Posts Tagged ‘science’

Shedding light on astrological nonsense

Dec 17th, 2010

Last night I was directed towards an article claiming that scientists had inadvertently found evidence to support astrology:

Principle of astrology proven to be scientific: planetary position imprints biological clocks of mammals

(NaturalNews) Mention the word “astrology” and skeptics go into an epileptic fit. The idea that someone’s personality could be imprinted at birth according to the position of the sun, moon and planets has long been derided as “quackery” by the so-called “scientific” community which resists any notion based on holistic connections between individuals and the cosmos.

Skeptics must be further bewildered by the new research published in Nature Neuroscience and conducted at Vanderbilt University which unintentionally provides scientific support for the fundamental principle of astrology — namely, that the position of the planets at your time of birth influences your personality.

As a member of the “so-called “scientific” community” I admit that I immediately suspected quackery, or woeful misinterpretation on the part of the astrologers writing the article. However, were I to write off their claims entirely based on this suspicion, then I would be guilty of the close mindedness that they accuse me of. So, in order to dissect their claims, I had to go back to the primary source, the paper they were referencing1 .

What do the astrologers claim?

Before we take a look at the original paper, lets have a look at what the astrologers claim. I’ll only concern myself with the claims directly relevant to the paper they are discussing; their claims regarding scientific arrogance, their straw-man scientists, and cold fusion can be left for someone else to tackle.

The first claim is that “according to the conventional view, your genes and your parenting determine your personality, and the position of planet Earth at the time of your birth has nothing to do with it.” This attempt to set out the conventional scientific viewpoint ignores the large number of other environmental effects that scientists accept can influence development. These environmental effects can be influenced indirectly by the position of the earth, as it is the movement of the earth that is responsible for influencing the seasons.

The astrologers then make the following claims regarding the findings of Ciarleglio et al.:

  1. That the position of the planets at the time of your birth influences your personality.
  2. That mice born in the winter show a “consistent slowing of their daytime activity”
  3. That mice born in the winter are more susceptible to Seasonal Affective Disorder (SAD).

They then summarise by claiming that “one of the core principles of astrology [is] that the position of the planets at the time of your birth (which might be called the “season” of your birth) can actually result in changes in your brain physiology which impact lifelong behavior.”

So, does the paper actually support the claims they make of it?

The Paper

Unfortunately the writers of the article don’t actually provide a link to the original paper, something which is sadly all too common . However, they do provide enough information to let us find the paper:

Perinatal photoperiod imprints the circadian clock

Christopher M Ciarleglio, John C Axley, Benjamin R Strauss, Karen L Gamble & Douglas G McMahon
Nature Neuroscience (2010) doi:10.1038/nn.2699
Received 24 August 2010 Accepted 21 October 2010 Published online 05 December 2010

Using real-time gene expression imaging and behavioral analysis, we found that the perinatal photoperiod has lasting effects on the circadian rhythms expressed by clock neurons as well as on mouse behavior, and sets the responsiveness of the biological clock to subsequent changes in photoperiod. These developmental gene × environment interactions tune circadian clock responses to subsequent seasonal photoperiods and may contribute to the influence of season on neurobehavioral disorders in humans.

As far as I can tell, the paper is open access, which means that anyone should be able to read it. I’m afraid the same can’t be said for all the papers I’ve referenced here.

What do they do?

The Circadian Rhythm

That nature responds to the cycle of day and night is easily observable, flowers track the sun, people and other animals sleep and awake, and other behaviour seems to correlate with the time of day. What is perhaps more surprising, is many of these behaviours continue to show a daily cycle, even if the sun is removed from the equation. For example, flowers will continue to track the position of the sun for several days after being placed in a dark room. Typically the cycles shown during these ‘free-running periods’ (either of constant light, or constant dark) are either slightly longer or slightly shorter than twenty-four hours, and the regular light-dark cycle is necessary to maintain calibration.

The impact of circadian rhythms on human behaviours should be apparent to anyone who has ever experienced jet lag, and the depression that can follow the shorter winter days (SAD), has been linked to the circadian cycles. In humans and other mammals, this internal biological clock has been tracked down to a region of the brain known as the suprachiasmatic nuclei (SCN), in which the expression of a number of genes, or associated hormone production, vary on an approximately twenty-four hour cycle. These cycles continue, even when exposed to constant light, or constant dark, thus providing an internal ‘body clock.’

The ‘clock genes’ are those whose expression (the level at which the cell makes protein from a given gene) varies over the cycle. For example, the gene per1 is most active during the day. By genetic manipulation, is is possible to ensure that per1 produces a product with a fluorescent tag, allowing its activity to be measured by monitoring cell florescence.

Mice were exposed to either short-day or long-day light cycles (8 or 16 hours of ‘daylight’ respectively) from before birth until weaning (The perinatal phase). Following weaning, mice were either maintained under the same light cycle, or were stitched to the opposite cycle for a further 28 days (The continuation phase, Figure 1). Experiments were repeated in both winter and summer, to take into account variations that may be induced by the actual season.

Figure 1: Mice were expose to either long or short day light cycles prior to weaning. Subsequently mice were either maintained under the same conditions, or were switched to the opposite cycle.

Following this treatment, the circadian rhythms of the rodents were studied, either by tracking the expression of specific ‘clock genes,’ or by monitoring rodent behavioural activity2.

What do they find?

The authors found that the ‘day length’ at birth continues to have an impact on the circadian rhythms of the mice, even after they have been shifted to a different cycle. In particular, long-day born mice, showed a narrower peak of activity in the SCN, and in addition showed a shorter internal clock cycle, this resulted in more consistency between subsequent exposure to either long or short day cycles. In contrast, short-day born mice generally showed wider peaks of activity, and longer internal clock cycles. They were also subject to more variation in circadian rhythm behaviour between subsequent ‘summer’ or ‘winter’ cycles.

What does this mean?

This indicates that the day length at birth may have long term effect on subsequent circadian rhythms, even when the day length changes. In particular, mice born during a ‘winter’ cycle seem to show more variation in subsequent seasonal changes. The authors indicate that this may have implications with respect to previous findings, which show that mice born during winter-like cycles show increased levels of depression like symptoms, and that winter born humans show increased levels of SAD, bipolar disorder and schizophrenia. However at this stage it is not possible to draw a firm link between the findings.

What are the limitations of the study?

One of the primary limitations of the study is that it only addresses a short time span, and the authors acknowledge that they have no indication as to how long the effects may last. This may be especially relevant when attempting to translate the results to humans: not only a different species, but one with a significantly longer lifespan.

Additionally, I am also concerned that the study only considered two phases, the perinatal phase, and then either a continuation of the initial levels, or a switch to the opposite seasonal cycle. The possibility remains that exposure to a long-day cycle outside the perinatal period is sufficient to, at least partially, imprint the same pattern as seen in the long-day born mice. In support of this possibility is the considerably lower variation between short-day and long-day born mice under long-day conditions. However it should be pointed out that there are still significant differences between shot-day and long-day born mice.

Does the paper support the claims of the original article?

In short no.

Firstly, the only planet whose position has effect on day length is planet earth, where the orientation of its axis relative to the sun determines the season, and hence the day length. The other planets have different orbital periods, which means that Mars won’t be at the same point in the sky on December 17th 2010, as it was on December 17th 2000. Furthermore, while the northern hemisphere is in the grip of winter, the southern hemisphere is in the middle of summer, meaning that any seasonal effects are going to depend on the hemisphere, as much as the location of the earth.

But importantly, the researchers have been careful to isolate day length as the variable, separating other seasonal effects, such as temperature, or indeed the earth’s location. Furthermore, by conducting the experiment in summer AND winter, the effectively prevent any actual seasonal variations from having an effect.

In short, the findings have nothing to do with astrology. Ironically, the ‘tabloid horoscopes’ derided in the article have more to gain; your star sign is correlated with day length when you were born, at least assuming we confine ourselves to a narrow latitude.

Oddly the article also ascribes the findings regarding depression like symptoms in winter-born mice to this study, when in fact they were conducted separately. But again, these findings were purely associated with day length, not planetary position.

So in summary we have either a gross misrepresentation of scientific findings, or a major misunderstanding. We also have a paper which is potentially interesting, although I’d like to see how stable the effects are through multiple changes in day-length. If the effect is isolated to a short period of possible imprinting, then it will be interesting to narrow this period down in different organisms.

  1. Ciarleglio, C. M., Axley, J. C., Strauss, B. R., Gamble, K. L., & McMahon, D. G. (2010). Perinatal photoperiod imprints the circadian clock. Nature neuroscience. doi:10.1038/nn.2699. []
  2. Wheel usage []

Mitochondrial proteins at the proteasome, are you MAD?

Dec 16th, 2010

About this post

This post was originally written for a job application, however I was never able to use it. It covers a growing field closely related to the subject of my PhD. As the article was originally intended to be written for a blog of a biology journal it is primarily written for those with training in the biological sciences, although I also tried to make it accessible to an informed lay audience. Unfortunately I think this attempt at pitching the article at a wide audience hasn’t been entirely successful, at times seeming too simplistic fro the primary audience, and at others too inaccessible to a lay audience. I also feel the article could do with being less formal, however given the original purpose of the article I felt it was better to lean towards too formal, than risk being perceived as too informal.

I should clarify that I don’t discuss any of my work in this article.

When proteins become damaged or are no longer required by the cell, they can be broken down into their component peptides, allowing these resources to be reclaimed. Much of this recycling occurs at proteasomes, hollow barrel like structures located in the cytoplasm and nucleus of the cell. Breakdown of proteins occurs in a catalytic chamber at the centre of the structure, and entry of potential substrates is tightly regulated by caps at either end of the chamber.

In most cases, a protein’s fate at the centre of the proteasome is determined by the attachment of a chain of ubiquitin: a small protein, which can be covalently attached to lysine residues on other proteins. This chain is recognised by components of the proteasome, as well as by shuttle factors, which help recruit substrates to the proteasome.

Proteins within the cytoplasm or nucleus have easy access to the proteasome, however those within membrane bound organelles must first be translocated into the cytosol. The first evidence for such processes occurring was found in association with the endoplasmic reticulum.

Endoplasmic reticulum associated degradation, or ERAD, describes the process by which unwanted proteins within the endoplasmic reticulum are retro-translocated to the cytosol. Here they are tagged with ubiquitin, and delivered to the proteasome. ERAD relies on the co-operation of a large number of factors. A series of chaperones identify proteins which are undergoing difficulty folding and in turn they deliver them to complexes in the ER membrane. From here, proteins are transferred to the cytosolic face of the organelle, and chains of ubiquitin are attached, marking them for proteasome mediated degradation. The hydrolysis of ATP by the hexameric Cdc48/p97 provides the energy to extract ubiquitinated proteins from the membrane, and co-factor proteins ensure efficient delivery to the proteasome or its shuttle factors.

For a long time it was assumed that no such system existed in mitochondria, the respiratory centres of the cell, as they have their own complement of proteases. However, increasing evidence is suggesting that the proteasome may play an important role in the degradation of some mitochondrial proteins, leading to the proposition of mitochondria associated degradation, or MAD.

Traditionally, the degradation of mitochondrial proteins has been seen to be the domain of the mitochondrially localised ATP dependent proteases. The inner mitochondrial membrane contains multi-subunit proteases with their catalytic activity orientated to face either the inter-membrane space, or the mitochondrial matrix. Additional proteases, such as Lon/PIM and ClpXP, are found within the mitochondrial matrix. This collection of proteases is sufficient to provide protein degradation in the mitochondrial matrix, inner mitochondrial membrane and the inter-membrane space, however analysis of the products of proteolysis indicate that inter-membrane space proteins are under-represented.

Some of the earliest evidence of proteasome dependent degradation of mitochondrial proteins came in 1985, when Rapoport et al.1discovered that some mitochondrial proteins were ubiquitinated, and degraded in an ATP dependent manner. Subsequent to this, other ubiquitinated proteins have been found to localise to the mitochondria, and appear to undergo proteasome mediated degradation.

More direct evidence arose when Margineantu et al.2 found that the heat-shock protein Hsp90 appeared to promote ubiquitination of OSCP, a matrix localised subunit of the mitochondiral F1F0-ATPase. Further investigation revealed that disruption of Hsp90 resulted in reduced turnover of OSCP and other mitochondrial proteins, resulting in accumulation on the outer mitochondrial membrane; similar changes were observed on proteasome inhibition. This accumulated protein appeared to be a result of retro-translocation of mature mitochondrial proteins, indicating that mitochondria possessed a pathway of retro-translocation and proteasome mediated degradation, analogous to the ERAD pathway.

Dissection of the mitochondria associated degradation pathway is still in its early stages, and as yet many of the required components remain speculative. Comparison with the better characterised ERAD pathway is inevitable, and it remains to be seen if any elements will be shared between the two pathways. Recent work by Heo et al.3 discovered that Cdc48/p97 was recruited to mitochondria in a stress responsive manner by a protein they called Vms1 (VCP/Cdc48-associated mitochondrial stress-responsive). Disruption of this process resulted in a reduction in ubiquitin-dependent degradation of mitochondrial proteins, leading the authors to propose that Cdc48/p97 may perform a key role in MAD, as well as in ERAD.

The highly oxidative environment of the mitochondria means that its proteins are particularly prone to damage. Mitochondrial proteases have long been known to provide one line of protein quality control, and it is increasingly apparent that the proteasome dependent degradation of the MAD pathway may provide another. Dissection of the MAD pathway will be essential for forming a complete picture of the mitochondrial protection against damaged proteins, and may provide insights into diseases such as amyotrophic lateral sclerosis, which are associated with an accumulation of misfolded proteins in the mitochondria.

  1. Rapoport, S., Dubiel, W., & Müller, M. (1985). Proteolysis of mitochondria in reticulocytes during maturation is ubiquitin-dependent and is accompanied by a high rate of ATP hydrolysis. FEBS letters, 180(2), 249-52. Pubmed. []
  2. Margineantu, D. H., Emerson, C. B., Diaz, D., & Hockenbery, D. M. (2007). Hsp90 inhibition decreases mitochondrial protein turnover. PloS one, 2(10), e1066. doi: 10.1371/journal.pone.0001066. []
  3. Heo, J.-M., Livnat-Levanon, N., Taylor, E. B., Jones, K. T., Dephoure, N., Ring, J., et al. (2010). A stress-responsive system for mitochondrial protein degradation. Molecular cell, 40(3), 465-80. doi: 10.1016/j.molcel.2010.10.021. []

Home Straight

Apr 4th, 2009

The end of my PhD is rapidly approaching, and suddenly it no longer seems some distant event. By the time Christmas comes around I very much hope to be out of the lab, and to have a good chunk of my thesis written up. However all of this means getting the lab work finished, or at least in a state in which it is possible to write up.

As things stand at the moment that goal has yet to be achieved, and there as still a few key experiments that need to be completed. The past week I gave the first run through of one such experiment, and am currently in the ‘debugging’ phase, in which I try to work out exactly where everything has been going wrong. Its one of those tasks which is okay in the short term, and can even be quite satisfying, but which gets demoralising if it runs on too long.

Fridays result was initially a bit confusing, until I realised that what it was actually telling me is that an earlier result was the misleading one. Fortunately everything is still in order, and it hopefully means that I’ll be able to address some of my problems on Monday. The rest of the problems however still need further scrutiny.

All this meant that I was in the lab this morning preparing materials for use on Monday. I have already decided that I’ll try and make the most of weekends between now and September, although that doesn’t quite mean pulling a 10/7. Don’t get me wrong, I’ve been no stranger to the lab at weekends, but previously I have tended to use them to facilitate the weeks work, rather than as working days in and of themselves.

Post on my Poster Post

Mar 12th, 2009

This pre-poster post will probably be followed by a post poster post, post poster. I’ll keep you posted.

Well its not a post exactly, but I will shortly be presenting a poster at the Rubicon Conference in Lisbon. While this is my third European conference, it is the first at which I’ve had a chance to present. At previous conferences I have been somewhat hampered by a lack of data, but fortunately lots has come together in the last six to eight months.

Unfortunately academic posters are somewhat removed from the coloured pens and large lettering of the posters of primary and secondary school. However I’m still actually looking forward to having the chance to discuss my work with people who I don’t already see on a day to day basis. As a result I’ve been bringing together the relevant material and deciding what to present, and what to leave. My limited data means that this isn’t too troublesome, however it still isn’t possible to throw everything I have on there. Instead I need to decide exactly what story I want to tell, and what data is needed to tell it.

Unfortunately as it stands my story is still more interesting than the data I actually have available. As it stand, and data are all still suggestive, and although my hypothesis are logical, and based firmly in evidence, they haven’t yet borne fruit. Which is a shame, as there’s a good chance I have a very exciting orange tree, albeit one which could still easily yield lemons. (See what I did there! And you thought I was going to torture that analogy.)

There is also the issue of timing, which is going to make me sound like a right liar to anyone keeping count. Much of my poster is cribbed directly from a presentation I gave a month ago, and since then I have been making all the strains and materials necessary for the next steps. In the last few weeks I haven’t actually got any new data, but I have been reasonably productive. This however does mean that there are several important experiments that I have queued up to run in the immediate future. Thus the number of results I can legitimately claim to have ready in the ‘next few weeks’ is frankly a touch silly1. There is also the serious possibility that I will get at least one of those results between printing the poster and attending the conference.

Sorry, that was a particularly rambling self interested entry. More of the pretentious pseudo intellectual claptrap, ill informed opinions, or embarrassing streams to derivative dreck classified as creative to follow soon. Not to mention plenty of self deprecating attention whoring.

  1. Having said that, results in science always seem perpetually three weeks away. Just like all those inventions which are always five or ten years in the future. []

I demand DOI’s!

Sep 6th, 2007

DOI stands for Digital Object Identifier, and in short is a permanent ‘address’ (like a URL) which will always point at a particular document. In particular DOI’s are used to make it easy to find academic papers, and saves one having to find the journal’s webpage, navigate to its archives, pick up the volume in question, and finally find the paper. More importantly unlike a URL you know that the DOI won’t change, and will still work when the journal decide to re-organise their system. For example, the DOI of Crick ans Watson’s DNA paper is doi:10.1038/171737a0.

As a scientist I have become used to reading heavily referenced papers and reviews. If someone says something they back it up, either by demonstrating it themselves, or otherwise pointing out where someone else has shown this. This will usually result in a huge list of references which, especially in review articles, can stretch on for an entire page or more. Typically a reference will provide the authors’ names, the year, the title of the paper (occasionally), the journal the paper appeared in (usually abbreviated), the volume, the issue (occasionally) and the page number. The DOI is also appearing in the bibliography with increasing regularity, and it certainly makes tracking down references much easier. But my issue isn’t with the academic journals so much as the newspapers.

Mainstream media coverage of science stories is often shockingly inaccurate and simplified to the point of inaccuracy. While a certain amount of this is understandable, your average science paper being outside the ken of most folks (and in some fields most scientists), it does leave me itching for more details. And here is the biggest problem… newspapers don’t reference. If you’re lucky you may get the journal, and then its a matter of clicking back through the past couple of issues, matching titles and abstracts with the story in the paper. However in many cases even this information is skipped, leaving me in the dark. (Of course, on some occasions the story in the paper reflects an as yet unpublished paper. Shockingly in some cases they haven’t even passed through peer review.)

Now I understand that in your average newspaper space is at a premium, they don’t want to spend column inches devoted to meticulously citing the paper they are reporting (Although frankly there is no excuse on the web). However a DOI is short, and provides all the information needed. It would allow for rapid finding of the paper in question, allowing people who are interested to find out the nitty-gritty. Furthermore, if a person happens across the article in a library archive in fifteen years time the DOI will still work.