Master AND commander

Master commanderAn 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

RagwormWhen 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

DNA Network logoSciencebase 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.

Genetic Research Hits Pay Dirt

DNAThe budget for the Human Genome Project and all that post-genomic, proteomic, metabonomic, immunomic…research was almost on a par with defense spending; it was almost c-omical really. Well, maybe not quite, but it stretches out with a lot of zeros nevertheless. At the time the grants were written and the funding given, we, as a society, were promised all kinds of medical miracles from gene therapies and new treatments to cure all those nasties – cystic fibrosis, sickle cell, thalassemia, cancer, heart disease and more.

We were promised personal medicine courtesy of pharmacogenomics. This would allow your doctor to profile your genome and tailor your medication to the particular set of enzymes running in your liver and whether or not you were likely to respond positively, suffer adverse effects, or simply not respond at all. We have even seen, this last few days, the sequencing of James Watson’s genome; an effort that cost less than $1m and took under four months. But do any of these promises add up to very much beyond myriad PhD theses and thousands of biotech startups many of which have already crashed?

Hopefully, the answer is yes. In the next few years, gene science will hit pay dirt as genes finally give up their real secrets and the true meaning of so-called junk DNA will become clear. Our understanding and ability to treat a wide range of disease from breast cancer and obesity to hypertension and bipolar disorder will come of age and perhaps finally succumb to all this genetic scrutiny and manipulation.

Nature, Science and the Wellcome Trust provided a useful summary of the genetic state of the art for a recent Times report by Mark Henderson on our genetic future. In the summary Henderson highlighted the latest “in press” results, most of which are now online, so I am providing here the hyperlinked executive summary:

Breast cancer – Three papers published in Nature and Nature Genetics at the end of May reported four new genes and one genomic region associated with increased risk. 10.1038/nature05887, 10.1038/ng2075, 10.1038/ng2064

Obesity – An obesity gene, the FTO gene, was published in Science in April and reported in Sciencebase at the time.

Diabetes – Again in Science (and 10.1126/science.1142382 and 10.1126/science.1142358, three common genes for increased diabetes type 2 risk were reported, bringing the total known genes associated with diabetes to nine.

Alzheimer’s disease – New results also published this week in Neuron discuss an Alzheimer’s gene

Data that were still under press embargo at the time Henderson’s feature appeared in The Times, however, meaning he could only hint at the true potential of human genome results were revealed today.

The largest ever study of genetics of common diseases in which almost 10 billion pieces of genetic information were analysed were published just one minute ago, so I can now outline the findings in a little detail. The new study compared 2000 cases each of seven common diseases with 3000 shared control patients, and reveals new genetic associations with these disorders. A pair of related papers in Nature Genetics (a and b) offer further insights into two of the seven diseases investigated.

In the Nature article, scientists from the Wellcome Trust Case Control Consortium report genetic variants associated with the development of bipolar disorder, Crohn’s disease, coronary heart disease, type 1 and type 2 diabetes, rheumatoid arthritis and hypertension. This is the first study from this large scope and it, the scientists found one genetic region newly associated with bipolar disorder, and another with coronary artery disease. A separate group of three markers have been found to be associated with rheumatoid arthritis. The researchers also identify nine new genetic associations for Crohn’s disease and ten chromosome regions that contain genes related to diabetes.

These new results would suggest a medical revolution is at hand and that the Human Genome Project and its spinoff -omics really are about to hit pay dirt. But, are we really on the verge of a new era in medicine, or are the various genetic revelations simply more grant-baiting hyperbole?

Combined effort makes for glowing report

Hybrid ramanOne of the most powerful techniques available to analytical scientists is Raman spectroscopy. Unfortunately, it is not easy to distinguish the low-intensity signals it produces when studying fluorescent species in cells because they are swamped by the much brighter glow from various cell components. Now, Dutch researchers have overcome this incompatibility to hybridize Raman with fluorescence microscopy by exploiting the optical properties of semiconductor fluorescent quantum dots (QDs). They have demonstrated hybrid Raman fluorescence spectral imaging in studies of single cells.

Biophysical engineers Henk-Jan van Manen and Cees Otto of the University of Twente, The Netherlands, have used fluorescent nanoparticles to broaden the scope of single-cell microscopy by combining it with intracellular chemical analysis based on Raman. The researchers explain that quantum dots allows weak Raman signals from DNA to shine through the ubiquitous glow from proteins and lipids.

You can read the full story in my SpectroscopyNOW column this week.

Possums, horses, and pigs do it

Brushtail possums, photo by wollombi http://www.flickr.com/photos/wollombi/I just received an early publication alert from the Australian research organisation CSIRO announcing the imminent publication of volume 19 of their journal on reproductive science, fascinating I thought as I opened the attachment.

First up in the list of contents was a paper that sounded rather intriguing from FC Molinia and colleagues entitled: “Uterine and vaginal insemination optimised in brushtail possums (Trichosurus vulpecula) superovulated with pregnant mare serum gonadotrophin and porcine luteinising hormone”.

So, let us just dissect what that convoluted title actually means. Basically, they stimulated brushtail possums with hormones from a horse and a pig to make it produce more eggs than normal and then artificially inseminated the females, with brushtail possum sperm, obviously. I am pretty sure it is all standard procedure for getting those little brushtails up the duff, and it is not so odd that they used horse hormones in the process, after all, one form of human hormone replacement therapy uses equine estrogen.

Something worries me a lot about this particular EarlyAlert. The abstract says that artificial insemination of brushtail possums (Trichosurus vulpecula) is being developed as an assisted breeding model for endangered marsupials, as well as a bioassay for testing fertility control vaccines to manage overabundant populations.

Hmmm…humans do not have a strong record on “assisting” animals in this way, and particularly not in Australia, I am thinking rabbits and mixomatosis, feral camels, and the infamous cane toad, to name but three. Why is it that we feel we can intervene and manage ecosystems in this way? The end results are usually disastrous and given the purportedly fragile nature of Australia’s ecosystems, should we not leave well alone?

The full paper can be accessed here.

Cervical fluids and boron nitride

Two more reports of general interest from my SpectroscopyNOW column. The first is on a new informatics approach to understanding cervical vaginal fluids and the second on a new study of boron nitride the technological wonder material of the future
Screening for premature problems
The application of multiple protein identification algorithms to an analysis of cervical vaginal fluid (CVF) can provide a detailed map of biological markers to help researchers understand the course of human pregnancy and the problems that can arise. Preliminary tests suggest it could be used to determine the likelihood of a premature birth.

Inelastic boron nitride
The results of inelastic X-ray scattering and other techniques have been combined with ab initio calculations to characterise and explain the behaviour of the superficially simple binary material boron nitride. Insights from the research could lead to new ways to exploit the electronic and mechanical properties of hexagonal boron nitride.

Obesity Gene

Obesity overweightToday’s claims in the media about the recently discovered obesity gene are at best overwrought and at worst downright dangerous. A vast study involving more than twenty research centres across the UK has allegedly demonstrated that almost one fifth of us carry a variant of the gene known as FTO that predisposes us to obesity or overweight.

According to the researchers, “Obesity is a serious international health problem that increases the risk of several common diseases.” Fair comment. They add that, “The genetic factors predisposing to obesity are poorly understood.” Another fair comment.

They then report that while carrying out a genome-wide search for type 2 diabetes susceptibility genes among 13 groups of almost 40000 participants they have identified a common variant in the FTO gene that predisposes to diabetes through an effect on body mass index (BMI).

Additionally, the team reports that there is a cumulative, or additive, association of the variant with BMI. They found that 16% of the adults with the risky genetics weighed about 3 kilograms more than the others and were almost twice as likely to be obese, when compared to people without the risk allele. Moreover, the team says that they observe this genetic risk factor in individuals age 7 years and older and say that it reflects a specific increase in fat mass.

But, all this talk of obesity being down to genes will provide many individuals with an excuse along the lines of “it’s my glands”, which has become something of a serious cliche for some people who simply refuse to reduce the calorie intake and to add serious amounts of exercise to their daily routine.

The politics of obesity aside, I contacted metabolic expert Jeremy Nicholson of Imperial College London who recently discovered that calorie restriction in dogs extends life, reduces the risk of diabetes and metabolic disorders, and could be due to a change in the behaviour of microbes in the gut. He is less than impressed with the response of the media to the Science paper on FTO. “Basically, no amount of genetics can explain how humans have got fat so fast,” he told me. I would have to agree, genetics has long-term effects one usually does not see major changes in body function and form happening across a single generation.

So, might there be an alternative explanation for the apparent obesity epidemic in the developed world? Nicholson thinks so. “Changes in the gut microbes and caloric bioavailability probably could be the explanation,” he says. If we are suffering severe disturbances in the profile of gut bacteria – either they have changed behaviour or the species have changed – then those heading for overweight or who are already obese could be absorbing far more calories even from the same amount of food because of it.

Liposuction, like Vaser, Smartlipo and laser liposuction is one option, but could a dose of live yogurt or an antibiotic regimen be the solution to obesity? We are only just starting the hors d’heuvre when it comes to understanding the interplay between our bodies and microbes. Much more work into metabolism and the role of the guy microflora needs to be done before we can cast aside obesity as yet another genetic construct and so abandon sufferers to the realm of the untreatable.

Nicholson explains that the microflora in our gut are laid down in infancy and there is not a lot we can do about that. However, he says, “The real secret is eating a lot of beans and pulses (lentils etc) – lots of them every day, they keep the lower gut microbes very happy and the products of their
breakdown (catabolism) do not cause diabetes.” Nicholson laments that the windy side-effects of such a diet are far less malign than the problems associated with a diet deficient in beans and pulses.

Genetics, microbes, and beans aside, Nicholson has what I think has to be the final word on the debate: “Even genes and bugs added together still fade into insignificance if you sit on your butt all day eating pork rinds – you will get fat but its not genetic!”

It’s a dog’s life

Puppy dogCutting out the French fries, burgers, chips, candy, beer, soda, and other delicious yet largely non-nutritious food and drink from your diet is generally a good idea. One of the reasons, health experts suspect, is that somehow a reduced-calorie diet leads to a longer life. Now, researchers at Imperial College London have looked at a dog’s life and discovered why dietary restriction could lead to a longer life.

Jeremy Nicholson and colleagues followed 12 “pairs” of dogs in which one partner in each pair was given 25% less food than the other. Nicholson and his colleagues found that the dogs who had less food lived almost 2 years longer (that perhaps equates to between 10 and 14 years). They also found that those dogs suffered less diabetes and osteoarthritis, and were older on average when plagued by the common diseases of old age.

But, why?

The scientists believe that differences in the populations of microbes in the dogs’ guts could partly explain the metabolic differences. The dogs that were not on a restricted diet had increased levels of potentially unhealthy aliphatic amines in their urine, the team found. The presence of higher levels of these compounds indicate reduced levels of choline, the compound essential for metabolizing fat. Such a microbial profile has, in other studies, been associated with the development of insulin resistance and obesity in humans.

Nicholson explains: “This fascinating study was primarily focused on trying to find optimized nutritional regimes to keep pet animals such as dogs healthy and as long-lived as possible. However these types of life-long studies can help us understand human diseases and aging as well, and that is the added bonus of being able to do long-term non-invasive metabolic monitoring.”

So, might this study be applicable to humans and should we too be cutting down on our doggy treats and Pedigree Chum? Potentially, yes. Despite superficial appearances and the sometimes disgusting things dogs choose to eat, the flora and fauna of our guts are very similar. It all depends on whether cutting your burger and soda intake by 25% is worth it for those extra 10 to 14 dog years.

Details of the study are published today in the Journal of Proteome Research. The paper is one in a special issue of the journal in “Metabolomics, Metabonomics, and Metabolic Profiling in Complex Organisms: The Portals to “Real-Life” Systems Biology”.

Choline chemical structure
InChI=1/C5H14NO/c1-6(2,3)4-5-7/h7H,4-5H2,1-3H3/q+1

In totally, unrelated canine news, scientists from the University of Utah and seven other institutions have identified a piece of doggy DNA that reduces the activity of a growth gene, ensuring that small breeds stay small. More on that via Newswise.

Hey good looking, what you got cooking, in those genes?

Attractive peopleHere’s a puzzle. If evolution ensures that ‘good’ genes spread through a population, then why are individuals so different? Why don’t people get better and better looking through each generation to the detriment of ugliness and lead to a population of real lookers?

The problem with current evolutionary theory is that it would seem that if females select the most attractive mates, then the genes responsible for their attractive features would spread quickly, leading to all males becoming equally attractive (think peacock tails). Ultimately, further sexual selection would then no longer take place and evolution would stop in its tracks.

This is the so-called lek paradox and it has remained a foil in the weaponry of the intelligent design advocate’s arsenal for many years. Until now.

Thanks to research at Newcastle University, England, this apparent fundamental flaw in Darwin’s theory of evolution, latched on to by creationists can be explained quite effectively by evolution itself. The findings of Newcastle’s Marion Petrie and Gilbert Roberts research suggests that sexual selection leads to increased genetic diversity by a mechanism not previously understood.

Petrie reasoned that as genetic mutations occur naturally anywhere in the genome, some will actually affect those used to produce the DNA repair kit enzymes found in all cells. This would lead to those individuals with a malfunctioning or inefficient repair kit, having more mutations left unrepaired and so greater variation in their genome.

Usually, damaged DNA leads to an unviable organism that either dies quickly of the effects or is otherwise unable to reproduce. However, if those variations are present in sections of the genome responsible for disease defence, then variation can actually be beneficial as greater variation in the genome at these points means more chance of warding of bacteria and viruses.

Petrie modelled the spread of genes in a population and demonstrated that the tendency towards reduction in genetic diversity caused by sexual selection is outweighed by the maintenance in greater genetic diversity generated by mutations affecting genome repair.

The researchers began this research a decade ago and their model genes are now a great fit for the observations of variations. “We find that sexual selection can promote genetic diversity despite expectations to the contrary,” Petrie says. The team publishes details of their findings today in the journal Heredity.