That picture is two genetically male frogs doing the do. One of them has had a sex change, and is now a laydee frog with ovaries! Why has this happened? It’s been blamed on atrazine.
The paper was published in the March early edition of PNAS. It adds further evidence against the weedkiller’s safety in an ongoing controversial debate.
Heading the team from California and Ohio was Dr. Tyrone Hayes of the University of California, Berkeley. Dr. Hayes has published several papers on the dangers of atrazine, a herbicide used extensively in Australia and the US. In the past he’s raised concerns that it can disrupt hormones even in small quantities, and this paper provides new evidence which is hard to ignore.
40 male frogs (Xenopus laevis) were raised from larva while exposed to 2.5 ppb atrazine. Their gender and testosterone levels were compared to male controls raised without the herbicide.
At sexual maturity 90% of the males exposed to atrazine had less testosterone than normal. In competition with control males, the atrazine treated frogs were less successful in mating. When they did mate, they were significantly less fertile.
The remaining four genetic males looked like females, and dissection of two revealed ovaries. The other two mated with control males and produced offspring which were all male.
Feminisation and decreased fertility spell disaster for frog populations. A drop in reproduction rate is bad enough, but it gets worse. With males masquerading as females they could breed themselves into extinction and we wouldn’t even know.
On the other hand, Dr. Hayes (pictured) has had a bit of a history with atrazine. I’d call it a crusade. He’s done a lot of research on it and some of it has been ripped to shreds by other researchers. In some cases his work has been deemed unreplicable, and that’s a big no-no in the science biz. Your results HAVE to be repeatable, otherwise it’s just not a good experiment.
On the other other hand, those people who’ve kicked the crap out of his work are largely people from EcoRisk, which are partially funded by the manufacturers of atrazine. It’s possible their designs were flawed so the amount of atrazine used wasn’t constant. Plus, well, it is a bit of a conflict of interest, right? But if that’s where the funding comes from…
So an activist on one side and a possibly bias company on the other. Hell, who’s right and who’s wrong? Do we want to take the risk? The Australian and US governments say that it’s a safe herbicide, but the European Union disagree.
While we wait for a decision, frogs may be the ones to suffer.
INSYS Therapeutics, Inc. announced positive results from the pivotal phase III efficacy trial for patients utilizing the Fentanyl Sublingual Spray (SL Spray) technology to treat breakthrough cancer pain. The company claims that all primary and secondary endpoints were achieved in the study, and the drug is the first product to ever show statistically significant pain relief when measuring the summary of pain intensity difference at five minutes (SPID(5)) in a phase III breakthrough cancer pain trial using Fentanyl.
Dr. Richard Rauck, a principal investigator in the Phase III study observed, the sublingual spray demonstrated very rapid, effective pain relief. Patients began to experience meaningful pain relief within five minutes. This observation was supported by the clinical research findings. As claimed by the researchers, to date, no other transmucosal Fentanyl (see the general structure) product has produced pain relief this quickly. This finding is supported with continued pain relief at all subsequent time intervals.
Hope this easy-to-use oral spray that can produce effective, potent and very rapid pain relief will be a tremendous advantage for the patients who experience moderate to severe cancer breakthrough pain.....
The Supreme Court has agreed to hear a vaccine-liability case, in an attempt to untangle conflicting lower court rulings. This all turns on the 1986 act that shields manufacturers from liability suits and a followup law that establishes a separate compensation system for injuries. A Georgia Supreme Court ruling has recently held that such suits can go on in state court, which seems to contradict other court decisions (and the intent of the 1986 law as well, you'd think).
I agree with Jim Edwards of BNET that although this particular case involves the DPT vaccine, the vaccines-cause-autism crowd will be watching this one very closely. Lawsuits will no doubt be ready to fly later this year in case the Supreme Court breaks that way - which seems to me unlikely, but I'm no judge. . .
Over the past semester and a half, one of my Biochemistry professors was dropping hints about a special book he had read that boasted to lower your cancer risk, increase vitality, and overall make you a happier and healthier person, while encouraging us to figure out what it was. I did a little looking, but was only able to find your standard self-help, get thin quickly, increase vitality with structured water and vitamin megadoses mumbo-jumbo. It would make sense that he would be suggesting something written by a credited scientist, but what kind of person who was a scientist (and not a practitioner of nonsense medicine) would write a self-help book?
The answer came later in this semester when one of the students actually figured it out: The China Study, written by Cornell scientist T. Colin Campbell and his son Thomas. The essence of the book is that it discusses the science behind nutrition, the reasons why the SAD (standard American diet) is the underlying cause of chronic disease in America, and this comprehensive study, conducted in China, that looks at nutrition trends and their connection to disease in a number of provinces throughout the country. It contains over 750 literature citations (it's like one big Chemical Reviews article!), and the contents were so overwhelmingly important that it caused my professor to go vegan after reading it.
I just started the book last night, so I can't say for certain what I'll think about it, but it's hard to argue against science of all things. Expect to hear back from me again when I finish the book!
In other news, if you're around an internet computer box at around 4 pm Eastern, go on over to the Runners Round Table and listen to me, along with Kiersten at 26 for 25, and Brian at TriBoomer talk about raising money for charity through running! FYI I'm going to run and work on my research proposal after the show, if anyone's concerned I'm not getting enough work done!
We haven't had a How Not to Do It around here in a while, so here's a companion piece to the famous Sealed-Up Liquid Nitrogen Tank. This incident happened (as far as I can tell) about ten years ago. It's been used in a number of safety presentations then, thanks to the Airgas Corp., whose safety officer assembled a number of photos (and this is the time to emphasize that they had nothing to do with the accident itself, because people who work for a pressurized-gas company actually know how to handle pressure vessels.
As opposed to the two guys who scavenged a liquid oxygen Dewar from a scrap metal yard and decided to put it back into service. According to the most detailed report, they tried to rig up a connection to refill the cylinder, but found that it vented immediately through the pressure-relief valve. So. . .well, yeah, you know what's coming next: they took the darn thing off and plugged it shut. No more pesky venting! They filled up their cylinder, which was loaded on the back of their pickup truck, and went rolling down the interstate at lunchtime. Whereupon they had a flat tire, and pulled over for a while to fix things. . .
OK, you can look out from behind your hands now. Although I can't imagine how, neither of these two cowboys managed to get themselves killed, nor did they take out anyone else, through what appears to be sheer blind luck. According to the report, one member of the Cylinder Kings ended up being blown across five lanes of traffic, while his partner was launched forty feet in another direction. You can see from the photo how the truck weathered things. I can't imagine that a pressure wave of straight oxygen hitting tank of gasoline can end well; it's a perfectly reasonable mixture to put a payload into low-earth orbit.
Which is a good note on which to take inventory here. We have the owners of the oxygen cylinder accounted for, and their truck. What about the cylinder itself? Well, similar to the nitrogen tank referenced above, it had failed at the bottom weld and thus departed the scene of the accident like an artillery shell. It re-entered the affairs of the world a quarter of a mile away, plunging through the roof of an apartment, completely trashing the place (and severing a natural gas line in the process). As I said, how a dozen people didn't end up killed by all this is a complete mystery to me. (The red circle in that photo is where the pressure-relief device used to be. )
So the moral of this story is, I suppose, that Pressure Relief Devices Are There For A Reason. Or maybe it's "don't scrounge gas cylinders from the scrap yard and try to get them to work". Or perhaps "just because you haven't seen a pressure vessel explode yet, it doesn't mean that they can't". Or "Gegen der Dummheit kämpfen Götter selbst vergebens." Or something.
Rexahn Pharmaceuticals, Inc., a clinical stage pharmaceutical company commercializing potential best in class oncology and CNS therapeutics, announced that the Japanese Patent Office has issued a patent for its novel anti-cancer compound, Archexin. As per the claim by the company, Archexin is a first in class, potent inhibitor of Akt protein kinase in the treatment of cancer.
The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. Akt regulates signal processes of cell proliferation and survival, angiogenesis, and drug resistance in cancer. Archexin is being developed to treat solid tumors and has FDA Orphan drug designation for RCC, pancreatic, stomach, glioblastoma, and ovarian cancers. Archexin is in Phase II clinical development for pancreatic cancer as lead indication.
Archexin(R) was fromerly named as RX-0201, is an oligonucleotide compound that inhibits the expression of human Akt-1. I am really happy for this approval because, in my opinion this will boost the new field of drugs (ologonucleotides/antisense). I have covered some developments in this field, those interested can read earlier articles...
"the Japanese patent award is another step forward in the development of one of our lead clinical drug candidates, Archexin;” said Dr. Chang Ahn, Rexahn’s Chairman and Chief Executive Officer. “In addition to strengthening our intellectual property portfolio, we are pleased with the progress of Archexin’s ongoing Phase II clinical trial for the treatment of pancreatic cancer. Patient enrollment continues at multiple sites in the US and abroad and we expect to have preliminary results in the fourth quarter of 2010"....
High Throughput Screening (HTS), with all its strengths and limitations, is still the single-best way to discover novel interesting molecules in drug discovery. Thomas Kodadek of Scripps Florida has an interesting article on screening in the latest issue of Nat. Chem. Biol which is a special issue on chemical probes.
Kodadek talks about the very different properties required for drugs and probes and the limitations and unmet needs in current HTS strategies. He focuses on mainly two kinds of screening; functional assays and binding assays. The former can consist of phenotypic screening wherein one is only interested in a particular cellular response. This is more useful for drugs. However for probes, target selectivity is important and one must have knowledge of the target. HTS hits can hit all kinds of protein targets, thus making it hard to find out if your compounds are being selective. Mutagenesis and siRNA studies can shed light on target selectivity but this is not easy to do.
One of the possible solutions Kodadek suggests to circumvent the problem of gauging selectivity is to use binding assays instead of functional assays. He notes a pretty clever idea used in binding assays; that of throwing in cell extracts with miscellaneous proteins that could mop up greasy, non-selective compounds. This strategy cannot be easily used in functional assays. Binding assays are also typically less expensive than functional assays.
There is also a discussion of some of the very practical problems associated with screening. Screening typically has low hit rates and more importantly, hits from screening are not leads. You usually need a dedicated team of synthetic chemists to make systematic SAR modifications to these hits to optimize them further. As the author says, few synthetic chemists wish to serve as SAR facilities for their biologist colleagues. Plus it is not easy to lure industrial chemists to serve this function in academia (although the present economic climate may have made this easier). Thus, biologists with no synthetic background need to be able to make at least some modifications to their hits. For this purpose Kodadek suggests the use of modular molecules with easily available building blocks which can be cheaply and easily connected together by relatively inexperienced chemists; foremost in his recommendations are peptoids, N-substituted oligoglycines which are biologically active and easy to synthesize. Thus, if libraries for screening are enriched in such kinds of molecules, it could make it easy for biologists without access to sophisticated synthetic chemists and facilities to cobble together leads. Of course this would lead to a loss of diversity in the libraries, but that's the tradeoff necessary for going down the long road from hit to lead.
Lastly, Kodadek briefly talks about prospects for screening in academia. Academic drug discovery is gradually becoming more attractive with the recent long lull in industry. However academic scientists are typically not very familir with the post-synthesis optimization of drugs including optimization of metabolic properties, bioavailability and PK. Academic scientists who can pursue such studies or partner with DMPK contracting companies may be paid back their dues.
One topic which Kodadek does not mention is virtual screening (VS). VS can complement HTS and at least some studies indicate that the rate of success in VS can match, if not exceed, that in HTS. In addition, new ligand-based methods which use properties such as molecular shape to screen for compounds similar to given hits can also valuably complement HTS follow up studies.
Screening is still the best bet for discovering new drugs, but hit rates are typically still very low (1% would be a godsend). Only a concerted effort at designing libraries, ensuring selectivity and synthetic accessibility will make it easier.
Kodadek, T. (2010). Rethinking screening Nature Chemical Biology, 6 (3), 162-165 DOI: 10.1038/nchembio.303
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I am unconvinced that getting the same type of shoe will be the best option, especially because the last time I did my injury flared up. I also have done a fair amount of reading/listening to experts and non-experts regarding barefoot running, minimalist shoes, forefoot striking, and the like.
What should I do? Go with the same model or try something different? I just don't want to be injured!
On the other hand, Dr. Hayes (pictured) has had a bit of a history with atrazine. I’d call it a crusade. He’s done a lot of research on it and some of it has been ripped to shreds by other researchers. In some cases his work has been deemed unreplicable, and that’s a big no-no in the science biz. Your results HAVE to be repeatable, otherwise it’s just not a good experiment.
