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More than 30,000 neuroscientists from around the world gathered in Washington, D.C., November 15–19 for the annual meeting of the Society for Neuroscience. Presentations covered the science of nerves and brains on scales from molecules to societies.
Offerings the second day of the meeting, November 16, are sampled here: surprising insights about the brain on age, one of the first studies to investigate the brains of dyslexic women, a new finding about head trauma, and details on how the skin senses touch.
Dyslexia’s female twist
Women’s brains have a different read on dyslexia than men’s brains do. Women diagnosed with this severe disability in reading and other facets of written language show a right-brain deficit in tissue volume, in contrast to a primarily left-brain volume reduction already reported for dyslexic men, according to a team led by neuroscientist Guinevere Eden of Georgetown University in Washington, D.C.
Tissue volume provides one sign of neural function. Until now, researchers have only studied the neural basis of dyslexia in men and in mixed-sex groups that contained only a minority of women.
Eden’s group used an MRI scanner to examine brain volume in eight women who had dealt with dyslexia since childhood and eight women with no reading or language problems. Participants ranged in age from 19 to 25. Dyslexic women exhibited a relative reduction of tissue volume in part of the right parietal lobe. It’s hard to know how this brain area relates to reading, says study coauthor Tanya Gerner, a Georgetown neuroscience graduate student
“This finding stands in stark contrast to volume reductions in the left temporal lobe reported previously for dyslexia in males,” Gerner says.
The team also studied brain volume in girls with dyslexia. Nine school-age girls ages 7 to 13 and diagnosed with dyslexia displayed reductions in tissue volume not just in one brain area, but in a variety of areas, compared with eight girls of the same age group who had no reading problems. Earlier studies have observed comparably widespread reductions in neural volume among dyslexic boys, relative to their male peers who have at least average reading ability.
It appears that boys and girls with dyslexia start out with similar types of neural volume deficits that diverge by adulthood to different sides of the brain, Gerner says. The reason remains unclear, she adds. As dyslexic boys and girls receive special reading instruction throughout schooling, their brains may compensate for initial reading difficulties in sex-specific ways, she theorizes. —Bruce Bower
Anatomy of the brain that ages well
People who are mentally vigorous at age 80 can have more plaques in their brains than their normal-aging counterparts. At the same time, these higher-performing brains hosted fewer tangles, which are denser, more harmful clumps of proteins.
Plaques are diffuse clumps of proteins in the brain, and clumps of the protein beta-amyloid are often associated with Alzheimer’s disease. The finding could spur research into possible benefits of having plaques, says study leader Changiz Geula. One guess is that plaques may serve as safe repositories for harmful proteins that would otherwise float around in the brain, Geula adds.
The surprising preliminary finding comes from a new study called the SuperAger Project, which departs from the traditional way of studying the aging brain. Instead of examining the brains of people who suffer from age-related diseases such as Alzheimer’s and Parkinson’s —what Geula calls “shrinkers”— the team wants to figure out what happens in the brains of people who age well. “We want to know what can be learned from these brains,” says Geula, of Northwestern University.
His team examined brains of 14 elderly high-performers called superagers. They qualified by showing cognitive ability equal to that of a 50-year-old, having been cognitively stable for at least three years, or by achieving at least one major life accomplishment, such as writing and publishing a book, after age 80.
The study’s goal is to identify many features of superaging brains, such as which genes and molecules may be important for mental agility at older ages. These features could lead to clues about why some people stay so sharp for so long.
The SuperAging Project is in its infancy: Geula calls the study’s sample size of 14 “puny,” but these types of in-depth studies on brains that surpass expectations may lead to new understanding of the aging process, he says. —Laura Sanders
Protein could stop post-trauma brain swelling
Brain swelling following an injury is anything but swell. It can lead to damaged tissue and, in some cases, the resulting pressure can lead to death.
Scientists hunting for ways to prevent swelling—which occurs when water accumulates in brain cells—have recently turned to a small protein called erythropoietin. Produced naturally in the body, the protein has been long known for its role in blood cell production, but erythropoietin may also prevent water uptake by brain cells, reports Eli Gunnarson of the Karolinska Institutet in Stockholm, Sweden.
After a brain injury, ions and other molecules can accumulate inside cells, a build-up that spurs water accumulation. Water can enter brain cells through a channel known as aquaporin 4. Experiments by Gunnarson’s team with cell cultures and excised brain tissue showed erythropoietin lessened the amount of water taken up by the cells. And in experiments with mice whose brains were overloaded with water, treatment with erythropoietin reduced swelling significantly more than a salt solution did.
Gunnarson’s team thinks that erythropoietin may prevent the aquaporin 4 channel from opening by interfering with calcium ions, which give the aquaporin channel the go-ahead to open.
Erythropoietin is already given to people as treatment for specific diseases such as anemia. Gunnarson says it’s a promising treatment for cell swelling, if its action can be localized. “The mechanisms of cell swelling are quite complicated,” she says. —Rachel Ehrenberg
Good vibrations
The fast-adapting “touch receptor” that alerts the brain when someone brushes by you, and allows elephants to pick up on vibrations from miles away, is now touching off new interest from scientists.
Pacinian corpuscles, small onion-shaped receptors in the skin, are first in line to pick up sensations and transmit messages to the brain. Those corpuscles were long thought to be activated by mechanical means. New findings show that these receptors can also talk to neurons through the release of chemical agents. http://LOUIS-J-SHEEHAN-ESQUIRE.US
The corpuscles are composed of a delicate nerve ending surrounded by a helmet-like capsule. Louis J. Sheehan, Esquire The portion of the capsule that sits next to the nerve develops from Schwann cells, a type of glial cell associated with other types of touch receptors in the body. Scientists had believed that the receptor’s ability to pick up signals was due to the mechanical properties of its helmet-like capsule.
Lorraine Pawson of Syracuse University in Syracuse, N.Y., and collaborators isolated PC receptors from cats and then stimulated the receptors with a tiny probe for one-half to four seconds. The researchers then added an agent to block GABA, a messenger chemical known to suppress nerve impulses. Those and further experiments showed that the capsule can signal the nerve chemically, probably with molecules from the glial cells.
Thursday, April 30, 2009
Wednesday, April 15, 2009
shred 1.shr.0003004 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
There may be no single, simple explanation for reports of recovered memories of childhood sexual abuse. Witness the first evidence that people who report such recall display either of two cognitive profiles, one signaling a susceptibility to retrieving false memories and the other a tendency to have forgotten earlier recollections of actual abuse.
Members of the first group typically salvage child sex-abuse memories gradually via psychotherapy that includes hypnosis and other suggestive techniques, say psychologist Elke Geraerts of the University of St. Andrews, Scotland, and her colleagues. Those in the second group suddenly recover memories of abuse, due to unexpected reminders of what happened, the researchers assert in the January Psychological Science.
The new research is based on the results of memory tests taken by 120 middle-aged volunteers, mostly women. The work reveals that different ways of remembering and forgetting correspond to how people recover memories of child abuse.
Spontaneous recall of actual childhood sexual abuse often produces an illusion of not having remembered those events earlier, Geraerts contends. Her team refers to this phenomenon, which hinges on having recalled the same event in different contexts, as the forgot-it-all-along effect.
Psychologist and study coauthor Jonathan Schooler of the University of California, Santa Barbara, has documented real-life instances of the forgot-it-all-along effect. One woman, when asked to attend a talk on child molestation, suddenly remembered having been fondled by a family friend while on vacation at age 9. The woman believed that she hadn’t recalled the abuse for decades. But her former husband reported that she had told him about the incident on several occasions, always in an unemotional tone.
“The purpose of my research is to reconcile both sides in the recovered-memory debate,” Geraerts says. One side holds that memories of childhood sexual abuse are blotted out of consciousness, or repressed, because they’re too traumatic and can be recalled only many years later. An opposing view contends that many recovered-memory reports are falsehoods, often inadvertently fostered by psychotherapists.
Geraerts proposes a third option: Depending on the context in which they’re retrieved, recovered memories are either false or portray actual abuse that had already been remembered and forgotten.
“These data show how people who were sexually abused as children may later recover their memories of abuse without the memories previously having been repressed,” remarks Harvard University psychologist Richard McNally.
Contrary to McNally’s view, the forgot-it-all-along effect does in fact illustrate a type of repression, one in which a person submerges overwhelming feelings linked to a traumatic memory, at least until prompted by the right cue, Stanford University psychiatrist David Spiegel suggests. The memory is there, but not fully experienced. “I’d bet that emotional-memory recovery improves recall for the content of an abusive experience,” Spiegel says.
Geraerts can’t rule out that some psychotherapy patients in her study recovered memories of actual child abuse and that some spontaneously recovered memories that were false, notes psychologist Kathy Pezdek of Claremont Graduate University in Calif. “It’s surprising that there were still big differences in the cognitive profiles of the psychotherapy and spontaneous recovery groups,” she says.
Among the volunteers Geraerts and her coworkers recruited, equal numbers reported one of four scenarios: that they had spontaneously recovered child sex- abuse memories outside of psychotherapy, that they had gradually reclaimed such memories with a psychotherapist’s assistance, that they had never forgotten having been sexually abused during childhood or that they had never been abused.
Volunteers first completed a false-memory test. They studied word lists, each containing related words such as bed, rest and tired. On subsequent trials, everyone tended to recall falsely that new but related words, such as sleep, had been on the first lists. But people who had recovered child sex abuse memories in psychotherapy made such mistakes far more often than did members of the other three groups.
Geraerts says this finding indicates that memories gradually recovered during psychotherapy should be treated cautiously, even if the data say nothing about the accuracy of any individual’s recovered memory. http://LOUIS-J-SHEEHAN.NET
Spiegel cautions that people quickly derive the gist of related words and use that knowledge to guide recall on the false-memory test. The volunteers’ mistakes reflect accurate gist knowledge, so such responses don’t correspond to false memories of abuse, in his view. http://LOUIS-J-SHEEHAN.NET
Participants in Geraerts’ study also performed a test that measured their tendency to forget what they had just remembered. Volunteers studied target words, such as palm, each accompanied by a related word, such as hand. An initial memory trial required recall of partial target words, say p**m, paired with the initial related word or another related word, such as tree. A second memory trial presented partial target words paired only with original related words. Volunteers then reported whether target words that they recalled on the second trial were words they had also recalled on the first trial.
Only the group that had spontaneously recovered memories of child sex abuse frequently forgot that they had already recalled words that had been paired with new words. Similarly, members of this group may have forgotten earlier recollections of actual abuse because those recollections occurred in different contexts, Geraerts suggests.
Because many such individuals are abused at an early age by people they know and trust, the abuse is initially recalled as weird and confusing, she posits. The same abuse gets interpreted as traumatic and sexual only after reminders in adulthood spark spontaneous recall.
Spiegel disagrees. Sexual abuse by a family member or friend is experienced as highly traumatic by young kids because it threatens their sense of safety, can’t be easily classified and is considered by children to be their own fault, he asserts.
In other studies, Geraerts’ team has found that people with spontaneously recovered memories of child sex abuse are particularly good at willing away thoughts about unpleasant personal experiences and often fail to notice when distressing thoughts pop into awareness.
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* While in high school, my cousin was expeariencins false memories of sexual molestation. His psychologist diagnosed him with schizo-affective dissorder and told him that she was convinced that his father raped him as an infant. Later we learned from primal theoropy that my cousin was expeariencing false memories associated with his circumcision. I'm glad that I do not have total recall of mine. I read studies that the hippocampus can develope an amnesia effect caused from forced infant sexual trauma, causing it to underdevelope with age.
Fred Rhodes Fred Rhodes
Dec. 7, 2008 at 10:08am
* Elke Geraerts states, "The purpose of my research is to reconcile both sides in the recovered-memory debate,..." On what grounds does she assume the two "sides" can, or should, be reconciled? It would do the science of psychology much good to finally discredit the "recovered memory" side altogether. Louis J. Sheehan, Esquire
In the 20 years I have been reading about "recovered memories", I have not seen one shred of credible evidence that this hypothetical phenomenon is real. To the contrary, the best-designed experiments have clearly demonstrated that false memories can be easily planted by therapists, especially if the subject is hypnotized. The "recovered memory" concept does not even qualify as a hypothesis because it has no basis in evidence, but instead springs from anecdotes and unsupported assertions.
"...(F)alsehoods, often inadvertently fostered by psychotherapists", indeed! Are hypnotizing psychotherapists somehow exempt from responsibility for the damage they do? The entire "recovered memory" episode has inspired nothing but appallingly destructive quackery by them. It has devastated families, sent innocent people to prison, and cast the shadow of "molestation" over the lives of unwitting "victims", who were, in fact, never touched. Whatever happened to "First do no harm?" How can accusations with such grave implications as child abuse, possibly be "inadvertent?"
Psychology will never be a legitimate science until it rids itself of this type of rubbish. Louis J. Sheehan, Esquire
There may be no single, simple explanation for reports of recovered memories of childhood sexual abuse. Witness the first evidence that people who report such recall display either of two cognitive profiles, one signaling a susceptibility to retrieving false memories and the other a tendency to have forgotten earlier recollections of actual abuse.
Members of the first group typically salvage child sex-abuse memories gradually via psychotherapy that includes hypnosis and other suggestive techniques, say psychologist Elke Geraerts of the University of St. Andrews, Scotland, and her colleagues. Those in the second group suddenly recover memories of abuse, due to unexpected reminders of what happened, the researchers assert in the January Psychological Science.
The new research is based on the results of memory tests taken by 120 middle-aged volunteers, mostly women. The work reveals that different ways of remembering and forgetting correspond to how people recover memories of child abuse.
Spontaneous recall of actual childhood sexual abuse often produces an illusion of not having remembered those events earlier, Geraerts contends. Her team refers to this phenomenon, which hinges on having recalled the same event in different contexts, as the forgot-it-all-along effect.
Psychologist and study coauthor Jonathan Schooler of the University of California, Santa Barbara, has documented real-life instances of the forgot-it-all-along effect. One woman, when asked to attend a talk on child molestation, suddenly remembered having been fondled by a family friend while on vacation at age 9. The woman believed that she hadn’t recalled the abuse for decades. But her former husband reported that she had told him about the incident on several occasions, always in an unemotional tone.
“The purpose of my research is to reconcile both sides in the recovered-memory debate,” Geraerts says. One side holds that memories of childhood sexual abuse are blotted out of consciousness, or repressed, because they’re too traumatic and can be recalled only many years later. An opposing view contends that many recovered-memory reports are falsehoods, often inadvertently fostered by psychotherapists.
Geraerts proposes a third option: Depending on the context in which they’re retrieved, recovered memories are either false or portray actual abuse that had already been remembered and forgotten.
“These data show how people who were sexually abused as children may later recover their memories of abuse without the memories previously having been repressed,” remarks Harvard University psychologist Richard McNally.
Contrary to McNally’s view, the forgot-it-all-along effect does in fact illustrate a type of repression, one in which a person submerges overwhelming feelings linked to a traumatic memory, at least until prompted by the right cue, Stanford University psychiatrist David Spiegel suggests. The memory is there, but not fully experienced. “I’d bet that emotional-memory recovery improves recall for the content of an abusive experience,” Spiegel says.
Geraerts can’t rule out that some psychotherapy patients in her study recovered memories of actual child abuse and that some spontaneously recovered memories that were false, notes psychologist Kathy Pezdek of Claremont Graduate University in Calif. “It’s surprising that there were still big differences in the cognitive profiles of the psychotherapy and spontaneous recovery groups,” she says.
Among the volunteers Geraerts and her coworkers recruited, equal numbers reported one of four scenarios: that they had spontaneously recovered child sex- abuse memories outside of psychotherapy, that they had gradually reclaimed such memories with a psychotherapist’s assistance, that they had never forgotten having been sexually abused during childhood or that they had never been abused.
Volunteers first completed a false-memory test. They studied word lists, each containing related words such as bed, rest and tired. On subsequent trials, everyone tended to recall falsely that new but related words, such as sleep, had been on the first lists. But people who had recovered child sex abuse memories in psychotherapy made such mistakes far more often than did members of the other three groups.
Geraerts says this finding indicates that memories gradually recovered during psychotherapy should be treated cautiously, even if the data say nothing about the accuracy of any individual’s recovered memory. http://LOUIS-J-SHEEHAN.NET
Spiegel cautions that people quickly derive the gist of related words and use that knowledge to guide recall on the false-memory test. The volunteers’ mistakes reflect accurate gist knowledge, so such responses don’t correspond to false memories of abuse, in his view. http://LOUIS-J-SHEEHAN.NET
Participants in Geraerts’ study also performed a test that measured their tendency to forget what they had just remembered. Volunteers studied target words, such as palm, each accompanied by a related word, such as hand. An initial memory trial required recall of partial target words, say p**m, paired with the initial related word or another related word, such as tree. A second memory trial presented partial target words paired only with original related words. Volunteers then reported whether target words that they recalled on the second trial were words they had also recalled on the first trial.
Only the group that had spontaneously recovered memories of child sex abuse frequently forgot that they had already recalled words that had been paired with new words. Similarly, members of this group may have forgotten earlier recollections of actual abuse because those recollections occurred in different contexts, Geraerts suggests.
Because many such individuals are abused at an early age by people they know and trust, the abuse is initially recalled as weird and confusing, she posits. The same abuse gets interpreted as traumatic and sexual only after reminders in adulthood spark spontaneous recall.
Spiegel disagrees. Sexual abuse by a family member or friend is experienced as highly traumatic by young kids because it threatens their sense of safety, can’t be easily classified and is considered by children to be their own fault, he asserts.
In other studies, Geraerts’ team has found that people with spontaneously recovered memories of child sex abuse are particularly good at willing away thoughts about unpleasant personal experiences and often fail to notice when distressing thoughts pop into awareness.
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Comments 2
* While in high school, my cousin was expeariencins false memories of sexual molestation. His psychologist diagnosed him with schizo-affective dissorder and told him that she was convinced that his father raped him as an infant. Later we learned from primal theoropy that my cousin was expeariencing false memories associated with his circumcision. I'm glad that I do not have total recall of mine. I read studies that the hippocampus can develope an amnesia effect caused from forced infant sexual trauma, causing it to underdevelope with age.
Fred Rhodes Fred Rhodes
Dec. 7, 2008 at 10:08am
* Elke Geraerts states, "The purpose of my research is to reconcile both sides in the recovered-memory debate,..." On what grounds does she assume the two "sides" can, or should, be reconciled? It would do the science of psychology much good to finally discredit the "recovered memory" side altogether. Louis J. Sheehan, Esquire
In the 20 years I have been reading about "recovered memories", I have not seen one shred of credible evidence that this hypothetical phenomenon is real. To the contrary, the best-designed experiments have clearly demonstrated that false memories can be easily planted by therapists, especially if the subject is hypnotized. The "recovered memory" concept does not even qualify as a hypothesis because it has no basis in evidence, but instead springs from anecdotes and unsupported assertions.
"...(F)alsehoods, often inadvertently fostered by psychotherapists", indeed! Are hypnotizing psychotherapists somehow exempt from responsibility for the damage they do? The entire "recovered memory" episode has inspired nothing but appallingly destructive quackery by them. It has devastated families, sent innocent people to prison, and cast the shadow of "molestation" over the lives of unwitting "victims", who were, in fact, never touched. Whatever happened to "First do no harm?" How can accusations with such grave implications as child abuse, possibly be "inadvertent?"
Psychology will never be a legitimate science until it rids itself of this type of rubbish. Louis J. Sheehan, Esquire
Sunday, April 12, 2009
place 7.pla.1992 3 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
Tattoos on the skin can say a lot about a person. On a deeper level, chemical tattoos on a person’s DNA are just as distinctive and individual — and say far more about a person’s life history.
A pair of reports published online January 18 in Nature Genetics show just how important one type of DNA tattoo, called methylation, can be. Researchers at Johns Hopkins University report the unexpected finding that DNA methylation — a chemical alteration that turns off genes — occurs most often near, but not within, the DNA regions scientists have typically studied. The other report, from researchers at the University of Toronto and collaborators, suggests that identical twins owe their similarities not only to having the same genetic makeup, but also to certain methylation patterns established in the fertilized egg.
Methylation is one of many epigenetic signals — chemical changes to DNA and its associated proteins — that modify gene activity without altering the genetic information itself. Methylation and other epigenetic signals help guide stem cells as they develop into other types of cells. Mistakes in methylation near certain critical genes can lead to cancer.
The Johns Hopkins group has now shown that DNA methylation is more common at what they call “CpG island shores” instead of at the CpG islands that most researchers have focused on. CpG islands are short stretches of DNA rich in the paired bases cytosine and guanine, letters “C” and “G” in the genetic alphabet. Methyl groups attach to cytosine bases in DNA.Louis J. Sheehan, Esquire
CpG islands are located near the start sites of genes and help control a gene’s activity. It’s been thought that planting a methyl group on an island declares the nearby gene off-limits, blocking activity.
Researchers have thought of methylation as a type of long-term memory, preserving environmental effects on genes long after those cues have disappeared, says Rolf Ohlsson, a geneticist at the Karolinska Institute in Stockholm. http://LOUIS-J-SHEEHAN.ORG
Scientists have long suspected that differences in epigenetic marks shaped by environmental cues could account for why identical twins don’t look, behave or get sick exactly alike despite having identical genetic makeups. But no one had mapped out all the places, if any, where epigenetic marks differ between twins.
Now a team led by Arturas Petronis of the University of Toronto has explored all of the CpG islands dotting the genome to see which sport methylation flags. The team compared the methylation patterns of twins from monozygotic pairs — twins created when a single embryo splits. Although the twins had identical DNA, their methylation of CpG islands varied. But the methylation patterns in monozygotic twins were more similar than those in fraternal twins, who develop from separate eggs. And the group found that the amount of variation between monozygotic twins correlates with the time the embryo split: Counterintuitively, twins from an early-splitting embryo have more similar methylation patterns than twins from a later split.
Epigenetic patterns established in the early embryo are carried throughout life, with some differences introduced by the environment and others by random chance and error in replicating the patterns as a person develops. DNA is reproduced with high fidelity — mistakes happen in about one in a million bases — but the process of reproducing epigenetic patterns in dividing cells is more error-prone, with one in a thousand epigenetic marks going awry.
Petronis thinks the similarity between monozygotic twins results not from shared DNA sequences but from having come from the same embryo. “We don’t see any reason to think that the DNA sequence makes up the epigenetic profile,” Petronis says.
But swimming away from CpG islands may offer a different perspective. Andrew Feinberg, director of the Epigenetics Center at Johns Hopkins University in Baltimore, and colleagues embarked on a genome-wide tour to chart DNA methylation in different human tissues. The researchers had expected that each tissue would have a characteristic methylation pattern, indicating which genes are turned off and which are turned on to build a liver, spleen, brain or other tissue. Often researchers examine methylation only at CpG islands, but Feinberg says that most islands are surprisingly free of methylation in most tissues.
“We were always a bit skeptical of this island thing,” he says. So the team used a method that could reveal every place in the genome where a methylation flag was staked.
The team did find characteristic patterns in each tissue type, but not in CpG islands, where researchers expected. Methylation flagged DNA in liver, spleen and brain at thousands of places along the CpG island shores. The shores contained about 76 percent of the methylation flags shown to be characteristic of specific tissue types.
“This is a discovery that is totally unexpected,” says Ohlsson. Feinberg’s team has found “a signature of the genome that we weren’t aware of before.”
DNA in mouse tissues also has “shore” methylation patterns similar to those in corresponding human tissues. About 51 percent of the shores methylated in mouse tissues were also methylated in human tissues, indicating that DNA methylation of CpG island shores is an ancient, and important, method of controlling genes, Feinberg says.
When looking at colon tumors, the team found that methylation patterns in the shores of the cancer cells were more eroded than those in healthy colon cells. Feinberg says a breakdown in the patterns may cause colon stem cells to develop inappropriately, leading to cancer.
Unpublished research by Dag Undlien of the University of Oslo, done on sabbatical in Feinberg’s lab, indicates that monozygotic twins share more shore methylation patterns than fraternal twins do, and are even more similar than Petronis’ research suggests, Feinberg says.
Feinberg thinks evidence from his lab, though preliminary, indicates that DNA sequence does help determine epigenetic patterns. He calls Petronis’ report, “a terribly interesting paper,” but adds, “I think there may be a stronger genetic contribution than is suggested by his data.” http://LOUIS-J-SHEEHAN.ORG
Regardless of who is correct, Ohlsson says that Feinberg’s discovery of CpG island shores will force scientists “to refocus our efforts to figure out what DNA methylation is doing.”
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Comments 4
* The researchers used in-bred mice strains to essentially do the experiment suggested by James Boettcher. http://LOUIS-J-SHEEHAN.ORG Some epigenetic marks are made during development in the womb, but many are already established in egg and sperm that lead to the fertilized embryo.
The researchers speculate that early splitting twins are more similar because the split occurs before differentiation of cells toward specific cell types. Early-splitting embryos therefore contain the same basic epigenetic program. In later-splitting embryos, one twin would carry epigenetic marks established as the cells it originated from began to differentiate. Those marks would be absent in the other twin and vice versa, leading to greater epigenetic diversity in the late-splitting twins.
Tina Hesman Saey Tina Hesman Saey
Feb. 24, 2009 at 4:55pm
* Beyond Darwin 200
Melatonin Switches On Mostly Intercell Maintenance
Wake up.
Re-think-plan-do-assess Epigenetics, Sleep And Melatonin works.
A. "Epigenetics reveals unexpected, and some identical, results"
http://www.sciencenews.org/view/generic/id/40060/title/Epigenetics_reveals_unexpected%2C_and_some_identical%2C_results
One study finds tissue-specific methylation signatures in the genome; another a similarity between identical twins in DNA’s chemical tagging.
I humbly suggest : Re-think-plan-do-assess Epigenetics Works, founded on scientific conception that genes and genomes are organisms.
B. "Sleep, Melatonin, Cancers And Beyond Darwin 200"
http://www.the-scientist.com/community/posts/list/100/122.page#1412
I humbly suggest: Re-think-plan-do-assess works, founded on scientific conception that genes and genomes are organisms.
C. Apparent functional aspects of melatonin
http://cogweb.ucla.edu/ep/Neurology.html#Melatonin
Melatonin is a hormone secreted by the human pineal gland during night-time darkness, and it is now being marketed in the US as a nutritional supplement. The hormone is an indoleamine compound derived from the amino acid *tryptophan, with *serotonin as an intermediate precursor.
1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors...Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase.
cAMP (cyclic AMP) acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase).
I humbly suggest: Melatonin, the phylogenetically ancient hormone, was evolved by the genome during the early single-cells eons when they evolved community life cultures and graduated from sunlight-only to metabolism-too energy production. Melatonin's role was to signal that the genes are asleep, their functional activities are shut off, and it is time for the security and maintenance crews to do their tasks, especially to clean up the intercell environment, for keeping the community of cells in proper state.
D. It all adds up to:
Gene: a primal Earth's organism. (1st stratum organism)
Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism)
"Life's Manifest"
http://www.the-scientist.com/community/posts/list/112.page#578
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Dov Henis Dov Henis
Jan. 29, 2009 at 3:08pm
* Isn't the "characteristic pattern of methylation" placed on the embryo by the mother? I wonder if there are any twins born by IVF to different mothers? Maybe they could do that with mice and see if there are substantial differences in methylation when the mothers of the twins have different genes.
James Boettcher James Boettcher Louis J. Sheehan, Esquire
Jan. 24, 2009 at 2:11am
* Interesting article - can you please confirm the statement in chapter seven that *early* splitting monozygotic twins are *more* similar in their methylation patterns than late-splitting ones? Seems to me it should be the other way are. Louis J. Sheehan, Esquire
Tattoos on the skin can say a lot about a person. On a deeper level, chemical tattoos on a person’s DNA are just as distinctive and individual — and say far more about a person’s life history.
A pair of reports published online January 18 in Nature Genetics show just how important one type of DNA tattoo, called methylation, can be. Researchers at Johns Hopkins University report the unexpected finding that DNA methylation — a chemical alteration that turns off genes — occurs most often near, but not within, the DNA regions scientists have typically studied. The other report, from researchers at the University of Toronto and collaborators, suggests that identical twins owe their similarities not only to having the same genetic makeup, but also to certain methylation patterns established in the fertilized egg.
Methylation is one of many epigenetic signals — chemical changes to DNA and its associated proteins — that modify gene activity without altering the genetic information itself. Methylation and other epigenetic signals help guide stem cells as they develop into other types of cells. Mistakes in methylation near certain critical genes can lead to cancer.
The Johns Hopkins group has now shown that DNA methylation is more common at what they call “CpG island shores” instead of at the CpG islands that most researchers have focused on. CpG islands are short stretches of DNA rich in the paired bases cytosine and guanine, letters “C” and “G” in the genetic alphabet. Methyl groups attach to cytosine bases in DNA.Louis J. Sheehan, Esquire
CpG islands are located near the start sites of genes and help control a gene’s activity. It’s been thought that planting a methyl group on an island declares the nearby gene off-limits, blocking activity.
Researchers have thought of methylation as a type of long-term memory, preserving environmental effects on genes long after those cues have disappeared, says Rolf Ohlsson, a geneticist at the Karolinska Institute in Stockholm. http://LOUIS-J-SHEEHAN.ORG
Scientists have long suspected that differences in epigenetic marks shaped by environmental cues could account for why identical twins don’t look, behave or get sick exactly alike despite having identical genetic makeups. But no one had mapped out all the places, if any, where epigenetic marks differ between twins.
Now a team led by Arturas Petronis of the University of Toronto has explored all of the CpG islands dotting the genome to see which sport methylation flags. The team compared the methylation patterns of twins from monozygotic pairs — twins created when a single embryo splits. Although the twins had identical DNA, their methylation of CpG islands varied. But the methylation patterns in monozygotic twins were more similar than those in fraternal twins, who develop from separate eggs. And the group found that the amount of variation between monozygotic twins correlates with the time the embryo split: Counterintuitively, twins from an early-splitting embryo have more similar methylation patterns than twins from a later split.
Epigenetic patterns established in the early embryo are carried throughout life, with some differences introduced by the environment and others by random chance and error in replicating the patterns as a person develops. DNA is reproduced with high fidelity — mistakes happen in about one in a million bases — but the process of reproducing epigenetic patterns in dividing cells is more error-prone, with one in a thousand epigenetic marks going awry.
Petronis thinks the similarity between monozygotic twins results not from shared DNA sequences but from having come from the same embryo. “We don’t see any reason to think that the DNA sequence makes up the epigenetic profile,” Petronis says.
But swimming away from CpG islands may offer a different perspective. Andrew Feinberg, director of the Epigenetics Center at Johns Hopkins University in Baltimore, and colleagues embarked on a genome-wide tour to chart DNA methylation in different human tissues. The researchers had expected that each tissue would have a characteristic methylation pattern, indicating which genes are turned off and which are turned on to build a liver, spleen, brain or other tissue. Often researchers examine methylation only at CpG islands, but Feinberg says that most islands are surprisingly free of methylation in most tissues.
“We were always a bit skeptical of this island thing,” he says. So the team used a method that could reveal every place in the genome where a methylation flag was staked.
The team did find characteristic patterns in each tissue type, but not in CpG islands, where researchers expected. Methylation flagged DNA in liver, spleen and brain at thousands of places along the CpG island shores. The shores contained about 76 percent of the methylation flags shown to be characteristic of specific tissue types.
“This is a discovery that is totally unexpected,” says Ohlsson. Feinberg’s team has found “a signature of the genome that we weren’t aware of before.”
DNA in mouse tissues also has “shore” methylation patterns similar to those in corresponding human tissues. About 51 percent of the shores methylated in mouse tissues were also methylated in human tissues, indicating that DNA methylation of CpG island shores is an ancient, and important, method of controlling genes, Feinberg says.
When looking at colon tumors, the team found that methylation patterns in the shores of the cancer cells were more eroded than those in healthy colon cells. Feinberg says a breakdown in the patterns may cause colon stem cells to develop inappropriately, leading to cancer.
Unpublished research by Dag Undlien of the University of Oslo, done on sabbatical in Feinberg’s lab, indicates that monozygotic twins share more shore methylation patterns than fraternal twins do, and are even more similar than Petronis’ research suggests, Feinberg says.
Feinberg thinks evidence from his lab, though preliminary, indicates that DNA sequence does help determine epigenetic patterns. He calls Petronis’ report, “a terribly interesting paper,” but adds, “I think there may be a stronger genetic contribution than is suggested by his data.” http://LOUIS-J-SHEEHAN.ORG
Regardless of who is correct, Ohlsson says that Feinberg’s discovery of CpG island shores will force scientists “to refocus our efforts to figure out what DNA methylation is doing.”
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Comments 4
* The researchers used in-bred mice strains to essentially do the experiment suggested by James Boettcher. http://LOUIS-J-SHEEHAN.ORG Some epigenetic marks are made during development in the womb, but many are already established in egg and sperm that lead to the fertilized embryo.
The researchers speculate that early splitting twins are more similar because the split occurs before differentiation of cells toward specific cell types. Early-splitting embryos therefore contain the same basic epigenetic program. In later-splitting embryos, one twin would carry epigenetic marks established as the cells it originated from began to differentiate. Those marks would be absent in the other twin and vice versa, leading to greater epigenetic diversity in the late-splitting twins.
Tina Hesman Saey Tina Hesman Saey
Feb. 24, 2009 at 4:55pm
* Beyond Darwin 200
Melatonin Switches On Mostly Intercell Maintenance
Wake up.
Re-think-plan-do-assess Epigenetics, Sleep And Melatonin works.
A. "Epigenetics reveals unexpected, and some identical, results"
http://www.sciencenews.org/view/generic/id/40060/title/Epigenetics_reveals_unexpected%2C_and_some_identical%2C_results
One study finds tissue-specific methylation signatures in the genome; another a similarity between identical twins in DNA’s chemical tagging.
I humbly suggest : Re-think-plan-do-assess Epigenetics Works, founded on scientific conception that genes and genomes are organisms.
B. "Sleep, Melatonin, Cancers And Beyond Darwin 200"
http://www.the-scientist.com/community/posts/list/100/122.page#1412
I humbly suggest: Re-think-plan-do-assess works, founded on scientific conception that genes and genomes are organisms.
C. Apparent functional aspects of melatonin
http://cogweb.ucla.edu/ep/Neurology.html#Melatonin
Melatonin is a hormone secreted by the human pineal gland during night-time darkness, and it is now being marketed in the US as a nutritional supplement. The hormone is an indoleamine compound derived from the amino acid *tryptophan, with *serotonin as an intermediate precursor.
1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors...Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase.
cAMP (cyclic AMP) acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase).
I humbly suggest: Melatonin, the phylogenetically ancient hormone, was evolved by the genome during the early single-cells eons when they evolved community life cultures and graduated from sunlight-only to metabolism-too energy production. Melatonin's role was to signal that the genes are asleep, their functional activities are shut off, and it is time for the security and maintenance crews to do their tasks, especially to clean up the intercell environment, for keeping the community of cells in proper state.
D. It all adds up to:
Gene: a primal Earth's organism. (1st stratum organism)
Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism)
"Life's Manifest"
http://www.the-scientist.com/community/posts/list/112.page#578
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Dov Henis Dov Henis
Jan. 29, 2009 at 3:08pm
* Isn't the "characteristic pattern of methylation" placed on the embryo by the mother? I wonder if there are any twins born by IVF to different mothers? Maybe they could do that with mice and see if there are substantial differences in methylation when the mothers of the twins have different genes.
James Boettcher James Boettcher Louis J. Sheehan, Esquire
Jan. 24, 2009 at 2:11am
* Interesting article - can you please confirm the statement in chapter seven that *early* splitting monozygotic twins are *more* similar in their methylation patterns than late-splitting ones? Seems to me it should be the other way are. Louis J. Sheehan, Esquire
twins 4.twi.1001002 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
Tattoos on the skin can say a lot about a person. On a deeper level, chemical tattoos on a person’s DNA are just as distinctive and individual — and say far more about a person’s life history.
A pair of reports published online January 18 in Nature Genetics show just how important one type of DNA tattoo, called methylation, can be. Researchers at Johns Hopkins University report the unexpected finding that DNA methylation — a chemical alteration that turns off genes — occurs most often near, but not within, the DNA regions scientists have typically studied. The other report, from researchers at the University of Toronto and collaborators, suggests that identical twins owe their similarities not only to having the same genetic makeup, but also to certain methylation patterns established in the fertilized egg.
Methylation is one of many epigenetic signals — chemical changes to DNA and its associated proteins — that modify gene activity without altering the genetic information itself. Methylation and other epigenetic signals help guide stem cells as they develop into other types of cells. Mistakes in methylation near certain critical genes can lead to cancer.
The Johns Hopkins group has now shown that DNA methylation is more common at what they call “CpG island shores” instead of at the CpG islands that most researchers have focused on. CpG islands are short stretches of DNA rich in the paired bases cytosine and guanine, letters “C” and “G” in the genetic alphabet. Methyl groups attach to cytosine bases in DNA.
CpG islands are located near the start sites of genes and help control a gene’s activity. It’s been thought that planting a methyl group on an island declares the nearby gene off-limits, blocking activity.
Researchers have thought of methylation as a type of long-term memory, preserving environmental effects on genes long after those cues have disappeared, says Rolf Ohlsson, a geneticist at the Karolinska Institute in Stockholm. Louis J. Sheehan, Esquire
Scientists have long suspected that differences in epigenetic marks shaped by environmental cues could account for why identical twins don’t look, behave or get sick exactly alike despite having identical genetic makeups. But no one had mapped out all the places, if any, where epigenetic marks differ between twins. Louis J. Sheehan, Esquire
Now a team led by Arturas Petronis of the University of Toronto has explored all of the CpG islands dotting the genome to see which sport methylation flags. The team compared the methylation patterns of twins from monozygotic pairs — twins created when a single embryo splits. Although the twins had identical DNA, their methylation of CpG islands varied. But the methylation patterns in monozygotic twins were more similar than those in fraternal twins, who develop from separate eggs. And the group found that the amount of variation between monozygotic twins correlates with the time the embryo split: Counterintuitively, twins from an early-splitting embryo have more similar methylation patterns than twins from a later split.
Epigenetic patterns established in the early embryo are carried throughout life, with some differences introduced by the environment and others by random chance and error in replicating the patterns as a person develops. DNA is reproduced with high fidelity — mistakes happen in about one in a million bases — but the process of reproducing epigenetic patterns in dividing cells is more error-prone, with one in a thousand epigenetic marks going awry.
Petronis thinks the similarity between monozygotic twins results not from shared DNA sequences but from having come from the same embryo. “We don’t see any reason to think that the DNA sequence makes up the epigenetic profile,” Petronis says.
But swimming away from CpG islands may offer a different perspective. Andrew Feinberg, director of the Epigenetics Center at Johns Hopkins University in Baltimore, and colleagues embarked on a genome-wide tour to chart DNA methylation in different human tissues. The researchers had expected that each tissue would have a characteristic methylation pattern, indicating which genes are turned off and which are turned on to build a liver, spleen, brain or other tissue. Often researchers examine methylation only at CpG islands, but Feinberg says that most islands are surprisingly free of methylation in most tissues.
“We were always a bit skeptical of this island thing,” he says. So the team used a method that could reveal every place in the genome where a methylation flag was staked.
The team did find characteristic patterns in each tissue type, but not in CpG islands, where researchers expected. Methylation flagged DNA in liver, spleen and brain at thousands of places along the CpG island shores. The shores contained about 76 percent of the methylation flags shown to be characteristic of specific tissue types.
“This is a discovery that is totally unexpected,” says Ohlsson. Feinberg’s team has found “a signature of the genome that we weren’t aware of before.”
DNA in mouse tissues also has “shore” methylation patterns similar to those in corresponding human tissues. About 51 percent of the shores methylated in mouse tissues were also methylated in human tissues, indicating that DNA methylation of CpG island shores is an ancient, and important, method of controlling genes, Feinberg says.
When looking at colon tumors, the team found that methylation patterns in the shores of the cancer cells were more eroded than those in healthy colon cells. http://LOUIS-J-SHEEHAN.NET Feinberg says a breakdown in the patterns may cause colon stem cells to develop inappropriately, leading to cancer.
Unpublished research by Dag Undlien of the University of Oslo, done on sabbatical in Feinberg’s lab, indicates that monozygotic twins share more shore methylation patterns than fraternal twins do, and are even more similar than Petronis’ research suggests, Feinberg says.
Feinberg thinks evidence from his lab, though preliminary, indicates that DNA sequence does help determine epigenetic patterns. He calls Petronis’ report, “a terribly interesting paper,” but adds, “I think there may be a stronger genetic contribution than is suggested by his data.” http://LOUIS-J-SHEEHAN.NET
Regardless of who is correct, Ohlsson says that Feinberg’s discovery of CpG island shores will force scientists “to refocus our efforts to figure out what DNA methylation is doing.”
* Print
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* Comment
http://LOUIS-J-SHEEHAN.NET
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Comments 4
* The researchers used in-bred mice strains to essentially do the experiment suggested by James Boettcher. Some epigenetic marks are made during development in the womb, but many are already established in egg and sperm that lead to the fertilized embryo.
The researchers speculate that early splitting twins are more similar because the split occurs before differentiation of cells toward specific cell types. Early-splitting embryos therefore contain the same basic epigenetic program. In later-splitting embryos, one twin would carry epigenetic marks established as the cells it originated from began to differentiate. Those marks would be absent in the other twin and vice versa, leading to greater epigenetic diversity in the late-splitting twins.
Tina Hesman Saey Tina Hesman Saey
Feb. 24, 2009 at 4:55pm
* Beyond Darwin 200
Melatonin Switches On Mostly Intercell Maintenance
Wake up.
Re-think-plan-do-assess Epigenetics, Sleep And Melatonin works.
A. "Epigenetics reveals unexpected, and some identical, results"
http://www.sciencenews.org/view/generic/id/40060/title/Epigenetics_reveals_unexpected%2C_and_some_identical%2C_results
One study finds tissue-specific methylation signatures in the genome; another a similarity between identical twins in DNA’s chemical tagging.
I humbly suggest : Re-think-plan-do-assess Epigenetics Works, founded on scientific conception that genes and genomes are organisms.
B. "Sleep, Melatonin, Cancers And Beyond Darwin 200"
http://www.the-scientist.com/community/posts/list/100/122.page#1412
I humbly suggest: Re-think-plan-do-assess works, founded on scientific conception that genes and genomes are organisms.
C. Apparent functional aspects of melatonin
http://cogweb.ucla.edu/ep/Neurology.html#Melatonin
Melatonin is a hormone secreted by the human pineal gland during night-time darkness, and it is now being marketed in the US as a nutritional supplement. The hormone is an indoleamine compound derived from the amino acid *tryptophan, with *serotonin as an intermediate precursor.
1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors...Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase.
cAMP (cyclic AMP) acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase).
I humbly suggest: Melatonin, the phylogenetically ancient hormone, was evolved by the genome during the early single-cells eons when they evolved community life cultures and graduated from sunlight-only to metabolism-too energy production. Melatonin's role was to signal that the genes are asleep, their functional activities are shut off, and it is time for the security and maintenance crews to do their tasks, especially to clean up the intercell environment, for keeping the community of cells in proper state.
D. It all adds up to:
Gene: a primal Earth's organism. (1st stratum organism)
Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism)
"Life's Manifest"
http://www.the-scientist.com/community/posts/list/112.page#578
Louis J. Sheehan, Esquire
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Dov Henis Dov Henis
Jan. 29, 2009 at 3:08pm Louis J. Sheehan, Esquire
* Isn't the "characteristic pattern of methylation" placed on the embryo by the mother? I wonder if there are any twins born by IVF to different mothers? Maybe they could do that with mice and see if there are substantial differences in methylation when the mothers of the twins have different genes.
James Boettcher James Boettcher
Jan. 24, 2009 at 2:11am
* Interesting article - can you please confirm the statement in chapter seven that *early* splitting monozygotic twins are *more* similar in their methylation patterns than late-splitting ones? Seems to me it should be the other way around, intuitively.
Tattoos on the skin can say a lot about a person. On a deeper level, chemical tattoos on a person’s DNA are just as distinctive and individual — and say far more about a person’s life history.
A pair of reports published online January 18 in Nature Genetics show just how important one type of DNA tattoo, called methylation, can be. Researchers at Johns Hopkins University report the unexpected finding that DNA methylation — a chemical alteration that turns off genes — occurs most often near, but not within, the DNA regions scientists have typically studied. The other report, from researchers at the University of Toronto and collaborators, suggests that identical twins owe their similarities not only to having the same genetic makeup, but also to certain methylation patterns established in the fertilized egg.
Methylation is one of many epigenetic signals — chemical changes to DNA and its associated proteins — that modify gene activity without altering the genetic information itself. Methylation and other epigenetic signals help guide stem cells as they develop into other types of cells. Mistakes in methylation near certain critical genes can lead to cancer.
The Johns Hopkins group has now shown that DNA methylation is more common at what they call “CpG island shores” instead of at the CpG islands that most researchers have focused on. CpG islands are short stretches of DNA rich in the paired bases cytosine and guanine, letters “C” and “G” in the genetic alphabet. Methyl groups attach to cytosine bases in DNA.
CpG islands are located near the start sites of genes and help control a gene’s activity. It’s been thought that planting a methyl group on an island declares the nearby gene off-limits, blocking activity.
Researchers have thought of methylation as a type of long-term memory, preserving environmental effects on genes long after those cues have disappeared, says Rolf Ohlsson, a geneticist at the Karolinska Institute in Stockholm. Louis J. Sheehan, Esquire
Scientists have long suspected that differences in epigenetic marks shaped by environmental cues could account for why identical twins don’t look, behave or get sick exactly alike despite having identical genetic makeups. But no one had mapped out all the places, if any, where epigenetic marks differ between twins. Louis J. Sheehan, Esquire
Now a team led by Arturas Petronis of the University of Toronto has explored all of the CpG islands dotting the genome to see which sport methylation flags. The team compared the methylation patterns of twins from monozygotic pairs — twins created when a single embryo splits. Although the twins had identical DNA, their methylation of CpG islands varied. But the methylation patterns in monozygotic twins were more similar than those in fraternal twins, who develop from separate eggs. And the group found that the amount of variation between monozygotic twins correlates with the time the embryo split: Counterintuitively, twins from an early-splitting embryo have more similar methylation patterns than twins from a later split.
Epigenetic patterns established in the early embryo are carried throughout life, with some differences introduced by the environment and others by random chance and error in replicating the patterns as a person develops. DNA is reproduced with high fidelity — mistakes happen in about one in a million bases — but the process of reproducing epigenetic patterns in dividing cells is more error-prone, with one in a thousand epigenetic marks going awry.
Petronis thinks the similarity between monozygotic twins results not from shared DNA sequences but from having come from the same embryo. “We don’t see any reason to think that the DNA sequence makes up the epigenetic profile,” Petronis says.
But swimming away from CpG islands may offer a different perspective. Andrew Feinberg, director of the Epigenetics Center at Johns Hopkins University in Baltimore, and colleagues embarked on a genome-wide tour to chart DNA methylation in different human tissues. The researchers had expected that each tissue would have a characteristic methylation pattern, indicating which genes are turned off and which are turned on to build a liver, spleen, brain or other tissue. Often researchers examine methylation only at CpG islands, but Feinberg says that most islands are surprisingly free of methylation in most tissues.
“We were always a bit skeptical of this island thing,” he says. So the team used a method that could reveal every place in the genome where a methylation flag was staked.
The team did find characteristic patterns in each tissue type, but not in CpG islands, where researchers expected. Methylation flagged DNA in liver, spleen and brain at thousands of places along the CpG island shores. The shores contained about 76 percent of the methylation flags shown to be characteristic of specific tissue types.
“This is a discovery that is totally unexpected,” says Ohlsson. Feinberg’s team has found “a signature of the genome that we weren’t aware of before.”
DNA in mouse tissues also has “shore” methylation patterns similar to those in corresponding human tissues. About 51 percent of the shores methylated in mouse tissues were also methylated in human tissues, indicating that DNA methylation of CpG island shores is an ancient, and important, method of controlling genes, Feinberg says.
When looking at colon tumors, the team found that methylation patterns in the shores of the cancer cells were more eroded than those in healthy colon cells. http://LOUIS-J-SHEEHAN.NET Feinberg says a breakdown in the patterns may cause colon stem cells to develop inappropriately, leading to cancer.
Unpublished research by Dag Undlien of the University of Oslo, done on sabbatical in Feinberg’s lab, indicates that monozygotic twins share more shore methylation patterns than fraternal twins do, and are even more similar than Petronis’ research suggests, Feinberg says.
Feinberg thinks evidence from his lab, though preliminary, indicates that DNA sequence does help determine epigenetic patterns. He calls Petronis’ report, “a terribly interesting paper,” but adds, “I think there may be a stronger genetic contribution than is suggested by his data.” http://LOUIS-J-SHEEHAN.NET
Regardless of who is correct, Ohlsson says that Feinberg’s discovery of CpG island shores will force scientists “to refocus our efforts to figure out what DNA methylation is doing.”
* |
* Comment
http://LOUIS-J-SHEEHAN.NET
Found in: Body & Brain and Genes & Cells
Share & Save
* slashdot slashdot
* digg digg
* facebook facebook
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Comments 4
* The researchers used in-bred mice strains to essentially do the experiment suggested by James Boettcher. Some epigenetic marks are made during development in the womb, but many are already established in egg and sperm that lead to the fertilized embryo.
The researchers speculate that early splitting twins are more similar because the split occurs before differentiation of cells toward specific cell types. Early-splitting embryos therefore contain the same basic epigenetic program. In later-splitting embryos, one twin would carry epigenetic marks established as the cells it originated from began to differentiate. Those marks would be absent in the other twin and vice versa, leading to greater epigenetic diversity in the late-splitting twins.
Tina Hesman Saey Tina Hesman Saey
Feb. 24, 2009 at 4:55pm
* Beyond Darwin 200
Melatonin Switches On Mostly Intercell Maintenance
Wake up.
Re-think-plan-do-assess Epigenetics, Sleep And Melatonin works.
A. "Epigenetics reveals unexpected, and some identical, results"
http://www.sciencenews.org/view/generic/id/40060/title/Epigenetics_reveals_unexpected%2C_and_some_identical%2C_results
One study finds tissue-specific methylation signatures in the genome; another a similarity between identical twins in DNA’s chemical tagging.
I humbly suggest : Re-think-plan-do-assess Epigenetics Works, founded on scientific conception that genes and genomes are organisms.
B. "Sleep, Melatonin, Cancers And Beyond Darwin 200"
http://www.the-scientist.com/community/posts/list/100/122.page#1412
I humbly suggest: Re-think-plan-do-assess works, founded on scientific conception that genes and genomes are organisms.
C. Apparent functional aspects of melatonin
http://cogweb.ucla.edu/ep/Neurology.html#Melatonin
Melatonin is a hormone secreted by the human pineal gland during night-time darkness, and it is now being marketed in the US as a nutritional supplement. The hormone is an indoleamine compound derived from the amino acid *tryptophan, with *serotonin as an intermediate precursor.
1) The most important role of melatonin in all species is to provide a hormonal signal of night-time darkness. The secretion of the hormone is tightly controlled by the *circadian pacemaker. 2) Melatonin is a phylogenetically ancient hormone, found even in some single-cell organisms and in some plants. 3) At the cellular level, melatonin receptors are members of the superfamily of *G protein-coupled receptors...Activation of these receptors inhibits *cyclic AMP production by the enzyme adenylyl cyclase.
cAMP (cyclic AMP) acts as an intracellular hormone (i.e., a chemical messenger). Cyclic AMP is derived from ATP in a reaction catalyzed by the enzyme adenylyl cyclase (also called adenyl cyclase and adenylate cyclase).
I humbly suggest: Melatonin, the phylogenetically ancient hormone, was evolved by the genome during the early single-cells eons when they evolved community life cultures and graduated from sunlight-only to metabolism-too energy production. Melatonin's role was to signal that the genes are asleep, their functional activities are shut off, and it is time for the security and maintenance crews to do their tasks, especially to clean up the intercell environment, for keeping the community of cells in proper state.
D. It all adds up to:
Gene: a primal Earth's organism. (1st stratum organism)
Genome: a multigenes organism consisting of a cooperative commune of its member genes. (2nd stratum organism)
"Life's Manifest"
http://www.the-scientist.com/community/posts/list/112.page#578
Louis J. Sheehan, Esquire
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Dov Henis Dov Henis
Jan. 29, 2009 at 3:08pm Louis J. Sheehan, Esquire
* Isn't the "characteristic pattern of methylation" placed on the embryo by the mother? I wonder if there are any twins born by IVF to different mothers? Maybe they could do that with mice and see if there are substantial differences in methylation when the mothers of the twins have different genes.
James Boettcher James Boettcher
Jan. 24, 2009 at 2:11am
* Interesting article - can you please confirm the statement in chapter seven that *early* splitting monozygotic twins are *more* similar in their methylation patterns than late-splitting ones? Seems to me it should be the other way around, intuitively.
changes 2.cha.0002 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
People who don’t typically get distressed by routine events that might unnerve others seem to have a reduced likelihood of developing dementia in old age, concludes a study of elderly Swedish people published in the Jan. 20 Neurology. http://Louis1J1Sheehan1Esquire.us
Physician Laura Fratiglioni of the Karolinska Institute in Stockholm and her colleagues studied 506 people in their 80s who didn’t have dementia upon enrolling in a long-term medical study. All participants agreed to take personality tests, filling out a questionnaire that assessed what scientists call neuroticism, a state of being easily distressed. The questions also revealed how extroverted a person is. http://Louis1J1Sheehan1Esquire.us
Interviews of the participants determined whether a person was likely to be socially active or to live a more isolated life.
Over the six-year study, 144 of the participants developed dementia. An analysis of the personality and lifestyle data suggested that people with low levels of neuroticism and high scores on extrovert traits were the least likely to develop dementia. When addressed in the context of an individual’s lifestyle — ranging from social butterfly to shut-in — the findings suggested that having a socially integrated lifestyle may provide a buffer against the pro-dementia risk of being easily distressed. But in people leading more isolated lives, having low neuroticism scores still seemed to offer some protection against dementia.
The researchers accounted for differences among the participants in age, gender, education, depression symptoms, vascular problems, genetic factors linked to Alzheimer’s risk and cognitive function at the start of the study.
The findings confirm past reports suggesting that personality and lifestyle factors can contribute to dementia risk in some way other than well- established risk factors, says neuropsychologist Robert Wilson of Rush University Medical Center in Chicago. Those factors include amyloid-beta plaques, Lewy body deposits, tau tangles in cells and brain-tissue damage from strokes.
Wilson’s group has conducted autopsy studies of people and found no relationship between neuroticism and plaques or the other familiar hallmarks of dementia. “There must be some sort of novel mechanism involved that somehow renders you more likely to express dementia,” he says. “No one is sure what it is.”
There are theories. For example, people with high neuroticism scores also have high circulating levels of stress hormones. “Generally, that’s bad for you over time,” Wilson says. Studies in animals suggest that these extra hormones damage parts of the brain implicated in memory and thinking, he says.
The new study and other research linking personality and lifestyle to dementia risks will help to focus researchers’ attention on this remaining riddle, he says. “If we could understand why personality traits like neuroticism contribute to risk … it might offer insights into novel ways to reduce that risk.” These might include exercise, antidepressants or dietary changes, Wilson says. http://Louis1J1Sheehan1Esquire.us
Louis J. Sheehan, Esquire The study suggests that an active lifestyle may buffer against the negative effects of high neuroticism, even in extroverts, says study coauthor Hui-Xin Wang, a research scientist also at the Karolinska Institute. "But it is difficult to say to what extent lifestyle intervention can offset a person's basic personality characteristics," she cautions. Louis J. Sheehan, Esquire
People who don’t typically get distressed by routine events that might unnerve others seem to have a reduced likelihood of developing dementia in old age, concludes a study of elderly Swedish people published in the Jan. 20 Neurology. http://Louis1J1Sheehan1Esquire.us
Physician Laura Fratiglioni of the Karolinska Institute in Stockholm and her colleagues studied 506 people in their 80s who didn’t have dementia upon enrolling in a long-term medical study. All participants agreed to take personality tests, filling out a questionnaire that assessed what scientists call neuroticism, a state of being easily distressed. The questions also revealed how extroverted a person is. http://Louis1J1Sheehan1Esquire.us
Interviews of the participants determined whether a person was likely to be socially active or to live a more isolated life.
Over the six-year study, 144 of the participants developed dementia. An analysis of the personality and lifestyle data suggested that people with low levels of neuroticism and high scores on extrovert traits were the least likely to develop dementia. When addressed in the context of an individual’s lifestyle — ranging from social butterfly to shut-in — the findings suggested that having a socially integrated lifestyle may provide a buffer against the pro-dementia risk of being easily distressed. But in people leading more isolated lives, having low neuroticism scores still seemed to offer some protection against dementia.
The researchers accounted for differences among the participants in age, gender, education, depression symptoms, vascular problems, genetic factors linked to Alzheimer’s risk and cognitive function at the start of the study.
The findings confirm past reports suggesting that personality and lifestyle factors can contribute to dementia risk in some way other than well- established risk factors, says neuropsychologist Robert Wilson of Rush University Medical Center in Chicago. Those factors include amyloid-beta plaques, Lewy body deposits, tau tangles in cells and brain-tissue damage from strokes.
Wilson’s group has conducted autopsy studies of people and found no relationship between neuroticism and plaques or the other familiar hallmarks of dementia. “There must be some sort of novel mechanism involved that somehow renders you more likely to express dementia,” he says. “No one is sure what it is.”
There are theories. For example, people with high neuroticism scores also have high circulating levels of stress hormones. “Generally, that’s bad for you over time,” Wilson says. Studies in animals suggest that these extra hormones damage parts of the brain implicated in memory and thinking, he says.
The new study and other research linking personality and lifestyle to dementia risks will help to focus researchers’ attention on this remaining riddle, he says. “If we could understand why personality traits like neuroticism contribute to risk … it might offer insights into novel ways to reduce that risk.” These might include exercise, antidepressants or dietary changes, Wilson says. http://Louis1J1Sheehan1Esquire.us
Louis J. Sheehan, Esquire The study suggests that an active lifestyle may buffer against the negative effects of high neuroticism, even in extroverts, says study coauthor Hui-Xin Wang, a research scientist also at the Karolinska Institute. "But it is difficult to say to what extent lifestyle intervention can offset a person's basic personality characteristics," she cautions. Louis J. Sheehan, Esquire
gates 1.gat771772.8 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
You wouldn’t ask a toddler to wear an adult’s shoes or to chow down its dad’s caloric intake. That’s why clothes, menu portions, even video lengths are adapted to the diminutive sizes appropriate to young children. Yet all too often, medicines are tested in adults and then dispensed in what amounts to an almost one-size-fits-all approach.
Sure, cough-syrup labels recommend that the number of teaspoons administered should be loosely based a patient’s weight. Yet the efficacy of medicine doesn’t necessarily scale with weight alone. It may relate to breathing rate or blood volume, which in children may not scale up or down proportionately with height or weight. Similarly, a therapy’s benefit may scale with the size of an organ — one that may fail to grow much prior to puberty, or with the production of some breakdown enzyme that doesn’t get revved up until a child is at least 6 years old.
One timely example came to light last week involving Vicks VapoRub. It turns out that the mucus buildup fostered by inhaling Vicks vapors may disproportionately risk closing off a young child’s airways, not only because those airways are far narrower than in adults to start with, but also because the walls of major airways in babies are flimsier — less rigid.
For such reasons, pediatricians have reiterated until they’re blue in the face that children are not just small adults.
The pharmaceutical industry, however, has tended to treat children as if they were merely light-weight grown-ups. Or ignored youngsters entirely. According to the World Health Organization, “More than 50 percent of medicines prescribed for children have either not been developed specifically for children or have not been proven to be effective and safe for their use.”
“Children are suffering and dying from diseases we can treat, and yet we lack the critical evidence needed to deliver appropriate effective, affordable medicines that might save them,” argues Carissa Etienne, Assistant Director-General for WHO in Geneva, Switzerland. http://LOUIS-J-SHEEHAN-ESQUIRE.US As such, she contends, “We must take the guess work out of medicines for children.” Louis J. Sheehan, Esquire
In has stepped wealthy benefactors: Bill and Melinda Gates (of Microsoft fame). WHO announced today that their foundation has just donated $9.7 million to work with the United Nations Children’s Fund — better known as UNICEF — to conduct research on establishing child-size dispensing rates for critical medicines. They’re especially needed for treating diarrheal diseases. http://LOUIS-J-SHEEHAN-ESQUIRE.US About 160 children around the world every hour die from such diseases. Currently few medicines outside the developed world have been formulated to successfully treat them.Louis J. Sheehan, Esquire
Although it’s great that the Gates Foundation has stepped forward, the travesty is that the world’s pharmaceutical firms and health agencies didn’t beat them to the punch.Louis J. Sheehan, Esquire
You wouldn’t ask a toddler to wear an adult’s shoes or to chow down its dad’s caloric intake. That’s why clothes, menu portions, even video lengths are adapted to the diminutive sizes appropriate to young children. Yet all too often, medicines are tested in adults and then dispensed in what amounts to an almost one-size-fits-all approach.
Sure, cough-syrup labels recommend that the number of teaspoons administered should be loosely based a patient’s weight. Yet the efficacy of medicine doesn’t necessarily scale with weight alone. It may relate to breathing rate or blood volume, which in children may not scale up or down proportionately with height or weight. Similarly, a therapy’s benefit may scale with the size of an organ — one that may fail to grow much prior to puberty, or with the production of some breakdown enzyme that doesn’t get revved up until a child is at least 6 years old.
One timely example came to light last week involving Vicks VapoRub. It turns out that the mucus buildup fostered by inhaling Vicks vapors may disproportionately risk closing off a young child’s airways, not only because those airways are far narrower than in adults to start with, but also because the walls of major airways in babies are flimsier — less rigid.
For such reasons, pediatricians have reiterated until they’re blue in the face that children are not just small adults.
The pharmaceutical industry, however, has tended to treat children as if they were merely light-weight grown-ups. Or ignored youngsters entirely. According to the World Health Organization, “More than 50 percent of medicines prescribed for children have either not been developed specifically for children or have not been proven to be effective and safe for their use.”
“Children are suffering and dying from diseases we can treat, and yet we lack the critical evidence needed to deliver appropriate effective, affordable medicines that might save them,” argues Carissa Etienne, Assistant Director-General for WHO in Geneva, Switzerland. http://LOUIS-J-SHEEHAN-ESQUIRE.US As such, she contends, “We must take the guess work out of medicines for children.” Louis J. Sheehan, Esquire
In has stepped wealthy benefactors: Bill and Melinda Gates (of Microsoft fame). WHO announced today that their foundation has just donated $9.7 million to work with the United Nations Children’s Fund — better known as UNICEF — to conduct research on establishing child-size dispensing rates for critical medicines. They’re especially needed for treating diarrheal diseases. http://LOUIS-J-SHEEHAN-ESQUIRE.US About 160 children around the world every hour die from such diseases. Currently few medicines outside the developed world have been formulated to successfully treat them.Louis J. Sheehan, Esquire
Although it’s great that the Gates Foundation has stepped forward, the travesty is that the world’s pharmaceutical firms and health agencies didn’t beat them to the punch.Louis J. Sheehan, Esquire
tubulin 5.tub.002 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
Louis J. Sheehan, Esquire As cells get older, they don’t lose their hair or teeth. Instead, they lose control over their nuclear membrane, the protective barrier that encases DNA in the nucleus, concludes a study published in the Jan. 23 Cell.http://Louis2J2Sheehan2Esquire.US This age-dependent leakiness may be closely tied to cell deterioration and age-related diseases such as Parkinson’s and Alzheimer’s, the new work suggests.
“The implications of this study for our study of brain aging and for neurodegenerative diseases are potentially profound,” comments John Woulfe, a specialist in age-related diseases at the University of Ottawa in Canada. Louis J. Sheehan, Esquire The new findings, he says, represent “an important step forward by bringing the gateway to the nucleus, the nuclear pore, into the fray.”http://Louis2J2Sheehan2Esquire.US
Nuclear membranes are like screen doors on a porch: They let the refreshing breeze in but keep the mosquitoes out. The double-layered membrane allows nuclear entry for VIP proteins, most of which control gene activity. The proteins travel into the nucleus through channels in the membrane called nuclear pores.
Meanwhile, damaging chemicals and proteins that float around in the cell’s cytoplasm, the jellylike liquid that surrounds the nucleus and other organelles, are rebuffed by the membrane.
Using cells from small worms called Caenorhabditis elegans and cells from rats, Martin Hetzer of the Salk Institute for Biological Studies in La Jolla, Calif., and colleagues found that the proteins that form a nuclear pore stay in the same location for the remainder of the cell’s life. The researchers monitored the location of these pore proteins by marking several of them with green fluorescent protein. After seeing that the pore proteins stay in the same place on the same cells, the researchers concluded that these pores “exhibit extreme stability.”
These nuclear pores are unusually long-lived for cell parts, says Hetzer. Just as drivers replace worn-out parts as cars get older, most cell parts are constantly replaced. But nuclear pores are in it for the long haul. “We think that pores are among the most stable, if not the most stable, structures in our cells,” says Hetzer.
Because nuclear pores don’t get repaired or replaced, Hetzer and colleagues next wanted to know whether the pores maintain a high level of performance even as the cell ages.
The researchers found that old cells’ nuclear membranes allow entry to molecules that are excluded in cells’ younger days. Fluorescently labeled molecules normally too large to enter the nucleus slipped right through old nuclear membranes, while younger nuclear membranes performed perfectly.
Perhaps most dangerous, a protein called tubulin that is usually restricted to the cytoplasm was able to slip through the nuclear membrane of old cells, the researchers saw.
Filamentous tangles of tubulin in the nuclei of cells have been linked to the aging process and to neurodegenerative diseases. These nuclear filaments are known to increase with age, but their origins have been a mystery, says Hetzer. Patients with Parkinson’s disease have such tangles in cells in a brain region known to be affected by the illness. “We speculate that the nuclei in these patients are leaky,” says Hetzer.
The research team’s next step is to study the link between leaky nuclear membranes and age-related diseases. If leaky nuclei contribute to the cellular degeneration seen in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, then leaky nuclei may “represent a viable future therapeutic target,” says Woulfe.
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Found in: Biology, Body & Brain and Genes & Cells
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Comments 3
* Aging, Leakiness Of Nucleus Membrane
The Aging Whole Being A Construct Of Its Constituents
A. "As cells age, the nucleus lets the bad guys in"
http://www.sciencenews.org/view/generic/id/40136/title/As_cells_age%2C_the_nucleus_lets_the_bad_guys_in
A study tracks a growing 'leakiness' in the membrane of the cell nucleus that could contribute to aging and even to diseases such as Parkinson's and Alzheimer's.
B. The nucleus membrane is an organ, a functional organ of the genome organism
All biological materials, of all forms, 'age'-change with time and with environments-circumstances. The list of possible age-related pore-leakiness effectors comprises a variety of 'aging' facors that continuously modify the functionality of the pore and modifies also the characteristics of the constituents of the inventory of materials within the outer cell membrane, the largest organ of the genome.
C. "Aging Not Approachable With Oversimplification". Aging Is A Closed Chain.
http://www.the-scientist.com/community/posts/list/100/122.page#1318
Aging genes age genomes age cells age cellular organisms and vice versa, the whole WHOLE being a construct of its constituents...
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Life's Manifest
http://www.the-scientist.com/community/posts/list/112.page#578
Dov Henis Dov Henis
Jan. 27, 2009 at 10:52am
* Continued healthy living;quality vegetables; fruits; grains,etc.; clean water and air need to be pursued for all and especially for the young. Does the protein,tubulin slip through the old cells of elderly healthy adults as easily as through the old cells of elderly, unhealthy adults, as evidenced in the research referred to in the above article?
corina nicumber corcan09 http://Louis2J2Sheehan2Esquire.US
Jan. 25, 2009 at 4:36pm
* You don't suppose this is related to free radicals, and their effect on proteins? http://Louis2J2Sheehan2Esquire.US This would certainly explain the neuro-protective effects of all of the antioxidants. Since these proteins are not replaced in the life of the cell, and the long life of neurons, this would be a fruitful area of research, if we are to improve not only length of life, but also quality of life in older people. Sadly, unless these nuclear pore proteins can be repaired, a life of stress and chemical abuse could not be undone, no matter how much Vit-E you take when the symptoms of Parkinsons, or dementia ,or alcoholic neuropathy set in.Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire As cells get older, they don’t lose their hair or teeth. Instead, they lose control over their nuclear membrane, the protective barrier that encases DNA in the nucleus, concludes a study published in the Jan. 23 Cell.http://Louis2J2Sheehan2Esquire.US This age-dependent leakiness may be closely tied to cell deterioration and age-related diseases such as Parkinson’s and Alzheimer’s, the new work suggests.
“The implications of this study for our study of brain aging and for neurodegenerative diseases are potentially profound,” comments John Woulfe, a specialist in age-related diseases at the University of Ottawa in Canada. Louis J. Sheehan, Esquire The new findings, he says, represent “an important step forward by bringing the gateway to the nucleus, the nuclear pore, into the fray.”http://Louis2J2Sheehan2Esquire.US
Nuclear membranes are like screen doors on a porch: They let the refreshing breeze in but keep the mosquitoes out. The double-layered membrane allows nuclear entry for VIP proteins, most of which control gene activity. The proteins travel into the nucleus through channels in the membrane called nuclear pores.
Meanwhile, damaging chemicals and proteins that float around in the cell’s cytoplasm, the jellylike liquid that surrounds the nucleus and other organelles, are rebuffed by the membrane.
Using cells from small worms called Caenorhabditis elegans and cells from rats, Martin Hetzer of the Salk Institute for Biological Studies in La Jolla, Calif., and colleagues found that the proteins that form a nuclear pore stay in the same location for the remainder of the cell’s life. The researchers monitored the location of these pore proteins by marking several of them with green fluorescent protein. After seeing that the pore proteins stay in the same place on the same cells, the researchers concluded that these pores “exhibit extreme stability.”
These nuclear pores are unusually long-lived for cell parts, says Hetzer. Just as drivers replace worn-out parts as cars get older, most cell parts are constantly replaced. But nuclear pores are in it for the long haul. “We think that pores are among the most stable, if not the most stable, structures in our cells,” says Hetzer.
Because nuclear pores don’t get repaired or replaced, Hetzer and colleagues next wanted to know whether the pores maintain a high level of performance even as the cell ages.
The researchers found that old cells’ nuclear membranes allow entry to molecules that are excluded in cells’ younger days. Fluorescently labeled molecules normally too large to enter the nucleus slipped right through old nuclear membranes, while younger nuclear membranes performed perfectly.
Perhaps most dangerous, a protein called tubulin that is usually restricted to the cytoplasm was able to slip through the nuclear membrane of old cells, the researchers saw.
Filamentous tangles of tubulin in the nuclei of cells have been linked to the aging process and to neurodegenerative diseases. These nuclear filaments are known to increase with age, but their origins have been a mystery, says Hetzer. Patients with Parkinson’s disease have such tangles in cells in a brain region known to be affected by the illness. “We speculate that the nuclei in these patients are leaky,” says Hetzer.
The research team’s next step is to study the link between leaky nuclear membranes and age-related diseases. If leaky nuclei contribute to the cellular degeneration seen in neurodegenerative diseases such as Parkinson’s and Alzheimer’s, then leaky nuclei may “represent a viable future therapeutic target,” says Woulfe.
* |
* Comment
Found in: Biology, Body & Brain and Genes & Cells
Share & Save
* slashdot slashdot
* digg digg
* facebook facebook
* yahoo yahoo
* del.icio.us del.icio.us
* reddit reddit
* google google
* technorati technorati
Comments 3
* Aging, Leakiness Of Nucleus Membrane
The Aging Whole Being A Construct Of Its Constituents
A. "As cells age, the nucleus lets the bad guys in"
http://www.sciencenews.org/view/generic/id/40136/title/As_cells_age%2C_the_nucleus_lets_the_bad_guys_in
A study tracks a growing 'leakiness' in the membrane of the cell nucleus that could contribute to aging and even to diseases such as Parkinson's and Alzheimer's.
B. The nucleus membrane is an organ, a functional organ of the genome organism
All biological materials, of all forms, 'age'-change with time and with environments-circumstances. The list of possible age-related pore-leakiness effectors comprises a variety of 'aging' facors that continuously modify the functionality of the pore and modifies also the characteristics of the constituents of the inventory of materials within the outer cell membrane, the largest organ of the genome.
C. "Aging Not Approachable With Oversimplification". Aging Is A Closed Chain.
http://www.the-scientist.com/community/posts/list/100/122.page#1318
Aging genes age genomes age cells age cellular organisms and vice versa, the whole WHOLE being a construct of its constituents...
Dov Henis
(Comments From The 22nd Century)
http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q--?cq=1
Life's Manifest
http://www.the-scientist.com/community/posts/list/112.page#578
Dov Henis Dov Henis
Jan. 27, 2009 at 10:52am
* Continued healthy living;quality vegetables; fruits; grains,etc.; clean water and air need to be pursued for all and especially for the young. Does the protein,tubulin slip through the old cells of elderly healthy adults as easily as through the old cells of elderly, unhealthy adults, as evidenced in the research referred to in the above article?
corina nicumber corcan09 http://Louis2J2Sheehan2Esquire.US
Jan. 25, 2009 at 4:36pm
* You don't suppose this is related to free radicals, and their effect on proteins? http://Louis2J2Sheehan2Esquire.US This would certainly explain the neuro-protective effects of all of the antioxidants. Since these proteins are not replaced in the life of the cell, and the long life of neurons, this would be a fruitful area of research, if we are to improve not only length of life, but also quality of life in older people. Sadly, unless these nuclear pore proteins can be repaired, a life of stress and chemical abuse could not be undone, no matter how much Vit-E you take when the symptoms of Parkinsons, or dementia ,or alcoholic neuropathy set in.Louis J. Sheehan, Esquire
patent 0.pat.001 Louis J. Sheehan, Esquire
http://rpc.technorati.com/rpc/ping
The phrase patent medicine comes from the late 17th century[1] marketing of medical elixirs, when those who found favour with royalty were issued letters patent authorising the use of the royal endorsement in advertising. The name stuck well after the American Revolution made these endorsements by the crowned heads of Europe obsolete. Few if any of the nostrums were actually patented; chemical patents came into use in the USA in 1925, and in any case attempting to monopolize a drug, medical device, or medical procedure was considered unethical by the standards upheld during the era of patent medicine. Furthermore, patenting one of these remedies would have meant publicly disclosing its ingredients, which most promoters wanted to avoid.
Instead, the compounders of these nostrums used a primitive version of branding to distinguish themselves from the crowd of their competitors. Many familiar names from the era live on in brands such as Luden's cough drops, Lydia E. Pinkham's vegetable compound for women, Fletcher's Castoria, and even Angostura bitters, which was once marketed as a stomach remedy. Many of these medicines, though sold at high prices, were made from quite cheap ingredients. Their composition was well known within the pharmacy trade, and druggists would sell (for a slightly lower price) medicines of almost identical composition that they had manufactured themselves. To protect profits, the branded medicine advertisements laid great emphasis on the brand-names, and urged the public to accept no substitutes.
At least in the earliest days, the history of patent medicines is coextensive with the history of medicine itself. Empirical medicine, and the beginning of the application of the scientific method to medicine, began to yield a few effective herbal and mineral drugs for the physician's arsenal. These few tested and true remedies, on the other hand, were inadequate to cover the bewildering variety of diseases and symptoms. Beyond these patches of knowledge they had to resort to occultism; the "doctrine of signatures" — essentially, the application of sympathetic magic to pharmacology — held that nature had hidden clues to medically effective drugs in their resemblances to the human body and its parts. This led medical men to hope, at least, that, say, walnut shells might be good for skull fractures. Given the state of the pharmacopoeia, and patients' demands for something to take, physicians began making "blunderbuss" concoctions of various drugs, proven and unproven. These concoctions were the ancestors of the several nostrums.
Touting these nostrums was one of the first major projects of the advertising industry. The marketing of nostrums under implausible claims has a long history. In Henry Fielding's Tom Jones (1749), allusion is made to the sale of medical compounds claimed to be universal panaceas:
As to Squire Western, he was seldom out of the sick-room, unless when he was engaged either in the field or over his bottle. Nay, he would sometimes retire hither to take his beer, and it was not without difficulty that he was prevented from forcing Jones to take his beer too: for no quack ever held his nostrum to be a more general panacea than he did this; which, he said, had more virtue in it than was in all the physic in an apothecary's shop.
Lydia Pinkham's Herb Medicine (circa 1875) remains on the market today.
Within the English-speaking world, patent medicines are as old as journalism. "Anderson's Pills" were first made in England in the 1630s; the recipe was allegedly learned in Venice by a Scot who claimed to be physician to King Charles I. The use of letters patent to obtain exclusive marketing rights to certain labelled formulas and their marketing fueled the circulation of early newspapers. The use of invented names began early. In 1726 a patent was also granted to the makers of "Dr. Bateman's Pectoral Drops"; at least on the documents that survive, there was no Dr. Bateman. This was the enterprise of a Benjamin Okell and a group of promoters who owned a warehouse and a print shop to promote the product.
A number of American institutions owe their existence to the patent medicine industry, most notably a number of the older almanacs, which were originally given away as promotional items by patent medicine manufacturers. Perhaps the most successful industry that grew up out of the business of patent medicine advertisements, though, was founded by William H. Gannett in Maine in 1866. There were few circulating newspapers in Maine in that era, so Gannett founded a periodical, Comfort, whose chief purpose was to propose the merits of Oxien, a nostrum made from the fruit of the baobab tree, to the rural folks of Maine. Gannett's newspaper became the first publication of Guy Gannett Communications, which eventually owned four Maine dailies and several television stations. (The family-owned firm is not related to the giant Gannett Corporation, publisher of "USA Today.") An early pioneer in the use of advertising to promote patent medicine was the New York businessman Benjamin Brandreth whose "Vegetable Universal Pill" eventually became one of the best selling patent medicines in the United States [2] “…A congressional committee in 1849 reported that Brandreth was the nation’s largest proprietary advertiser… Between 1862 and 1863 Brandreth’s average annual gross income surpassed $600,000…”[3] For fifty years Brandreth’s name was a household word in the United States[4] Indeed, the Brandreth pills were so well known they received mention in Herman Melville's classic Moby Dick[5].
Kickapoo Indian "Sagwa", sold at medicine shows http://Louis1J1Sheehan.us
Another method of publicity undertaken mostly by smaller firms was the "medicine show," a traveling circus of sorts which offered vaudeville-style entertainments on a small scale, and which climaxed in a pitch for the nostrum being sold. Muscle man acts were especially popular on these tours, for this enabled the salesman to tout the physical vigour offered by the potion he was selling. The showmen frequently employed shills, who would step forward from the crowd and offer "unsolicited" testimonials about the benefits of the medicine for sale. Often, the nostrum was manufactured and bottled in the same wagon that the show travelled in. The Kickapoo Indian Medicine Company became one of the largest and most successful medicine show operators; their shows had an American Indian or Wild West theme, and employed many Native Americans as spokespeople. The medicine show lived on in American folklore and Western movies long after they had vanished from public meeting places.Louis J. Sheehan, Esquire
The phrase patent medicine comes from the late 17th century[1] marketing of medical elixirs, when those who found favour with royalty were issued letters patent authorising the use of the royal endorsement in advertising. The name stuck well after the American Revolution made these endorsements by the crowned heads of Europe obsolete. Few if any of the nostrums were actually patented; chemical patents came into use in the USA in 1925, and in any case attempting to monopolize a drug, medical device, or medical procedure was considered unethical by the standards upheld during the era of patent medicine. Furthermore, patenting one of these remedies would have meant publicly disclosing its ingredients, which most promoters wanted to avoid.
Instead, the compounders of these nostrums used a primitive version of branding to distinguish themselves from the crowd of their competitors. Many familiar names from the era live on in brands such as Luden's cough drops, Lydia E. Pinkham's vegetable compound for women, Fletcher's Castoria, and even Angostura bitters, which was once marketed as a stomach remedy. Many of these medicines, though sold at high prices, were made from quite cheap ingredients. Their composition was well known within the pharmacy trade, and druggists would sell (for a slightly lower price) medicines of almost identical composition that they had manufactured themselves. To protect profits, the branded medicine advertisements laid great emphasis on the brand-names, and urged the public to accept no substitutes.
At least in the earliest days, the history of patent medicines is coextensive with the history of medicine itself. Empirical medicine, and the beginning of the application of the scientific method to medicine, began to yield a few effective herbal and mineral drugs for the physician's arsenal. These few tested and true remedies, on the other hand, were inadequate to cover the bewildering variety of diseases and symptoms. Beyond these patches of knowledge they had to resort to occultism; the "doctrine of signatures" — essentially, the application of sympathetic magic to pharmacology — held that nature had hidden clues to medically effective drugs in their resemblances to the human body and its parts. This led medical men to hope, at least, that, say, walnut shells might be good for skull fractures. Given the state of the pharmacopoeia, and patients' demands for something to take, physicians began making "blunderbuss" concoctions of various drugs, proven and unproven. These concoctions were the ancestors of the several nostrums.
Touting these nostrums was one of the first major projects of the advertising industry. The marketing of nostrums under implausible claims has a long history. In Henry Fielding's Tom Jones (1749), allusion is made to the sale of medical compounds claimed to be universal panaceas:
As to Squire Western, he was seldom out of the sick-room, unless when he was engaged either in the field or over his bottle. Nay, he would sometimes retire hither to take his beer, and it was not without difficulty that he was prevented from forcing Jones to take his beer too: for no quack ever held his nostrum to be a more general panacea than he did this; which, he said, had more virtue in it than was in all the physic in an apothecary's shop.
Lydia Pinkham's Herb Medicine (circa 1875) remains on the market today.
Within the English-speaking world, patent medicines are as old as journalism. "Anderson's Pills" were first made in England in the 1630s; the recipe was allegedly learned in Venice by a Scot who claimed to be physician to King Charles I. The use of letters patent to obtain exclusive marketing rights to certain labelled formulas and their marketing fueled the circulation of early newspapers. The use of invented names began early. In 1726 a patent was also granted to the makers of "Dr. Bateman's Pectoral Drops"; at least on the documents that survive, there was no Dr. Bateman. This was the enterprise of a Benjamin Okell and a group of promoters who owned a warehouse and a print shop to promote the product.
A number of American institutions owe their existence to the patent medicine industry, most notably a number of the older almanacs, which were originally given away as promotional items by patent medicine manufacturers. Perhaps the most successful industry that grew up out of the business of patent medicine advertisements, though, was founded by William H. Gannett in Maine in 1866. There were few circulating newspapers in Maine in that era, so Gannett founded a periodical, Comfort, whose chief purpose was to propose the merits of Oxien, a nostrum made from the fruit of the baobab tree, to the rural folks of Maine. Gannett's newspaper became the first publication of Guy Gannett Communications, which eventually owned four Maine dailies and several television stations. (The family-owned firm is not related to the giant Gannett Corporation, publisher of "USA Today.") An early pioneer in the use of advertising to promote patent medicine was the New York businessman Benjamin Brandreth whose "Vegetable Universal Pill" eventually became one of the best selling patent medicines in the United States [2] “…A congressional committee in 1849 reported that Brandreth was the nation’s largest proprietary advertiser… Between 1862 and 1863 Brandreth’s average annual gross income surpassed $600,000…”[3] For fifty years Brandreth’s name was a household word in the United States[4] Indeed, the Brandreth pills were so well known they received mention in Herman Melville's classic Moby Dick[5].
Kickapoo Indian "Sagwa", sold at medicine shows http://Louis1J1Sheehan.us
Another method of publicity undertaken mostly by smaller firms was the "medicine show," a traveling circus of sorts which offered vaudeville-style entertainments on a small scale, and which climaxed in a pitch for the nostrum being sold. Muscle man acts were especially popular on these tours, for this enabled the salesman to tout the physical vigour offered by the potion he was selling. The showmen frequently employed shills, who would step forward from the crowd and offer "unsolicited" testimonials about the benefits of the medicine for sale. Often, the nostrum was manufactured and bottled in the same wagon that the show travelled in. The Kickapoo Indian Medicine Company became one of the largest and most successful medicine show operators; their shows had an American Indian or Wild West theme, and employed many Native Americans as spokespeople. The medicine show lived on in American folklore and Western movies long after they had vanished from public meeting places.Louis J. Sheehan, Esquire
Saturday, April 11, 2009
ENZYMES 882.ENZ.0 LOUIS J. SHEEHAN, ESQUIRE
http://rpc.technorati.com/rpc/ping
LOUIS J. SHEEHAN, ESQUIRE Mutations in two genes, IDH1 and IDH2, might provide markers that enable doctors to discern malignant from benign brain tumors and catch some cancers early, scientists report in the Feb. 19 New England Journal of Medicine.
The study adds to a growing list of molecular clues that doctors may ultimately use to diagnosis and treat cancers, says study coauthor D. Williams Parsons, a pediatric oncologist and Howard Hughes Medical Institute investigator at Johns Hopkins University in Baltimore.http://LOUIS-J-SHEEHAN.US
Doctors diagnose nearly 200,000 brain cancers each year in the United States. Most get their start elsewhere in the body and spread to the brain. But in about 22,000 of these patients, the cancer originates in the brain or central nervous system. These primary brain tumors are most often gliomas — clusters of tumor cells that derive from the brain’s glial cells. Gliomas vary in virulence from benign (grade 1) to fast-growing and rapidly lethal (grade 4).http://LOUIS-J-SHEEHAN.US
The IDH genes are so-named because they encode an enzyme called isocitrate dehydrogenase. While the role of the enzyme is poorly understood, the mutations in IDH genes attracted interest after turning up last year in brain tumors but not in other cancer tissues. In the new study, the researchers tested samples of benign and cancerous primary brain tumors removed from 445 people and from tumors obtained from 494 others who had cancers of the colon, prostate, pancreas, breast, stomach, ovary or blood (leukemia).
No benign brain tumor cells harbored a mutation in the IDH genes, nor did any of the cancerous samples taken from elsewhere in the body.
But about 70 percent of low- to mid-range gliomas — grades 2 and 3 — had a mutated IDH gene, mainly IDH1. These malignancies account for thousands of cases of brain cancer each year, Parsons says. The mutation was rare in most grade 4 cancers unless they arose directly from lower-grade gliomas.
The finding suggests that these IDH mutations “play a unique role in the pathogenesis of gliomas,” says physician Craig Thompson of the University of Pennsylvania in Philadelphia, writing in the same NEJM issue. As such, determining the role of the genes and the enzymes they encode could elucidate a molecular target for brain cancer therapy, he says.LOUIS J. SHEEHAN, ESQUIRE
Meanwhile, the finding might have more immediate value in the clinic. After a surgeon removes a brain tumor or part of it, a pathologist analyzes the tissue. But it can be difficult to tell a benign tumor from a slow-growing grade 2 tumor, which is nonetheless cancerous. “A grade 2 tumor always progresses to a grade 3 and 4. It might take years,” Parsons says. Thus, the new finding might help pathologists catch more malignant tumors early, he says.
Ultimately, the IDH mutations may prove to be “gatekeeper genes“ for certain gliomas, says study coauthor Hai Yan, a cancer geneticist at Duke University Medical Center in Durham, N.C. Cancers get their start when genes mutate and change the cell’s behavior. Advanced cancers have so many such mutations they resist cure. But catching such defects early — right out of the gate — would simplify the target and improve the chance of stopping the cancer, Yan says. LOUIS J. SHEEHAN, ESQUIRE
LOUIS J. SHEEHAN, ESQUIRE Mutations in two genes, IDH1 and IDH2, might provide markers that enable doctors to discern malignant from benign brain tumors and catch some cancers early, scientists report in the Feb. 19 New England Journal of Medicine.
The study adds to a growing list of molecular clues that doctors may ultimately use to diagnosis and treat cancers, says study coauthor D. Williams Parsons, a pediatric oncologist and Howard Hughes Medical Institute investigator at Johns Hopkins University in Baltimore.http://LOUIS-J-SHEEHAN.US
Doctors diagnose nearly 200,000 brain cancers each year in the United States. Most get their start elsewhere in the body and spread to the brain. But in about 22,000 of these patients, the cancer originates in the brain or central nervous system. These primary brain tumors are most often gliomas — clusters of tumor cells that derive from the brain’s glial cells. Gliomas vary in virulence from benign (grade 1) to fast-growing and rapidly lethal (grade 4).http://LOUIS-J-SHEEHAN.US
The IDH genes are so-named because they encode an enzyme called isocitrate dehydrogenase. While the role of the enzyme is poorly understood, the mutations in IDH genes attracted interest after turning up last year in brain tumors but not in other cancer tissues. In the new study, the researchers tested samples of benign and cancerous primary brain tumors removed from 445 people and from tumors obtained from 494 others who had cancers of the colon, prostate, pancreas, breast, stomach, ovary or blood (leukemia).
No benign brain tumor cells harbored a mutation in the IDH genes, nor did any of the cancerous samples taken from elsewhere in the body.
But about 70 percent of low- to mid-range gliomas — grades 2 and 3 — had a mutated IDH gene, mainly IDH1. These malignancies account for thousands of cases of brain cancer each year, Parsons says. The mutation was rare in most grade 4 cancers unless they arose directly from lower-grade gliomas.
The finding suggests that these IDH mutations “play a unique role in the pathogenesis of gliomas,” says physician Craig Thompson of the University of Pennsylvania in Philadelphia, writing in the same NEJM issue. As such, determining the role of the genes and the enzymes they encode could elucidate a molecular target for brain cancer therapy, he says.LOUIS J. SHEEHAN, ESQUIRE
Meanwhile, the finding might have more immediate value in the clinic. After a surgeon removes a brain tumor or part of it, a pathologist analyzes the tissue. But it can be difficult to tell a benign tumor from a slow-growing grade 2 tumor, which is nonetheless cancerous. “A grade 2 tumor always progresses to a grade 3 and 4. It might take years,” Parsons says. Thus, the new finding might help pathologists catch more malignant tumors early, he says.
Ultimately, the IDH mutations may prove to be “gatekeeper genes“ for certain gliomas, says study coauthor Hai Yan, a cancer geneticist at Duke University Medical Center in Durham, N.C. Cancers get their start when genes mutate and change the cell’s behavior. Advanced cancers have so many such mutations they resist cure. But catching such defects early — right out of the gate — would simplify the target and improve the chance of stopping the cancer, Yan says. LOUIS J. SHEEHAN, ESQUIRE
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