David Bradley – Page 290

PubChem Statistics

In March 2006, I interviewed PubChem’s Steve Bryant for the Reactive Reports chemistry webzine and he revealed some of the inner workings and the aims of the PubChem chemistry database. Ever since, I’ve been rather curious about the growth of the site. How many scientists are using it. Unfortunately, Bryant tells me, getting a handle on that kind of data is difficult. “It’s a very tricky business to accurately condense all the raw log info on hits and IP addresses into an accurate summary of who’s using a given resource and how,” he explains.

However, there are a few tips you might use to extract some useful information from the site nevertheless. There is an easy way to look at current contents of the databases, for instance. The best trick is to go to the “global query” page:

http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi

Then enter “all[filter]” (no quotes) in the search box. This gives counts of how many records in each database, e.g. 10,358,219 PubChem compounds, 552 assays, etc. There is also a summary of contributors to PubChem, that lists numbers of substances or assays by organization:

http://pubchem.ncbi.nlm.nih.gov/sources/sources.cgi

Now, obviously that doesn’t provide usage stats, but it does highlight a newsworthy aspect of developments at PubChem. Over the past year, there has been an increasing number (and diversity) of the screening assay results. “We’re now up to over 10 million substance test results (sum of the number of substances tested in each assay, across all assays),” says Bryant, “We’ve also put some work into structure-activity analysis tools. For example, from the first
assay answering the all[filter] query (AID 728, Factor XIIa Dose Response Confirmation), try “Related BioAssays | Related BioAssays, by Target Similarity”, the “Structure Activity Analysis”.”

Bryant points out that this “heatmap” display isn’t useful to all users. However, screeners who want to check on the selectivity of their “hits” are using these tools more and more, he says.

Master AND commander

Master commander An fMRI scan of the upper echelons of the human brain, reveals that there are apparently two commanders at the helm, according to US neuroscientists; it is as if Russell Crowe were joined by his twin brother to captain the ship. The work may suggest new insights into behavioural problems that occur following brain injury.

Neuroscientist Steven Petersen and his team at Washington University School of Medicine in St. Louis also found that these two captains at a single helm do not consult each other in the control of voluntary, goal-oriented behaviour. Such behaviour encompasses a vast range of activities from reading and surfing the net to singing a song or even sailing a ship. In contrast, involuntary behaviour, such as pulse rate, breathing, and digestion are not controlled in this way.

You can read the full story in my SpectroscopyNOW column in the MRI channel.

Fire-extinguishing Grenades and Laser Remotes

Fire fighting grenade A fire-extinguishing “grenade”, a “laser finger” remote control for quadriplegic individuals, and a pocket-sized water purifier. A stack of cutting-edge innovations that have not come from a hi-tech thinktank but from teams of high school students in the US.

Twenty InvenTeams recently showcased these and other inventions at the 2007 Odyssey event at the Massachusetts Institute of Technology. The teams are set to receive grants of up to $10,000 in October to help them develop an invention prototype.

Among the other amazing creations are:

Solar-powered biodiesel processor
Driver Awake dozing driver waking system
Underground locator and communicator

Organising spokesperson Sarah Piperato told me that, “These high schoolers’ inventions show great innovation. This is what ambitious American teens are accomplishing with science and technology.” Now, these truly are winning science projects that put things like squeezing a boiled egg into a bottle to shame. That said, not everyone can be a Faraday, Edison, or a Lovelace.

Pirouetting DIABN

It seems to be no coincidence that tens of thousands of molecules line up to pirouette around a photochemical reaction centre, according to German researchers, given the superficial resemblance of the molecule, 4-(diisopropylamino)benzonitrile (DIABN), to a ballet dancer en pointe. They have shown, for the first time, that the ultrafast intramolecular electronic charge separation that takes place during a photochemical reaction leads to light-induced reorientation in an organic molecular crystal.

Whether or not the same will apply to other molecular crystals remains to be seen. The results appear in Phys Rev Lett and you can read David Bradley’s write-up in the latest issue of the SpectroscopyNOW X-ray ezine. This and related studies could pave the way for investigations of more complex systems including crystalline biological macromolecules.

InChI=1/C13H18N2/c1-10(2)15(11(3)4)13-7-5-12(9-14)6-8-13/h5-8,10-11H,1-4H3

Yoga Stretches Brain Chemical

GABA yoga posture US researchers have used a specialist brain scanning technique, magnetic resonance spectroscopic imaging, which is effectively an MRI scan carried out at the molecular level to reveal the effects of yoga practice on the brain. Specifically, they have investigated how concentrations of the feel-good compound gamma-aminobutyric (GABA), an inhibitory neurotransmitter, change after regular practice of yoga postures.

Eric Jensen and colleagues at Harvard Medical School looked at eight subjects prior to and after one hour of yoga as well as eleven control subjects who read a book rather than undertaking the yoga exercises. Although the samples are very small, they saw a marked difference in GABA levels in the yoga practitioners compared to the readers. Their findings suggest that yoga, and perhaps other forms of exercise, should be investigated as a complementary treatment for depression and anxiety disorders, which are commonly associated with low levels of GABA.

You can read more on this in my write-up over on SpectroscopyNOW.com. Click here for the Sciencebase complementary medicine roundup

Alchemy and Infamy

This week, I filled my regular fortnightly slot on ChemWeb with some applied chemistry, chemical engineering, and more:

volunteer work gets rewarded right from the top at the American Chemical Society, a novel approach to coupling unreactive arenes solves a century-old problem, sidesteps several synthetic steps and cuts down on waste, while a Stanford chemist reveals a PUG that can hack the PubChem database. Also, this week The Alchemist discovers that forests of nanotubes can be bundled together like so many logs in a molecular scale timberyard and new European regulations on chemicals came into force at the beginning of June, but may not reach consumers for years. Finally, yet another answer to the problem of binge-eating and obesity, a synthetic version of the hormone amylin gives positive rewards in the latest clinical tests.

Free offline science magazines

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Ragworm Ragtime

Ragworm When I was a youngster I used to do a spot of sea fishing on the freezing cold north east coast. It wasn’t so much a hobby as an obsession at one point. Key to success was a plentiful supply of lugworm which could be dug from the wet golden sand at lowtide and stored ready for the next angling venture, while ragworm, which have a nasty bite, came from the local fishing bait supplier. Never would it have occurred to my 11-year old self that these lowly creatures could harbour the secrets of our own evolution.

However, apparently it does. Detlev Arendt of the European Molecular Biology Laboratory has been studying the multifunctional neurones that sense the environment and release hormones in vertebrates (including ourselves), flies, and worms. The last common ancestor of all of these creatures must provide the evolutionary basis of our modern brains that endow us with the skills to varying degrees of success to dig up ragworm, take part in fishing trips, and ponder our origins.

Hormones control growth, metabolism, reproduction and other biological processes. In humans, as indeed in all vertebrates, the chemical signals are produced by the hypothalamus and other specialist brain centres and secreted into the blood for circulation around the body. This signalling system is not, it turns out, the preserve of those creatures with a backbone. Arendt and his colleagues now believe that the hypothalamus and its hormones have their evolutionary origins in an ancient worm-like creature that lived hundreds of millions of years ago and is the common ancestor of vertebrates, flies, and worms.

Hormones work slowly, on the whole, and have body-wide effects. Insects and nematode worms use hormones, but the specific molecules they use are very different from their vertebrate counterparts.

“This suggested that hormone-secreting brain centres arose after the evolution of vertebrates and invertebrates had split,” explains Arendt, “But then found vertebrate—type hormones in annelid worms and molluscs, indicating that these centres might be much older than expected.” Comparisons of two types of hormone-secreting nerve cells from zebrafish, a vertebrate, and the annelid worm Platynereis dumerilii, in Arendt’s lab have now revealed some stunning similarities that point to a shared and ancient ancestry for our hormonal systems.

“These findings revolutionise the way we see the brain,” says Kristin Tessmar-Raible who carried out the comparison, “So far we have always understood it as a processing unit, a bit like a computer that integrates and interprets incoming sensory information. Now we know that the brain is itself a sensory organ and has been so since very ancient times.” The research appears in detail in the journal Cell.

Bewildering to think that I used to skewer these little creatures on a barbed hook and cast them into the sea to catch scaly marine creatures. It almost makes no sense.

Burying Carbon to Save the Planet

Recent research has highlighted the possibility of burying, or sequestering carbon dioxide in deep, disused coal mines. Not only might this allow us to reduce atmospheric carbon dioxide levels but the process would displace usable methane (natural gas) from the coal and extend the length of time we will have this resource available to us as a fuel and chemical feedstock.

However, I felt that the while the concept sounds viable initially, there are several loopholes in the whole carbon burial argument, especially when releasing methane is also brought into the equation. I asked team leader Thomas Brown of the US Department of Energy’s National Energy Technology Laboratory about my concerns.

First the whole process will require its own energy supply, which will in turn release CO2, as well as being expensive to undertake in practice. Moreover, most of the methane retrieved in this way will end up being burned as fossil fuel and adding still further to the global carbon footprint.

“You are correct,” Brown told me, “Cost projections for CO2 sequestration indicate it will be expensive and a great deal of research is currently underway to bring these costs down.” He points out the methane release process is quite encouraging because for every 2-4 units, or moles, of CO2 trapped, just one unit of methane is released.

“This suggests that [the process] has the potential to be more cost effective than the [alternative approach] of sequestration in deep saline aquifers,” Brown adds.

The coal bed methane will certainly be useful nevertheless and Brown points out that CO2 released by burning it will in turn have CO2 capture systems in place. “It is an additional energy source that can be utilized instead of venting it from coal seams to the atmosphere,” he says, “it also provides some offset for the cost of sequestering CO2 – methane is much more detrimental to the environment as a greenhouse gas than CO2.”

He adds that sequestration in coal seams my not be a viable option owing to low permeability values and swelling of the coal itself, which he discusses in his research paper. “More R&D is required,” he told me.

Bad Apples, Colds and Echinacea

Echinacea - Photo by Bruce Marlin Recent media reports seem to have strengthened the case for using echinacea to ward off or treat the common cold. But, are they based on valid new evidence?

The LATimes [item no longer available by link] for instance, says researchers carried out an “analysis of 1,600 patients pooled from 14 previously published studies found that echinacea reduced the chances of catching a cold by 58% and shaved 1.4 days off the duration of a cold.”

The researchers who carried out this analysis point out that none of the previous trials was large enough to be valid, but somehow they attempt to give them new credence by mixing together the data from lots more dubious studies. One bad apple can almost certainly spoil the barrel, but throw together a couple of dozen bad apples and that barrel is going to be humming before the day is out, surely?

Meta analyses of solid double-blind, placebo-controlled clinical trials certainly can shed new light on old findings, but what they do not do is create new data points, they are simply a re-analysis of old results pooled.

Craig Coleman of the University of Connecticut whose team carried out the meta analysis, point out that none of the trials analysed individually were big enough to reveal the benefits of Echinacea. Somehow his new analysis of old data demonstrates an almost two-thirds reduction in the risk of catching a cold compared to a person not using Echinacea. But, how could that be, if those earlier trials succumbed to serious wishful thinking and the placebo effect, then the whole argument is in doubt.

Wallace Sampson, an emeritus adjunct professor of medicine at Stanford University School of Medicine is quoted as saying that because the methodologies of some of the earlier studies are so suspect, this casts doubts on the pooled result. Exactly.

The team also reports that of 800 products containing Echinacea they investigated, there are large variations in the quality, which part of the plant was used – flower, stem or root – and how much so-called active ingredient is present. In addition, they suggest that more work is needed to check the safety of the countless formulations available. Their warning echoes other studies that have pointed to toxicity problems associated with long-term use of Echinacea products, although admittedly some of those studies might also be considered invalid because of poor methodology.

So, should we run to our local herbalist on the off-chance that we might catch a cold or if you’ve already caught one quickly down a dose of Echinacea to “shave off” 1.4 days or runny noses and sneezing? I don’t think so, not unless you don’t mind putting up with a whole lot of bad apples.