Recently we've discussed the first step in how to build a neuron. Today we will discuss step 2: reconstructing that stained cell.Hippocampus CA1 Pyramidal neuron (from Neuromorpho.org)There are a couple of ways that you turn an image (or image stack) of a neuron into a digital neuron file like the one pictured above. Basically there is an easy way and a hard way. The hard way is to reconstruct the neuron manually, where you literally trace the neuron by hand. The easy way is to auto-trace the neuron.In a recent Frontier's in Neuroinformatics article, Myatt et al. (2012) explain the hard to easy gradient in reconstruction methods."Manual (Camera lucida). Prisms are employed to visually overlay the microscope image onto a piece of paper, and the neuron is then traced by hand. Although primarily used for 2D tracings, 3D reconstructions can be derived from these with time consuming post-processing (Ropireddy et al., 2011).Semi-manual (e.g., Neuron_Morpho, Neurolucida). Digital segments are added by hand through a software interface, typically sequentially, beginning at the soma, and working down the dendritic tree.Semi-automatic [e.g., NeuronJ (Meijering et al., 2004; 2D reconstruction only) and Imaris (3D reconstruction)]. User interaction defines the basic morphology, such as identifying the tree root and terminations, but branch paths are traced by the computerFully automatic (e.g., Imaris, NeuronStudio; Rodriguez et al., 2003, AutoNeuron add-on for Neurolucida). The entire morphology is extracted with minimal user-input. " (Myatt et al., 2012)You may ask: "Why not just do it the easy way?" Good question. It is actually surprisingly difficult to make a versatile program that can accurately reconstruct neurons. So difficult in fact that in 2010 an open challenge was issued with a monetary prize for the best automatic reconstruction algorithm. Five teams competed in this DIADEM challenge and the results and process are explained in detail in a special issue of Neuroinformatics. (And in less detail in this HHMI press release)automatic reconstructions of neurons (source)Advances in automatic reconstruction are being made at an astounding pace, but most neural reconstructions are still being done in a semi-manual or semi-automatic way. If you are interested in reconstructing some neurons, you can download Neuromantic for free or Neurolucida for money. There is other reconstruction software available, summarized nicely in Myatt et al. 2012, but these are the two I am most familiar with. In the next edition of "How to Build a Neuron" I will tell you how you can completely skip step 1 (the staining of the neuron) and step 2 (the reconstruction of the neuron). For ease of access, the whole "How to Build a Neuron" series is archived. © TheCellularScaleMyatt DR, Hadlington T, Ascoli GA, & Nasuto SJ (2012). Neuromantic - from semi-manual to semi-automatic reconstruction of neuron morphology. Frontiers in neuroinformatics, 6 PMID: 22438842... Read more »
Myatt DR, Hadlington T, Ascoli GA, & Nasuto SJ. (2012) Neuromantic - from semi-manual to semi-automatic reconstruction of neuron morphology. Frontiers in neuroinformatics, 4. PMID: 22438842
Having grown up with reduce, reuse, recycle campaigns (Tweety’s Global Patrol circa 1990), recycling is part of my daily routine. In fact, I’ve even spent time at a Japanese university lab [...]... Read more »
As we’re starting to test artificially grown organs, scientists are wondering how to make sure that their methods result in viable tissues. One of the first steps was to take organ growth into three dimensions, letting the cells grow on a scaffold and self-organize into the right muscles, valves, and other soft tissue. Usually these scaffolds are derived from existing organs purified of all their old cells and many are designed to break down into [...]... Read more »
Bozhi Tian,, Jia Liu,, Tal Dvir,, Lihua Jin,, Jonathan H. Tsui,, Quan Qing,, Zhigang Suo,, Robert Langer,, Daniel S. Kohane,, & Charles M. Lieber. (2012) Macroporous nanowire nanoelectronic scaffolds for synthetic tissues. Nature Materials. DOI: 10.1038/nmat3404
The field of synthetic biology has been simmering for quite a while. It occasionally takes a big leap, such as when Venter’s team published about their work on M. genitalium, and it took a big leap recently with the paper about modeling a lot of the cellular processes in a simple cell that I talked [...]... Read more »
Wilson ML, Hertzberg R, Adam L, & Peccoud J. (2011) A step-by-step introduction to rule-based design of synthetic genetic constructs using GenoCAD. Methods Enzymol. , 173-188. DOI: 10.1016/B978-0-12-385120-8.00008-5
Cai Y., Wilson M. L., & Peccoud J. (2010) GenoCAD for iGEM: a grammatical approach to the design of standard-compliant constructs. Nucleic Acids Research, 38(8), 2644. DOI: 10.1093/nar/gkq086
Tyson John J., & Novák Béla. (2010) Functional Motifs in Biochemical Reaction Networks. Annual Review of Physical Chemistry, 61(1), 240. DOI: 10.1146/annurev.physchem.012809.103457
A recent study looking at how colonies of ants regulate their foraging behaviour has caused a bit of a buzz online. A …Continue reading »... Read more »
Balaji Prabhakar, Katherine N. Dektar, & Deborah M. Gordon. (2012) The Regulation of Ant Colony Foraging Activity without Spatial Information. PLoS Computational Biology, 8(8). DOI: 10.1371/journal.pcbi.1002670
A team of biomedical engineering researchers from Carnegie Mellon University and the University of Louisville are developing surgical tools that could be used for future expeditionary spaceflights to the moon, an asteroid or Mars.
“In deep space, surgical procedures will be severely complicated by absence of gravity, where it becomes difficult to prevent cabin contamination from blood and body fluids,” said James Antaki, a professor of biomedical engineering at CMU.... Read more »
Carnegie Mellon University. (2012) Press Release: Carnegie Mellon University Biomedical Engineers Lead Collaborative Team Developing New Astro Surgery Tools for NASA Deep Space Missions. Press Release: Carnegie Mellon University. info:/
Over the last few months, I’ve noticed an growing number of reports about declining opportunities and increasing pressure for early stage academic researchers (Ph.D. students, post-docs and junior faculty). For example, the Washington Post published an article in early July about trends in the U.S. scientific job market entitled “U.S. pushes for more scientists, but [...]... Read more »
Kealey T. (2000) More is less. Economists and governments lag decades behind Derek Price's thinking. Nature, 405(6784), 279. PMID: 10830939
Sauermann H, & Roach M. (2012) Science PhD career preferences: levels, changes, and advisor encouragement. PloS one, 7(5). PMID: 22567149
Researchers have created a new type of biosensor that can detect minute concentrations of glucose in saliva, tears and urine and might be manufactured at low cost because it does not require many processing steps to produce.... Read more »
Emil Venere. (2012) Sensor detects glucose in saliva and tears for diabetes testing. Purdue University News. info:/
The other day a tweet came over my “genome” search column that intrigued me: RT @oshaer: Our paper on a tabletop interface for collaborative exploration of genomic data is finally available online: http://t.co/VQMD67wi Tabletop interface? Wha? Ok–I had to check this out. And, in fact, this group has software that will let you explore eukaryotic [...]... Read more »
Shaer O., Strait M., Valdes C., Wang H., Feng T., Lintz M., Ferreirae M., Grote C., Tempel K., & Liu S. (2012) The design, development, and deployment of a tabletop interface for collaborative exploration of genomic data. International Journal of Human-Computer Studies, 70(10), 764. DOI: 10.1016/j.ijhcs.2012.05.003
There are many reasons to try to build a neuron, but fully building a model neuron is an extensive process with many steps. Today we will discuss the very first step in the neuron-building process: determining the activity and shape of the neuron. Biocytin filled cortical neurons (source)To determine the shape of neuron, you have to stain it somehow. There are several ways to do this, but we will focus on the biocytin filling method. To determine the activity of a neuron, you have to use electrophysiology to record its electrical activity. The biocytin filling method makes use of the same patch clamp electrode to record the electrical activity of the neuron and to fill it with the biocytin molecule that can be later dyed. So this method is perfect for building a neuron because with it you can correlate the shape of the neuron directly with its activity patterns. Neural activity correlated with neural morphology (source)A recent Nature Protocols paper by Marx et al. (2012) provides step by step details for how to fill and dye a neuron using the biocytin method. The basic biocytin staining protocol is as follows:1. make brain slices2. fill the neuron with biocytin while recording its electrical activity3. fix the brain slice in paraformaldehyde4. quench the endogenous peroxidase5. connect the biocytin to avidin (using the vectastain ABC kit)6. colorize the avidin (using DAB and nickel)7. mount the slices on gelatin subbed slides8. dehydrate the slices SLOWLY through very small steps of ethanol concentration9. clear with xylene and coverslipMarx et al. provide some excellent specifics in the paper that make the whole process understandable and more importantly, doable. They even have a troubleshooting section which explains what might have gone wrong under several conditions.Marx et al., 2012 Figure 2 One of their best tips in the paper is to dehydrate the slices very slowly. They show that when you dehydrate the tissue quickly, you get a cork-screw artifact (A) that is not physiologically meaningful, but when you dehydrate slowly, you get a more accurate morphology. So there you have it, Step 1 of neuron building. Step 2 will be coming soon. © TheCellularScaleMarx M, Günter RH, Hucko W, Radnikow G, & Feldmeyer D (2012). Improved biocytin labeling and neuronal 3D reconstruction. Nature protocols, 7 (2), 394-407 PMID: 22301777... Read more »
Marx M, Günter RH, Hucko W, Radnikow G, & Feldmeyer D. (2012) Improved biocytin labeling and neuronal 3D reconstruction. Nature protocols, 7(2), 394-407. PMID: 22301777
What happened was, I was looking for a Creatively Commons licensed picture of Pedro Mendes to upload to commons.wikimedia.org. That’s not the footballing Pedro Mendes who played for Rangers, Spurs, Pompey and Porto but the systems biologist Pedro Mendes who plays for Virginia Tech and Manchester. Thankfully, another systems biologist, Michael Hucka kindly pointed to his impressive collection of pictures, taken at various events over the years which include some shots of Pedro. Looking at these pictures made me idly wonder: What is the collective noun for a group of systems biologists?
Systems biology is the study networks of various kinds [2,3] so it’s ripe for a collective noun, and there were several suggested on twitter. Since twitter has recently developed a nasty habit of disappearing tweets, here is a collection gathered and preserved for posterity from the twitterome...... Read more »
On Microfluidic Future I like reviewing advancements in therapeutic or diagnostic devices because I’m really drawn to those areas of research. Every once in a while, however, I take interest in research for the sake for knowledge, like the Root Chip. I recently came across an article from Dino Di Carlo of UCLA that describes a microfluidic device used to study cancer cells. The article, “Increased Asymmetric and Multi-Daughter Cell Division in Mechanically Confined Microenvironments” appeared in PLoS ONE, which is an open access journal (very cool!).... Read more »
Henry Tat Kwong Tse, Westbrook McConnell Weaver, & Dino Di Carlo. (2012) Increased Asymmetric and Multi-Daughter Cell Division in Mechanically Confined Microenvironments. PLoS ONE, 7(6). info:/
Let Me Answer Your Questions: part 2, in which I answer your very important questions via google search terms. Part 1 and all subsequent LMAYQ posts will be archived in the LMAYQ index.by LikariousSo let's get to it, what fascinating questions are you asking google? 1. "Can odor be recorded?" This likely brought someone to my post "You can't trust your receptors:smell" in which I discuss the EOG (electrolfactogram) where you can record the electrical activity of a smell receptor while certain smells are presented. But it does not answer the question of whether a smell itself can be recorded.So I looked into it a little bit and surprisingly, the answer is yes! Nakamoto and others have created an "odor recorder" Nakamoto 2005 figure 1Unlike visual recording, which only need red, green, and blue to make essentially all the colors, odor recording requires a few more components. For example, the authors created an apple smell using 8 components. I would love to say that this odor recorder is going to appear in every living room and plug into the TV so that restaurant and perfume marketing can be truly effective, I just don't see the demand being strong enough to make it worth mass producing. Though, I think it would be pretty amazing. I also had doubts as to whether the odor recorder could accurately transmit the scent of a really nice perfume which is not static, but develops over time. But The 2005 Nakamoto paper shows that they can actually record the changes of an odor over time! While there is always the fact that a perfume reacts differently with every one's skin, the odor recorder actually seems like a promising device and might find a market in die hard perfume fans. or..."odor recorder prevents murder"The quest to permanently record the scent of a woman drives a man to murder in the mediocre movie "Perfume: the Story of a Murderer." If only he was in possession of an odor recorder.© TheCellularScaleNakamoto T (2005). Study of odor recorder for dynamical change of odor. Chemical senses, 30 Suppl 1 PMID: 15738143... Read more »
Nakamoto T. (2005) Study of odor recorder for dynamical change of odor. Chemical senses. PMID: 15738143
Concerns about the likely consequences of continuing climate change have greatly increased interest in geoengineering – whether the Earth’s climate could be deliberately modified to counteract global warming due to anthropogenic greenhouse gas emissions. In November 2010, the Royal Society hosted a Discussion Meeting: ‘Geoengineering: taking control of our planet’s climate’ that critically assessed many of the schemes currently being considered. The meeting also took stock of the relationship of geoengineering to conventional greenhouse gas mitigation as well as how geoengineering is perceived by the public. Papers in this issue directly reflect the outcome of that Discussion Meeting.... Read more »
Andy Ridgwell, Chris Freeman, & Richard Lampitt. (2012) Geoengineering: taking control of our planet's climate?. Phil. Trans. R. Soc. A 13 , 370 (1974), 4163-4165. DOI: 10.1098
From Dilbert’s PHB to The Office, the incompetent manager is such a popular trope that it’s in danger of becoming …Continue reading »... Read more »
Alessandro Pluchino, Andrea Rapisarda, & Cesare Garofalo. (2009) The Peter Principle Revisited: A Computational Study. Physica A 389 (2010) 467-472. arXiv: 0907.0455v3
The Canadian National Exhibition (CNE) opens in Toronto next Friday (can’t wait!) and they hold an international sand sculpting competition every year. I’m always impressed by the size and detail [...]... Read more »
An L-system or Lindenmayer system is a parallel rewriting system, namely a variant of a formal grammar.I have implemented a simple L-system class with HTML5 Canvas or WebGL output. Feel free to explore the predefined models or create your own.... Read more »
Insects are experts when it comes to adhesion on dry surfaces. However, in nature, plants may be covered by water for quite a long period of time, especially after rain. The bionic expert Professor Stanislav Gorb of Kiel University, Germany, and the material scientist Professor Naoe Hosoda of the National Institute for Material Science in Japan, discovered the remarkable ability of the terrestrial leaf beetle to walk underwater. Picking up the beetle’s locomotion mechanism, they designed an artificial material, which sticks to surfaces underwater. Their scientific results are published today (8th August) in the online journal “Proceedings of the Royal Society B”.... Read more »
Kiel University Press, Text: Claudia Eulitz, & Translation: Ann-Christin Wimber. (2012) “The beetle shows us how”. Proceedings of the Royal Society B . info:/
I've been itching to announce this for months, but I've been biting my tongue. Now I can finally let the neuron out of the bag.Ladies and gentlemen I'm proud to introduce to you a joint project between my wife Jessica Voytek and our friend Erica Warp: The Adventures of Ned the Neuron! To get the important pitch out of the way first, please go contribute some money to their Kickstarter campaign to help them get started if you want to help. Also, please consider following their company on Facebook. I promise they're not spammy.For several months now Jessica and Erica have been working on their company, Kizoom, to develop the first of what I hope to be many science education eBooks for kids. The fact that this is being built using open or semi-open tools and platforms is also pretty amazing.Note that I'm in no way connected to this company, though the obvious disclosure is that my wife and I are financially entwined and, as unbiased as I try to be, I of course cannot be completely so. I mean, I'm writing this post, aren't I? But... as a new father I'm coming to appreciate more and more the joys of well-written, scientifically accurate educational materials.So who are Erica and Jessica and why should you trust what they write?Erica earned her PhD in neuroscience from Berkeley working on spinal cord development. She published three super cool papers during that time, one each in Nature, PNAS, and Current Biology. I promise you she knows her brains.Jessica is the primary author on our brainSCANr paper which we published in The Journal of Neuroscience Methods earlier this year. She earned her Masters degree in Information Management and Systems at Berkeley, which she completed while very pregnant with our son. Not only does she know her brains, she's also technically and artistically very savvy.The two of them have been working hard on this baby of theirs (that's them celebrating after submitting their NIH grant). They have managed to put together a book that is fun and interactive for kids (their target audience) while being educational and totally neuroscientifically accurate.No neuro nonsense. Just good science and good fun.So many of us neuroscientists complain about the poor public understanding of our field that it's time for us to stop being critics and start trying to make the changes we want to see. And that's what I love about Kizoom and The Adventures of Ned the Neuron: two very smart neuroscientists and techies are putting themselves forward and trying to make science more approachable to the most scientifically vulnerable group.Kids.Erica wrote the story and drew the early artwork while Jessica has been working on getting the whole thing coded up, animated, etc. Basically the techy nerd work.What's impressed me the most is that, throughout all of this had work, they've also been doing a lot of science outreach and communication for kids. Jessica worked for the Girl Scouts for years, including developing a cookie booth finder to help people locate the nearest Girl Scout troop selling cookies in their area!In May Jessica and Erica volunteered at a Girl Scout event to teach young women about neuroscience and the brain with the help of Ned the Neuron!We also recently learned that, out of the thousands of abstracts and poster submissions to the Society for Neuroscience Conference this October, their poster "User experience design for children's neuroscience education" has been selected as one of nine in the new "Dynamic Posters" session.What's that? Well, according to the email they received,A dynamic poster is an electronic version of the current paper-based format, displayed on an LCD screen rather than a poster board. However, it’s more than just an e-poster, which is typically an electronic - but still static - PDF version of a paper poster. Embedding multimedia content is encouraged such as videos, slides, animated charts or graphs, scrolling text, or a 3D rotation of a model. A dynamic poster presentation is designed for face-to-face interaction: like a regular poster presentation, the dynamic presentation will be driven by the primary author while attendees visit the poster. Some text elements of the poster will always be viewable for browsing by people walking by or waiting for their turn to speak with the presenter. Other parts of the poster will be operated by the presenter, who can click on and play a video or enlarge a graph to better illustrate a method or result.I definitely applaud the Society for Neuroscience for finally taking this kind of tech-based approach.I wish I could convey to you in words the emotional love the both of them have for this project. I'm really proud to have seen it grow from nothing into a nearly completed project. Please check it out and consider helping if you can.Thanks everyone.Voytek JB, & Voytek B (2012). Automated cognome construction and semi-automated hypothesis generation. Journal of neuroscience methods, 208 (1), 92-100 PMID: 22584238Warp E, Agarwal G, Wyart C, Friedmann D, Oldfield CS, Conner A, Del Bene F, Arrenberg AB, Baier H, & Isacoff EY (2012). Emergence of patterned activity in the developing zebrafish spinal cord. Current biology : CB, 22 (2), 93-102 PMID: 22197243... Read more »
Voytek JB, & Voytek B. (2012) Automated cognome construction and semi-automated hypothesis generation. Journal of neuroscience methods, 208(1), 92-100. PMID: 22584238
Warp E, Agarwal G, Wyart C, Friedmann D, Oldfield CS, Conner A, Del Bene F, Arrenberg AB, Baier H, & Isacoff EY. (2012) Emergence of patterned activity in the developing zebrafish spinal cord. Current biology : CB, 22(2), 93-102. PMID: 22197243
Marriott G, Mao S, Sakata T, Ran J, Jackson DK, Petchprayoon C, Gomez TJ, Warp E, Tulyathan O, Aaron HL.... (2008) Optical lock-in detection imaging microscopy for contrast-enhanced imaging in living cells. Proceedings of the National Academy of Sciences of the United States of America, 105(46), 17789-94. PMID: 19004775
Wyart C, Del Bene F, Warp E, Scott EK, Trauner D, Baier H, & Isacoff EY. (2009) Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature, 461(7262), 407-10. PMID: 19759620
Over at @BBCSport and @BBC2012 there are some Olympian feats of big data wrestling going on behind the scenes for London 2012 . While we all enjoy the Olympics on a range of platforms and devices, a team of twenty engineers is busy making it all happen. It’s great that the BBC, unlike other large organisations, can talk openly about their technology and share hard-won knowledge widely.... Read more »
Loasby Karen. (2006) Changing approaches to metadata at bbc.co.uk: From chaos to control and then letting go again. Bulletin of the American Society for Information Science and Technology, 33(1), 26. DOI: 10.1002/bult.2006.1720330109
Butkus Andrius, & Petersen Michael. (2007) Semantic Modelling Using TV-Anytime Genre Metadata. Lecture Notes in Computer Science, 234. DOI: 10.1007/978-3-540-72559-6_24
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