Biology – Page 72 – David Bradley

Googling for Genes

Those clever people at Harvard are using Google‘s API to allow users to search for gene sequence fragments on the Web in combination with a text query. You’re limited to 1000 searches per day and have to enter your own API key to get the maximum benefit. But. that’s probably enough to be going on with.

From the site: Query Gene is distinctive because it is not limited to a single database. Instead it captures genetic information across the net using Google. It works by taking a gene sequence in combination with other search terms, finds similar sequences using NCBI’s MegaBlast, retrieves the descriptions of those matching genes from NCBI’s Entrez Nucleotide database, and performs a series of Google searches using the combination of your original search terms and each gene description. The percent sequence identity is indicated alongside each match: this indicates how much of your queried sequence is contained in the sequence it matches.

You might want to find out what disease states are associated with a specific nucleotide sequence. No problem. Paste in the sequence and enter a text phrase, such as “genetic disease associated with” and up pop the results. Well, actually, they didn’t with the test I tried, but that could be down to my browser configuration. I got “Sorry, we are under maintenance: Please try again in a few weeks”.

A sample sequence is given here. If someone else could confirm or refute the maintanance outage for ChemSpy readers that would be very helpful.

Murine faeces

I’m not sure whether I should admit to the following, but this morning I found little scatterings of murine faeces and could detect a musky yet strong smell of ammonia in the storage area where we keep our dog and cat food. Not nice. In case you haven’t guessed, we got mice.

Odd that these little critters should be so brave as to venture into the part of the house in which the cat spends some of its time and although he is getting on in years, he does still have the legs for a chase (especially when the dog slips her lead and chases him out of the door. Anyway, traps have been bought and placed, droppings have been removed and traces of murine urine have been mopped up (with a cotton bud) and the whole area disinfected.

I got to thinking about that word I used just now. Murine. The “ine” suffix means just means “of”, “like”, or “referring to”, while the “mur” was derived from “mus” then “mur” for mouse in an originating Indo-European language and thence to Latin – “murinus” meaning of mice. The root gives rise to the scientific group name for both mice and rats Muridae or sub-family Murinae. Others words of similar structure include porcine (pigs), bovine (cattle), ursine (bears), ovine (sheep), equine (horses), and of course feline and canine, but not supine.

Shopping for Genes

Leaning strongly towards the bio today, I thought I’d mention a new database for biologists that works like a shopping mall. An international team has opened a virtual bazaar, called PAZAR, which allows biologists to share information about gene regulation through individually managed boutiques. Customers may draw data for free from any boutique or extract information from the “superstores” that aggregate data of similar types.

In deciphering the human genome sequence, researchers hope to understand the “when and where” of gene expression because it could underpin novel cancer therapies, stem cells treatments for degenerative disease, and explain complex diseases such as diabetes.

Male-Female Crabs Split their Difference

Male-Female Crab

David Johnson and Robert Watson thought they had seen all there was to see in the Chesapeake Bay in almost three decades until they pulled out a crab from the way that had a male left half and a female right half. Now, that crab, acquired by Romuald Lipcius of the Virginia Institute of Marine Science at the College of William & Mary, has moved sideways into the world of natural metabolites where its gynandromorphic peculiarities have helped scientists, for the first time, discover that some molecules can be made only by one sex and not the other.

The male-female crab is a unique example of the blue crabs. It turns out that the males of this species produce a natural metabolite that is absent in females. This suggests that some complex biochemistry is underway that is activated only in males. Robert Kleps of the University of Illinois at Chicago and colleagues have isolated this small molecule and identified it as 2-aminoethylphosphonic acid (AEP), an uncommon but well-documented natural metabolite.

We used low-field NMR using phosphorus-31, to observe the small molecule, explains Kleps. He points out that science tends to get lost in the rush for higher field NMR running hydrogen-1 and carbon-13 on 100 kilodalton proteins. However, he adds that, “Even low-field NMR spectroscopists can make interesting discoveries. I’m very happy to have stumbled over this metabolite, while doing basic research on invertebrate metabolism.”

So, why might the existence of a metabolite in the males of this blue crab species and not the females have any bearing on our everyday lives? Well, there are well known differences between the sexes in people, such as disease susceptibility, anatomy and drug metabolism. Kleps points out that these differences might in fact be due to the presence or absence of a crucial metabolite.

Now that the existence of a sex-specific metabolite has been found for one animal the search is on for others, including ones that might exist in people.

For more details on the NMR study check out my column on SpectroscopyNOW.com, the research paper itself is available in Plos One.

You can hear a description of the crab from Lipcius here and listen to Kleps’ podcast

MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Intellectual genetics

Tug of war

Two worthy legal moratoria – the Agreement on the Trade-Related Aspects of Intellectual Property Rights (TRIPS)
and the Convention on Biological Diversity (CBD) – are potentially in direct conflict when it comes to plant genetic resources and intellectual property rights, at least that is the conclusion of legal expert Megan Bowman. However, potential conflicts could be reconciled in this context by applying the common sense notion of remaining true to the over-arching principle of global welfare-maximisation in TRIPS and by utilising patent exemptions in appropriate circumstances. This, Bowman claims, will allow TRIPS and CBD to operate in a way that achieves both their objectives equally well so that intellectual property rights can be appropriately recognised and biodiversity can be sustained.

Writing in the International Journal of Intellectual Property Management (2007, Vol. 1, pp 277-292), who is a trained barrister and a lecturer in the Law School and Centre of Strategic Economic Studies, at Victoria University, Melbourne, Australia, points out that international recognition of intellectual property rights has grown, particular in the biotech arena, as biodiversity levels have fallen across the globe. Bowman points out that these two trends have become related since the creation of TRIPS and CBD in 1993 whose spheres of operation overlap significantly, particularly in relation to plant genetic resources and intellectual property rights. Bowman states that this is because biological diversity, at both genetic and physical levels, is being exploited as the key ingredient for lucrative biotech and pharmaceutical industrial creation. Patent protection of that creation raises questions about biodiversity sustainability and also access to the resultant benefits and technologies derived from use of a raw product ‘owned’ by source countries or communities.

Currently we are experiencing global biodiversity degradation and decimation due to causes such as global warming that may result in the extinction of nearly half the current lifeforms by 2050. Bowman comments: ‘Apart from the intrinsic value of biological diversity, without healthy and diverse ecological systems on this planet there is no quality of life for humans — no fresh air or water, no arable land or edible food, and exposure to devastating storms, floods and droughts. But at the same time, humans are evolutionary creatures and we see that clearly with technological innovation. We are also wed to the dollar and we see that, in the context of this discussion, in the jealous guarding of rent for patents, specifically in the growing sector of biotechnology and pharmaceuticals based on plant genetic resources. So the question is how do we marry these components in a way that honours each of them? I look at this question from a purely legal standpoint. Undoubtedly any solution is complex, multi-faceted and multi-disciplined. Nonetheless, the legal principles embedded in the key international treaties on protection of biodiversity and protection of intellectual property rights in plant genetic resources share a commitment to global welfare enhancement. So it becomes clear that the legal foundations exist for cooperation between these two sectors. This knowledge paves the way for productive dialogue and action in boardrooms, patent offices and parliaments around the world.’

Related article from the Sciencebase archives on corporate academia: Will publicly funded research become mired in patent protection and intellectual property rights or remain purely altruistic?

(Updated: August 21, 2007)

Mice and a slice

Raman brain slice A new methodology for fibre-optic Raman mapping and FTIR imaging of secondary cancer cells, metastases, and detecting tumour cells has been developed by researchers in Germany. The technique facilitates imaging of samples thicker than 50 micrometres and could be used in detecting cancer cells, as a tool for molecular histopathology, in metabolic fingerprinting, general disease diagnostics.

Team member Christoph Krafft is currently in the Department of Materials and Natural Resources, at the University of Trieste, Italy, but will be returning to Dresden University of Technology with a new research grant in September. I spoke to him about the research and he told me that, “This fibre-optic Raman method will allow detecting tumour cells and tumour tissue in vivo and enable studies of tumor development.” You can read more details in the latest issue of SpectroscopyNOW.com in the Raman ezine.

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.

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.

DNA Network

Sciencebase was recently invited to join the excellent DNA Network and as such our genetics news feed is now being pulled by the network’s feed system. If I had been a little slower off the mark, I could have been site number twenty in the list, but when I joined I think I jumped in at #18. There are, at the time of writing, nineteen members, no DNAying it.

So, here is a quick random selection of fellow network members. The links will take you to the individual RSS feed for each site whereby you can subscribe (for free) and get some great and timely information on DNA and the latest happenings and business news in genetics and DNA research.

VentureBeat Life Sciences

Discovering Biology in a Digital World

DNA Direct Talk

Epidemix

The Daily Transcript

henry: the human evolution news relay (genetics)

Mary Meets Dolly

Genetics News

Microarray and Bioinformatics

Gene Sherpas: Personalized Medicine and You

The Personal Genome

All excellent newsfeeds, all focused on one thing, DNA. You can find links to the others, including Eye on DNA, the owner of which led me to the DNA Network in the first place, via DNA Network. I’ll do another round-up of the remaining members later.