and his colleagues recently completed validates that Prozac (chemical name fluoxetine) dramatically enhances the effectiveness of a widely used anti-cancer drug.

“The good news is that the medical community won't have to wait — Prozac can be used for this purpose right away,” says Dr. Peer, noting that doctors in the U.S. already prescribe it to treat depression in chemotherapy patients.

Fighting Drug Resistance in Colon Cancer Patients

“Prozac is a very interesting non-specific blocker of cancer resistance,” says Dr. Peer, whose study focused on colon cancer and the anti-cancer drug doxorubicin.

In their laboratory experiments, the Tel Aviv University scientists led by graduate student Mirit Argov together with Prof. Rimona Margalit, found that Prozac enhanced doxorubicin's efficacy more than 1,000%. Prozac, in effect, worked to block the cancer drug from leaving the interior of the cancer cell and poisoning the healthy non-cancerous cells that surrounded it.

In animal models, a mild doxorubicin-fluoxetine treatment combination slowed down tumor progression significantly. These results suggest that pairing Prozac with chemotherapeutic drugs to curb drug resistance warrants further clinical study, says Dr. Peer.

His research was just published in Cancer Letters, and his suggestions are now listed as recommendations in the latest version of Cancer Encyclopedia.

Working Backward to Make Great Advances

“Working with a major drug developer, we have validated Prozac's potential, and now Tel Aviv University can lead a humanitarian effort to save lives around the globe,” he says.

Since it is very hard to protect this patent because any clinician can prescribe Prozac, it is impossible for Tel Aviv University to commercialize its research, says Dr. Peer. Instead, he suggests that researchers join forces internationally to implement retrospective studies of all the types of cancer treatment in which Prozac was prescribed. And further clinical experiments to validate the use of Prozac with chemotherapy is also needed, he stresses.

“The next step is to take the files of chemo patients and determine whether they received Prozac for their depression,” says Dr. Peer. “This will streamline the understanding in the scientific community of whether, how and for which cancer-fighting drugs Prozac can be an effective partner. It will also give us invaluable information on how to design new drugs."

Dr. Peer's Tel Aviv University lab is also developing several new drug delivery nanotechnologies to bring novel therapeutics into breast, blood, pancreatic and brain cancers. A recent technological breakthrough to reprogram immune cells involved in ulcerative colitis and Crohn’s disease was reported in Science earlier this year and it is the basis of a new platform technology developed in his group.

Кофеин сильнее влияет на мужчин...

Вот такое интересное исследование.
http://www.scientificblogging.com/news_releases/men_caffeine_more_effective_and_starts_working_10_minutesA study headed by researchers from the University of Barcelona (UB) shows that caffeine has a greater effect on men than women, and that these effects start just 10 minutes after it is drunk. In addition, contrary to what was previously thought, it has also been shown that decaffeinated coffee also produces an increased state of alertness.

“Numerous studies have demonstrated the stimulant effects of caffeine, but none of these have looked at their effects in terms of the consumer’s gender,” Ana Adan, lead author of the study and a researcher in the Psychiatry and Clinical Psychobiology Department of the UB, tells SINC.

Research into the effects of caffeine tends to be carried out using preparations in which the caffeine level is much higher than normal intake. According to Adan, the novelty of this study lies in “the difference seen in the effects on men and women, based on the quantities of caffeine people take in 99% of cases (espresso coffee and decaffeinated espresso coffee, containing 100mg and 5mg of caffeine, respectively)”.

In order to measure the effects, the scientists used a sample of 668 university students (238 male and 450 female) with an average age of 22 years. Measurements were taken before and after the caffeine was ingested (10, 20 and 30 minutes) and were carried out at mid-day (11am to 1pm) and in the afternoon (4pm to 6pm), to act as a control in case of possible differences caused by the time.

“Although both the men and women saw an improvement in their activity levels with the coffee, which increased in later measurements, we observed a greater impact among the males,” the Catalan researcher tells SINC.

When the decaffeinated version was introduced into the study, the authors also found a small subjective improvement in the participants’ state of alertness, which did not rise so strikingly in the later measurements. “Although we can’t say it is a placebo, we did note an effect resulting from drinking a decaffeinated coffee (at a quantity insufficient to actually affect mood),” adds Adan.

The results showed a small impact among both men and women who drank the decaffeinated coffee, although this time the effect was slightly more noticeable among the women. The effect of decaffeinated drinks on alertness had not been previously studied.

As the author says, “if a person cannot drink normal coffee, a decaffeinated one might provide some benefits. It remains to be evaluated whether these effects are simply subjective, or if they do have an impact on performance”.

Coffee produces fast-acting effects

Caffeine has an almost immediate effect. Previous studies had shown that alertness starts to increase 30-45 minutes after consumption, but the new study shows that the effects begin after as little as 10 minutes. According to the researcher “45 minutes is the time needed for maximum caffeine concentration to be reached in the blood, but levels reach half this concentration after just a few minutes”.

The experts say the effects of caffeine last for between two and three hours, although some authors extend this to up to four or five hours according to an individual’s particular sensitivity and metabolic rate, which varies greatly with age.

Article: Ana Adan, Gemma Prat, Marco Fabbri, Miquel Sánchez-Turet. “Early effects of caffeinated and decaffeinated coffee on subjective state and gender differences”. Progress in Neuro-Psychopharmacology&Biological Psychiatry 32 1698–1703 OCT 2008.


Ещё о пчёлах и кокаине. Видео.

Пчёлки любят кокс?!

Без комментариев... :) Читаем на scientificblogging.com/news_releases/honeybees_cocaine
Since its discovery in the 18th century, cocaine has been a scourge of western society. Strongly stimulating human reward centers in low doses, cocaine is extremely addictive and can be fatal in high doses.

But this potent compound did not evolve to ensnare humans in addiction, it is a powerful insect neurotoxin, protecting coca bushes from munching insects - without rewarding them.

Knowing that foraging honey bees are strongly motivated by rewards (they dance in response to the discovery of a rewarding nectar or pollen supply) and that this behavior is controlled by similar mechanisms to the ones that leave humans vulnerable to cocaine addiction, Andrew Barron from Macquarie University, Australia and Gene Robinson from the University of Illinois at Urbana-Champaign wondered whether bees may be vulnerable to cocaine's allure at the right dose.

Teaming up with Ryszard Maleszka at the Australian National University, Barron set about testing how honeybees respond to cocaine. They publish their results on 26th December 2008 in The Journal of Experimental Biology.

Setting up his hives on a farm just outside Canberra, Barron trained the insects to visit a feeder stocked with a sugar solution. Then he gently applied a tiny drop of cocaine solution to the insect's back, and waited to see how enthusiastically the foraging insects danced when returning to the hive.

Amazingly, low doses of the drug stimulated the insects to dance extremely vigorously. They behaved as if the sucrose solution was of a much higher quality than it really was. The cocaine seemed to be hitting the insects' reward centers, but were they really responding to the drug like humans or was the drug stimulating some other aspect of the insects' behavior to look as if they were becoming addicted?

Working with a team of undergraduate students, Barron tested whether cocaine stimulated the insects' locomotion centers by monitoring their movements after a dose of the drug. The insects behaved normally, so the drug probably doesn't affect their movements. However, when Paul Helliwell tested the bees' sensitivity to sugar solutions, the drugged bees responded more strongly than the undrugged insects, so cocaine was increasing their sugar sensitivity.

But was it only increasing their sensitivity to sugar, or increasing their response to all rewards? Barron offered the drugged insects pollen to see if cocaine increased their sensitivity to other floral rewards and found that the foragers were equally overenthusiastic, dancing as if the pollen quality was much better than it really was.

Finally Barron and Helliwell wondered whether bees that had been on cocaine for a few days had become dependent and went into withdrawal when the drug was withheld. Testing the insects' ability to learn to distinguish between lemon and vanilla scents, they found that the bees were fine so long as their cocaine supply was maintained. But as soon as the drug was withdrawn the bees had difficulty learning the task, just like humans going into withdrawal.

Barron is confident that honeybees are as susceptible to cocaine's allure as humans, and is keen to find out more about the drug's effects. He hopes to identify the neural pathways that it targets to find out more about the mechanisms involved in human addiction and to find out whether the drug has as devastating an effect on honey bee society as it does on human society.


Новый способ детекции активных форм Кислорода.

Активные формы Кислорода, окислительный стресс - это одни из наиболее интересующих меня проблем. Занятная статья об использовании нового флюоресцентного красителя для определения наличия АФК на http://www.biologynews.net/archives/2008/12/16/researchers_create_new_class_of_fluorescent_dyes_to_detect_reactive_oxygen_species_in_vivo.html
Researchers have created a new family of fluorescent probes called hydrocyanines that can be used to detect and measure the presence of reactive oxygen species. Reactive oxygen species are highly reactive metabolites of oxygen that have been implicated in a variety of inflammatory diseases, including cancer and atherosclerosis.

"We've shown that the hydrocyanines we developed are able to detect the reactive oxygen species, superoxide and the hydroxide radical, in living cells, tissue samples, and for the first time, in vivo," said Niren Murthy, assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

Details of the hydrocyanine synthesis process and experimental results showing the ability of the dyes to detect reactive oxygen species in cells, tissues and mouse models were reported on December 8 in the online version of the journal Angewandte Chemie International Edition. This research is supported by the National Institutes of Health and the National Science Foundation.

The researchers have created six hydrocyanine dyes to date – hydro-Cy3, hydro-Cy5, hydro-Cy7, hydro-IR-676, hydro-IR-783 and hydro-ICG – but say that there are potentially 40 probes that could be created. The dyes vary in their ability to detect intracellular or extracellular reactive oxygen species and by their emission wavelength – from 560 to 830 nanometers.

Fluorescing at higher wavelengths allows the hydrocyanine dyes to be used for deep tissue imaging in vivo, a capability that dihydroethidium (DHE), the current "gold standard" for imaging reactive oxygen species, does not have. The dyes also have other advantages over DHE.

"When DHE comes into contact with reactive oxygen species, it oxidizes into ethidium bromide, a common mutagen, which means it's toxic and can't be injected inside the body," explained Murthy. "DHE also auto-oxidizes in the presence of aqueous solutions, which creates high levels of background fluorescence and interferes with reactive oxygen species measurements."

Hydrocyanines are also simple and quick to synthesize, according to Coulter Department postdoctoral fellow Kousik Kundu. Sodium borohydride is added to commercially available cyanine dyes and the solvent is removed – the one-step process takes less than five minutes.

W. Robert Taylor, a professor in the Coulter Department and Emory's Division of Cardiology, and Emory postdoctoral fellow Sarah Knight, tested the ability of the dyes to detect reactive oxygen species inside of cells and animals.

For their first experiment, they tested the ability of hydro-Cy3, which has an emission wavelength of 560 nanometers, to detect reactive oxygen species production in the aortic smooth muscle cells of rats. They incubated the cells with hydro-Cy3 and angiotensin II, which is a stimulator of reactive oxygen species that is implicated in the development of atherosclerosis and hypertension.

Results showed that cells incubated with angiotensin II and hydro-Cy3 displayed intense intracellular fluorescence, whereas control cells incubated with hydro-Cy3 and phosphate buffer saline displayed significantly lower fluorescence. When they introduced TEMPOL, a molecule that intercepts the reactive oxygen species so that they cannot interact, the cells treated with angiotensin II and hydro-Cy3 displayed a dramatic decrease in fluorescence.

"This test demonstrated that the cellular fluorescence was due to intracellular reactive oxygen species production," said Murthy. "What was even more exciting was that we saw that once the hydrocyanine dye was oxidized, it stayed in the cell and the fluorescence was not extinguished by cellular metabolism, which is what happens with DHE."

The researchers also investigated the ability of hydro-Cy3 to image reactive oxygen species production in live mouse aorta tissue, which exhibit a physiological environment that closely resembles in vivo conditions. Explants were incubated with hydro-Cy3 and either lipopolysaccharide endotoxin (LPS), an inflammatory molecule that binds to aortic cells and causes reactive oxygen species to be produced, or the control saline solution.

Samples treated with hydro-Cy3 and LPS showed fluorescence intensity almost four times greater than explants treated with hydro-Cy3 and saline. Once more, adding TEMPOL to the sample with hydro-Cy3 and LPS decreased the fluorescence to a level comparable to the control saline explants.

After the successful cell culture and tissue experiments, the researchers progressed to in vivo mouse imaging studies. Hydro-Cy7 was selected for the in vivo tests because of its higher emission wavelength of 760 nanometers. LPS-treated mice showed twofold greater fluorescence intensity in the abdominal area than those treated with saline.

"Given their ability to detect reactive oxygen species in living cells, tissue samples and in vivo, we believe these dyes will enhance the ability of researchers to measure reactive oxygen species," noted Murthy.

The researchers' ultimate goal, though, is to use the dyes in clinical applications.

"We want to use these hydrocyanine dyes to detect overproduction of reactive oxygen species at an early stage inside the body so that we can identify patients who are more likely to suffer from these inflammatory diseases," added Murthy.

Source : Georgia Institute of Technology Research News


О генах и моноаминооксидазе.

Отличная статья. О полиморфизме генов, кодирующих МАОА, и связанных с этим нарушениях поведения. http://www.eurekalert.org/pub_releases/2008-12/ace-aaa120808.php

Contact: Roope Tikkanen, M.D.
University of Helsinki

Alcoholism: Clinical & Experimental Research
Alcohol and a polymorphism of the monoamine oxidase A gene predict impulsive violence

The monoamine oxidase A (MAOA) gene is an outer membrane mitochondrial enzyme that breaks down monoamines such as serotonin, noradrenalin and dopamine. A common polymorphism in MAOA results in high- or low-activity MAOA, and both genotypes have been linked to aggression and violence. A Finnish study has found that drinking and high-activity MAOA can predict the risk of impulsive violence, while aging may decrease this risk.

Results will be published in the March issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Alcoholism, alcohol consumption and violence are clearly related," said Roope Tikkanen, a researcher in the department of psychiatry at Helsinki University Central Hospital and corresponding author for the study. He noted that crime statistics show that most impulsive homicides occur among adolescent and middle-aged groups rather than among the elderly, and habitually violent-impulsive offenders are often expected to "grow out of their difficulties" with increasing age. "Surprisingly little accurate information, however, is available on this aging-impulsive aggression issue," he said.

Tikkanen and his colleagues decided to look at the MAOA gene, alcohol consumption and aging as predictors for recidivism in impulsive violent behavior among a sample of 174 Finnish alcoholic male offenders originally recruited between 1990 and 1998. Each offender was given a psychiatric assessment; in addition, their alcohol consumption was measured, their violent behavior was assessed, and they were genotyped for polymorphisms of MAOA.

"Increased alcohol consumption and aging seem to predict violence," said Tikkanen, "although these risk factors 'work' in opposite directions, and only concern individuals who have been given by nature a high-activity variant of MAOA." On the other hand, he added, additional research has suggested that individuals with low-activity MAOA seem to be at risk for criminality and violence after exposure to severe childhood maltreatment.

"People react quite differently to acute alcohol exposure," Tikkanen continued. "Most individuals become relaxed and talkative, while some – particularly persons who are introverted while sober – become expansively extroverted and aggressive. A dramatic change from a normally introverted personality to extroverted aggressiveness and uncontrolled behaviors under the influence of alcohol was formerly called 'pathological intoxication' in Finland."

Regarding the decline in impulsive-aggressive behavior with aging among high-activity MAOA offenders, Tikkanen hypothesized that it may be due to a correction of low central serotonin levels in the central nervous system.

Tikkanen cautioned against genetic testing for individuals who may be worried for one reason or another about their risk. "Even though whole genome scans will one day be affordable, the average person probably has very many factors that differ from the violent offenders in the study," he said. "For instance, the average Finnish consumption is two drinks a day or 10 kg pure alcohol per year, whereas the upper 10 percent of violent offenders drink approximately one 0.75 liter bottle of liquor a day or around 100 kg pure alcohol a year."

Tikkanen and his co-authors suggest that high-activity MAOA offenders may be helped to control their violent behaviors by coaching to maintain alcohol abstinence, and possibly by psychopharmacological treatment to increase central serotonin levels.

"In some countries, prison sentences may be very long – even a lifetime or more – and the reason for the sentence may be an accumulation of minor convictions committed in a drunken state," said Tikkanen. "In such cases, it could perhaps benefit all parties to decrease the length of the sentence. Our results suggest that the risk for new violent crimes decreases by 150 percent when high-activity MAOA individuals become 20 years older. Perhaps we could increase the efficacy of addiction rehabilitation by focusing resources particularly on younger heavy-drinking high-activity MAOA individuals."


Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Effects of MAOA-genotype, Alcohol Consumption, and Ageing on Violent Behavior," were: Richard L. Sjöberg of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism, the Center for Clinical Research at Uppsala University in Västerås, Sweden, and the Department of Neurosurgery at University Hospital in Umeå, Sweden; Francesca Ducci of King's College in London; Davie Goldman of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism; Matti Holi and Matti Virkkunen of the Department of Psychiatry in the Institute of Clinical Medicine at the University of Helsinki; and Jari Tiihonen of the Department of Forensic Psychiatry and Clinical Physiology at the University of Kuopio, Finland. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the Olle Engkvist Byggmästare foundation.


Однозначно - за! Лекарства для улучшения работы мозга.

Одна из самых животрепещущих тем - допинг для мозга. Статья на http://blog.wired.com/wiredscience/2008/12/brain-enhancing.html:
If drugs can safely give your brain a boost, why not take them? And if you don't want to, why stop others?

In an era when attention-disorder drugs are regularly — and illegally — being used for off-label purposes by people seeking a better grade or year-end job review, these are timely ethical questions.

The latest answer comes from Nature, where seven prominent ethicists and neuroscientists recently published a paper entitled, "Towards a responsible use of cognitive-enhancing drugs by the healthy."

In short: Legalize 'em.

"Mentally competent adults," they write, "should be able to engage in cognitive enhancement using drugs."

Roughly seven percent of all college students, and up to 20 percent of scientists, have already used Ritalin or Adderall — originally intended to treat attention-deficit disorders — to improve their mental performance.

Some people argue that chemical cognition-enhancement is a form of cheating. Others say that it's unnatural. The Nature authors counter these charges: Brain boosters are only cheating, they say, if prohibited by the rules — which need not be the case. As for the drugs being unnatural, the authors argue, they're no more unnatural than medicine, education and housing.

In many ways, the arguments are compelling. Nobody rejects pasteurized milk or dental anesthesia or central heating because it's unnatural. And whether a brain is altered by drugs, education or healthy eating, it's being altered at the same neurobiological level. Making moral distinctions between them is arbitrary.

But if a few people use cognition-enhancing drugs, might everyone else be forced to follow, whether they want to or not?

If enough people improve their performance, then improvement becomes the status quo. Brain-boosting drug use could become a basic job requirement.

Ritalin and Adderall, now ubiquitous as academic pick-me-ups, are merely the first generation of brain boosters. Next up is Provigil, a "wakefulness promoting agent" that lets people go for days without sleep, and improves memory to boot. More powerful drugs will follow.

As the Nature authors write, "cognitive enhancements affect the most complex and important human organ and the risk of unintended side effects is therefore both high and consequential." But even if their safety could be assured, what happens when workers are expected to be capable of marathon bouts of high-functioning sleeplessness?

Most people I know already work 50 hours a week and struggle to find time for friends, family and the demands of life. None wish to become fully robotic in order to keep their jobs. So I posed the question to Michael Gazzaniga, a University of California, Santa Barbara, psychobiologist and Nature article co-author.

"It is possible to do all of that now with existing drugs," he said. "One has to set their goals and know when to tell their boss to get lost!"

Which is not, perhaps, the most practical career advice these days. And University of Pennsylvania neuroethicist Martha Farah, another of the paper's authors, was a bit less sanguine.

"First the early adopters use the enhancements to get an edge. Then, as more people adopt them, those who don't, feel they must just to stay competitive with what is, in effect, a new higher standard," she said.

Citing the now-normal stresses produced by expectations of round-the-clock worker availability and inhuman powers of multitasking, Farah said, "There is definitely a risk of this dynamic repeating itself with cognition-enhancing drugs."

But people are already using them, she said. Some version of this scenario is inevitable — and the solution, she said, isn't to simply say that cognition enhancement is bad.

Instead we should develop better drugs, understand why people use them, promote alternatives and create sensible policies that minimize their harm.

As Gazzaniga also pointed out, "People might stop research on drugs that may well help memory loss in the elderly" — or cognition problems in the young — "because of concerns over misuse or abuse."

This would certainly be unfortunate collateral damage in the 21st century theater of the War on Drugs — and the question of brain enhancement needs to be seen in the context of this costly and destructive war. As Schedule II substances, Ritalin and Adderall are legally equivalent in the United States to opium or cocaine.

"These laws," write the Nature authors, "should be adjusted to avoid making felons out of those who seek to use safe cognitive enhancements."

After all, according to the law's letter, seven percent of college students and 20 percent of scientists should have done jail time — this journalist, too.

Towards responsible use of cognitive-enhancing drugs by the healthy [Nature]


Гены и плацебо

Всё в нашем организме зависит от экспрессии генов. Оказывается, и эффективность таблеток-пустышек - тоже. Описан интересный эксперимент. Нашла - на http://www.scienceblog.com/cms/genes-determine-whether-placebos-work-17920.html

It is a well-known fact in drug trials that individuals can respond just as well to placebos, sugar pills, as to the active drug. On the other hand, it is difficult to explain why only certain people get better from placebos. A team of researchers from Uppsala University and Gothenburg University have now found gene variants that can impact the placebo effect and a mechanism in the brain that characterizes those who respond to placebos.

The study, published in Journal of Neuroscience, examined 108 individuals suffering from social phobia using a brain camera (PET, positron emission tomography). The individuals were participating in a treatment study looking into how anxiety-moderating drugs affect brain activity. Just under one fourth of the subjects were given a placebo instead of a drug. This was a double-blind study, meaning that neither the subjects nor the research team know who was taking the drug or the sugar pill.

Before and after an eight-week period of treatment, the participants were asked to give a stressful oral presentation while their brain activity was monitored. When all the metering was finished and the study was decoded, it turned out that 40 percent of the placebo group had received the same degree of anxiety relief from the sugar pill as other groups got from a drug.

Those who responded well to the placebo had a significant reduction in activity in the amygdala in the temporal lobe, while this reduction was not found in the others. In previous research the amygdala has stood out as a key structure for emotional reactions. Both serotonin-active drugs (SSRI preparations) and cognitive behavioral therapy moderate activity in this area.

"Thus, successful placebo treatment works through the same mechanism in the brain," says Tomas Furmark at the Uppsala University Department of Psychology, who directed the study.

The study also analyzed two genes that influence the reabsorption and synthesis of serotonin in the brain (the serotonin transporter gene and the tryptophan hydroxylase-2 gene). The findings showed that only individuals who had certain variants, alleles, of these genes had a moderation of activity in the amygdala. Above all, the tryptophan hydroxylase-2 genes variants could predict the degree of relief from anxiety achieved by the placebo pill as well as the moderation of the amygdala.

Statistical analyses showed that it is a genetic effect on the activity in the amygdala that influences the propensity to respond to a placebo, that is, a path from the gene, via the brain, to behavior.

The study shows for the first time that genes influence the placebo effect by regulating the propensity to react in an area of the brain that is important for our feelings.

This could have significant consequences for all drug testing and other treatment studies that use a placebo.

"The findings show that the possibilities of demonstrating that an active treatment functions better than a placebo can be affected by the gene variants in the trial subjects. It is also possible that genes can explain why certain people respond well or poorly to anxiety-moderating drugs and psychotherapy respectively," says Tomas Furmark.


Повреждения ДНК и старение

Как вы уже поняли, повреждения ДНК - моя любовь. А их роль в процессах старения - одна из интереснейших тем... Поэтому не могу не запостить заметку, прочитанную на http://www.scientificblogging.com/news_releases/did_these_researchers_discover_universal_mechanism_aging
Researchers have discovered that DNA damage decreases a cell's ability to regulate which genes are turned on and off in particular settings. This mechanism, which applies both to fungus and to us, might represent a universal culprit for aging.

"This is the first potentially fundamental, root cause of aging that we've found," says Harvard Medical School professor of pathology David Sinclair. "There may very well be others, but our finding that aging in a simple yeast cell is directly relevant to aging in mammals comes as a surprise."

Their findings appear in the November 28 issue of the journal Cell.

For some time, scientists have know that a group of genes called sirtuins are involved in the aging process. These genes, when stimulated by either the red-wine chemical resveratrol or caloric restriction, appear to have a positive effect on both aging and health.

Nearly a decade ago, Sinclair and colleagues in the Massachusetts Institute of Technology lab of Leonard Guarente found that a particular sirtuin in yeast affected the aging process in two specific ways—it helped regulate gene activity in cells and repair breaks in DNA. As DNA damage accumulated over time, however, the sirtuin became too distracted to properly regulate gene activity, and as a result, characteristics of aging set in.

"For ten years, this entire phenomenon in yeast was considered to be relevant only to yeast," says Sinclair. "But we decided to test of this same process occurs in mammals."

Philipp Oberdoerffer, a postdoctoral scientist in Sinclair's Harvard Medical School lab, used a sophisticated microarray platform to probe the mammalian version of the yeast sirtuin gene in mouse cells. The results in mice corroborated what Sinclair, Guarente, and colleagues had found in yeast ten years earlier.

Oberdoerffer found that a primary function of sirtuin in the mammalian system was to oversee patterns of gene expression (which genes are switch on and which are switch off). While all genes are present in all cells, only a select few need to be active at any given time. If the wrong genes are switched on, this can harm the cell. (In a kidney cell, for example, all liver genes are present, but switched off. If these genes were to become active, that could damage the kidney.) As a protective measure, sirtuins guard genes that should be off and ensure that they remain silent. To do this, they help preserve the molecular packaging—called chromatin—that shrink-wraps these genes tight and keeps them idle.

The problem for the cell, however, is that the sirtuin has another important job. When DNA is damaged by UV light or free radicals, sirtuins act as volunteer emergency responders. They leave their genomic guardian posts and aid the DNA repair mechanism at the site of damage.

During this unguarded interval, the chromatin wrapping may start to unravel, and the genes that are meant to stay silent may in fact come to life.

For the most part, sirtuins are able to return to their post and wrap the genes back in their packaging, before they cause permanent damage. As mice age, however, rates of DNA damage (typically caused by degrading mitochondria) increase. The authors found that this damage pulls sirtuins away from their posts more frequently. As a result, deregulation of gene expression becomes chronic. Chromatin unwraps in places where it shouldn't, as sirtuin guardians work overtime putting out fires around the genome, and the unwrapped genes never return to their silent state.

In fact, many of these haplessly activated genes are directly linked with aging phenotypes. The researchers found that a number of such unregulated mouse genes were persistently active in older mice.

"We then began wondering what would happen if we put more of the sirtuin back into the mice," says Oberdoerffer. "Our hypothesis was that with more sirtuins, DNA repair would be more efficient, and the mouse would maintain a youthful pattern gene expression into old age."

That's precisely what happened. Using a mouse genetically altered to model lymphoma, Oberdoerffer administered extra copies of the sirtuin gene, or fed them the sirtuin activator resveratrol, which in turn extended their mean lifespan by 24 to 46 percent.

"It is remarkable that an aging mechanism found in yeast a decade ago, in which sirtuins redistribute with damage or aging, is also applicable to mammals," says Leonard Guarente, Novartis Professor of Biology at MIT, who is not an author on the paper. "This should lead to new approaches to protect cells against the ravages of aging by finding drugs that can stabilize this redistribution of sirtuins over time."

Both Sinclair and Oberdoerffer agree with Guarente's sentiment that these findings may have therapeutic relevance.

"According to this specific mechanism, while DNA damage exacerbates aging, the actual cause is not the DNA damage itself but the lack of gene regulation that results," says Oberdoerffer. "Lots of research has shown that this particular process of regulating gene activity, otherwise known as epigenetics, can be reversed—unlike actual mutations in DNA. We see here, through a proof-of-principal demonstration, that elements of aging can be reversed."

Recent findings by Chu-Xia Deng of the National Institute of Diabetes, Digestive and Kidney Diseases, has also found that mice that lack sirtuin are susceptible to DNA damage and cancer, reinforcing Sinclair's and Oberdoerffer's data.

Пингвины-геи крадут яйца у птиц-натуралов! :)

Вот такие реалии животного гомосексуализма... :) Читаю на http://scienceblogs.com/zooillogix/2008/12/gay_penguins_steal_straight_co.phpGay Penguins Steal Straight Couples' Eggs
Category: penguins
Posted on: December 1, 2008 8:02 PM, by Benny Bleiman

A pair of gay penguins at Polar Land in Harbin, north east China has taken to stealing the eggs of straight couples and leaving rocks in place to fool their victims. The penguins, named Anderson Cooper and Clay*** by the zoo keepers, have been outed by their fellow penmates and have since been ostracized by the flock. Fearing for the stress levels of the flock, keepers have taken Anderson and Clay out of their enclosure and segrated them alone in a pen of their own.

"Did you see little miss happy feet the other day? That new bleak gloss was a travesty against all things good in this world!..." "Um, I KNOW it. I mean, wooo-ooooh, wooo-ooooh, someone call the Antarctic Fashion Police!"

When asked about the decision to separate the gay penguin couple, one keeper told the Austrian Times newspaper as reported in the Daily Telegraph, "It's not discrimination. We have to fence them separately, otherwise the whole group will be disturbed during hatching time."

Either way, 51 percent of Californians applauded the zoo's decision. "When it comes to penguin rights, separate but equal sounds good to us," a spokesman for the Church of Jesus Christ of Latter Day Saints from nearby Utah was quoted as saying.

Instances of animal homosexuality are recorded all over the science kingdom (including by us), and prove, once and for all, that when you don't believe in genes, evolution or science, homosexuality is merely a choice of lifestyle.

***The names Anderson Cooper and Clay may not have actually been used by the keepers at the zoo, and may in fact have been invented by me.


Псевдоэфедрин и дети!

Детки часто кушают псевдоэфедрин... и много... http://www.eurekalert.org/pub_releases/2008-12/bu-puc120108.phpPublic release date: 1-Dec-2008

Contact: Gina DiGravio
Boston University

Pseudoephedrine use common among young children
Boston, MA—Researchers from Boston University's Slone Epidemiology Center have found that exposure to pseudoephedrine, a decongestant found in many cough-and-cold and allergy medications, has been common among U.S. children, especially those under the age of two years who are at the highest risk for toxicity and for whom safe dosing recommendations are lacking. These findings appear in the December issue of the journal Pediatrics.

Pseudoephedrine has been associated with deaths and adverse events in young children. However, the absolute risks of pediatric pseudoephedrine use are difficult to determine because the number of children exposed to this medication and typical patterns of use are unknown. In addition, use may be changing because of the Combat Methamphetamine Act of 2005, a law which limited availability of pseudoephedrine-containing products.

To define the frequency and patterns of use, the researchers analyzed data from 1999 through 2006 on pseudoephedrine use among 4,267 children, aged 0 to 17 years, who were enrolled in the Slone Survey, a national random-digit-dial telephone survey of medication use in the U.S.

The researchers found 4.9 percent of children took pseudoephedrine in a given week. Use was highest in children under two years of age (8.1 percent). Sixteen children (7.5 percent of users) took more than one pseudoephedrine-containing product within the same week, including six children under two years old. Of the pseudoephedrine products used, most were multiple-ingredient liquids (58.9 percent) and multiple-ingredient tablets (24.7 percent). Fifty-two subjects (25 percent of users) took pseudoephedrine for longer than one week, including seven children under two years of age. Perhaps reflecting reduced availability, use in 2006 (2.9 percent) was significantly lower than in 1999-2005 (5.2 percent).

Concerning patterns of use identified in the study include taking more than one pseudoephedrine-containing product at the same time and using pseudoephedrine for long periods of time. Pediatric pseudoephedrine use appears to be declining since the institution of the 2005 Combat Methamphetamine Act. "Pseudoephedrine exposure, mostly in the form of multiple-ingredient products, is common among U.S. children and needs to be monitored closely because of the potential for this medication to cause harm, particularly to children under two" said lead author Louis Vernacchio, MD, MSc, an assistant professor of epidemiology and pediatrics at Boston University School of Medicine.


Опять о повреждениях ДНК.

Тянется моё сердце к этой теме, ничего поделать не могу. :) Вот и очередные новости о проблеме: http://www.biologynews.net/archives/2008/11/20/misreading_of_damaged_dna_may_spur_tumor_formation.html
The DNA in our cells is constantly under assault from oxygen, the sun's radiation and environmental stresses. Most of the time, our cells can repair the damage before it gets copied into a permanent mutation that could lead to cancer.

Adding a wrinkle to our understanding of how cancers begin, scientists have found that cells can turn on tumor-promoting growth circuits as a result of misreading damaged DNA without copying it: a process called "transcriptional mutagenesis."

The results are published online this week in Proceedings of the National Academy of Sciences.

"This reveals a new aspect of tumor development that could be especially important for cells that make up most of the body's tissues: differentiated cells that are not replicating their DNA," says Paul Doetsch, PhD, professor of biochemistry at Emory University School of Medicine and deputy director of basic research at Emory Winship Cancer Institute.

All cells, including non-dividing cells that are not replicating their DNA, continue to transcribe, or make RNA, from some of their genes in order to produce proteins and carry out their normal functions.

Doetsch and postdoctoral researcher Tina Saxowsky, PhD, examined what happens when mouse cells are presented with DNA pre-loaded with a damaged building block in a critical place.

The DNA encoded the gene Ras, one of the genes most often mutated in human cancers. The damage came in the form of 8-oxoguanine, which is generated when guanine, one of the four bases making up DNA, reacts with oxygen. (The four bases are: Adenine, Guanine, Cytosine and Thymine.) Cells unable to repair the damage tend to replace the modified guanine (G) with thymine (T).

"It's one of the most common forms of genetic damage," Doetsch says. "Constantly dealing with oxidation is the price we pay for breathing air."

If the cells misread the G as T during the process of transcription, some of the Ras protein they make comes in the hyperactivated form found in cancers. By looking at other proteins controlled by Ras, the authors could detect some of the cell's growth circuits starting to turn on.

By reading the RNA the cells make from the Ras DNA, Saxowsky found that even normal mouse cells misread the damaged DNA about three percent of the time. Sometimes the cell's machinery sees the damaged G as T, and sometimes it skips a letter. However, the mouse cells were more likely to misread the 8-oxoguanine (14 percent of the time) if they came from mice engineered to lack an enzyme that normally repairs the damage, called 8-oxoguanine glycosylase.

Doetsch says his group's findings suggest that DNA damage, if it hits certain critical genes in a cell, could lead to transcriptional mutagenesis that in turn spurs the cell to divide.

"Let's say that DNA damage lands in a gene that normally prevents a cell from dividing when it's not supposed to," Doetsch says. "If enough mutant proteins get made from the gene, the cell divides and the DNA is copied. Now, in one of the daughter cells the damage becomes a permanent mutation driving further growth. It's another way for tumor promotion to happen, except the growth signal needed to push the process along isn't coming from a chemical or a hormone."

He and Saxowsky are performing additional experiments to test the hypothesis that transcriptional mutagenesis can lead to cell division directly.

Transcriptional mutagenesis could explain a phenomenon seen in bacteria called adaptive mutagenesis, Doetsch says. When faced with starvation conditions, bacteria can relax their standards of accuracy when copying their DNA, apparently in an effort to mutate their way out of a dead end.

It appears that bacterial enzymes that make RNA from DNA are more susceptible to transcriptional mutagenesis than those from mammals, Doetsch notes, but further studies are required.

Cancer is essentially the "selfish" growth of a small group of cells at the expense of the person they came from, an issue that does not arise in one-celled organisms such as bacteria, he says.

Source : Emory University


Немного о влиянии амфетамина на детей.

Некоторые новые данные: http://www.scientificblogging.com/news_releases/adhd_medication_dispute_methylphenidate_and_amphetamine_do_not_cause_genetic_damage_kids_says_study

ADHD is a disorder characterized by attention problems, impulsivity, and hyperactivity. About 3 percent of children in the United States have been diagnosed with the disorder, although some studies suggest 7 to 12 percent of children may be affected.

The study published online this month in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) provides new evidence that therapeutic doses of stimulant medications, such as methylphenidate and amphetamine, do not cause cytogenetic (chromosomal) damage in humans. The researchers looked at three measures of cytogenetic damage in white blood cells of each child participating in the study and found no evidence of any changes after three months of continuous treatment.

"This is good news for parents," said Kristine L. Witt, M.Sc., a genetic toxicologist at the National Institute of Environmental Health Sciences (NIEHS) and co-author on the study, which was funded through the Best Pharmaceuticals for Children Act by NIEHS and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), both parts of NIH. "Our results indicate that methylphenidate- and amphetamine-based products do not induce cytogenetic damage in children."

The researchers involved emphasize that the findings should not be interpreted as final proof of the long-term safety of stimulant drugs for the treatment of ADHD. "More research and close monitoring of children taking these medications for extended periods of time is needed to fully evaluate the physical and behavioral effects of prolonged treatment with stimulants," noted Scott H. Kollins, Ph.D., director of the Duke ADHD Program, where the study was conducted and a co-author of the paper.

The current study included 63 children, ranging from 6-12 years of age, who met full criteria for ADHD but who had not previously been treated with stimulant medications. Children in the study were divided into two groups and treated by a board-certified child psychiatrist with either methylphenidate (commercially available as Ritalin LA and Concerta) or with mixed amphetamine salts (Adderall and Adderall XR). Blood samples were taken before the medication was started to establish baseline values for the cytogenetic measures that were analyzed in the study, and a second sample was collected after three months of continuous treatment. Forty-seven children completed the full three-month treatment schedule.

The researchers found no significant differences between the two groups of children with regard to age, gender, race, body weight, height, or ADHD subtype. The groups also showed very similar ADHD symptom levels at initial screening and children in both groups responded equally well to the medication.

The researchers looked at three standard indicators of chromosomal damage: structural chromosomal aberrations (breaks in chromosomes), micronuclei (small nuclei consisting of chromosome fragments produced by breakage or whole chromosomes lost from the main nucleus after the cell divides), and sister chromatid exchanges (exchanges of genetic material between a pair of identical chromosomes). "We did not see any significant treatment-related increases in any of these three endpoints," said Donald R. Mattison, M.D., senior advisor to the director at NICHD. "These results add to a growing body of evidence that therapeutic levels of these medications do not damage chromosomes," he said.

The study was designed to determine the reproducibility of findings from a previously published paper that reported methylphenidate-induced chromosomal changes in children with ADHD. That paper raised concern for the medical community and parents, given that some of the changes have been associated with an increased risk of cancer. The current study was not able to replicate the findings from the previous study. The new JAACAP paper extends the literature by using a larger sample size than previous studies, investigating more than one commonly prescribed medication, and providing well-characterized results that can be generalized to other ADHD populations.

"One way scientists evaluate each other's work is by attempting to reproduce the original experiment or study," said Witt. "We designed a study with specific modifications to address issues raised with the original study. Thus, our results are based on a significantly larger number of children who were carefully evaluated using rigorous, accepted standards, which allowed us to produce high-confidence data at the end of our study."


Немного о нейрогенезе

Интересненько... Читаю http://www.scientificblogging.com/news_releases/neurogenesis_happens_throughout_life_and_new_neurons_improve_memory

Neurogenesis Happens Throughout Life And New Neurons Improve Memory
By News Staff | October 25th 2008 12:00 AM

The birth of new neurons (neurogenesis) does not end completely during development but continues throughout all life in two areas of the adult nervous system, i.e. subventricular zone and hippocampus. Recent research has shown that hippocampal neurogenesis is crucial for memory formation. These studies, however, have not yet clarified how the newborn neurons are integrated in the existing circuits and thus contribute to new memories formation and to the maintenance of old ones.

The team of researchers of CNR-LUMSA-EBRI at the European Centre for Brain Research, organization established in Rome with the key contribution of the Santa Lucia Foundation, has taken a step forward to understand the requirements of newborn neurons in the process of learning and memory. The neuroscientists coordinated by dr. Felice Tirone of the Institute of Neurobiology and Molecular Medicine (INMM) of CNR, in collaboration with prof. Vincenzo Cestari of the Institute for Neuroscience of CNR and the LUMSA University and with dr. Alberto Bacci of the European Brain Research Institute, have shown that a key factor for neurogenesis is represented by the speed of differentiation of progenitors (stem cells that give rise to neurons) in hippocampus. From such speed will in fact depend the success of the whole process. “New neurons must maturate according to a correct temporal sequence in order to become able to acquire new memories and retrieve the existing ones”, explains Tirone.

This study is based on a new experimental approach, that involves the generation of a mice line in which the differentiation of newborn neurons is accelerated without altering their number. This is obtained by the selective expression in neural progenitors of the hippocampus of PC3/Tis21, a gene specifically able to accelerate the differentiation of these and other types of neural progenitors.
“Compelling new neurons to rush ahead in their differentiation for a predefined time period, we have observed that a small number of neurons of 2-3 weeks of age is critical for learning,” continues the INMM-CNR researcher. “In fact, mice so treated are not only unable to learn new spatial information, but they are also unable to use previously acquired memories.”

“PC3/Tis21, of which we have previously observed an action against brain tumors in consequence of its ability to promote differentiation of neural progenitor cells, might indeed have other practical outcomes” continues Tirone “since it is activated by Nerve Growth Factor, a molecule whose deprivation appears to be an important component of Alzheimer’s disease. In fact hippocampus is one of the first brain regions damaged by Alzheimer’s disease, which is characterized mainly by temporal and spatial disorientation and by a memory deficit. We might gain some useful information also to understand the mechanisms underlying this disease.”

Thus, it is an open and relevant question in neuroscience the understanding of mechanisms and factors that control or influence adult neurogenesis, in the field of memory as these researches now indicate, but also of depression, which, as some researchers have suggested, might take place in consequence of a defective adult neurogenesis.

Article: Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cinà I, et al. (2008) The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory. PLoS Biol 6(10): e246


Допаминовые рецепторы и контоль веса.

Вот они какие - мои любимые... :))) Нашла инфу на http://www.scientificblogging.com/news_releases/dopamine_signaling_why_some_like_chocolate_milkshakes_too_much

Dopamine Signaling - Why Some Like Chocolate Milkshakes Too Much
Submitted by News Staff on 16 October 2008 - 2:00am. Neuroscience

Using brain imaging and chocolate milkshakes, scientists have found that women with weakened "reward circuitry" in their brains are at increased risk of weight gain over time and potential obesity. The risk increases even more for women who also have a gene associated with compromised dopamine signaling in the brain.

The results, drawn from two studies using functional magnetic resonance imaging (fMRI) at the University of Oregon's Lewis Center for Neuroimaging, appear in the Oct. 17 issue of the journal Science. The first-of-its-kind approach unveiled blunted activation in the brain's dorsal stratium when subjects were given milkshakes, which may reflect less-than-normal dopamine output.

"Although recent findings suggested that obese individuals may experience less pleasure when eating, and therefore eat more to compensate, this is the first prospective evidence for this relationship," said Eric Stice, lead author and senior researcher at the Oregon Research Institute (ORI) in Eugene. "The evidence of temporal precedence suggests it is a true vulnerability factor that predates obesity onset. In addition, the evidence that this relation is even stronger for individuals at genetic risk for compromised signaling in these brain regions points to an important biological factor that appears to increase risk for obesity onset."

Stice, who has a courtesy appointment in the UO psychology department, has studied eating disorders and obesity for 18 years. He was joined in the new research by ORI colleague Sonja T.P. Spoor, Cara Bohon, a UO doctoral student in clinical psychology, and Dana M. Small of the John B. Pierce Laboratory in New Haven, Conn., and the Yale University School of Medicine.

Dopamine is the primary neurotransmitter in the brain's reward pathways. Food intake is associated with dopamine release, while pleasure from eating correlates with the amount of dopamine release. Previous studies have suggested that obese individuals have fewer dopamine receptors in the brain and have to eat more than lean people to be satisfied.

Using fMRI, Stice's team measured the extent to which the dorsal striatum was activated in response to an individual's receipt of a taste of chocolate milkshake or a tasteless solution.

One study involved 43 female college students ranging in age from 18 to 22 with a mean body mass index (BMI) of 28.6. The second study looked at 33 adolescent girls, ages 14-18, with a mean BMI of 24.3. Most of the participants were tested for the presence of a genetic variation known as the Taq1A1 allele, which is linked to a lower number of dopamine D2 receptors.

Researchers tracked changes in BMI over a year. Results showed that participants with decreased striatal activation in response to receiving milkshake and those with the A1 allele were more likely to gain weight over time.

"I was quite excited by the study itself, as it is the first prospective study to utilize fMRI and genetic data to predict unhealthy weight gain," said Bohon, whose doctoral work is done on both the UO campus and the nearby ORI facility. "The findings suggest that certain biological factors may impact one's risk for weight gain, which is important in order to better understand how we can eventually intervene and prevent obesity."


Морфий больше не актулен!

Встречайте новооткрытый белочек! Прочитала на http://www.biologynews.net/archives/2008/10/08/cell_protein_suppresses_pain_8_times_more_effectively_than_morphine.html

More people suffer from pain than from heart disease, diabetes and cancer combined, but many of the drugs used to relieve suffering are not completely effective or have harmful side effects.
Now researchers at the University of North Carolina at Chapel Hill School of Medicine and the University of Helsinki have discovered a new therapeutic target for pain control, one that appears to be eight times more effective at suppressing pain than morphine.

The scientists pinpointed the identity and role of a particular protein that acts in pain-sensing neurons, or nerve cells, to convert the chemical messengers that cause pain into ones that suppress it.

"This protein has the potential to be a groundbreaking treatment for pain and has previously not been studied in pain-sensing neurons," said lead study author Mark J. Zylka, Ph.D., assistant professor of cell and molecular physiology at UNC. The results of the study will be published online in the journal Neuron, on Wednesday (Oct. 8) and in the print edition the following day.

The biological basis of pain is complex. To study the transmission of painful signals throughout the body, many researchers use "marker" proteins that label pain-sensing neurons. One such marker, FRAP (fluoride-resistant acid phosphatase), has been employed for this purpose for nearly 50 years, but the gene that codes for its production was never identified.

That is, until researchers at UNC found that FRAP is identical to PAP (prostatic acid phosphatase), a protein routinely used to diagnose prostate cancer whose levels increase in the blood of patients with metastatic prostate cancer.

Previous research hinted that FRAP and PAP may have a shared identity. To determine whether or not this was the case, Zylka teamed up with Dr. Pirkko Vihko, a professor from the University of Helsinki who had genetically engineered mice that were missing the gene for PAP. When Zylka and his colleagues studied tissues from these mutant mice, they were happy to see that FRAP activity was missing. This revealed that the two proteins were in fact identical.

Further, the mutant mice proved more sensitive than normal mice to inflammatory pain and neuropathic pain, two common forms of chronic pain in humans. These increased sensitivities diminished when researchers injected excess amounts of PAP into the spinal cords of the mutant mice.

"We were really blown away that a simple injection could have such a potent effect on pain," Zylka said. "Not only that, but it appeared to work much better than the commonly used drug morphine."

The new protein suppressed pain as effectively as morphine but for substantially longer. One dose of PAP lasted for up to three days, much longer than the five hours gained with a single dose of morphine.

The next question for the researchers was how PAP suppressed pain. It is already known that when pain-sensing neurons are stimulated, they release chemicals known as nucleotides, specifically adenosine triphosphate (ATP). This in turn sets off the events that invoke a painful sensation. But if ATP degrades to adenosine, that inhibits the neurons that transmit pain signals, thus relieving pain. Through a series of experiments, the UNC researchers showed that PAP removes the phosphate group, generating adenosine. Their study is the first to identify and characterize the role of such a protein in pain-sensing neurons.

Zylka and his colleagues are now searching for additional proteins that degrade nucleotides in these neurons. They are also working to develop small molecules that interact with PAP to enhance or mimic its activity.

"It is entirely possible that PAP itself could be used as a treatment for pain, through an injection just like morphine," Zylka said. "But we would like to modify it to be taken in pill form. By taking this field in a new direction, we are encouraged and hopeful that we will be able to devise new treatments for pain."

Source : University of North Carolina School of Medicine


Культуры клеток в 22х измерениях скоро станут реальностью! :)

Какая прелесть! Это ведь именно то, что нужно сейчас нашим культуральщикам! Трёхмерная культура клеток!!! Это, конечно, не 22 и даже не 11 измерений, но нет ничего невозможного... Информация с http://www.biology-blog.com/blogs/permalinks/9-2008/reversible-3-d-cell-culture-gel-invented.html
Reversible 3-D cell culture gel invented

Reversible 3-D cell culture gel invented
Singapore's Institute of Bioengineering and Nanotechnology (IBN), which celebrates its fifth anniversary this year, has invented a unique user-friendly gel that can liquefy on demand, with the potential to revolutionize three-dimensional (3D) cell culture for medical research.

As reported in Nature Nanotechnology (Y.S. Pek, A. C. A. Wan, A. Shekaran, L. Zhuo and J. Y. Ying, "A Thixotropic Nanocomposite Gel for Three-Dimensional Cell Culture"), IBN's novel gel media has the unique ability to liquefy when it is subjected to a moderate shear force and rapidly resolidifies into a gel within one minute upon removal of the force. This phenomenon of reverting between a gel and a liquid state is known as thixotropy.

IBN's thixotropic gel is synthesized from a nanocomposite of silica and polyethylene glycol (PEG) under room temperature, without special storage conditions. This novel material facilitates the safe and convenient culture of cells in 3D since cells can be easily added to the gel matrix without any chemical processes.

As per IBN Executive Director Jackie Y. Ying, Ph.D., "Cell culture is conventionally performed on a flat surface such as glass slides. It is an essential process in biological and medical research, and is widely used to process cells, synthesize biologics and develop therapys for a large variety of diseases.

"Cell culture within a 3D matrix would better mimic the actual conditions in the body as in comparison to the conventional 2D cell culture on flat surfaces. 3D cell culture also promises the development of better cell assays for drug screening," Dr. Ying added.

Another key feature of IBN's gel is the ease with which scientists can transfer the cultured cells from the matrix by pipetting the mandatory amount from the liquefied gel.

Unlike conventional cell culture, trypsin is not mandatory to detach the cultured cells from the solid media. As trypsin is an enzyme that is known to damage cells, particularly in stem cell.

cultures, the long-term quality and viability of cells cultured using IBN's thixotropic gel would improve substantially without the exposure to this enzyme.

Scientists are also able to control the gel's stiffness, thus facilitating the differentiation of stem cells into specific cell types.

"Ways to control stem cell differentiation are important as stem cells can be differentiated into various cell types. Our gel can provide a novel method of studying stem cell differentiation, as well as an effective new means of introducing biological signals to cells to investigate their effect in 3D cultures," said Shona Pek, IBN Research Officer.

Andrew Wan, Ph.D., IBN Team Leader and Principal Research Scientist, added, "Another interesting property of the gel is its ability to support the extracellular matrix (ECM) secretions of cells. Gel stiffness is modulated by ECM secretions, and can be used to study ECM production by cells responding to drug therapys or disease conditions.

"The thixotropic gel may then provide new insights for basic research and drug development," Dr. Wan added.

Posted by: Janet http://www.a-star.edu.sg/astar/index.jsp


Жир жиру рознь!

Жировые клетки людей с лишним весом отличаются от таковых у стройных товарищей. Об этом - статья на http://www.scientificblogging.com/news_releases/fat_in_fat_people_different_than_fat_in_thin_people

Fat In Fat People Different Than Fat In Thin People
Submitted by News Staff on 27 August 2008 - 12:30am. Microbiology

Not all fat is created equal, it seems. A Temple University study finds fat in obese patients is "sick" when compared to fat in lean patients.

Why 'sick? When our bodies don't work properly, we say we're sick. The study in the September issue of Diabetes finds that the same could be said for fat tissue found in obese patients. The cells in their fat tissue aren't working properly and as a result, are sicker than cells found in lean patients' fat tissue.

Lead author Guenther Boden, M.D. theorizes that "sick fat" could more fully explain the link between obesity and higher risk of diabetes, heart disease and stroke.

Researchers from the departments of endocrinology, biochemistry and surgery at the Temple University School of Medicine took fat biopsies from the upper thighs of six lean and six obese patients and found significant differences at the cellular level.

"The fat cells we found in our obese patients were deficient in several areas," said Boden, Laura H. Carnell Professor of Medicine and chief of endocrinology. "They showed significant stress on the endoplasmic reticulum, and the tissue itself was more inflamed than in our lean patients."

Endoplasmic reticulum (ER) is found in every cell and helps synthesize proteins and monitor how they're folded. The stress that Boden describes causes the ER in fat cells to produce several proteins that ultimately lead to insulin resistance, which has been found to play a major role in the development and progression of obesity-related conditions.

The National Institutes of Health recently reported that each time a body mass index (BMI) over 25 is raised by one point, the risk for diabetes increases 25 percent and the risk for heart disease increases 10 percent.

Reducing weight can help reduce stress on the ER, which can lower the risk of insulin resistance and the resulting conditions. Currently Boden and his team are looking at whether free fatty acids are a potential cause for this ER stress.

Other authors on this study include Xunbao Duan, Carol Homko, Ezequiel J. Molina, WeiWei Song, Oscar Perez, Peter Cheung and Salim Merali of Temple University School of Medicine. Funding for this research was provided by grants from the National Institutes of Heath, the Groff Foundation and a mentor-based training grant from the American Diabetes Association.

Новые лекарства от шизофрении!

Ангельская пыль может быть очень полезна... для исследований. Прочитала на http://blog.wired.com/wiredscience/2008/09/four-experiment.html
Angel Dust Inspired a New Schizophrenia Drug
By Aaron Rowe EmailSeptember 15, 2008 | 11:32:36 PMCategories: Big Pharma, Chem Lab, Chemistry, Medicinal Chemistry, Psychiatry


When scientists learned that PCP, also known as angel dust, can cause every single symptom of schizophrenia, they wondered if chemicals that have the opposite effect could fight mental disorders. That insight led to them to discover a new class of antipsychotic medications.

To understand how the recreational drug plays tricks on the mind, neuroscientists gave it to lab rats. Those researchers could counteract the strange behavior of their furry assistants by stimulating brain proteins called glutamate receptors. Big drug companies, including Eli Lilly, took note of that discovery and started searching for molecules that can push the same psychological buttons in humans.

In the Sept. 15 issue of Chemical and Engineering News, Carmen Drahl told that story, along with the tales of three other experimental medications that could turn the tide against schizophrenia. Each compound operates in a completely different way, and all of them have been tested on human volunteers.

That is really big news because doctors have been stuck using the same class of pills -- dopamine blockers -- since the 1950's.

Drahl got the scoop on the new treatments during a special seminar about schizophrenia, which took place last month during the American Chemical Society meeting in Philadelphia.

LY404039 was discovered by Eli Lilly and works by activating glutamate receptors. It is furthest along in the approval process. Unlike other schizophrenia drugs, it does not cause excessive weight gain.
DCCCyB was developed by Merck, and it does the job by blocking glycine transporters
PF-2545920 was tested by Pfizer, and it gums up a phosphodiesterase enzyme.
TC-5619 was invented at Targacept and it excites nicotine receptors with far more precision than the finest cigarettes. Schizophrenics tend to medicate themselves by smoking, and new drugs may offer them a similar kind of relief without the serious health risks that come from tobacco products.

If these drugs are approved by the FDA, the social implications could be profound: A great deal of homelessness is caused by psychological problems. Perhaps some of these new substances will allow people with serious mental illness to become functional and live somewhat normal lives.


68 ключевых молекул!

68 - ЭТО ПОЧТИ 69 :) Читаем!


68 Molecules May Hold the Key to Understanding Disease
Submitted by News Staff on 4 September 2008 - 12:00am. Microbiology

Why is it that the origins of many serious diseases remain a mystery? In considering that question, a scientist at the University of California, San Diego School of Medicine has come up with a unified molecular view of the indivisible unit of life, the cell, which may provide an answer.

Reviewing findings from multiple disciplines, Jamey Marth, Ph.D., UC San Diego Professor of Cellular and Molecular Medicine and Investigator with the Howard Hughes Medical Institute, realized that only 68 molecular building blocks are used to construct these four fundamental components of cells: the nucleic acids (DNA and RNA), proteins, glycans and lipids. His work, which illustrates the primary composition of all cells, is published in the September issue of Nature Cell Biology.

Like the periodic table of elements, first published in 1869 by Russian chemist Dmitri Mendeleev, is to chemistry, Marth’s visual metaphor offers a new framework for biologists.

Illustration of "molecular building blocks."

This new illustration defines the basic molecular building blocks of life and currently includes 32 glycans (sugar linkages found throughout the cell) and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA.

“These 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell,” said Marth. “And two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may now hold the keys to uncovering the origins of many grievous diseases that continue to evade understanding.”

Currently, the vast majority of medical research looks to the human genome and proteome for answers, but those answers remain elusive, and perhaps for good reason.

“We have now found instances where the pathogenesis of widespread and chronic diseases can be attributed to a change in the glycome, for example, in the absence of definable changes in the genome or proteome,” Marth said, adding that, as biomedical researchers, “we need to begin to cultivate the integration of disciplines in a holistic and rigorous way in order to perceive and most effectively manipulate the biological mechanisms of health and disease.”

“What is important is that no one has composed it and laid it out so clearly before,” said Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine and founder and co-director of the Glycobiology Research and Training Center at UC San Diego School of Medicine, and chief editor of the major textbook in the field, The Essentials of Glycobiology. “Glycobiology, for example, is a relatively new field of study in which researchers at UC San Diego have much expertise, and Dr. Marth’s work further illustrates the importance of these glycan molecules.”

Marth believes that biology should become more integrative both in academic and research settings. “I’m one who believes that we don’t need to sacrifice breadth of knowledge in order to acquire depth of understanding.”


Начало всех начал :))) Стволовая клетка-мама.

Мама крови. Вот она! Наконец, эмбриональная предшественница клеток крови - чётко определена. Информация с http://www.scientificblogging.com/news_releases/discovery_mother_of_all_blood_stem_cells
Discovery - 'Mother' Of All Blood Stem Cells

Submitted by News Staff on 29 August 2008 - 1:00am. Developmental
Johns Hopkins researchers say they have discovered the earliest form of human blood stem cells and deciphered the mechanism by which these embryonic stem cells replicate and grow. They also found a surprising biological marker that pinpoints these stem cells, which serve as the progenitors for red blood cells and lymphocytes.

The research reported today used federally approved embryonic stem cell lines.

The biochemical marker, angiotensin-converting enzyme (ACE), is well known for its role in the regulation of blood pressure, blood vessel growth, and inflammation. ACE inhibitors are already widely used to treat hypertension and congestive heart failure, and the findings are, the researchers say, likely to hold promise for developing new treatments for heart diseases, anemias, leukemia and other blood cancers, and autoimmune diseases because they show for the first time that ACE plays a fundamental role in the very early growth and development of human blood cells.

"We figured out how to get the 'mother' of all blood stem cells with the right culture conditions," says Elias Zambidis, M.D., Ph.D., of the Institute of Cell Engineering at the Johns Hopkins University School of Medicine and the Division of Pediatric Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

"There is real hope that in the future we can grow billions of blood cells at will to treat blood-related disorders, and just as critically if not more so, we've got ACE as a 'new' old marker to guide our work," Zambidis adds.

Researchers did not expect ACE to have a role in blood stem cells, he notes, "but were very pleasantly surprised to discover it as a beacon for finding the earliest blood stem cells known, as well as new ways to find and manipulate this marker to make them grow."

The team's findings, published Aug. 26 in the online edition of the journal Blood, explain that these earliest stem cells marked by ACE, called hemangioblasts, first arise normally in the developing human fetus, when a woman is three or four weeks pregnant. Hemangioblasts can now be derived in unlimited supply experimentally from cultured human embryonic stem cells, which are the origin of all cell types in the body. These hemangioblasts go on to become either blood cells or endothelial cells, which form the inner lining of the heart, veins and arteries, and lymph vessels.

The research grew out of Zambidis' interest in understanding the complex biological processes of blood development and the transformation of embryonic stem cells into the various types of cells that make up the human body.

Hemangioblasts make the body's earliest form of blood in the fetal yolk sac, which nourishes a fertilized egg, and later in the fetal liver and bone marrow. However, because human embryonic cells disappear early in gestation, their role in the early production of blood could not, to the researchers' knowledge, be studied in humans because scientists had no way to identify these human progenitor blood stems cells to follow their development. The scientists suspected they existed in humans, however, because they have been found in mice and zebra fish.

To find the blood stem cell, Zambidis' team grew human embryonic stem cells in culture and fed them growth factors over 20 days. Each time the cell colonies expanded, the researchers sampled individual cells, searching for ones capable of making both endothelial and blood cells, the hallmark of hemangioblasts.

They plucked the newly discovered hemangioblasts from culture dishes, grew them in conditions that Zambidis and his team developed to speed replication, and tested cells for their ability to make endothelial and blood cells. Cells capable of making endothelial cells and all the elements of blood (platelets, and white and red cells) were specifically marked with ACE on their outer surface.

The researchers found not only that ACE was a marker for hemangioblasts, but turning off the enzyme also helps guide the cells' replication and maturation into either blood or endothelial cells. By treating the hemangioblasts with losartan, an ACE pathway blocking agent routinely used to treat high blood pressure, dramatically increased the rate of blood cell production.

The next step, Zambidis adds, is to test this research in animal models and show that "we can make lots and lots of blood cells from human stem cells for transfusions, regenerate new vascular trees for heart diseases, as well as create test tube factories for making transplantable blood cells that treat diseases. We are very far from treatment," Zambidis cautions, "but this is a big step."

If the new technique of mass producing progenitor blood cells is eventually proven to work in humans, it would allow patients getting bone marrow transplants to have their own stem cells creating the blood they need, significantly reducing rejection risk.

The research reported today used federally approved embryonic stem cell lines, but other related research by the team comes from nonapproved lines. The study was supported by grants from the National Institutes of Health and the Maryland Stem Cell Research Fund.

Загадка клеточного деления - разгадана!

Ну разве не радость? Прочитала на http://www.scientificblogging.com/news_releases/50_year_cell_division_mystery_solved_say_researchers

Researchers from Oregon State University say they have resolved a controversy that cellular biologists have been arguing over for nearly 50 years, with findings that may aid research on everything from birth defects and genetic diseases to the most classic "cell division" issue of them all – cancer.

The exact mechanism that controls how chromosomes in a cell replicate and then divide into two cells, a process fundamental to life, has never been completely pinned down, researchers say. You can find the basics in any high school biology textbook, but the devil is in the details.

"Researchers have been debating cell cleavage ever since the cell was discovered, with two basic models proposed around 1960 of how a contractile ring pulls together and allows a single cell to split into two," said Dahong Zhang, an OSU associate professor of zoology. "Part of the problem is that until now there was no decisive way to manipulate the cytoskeleton, such as the microtubules and filaments that are involved, and see what was happening as it occurred."

To address that, Zhang developed some new instrumentation that uses "microneedles" and state-of-the-art imaging techniques which allow direct manipulation of the cytoskeleton, while capturing the results of contractile ring formation. The system has not only solved this decades-old riddle, but "the technology is a very powerful new approach," Zhang said, that should find applications in other cell biology research issues.

It has been known for some time, scientists say, that a "contractile ring," which is composed of some of the same fibers used in muscle contraction, move into the correct position, pull and split a cell in two after its chromosomes have been separated. This is distribution of genetic materials at its most basic level, and it has to be done at exactly the right place and time. When the process breaks down, cancer and other serious medical or genetic issues can be a result.

But if you think of the cell as a sphere, what was less clear was whether the "equator" contracted or the "poles" relaxed to allow this contraction and division. Two distinct theories were formed, called polar relaxation and equatorial stimulation, to explain this aspect of cell division – and some scientists have spent much of their careers arguing for one side or the other.

Turns out, Zhang said, that both sides were correct. Nature and evolution have actually created a basic way for a cell to divide with a backup system that can work if the other approach fails.

"Accurate cell division is one of the most critical of all life functions, and there clearly is an evolutionary value to having redundancy, a system able to do it two different ways," Zhang said. "It makes perfect sense when you think about it. The findings speak plainly for themselves, and there should no longer be a question over which model is right."

By labeling cells and moving microtubules around while still being able to see them and their impact on microfilaments, OSU researchers were able to selectively inhibit one mechanism of cell division or the other. They discovered that in the same cell type, it could divide either by polar relaxation or equatorial stimulation – the two mechanisms are not mutually exclusive.

The findings, Zhang said, add significantly to the basic understanding of cell biology, and should be of special interest to cancer researchers. Cancer is essentially the loss of normal control over cell division and migration. In fact, a compound used in Zhang's laboratory to inhibit cell division while they studied it was taxol – a commonly used cancer drug.

Accurate and effective cell division, researchers say, is also key to the understanding of some genetic diseases, miscarriages, birth defects and other issues.

The studies were supported by the National Science Foundation and the American Heart Association.


ДНКовые катапульты!

Эозинофилы "выплёвывают" свою нуклеиновую кислоту, чтоб победить инфекцию. Об этом пишут на
Contact: Gerald J. Gleich, M.D.
University of Utah Health Sciences

White blood cell uses DNA 'catapult' to fight infection
Eosiniphils help prevent uncontrolled bacterial invasion
SALT LAKE CITY – U.S. and Swiss scientists have made a breakthrough in understanding how a type of white blood cell called the eosinophil may help the body to fight bacterial infections in the digestive tract, according to research published online this week in Nature Medicine.

Hans-Uwe Simon, from the University of Bern, Switzerland, Gerald J.Gleich, M.D., from the University of Utah School of Medicine, and their colleagues discovered that bacteria can activate eosinophils to release mitochondrial DNA in a catapult-like fashion to create a net that captures and kills bacteria.

"This is a fascinating finding," says Gleich, professor of dermatology and internal medicine at the University of Utah and a co-author of the study. "The DNA is released out of the cell in less than a second."

Eosiniphils, which comprise only 1 to 3 percent of human white blood cells, are known to be useful in the body's defense mechanisms against parasites. But their exact role in the immune system is not clear. Unlike other white blood cells, which are distributed throughout the body, eosinophils are found only in selected areas, including the digestive tract. Mitochondria – often referred to as the power plants of the cell – are components within cells that are thought to descend from ancient bacteria. Although most cellular DNA is contained in the nucleus, mitochondria have their own DNA.

Previous research has shown that eosinophils secrete toxic granule proteins during parasite infections and that these granule proteins kill bacteria. Simon, Gleich, and their colleagues found that when eosinophils are stimulated by infection, such as E. coli, they rapidly secrete mitochondrial DNA. This DNA binds to the granule proteins and forms a net that is able to trap and kill bacteria. The researchers also found higher levels of eosinophils were linked to improved survival and lower numbers of bacteria in the blood of mice with widespread bacterial infections.

The toxic proteins released by eosinophils are not always helpful to the body, however, and can damage nearby tissues. The inflammation in some types of asthma and Crohn's disease, a chronic inflammatory disease of the bowel, is attributed to eosinophils. In fact, Simon and his team first found evidence of these DNA-protein traps in tissue taken from the digestive tracts of people with Crohn's disease.

Earlier studies suggested another type of white blood cell – the neutrophil – also expels DNA and granule proteins to kill bacteria. However, this DNA comes from the nucleus and its release causes the neutrophil to die. The eosinophil is able to survive after expelling its mitochondrial DNA.

The researchers hope to learn more about how eosiniphils expel mitochondrial DNA. They speculate that the explosive mechanism might rely on stored energy, similar to the way plants release pollen into the air. "We don't know how eosinophils are capable of catapulting mitochondrial DNA so quickly," says Gleich.

Future investigation may focus on how this energy is generated and how this new knowledge can be applied to the treatment of bacterial infections and inflammatory diseases related to eosinophils.

Митохондриальная ДНК - новая информация.

Загадки митохондриальной ДНК - это нечто... Пишут о ней много, часто мнения очень противоречивы. Вот - немного новых данных, которые я читала на http://www.biologynews.net/archives/2008/08/12/large_reservoir_of_mitochondrial_dna_mutations_identified_in_humans.html:

Researchers at the University of Newcastle, England, and the Virginia Bioinformatics Institute at Virginia Tech in the United States have revealed a large reservoir of mitochondrial DNA mutations present in the general population. Clinical analysis of blood samples from almost 3,000 infants born in north Cumbria, England, showed that at least 1 in 200 individuals in the general public harbor mitochondrial DNA mutations that may lead to disease. The findings, which highlight the need to develop new approaches to prevent the transmission of mitochondrial diseases, were published in The American Journal of Human Genetics.

Mitochondria, the "engines" present in each cell that produce adenosine triphosphate, are passed from mother to offspring. Mutations in mitochondrial DNA inherited from the mother may cause mitochondrial diseases that include muscle weakness, diabetes, stroke, heart failure, or epilepsy. In almost all mitochondrial diseases caused by mutant mitochondrial DNA, the patient's cells will contain a mixture of mutant and normal mitochondrial DNA. The proportion of mutant mitochondrial DNA in most cases determines the severity of disease.

Previous estimates from epidemiological studies suggested that mitochondrial diseases affect as many as one person in 5,000. However, the incidence of new mitochondrial mutations and the prevalence of those carrying these mutations were never fully established due to limitations in the methods used. Most of the earlier estimates of the frequency of mitochondrial DNA mutations in the general population, for example, have depended on identification of clinically affected patients and subsequent retracing of inheritance on the maternal side of the family. This approach fails to detect the gradual accumulation of mutations in some members of the population, including those individuals who harbor mitochondrial DNA mutations but who otherwise do not show the symptoms of disease.

Dr. David Samuels, Assistant Professor at the Virginia Bioinformatics Institute and an author on this study, commented: "We know from many clinical studies of patients and their families that our cells can tolerate a rather large amount of mutant mitochondrial DNA with no significant loss of function. From that observation we have suspected that there may be a large number of people in the general population who carry pathogenic mitochondrial DNA mutations, but who are not obviously ill with a mitochondrial disease. This study gives us, for the first time, a measurement of the number of these carriers of pathogenic mitochondrial DNA mutations in the general population. One in every 200 individuals is a lot of people – around 1.5 million people in the United States alone. "

The scientists looked at 10 mitochondrial DNA mutations (arising from single nucleotide replacements) often found in patients with mitochondrial disease. By taking advantage of a high-throughput genotyping system that uses mass spectrometry measurements, the researchers were able to detect mutated mitochondrial DNA at high sensitivity. In each positive case, DNA cloning and sequencing were used to confirm the findings. By looking at differences in tissue samples from mother and child, the researchers were also able to estimate the rate at which new DNA mutations had arisen in the population. The incidence of new mutations was close to 100 for every 100, 000 live births.

Dr. Samuels commented: "These new clinical measurements have given direct evidence for the widespread incidence of pathogenic mitochondrial DNA mutations in the human population. These findings emphasize the pressing need to develop effective ways to interrupt the transmission of these mutations to the next generation."

Source : Virginia Tech


22 волшебных гена.

22 - моё любимое число. :) А стволовые клетки - одна из любимых тем. Данная статейка - объединяет эти позитивы. Судьба и "выбор ориентации" стволовых клеток - актуальнейшая область клеточной и молекулярной биологии. Поэтому - читайте, найденную на http://www.scientificblogging.com/news_releases/22_genes_that_control_embryonic_stem_cell_fate_identified заметку:

22 Genes That Control Embryonic Stem Cell Fate Identified

Submitted by News Staff on 10 July 2008 - 12:00am. Developmental
Scientists have identified about two dozen genes that control embryonic stem cell fate. The genes may either prod or restrain stem cells from drifting into a kind of limbo, they suspect. The limbo lies between the embryonic stage and fully differentiated, or specialized, cells, such as bone, muscle or fat.

By knowing the genes and proteins that control a cell's progress toward the differentiated form, researchers may be able to accelerate the process – a potential boon for the use of stem cells in therapy or the study of some degenerative diseases, the scientists say.

Their finding comes from the first large-scale search for genes crucial to embryonic stem cells. The research was carried out by a team at the University of California, San Francisco and is reported in a paper in the July 11, 2008 issue of Cell.

"The genes we identified are necessary for embryonic stem cells to maintain a memory of who they are," says Barbara Panning, PhD, associate professor of biochemistry and biophysics at UCSF, and senior author on the paper. "Without them the cell doesn't know whether it should remain a stem cell or differentiate into a specialized cell."

The scientists used a powerful technique known as RNA interference, or RNAi, to screen more than 1,000 genes for their role in mouse embryonic stem cells. The technique allows researchers to "knock down" individual genes, reducing their abundance in order to determine the gene's normal role.

The research focused on proteins that help package DNA. In the nucleus, DNA normally wraps around protein complexes called nucleosomes, forming a structure known as chromatin. This is what makes up chromosomes.

They found 22 proteins, each of which is essential for embryonic stem cells to maintain their consistent shape, growth properties, and pattern of gene expression.

Most of the genes code for multi-protein complexes that physically rearrange, or "remodel" nucleosomes, changing the likelihood that the underlying genes will be expressed to make proteins.

The main player they identified is a 17-protein complex called Tip60-p400. This complex is necessary for the cellular memory that maintains embryonic stem cell identity, Panning explains. Without it, the embryonic stem cells turned into a different cell type, which had some features of a stem cell but many features of a differentiated cell.

The scientists believe that Tip60-p400 is necessary for embryonic stem cells to correctly read the signals that determine cell type. These findings are not only important for understanding cellular memory in embryonic stem cells, but will also likely be relevant to other cell types, they say.

Inactivation of other genes disrupted embryonic stem cell proliferation. These genes were already known to have only slight influence on viability of mature cells in the body. This suggests that embryonic stem cells are "uniquely sensitive to certain perturbations of chromatin structure," the scientists report.

If other types of stem cells are also found to be sensitive to these chromatin perturbations, this could lead to novel cancer therapies in the future, Panning says.

Lead author on the paper is Thomas G. Fazzio, PhD, a postdoctoral fellow. Co-author is Jason T. Huff, BSc, a graduate student. Both are in Panning's lab.

The research is supported by the National Institutes of Health.