Today concluded the last session day of the #ISCBFM15 Brain 2015 meeting, it concluded as it began, with a lot of good talks and sessions that makes you very happy and invigorated.
It started this morning with the Nielssen Award attributed to one of the four finalists (all young investigators) selected by a panel and presented their talk. One of this talk was presented by Dr. Shi (U of Pittsburgh) and involved changes in actin cytoskeleton at the BBB during stroke injury. It was followed by a closing keynote lecture by Dr. Martha O’Donell (UC San Diego) and was very well articulate about the importance to consider ion channels and transporters at the BBB during cerebral ischemia and stroke, in particular how these proteins triggers the cascade that will eventually lead to cerebral edema formation.
The afternoon session was also very good with a BBB session in which there were very interesting talks, including some presentation from Dr. Tom Davis (University of Arizona-Tucson) that really show how P-glycoprotein, a key drug efflux pumps interacts with a vast complex of different proteins, very far-strectched from the classical textbook sketch of P-gp being alone in the cell membrane. Another talk came from a faculty member from the University of Manchester and documented that maybe the BBB TJs are not breaking down during cerebral ischemia but rather there may be an increase in transcytosis. It is like having a boat not sinking because you have a breach in the hull, instead because there is someone that is filling up the boat with seawater using a bucket.
Then came the sad part, wrapping up the poster, leaving the conference site and packing my bag. Next time it will be under the Brandenburg Tor, wandering on the Ku’damm. Ja, next time it will be Berlin. Bis 2017!
PS: I knew Vancouver was a nice filming set but it was just insanely great to learn that the same convention centre we had our meeting was also a gunfight scene in the remake of “Robocop” http://www.vancitybuzz.com/2014/02/vancouver-convention-centre-destroyed-robocop-movie/
Brain 2015 meeting Day 2 Debriefing (after a long night chit-chatting on a boat touring Vancouver).
Very good session yesterday, lots of interesting topics. The AM session was very interesting talks, especially from Dr. Lin (University of Kentucky) about caloric restriction and enhanced CBF during aging. She proposed that glucose-rich diet may contribute in decrease in CBF during aging and thus may contribute to vascular cognitive impairment. She also suggested ketogenic diet maybe an alternative to carb-rich diet to improve CBF.
It would be interesting to see how ketone bodies may affect CBF and in especially how it impacts cognitive outcome, as some patients have to be on a ketogenic diet by necessity (GLUT1 deficiency syndrome) or by medical condition (epileptic-drug resistant patients).
Another interesting talk came from Dr. Lazarov (University of Illinois-Chicago) about the importance of caveolin-1 during post-stroke neurogenesis. Interestingly enough, caveolin-1 is a protein noramally present at the BBB that may have some function on drug diffusion by receptor-mediated transcytosis or by pinocytosis. A common sense would have expected that such protein would increase during hypoxia-ischemia. Indeed it seems that is going a certain down-regulation. Furthermore, Cav-1 KO mice showed less neurogenesis at the SVZ following hypoxia. That was very interesting.
Another series of good AM talks came from Dr. Iadecola bringing more lights on a very interesting transporter recently described: Msfd2a and its contribution in hypertension-mediated BBB disruption and from Dr. Zlokovic (USC) that described the contribution of GLUT1 on Abeta metabolism and clearance at the BBB, as well as a novel of proteins involved in cell trafficking: PICALM. Finally the session closed with Dr. Edith Hamel (McGill University) on trying to rebrand two FDA-approved molecules used commonly against cholesterol (simvastatin) and hypertension (losartan) as a possible tool to improve outcomes in patients suffering from cognitive impairment due to vascular cognitive impairment and Alzheimer’s diseases.
A particular feature that I felt well designed was the Journal of Cerebral Blood Flow & Metabolism (the official journal of the society) have a highlights of the most cited papers between this conference and the previous one.
An interesting talk from Katya Park (U of Toronto) showed some interesting results of BM-derived EPCs as secreting cells capable to partially help neurons recovery from stroke injury. However these BM-derived EPCs were remotely acting and secreting their factors, whereas another kind of stem cells called Human Umbilicial Cord perivascular cells (HUCPVC) were capable to show similar results but appeared to migrate in the perivascular space of the affected region. Thats sounded very interesting and in par from what Dr. Dore-Duffy and early clinical trials using MSCs described: a selective homing in the perivascular space then secretion of survival factors from there.
Finally the session closed with Dr. Gary Rosenberg (University of New Mexico), a well-known BBB researcher about vascular cognitive impairments, biomarkers and prognosis.
He described three important points: 1) Hypertension that triggers the onset of the pathology, followed by 2) Hypoxia and the fairly sustained HIF-1alpha activation (I was curious to see whats happens to HIF-2a) and finally 3) inflammation.
The day ended with a nice Banquet on a boat that toured us through Vancouver coast line, it was some great time to meet and greet and also sparked some discussion about how the Brain and BBB people are not really matching together. Very few BBB people here but also very good sciences that can benefit BBB people either at the Gordon or at the CVB meeting. Maybe the next venue of Brain 2017 is distant enough in terms of time to have more BBB people attending and maybe from Brain people attending the CVB meeting as until now both were close in terms of time but also “pricy” in terms of venues.
Since last night I have I am in Vancouver for a scientific meeting. First time in Vancouver and second time I visit our northern neighbors. Canadians always amaze me, easy going folks up here. Vancouver is a very nice city indeed, I don’t ask much but seeing such a nice landscape made of mountains, a seas with water-plane docked on the piers and skyscrapers everywhere is a great experience. Thats a lot of change from the Texas Panhandle. So today closes the first day of #Brain2015, a lot of symposium, talks, posters but very interesting take home messages indeed. I will not spoil much but this is what I found very interesting and relevant as a BBB scientist: * Professor Constantin Iadecola was the keynote lecturer today and talked a lot about stroke and immunity. I grew up learning from textbooks that inflammation was the bad guy for stroke recovery. Indeed, it appears clear now that “its complicated”. There is indeed a fine balance between the good “innate immunity” and the bad one, it is all about a fine equilibrium. And it all revolves about DAMPs (Damage Associated Molecular Patterns), these are some cellular components from damaged that will trigger the inflammation cascade by an array of different transporters. This term is fairly new and well coined and I believe that is just started to get hot topic. Another remarkable take home message was the contribution of the gut microbiota in the neuroinflammatory response following stroke! It seems (at least in mice) that your gut microbiota is driving your stroke outcome in terms of inflammatory standpoint, you either have a good outcome or a bad one. However, it is very important to note, at this point we only barely know about such gut-brain axis and we just start to understand the role of the microbiota. We are still far away from a cure or a treatment and calling now that such cure exist is simply a fallacious treatment. However, that gut-brain interactions really got me in and I would bet that this is the next hot topic. The second session was this afternoon about cellular and molecular response to ischemic injury. A very interesting study performed by a group from Mario Neggri Institute (Milan, Italy) about the use of amniotic mesenchymal stem cells as a source of paracrine factors following OGD stress, that have a cutoff of less than <700Da. I am guessing that is surely some small molecules, maybe lipid based or something similar but also very small peptide sequences. Another interesting talk came from a group at the University of Glasgow and showed how some microRNA was driving neurons cell survival during hypoxia/ischemia OGD stress, however it seems such miRNA are cargoed inside small vesicles called extracellular vesicles. I may bet that they be exosomes but I am still pretty new on this and this is also some trend I see coming in the field, using exosomes as parcel services to deliver small codes fragments between cells to cells. Finally, the last session of the day was about pericytes. These are some guys I have been playing when I was younger and then I got diverted. Richard Daneman (UC Davis) have shown some remarkable work, some deja vu but some very interesting. Richard has been already before marked the field with his work on transcriptomics and pericytes. He has been working on trying to get a transcriptomics framework between four majors animals models of neurological diseases and how they affect the BBB: stroke (MCAo), epilepsy (kainate), multiple sclerosis (EAE) and traumatic brain injury. What was very interesting was the fact that there is a number of genes that are altered in all four diseases, and a consequent number of them altered in three diseases. That was very fascinating and suggest that the BBB may have some generic “first responder kit” to tackle these injuries. Of course he refrained to mention these candidates but this is something to keep an eye on. Finally we had a talk from David Attwell (UCL) that was on pericytes coupling in cerebral blood flow regulation and two things stroke me: the parasite hug of death that a boa constrictor encircle micro vessels during ischemia and die by keeping up these vessels strangulated and also some hot debate about defining “what is a pericyte”? So far, Day 1 have been a very good success, maybe weak in setting some collaborations and get to make new colleagues. However I still have two days left and already some collaboration in mind. To be continued….. P.S.: This is Mars. I missed you Mars! (You have to be European and living long enough in the US to understand my joy to see this treat next to my PM coffee cup :p)
There are few games that brought me excitement and passion during my life. If I have to cite some of them, that would be the Phantasy Star series (SEGA Master System, the Shining Force series (SEGA Genesis), the Fallout Series (PC, Xbox 360) and finally at the center of this blog the Bioshock series.
I never have developed a particular attraction before, God knows why until I once offered myself a bundle of 2K games including XCom, Borderlands and finally Bioshock. Once I started the game, it was love at first sight! Why? Maybe because the games timeline taking place in 1959 that brings in it very close of Fallout pre-war. Before I go further down my feedback and thoughts about the Bioshock Franchise I will just warn of ****SPOILER ALERTS****. If you want to have a great experience, you should not read the rest of this post.
Bioshock was indeed really a shock as the way you start. You are on a plane, in 1959 flying over the sea. You would think what could go wrong? Well this is just the beginning. Your plane crash in the sea and you are the sole survivor capable to escape the sinking plane. Fortunately for you, there is a lighthouse that seems like a beacon of light in this darkness. Indeed, this is more than a lighthouse and is the entrance of a utopian project carried by Andrew Ryan, highly influenced by Ayn Rand philosophies. A world where there is something people call libertarianism, in which you are your own master. You know that utopian dreams are deemed to fail and you will just get a taste of it. Here you are, finding a bathyscaphe that brings you down the “Rapture”: a complete city located hundreds of feet underwater.
And things starts wild: you are the witness of a murder from your bathyscaphe and got it hammered by a spider Splicer. You are alone, lost in a deserted underwater city. How else it can becomes more gloomy than that? As a providence, you start with a radio in which a man called Atlas, posing as a revolutionary leader, is here to help you to survive and get you both out this place. Hearing Atlas voice brings some solace from such chaotic start.
What seems as an altruist is only masking his real intentions. In French we say “Hell is paved by good deeds”. The more you advance towards the story, the more you start to doubt about his real plans behind him. Oh yes, have you noticed the chain tattooed on your wrists? Time will come to talk about it.
You face an army of splicers, that are humans that have abused plasmids. Plasmids are some perks that can be found in the Rapture, it modifies your DNA (as real plasmids would do) giving you extra perks such as throwing lightning bolts from your hands or giving you telekinesis perks. These splicers were former Rapture inhabitants that progressively became insane by the isolation from the daylight and by the abuse of plasmids. It brings back that even in the brave new world people will never find satisfaction and will have to find ways to escape even the most perfect world. Thats brings some parallel to the Prohibition in the 1920s. Some politicians saw alcohol as the cause of society illness and decided to outlaw its consumption. Guess what? After a decade, it what just removed because it just proved to be ineffective and brought more criminal activity due to bootlegging and smuggling than before.
In utopian dreams, everyone have access to same privileges and same luxury. Of course this system is doomed to fail. Unless you live in a desert island, you will have a hierarchy composed by a ruling class and an ruled class. This is the structure of any society, societies will try to accommodate it as much as they can to reduce these differences or in contrast widens the gap between these two classes. If you widen such gap too much, you will instigate a call for change from the ruled class that will result in the Revolution and eventually into a Civil War.
This is what happened during the French Revolution. The majority of French population were either peasants or “bourgeois” (that would be something similar to the current middle class), above them where the ruling elite composed by the Noblesse (including the Royal hierarchy) and the Catholic Church. The ruling elite was nurtured by the ruled class through the collections of taxes. In the counterpart, the ruling class will provide physical (army) and spiritual (Church) protection to the ruled class.
In the end of the 18th century (1780-1800), the ruled class had enough of being heavily taxed and following the call of King of France, started to collect complains into delegates from all over the Kingdom. We can see a similar parallel to Andrew Ryan utopian city. Ryan tried to compensate such complains by letting the smuggling of good from the surface (through Frank Fontaine), the promotion of culture (through Cohen) and by bringing some psychological counseling in the person of Sofia Lamb (she will be discussed more about in Bioshock 2). With any utopian dream, you will have people attracted by benefits that will work to make such system efficient to their profit and get their share of power.
Thats introduce us to Frank Fontaine. Fontaine is one of these shark that can smell some good profits and will make the dirty job for a while. Frank is a seasoned con-man (if we rely on the Bioshock Wiki) and surely a smooth-talker as Atlas and is the man behind the smuggling and contraband. He is also the man behind Fontaine Futuristics and made huge profits from ADAM and did not have remorse to kidnap orphan girls to turn them into Little Sisters. This greed of power and lack of morality is raised when you face for the first time a little sister. It puts into a dilemma: should you harvest a little sister from her ADAM or should you rescue her by removing the parasite and having less ADAM harvested? Thats put you in a delicate situation and Fontaine will not mind to tell to just harvest them.
This lust of power surely raised concern from Ryan and decided to get rid of Fontaine once for all by “nationalizing” Fontaines businesses (a complete contradiction of Ryan’s utopian philosophy and show how short-lived utopians are when facing the reality) and by eliminating the competition. Fontaine escaped his death and indeed planned his takeover of Rapture by posing as Atlas. Again a direct allusion to Ayn Rand “Atlas Shrugged”.
By posing as Atlas, an Irish fishermen, Fontaine use the anger and misery of the low-income workers of Rapture that are servile mass to Ryan’s elite inhabitants of Rapture.
We can see that the Rapture reached a point of rupture as marked by the overall chaos and signs posted all over the game. Such event is referred as the Civil War in which Fontaine posing as a revolutionary leader promising a bright future to the working class once the despot will be deposed. Can anyone see some parallels with the Russian revolution?
The superchery is revealed at the end when we met Andrew Ryan and in a formidable twist learn about our origin Jack and the meaning of the word “would you kindly?”. An “Ace in the Hole” as referred by Suchong. It shows how easily we have been fooled from the beginning. We are alone, afraid and powerless against an army of splicers. Fontaine was making us feel we were not alone and someone was giving us an helping hand to get out this quagmire. He was nice and polite asking us to do what he asked by “would you kindly?”. And we did it without questioning it. Until we arrive up to Ryan and now we are just a puppet of Fontaine. A man thinks, a slave obeys.
But the game gives us the choice. The choice of following our primal instincts such as greed and selfishness (through Fontaines) or to follow the reason and the best of humankind (as symbolized by Tennenbaum)?
That deep implication in a game made it great and put the same formula found in Fallout’s Karma. None will tell you which directions to take but the decisions you will make will affect the future outcome.
A nice sunset on Amarillo, straight from my backyard.
Today marks my first year anniversary of my arrival in Amarillo, TX. Amarillo, also known as “Yellow City”. A 200’000 inhabitants city located straight in the Texas panhandle, what I called the Wild West. What Amarillo is known about? Its “Big Texan” 72oz steak, its helium, its historical connection to the Route 66 and also for the nearby Palo Duro canyon, the second largest canyon in the United States.
It is also a rural town, located in the Texas High Plains, located among one of the largest cattle ranches in Texas. Being in Amarillo brings you advantages and inconveniences. Amarillo is by definition far from everything: The I40-West will take you to Albuquerque, NM in 4 hours, the I40-East will take you to Oklahoma City, OK in 4 hours. Dallas-Fort Worth Metroplex is 5.5 hours away and Denver, CO is 6.5 hours drive away. Thats brings you not much options. But you are also fairly well located so you can access to big city in a 5 hours drive radius (that can be an interesting option if you want to attend a concert, you can aim OKC, DFW or DEN).
When I left Madison, Wisconsin for my new faculty position here, I left it with a feeling of bitterness and sadness. I left a place I got used to love despite its harsh winter (being snowed up from November to mid-April, with sub zeros temperatures in January). I left a piece of me there, I left three years of living in one of the greatest place to live (according to several surveys) and left it with a broken heart as well. It was with tears in my eyes I left Wisconsin.
Arriving here after 2 days of driving southwards (ironically I have drove the same roads that brought me from Aggieland to Madcity three years before), we were here in our townhouse. No furniture, no TV, no Internet, no chairs (the moving company came the day after however and was a huge relief to have back some comfort)!
Anyone that say moving is easy is a blatant liar. You are lost, you have to learn back finding strategic spots (where is the nearest Walmart? Where is the French Bakery? Where is the nearby Bestbuy? Where is the nearest Starbucks? Where is the nearest school?)
But Amarillo also show me a great thing about Texas: Its Southern hospitality. An hospitality found in my workplace, an hospitality found in the nearby grocery store, an hospitality in the community with the typical “Thank you sweetie, y’all have a good day”.
Amarillo gave me a helping hand when in my academic career it was dark and gloomy (I was on my fifth year of postdoc, my H1 visa was ending and no academic future back in Europe). It felt like a relief and since my first day in my faculty appointment, I decided to show to my employers that their trust in my profile was worthing it.
After one year, here I am. Completely integrated into the community, giving back to the community by participating in local fundraising events (in particular the Amarillo Heart Walk and the Autism Speaks March in Amarillo), having my research lab up and running, two graduate students under my patronage. My first commencement ceremony as a faculty (I wished that Europe would implant this Anglo-Saxon habit, it is a great way to celebrate the completion of a degree), my first teachings done with future healthcare practitioners. A full academic year in which the kiddos not only adopted their new school but also thrived as never before! It is funny to see my little son learning Spanish in his preschool class and coming home excited to tell me his new words.
The winter in Amarillo was something fairly new to me: one weekend you may have a foot of snow in your garden and unable to drive outside, the next weekend you would stand in your backyard in a tee-shirt and grill some patties under a warm winter!
If I have to complain about some things? Well the poor quality and choice of thrift stores in town (driving an 1.5 hours to Lubbock partially solve it) and the presence nearby of Hereford that reminds you that you are indeed in a rural area (they call it the smell of money…I let you decide the meaning of it). Also the strong winds and T-storms hitting the area. I still remember two weeks after my arrival experiencing my first Tornado Alert in the middle of the night, hearing the strong wind currents and the sirens. We hid in the bathroom waiting for the winds to calm down, that was some freaking experience.
I came in Amarillo full of nostalgia from Madcity and the Badger State and the Yellow City (as amarillo means yellow in Spanish) brought me some balming sunshine coupled with the Southern hospitality when I needed it.