The same group did a study last year that used unmodified mice (well, largely unmodified- they had been put on a diet that promoted obesity, but they were not transgenic).
Based on the alterations in energy metabolism and gene expression we observed in normal C57BL6 and Balb/c mice, we sought to examine whether a REV-ERB alpha/beta agonist would be efficacious in a rodent model of obesity. We initiated the study with 20-week old C57BL6 mice (average weight = 41g) that had been maintained on a high fat diet for 14 weeks (20% carbohydrate 60% fat). The mice continued on the HF diet and we initiated twice per day dosing (i.p.) of SR9009. While the stress of handling and twice-daily injections caused weight loss in vehicle-treated controls, weight loss of SR9009-treated animals was 60% greater (Fig. 5a). During the treatment period, there was no significant difference in the food intake of SR9009 and vehicle treated animals, although handling itself reduced food intake explaining the weight loss observed in the controls. SR9009 treated mice exhibited a more severe reduction in adiposity (Fig. 5b). In addition to the decrease in fat mass we also observed a 12% decrease in plasma triglycerides (TGs) and a 47% decrease in plasma total cholesterol (Chol) (Fig. 5c). Plasma non-esterified fatty acids (NEFA) were also reduced (23%) along with plasma glucose (19%) in the SR9009 treated animals (Fig. 5c). There was also a trend toward a decrease in plasma insulin levels (35%).
SR9009 is available for research purposes, $150 for 25 mg. From the structure, I would say it's likely to be only slightly soluble in water; also, the only solubility data given is in DMSO. It requires storage by refrigeration or freezing, and comes packaged under inert gas, so I would say its environmental persistence would be rather low. I don't know if a molecule like this would be stable enough for oral administration, actually. In their mouse study, injections were made.
From the non-chemistry side of the etymology, it is apparently not known with certainty why a short rifle is called a carbine in the first place:
short rifle, 1580s, from French carabine (Middle French carabin), used of light horsemen and also of the weapon they carried, of uncertain origin, perhaps from Medieval Latin Calabrinus "Calabrian" (i.e., "rifle made in Calabria"). A less-likely theory (Gamillscheg, etc.) connects it to Old French escarrabin "corpse-bearer during the plague," literally (probably) "carrion beetle," said to have been an epithet for archers from Flanders.
The -yne ending is already in common use for carbon compounds with a triple bond. For example, ethyne (the IUPAC systematic name for acetylene). It's not a very good name in this case though- "carbyne" already refers to a type of reactive species of carbon with three unpaired electrons, in analogy to the more common "carbene" which has two unpaired electrons. Wikipedia suggests a better name for the carbon chain to be "linear acetylenic carbon," though I'll admit it doesn't roll off the tongue. Shorter versions of this molecular chain, which terminate with a hydrogen on each end are generally called polyacetylenes or polyynes.
There is reason to think that a drug like this would be broadly effective against different kinds of cancer. TR100 disrupts the actin cytoskeleton vital to all cells, and specifically disrupts its formation by targeting an isoform of the protein tropomyosin. Isoforms are different structures for the the same protein- every cell needs tropomyosin to regulate their actin filaments, but cancer cells preferentially use a certain structure of tropomyosin. Compounds with anti-actin activity have been looked at for a long time as anticancer compounds, but the known ones have been nonspecific. TR100 also has the advantage of being a relatively simple small molecule instead of a complicated biomolecule, which could make its development as a commercial drug much easier.
It is however, still (potentially) just a new chemotherapy agent, one of many out there. From what has been observed from other chemo agents, just because a compound targets a basic cellular function doesn't mean a cancer can't develop resistance. The taxanes and the Vinca alkaloids arrest mitosis (by targeting microtubules), and are excellent, widely used drugs, but are not the The Cure for Cancer. I'd imagine this compound to be along those lines- another weapon in the oncology arsenal, but not a magic bullet.
Right, but the object of the paper is to then advance what is known in that very area, in which I think it is highly successful. Varieties of thioredoxins are present in every free-living organism on earth. One of their many functions is to donate electrons to an enzyme called ribonucleotide reductase which converts ribonucleotides into deoxyribonucleotides, so in a roundabout way, working thioredoxin proteins are necessary to make DNA. Between its ubiquity and general structural similarities in modern organisms, there is reason to think that the general structure of thioredoxins was settled long ago in the history of life, before archaea and eukaryotes split off from bacteria. As other posters have noted, the timeframe of this event is generally held to have been ~3.5-3.8 billion years ago.
From the experiments that were done to find this new layer, it seems that it is very difficult to separate from the adjoining layer (Descemet's membrane). Getting Dua's layer to separate from Descemet's membrane was a serendipitous result of simulating eye surgery (a lamellar keratoplasty, which is a partial corneal graft) involving the "big bubble technique," which uses an injection of air to separate Descemet's membrane from the corneal stroma. It turned out that it was sometimes possible to create this air bubble in specimens where Descemet's membrane had been removed, meaning there had to be another layer for air to get into. Otherwise, it wouldn't be easily detected as a separate layer.
Here's what the "big bubble technique" looks like. It's pictures of eye surgery, so don't say you weren't properly warned.
That seems likely- data from other instruments on Cassini has suggested that aromatic hydrocarbons such as benzene and anthracene form high in Titan's atmosphere. The altitude (~1000km) is consistent with the location of the glow, and the emission line fits- a mix of polycyclic aromatic hydrocarbons has long been thought to be the source of a 3.3 micron emission line seen in interstellar dust.
OK, I did the research, by which I mean I used Google to find out what research had already been done. Honestly, these guys just about took care of it back in 2006. The answer appears to be a qualified "yes," in that many of the basic features of experimental autoimmune encephalomyelitis translate to MS, but MS is known to have more involvement from some pathways and less from others. In particular, the method of inducing EAE infection in mice led to a focus on the role of CD4+ cells (which include the TH17 cells) for years, until it was discovered that CD8+ cells also play a major role in MS. It turns out that treatments developed using EAE have had mixed results in treating human MS. For instance, there was a lot of hope in the late 1990s for a tumor necrosis factor blocker called lenercept, which was effective against EAE, but actually made MS worse. On the other hand, secukinumab, an antibody against interleukin-17 itself, has shown positive results against MS in a early proof-of-concept trial.
As the Gold, et al. paper concludes, "Autoimmune encephalomyelitis is, thus, an excellent tool for studying basic mechanisms of brain inflammation and immune-mediated CNS tissue injury, and for obtaining proof of principle, whether a certain therapeutic strategy has the potential to block these pathways. Whether they are relevant for multiple sclerosis patients in general and, if yes, for what subpopulation of patients has to be determined in respective clinical studies."
Virtually all of what is sold as Himalayan pink salt comes from a gigantic salt mine in Pakistan. It does come from out of a mountain, in the descripitively named Salt Range, but it's as far away from the actual Himalayas as Kansas is from the Rockies. It's solely a marketing term. It's also just rock salt, and that pink color is just from iron oxide.
An issue I've seen with the use of mouse models in several places is that studies in mice (including this one) are based around a disease called EAE which can be readily induced in mice and which has many features similar to human multiple sclerosis. It's of course convenient experimentally to be able to induce what is normally a rare and unpredictable autoimmunity, but how well does that compare to human patients? Induction of EAE involves injecting mice with brain matter and pertussis toxin, in order to generate an inflammatory response to the mouse's own myelin. I wonder if the pathways for that induced imflammation are the same as for genuine autoimmunity, and whether the pathways of EAE really translate to multiple sclerosis, the causes of which are still rather mysterious.
The analogy between Battletoads and Groupon goes even deeper. Just as Battletoads had an infamous bug that prevented Player 2 from completing Level 11 (they would just sit motionless until they lost all their lives), Groupon looks like in the near future it will be stuck in Chapter 11.
Looking again at the BBC article, they do mention physical attacks (and the page picture seems to be depicting one), so I went looking for the researcher's' own page, and it turns out there are some videos of sparrows attacking a taxidermied sparrow. From the looks of it, they may have used the "robosparrow" with the motorized wing in a cage, since it was fragile and they only had one. This video from 2011 of a live sparrow attacking a stationary taxidermied sparrow seems to suggest that there's no way the Robosparrow makes it two months in the wild if this is the kind of treatment sparrows dish out to rivals. Go for the eyes, Boo!
There's video of the sparrow in the supplementary information tab on the abstract page in Quicktime format. The file 265_2013_1478_MOESM2_ESM.m4v is the one with footage of the reanimated sparrow. I'll warn you that it isn't exactly thrilling. No lurid sparrow on cybersparrow violence.
Of note is that they actually operated the mechanical bird inside a cage. I think the quote "Eventually the head fell off and the wing stopped moving" from the BBC article meant precisely that: the robobird fell apart from exposure to the elements and repeated trials.
The/. submitter appears to have wrongly inferred that this damage was from other sparrows tearing it apart, when in fact their aggressive behavior was "got close and waved menacingly."
They established the origin of the hydrocarbons by measuring the carbon-14/carbon-12 ratio. Organic compounds made by living things on the surface of the earth will have a small amount of carbon-14 incorporated. Just about all the carbon-14 that had been present in the oil will have decayed with no opportunity for replacement, Their results for their oil-soaked sand show ratios of a few tenths of a percent of the atmospheric value, making it it likely that the vast majority of the hydrocarbons present were from sources which had been dead for eons.
Also, they have profiles of the same oil taken at the source well, surface slicks, and contaminated sand. While the oil degrades with environmental exposure, there is clear similarity among the compositions of the samples. The supporting information gives a lot of details on the experimental methods.
It's actually well known that muons do not orbit at the same distance at electrons (orbit in the quantum atomic orbital sense, of course, but since we're talking about hydrogen-like atoms, they can be described with the Bohr model). The calculations of energy levels do include the rest mass of the electron or muon as appropriate. The very reason to use muons in an experiment like this is their greater mass amplifies certain quantum electrodynamic interactions, allowing scientists to take experimental measurements of these interactions and plug them into QED calculations to determine basic physical properties (like the sizes of particles).
In this case, they used a phenomenon known as the Lamb shift. Essentially, two energy levels that should be identical have a slight difference due to a self-interaction effect. This difference can be measured by spectroscopy.
As they are both the same sort of particle (leptons), electrons and muons should behave identically in this experiment except for the 207 times greater rest mass of the muon, which is accounted for in the calculations. What this result suggests is either the Lamb shift of the electron and of the muon work the same and the experimental setup measures them differently somehow, or that they work differently and there is some sort of new interaction not being accounted for.
These are artificial DNA oligos, so there shouldn't be any of those sorts of modifications. However, a figure of MW 150 per base leaves out the sugar-phosphate backbone, and doesn't account for this being double-stranded DNA. Molecular weight per base pair should be around 700 g/mol..
Of course, that's really nitpicking, What really accounts for the low ratio of achieved versus theoretical is that they made "~1.2x10^7 copies of each DNA string."
They go on to explain in the supplementary materials that "With the latest platform, up to 244,000 unique sequences are synthesized in parallel and delivered as ~1-10 pmol pools of oligos... In our experiment, three runs were used to synthesize 153,335 designs, leading to the higher figure of ~12-120x10^6 (= 3-30 x 10^-12 x6.02x10^23/153,335)." A more accurate assessment of their coding scheme is that they used 153335 strings of 117 nucleotides ( 17940195 total) to encode 5165800 bits of Shannon information, or about 0.29 bits per nucleotide.
The fact they made ten million copies of each string is more of a current technical limitation of DNA oligo synthesis and automated DNA sequencing than an limit on the efficiency of the encoding itself. With the appropriate technology, you could make a few thousand copies (for appropriate error correction) instead of ten million, and your mass of DNA would be in the femtograms instead of hundreds of picograms.
There are many types of lipids involved with the nervous system, and a wide variety of disorders associated with abnormal levels. For example, the neurological problems often seen in severe vitamin deficiencies can usually be traced to the roles vitamins play as cofactors in lipid metabolism. Problems with lipid transport and breakdown are thought to play important roles in many neurodegenerative diseases- for example, vcertain ariants of a protein involved in lipid transport called apoliprotein E are associated with a much higher Alzheimer's risk.
Normally, GM2 levels should remain fairly static. It's a fatty acid that resides in the plasma membrane of your neurons and acts as a cell surface marker- it has a small chain of sugars that extend off the surface. If cell machinery is acting normally, GM2 will be recycled by an enzyme called hexosaminidase A. In Tay-Sachs disease, a mutant copy of HEXA with no activity means GM2 is not broken down, and its accumulation eventually kills neurons.
Of course, in the case of traumatic brain injury, the affected have working HEXA. The spike in GM2 may be a direct result of neuronal damage (membrane lipids spilling out into the extracellular space), or a temporary hiccup in the metabolism of GM2 (normal bodily processes often get shut down in case of emergency). There has been some research done into the drug pyrimethamine that has shown it can increase HEXA activity and slow the progression of the late-onset form of Tay-Sachs. Perhaps it might be of use with traumatic brain injury patients?
Yeah, I could stand to get in the habit of submitting more chemistry stories. I actually saw the autograph story yesterday in C&EN, but never even considered submitting it here. I guess it's not "real stuff, " but I found it charming, and a nice illustration of personal connections in science.
I'll admit that there are at least a couple stories about actual work in the field each week in Chemical & Engineering News that could readily be submitted here. Paywalls are a problem when it comes to sharing chemical research with a wider audience, but they're a factor in physics, astronomy, and molecular biology research too, and that hasn't stopped the steady appearance of those topics here.
I've seen some truly inscrutable theoretical physics and mathematics stories here where half the comments were "LOLWTF someone explain," and someone comes along and posts a good explanation, and all are (at least somewhat) enlightened, so I don't believe difficulty and obscurity are necessarily reasons to not submit a story. Let the Firehose decide if it's too hard. I do think overall chemistry gets less attention in the pop science press (except when it's responsible for something terrible), so there do tend to be fewer accessibly written stories to draw on.
According to this article from last year on the same event, the event caused an increase in the concentration of carbon-14 in the atmosphere of about 1.2%. That's apparently about 20 times the normal rate of variation, but the baseline level of carbon-14 is about a part per trillion, so we'd be talking about increasing the concentration of carbon-14 by about 10 parts per quadrillion. In contrast, the period of above-ground nuclear testing almost doubled the concentration at its peak in the early 1960s.
Given our indirect knowledge of the event in 775, it's unknown whether other radiological hazards would have been present in addition to the C14 spike, but there don't seem to be indications of mass dieoffs or famines.
I can't say for certain without full access to the paper, but based on the use of a retroviral vector and Dr. Harrich's comments in the video interview, I think the idea would be to infect a population of your hematopoietic stem cells with retroviruses that carry the Nullbasic (mutant copy of Tat) gene. That procedure would be similar to the autologous HSC transplants used in treatment of some leukemias and lymphomas- but then they'd infect the HSCs with the retroviral vector before they put them back in you.
Upon successful infection, the RNA genome of the vector is converted via reverse transcriptase to a DNA sequence. The vector will also produce some enzymes that will integrate the Nullbasic-DNA gene into the DNA genome of your stem cells. If successful, those cells will now produce Nullbasic protein. Since they are stem cells, they will produce Nullbasic-positive blood cells, some of which will be the CD4+ T-cells that HIV infects.
HIV will still infect these cells, inject its RNA genome into the cell, which will be converted to DNA, integrated into the host cell genome, transcribed back to RNA, then translated to viral proteins by the cell's machinery. However, the host cell also makes Nullbasic protein, which act like HIV's Tat, and will interact with the same enzymes, transcription factors, etc., but instead of boosting their functions, it will inhibit them. In theory, HIV would reproduce so slowly in your population of Nullbasic+ T-cells that it simply wouldn't be a disease- the population would never fall to the point of causing immunodeficiency.
The phrase, "in theory" could also apply to most of the other steps I outlined above, of course.
Slashdot Mirror
The same group did a study last year that used unmodified mice (well, largely unmodified- they had been put on a diet that promoted obesity, but they were not transgenic).
SR9009 is available for research purposes, $150 for 25 mg. From the structure, I would say it's likely to be only slightly soluble in water; also, the only solubility data given is in DMSO. It requires storage by refrigeration or freezing, and comes packaged under inert gas, so I would say its environmental persistence would be rather low. I don't know if a molecule like this would be stable enough for oral administration, actually. In their mouse study, injections were made.
From the non-chemistry side of the etymology, it is apparently not known with certainty why a short rifle is called a carbine in the first place:
The -yne ending is already in common use for carbon compounds with a triple bond. For example, ethyne (the IUPAC systematic name for acetylene). It's not a very good name in this case though- "carbyne" already refers to a type of reactive species of carbon with three unpaired electrons, in analogy to the more common "carbene" which has two unpaired electrons. Wikipedia suggests a better name for the carbon chain to be "linear acetylenic carbon," though I'll admit it doesn't roll off the tongue. Shorter versions of this molecular chain, which terminate with a hydrogen on each end are generally called polyacetylenes or polyynes.
There is reason to think that a drug like this would be broadly effective against different kinds of cancer. TR100 disrupts the actin cytoskeleton vital to all cells, and specifically disrupts its formation by targeting an isoform of the protein tropomyosin. Isoforms are different structures for the the same protein- every cell needs tropomyosin to regulate their actin filaments, but cancer cells preferentially use a certain structure of tropomyosin. Compounds with anti-actin activity have been looked at for a long time as anticancer compounds, but the known ones have been nonspecific. TR100 also has the advantage of being a relatively simple small molecule instead of a complicated biomolecule, which could make its development as a commercial drug much easier.
It is however, still (potentially) just a new chemotherapy agent, one of many out there. From what has been observed from other chemo agents, just because a compound targets a basic cellular function doesn't mean a cancer can't develop resistance. The taxanes and the Vinca alkaloids arrest mitosis (by targeting microtubules), and are excellent, widely used drugs, but are not the The Cure for Cancer. I'd imagine this compound to be along those lines- another weapon in the oncology arsenal, but not a magic bullet.
Right, but the object of the paper is to then advance what is known in that very area, in which I think it is highly successful. Varieties of thioredoxins are present in every free-living organism on earth. One of their many functions is to donate electrons to an enzyme called ribonucleotide reductase which converts ribonucleotides into deoxyribonucleotides, so in a roundabout way, working thioredoxin proteins are necessary to make DNA. Between its ubiquity and general structural similarities in modern organisms, there is reason to think that the general structure of thioredoxins was settled long ago in the history of life, before archaea and eukaryotes split off from bacteria. As other posters have noted, the timeframe of this event is generally held to have been ~3.5-3.8 billion years ago.
To be fair to the journalists, it wasn't them doing the rounding: Conservation of Protein Structure over Four Billion Years.
From the experiments that were done to find this new layer, it seems that it is very difficult to separate from the adjoining layer (Descemet's membrane). Getting Dua's layer to separate from Descemet's membrane was a serendipitous result of simulating eye surgery (a lamellar keratoplasty, which is a partial corneal graft) involving the "big bubble technique," which uses an injection of air to separate Descemet's membrane from the corneal stroma. It turned out that it was sometimes possible to create this air bubble in specimens where Descemet's membrane had been removed, meaning there had to be another layer for air to get into. Otherwise, it wouldn't be easily detected as a separate layer.
Here's what the "big bubble technique" looks like. It's pictures of eye surgery, so don't say you weren't properly warned.
Welcome to Wine Cue!
INPUT: Chateau Petrus, 1998 vintage, Pomerol primarily of Merlot grapes, estimated retail 3500USD
RECOMMENDATION: Charles Shaw, 2010 vintage, Merlot, estimated retail 2USD
That seems likely- data from other instruments on Cassini has suggested that aromatic hydrocarbons such as benzene and anthracene form high in Titan's atmosphere. The altitude (~1000km) is consistent with the location of the glow, and the emission line fits- a mix of polycyclic aromatic hydrocarbons has long been thought to be the source of a 3.3 micron emission line seen in interstellar dust.
OK, I did the research, by which I mean I used Google to find out what research had already been done. Honestly, these guys just about took care of it back in 2006. The answer appears to be a qualified "yes," in that many of the basic features of experimental autoimmune encephalomyelitis translate to MS, but MS is known to have more involvement from some pathways and less from others. In particular, the method of inducing EAE infection in mice led to a focus on the role of CD4+ cells (which include the TH17 cells) for years, until it was discovered that CD8+ cells also play a major role in MS. It turns out that treatments developed using EAE have had mixed results in treating human MS. For instance, there was a lot of hope in the late 1990s for a tumor necrosis factor blocker called lenercept, which was effective against EAE, but actually made MS worse. On the other hand, secukinumab, an antibody against interleukin-17 itself, has shown positive results against MS in a early proof-of-concept trial.
As the Gold, et al. paper concludes, "Autoimmune encephalomyelitis is, thus, an excellent tool for studying basic mechanisms of brain inflammation and immune-mediated CNS tissue injury, and for obtaining proof of principle, whether a certain therapeutic strategy has the potential to block these pathways. Whether they are relevant for multiple sclerosis patients in general and, if yes, for what subpopulation of patients has to be determined in respective clinical studies."
Virtually all of what is sold as Himalayan pink salt comes from a gigantic salt mine in Pakistan. It does come from out of a mountain, in the descripitively named Salt Range, but it's as far away from the actual Himalayas as Kansas is from the Rockies. It's solely a marketing term. It's also just rock salt, and that pink color is just from iron oxide.
An issue I've seen with the use of mouse models in several places is that studies in mice (including this one) are based around a disease called EAE which can be readily induced in mice and which has many features similar to human multiple sclerosis. It's of course convenient experimentally to be able to induce what is normally a rare and unpredictable autoimmunity, but how well does that compare to human patients? Induction of EAE involves injecting mice with brain matter and pertussis toxin, in order to generate an inflammatory response to the mouse's own myelin. I wonder if the pathways for that induced imflammation are the same as for genuine autoimmunity, and whether the pathways of EAE really translate to multiple sclerosis, the causes of which are still rather mysterious.
Bisphenol-A is not a lubricant, it's a compound present in the plastic liners used in aluminum cans.
The analogy between Battletoads and Groupon goes even deeper. Just as Battletoads had an infamous bug that prevented Player 2 from completing Level 11 (they would just sit motionless until they lost all their lives), Groupon looks like in the near future it will be stuck in Chapter 11.
Looking again at the BBC article, they do mention physical attacks (and the page picture seems to be depicting one), so I went looking for the researcher's' own page, and it turns out there are some videos of sparrows attacking a taxidermied sparrow. From the looks of it, they may have used the "robosparrow" with the motorized wing in a cage, since it was fragile and they only had one. This video from 2011 of a live sparrow attacking a stationary taxidermied sparrow seems to suggest that there's no way the Robosparrow makes it two months in the wild if this is the kind of treatment sparrows dish out to rivals. Go for the eyes, Boo!
There's video of the sparrow in the supplementary information tab on the abstract page in Quicktime format. The file 265_2013_1478_MOESM2_ESM.m4v is the one with footage of the reanimated sparrow. I'll warn you that it isn't exactly thrilling. No lurid sparrow on cybersparrow violence.
Of note is that they actually operated the mechanical bird inside a cage. I think the quote "Eventually the head fell off and the wing stopped moving" from the BBC article meant precisely that: the robobird fell apart from exposure to the elements and repeated trials.
The /. submitter appears to have wrongly inferred that this damage was from other sparrows tearing it apart, when in fact their aggressive behavior was "got close and waved menacingly."
They established the origin of the hydrocarbons by measuring the carbon-14/carbon-12 ratio. Organic compounds made by living things on the surface of the earth will have a small amount of carbon-14 incorporated. Just about all the carbon-14 that had been present in the oil will have decayed with no opportunity for replacement, Their results for their oil-soaked sand show ratios of a few tenths of a percent of the atmospheric value, making it it likely that the vast majority of the hydrocarbons present were from sources which had been dead for eons.
Also, they have profiles of the same oil taken at the source well, surface slicks, and contaminated sand. While the oil degrades with environmental exposure, there is clear similarity among the compositions of the samples. The supporting information gives a lot of details on the experimental methods.
It's actually well known that muons do not orbit at the same distance at electrons (orbit in the quantum atomic orbital sense, of course, but since we're talking about hydrogen-like atoms, they can be described with the Bohr model). The calculations of energy levels do include the rest mass of the electron or muon as appropriate. The very reason to use muons in an experiment like this is their greater mass amplifies certain quantum electrodynamic interactions, allowing scientists to take experimental measurements of these interactions and plug them into QED calculations to determine basic physical properties (like the sizes of particles).
In this case, they used a phenomenon known as the Lamb shift. Essentially, two energy levels that should be identical have a slight difference due to a self-interaction effect. This difference can be measured by spectroscopy.
As they are both the same sort of particle (leptons), electrons and muons should behave identically in this experiment except for the 207 times greater rest mass of the muon, which is accounted for in the calculations. What this result suggests is either the Lamb shift of the electron and of the muon work the same and the experimental setup measures them differently somehow, or that they work differently and there is some sort of new interaction not being accounted for.
Yeah, they knew about the universe before it was cool.
These are artificial DNA oligos, so there shouldn't be any of those sorts of modifications. However, a figure of MW 150 per base leaves out the sugar-phosphate backbone, and doesn't account for this being double-stranded DNA. Molecular weight per base pair should be around 700 g/mol..
Of course, that's really nitpicking, What really accounts for the low ratio of achieved versus theoretical is that they made "~1.2x10^7 copies of each DNA string."
They go on to explain in the supplementary materials that "With the latest platform, up to 244,000 unique sequences are synthesized in parallel and delivered as ~1-10 pmol pools of oligos... In our experiment, three runs were used to synthesize 153,335 designs, leading to the higher figure of ~12-120x10^6 (= 3-30 x 10^-12 x6.02x10^23/153,335)." A more accurate assessment of their coding scheme is that they used 153335 strings of 117 nucleotides ( 17940195 total) to encode 5165800 bits of Shannon information, or about 0.29 bits per nucleotide.
The fact they made ten million copies of each string is more of a current technical limitation of DNA oligo synthesis and automated DNA sequencing than an limit on the efficiency of the encoding itself. With the appropriate technology, you could make a few thousand copies (for appropriate error correction) instead of ten million, and your mass of DNA would be in the femtograms instead of hundreds of picograms.
There are many types of lipids involved with the nervous system, and a wide variety of disorders associated with abnormal levels. For example, the neurological problems often seen in severe vitamin deficiencies can usually be traced to the roles vitamins play as cofactors in lipid metabolism. Problems with lipid transport and breakdown are thought to play important roles in many neurodegenerative diseases- for example, vcertain ariants of a protein involved in lipid transport called apoliprotein E are associated with a much higher Alzheimer's risk.
Normally, GM2 levels should remain fairly static. It's a fatty acid that resides in the plasma membrane of your neurons and acts as a cell surface marker- it has a small chain of sugars that extend off the surface. If cell machinery is acting normally, GM2 will be recycled by an enzyme called hexosaminidase A. In Tay-Sachs disease, a mutant copy of HEXA with no activity means GM2 is not broken down, and its accumulation eventually kills neurons.
Of course, in the case of traumatic brain injury, the affected have working HEXA. The spike in GM2 may be a direct result of neuronal damage (membrane lipids spilling out into the extracellular space), or a temporary hiccup in the metabolism of GM2 (normal bodily processes often get shut down in case of emergency). There has been some research done into the drug pyrimethamine that has shown it can increase HEXA activity and slow the progression of the late-onset form of Tay-Sachs. Perhaps it might be of use with traumatic brain injury patients?
Yeah, I could stand to get in the habit of submitting more chemistry stories. I actually saw the autograph story yesterday in C&EN, but never even considered submitting it here. I guess it's not "real stuff, " but I found it charming, and a nice illustration of personal connections in science.
I'll admit that there are at least a couple stories about actual work in the field each week in Chemical & Engineering News that could readily be submitted here. Paywalls are a problem when it comes to sharing chemical research with a wider audience, but they're a factor in physics, astronomy, and molecular biology research too, and that hasn't stopped the steady appearance of those topics here.
I've seen some truly inscrutable theoretical physics and mathematics stories here where half the comments were "LOLWTF someone explain," and someone comes along and posts a good explanation, and all are (at least somewhat) enlightened, so I don't believe difficulty and obscurity are necessarily reasons to not submit a story. Let the Firehose decide if it's too hard. I do think overall chemistry gets less attention in the pop science press (except when it's responsible for something terrible), so there do tend to be fewer accessibly written stories to draw on.
Now, off to find a story to submit....
According to this article from last year on the same event, the event caused an increase in the concentration of carbon-14 in the atmosphere of about 1.2%. That's apparently about 20 times the normal rate of variation, but the baseline level of carbon-14 is about a part per trillion, so we'd be talking about increasing the concentration of carbon-14 by about 10 parts per quadrillion. In contrast, the period of above-ground nuclear testing almost doubled the concentration at its peak in the early 1960s.
Given our indirect knowledge of the event in 775, it's unknown whether other radiological hazards would have been present in addition to the C14 spike, but there don't seem to be indications of mass dieoffs or famines.
I can't say for certain without full access to the paper, but based on the use of a retroviral vector and Dr. Harrich's comments in the video interview, I think the idea would be to infect a population of your hematopoietic stem cells with retroviruses that carry the Nullbasic (mutant copy of Tat) gene. That procedure would be similar to the autologous HSC transplants used in treatment of some leukemias and lymphomas- but then they'd infect the HSCs with the retroviral vector before they put them back in you.
Upon successful infection, the RNA genome of the vector is converted via reverse transcriptase to a DNA sequence. The vector will also produce some enzymes that will integrate the Nullbasic-DNA gene into the DNA genome of your stem cells. If successful, those cells will now produce Nullbasic protein. Since they are stem cells, they will produce Nullbasic-positive blood cells, some of which will be the CD4+ T-cells that HIV infects.
HIV will still infect these cells, inject its RNA genome into the cell, which will be converted to DNA, integrated into the host cell genome, transcribed back to RNA, then translated to viral proteins by the cell's machinery. However, the host cell also makes Nullbasic protein, which act like HIV's Tat, and will interact with the same enzymes, transcription factors, etc., but instead of boosting their functions, it will inhibit them. In theory, HIV would reproduce so slowly in your population of Nullbasic+ T-cells that it simply wouldn't be a disease- the population would never fall to the point of causing immunodeficiency.
The phrase, "in theory" could also apply to most of the other steps I outlined above, of course.