Once upon a time, journals were made of paper and ink. However, we left the dark ages of dead woods behind us and moved forward to an age in which authors don’t need to publish in journals (but still want to). There’s an increasing decoupling between the individual article and its publishing journal, created by [...]
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George A. Lozano, Vincent Lariviere, & Yves Gingras. (2012) The weakening relationship between the Impact Factor and papers' citations in the digital age. ArXiv. arXiv: 1205.4328v1
Components of Brain Limbic SystemAdvances in the diagnosis and treatment of brain disorders like bipolar disorder, schizophrenia and autism are a public health priority.Dr. Thomas Insel, director at NIMH recently presented a TED talk that emphasized the need to rethink how we conceptualize and study these types of disorders. He argues for a need to redefine mental disorders as brain disorders. Advances in brain research tools are likely to provide improvements in early diagnosis and early treatment to reduce the morbidity and mortality of these brain disorders.I am posting my notes on Dr. Insel's presentation, as well as the fifteen minute YouTube video of the presentation.Additionally, I have provided links to two free full-text manuscripts on this topic for readers with more interest.MY NOTES on TED presentation Mental Disorders as Brain Disorders: Dr. Thomas InselScience can save lives-evidenced by many startling advances in medicine over the last 20 to 30 yearsChildhood cute lymphoblastic leukemia mortality decreased dramatically (90% to 10%)63% reduction in mortality due to heart diseaseAIDS mortality decliningStroke mortality decreasing due to early intervention programsEarly detection and early intervention are keyHowever, some areas are not improvingOne example of this is suicide--38,000 suicides per year in U.S., one every 15 minutesSuicide rates have not declined over the last 20 to 30 years90% of suicides linked to diagnosable mental disorders, depression, bipolar disorder, schizophreniaDisability is also common in mental disorders30% of all disability can be traced to disorders of the brain or neuropsychiatric disordersDisability in mental disorders due to fact many have early age of onsetMany are chronic disorder beginning in adolescents and young adultsNew terminology needed to change our thinking and research focusThese diseases are not mental disorders or behavioral disorders but brain disordersHuman brain complex 100 billion neurons, 100 trillion synapsesEvidence these are disorders of the human connectome (wiring circuites of the brain)Depression, OCD, PTSD show evidence of connectivity deficitsSchizophrenia: early deficits in brain gray matter volume of brain cortexGray matter pruning excess in schizophrenia crosses the threshold for psychosisBehavior often the last thing to to change in brain disordersNew tools are emerging in brain disordersThese tools promise early detection and early intervention in brain disordersHow soon with this occur? We don't know but the following quote is relevant:"We always overestimate the change that will occur in the next two years and underestimate the change that will occur in the next ten." quote by Bill Gates, Jr.MY COMMENTS: I agree with the need to redefine many disorders previously defined as mental disorders as brain disorders. The motto of this blog with continue to be "Translating neuroscience research into better care for brain disorders". I believe new brain research tools can lead the way to early diagnosis and treatment. Brain image is an iPad screen shot from the Brain Tutor app.Collins, P., Insel, T., Chockalingam, A., Daar, A., & Maddox, Y. (2013). Grand Challenges in Global Mental Health: Integration in Research, Policy, and Practice PLoS Medicine, 10 (4) DOI: 10.1371/journal.pmed.1001434 Insel, T. (2011). A bridge to somewhere Translational Psychiatry, 1 (4) DOI: 10.1038/tp.2011.4... Read more »
Collins, P., Insel, T., Chockalingam, A., Daar, A., & Maddox, Y. (2013) Grand Challenges in Global Mental Health: Integration in Research, Policy, and Practice. PLoS Medicine, 10(4). DOI: 10.1371/journal.pmed.1001434
He saw respected journals getting hijacked, bogus articles being published quasi-professionally and so-called open access websites covered with “BUY NOW” buttons. So librarian Jeffrey Beall decided to do something about it. He created a black list of all the journals (343!) he thinks are questionable and put it on his website scholaryoa.com. In this interview he explains why.... Read more »
Exactly one year ago, The Beast, the Bard and the Bot were born. Time for some reflection. But first, a bit of numerical material (current at the time of writing). Some Numbers Posts: 96, including this one. Total views: 19672 Max views on single day: 631 Top 5 countries providing visitors: United States (8264) United [...]... Read more »
Fausto, S., Machado, F., Bento, L., Iamarino, A., Nahas, T., & Munger, D. (2012) Research Blogging: Indexing and Registering the Change in Science 2.0. PLoS ONE, 7(12). DOI: 10.1371/journal.pone.0050109
Shema, H., Bar-Ilan, J., & Thelwall, M. (2012) Research Blogs and the Discussion of Scholarly Information. PLoS ONE, 7(5). DOI: 10.1371/journal.pone.0035869
Putting the woof in tweet! (source)Hi Julie,Wow! Thanks for sharing the amazing fun tweet-week we had posting for @realscientists on Twitter. It was great to engage with so many people about so many areas of dog (and other animal!) behaviour and research. And poo. So many questions about dog poo! Some things can be relied upon in life; it’s good to know people are always curious about dog poo.If you want to revisit any of those posts or links we exchanged as part of the Real Scientists project, check out the amazing collection of our tweets, compiled via Storify by the fabulous Sarah, genius behind Science for Life . 365. This week, they have an astrophysicist/cosmologist who studies exploding stars and dark energy tweeting – so interesting! He has a beagle named Bagel who has learned to open doors on everything – the house, the fridge, the microwave – he’s keeping himself and everyone following on Twitter entertained!Over recent weeks I have been talking to working dog industry groups and visiting a variety of kennel facilities as part of my ongoing work with the Australian Animal Welfare Strategy. It’s been great being back around the wagging tails and eager faces of working dogs again. Seeing a wide range of kennel facilities has been fantastic and has given me some good motivation to complete my PhD research in the area of kennelled working dogs.(source)Kennel facilities (including shelter, boarding/breeding and working dog kennel contexts) are often built to house as many individuals as they can in the space available and to be easily cleaned (usually via chemical wash down and hosing) in order to maintain a hygienic environment. This has historically resulted in spaces formed in concrete and metal that we (as people) readily perceive as barren and sterile. (source)Modern facilities are often built with different materials, and can seem more pleasing to our eye, but I wonder if they’re actually any different in meeting dogs’ behavioural needs? It’s been interesting while visiting the recent facilities to consider the dogs’ experience of living in them. One point of difference that I noted was that some facilities offer the dog/s a view. Others didn’t. (source)This view might be limited to the dog opposite their kennel run, or fairly open to many other dogs, people, surrounding scenery, traffic, animals, etc. especially in areas where dogs have a choice to be in- or outside. The limited research in this area suggests that in situations where dogs are housed singly and have the opportunity to view other dogs, they take it. I find it interesting that human studies have illustrated positive effects of proximity to windows with a view in hospital and workplace environments: improved recovery times and reduced job stress. A review paper by Taylor and Mills (see below) suggests that sensory overstimulation may occur in kennel environments, so what does that mean when we consider what provision should be made for dogs to see outside of their kennel?Someone thinks it's important, with a fence porthole having been launched for pet dogs a few years ago. So is this marketing to the dogs' needs or the people's perceptions? Dogs certainly seem to actively seek out visual information about the world around them.... Read more »
Wells Deborah L., & Hepper Peter G. (1998) A note on the influence of visual conspecific contact on the behaviour of sheltered dogs. Applied Animal Behaviour Science, 60(1), 83-88. DOI: 10.1016/S0168-1591(98)00146-4
Taylor K, & Mills D. (2007) The effect of the kennel environment on canine welfare: a critical review of experimental studies. Animal Welfare, 16(4), 435-447. http://www.ingentaconnect.com/content/ufaw/aw/2007/00000016/00000004/art00003
Sop Shin Won. (2007) The influence of forest view through a window on job satisfaction and job stress. Scandinavian Journal of Forest Research, 22(3), 248-253. DOI: 10.1080/02827580701262733
Verderber Stephen, & Reuman David. (1987) Windows, views, and health status in hospital therapeutic environments. Journal of Architectural and Planning Research, 4(2), 120-133. http://psycnet.apa.org/psycinfo/1988-30782-001
Does good will and intentions equals what primary care physicians actually do when helping patients with non-specific pain complains like low back pain?
No, according to a new study.
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Kim Kristiansen, M.D:. (2014) Low Back Pain – What Healthcare Professionals THINK They Do and ACTUALLY Do. Picture of Pain. info:/
The new Leiden Ranking (LR) has just been published, and I would like to talk a bit about its indicators, what it represents and equally important – what it doesn’t represent. The LR is a purely bibliometrical ranking, based on data from Thomson-Reuters’ Web of Science database (there’s another bibliometrical ranking, Scimago, but it’s based [...]
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Ludo Waltman, Clara Calero-Medina, Joost Kosten, Ed C. M. Noyons, Robert J. W. Tijssen, Nees Jan van Eck, Thed N. van Leeuwen, Anthony F. J. van Raan, Martijn S. Visser, & Paul Wouters. (2012) The Leiden Ranking 2011/2012: Data collection, indicators, and interpretation. ArXiv. arXiv: 1202.3941v1
Last week Science published a study (a follow-up of Salimpoor et al., 2011) in which Canadian researchers showed that music can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. ... Read more »
Salimpoor, V., van den Bosch, I., Kovacevic, N., McIntosh, A., Dagher, A., & Zatorre, R. (2013) Interactions Between the Nucleus Accumbens and Auditory Cortices Predict Music Reward Value. Science, 340(6129), 216-219. DOI: 10.1126/science.1231059
Salimpoor, V., Benovoy, M., Larcher, K., Dagher, A., & Zatorre, R. (2011) Anatomically distinct dopamine release during anticipation and experience of peak emotion to music. Nature Neuroscience. DOI: 10.1038/nn.2726
Physicists are notorious for infecting other disciplines. Sometimes this can be extremely rewarding, but most of the time it is silly. I’ve already featured an example where one of the founders of algorithmic information theory completely missed the point of Darwinism; researchers working in statistical mechanics and information theory seem particularly susceptible to interdisciplinitis. The [...]... Read more »
Wissner-Gross, A.D., & Freer, C.E. (2013) Causal Entropic Forces. Phys. Rev. Lett., 110(16), 168702. info:/10.1103/PhysRevLett.110.168702
It’s not quite clear why human males continue to have facial hair. There are other ways to keep warm, and we’ve lost our hair over most of the rest of our bodies (or they’re at best residual). But facial hair serves another important purpose—determining male attractiveness to females... Read more »
Dixson, B., & Brooks, R. (2013) The role of facial hair in women's perceptions of men's attractiveness, health, masculinity and parenting abilities. Evolution and Human Behavior, 34(3), 236-241. DOI: 10.1016/j.evolhumbehav.2013.02.003
As a researcher, one of the biggest challenges I face is keeping up with the scientific literature. This is further exasperated by working in several disciplines, and without a more senior advisor or formal training in most of them. The Evolutionary Game Theory Reading Group, and later this blog, started as an attempt to help [...]... Read more »
Davis, A., Wiegers, T., Johnson, R., Lay, J., Lennon-Hopkins, K., Saraceni-Richards, C., Sciaky, D., Murphy, C., & Mattingly, C. (2013) Text Mining Effectively Scores and Ranks the Literature for Improving Chemical-Gene-Disease Curation at the Comparative Toxicogenomics Database. PLoS ONE, 8(4). DOI: 10.1371/journal.pone.0058201
I remember the first time I realized just how easily false information gets spread about.A terrifying starry nightI was in French class in high school. Our homework had been to find out 1 interesting fact about Van Gogh and tell it to the class. When it was my turn, I said some boring small fact that I no longer remember. My friend sitting behind me, however, had a fascinating fact: When Van Gogh was a young child, he was actually afraid of the moon.The teacher and the class were all quite impressed and thought about how interesting that was and how that fact might be reflected in the way that he paints the Starry Night. Though this fact was new to everyone, including the teacher, no one even thought to question its truth. In fact, the teacher was so enthralled by this idea that she passed the information on to all the other French classes that day.When talking to my friend later that day, he admitted that he had not done the assignment, and just made the 'fact' up. I was completely surprised, not only that someone had not done their homework *gasp*, but that I hadn't even thought to question whether this was true or not. The best lies have an element of truth (source) Misinformation like this spreads like wildfire and is exceptionally difficult to undo. The more things you can link this piece of information to in your brain, the more true you might think it and even after your learn that it's not true, you still might inadvertently believe it or fit new ideas into the context it creates. Myths like the corpus callosum is bigger in women than in men is just one of those things that is easy to believe.An interesting paper by Lewandowsky et al. (2012) explains how this kind of persistent misinformation is detrimental to individuals and to society with the example of vaccines causing autism. This particular piece of misinformation is widely believed to be true despite numerous attempts to publicize the correct information and the most recent scientific findings showing no evidence for a link between the two. The authors of this paper give some recommendations for making the truth more vivid and effectively replacing the misinformation with new, true information. For example:"Providing an alternative causal explanation of the event can fill the gap left behind by retracting misinformation. Studies have shown that the continued influence of misinformation can be eliminated through the provision of an alternative account that explains why the information was incorrect." Lewandowsky et al. (2012)Misinformation can be replaced with information, but it takes more work to replace a 'false fact' than to just have the truth out there in the first place. It is much better when misinformation is not spread around in the first place, than when it is retroactively corrected. This paper is also covered over at The Jury Room. © TheCellularScaleLewandowsky, S., Ecker, U., Seifert, C., Schwarz, N., & Cook, J. (2012). Misinformation and Its Correction: Continued Influence and Successful Debiasing Psychological Science in the Public Interest, 13 (3), 106-131 DOI: 10.1177/1529100612451018... Read more »
Lewandowsky, S., Ecker, U., Seifert, C., Schwarz, N., & Cook, J. (2012) Misinformation and Its Correction: Continued Influence and Successful Debiasing. Psychological Science in the Public Interest, 13(3), 106-131. DOI: 10.1177/1529100612451018
Badgers (Meles meles) In Ireland...... Read more »
Del Cerro, I., Marmi, J., Ferrando, A., Chashchin, P., Taberlet, P., & Bosch, M. (2010) Nuclear and mitochondrial phylogenies provide evidence for four species of Eurasian badgers (Carnivora). Zoologica Scripta, 39(5), 415-425. DOI: 10.1111/j.1463-6409.2010.00436.x
O'Meara, D., Edwards, C., Sleeman, D., Cross, T., Statham, M., Mcdowell, J., Dillane, E., Coughlan, J., O'Leary, D., O'Reilly, C.... (2012) Genetic structure of Eurasian badgers Meles meles (Carnivora: Mustelidae) and the colonization history of Ireland. Biological Journal of the Linnean Society, 106(4), 893-909. DOI: 10.1111/j.1095-8312.2012.01927.x
Zachos, F., Apollonio, M., Bärmann, E., Festa-Bianchet, M., Göhlich, U., Habel, J., Haring, E., Kruckenhauser, L., Lovari, S., McDevitt, A.... (2013) Species inflation and taxonomic artefacts—A critical comment on recent trends in mammalian classification. Mammalian Biology - Zeitschrift für Säugetierkunde, 78(1), 1-6. DOI: 10.1016/j.mambio.2012.07.083
Hi Julie,I hope you have an awesome time at Science Online Teen tomorrow! I hope you get asked lots of questions about your presentation, Dogs: Science in Your Living Room. It's so true that dogs make for a sensational gateway to scientific enquiry - and they're right there, in front of us!If anyone happens to ask you "What's it like being a scientific canine behavioural researcher?", be sure to tell them to tune in to the @realscientists Twitter project from Sunday (or Saturday evening, USA time). They can follow you and I for a whole week as we tweet from the @realscientists account, giving insight into our every day activities as canine scientists. Will our tweets sound like woofs? (source)If anyone out there isn't already on Twitter and/or hasn't been following @realscientists, you really should! It's a super fun insight into the world of science, science communication, writers, clinicians and more. Each week features a different flavour of scientific endeavour and I like to think we'll be bringing the real lab science into the spotlight! So far, I've seen wild jaguars while canoeing down a river in the Amazon with Phil Torres; learned about mosquito-borne disease management from Cameron Webb and whisked along for the ride of a week in the life of futurist, with Kristin Alford. Hypnotised by the eyes (source)It's so much fun and really important, because some people genuinely believe that scientists look like this and that conducting science looks like this. Scary stuff! I'm hoping that while we might not be in particularly exotic locations, we can make up for that with our enthusiasm for all things dog and science. Plus, between the two of us, being here in Australia and there New York, we're always here. The-blog-that-never-sleeps can now be be the scientists-who-always-tweet! If anyone out there wants to know how to find out how we spend our week, you can:Follow our introductions at the Real Scientists blog hereKeep track of our tweets on Twitter hereParticipate in our live TweetUp session, being held for one hour from 10.30am Thu 18 April Melbourne time / 8.30pm Wed 17 April New York time (... Read more »
Brossard Dominique, & Scheufele Dietram A. (2012) Social science. Science, new media, and the public. Science (New York, N.Y.), 339(6115), 40-41. PMID: 23288529
The previous post in this series can be found here.
It may seem sometimes that nature is a cruel mistress. We are all dealt our hand from the moment of liaison between our lucky gold-medalist sperm and its egg companion. We are short or tall, broad or skinny, strong or weak because of the haphazard combination of genes that we wind up with, and that should be the end of the matter. Yet, as any seasoned card player will tell you, it is not the hand that matters, but how you play it! This, it turns out, also holds true when it comes to our genetic makeup - we can only play the cards we're dealt, but we don't have to play them all and can rely on some more heavily than others. In this post I'm going to discuss the ways in which DNA is organised and its activity regulated, and how this regulation is a dynamic, ever-changing process with cards moving in and out of play all the time. What's more, we'll explore the ways in which we can all consciously take control of our own DNA to help promote good health and long life!
Esoteric instructions laid bare
Most people are familiar with the concept of DNA - the instruction manual for every component that makes you you - but most are perhaps unaware of how DNA is actually organised within your cells. The importance of DNA has led to it achieving a somewhat mystical image in the public perception: a magical substance that sits inside you with omnipotent influence over every aspect of your construction. This perhaps might lead a layperson to think that we don't really understand how genes work, a perception that is encouraged by the abstract way in which the link between genetics and diseases is reported in the mainstream media. However, this impression is entirely false; we understand very well how genes work: DNA acts as a template for the generation of information-encoding molecules called RNA, which are in turn used as templates to make proteins, which then make everything else. This is called the 'central dogma' of molecular biology, which I'm not going to go into in detail now but have touched upon more thoroughly in a previous post: here.
The mystification of genetics in the mainstream perception can encourage people to forget that DNA is just a molecule, with as much physical presence and chemical potential as any other molecule in your body. As such, its supreme influence over you is dependent on pure chemistry and physics. The most obvious consequence of its being a physical entity is that it needs, in some way, to be arranged and organised. DNA exists within the nuclei of your cells, but it doesn't just float around randomly and aimlessly - its organisation is tightly regulated. First of all, DNA exists as a number of different strands, each its own molecule. These are chromosomes, humans have 46 in each cell nucleus, 23 of which you inherit from your mother, and 23 from your father. The classic image of a chromosome is the tightly packed 'X' shape like those in the image below, but actually this is a comparatively rare structure in the life of DNA as this only forms as the cell is dividing.
Chromosomes seen under an electron microscope. Image is from http://trynerdy.com/?p=145.
In non-dividing cells, DNA does not exist in the cosily familiar 'X' shapes, but instead spreads out to fill the whole nucleus. This is out of physical necessity - the DNA in compact chromosomes like those above is simply too tightly packed to do anything! Proteins and other molecules that need to interact with the DNA in order for its influence to be felt just can't get to it because there's no space. If the DNA spreads out to fill the nucleus, however, there's plenty of room for manoeuvre. Nonetheless, this organisation is not random and is still highly organised. DNA never exists on its own in a live cell - it is always bound to proteins called histones, which act as a scaffold around which DNA is able to wind, like a string around a ball. There is about 1.8m of DNA in each cell of your body, but once wound around histones it has a length of only around 0.09mm - a pretty significant space saving measure! Each little ball of DNA and histone is called a nucleosome; it is held together by attraction between the negatively charged backbone of the DNA and the positively charged side chains of the amino acids making up the histone proteins.
DNA wrapped around histone proteins to form nucleosomes. Adapted from Muthurajan et al. (2004) EMBO J. 2004; 23(2):260-71
Going up another level of scale now: these nucleosomes can be organised in different ways depending on the intended activity of the DNA therein. These complex organisations of nucleosomes are collectively known as chromatin, which can broadly be split into two forms: heterochromatin and euchromatin. The difference between hetero- and euchromatin is basically how tightly they are packaged. In euchromatin the nucleosomes are arranged much as in the image above - loosely packed and with short free segments of DNA in between. This is known as the 'beads on a string' form of DNA for hopefully obvious reasons. Heterochromatin, on the other hand, is far more tightly packed - nucleosomes are very closely associated and there is very little DNA between individual nucleosomes. This is called the '30nm fibre' because it is 30nm in diameter, and is quite similar to the kind of fibres that pack together the form the X-shaped chromosomes mentioned earlier.
DNA's many forms. Euchromatin corresponds to the 'beads on a string', whilst heterochromatin is the fibre of packed nucleosomes. Image from http://dellairelab.medicine.dal.ca/research.html.
These two types of DNA packing mean that all genes are not created equally! Heterochromatin and euchromatin have very different levels of activity - euchromatin's loose structure allows easy access to the machinery that relay DNA's instructions and so genes in this r... Read more »
Barrès, R., Yan, J., Egan, B., Treebak, J., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D., & Zierath, J. (2012) Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle. Cell Metabolism, 15(3), 405-411. DOI: 10.1016/j.cmet.2012.01.001
Hackett, J., Sengupta, R., Zylicz, J., Murakami, K., Lee, C., Down, T., & Surani, M. (2012) Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine. Science, 339(6118), 448-452. DOI: 10.1126/science.1229277
“Excuse me; the whole tenure system is ridiculous. A guaranteed job for life only encourages the faculty to become complacent. If we really want science to advance, people should have chips implanted in their skulls that explode when they say something stupid.” Sheldon Cooper, The Big Bang Theory Between the recent ACUMEN (academic careers understood [...]
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The previous post in this series can be found here.
This week, inspired by Shaun's most recent post covering exciting new results in cosmology, I have decided to also take a quick look at one of the fascinating recent findings of molecular biology. I hope to give some insight into how this work is done, and why it is not only intellectually interesting, but also potentially practically useful.
What do we know?
Those of you who have been following this series for a while might remember a post that I wrote last year (biological batteries and motors) where I discuss how energy is converted from myriad chemical forms in your food into the single energy currency of the cell, ATP. The system by which this is achieved is quite beautiful, chemical energy is converted into an electrical current within the mitochondria of your cells, which is in turn converted into a current of protons. This proton current drives a motor (ATP synthase) that churns out ATP, thereby converting it back into chemical energy. I'm not going to go into the whole process again here, but if you'd like a quick refresher then just hop back to my older post here, go on - you know you want to! I don't mind waiting.
So, a key player in this whole process is the so-called respiratory complex I (or NADH dehydrogenase), which is the first link in the chain that converts electrical current into proton current. Complex I takes electrons from a molecule known as NADH, which is produced from energy in your food by a range of complex metabolic chemical reactions. It moves the electrons that it takes from NADH and sticks them onto a molecule called ubiquinone, which then moves on to the next stage in the process: the perhaps confusingly named complex III.
Complex I is not just a relay for electrons, though. In fact it also directly moves protons from one side of the mitochondrial membrane to the other, thereby contributing to the aforementioned proton current that drives ATP synthase. For every electron that it transfers from NADH to ubiquinone, four protons get moved across the membrane. Until recently we knew little more than this because we didn't really know what complex I looked like. Molecular biologists had been able to purify it out from our cells and determine that it is pretty massive (containing 44 individual proteins arranged together) and identify a couple of candidate proteins in that mess that might be responsible for some of the complex's functions, but we didn't know how they all fitted together and so how they might work on a large scale. This is important because mutations in complex I are the most common cause of human neurodegenerative diseases. This is because a mutated complex I can go a bit wrong and start sticking electrons where it isn't meant to - most significantly onto oxygen-containing molecules to generate reactive oxygen species that cause damage to mitochondrial DNA and so impair neuronal function in particular. Parkinson's disease and Leigh's disease are two of the more common disorders associated with complex I, but there is also evidence that the speed of ageing is also linked to the activity of your complex I assemblies. It is, needless to say, quite an important protein.
As you may have already guessed from the overall tone - there has recently been some light shed on the mystery that is complex I. Last week, Nature published a study by Leonid Sazanov's research group in Cambridge in which they uncover the full structure of complex I for the first time. Bits of the structure had been known before, but this is the first time that we've had the whole thing revealed before us!
Sazanov's group have achieved this by using a technique commonly used in structural biology - X ray crystallography. I touched briefly on crystallography in my post looking at G protein-coupled receptors in case the term seems vaguely familiar. The problem that arises when looking at very small things is that light is actually too big to use as a tool to see things. By "too big", what I mean is that the wavelengths of what we would generally call 'light' (i.e. the visible and near-visible spectrum) are actually larger than the fine details of the thing you want to look at, so there is an inherent maximum resolution that can be achieved. In order to go into finer detail we need to use electromagnetic radiation with a much higher energy and so shorter wavelength - X-rays.
When you fire a beam of X-rays at a protein, some of the X-rays interact with the electrons in the protein's constituent atoms. These interacting X-rays are then scattered out in various directions and so if you detect them then you can use some clever tricks to work out how the atoms in the protein are arranged. However, the vast, vast majority of X-rays will not interact with the electrons in your protein and the scattering will be pretty damn weak. In order to bulk up the signal you need to get many copies of your protein (millions of millions of copies) and arrange them into an ordered fashion so that they all scatter in the same way. To do this you have a grow your purified protein into a crystal where each one is identical to the next and in exactly the same orientation. This is the tricky bit. Biochemists have been making protein crystals for over half a century with great success, but the bigger and more complicated your protein is then the harder it is to crystallise. Moreover, if you protein usually sits in a membrane then it makes it even more difficult to force into a crystal. Complex I ticks both these boxes and so making a successful crystal is nothing short of a scientific miracle! They don't say in their paper, but I imagine that Sazanov and colleagues have been trying to get this crystal for a LONG time! It was, however, undoubtedly worth it. The structure is quite beautiful.
The structure of respiratory complex I - taken from Baradaran et al, Nature, 2013.
The multi-coloured structures in the figure above represent the individual proteins involved the complex, with different peptide structures represented as different shapes (ribbons, loops etc). What is immediately apparent is that there is a large region that is embedded in the membrane (the flat bit at the bottom) and a separate segment that extends upwards and away from this membranous section (the bit at the top right). Analysis of the amino acids present at different regions reveal that the top-right protrusion is the binding site for NADH and ubiquinone, and so is where electron transfer must occur. Conversely, the membrane-embedded regions are where the protons get pumped across the membrane, so the two processes must be coupled in some way.
This structure allows us to suggest mechanisms in which the two might be coupled as it identifies 4 distinct channels through which protons can cross the membrane. As I mentioned earlier - the transfer of one electron from NADH to ubiquinone resul... Read more »
Baradaran, R., Berrisford, J., Minhas, G., & Sazanov, L. (2013) Crystal structure of the entire respiratory complex I. Nature, 494(7438), 443-448. DOI: 10.1038/nature11871
What’s the story?
It’s great news for leering men! A study in none other than the New England Journal of Medicine found that men who stare at large breasts live longer than men who don’t. A German research group, headed by an aging specialist named Karen Weatherby, found that staring at large breasts for longer than 10 minutes is equivalent to a 30 minute workout. The study, which took five years, revealed that breast watching men had lower blood pressure, slower resting pulses and fewer instances of coronary artery disease.... Read more »
Campbell, J. (2011) Getting it wrong: ten of the greatest misreported stories in American journalism. Choice Reviews Online, 48(12), 48-48. DOI: 10.5860/CHOICE.48-6722
An analysis of the proposal to legalize the trade in rhino horn in order to reduce the poaching of the remaining wild rhinos. Legalizing the trade of rhino horn is claimed to reduce the demand on the black market and is likely to be the best method for conserving the remaining rhinos, however other factors can influence the potential success of this. ... Read more »
E Markham. (2013) Counterintuitive Conservation. Blogspot. info:/
There have been a number of heated discussions about genetic privacy recently. Lately the discussion of the Henrietta Lacks (HeLa) genome paper erupted into wide-ranging awareness of some of the issues and complexities around genome data and family relationships. The paper by Yaniv Erlich’s team about re-identification of study participants using genealogy site details also [...]... Read more »
Presidential Commission for the Study of Bioethical Issues. (2012) Privacy and Progress in Whole Genome Sequencing. www.bioethics.gov. info:other/
Do you write about peer-reviewed research in your blog? Use ResearchBlogging.org to make it easy for your readers — and others from around the world — to find your serious posts about academic research.
If you don't have a blog, you can still use our site to learn about fascinating developments in cutting-edge research from around the world.
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