The blood-cerebrospinal fluid barrier….that other barrier that drain the brain!

Seeing good science highlighted on mainstream media is always good for us scientist as an outreach lesson. This one comes from Pr. Maiken Nedergaard, a well established researcher in the blood-brain barrier field (comparable to a big rock star in the scene, as Adrian use to give that analogy).

In this elegant story published in Science, the authors have shown that sleep are essential to purge the brain from waste. It has hypothesized that what enters through the blood-brain barrier has to leave through the cerebrospinal fluid and it has been longly hypothesized that the blood-cerebrospinal fluid-barrier was playing this role. It is also the most obscure barrier of the central nervous system. It is very interesting to see how important the system it is, but also showing how important sleep plays in that role. It is very interesting to understand if it is like a maintenance routine that the brain perform during its “idle” cycle and would be interesting to see how such system gets impaired in neurological diseases.

Also it is also a good reminder that good science can only be done if there resources available to do so. At this time of shutdown and debt ceiling, I would to salute again the remarkable work of the National Institute of Health and in particular the National Institute of Neurological Diseases and Stroke (NINDS) for providing the support of good science, but also thanks the taxpayers that help us build our scientific knowledge.


Nobel Prize of Chemistry 2013….Reflections about how a teacher drifted me away from Bioinformatics


Nobel Chemistry

As each October of each year, it is one of the most waited event….Nope it is not Halloween….It is the Nobel Prize in science (I will not give my opinion about the Peace one because these last few years I found it it was given with a lot of flaws and not justified rationales).
Yes, today it was the Chemistry one, after the Physiology/Medicine one (that is also impressive as a neuroscientist geek) and the Physic one (Higgs boson, this one I was guessing was on the hotlist after the excitement earlier this year).
Today I found was a well deserved Prize and also a bit chauvinistic to have a professor of my alma matter brought another prize home. It also reminded me 10 years earlier on when I was a sophomore at college and I was hit with the buzz word “Bioinformatics”. That was sounding so awesome for the geek I was. Imagine that, blending my love for Biology and my love for computer (well maybe I was not even to a stage of a script-kiddie back then). I wanted to go to that direction and took the path for getting a degree then.
At first I liked it, because it was chem-intensive but I liked organic chemistry and biochemistry but then something got wrong. Something got sour. Something or I rather say someone, especially two faculty members well-established in the structural biology field. One was in nucleic acid and one in protein folding. I dont know why but their lecture were very aggressive and few considerate of students….It was like we were idiots lazy party goers that it was a waste of time to take them out of their lab to come teach us, that we were not deserving their science to be taught on us.
And that was it, my cold shower, that little voice to me said “No way! Never again!”. Then I gave up in pursuing that career and found myself much more happy in Neurosciences and Pharmacology. Although the teacher were harsh on assignments and notations, they had that kind of respect, that engaging lectures and interactions with the students that makes them go over the challenge of passive learning into an active learning. I felt so good about it that I switched my Master into a Neurosciences/Pharmacology one, pursued in Pharmacology and even faced again the same “bioinformatics” but this time realized how useful it can be and how interested it can if you have the right teacher, the right instructor. But then my interest was somewhere else and have other research endeavors I was deep in. I was this generation of students in which G-protein coupled receptor crystallography was the next “Nobel Prize” because it was a pain to have such structure crystallized, when the cDNA microarray by Affymetrix was in and trendy and just having a sequence was a paper per se (I think now you gonna have to go way beyond and Affymetrix is so 2000’s).
I am still here, still in science, enjoying the tidbit of science because it is like a puzzle in whcih you generate jigsaw and firstly trouble to assemble these pieces together and then you start to assemble them and get a clearer picture.
It also reminds me that a teacher plays an important model for students and it should be done by interests not by burden. A great teacher is the one that engage the students and go over his status. A great teacher is the one that brings this excitement of learning and how science works and does not. A great teacher is the one that set challenges but also recognize the effort and acknowledge the student for it.
Dear Eric W. and Jean C. (because I am now a colleague), I wished you changed your mind on students and hopefully embraced an active learning in your class. There are some wizkids outside in the class than be fantastic for bioinformatics, but if you want to get them into your rank, engage them.

PETA wastes no time going after UW after they are CLEARED of any wrongdoing

PeTA and the animal research ongoing at UW-Madison: I can see the cat that is in pseudo-pain but I completely oversee how animal research is the reason I am alive and healthy.


<sigh> Today, PETA sent another attack to UW after they were only just today CLEARED of ANY wrongdoing. You can read more about their campaign here.

So I ask you, why is PETA taking on this fight again? They have already forced a government agency to review the program claiming animals were being tortured, yet as soon as that report comes out that says those claims were unsubstantiated, they dismiss it! Ha, they did not even dismiss it, they did not even ACKNOWLEDGE it happened! Bottom line is that they LOST the battle but instead of going back to their home base to come with another plan, they hit the rolodex of celebrities to find someone willing to go forward with their harassment plan. The entire UW campus with get this message.

PETA is very slick and sly. They are not afraid to use any tool they can…

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Joseph Lister bringing the concept of anesthesia and aseptic conditions, Alexander Fleming miraculous finding of Penicillin, Pasteur discovery of the anti-rabies vaccine…..Science is full of these unexpected findings and discoveries that brought us these heroic moments. But are these stories really true?

Read the latest scientific history article co-authored by Dr. Heloise Dufour, a remarkable colleague here at UW-Madison, also a talented HHMI teaching fellow and proven science out-reacher. A must-read.

Happy Stem Cell Awareness Day (sorry for being late)!


Happy Stem Cell Awareness Day (sorry for being late)!

What drives me to keep in science is the wonder and creativity that this job ask from me, and also I enjoy being able to have this continuous thinking machine on my mind that brings me to the next question following my answer.
Yesterday was the stem cell awareness day and I am proud how this field blossomed so much in less than 15 years. It is also a blessing to work on an institution that hit the field with two major milestones: the first human embryonic stem cell (hESCs) (Thompson et al., Nature 1998) and the first human induced pluripotent stem cell (iPSCs) (Yu et al., Science 2007).
We are still away for using stem cells as a cure, but what we have right now that is palpable is having iPSCs from patients that help us better understanding what is wrong with the cells and how can we fix it using molecular tools. Indeed we are already entering the area of personalized medicine.
Because science is also an artistic form of expression, I have posted some of my stem cells (iPSCs) that underwent differentiation for forming blood-brain barrier cells. Without any external molecular guidance, one subset of cells decided to become neurons (left side, green depict bIII-tubulin, red nestin), whereas the other set of cells decided to undergo another pathway and to become brain microvascular endothelial cells.
Enjoy the beauty of the stem cell biology.

War…..War never changes. Happy Birthday Fallout!


War.....War never changes. Happy Birthday Fallout!

Vey few video-games hooked me up in front of my screen. Nope, no Sonic or Mario in my hand. It was too much dexterity and low-order task for my brain. Games that hunted by mind are those games where you can have your mind blown by the rich storytelling behind (most of the cases): Pitfall II (Atari 2600), Batman (Amstrad CPC), Bargon Attack (Atari ST), Phantasy Star II and IV (Sega Megadrive), Shining Force I and II (Sega Megadrive), Buck Rodgers (Sega Megadrive), Rings of Power (Sega Megadrive), Space Hulk (Sega Saturn), Labyrinth of Time (Amiga CD32), Angel and Demons (Philips CD-i), Star Flight (Sega Megadrive)……..and then came Fallout. A post-nuclear role playing game. Fallout have this notion of wasteland, post-nuclear world that maybe was driven by my inconscious mind. This mind haunted by the atomic bombs, the Cold War, Chernobyl catastrophe, former President Chirac resuming his underground nuclear tests (Bordel de merde!) but also experiences like Mad Max….
Fallout was like that girl that you can fall in love at first sight before even not saying hi. It blew my mind by this deep and sense atmosphere where you are sent out of your Vault, this nice and warm cocoon to find a water chip for your community. Everything in this game is tightly linked to another, rarely an action you have performed will influence the future, rarely a game put you in a situation where you may decide to act as a good Samaritan or like the dreaded scoundrel on Earth. Rarely a game makes you evolve your mind and dispute an established order. Then came Fallout II that brought you another experience of awesomeness.
Some fans decried Fallout 3 and Fallout New Vegas but these games albeit not perfect brought me into the first person, and have this feeling of immersion one step ahead. They also brought contemporary thematics and problems of our modern society, about a dystopian historical timeline in which technology ceased to evolve over (that I attribute to the non-discovery of the transistor) giving this touch of postnuclear 50’s, about how our humanity wrecked havoc following the end of “unlimited resources” and how we as human being put ourselves to the end in just few hours, with no help of an meteorite passing nearby.
I am very curious to see how Tim Cains’ kickstarter project “Wasteland 2” will look like but this approach show how can breaking walls behind the storyteller and his listener can bring an awesome experience, especially for gamers.
Maybe in my mid-life crisis I may go wild and attend this crazy thing called “Wasteland party” holding somewhere in the Californian desert in September. Since then….
War…..war never changes.


Painting brain tumor? Why not if…..

… can cross the blood-brain barrier. This article was very interesting as it crosses some of my current collaborative research. But what I have learned from attending the second Neuro-Oncology Symposium in Minneapolis last week that brain tumors are extremely diverse even within a “group” brain tumors. For instance, the same type of tumor described in the article, the medulloblastoma are indeed split so far into four major groups that are genetically distinct from each others: the Sonic Hedgehog (Shh), the Wnt/beta-catenin, the group C (the most aggressive one) and the group D.

Each of them will not respond the same to the treatment. Adding that so far there is no magical compounds capable to cross the BBB (we are talking about 10-100 times less drug entering the brain than entering other tissues). As I mentioned in my comments section, we have to be very precocious when we talk to science to general audience as we may raise very high hopes but failed miserably in the limbo of clinical trials. What is true in a mouse is not true for a human (especially when we talk about the brain) and what is true for a lung tumor may not true for a brain tumor.

Unless we seriously think about this “fine impermeable barrier” that was discovered by Paul Ehrlich and Edwin Goldmann 100 years ago and learns about how things cross and can be designed to cross, we will miserably fail by constantly hitting the wall. And so far, unfortunately, brain tumors have a clear upper hand on us….Remember, average life expectancy: 18 months, less than 5% reach the 5-year survival set point.