Today's Elites
Friday, April 29, 2011
The Disgusting Malodorous Media
This morning, when I arose to exercise, as is my wont, I turned on the television to view what passes as "the news." Every single "news" channel and then some, had interrupted their "normal programming" to provide us with the nauseating spectacle of the Royal Wedding. The same Royal family which our founders suffered the ultimate sacrifice from which to free ourselves. Here "liberal" and "conservative" networks alike abjectly fawned over and gushed their hardly hidden preference that we might have once again the pageantry of such a royal family here. The same Royal family whose current figurehead's consort openly avows that he so hates humanity that he wishes to be reincarnated as a deadly virus to reduce the population. Like Poe's purloined letter the truth is right under your nose, but you will not see it. If you would but stop larding on the perfume provided by our disgraceful media "stars," the stench of this Royal Rot would make you very, very ill, indeed...
Pacemaker or Autowaves, Biophysical and Noetic Curvature, and Shockwaves
For the first time, it has been shown by researchers at UC San Diego that regular electrical oscillatory waves in the brain are a requirement for the proper firing of neurons that provide a nodal grid that acts as a conformal mapping as a kind of spatial sensory compass. There are a number of profound implications of this development which I will attempt to illustrate here.
The first broad implication has to do with the concept of a conformal mapping per se. Gauss showed that the natural alternation of negative to positive curvature of surfaces that we encounter everywhere in nature may be conformally mapped via normals to a tangent plane onto a unit hypersphere. (Hilbert gives a visual illustration of this in his book Geometry and the Imagination.) Riemann continued and expanded upon this concept to evolve the so-called Riemann surface function, which provides a framework for a rigorous network of nodes or branch points that allow functional passage from imaginary sheets (imaginary understood here in the sense of the complex plane) on this Gaussian unitary sphere. Now, pause here and consider how this non Euclidean geometric model might apply to the research cited above. What do we have but such a one to one mapping by our mental sensorium of the "outer space" through which we must navigate. As we move through this space, neurons can fire appropriately to provide layer upon layer of continuous maps so that we may consciously access a memory through the processing of electrical impulses at these nodes. I will return to this theme shortly after a necessary ellipsis below.
This, I hope, aptly illustrates what to most readers is a remarkable sort of prescience of the genius of a Gauss and a Riemann. However, this quality of thinking needs to be demystified, if humanity is to meet the pressing requirements of the mission of getting off this planet and colonizing space, such that these apparently inaccessible powers of mind become the common property of all. Gauss and Riemann built upon the revolution in scientific methodology introduced by Cardinal Nicholas of Cusa. Here, I must point out that the attempt to characterize Cusa as a Christian "mystic" by modern academics is a completely obfuscatory slander, either resulting from ignorant incompetence or worse intentional malevolence. Ironically, it is Cusa's concept that the microcosm and the macrocosm are necessarily intimately connected in their mutually evolving creative development that laid the foundation for breaking the chains of the destructive and insane precepts of Ptolemaic/Euclidean mystical scholasticism. This too, followed upon Dante's revolutionary ecumenical characterization in the Paradisio, where he foreshadowed Kepler's and Einstein's relativity by placing his frame of reference on the moon and thereby dispelling the mythology that there is some mystical priority of earth's place somehow mirrored in a pantheon of fixed feudal relationships. Thus, Cusa promoted the return to the Platonic/Pythagorean measurement of the curvature of the earth by the very same Gaussian normal vector to the tangent plane method by Eratosthenes in Egypt some 1700 years earlier. It is no accident, that Cusa recognized that what was to become the colonization of the new world was a necessary flanking precursor of the universal rights of humanity for development that he enunciated in his writings. This method of Cusa of comprehending and hypothesizing the underlying continuous creative composition of the physical macrocosm and noetic microcosm then, constitutes the basis for a true scientific method of investigation. This revolutionary method so challenges the authority of the establishment arbiters of the second law of thermodynamic plodding, Ockhamite sense certainty method that it is all but forbidden in accepted "peer reviewed" publications to merely allude to these actual facts.
Returning to the matter at hand, I turn next to the question of the pacemaker wave referenced above or what many Russian scientists have labeled the autowave. Again, here in writing of wave phenomena, I must return to the towering figure of Bernhard Riemann. Before there was any physical proof of sonar/pressure shockwaves, Riemann used his method of starting from elements of known physical constraints to adumbrate how shockwaves would develop. He reasoned in his paper from 1860 "The propagation of planar air waves of finite amplitude" that there is a sort of limit imposed for the propagation of waves through a medium. Furthermore, if the source of propagation of wave exceeded this limit a bunching up of waves would occur that might disrupt the medium itself. This we know today, of course, as the familiar sonic boom. (As an update, I learned that shockwaves emanating from the sun in the early solar system have been identified as responsible for stripping volatile elements from chondrites that then coalesced to form planets.)
Let us extrapolate this principal given what we have uncovered of some other wavelike phenomena since Riemann's time. The general phenomena of solitonic waves, I believe are examples of extreme wave formations that tend to bridge what Vernadsky characterized as the disparate domains of the lithosphere and biosphere (and as I believe also have a correlative in the noosphere.) It has recently been hypothesized for instance that soliton/anti soliton energetics in phage dynamics can account for transitions from active lysogenic to dormant lytic states. Long lived relatively stable wave phenomena that underlie the proper functioning of the biosphere are evident, whether they be aortic pacemaker waves, calcium brainwaves or quantum wave phenomena along the double helix of DNA.
A question that we may pose, building upon Riemann's work, is what happens in the biophysical domain when the velocity of wave propagation tends to surpass the transparency for propagation in that medium? Certainly, the catastrophic malfunction of a heart attack and epilepsy, for example, are evidence that these pacemaker waves have dynamically overloaded the biological medium. The means to solving such anomalies, is of course the appropriate province of medical research. Further we see similar destructive such anomalies in the domain of Vernadsky's lithosphere, for what are hurricanes but a kind of soliton dynamic, similarly earthquakes are characterized by disruptive gravity waves, solar flares as plasma wave events, and are not the very phenomena of black holes that can rip apart the center of galaxies themselves a type of soliton? Likewise here, it must be a mission of science to secure humanity against such threats.
Now, finally let us drive the analogy with these anomalous soliton-like formations into the domain of the noosphere. One can think of the radiation of technology in human society over time as operating similarly to the kind of standing waves in the brain. For a society, the successive "waves" of transmission of knowledge through culture and education provides the preconditions for its continued functioning and survival. However, a crisis is encountered whenever there is a limit of resource transparency for the prevailing mode of technology. As LaRouche has shown, what constitutes resources must be redefined via a breakthrough in scientific creativity. This is the quality that uniquely distinguishes the noosphere. This is what Cusa characterizes as an immanent power of humanity. But it is a mission which is also a choice. Nowhere else is there freedom in this sense. And it is truly this gift that Cusa proffered when he collaborated with Toscanelli to revive Eratosthenes non Euclidean method to send Columbus to the new world so that humanity might escape the clutches of those that would have us be slaves.
The first broad implication has to do with the concept of a conformal mapping per se. Gauss showed that the natural alternation of negative to positive curvature of surfaces that we encounter everywhere in nature may be conformally mapped via normals to a tangent plane onto a unit hypersphere. (Hilbert gives a visual illustration of this in his book Geometry and the Imagination.) Riemann continued and expanded upon this concept to evolve the so-called Riemann surface function, which provides a framework for a rigorous network of nodes or branch points that allow functional passage from imaginary sheets (imaginary understood here in the sense of the complex plane) on this Gaussian unitary sphere. Now, pause here and consider how this non Euclidean geometric model might apply to the research cited above. What do we have but such a one to one mapping by our mental sensorium of the "outer space" through which we must navigate. As we move through this space, neurons can fire appropriately to provide layer upon layer of continuous maps so that we may consciously access a memory through the processing of electrical impulses at these nodes. I will return to this theme shortly after a necessary ellipsis below.
This, I hope, aptly illustrates what to most readers is a remarkable sort of prescience of the genius of a Gauss and a Riemann. However, this quality of thinking needs to be demystified, if humanity is to meet the pressing requirements of the mission of getting off this planet and colonizing space, such that these apparently inaccessible powers of mind become the common property of all. Gauss and Riemann built upon the revolution in scientific methodology introduced by Cardinal Nicholas of Cusa. Here, I must point out that the attempt to characterize Cusa as a Christian "mystic" by modern academics is a completely obfuscatory slander, either resulting from ignorant incompetence or worse intentional malevolence. Ironically, it is Cusa's concept that the microcosm and the macrocosm are necessarily intimately connected in their mutually evolving creative development that laid the foundation for breaking the chains of the destructive and insane precepts of Ptolemaic/Euclidean mystical scholasticism. This too, followed upon Dante's revolutionary ecumenical characterization in the Paradisio, where he foreshadowed Kepler's and Einstein's relativity by placing his frame of reference on the moon and thereby dispelling the mythology that there is some mystical priority of earth's place somehow mirrored in a pantheon of fixed feudal relationships. Thus, Cusa promoted the return to the Platonic/Pythagorean measurement of the curvature of the earth by the very same Gaussian normal vector to the tangent plane method by Eratosthenes in Egypt some 1700 years earlier. It is no accident, that Cusa recognized that what was to become the colonization of the new world was a necessary flanking precursor of the universal rights of humanity for development that he enunciated in his writings. This method of Cusa of comprehending and hypothesizing the underlying continuous creative composition of the physical macrocosm and noetic microcosm then, constitutes the basis for a true scientific method of investigation. This revolutionary method so challenges the authority of the establishment arbiters of the second law of thermodynamic plodding, Ockhamite sense certainty method that it is all but forbidden in accepted "peer reviewed" publications to merely allude to these actual facts.
Returning to the matter at hand, I turn next to the question of the pacemaker wave referenced above or what many Russian scientists have labeled the autowave. Again, here in writing of wave phenomena, I must return to the towering figure of Bernhard Riemann. Before there was any physical proof of sonar/pressure shockwaves, Riemann used his method of starting from elements of known physical constraints to adumbrate how shockwaves would develop. He reasoned in his paper from 1860 "The propagation of planar air waves of finite amplitude" that there is a sort of limit imposed for the propagation of waves through a medium. Furthermore, if the source of propagation of wave exceeded this limit a bunching up of waves would occur that might disrupt the medium itself. This we know today, of course, as the familiar sonic boom. (As an update, I learned that shockwaves emanating from the sun in the early solar system have been identified as responsible for stripping volatile elements from chondrites that then coalesced to form planets.)
Let us extrapolate this principal given what we have uncovered of some other wavelike phenomena since Riemann's time. The general phenomena of solitonic waves, I believe are examples of extreme wave formations that tend to bridge what Vernadsky characterized as the disparate domains of the lithosphere and biosphere (and as I believe also have a correlative in the noosphere.) It has recently been hypothesized for instance that soliton/anti soliton energetics in phage dynamics can account for transitions from active lysogenic to dormant lytic states. Long lived relatively stable wave phenomena that underlie the proper functioning of the biosphere are evident, whether they be aortic pacemaker waves, calcium brainwaves or quantum wave phenomena along the double helix of DNA.
A question that we may pose, building upon Riemann's work, is what happens in the biophysical domain when the velocity of wave propagation tends to surpass the transparency for propagation in that medium? Certainly, the catastrophic malfunction of a heart attack and epilepsy, for example, are evidence that these pacemaker waves have dynamically overloaded the biological medium. The means to solving such anomalies, is of course the appropriate province of medical research. Further we see similar destructive such anomalies in the domain of Vernadsky's lithosphere, for what are hurricanes but a kind of soliton dynamic, similarly earthquakes are characterized by disruptive gravity waves, solar flares as plasma wave events, and are not the very phenomena of black holes that can rip apart the center of galaxies themselves a type of soliton? Likewise here, it must be a mission of science to secure humanity against such threats.
Now, finally let us drive the analogy with these anomalous soliton-like formations into the domain of the noosphere. One can think of the radiation of technology in human society over time as operating similarly to the kind of standing waves in the brain. For a society, the successive "waves" of transmission of knowledge through culture and education provides the preconditions for its continued functioning and survival. However, a crisis is encountered whenever there is a limit of resource transparency for the prevailing mode of technology. As LaRouche has shown, what constitutes resources must be redefined via a breakthrough in scientific creativity. This is the quality that uniquely distinguishes the noosphere. This is what Cusa characterizes as an immanent power of humanity. But it is a mission which is also a choice. Nowhere else is there freedom in this sense. And it is truly this gift that Cusa proffered when he collaborated with Toscanelli to revive Eratosthenes non Euclidean method to send Columbus to the new world so that humanity might escape the clutches of those that would have us be slaves.
Saturday, April 23, 2011
Humanity's Necessary Mission
It is self evident to any thinking and sentient mortal dwelling on this planet that we as a species must colonize space. This is the case for a multitude of reasons, not the least of which is to put an end to the lunacy of warfare among us. Therefore, in a well ordered society which we must strive to create, anything that contributes to this goal must be promoted and nurtured and that which deflects us from that mission must be deterred. It is for this simple reason that the current President of these United States, Barack Obama, and his co-conspirators are treasonous to our nation's and humanity's raison d'etre. Therefore his removal from office as unfit to serve under the 25th amendment should be invoked. This, of course, would apply to most of our so-called leading figures in both of our political parties today. Let this serve as a fitting prayer and invocation on this Saturday before Easter.
Wednesday, April 20, 2011
On the Other Hand
This article however, must be commended. It is my opinion that if biophysics and the sciences in general were presented in this way, we would not have such a nation of blockheads and dunces to deal with...
Enlarge
Scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab), working with cell lines of the fruit fly Drosophila melanogaster, have discovered an unsuspected and dramatic process by which double-strand breaks in heterochromatin – one of the two major kinds of chromatin that make up chromosomes, which accounts for a third of the chromatin in both humans and fruit flies – are repaired in a series of steps. The repair starts where the break occurs, but stalls until the repair site physically moves away from the original heterochromatin region, before continuing to completion.
Unlike euchromatin, where most of an organism’s genes reside and where most DNA consists of long, unrepetitive sequences of base pairs, DNA in heterochromatin consists mostly of short repeated sequences that don’t code for proteins; indeed, heterochromatin was long regarded as containing mostly “junk” DNA.
Heterochromatin is now known to be anything but junk, playing a crucial role in organizing chromosomes and maintaining their integrity during cell division. It is concentrated near centromeres, where chromatids are in closest contact, which are required to transmit chromosomes from one generation to the next. Maintaining heterochromatin structure is necessary to the normal growth and functions of cells and organisms.
“Heterochromatin poses more of a problem for DNA repair than euchromatin,” says Gary Karpen, whose group in Berkeley Lab’s Life Sciences Division discovered the new repair mechanism. “It has lots of short sequences – many of them only about five base-pairs each – which are repeated millions of times.”
“Repair of simple repeated sequences is particularly challenging,” says Irene Chiolo, first author of the group’s paper reporting the results in the journal Cell. “They can promote chromosome aberrations, with severe consequences for the genome stability of dividing cells” – abnormalities that are a hallmark of cancer cells and cause birth defects.
Finding the right path
With the stakes so high, how can cells insure fast, accurate repair of double-strand breaks? Two main repair pathways are available. One method, nonhomologous end-joining, simply cleans up the ends of the broken strands and glues them back together regardless of sequence. This might seem a good choice for heterochromatin: it almost always creates small deletions or mutations, but these are in repetitive, noncoding sequences and do not affect genes.
Far more accurate but more complex is homologous recombination, a mechanism involving many steps where something could go wrong. Upon detecting a double-strand break in DNA, several proteins rush to the damaged area. The protein machinery trims back the ends of the broken strands (called ‘resection’)to produce single-strand regions recognized by other proteins, including one called ATRIP.
Another protein, Rad51, is recruited to form filaments on the single-stranded DNA. Rad51 and its associated proteins search for a complementary sequence of DNA in a neighboring chromatid or homologous chromosome. They invade and open that DNA to form a “D-loop” – like untwisting a rope to open and expose its individual strands. Using the exposed complementary sequence as a template, proteins rebuild the broken DNA into a copy of the sequence that was originally damaged; in this way the broken double strand is remade with its damaged section accurately reproduced.
It’s an ideal method for repairing breaks in gene-rich euchromatin. In repetitive heterochromatin, however, danger arises because completely different chromosomes lying close to the site of the break may have great lengths of repeated short sequences that look identical to the region around the break itself. What starts as a repair process may end up splicing different chromosomes together, a common abnormality in cancer cells.
Enlarge
After half an hour, however, these signs too – signals from modified histones, the component proteins that form the “spools” around which the DNA “thread” is wound in chromatin, as well as signals from ATRIP recruitment – were missing from the heterochromatin domain. What had become of the repair process?
Now you see it, now you don’t
In a series of experiments, Karpen and Chiolo and their colleagues found that in heterochromatin the early stages of homologous recombination – resection and ATRIP loading – appear within three minutes after the damage occurs. The next steps in homologous recombination seemed blocked from entering the heterochromatin at this stage. These steps – the activity of the Rad51 proteins in preparing invasive filaments of single-strand DNA – are the most dangerous, where mistaken recombination could easily occur.
By 30 minutes after radiation damage was inflicted, the entire domain had swollen and began sending out expanding and contracting ‘fingers’ of chromatin. Now, after the relocation of the damaged DNA to outside the heterochromatin, the Rad51 proteins did appear; the researchers found them moving with the ends of the heterochromatin ‘fingers’. After an hour the whole domain partially contracted again, indicating that the broken DNA had moved to the periphery of the heterochromatin domain in order to load Rad51 protein and complete the repair process.
“There are a lot of moving parts here,” says Karpen. “It opens new ways of thinking about DNA repair and investigating the process.”
It’s common to picture chromosomes as rather floppy tubes of stuff that are tightly cinched in their middles to form X-shaped figures, but in fact this is a condensed state that occurs only briefly during mitosis, when cells divide. Most of the time chromosomes aren’t condensed – instead they exist as somewhat diffuse clouds of DNA.
“In the last 20 years researchers have found that the DNA for each chromosome occupies a separate domain in the nucleus, even when chromosomes are decondensed,” says Chiolo. “From these ‘chromosomal territories’ the DNA moves to accomplish certain functions, for example gene transcription, by going to where the proteins are. We now observe that similar movements occur even during DNA repair.”
Says Karpen, “The process we discovered is an extreme version of this dynamism, where the DNA repair process starts in one domain, then the damaged DNA goes elsewhere to complete repair. It would seem that starting repair in one place, then moving elsewhere is risky, and could result in unrepaired damage, which is just as dangerous to the cell as abnormal recombination with a different chromosome.”
Says Chiolo, “Stability is the key. The presence of resected DNA ends is extremely dangerous in heterochromatin only if Rad51 is loaded onto broken DNA.” Sure enough, the researchers discovered that a protein complex called Smc5/6 blocks Rad51 recruitment until the damaged DNA is moved outside the heterochromatin.
Chiolo says, “This mechanism is crucial for safeguarding the genome by blocking aberrant recombination between different chromosomes, and promoting safe repair from a sister chromatin, or homolog, after the double-strand break has relocated outside the heterochromatin domain”.
Homologous recombination is a complex mechanism with multiple steps, but also with many points of regulation to insure accurate recombination at every stage. This could be why this method has been favored during evolution. The machinery that relocalizes the damaged DNA before loading Rad51 might have evolved because the consequences of not having it would be terrible.
Karpen and Chiolo and their colleagues are now at work on the next steps in the research, investigating the many unanswered questions about how this surprisingly dynamic mechanism of DNA repair works and what happens when it fails. Perhaps most important is learning whether the unexpectedly sophisticated approach to homologous recombination in Drosophila heterochromatin is conserved in other organisms, including humans.
“Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair,” by Irene Chiolo, Aki Minoda, Serafin U. Colmenares, Aris Polyzos, Sylvain V. Costes, and Gary H. Karpen, appears in the March 4, 2011 issue of Cell and is available online to subscribers.
Provided by Lawrence Berkeley National Laboratory (news : web)
Safeguarding genome integrity through extraordinary DNA repair
April 19, 2011 by Paul PreussEnlarge
Heterochromatin (purple) accounts for a third of the chromatin in both humans and fruit flies. Some heterochromatin forms the telomeres that cap the ends of the chromatids, and much is concentrated near the centromere, where sister chromatids are joined. Accurate repair of double-strand breaks in heterochromatin is challenging, because most of its DNA consists of short, repeated sequences.
(PhysOrg.com) -- DNA is under constant attack, from internal factors like free radicals and external ones like ionizing radiation. About 10 double-strand breaks – the kind that snap both backbones of the double helix – occur every time a human cell divides. To prevent not only gene mutations but broken chromosomes and chromosomal abnormalities known to cause cancer, infertility, and other diseases in humans, prompt, precise DNA repair is essential.
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Unlike euchromatin, where most of an organism’s genes reside and where most DNA consists of long, unrepetitive sequences of base pairs, DNA in heterochromatin consists mostly of short repeated sequences that don’t code for proteins; indeed, heterochromatin was long regarded as containing mostly “junk” DNA.
Heterochromatin is now known to be anything but junk, playing a crucial role in organizing chromosomes and maintaining their integrity during cell division. It is concentrated near centromeres, where chromatids are in closest contact, which are required to transmit chromosomes from one generation to the next. Maintaining heterochromatin structure is necessary to the normal growth and functions of cells and organisms.
“Heterochromatin poses more of a problem for DNA repair than euchromatin,” says Gary Karpen, whose group in Berkeley Lab’s Life Sciences Division discovered the new repair mechanism. “It has lots of short sequences – many of them only about five base-pairs each – which are repeated millions of times.”
“Repair of simple repeated sequences is particularly challenging,” says Irene Chiolo, first author of the group’s paper reporting the results in the journal Cell. “They can promote chromosome aberrations, with severe consequences for the genome stability of dividing cells” – abnormalities that are a hallmark of cancer cells and cause birth defects.
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With the stakes so high, how can cells insure fast, accurate repair of double-strand breaks? Two main repair pathways are available. One method, nonhomologous end-joining, simply cleans up the ends of the broken strands and glues them back together regardless of sequence. This might seem a good choice for heterochromatin: it almost always creates small deletions or mutations, but these are in repetitive, noncoding sequences and do not affect genes.
Far more accurate but more complex is homologous recombination, a mechanism involving many steps where something could go wrong. Upon detecting a double-strand break in DNA, several proteins rush to the damaged area. The protein machinery trims back the ends of the broken strands (called ‘resection’)to produce single-strand regions recognized by other proteins, including one called ATRIP.
Another protein, Rad51, is recruited to form filaments on the single-stranded DNA. Rad51 and its associated proteins search for a complementary sequence of DNA in a neighboring chromatid or homologous chromosome. They invade and open that DNA to form a “D-loop” – like untwisting a rope to open and expose its individual strands. Using the exposed complementary sequence as a template, proteins rebuild the broken DNA into a copy of the sequence that was originally damaged; in this way the broken double strand is remade with its damaged section accurately reproduced.
It’s an ideal method for repairing breaks in gene-rich euchromatin. In repetitive heterochromatin, however, danger arises because completely different chromosomes lying close to the site of the break may have great lengths of repeated short sequences that look identical to the region around the break itself. What starts as a repair process may end up splicing different chromosomes together, a common abnormality in cancer cells.
Enlarge
In this highly simplified and abbreviated impression of homologous repair, proteins (not shown) first trim back the ends of the broken strands (‘resection’), which are recognized by other proteins including ATRIP. Still more proteins, including Rad51, are recruited to form filaments that invade a neighboring chromatid or homologous chromosome having the complementary sequence. Both filaments use these templates (only one filament is shown working here) to accurately reproduce the damaged double strand.
For heterochromatin to employ such a potentially risky repair process seemed counterintuitive. In earlier experiments looking for key signs of repair in mouse heterochromatin after irradiation, classic markers of double-strand break repair by either nonhomologous end-joining or homologous recombination were both absent. In fact it seemed possible that, somehow, such breaks didn’t occur in heterochromatin. “There were no signs of repair half an hour after the cells were exposed to ionizing radiation,” says Karpen. “But our group looked at Drosophila cells just 10 minutes after radiation exposure. Now the early signs of homologous recombination were clearly evident.”After half an hour, however, these signs too – signals from modified histones, the component proteins that form the “spools” around which the DNA “thread” is wound in chromatin, as well as signals from ATRIP recruitment – were missing from the heterochromatin domain. What had become of the repair process?
Now you see it, now you don’t
In a series of experiments, Karpen and Chiolo and their colleagues found that in heterochromatin the early stages of homologous recombination – resection and ATRIP loading – appear within three minutes after the damage occurs. The next steps in homologous recombination seemed blocked from entering the heterochromatin at this stage. These steps – the activity of the Rad51 proteins in preparing invasive filaments of single-strand DNA – are the most dangerous, where mistaken recombination could easily occur.
By 30 minutes after radiation damage was inflicted, the entire domain had swollen and began sending out expanding and contracting ‘fingers’ of chromatin. Now, after the relocation of the damaged DNA to outside the heterochromatin, the Rad51 proteins did appear; the researchers found them moving with the ends of the heterochromatin ‘fingers’. After an hour the whole domain partially contracted again, indicating that the broken DNA had moved to the periphery of the heterochromatin domain in order to load Rad51 protein and complete the repair process.
“There are a lot of moving parts here,” says Karpen. “It opens new ways of thinking about DNA repair and investigating the process.”
It’s common to picture chromosomes as rather floppy tubes of stuff that are tightly cinched in their middles to form X-shaped figures, but in fact this is a condensed state that occurs only briefly during mitosis, when cells divide. Most of the time chromosomes aren’t condensed – instead they exist as somewhat diffuse clouds of DNA.
“In the last 20 years researchers have found that the DNA for each chromosome occupies a separate domain in the nucleus, even when chromosomes are decondensed,” says Chiolo. “From these ‘chromosomal territories’ the DNA moves to accomplish certain functions, for example gene transcription, by going to where the proteins are. We now observe that similar movements occur even during DNA repair.”
Says Karpen, “The process we discovered is an extreme version of this dynamism, where the DNA repair process starts in one domain, then the damaged DNA goes elsewhere to complete repair. It would seem that starting repair in one place, then moving elsewhere is risky, and could result in unrepaired damage, which is just as dangerous to the cell as abnormal recombination with a different chromosome.”
Says Chiolo, “Stability is the key. The presence of resected DNA ends is extremely dangerous in heterochromatin only if Rad51 is loaded onto broken DNA.” Sure enough, the researchers discovered that a protein complex called Smc5/6 blocks Rad51 recruitment until the damaged DNA is moved outside the heterochromatin.
Chiolo says, “This mechanism is crucial for safeguarding the genome by blocking aberrant recombination between different chromosomes, and promoting safe repair from a sister chromatin, or homolog, after the double-strand break has relocated outside the heterochromatin domain”.
Homologous recombination is a complex mechanism with multiple steps, but also with many points of regulation to insure accurate recombination at every stage. This could be why this method has been favored during evolution. The machinery that relocalizes the damaged DNA before loading Rad51 might have evolved because the consequences of not having it would be terrible.
Karpen and Chiolo and their colleagues are now at work on the next steps in the research, investigating the many unanswered questions about how this surprisingly dynamic mechanism of DNA repair works and what happens when it fails. Perhaps most important is learning whether the unexpectedly sophisticated approach to homologous recombination in Drosophila heterochromatin is conserved in other organisms, including humans.
“Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair,” by Irene Chiolo, Aki Minoda, Serafin U. Colmenares, Aris Polyzos, Sylvain V. Costes, and Gary H. Karpen, appears in the March 4, 2011 issue of Cell and is available online to subscribers.
Provided by Lawrence Berkeley National Laboratory (news : web)
The Trouble with Mathematics Masquerading as Science
Here, dear friends, in one fell swoop is a sort of preamble to everything that is wrong with today's so called scientific method:
Generalized entropies and the transformation group of superstatistics
+ Author Affiliations
- Contributed by Murray Gell-Mann, March 3, 2011 (sent for review February 17, 2011)
Abstract
Superstatistics describes statistical systems that behave like superpositions of different inverse temperatures β, so that the probability distribution is 
, where the “kernel” f(β) is nonnegative and normalized [∫f(β)dβ = 1]. We discuss the relation between this distribution and the generalized entropic form 
. The first three Shannon–Khinchin axioms are assumed to hold. It then turns out that for a given distribution there are two different ways to construct the entropy. One approach uses escort probabilities and the other does not; the question of which to use must be decided empirically. The two approaches are related by a duality. The thermodynamic properties of the system can be quite different for the two approaches. In that connection, we present the transformation laws for the superstatistical distributions under macroscopic state changes. The transformation group is the Euclidean group in one dimension.
, where the “kernel” f(β) is nonnegative and normalized [∫f(β)dβ = 1]. We discuss the relation between this distribution and the generalized entropic form . The first three Shannon–Khinchin axioms are assumed to hold. It then turns out that for a given distribution there are two different ways to construct the entropy. One approach uses escort probabilities and the other does not; the question of which to use must be decided empirically. The two approaches are related by a duality. The thermodynamic properties of the system can be quite different for the two approaches. In that connection, we present the transformation laws for the superstatistical distributions under macroscopic state changes. The transformation group is the Euclidean group in one dimension. Tuesday, April 19, 2011
Update on Model of Hearing
The researchers, Reichenbach and Hudspeth, that hypothesized a mechanism for sound amplification of the inner ear that I reported on in this blog from last September, have now put their theory in practice in design of a microphone that eliminates feedback and provides a capacity for tremendous sensitivity.
Unidirectional mechanical amplification as a design principle for an active microphone
(Submitted on 14 Apr 2011)
Amplification underlies the operation of many biological and engineering systems. Simple electrical, optical, and mechanical amplifiers are reciprocal: the backward coupling of the output to the input equals the forward coupling of the input to the output. Unidirectional amplifiers that occur often in electrical and optical systems are special non-reciprocal devices in which the output does not couple back to the input even though the forward coupling persists. Here we propose a scheme for unidirectional mechanical amplification that we utilize to construct an active microphone. We show that amplification improves the microphone's threshold for detecting weak signals and that unidirectionality prevents distortion.
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