balapagos

This is a deeply moving photo-essay by xdrtb.org based on James Nachtwey's photographs. It is likely that the drug-resistant-TB problem may become one of the most urgent ones to solve in the light of this worrisome news from India.

While poverty alleviation programs (combined with free-health-care) are fundamental in battling such outbreaks, to decisively eradicate such preventable infections, free biology-education of the masses and a role for NGOs in providing information on the best anti-TB drugs must be combined with it.

This quote from the Letter to the Editor by Udwadia et al prompts the necessity for a multi-level approach:

"The vast majority of these unfortunate patients seek care from private physicians in a desperate attempt to find a cure for their tuberculosis. This sector of private-sector physicians in India is among the largest in the world and these physicians are unregulated both in terms of prescribing practice and qualifications. A study that we conducted in Mumbai showed that only 5 of 106 private practitioners practicing in a crowded area called Dharavi could prescribe a correct prescription for a hypothetical patient with MDR tuberculosis [5]. The majority of prescriptions were inappropriate and would only have served to further amplify resistance, converting MDR tuberculosis to XDR tuberculosis and TDR tuberculosis."

As the year ends, a paper that I will carry in my mind is the one by Fried et al. In the video summary above, I thought the observation of the patient response - "I have an urge to move my hand!" upon the stimulation of a particular area in the brain was pretty neat! Fried et al thus had the unique opportunity to analyze the neuronal spike train data from 12 epileptic patients while running a behavioral-protocol previously established by Libet et al. 1983. Just to recap, the subjects were asked to press a laptop key "when they felt the urge to do so" while watching a clock hand sweep around (as described in the video). At key-press (P) the clock would stop and the subjects would indicate the time point when they felt the urge (W, "wanting") to press the key. Here is a schematic of the procedure:

An example of neurons in the SMA area whose firing precedes the W point (indicated by 0):

I wonder if we can detect such higher-order interneurons in the Drosophila brain using live-imaging methods. If they do exist, then it should be possible to bias the decision-outcomes predictably by opto-genetically triggering their activity at specific time-points during the behavior routine of an individual fly or the larva. May be the on-going larval and adult fly olympiads will stumble upon such candidate interneurons that can then be characterized further.

Oh, of course! this would make an excellent journal club paper as well, with the potential to trigger some very lively philosophical discussions that'd spill-over after the session has ended!

This fall, CRG hosted Aled Edwards from the University of Toronto. Because the title of the talk had "Open access" in it, and also since I dabble off and on (pun intended!) in using small-molecules to interact with gene expression, I just had to attend it.

Al is a very good speaker and his introduction into "open-science" was just fantastic. Here is an interview with Al that delves into this concept and its future. But there was another thing I remember from Al's talk, what struck me was the absence of Drosophila-collaborators in helping screen through the libraries of synthetic molecules (that Al et al. have access to) for significant in vivo biological effects. I think there is an opportunity here for flypushers in Toronto.

Thanks Alex, Jay Bradner's talk is indeed excellent, quite similar to Al's approach to drug discovery. May be "open science" is starting to take hold and will soon encourage the major funding agencies to revise their models so that more labs are encouraged to participate in it. This could very well result in the much needed cultural-shift.

Just imagine a "papers" software that downloads "nightly-builds" for a given topic of interest that one may have chosen to follow regularly. One could contribute into that platform freely as a critique or even decide to upload some unpublished data and then try to mature it into an excellent paper. May be there is a market here for media-Wikis (like Confluence) to help create collaborative-networks? Publishing houses must have also taken note of this. Hopefully, the licensing and IP issues will get worked out relatively smoothly, thanks to the software world that has already traveled this route. Biology is after all a type of software, an incredibly good one when it works well, but needs some serious bug-fixing talents and approaches to address all known issues while finding new ones as well.

Funktionide Part II (long version) from eltopo on Vimeo.

This is an interesting idea no-doubt as a mobile interior decor item that could respond to human presence and contact, to bring about a sense of peace and quite as it silently moves about the room -- the usefulness of the so-called "Heraclitean motion" amidst us (thanks to artificial muscles and new developments in that area). What will be more impressive is its ability to store a lot of junk picked up from the floor, gadget screws, toy parts etc.. Thanks for the link, Aljosh'!

Here is a mock-up video of the whole mission:

Would be fun if we can watch the sky crane in operation live as well, and that'll happen in Aug. 2012! 

This winning Eppendorf essay, titled - "The language of dendrites" made me appreciate the function of dendrites more than ever before. I particularly like this portion:

"I measured how different regions of single dendritic branches integrated increasing numbers of activated synapses and how they responded to different degrees of input synchrony (7). I found that distal regions amplified synaptic input with high gain, displaying a very steep sigmoidal input-output function, and were remarkably insensitive to input timing. In contrast, moving the input toward the proximal part of the branch progressively generated more linear integration curves with small gain, which required high input synchrony for summation (figure, panels C and D)." -- Tiago Branco

Incidentally, I was just admiring the beauty of dendritic structures in the Drosophila larval CNS last night! Here are the confocal images that I made very recently:

1. An interneuron in the Drosophila 3rd instar larval ventral cord (spanning the thoracic segments). The spatial separation of input (dendrites) and output (pre-synaptic boutons) compartments is a striking feature here.

2. An ascending interneuron with dendrite-like projection localized to a pocket within the ventral cord neuropile (in red, bottom image). Inset shows an optical slice where it appears that the GFP-puncta are adjacent to the pre-synaptic red-immunolabel.

3. Two GFP-labeled interneurons displaying their dendrite-like fine arbors with intermittent punctate profiles and varicose pre-synaptic boutons in the larval brain. I think the innervations here are predominantly located in the Dorso-Anterior (DA) neuropile compartment.

This dominant marker of the TM6B third chromosome balancer can be tricky to catch sometimes. I went looking around the interwebs for a good image of this but no luck. So I snapped these pics using an Olympus DP20 camera attached to a stereomicroscope. On the top is a normal wild type bristle pattern and the bottom image shows the mutant version. I hope that helps, Jeff.

Here is the blurb on the Supplementary Movie S1 (above) from the Zhao et al. paper:

"Time-lapse three-color fluorescence imaging of HeLa cells transfected with plasmids encoding R-GECO1 targeted to the nucleus (top right), G-GECO1targeted to the cytoplasm (top left), and GEM-GECO1 to the mitochondria(bottom left). Filter specifications are provided in Table S5. For GEM-GECO1,the ratio of blue to green fluorescence emission has been pseudocolored by usingthe color bar shown. (Bottom right) Image merges the three color channels, with the GEM-GECO1 emission ratio pseudocolored magenta rather than the rainbow representation used in the adjacent panel."

At room temperature:

Ramped to 38-39 °C (leading to exhaustion?):

A write-up on this later.

Simple behavior assays in a genetically tractable model system can be quite powerful in allowing us to understand how sensory information is encoded in the nervous system. So, when I spotted this recent paper by Oswald et al., I had to check it out immediately. Thanks to Sean Sweeny for sending me a copy. 

Now, when it comes to thermal nociception assays involving the Drosophila larva one method is to use a customized "hot probe" whose temperature is well-controlled (example paper). A micro-infrared-laser beam (~1000 nm, 1.5 mm dia) may also be used to deliver the stimulus in the desired area of interest. But there is a problem with this approach, an experimenter will find it very difficult to make contact with the moving larva in a consistent manner in terms of the precise location on the body, moreover, for the heat-probe, the contact force applied is also an issue. It is also conceivable that one could sometimes land the probe/or laser spot in an area that is relatively less populated by sensory neuron dendrites or has a different pattern of innervations. For eg. the response provoked by delivering the heat stimulus towards the anterior-half of the larva could be different as opposed to the posterior-half. May be there is a thermal sensitivity gradient as well.

Oswald et al. describe an excellent and simpler alternative test. Here, a single larva is placed into a 30ul drop of water and then the temperature of the water is rapidly increased. As one measures the water temperature using a thermocouple one can see that the larva exhibits diffferent types of motor responses as the water gets warmer. Here are a couple of relevant screen-grabs from the paper: