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Comment Re:Cancer vs common cold (Score 3, Informative) 52 52

E47-inducible cell lines were generated by infection with
a retroviral vector expressing E47 fused to a tamoxifen-inducible
modified estrogen receptor (MER).

The way this was done was really clever: it uses a virus that causes cancer to treat cancer. Specifically, the retroviral vector is an engineered strain of Moloney Murine Leukemia Virus (MoMuLV), which can cause leukemia in mice (it is not known to cause disease in humans, though retroviral infection does carry at least a small risk of mutagenesis). The viral vector inserts a gene that expresses the protein E47, which acts in a variety of ways to make cancer cells revert to acting like healthy cells.

This is an exciting idea, though as the press release notes, "we are screening for molecules—potential drugs—that can induce overexpression of E47." That's a way of noting that retroviral vector gene therapy is in its infancy, and that it would be much better if we could find a small molecule instead.

These findings prompted us to ask whether
the growth arrest and acinar gene expression induced in vitro
might be sufficient to diminish the tumor-forming potential of
these aggressively growing cells. Indeed, temporary induction of
E47 for 2 to 8 days in vitro produced stable cell cycle arrest and
trypsinogen expression in transplanted human PDA cells. It will
now be of interest to investigate the effects of E47 on the growth
dynamics of established tumors.

And also the above- established tumors notoriously mutate and become genetically heterogeneous over time, greatly increasing the chances that at least some of the cancer cells are resistant to whatever line of attack you throw at them. Cancer cells that have mutant forms of E47's targets wouldn't be reprogrammed. Still, any advance against pancreatic cancer is highly welcome.

Comment Re:photo too blurry (Score 4, Informative) 78 78

If you do an image search, nearly half of the artist renderings still depict Pluto as blue-grey in color. I think the reasoning was that the planet was thought to be largely covered in methane ice, which has that color. And they were right about the ice, but UV radiation can initiate reactions in methane and diatomic nitrogen to produce a mix of simple hydrocarbons and nitriles, similar to the orange-brown haze that shrouds Titan, just on a much less dramatic scale.

Comment Re:Not 3D chemical printing (Score 4, Informative) 132 132

Yes, it's a lot like existing solid-state nucleic acid or peptide synthesis setups, but with the major advantage of forming carbon-carbon bonds instead of phosphodiester or amide linkages, making the technique a lot more general. The setup involves a useful reaction called Suzuki coupling. In Suzuki coupling, a metal (usually palladium) catalyzes a reaction between a halide (that is to say, chlorine, bromine, etc.) and an organoboron compound. The mechanism is complex, but the result is a carbon-carbon single bond. This reaction and similar ones are already widely used in the pharmaceutical industry since they can reliably glue together smaller structures together to make a larger molecule. The smaller structures are not individual atoms, though- they tend to have maybe 10-20 atoms or so. Drugs with biaryl structures like the blood pressure drug valsartan are now often made this way.

In previous work, the Burke lab showed that the reaction could be made more convenient by using a specific type of boronate salt which can be easily added and removed from a molecule, and generally produces derivatives that are stable long-term. They then found that these salts can bind to silica and will only be released in the presence of the solvent tetrahydrofuran. So what they did was build a setup that can run this reaction iteratively; at each step, you add another bit of the molecule; each bit has a halide at one end and a boronate salt at the other. This is a lot like an amino acid, which has an amine at one end and a carboxylic acid at the other, which can each react with other amino acids to form chains. Since the molecule bits are shelf-stable, conceivably you could load a machine with a library of commonly used "puzzle pieces" (which you probably bought from a specialty chemicals manufacturer like Sigma-Aldrich or EMD) and assemble them, then wash off the finished product in THF. The yields demonstrated thus far are...not great, but the idea that it can run automated means that it could brute-force some syntheses and allow for the production of complex molecules from more common starting materials. It's a major advance in synthetic organic chemistry, but it's not so much a universal printer as more like an early mechanical printing press, where you still need to provide the type blocks and set the letters yourself.

Comment Re:I blame the FDA (Score 3, Interesting) 365 365

Nicotine is only distantly related structurally to the vitamin nicotinic acid (aka vitamin B3 or niacin). While nicotinic acid is an intermediate in tobacco's biosynthesis of nicotine, the final nicotine molecule also has an N-methylpyrrolidine ring not present in the vitamin. Nicotinic acid is the active form of vitamin B3, but the amide derivative (nicotinamide, as the parent notes) is also a bioavailable form, as it is converted in the body to nicotinic acid. Nicotinic acid is not named for a direct biological relationship to nicotine, but rather a synthetic chemical relationship. Nicotinic acid was first prepared synthetically by reacting nicotine with nitric acid; it was only later that nicotinic acid was isolated from biological systems, and was eventually found to be essential in the prevention of pellagra.

The physiological effects of nicotine are for the most part not due to its similarity with the vitamin niacin, but because it can bind to and activate a certain type of acetylcholine neuronal receptor: that is to say it mimics a neurotransmitter. Notably, nicotine does not bear much structural similarity to acetylcholine, but its agonist activity at these particular receptors is an identifying property of their type, to the point where they are called nicotinic acetylcholine receptors.

Comment Re:What, no MSDS? (Score 4, Interesting) 87 87

I don't know- I went looking for an MSDS for a modern firefighting foam, and the composition listed is:

Polyethylene glycol: 2.5-10%
Other components below reportable levels: Greater than 90%

Now, this is for Ansul-3 Fluoroprotein foam concentrate. It definitely contains some sort of fluorinated compound (fluoroprotein foam agents are at least known to contain a fluorinated surfactant and hydrolyzed protein); the MSDS has absolutely no mention of what it is. In the Environmental Handling section, all it says is "An environmental hazard cannot be excluded in the event of unprofessional handling or disposal." Nothing about how fluorinated surfactants are persistent environmental contaminants or can cause kidney damage in high doses. It is simply written like innocuous polyethylene glycol is the only component. I've seen material safety data sheets for shampoo that have far more information.

Now, in the specific case covered by the research paper, the "unknown compounds" aren't really that mysterious. They're all either metabolites, chemical precursors, or close chemical relatives (if you're making some some sort of octane derivative, you can expect some hexane to be in there too). And they're all given as 0.1%-1% of the main PFOS surfactant; certainly chemical manufacturers need to exert better control over their processes, minimize byproducts, perform long-term safety studies, etc. And that goes double for anyone making halogenated organic compounds, which now have a substantial record of turning out to be accumulative toxins. But I think if you look at many common manufactured products at trace levels with tandem mass spec, you're going to find some compounds that aren't in the literature.

Comment Re:How are they rocky? (Score 2) 67 67

What's interesting about this star though, is that according to the paper, Kepler-444 is not some primordial supergiant, but a K dwarf (orange, of the same type as Alpha Centauri) with a smaller companion red dwarf (or possibly two companion red dwarf stars which are closely bound to each other).

Comment Re:Mass production ? (Score 3, Informative) 187 187

Mass production- of graphene powder. Cambridge Nanosystems' process makes flakes of graphene in the 200-800 nm diameter range; cf. this interview with their chief scientist. It's still a valuable material with many potential uses; that interview talks about composite materials and conductive inks. However, it's a very different product with different applications from a large-scale monolayer sheet.

Comment May not be a practical drug. (Score 4, Informative) 153 153

The original paper for this was discussed yesterday on In The Pipeline. The point was raised that the mechanism involved, the JAK-STAT signalling pathway is used quite broadly throughout the body in the control of cell growth and differentiation. There are several Janus Kinase (that's JAK) inhibitors already on the market or in development, and they are powerful immunosuppressants indicated for the treatment of things like rheumatoid arthritis or leukemia. They tend to be the sorts of drugs whose advertisements say stuff like, "Xeljanz may increase your risk of serious infection." Notably, Xeljanz (tofacitinib) popped up in the news a few months ago when it was used to grow hair in a patient with alopecia universalis (who was already taking the drug for an autoimmune disease) and the headlines exclaimed that a cure for baldness was on the horizon. Now, a single drug that burns fat, grows hair, and relieves psorasis sounds like a miracle, but the reality is that's a sign that these compounds act more broadly than is desirable.

As the paper's authors themselves put it:

The utility of JAK inhibition as a therapeutic strategy for obesity is complicated by the well-described role of this signalling pathway in the immune system. In fact, tofacitinib is approved in the United States to treat rheumatoid arthritis. Thus, if one were to imagine targeting adipose tissue by in vivo administration of an IFN–JAK–STAT inhibitor or similar compound it would almost certainly need to be delivered locally and prevented from spreading systemically or alternatively targeted selectively to white adipocytes. One could also conceive of a cell-based therapy wherein JAK inhibition of patient-derived adipocytes ex vivo is followed by transplantation to treat obesity, but this therapeutic modality would need to overcome numerous and significant obstacles before becoming a reality.

Comment Re:Toxic light (Score 3, Informative) 34 34

The toxicity is actually an indirect effect. The fluorescent dyes can in their excited states react with molecular oxygen to produce reactive oxygen species that damage tissues. By reducing the time and energy of excitation of the fluorophores (by only exciting those actually about to be scanned by the microscope), this technique reduces the amount of toxic byproducts.

Comment Re:More details (Score 2) 294 294

Most artificial sweeteners sold in powder form contain a simple sugar or starch to add bulk and give the product free-flowing granules more similar to sugar. Since saccharin, sucralose, and aspartame all taste hundreds of times sweeter than sugar, they are used in much lower amounts, with bulk added for the consumer-serving preparations so that you don't have to add micrograms of sweetener to your coffee to get the equivalent sweetness of sugar. Either glucose (usually listed as dextrose) or maltodextrin are generally used, which is interesting since it means that sugar substitutes generally contain a small amount of carbohydrates. The little single-serving packets tend to have about 3 (kilo)calories each; in the US, the FDA allows foods with less than 5 calories to be labeled as "zero calorie," so they generally are.

I note that this study did happen to use all powder-form sweeteners (dissolved in water) which means that there would some small amount carbohydrate in the solution. That's a perfectly reasonable way to run this study, since these are widely used preparations of these sweeteners, but I do wonder if there might be a difference with a genuinely digestible-carbohydrate-free preparation.

Comment Re:Would YOU be able to sleep in space?? (Score 3, Interesting) 106 106

I read the Apollo 11 Lunar Surface Journal during the anniversary back on July 20th, and one of the entries that stood out to me was a section called "Trying to Rest," which detailed a time between the end of the astronauts' moonwalk, but prior to when they needed to make preparations to liftoff from the Moon. A period of about 7 hours was scheduled for the astronauts to sleep, but

[Armstrong - "(The quality of the rest) was poor in my case."]

[Aldrin - "I'd say the same thing."]

In their technical debrief, Armstrong and Aldrin detailed some problems with their sleep environment- too cold, too bright, too noisy, but yeah, that they were also just too excited to sleep. (It does mention that most of the technical problems were worked out by Apollo 15, and the last few crews got decent sleep on the lunar surface. I'm still convinced that if it were me, I would have responded to planned rest periods with "HOUSTON, I CAN SLEEP WHEN I GET BACK FROM THE MOON, OVER.")

Comment Re:Federation of Am... Soc.. for Exper... Biology? (Score 1) 63 63

Ah, I didn't think to look at the other societies. They do apparently have a large campus at that address, so I guess they probably have real office space for those societies there. The property was a country estate when they bought it- now it's inside the Beltway.

Comment Re:Federation of Am... Soc.. for Exper... Biology? (Score 1) 63 63

27, according to their website. They do cover a wide range of disciplines at least. I was going to note that the Genetics Society of America and the American Society of Human Genetics seem like they'd have a lot of overlap, but then I noticed that they're headquartered at the same address, so I imagine they came to a similar conclusion at some point.

Machines certainly can solve problems, store information, correlate, and play games -- but not with pleasure. -- Leo Rosten

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