Category: Science

The grass isn’t always greener…

Research bloggingTHERE you are, stood in a green grocers poring over your favourite variety of apple. Suddenly you catch the scent of something heavenly; a smell not unlike the apple you have in your hand, only better. You abandon your apple and follow the scent to the next aisle where you find more apples of the same variety. They smell superior to the others. You pick one up and are compelled to take a bite; on doing so you realise something – it’s pretty bloody awful. You put down the unpalatable apple and move on to alternative apples.

I could be describing a situation reminiscent of the selectively bred, brightly coloured, sweet smelling fruits that line our supermarket shelves; those that in fact taste like  tasteless facsimiles of the original spots-and-all varieties. In this situation we are being manipulated by the supermarkets, but in nature it may be viruses doing the manipulating.

CMV by RG Milne, Istituto di Fitovirologia Applicata (http://www.ncbi.nlm.nih.gov/ICTVdb/Images/Milne/cucumsv.htm)
Cucumber Mosaic Virus (CMV)

Viruses are parasites, making use of infected host cells to replicate more virus. Of course, it isn’t enough just to replicate, viruses also need to spread to new cells, and new hosts. Plant viruses are often carried from plant to plant by insects; the insects become known in this context as ‘vectors’. The study of the biology of insect vectors is, as you may imagine, fundamentally important to understanding the transmission of a whole range of parasites (viral, bacterial and protozoan) between plants, or between humans and animals. Of particular interest is how parasites, such as viruses, manipulate their insect vectors by altering the physical properties of the host they infect.

A Penn State based group, headed by Mark Mescher, have been using Cucumber Mosaic Virus (CMV), a known generalist plant pathogen, to study the effect it has on the interaction between cultivated squash plants and aphids (sap sucking bugs). The results of this study are reported by Kerry Mauck et al. in a recent paper.

They show that CMV-infected plants have elevated volatile (readily dispersing in air) emissions that attract aphid vectors. This in itself is not a revelation;  the authors cite two well documented examples of this phenomenon, from Potato leaf roll virus (PLRV) and Barley yellow dwarf virus (BYDV), where infected plants release volatiles that attract aphids. However, these other viruses employ a different method of transmission to CMV, and the main thrust of this paper is to identify how the mode of transmission modifies the host-insect interaction.

Continue reading “The grass isn’t always greener…” →

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A radical source of antibiotic resistance…

A FEW years ago, a Boston University team headed by Jim Collins published findings that suggested the means by which bactericidal antibiotics result in cell death. Rather than the cause being the cellular target of the drug, the team showed it was the secondary effects of stimulating the production of hydroxyl radicals, a reactive oxygen species 1. The hydroxyl radical is known to cause significant damage to cellular DNA, proteins and cell wall, leading to cell death.

Their 2007 study 1 was initially met with a few raised eyebrows in some quarters, coming in for some criticism for having a few gaps; namely whether the role of the hydroxyl radical was even pertinent in a real world infections settings, which are often in the low-oxygen environment of biofilms 2. There was also some question of whether it was adequately demonstrated that the oxidative stress was a source or the result of cell damage. However, subsequent studies reported by Kohanski, as well as other labs, have described a more defined link between a bactericidal drug and resulting hydroxyl radical formation 3.

In the latest edition of Molecular Cell, a new article from Mike Kohanski, Mark DePristo and Jim Collins reports that prolonged exposure to sub-lethal concentrations of antibiotics can induce multiple drug resistance in E. coli and Staphylococcus aureus strains that were initially drug sensitive 4. E. coli strains were tested with sub-lethal levels of  three major classes of bactericidal antibiotics (quinolone, B-lactam and aminoglycoside), which were found to significantly increase the mutation rate, confirming their expectations.

Continue reading “A radical source of antibiotic resistance…” →

Heat shocking adaptive evolution…

Research bloggingIN evolutionary theory there is a phenomenon known as canalisation, a process in which the phenotype (i.e. the outward physical appearance of an organism) remains unchanged, despite genetic or environmental influences.  This suggests that a mechanism exists to buffer the physical appearance from such changes, which may explain why some species can remain mostly unchanged for millions of years.

The buffering afforded by this mechanism permits the accumulation of genetic variation, in effect storing it up like an evolutionary capacitor. Also, presumably the accumulated genetic variation may be released by an event that overcomes the evolutionary capacitor, releasing fuel (in the form of variation) that provides a substrate for natural selection and potentially accelerating evolution. But how?

The idea of capacitance was first suggested by Rutherford and Lindquist 1 following experiments on a protein called heat shock protein 90 (Hsp90) in fruitflies. Generally speaking, heat shock proteins assist in the maintenance and correct folding of cellular proteins, especially when under temperature stress; Hsp90 plays a particular role in maintaining the unstable signalling proteins that act as key regulators of growth and development.

They suggested that in nature, a stressing event such as high or low temperatures may overcome the protective buffering effect that Hsp90 has on maintaining these key regulators. As Hsp90 becomes diverted from its usual role, due to an increase of stress-damaged proteins in the cell, those cell signalling proteins it normally maintains are free to adopt a range of altered behaviours, interfering with the development of the organism. The result is morphological variants upon which natural selection can act. Rutherford and Lindquist found as much, with chemically and environmentally compromised Hsp90 resulting in flies with abnormal wings, legs or eyes, they observed a broad variety of phenotypes.

Rutherford and Lindquist went on to demonstrate that the capacity for such remarkable variation was pre-existing, i.e. it was encoded genetically prior to the stressing event, but had been silenced. Evolutionary capacitance may therefore provide a mechanism of adaptive evolution in which a population under stress may release previously silent variation, resulting in the appearance of certain individuals with more desirable traits in that changed environment. When such revealed traits are selected for they can become fixed and independently of the buffering action of Hsp90.

This week, in a letter to Nature, Valeria Specchia et al.2 report some fascinating evidence that indicates that beyond merely acting as a gate-keeper to unleash variation, mutations of Hsp90 that compromise its functionality result in new, rather than pre-exisiting, variation. They observed that mutations in Hsp90 affect the production of piRNAs. These are small RNA molecules that are involved in the silencing of genes, particularly those involved in development, i.e. sex cells like eggs and sperm, and all the cell types that give rise to these cells. These piRNAs are also responsible for repressing genetic elements called transposons.

Continue reading “Heat shocking adaptive evolution…” →

Strategies for communication…

FURTHER to my recent post on why people don’t accept evidence, it turns out that an editorial 1 and an opinion 2 piece in this week’s Nature, the latter unfortunately behind a pay-wall, actually focus on just this issue. The editorial states:

“Empirical evidence shows that people tend to react to reports on issues such as climate change according to their personal values (see page 296). Those who favour individualism over egalitarianism are more likely to reject evidence of climate change and calls to restrict emissions. And the messenger matters perhaps just as much as the message. People have more trust in experts — and scientists — when they sense that the speaker shares their values.”

So people tend to accept the evidence that supports their personal proclivities, and in fact interpret evidence in a manner than does so, thus people tend to persist in cherished beliefs and views even when confronted with contradictory evidence. This of course is something probably appreciated by most of us. Dan Kahan, in his opinion piece, points out:

“People endorse whichever position reinforces their connection to others with whom they share important commitments. As a result, public debate about science is strikingly polarized. The same groups who disagree on ‘cultural issues’ — abortion, same-sex marriage and school prayer — also disagree on whether climate change is real and on whether underground disposal of nuclear waste is safe.”

Another factor that weighs heavily in the public perception, and acceptance, of facts is the messenger. Owing to the fact that most people are ill-equipped to evaluate the raw data from scientific studies, they rely on the position of credible experts; it seems that those experts laypersons see as credible are those perceived to share the same values.

Research into the mental processes involved in such public perception is, Dan tells us, being conducted by Donald Braman at George Washington University Law School in Washington DC, Geoffrey Cohen at Stanford University in Palo Alto, California, John Gastil at the University of Washington in Seattle, Paul Slovic at the University of Oregon in Eugene and Dan Kahan, the Elizabeth K. Dollard professor of law at Yale Law School. These processes are collectively referred to as ‘cultural cognition’.

So what is cultural cognition? Kahan describes it as, ‘the influence of group values (ones relating to equality and authority, individualism and community) on risk perceptions and related beliefs.’ I would imagine that peer-pressure represents one example within a spectrum of influences in cultural cognition.

Continue reading “Strategies for communication…” →

Changing your beliefs…

FOLLOWING on from my post yesterday regarding people’s concept, or lack thereof, of evidence, it was suggested that it would be an interesting thought experiment for those of us who are willing to offer criticism on a subject to put ourselves on the receiving end. I think it’s a good idea to find something that each of us holds dear or true, and see if we can challenge ourselves to imagine how we’d feel if someone argued against that view. By understanding this, perhaps we can better approach our means of approaching such as subject with someone for whom such criticism would represent a paradigm shift.

As I managed to shake silly beliefs such as ghosts and ley-lines as a child, the only examples I have as a thinking adult are with particular scientific hypotheses that I’ve subscribed to, but subsequently had to ditch. This is the general method of science, and in my own research there have been any number of hypotheses I’ve formed and subsequently disproved on the basis of new evidence.

However, there have also been explanations for some natural phenomena that pre-date my research career, and to which I subscribed whole-heartedly. One example dates from my time as a first-year undergraduate studying marine biology. I had a particular interest in marine invertebrates and once attended a lecture by Donald Williamson, who was the major proponent of a larval evolution hypothesis, and recently came to light as being accused of ‘fringe science’ and getting a paper in the Proceedings of the National Academy of Sciences (PNAS) under the radar; thus also highlighting the pitfalls of the ‘I’ve got a mate in the club’ attitude to publishing.

Essentially Williamson felt that the immature forms (larvae) of many such invertebrates can be thought of as distinct organisms from the adult form, which are often comprehensively different both physically and physiologically; think caterpillar to butterfly, or blobby polyp jellyfish to its adult ‘medusa’ form.

Williamson felt that these different forms arose through hybridization — the fusing of two genomes (of two distinct organisms), one of which is now expressed early in an animal’s life, and the other late.

You can read an Sci. Am. article about it here.

I have to say, I absolutely LOVED this hypothesis, it was very exciting and I lapped it up with the typical fervour of an undergraduate.

Trouble is, since then it has been rebuked often and has not been substantiated by the experiments that were performed to test the hypothesis. I was quite recalcitrant about such rebukes up until the most recent PNAS rebuke that I’ve just linked to.

You can read rebukes to the Sci. Am. article here.

Changing my view about this hypothesis was hard, and a little embarrassing given I so animatedly communicated it to all my friends until I learnt it didn’t have strong grounding.

This is very true of many areas in which we are not experts, whether you are a scientist or not, and the fact is that we do tend to confer a great deal of trust in some individuals depending on their position. I would add that Donald Williamson was not ‘wrong’ to form this hypothesis at that time; scientific knowledge is by its very nature transitory, but once it has been tested, and alternatives developed, then we should seek to move on.

I could have easily ignored the evidence that Williamson’ hypothesis did not hold up to, and continued telling people an interesting and captivating story about why adult and juvenile forms of invertebrates are so different, but I didn’t. There’s still a part of me that thinks that there may still be something in it, which is why I can relate – to a point – with those people facing their first reality-check with regards some pseudoscience that they’ve hitherto believed in.

Donald Williamson is now retired and still stands by his hypothesis.

I don’t.

Your microbiome and you (part I): Gut

This post was chosen as an Editor's Selection for ResearchBlogging.orgYOU probably think that your body has things pretty much under control, being the finely evolved machine that it is, it knows where its at, and does a generally good job of looking after itself. You’d be right of course, but it doesn’t do this without a little help.

Some of this help comes in the form of your microbiome.

I have written previously about the exciting concept of the human microbiome in which I described how the number of bacterial cells on your body out number your own cells 10 to one, and asked to what degree you consider yourself to be human? The vast majority of these co-residents of you are organised into defined communities, the structure and diversity of which vary depending on where on the body they’re found: your mouth, your nose, various areas of your skin, your gut and urogenital tract. By understanding the interactions between each of these communities and our body, we can better understand their role in health and disease.*

In this the first of two posts on your microbiome, we’ll take a look at your gut.

The gut

probiotics-good-bacteriaMost people are undoubtedly familiar with the idea of ‘good bacteria’, in particular those of your gut, which we are encouraged to top-up on a daily basis with sickly sweet probiotic supplements containing various species of Lactococcus and/or Bifidobacterium. One can only imagine how on Earth we’ve coped throughout the course of evolutionary history without our daily supplement of Yakult.

The general scientific consensus on probiotics is that they don’t do any particular harm to most people, except perhaps your wallet, but occasionally the claims made by the manufacturers are often circumstantial, based on studies with poor methodologies, or are based solely upon observations from a petri dish or mouse model. Furthermore, when reliable evidence is documented, it is invariably for a very specific strain, thus there can be little confidence that is is a general property of the bacterial species as a whole.

Where the use of probiotics moves away from a general supplementation to being part of an active treatment for a condition, there is some evidence to suggest they may be of benefit, but on the whole, evidence is lacking and more research is certainly warranted. A Cochrane review (an international not-for-profit organization, providing up-to-date information about the effects of health care) in 2004, concluded:

“Probiotics appear to be a useful adjunct to rehydration therapy in treating acute, infectious diarrhoea in adults and children. More research is needed to inform the use of particular probiotic regimens in specific patient groups.”

However, in general there are insufficient data for the use of probiotics, over current standard therapies, in conditions such as eczema, Crohn’s disease, bacterial vaginosis and a slew of others. This is probably not helped by the fact that there is a good chance that the little pot of living bacterial joy you are consuming doesn’t actually contain any live bacteria of the type you think you’re getting.

A study published last month in the International Journal of Food Microbiology by an Italian team based the Istituto Superiore di Sanità in Rome, described a survey of such probiotics in Italy between 2005-6, seeking to identify and enumerate bacteria in commercially available supplements 1. A whopping 87% of samples showed evidence of not conforming to the Italian guidelines.

“Even though most labelled supplements (25 samples) indicated the presence of Bifidobacterium bifidum, this organism was only detected sporadically and always as dead cells.”

They also noted contaminants such as the food-poisoning pathogen Bacillus cereus, yikes.

Continue reading “Your microbiome and you (part I): Gut” →

The ‘negatome’ – a database of negative information…

Research bloggingWE researchers often joke that no-one ever publishes negative results, but that doesn’t mean to say that negative results aren’t extremely useful. On one level, knowledge of such negative results can prevent you repeating the same mistakes that countless other researchers, in other labs, have undoubtedly made over the years. On the other hand, they can provide a valuable dataset with which to generate new and useful information. One such example is the ‘Negatome Database‘, which has been reported by Smialowski et al.1 in Nucleic Acids Research advance access (November 17, 2009).

The Negatome is a collection of protein and domain (functional units of proteins) pairs that are unlikely to be engaged in direct physical interactions. But why on Earth would we want to know about proteins that don’t interact with each other; in fact, why do we need to know about proteins that interact at all?

Macromolecular machineResearchers recognize that that a cell doesn’t function purely by the action of individual proteins, but instead by large macromolecular complexes mediated by many interacting proteins.  The image to the left indicates an example macromolecular ‘machine’, in this case those involved in signal processing at the neuronal synapses (and which are likely to be working quite hard right now!).

Continue reading “The ‘negatome’ – a database of negative information…” →

Windshield splatter analysis…

rb1A few years ago I took part in an RSPB survey called the Big Bug Count, which sought to quantitate what had hitherto been anecdotal accounts that the number of insect splats on car windscreens had decreased in recent years. Essentially it was a sticky pad of define area that was placed on the front registration plate of your car. Following a car journey (I drove the 20 miles from from Keswick to Windermere), the number of bugs splats were counted and the results submitted.

Some suggested that the dwindling insect splats may in fact be due to cars being more aerodynamic, and not the tin boxes of previous decades. However, even I had noticed that I was swallowing fewer bugs on my bike rides around Cumbria than my childhood years, but hardly scientifically rigorous data – I do after all scream with glee less now than I used to.

Unfortunately, because the ‘bug splat’ survey, as it became known, was the the first such study by the RSPB, they could draw no conclusions as to whether the insect population was dwindling (despite what some press articles claimed) until subsequent seasonal surveys, over multiple years, were performed.

Of course, what some of you may have noticed is that the RSBP doesn’t seem to have followed up with any further surveys – at least none that I’ve been able to find in 30 mins of googling and scouring their website. Shame, so we had a baseline, of sorts, against which nothing further has been measured.

But assessing species diversity is an important task, as I’m sure anyone can appreciate. Changes in biodiversity act as markers of climate change or pollution, and have knock on effects on the food chain, such as bird life.

Continue reading “Windshield splatter analysis…” →

Stand up for research…

I’VE had a bit of an axe to grind recently about the government’s proposed policy on requiring such a large proportion of research funding to be allocated on the basis of economic and social impact. The University & College Union (UCU) is curently hosting a petition, signed against the statement that I’ve copied from their site below.

Sign it if you care to.

From the UCU’s website:

The latest proposal by the higher education funding councils is for 25% of the new Research Excellence Framework (REF) to be assessed according to ‘economic and social impact’. As academics, researchers and higher education professionals we believe that it is counter-productive to make funding for the best research conditional on its perceived economic and social benefits.

The REF proposals are founded on a lack of understanding of how knowledge advances. It is often difficult to predict which research will create the greatest practical impact. History shows us that in many instances it is curiosity-driven research that has led to major scientific and cultural advances. If implemented, these proposals risk undermining support for basic research across all disciplines and may well lead to an academic brain drain to countries such as the United States that continue to value fundamental research.

Universities must continue to be spaces in which the spirit of adventure thrives and where researchers enjoy academic freedom to push back the boundaries of knowledge in their disciplines.

We, therefore, call on the UK funding councils to withdraw the current REF proposals and to work with academics and researchers on creating a funding regime which supports and fosters basic research in our universities and colleges rather than discourages it.

[12,007 signatures at 11:43, 16 Nov 2009]

Sign the petition here.