[BBB/Sciences] Study on a iPSC-derived model of the blood-brain barrier inclusive of astrocytes, neurons and pericytes retracted.

According to RetractionWatch “an investigation by Kyoto University in Japan has found a researcher guilty of falsifying all but one of the figures in a 2017 stem cell paper. Yesterday, Kyoto University announced that the paper’s first author, Kohei Yamamizu, had fabricated and falsified data in the Stem Cell Reports paper.

I remember reading this paper (http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30039-5) last year with my student. We found it interesting but also odd and with several caveats. Turned out that almost every figures have been doused with falsified or manipulated data.

First time I see a paper in our field being retracted for scientific fraud. Wow.

Source: Researcher at Japan stem cell institute falsified nearly all images in 2017 paper – Retraction Watch at Retraction Watch

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[Science/BBB] Zakłócenie bariery krew-mózg wywołane histaminą u dzieci ząbkujących: błąd logiczny.

[Note] I am not a Polish speaker, so I would like to thanks a follower from Poland (Ania D) for the translation of my blog post. 
This is a special translation for Polish readers of one my previous blog post ([Sciences/BBB] Histamine-induced blood-brain barrier disruption in teething children: a “post hoc ergo” on glucocorticoids.). I got informed that a certain Polish anti-vaxxer group used that same blog post to make fallacious claims on histamine and the blood-brain barrier, using my post as a “source” for their claims as depicted below (look at the citation on the bottom line).

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Not only their allegations are false, but they also failed to check their citations to their claims. A respectable person making a claim checks his/her sources, especially when such claims are completely nullified by the source. Here goes the translation in Polish.

Niedawno dotarła do mnie informacja, o tym, że mój artykuł został podlinkowany pod memem, w którym pojawia się informacja o tym, że ząbkowanie powoduje rozszczelnienie się bariery krew-mózg, a to z kolei stanowi przeszkodę w wykonaniu szczepień. Czy jest to prawda? Oczywiście nie. Chciałbym teraz w kilku zdaniach wyjaśnić dlaczego jest to kłamstwem. Po pierwsze, ząbkowanie (lub erupcja zębów) jest procesem obejmującym zapalenie dziąseł: są czerwone, gorące i opuchnięte, w trakcie tego procesu uwalniane jest wiele różnych substancji chemicznych, które wywołają to, co nazywamy odpowiedzią zapalną, m.in.histamina- uwalniana miejscowo, w ognisku zapalnym. To daje nam prosty wniosek- jedyną możliwością, żeby histamina naruszyła barierę krew- mózg (BBB) jest pojawienie się zębów w mózgu, a to o ile mi wiadomo nie jest możliwe.
Po drugie, załóżmy na chwilę, że to twierdzenie jest prawdą, załóżmy, że histamina może się gromadzić i osiągać stężenie na tyle wysokie, aby spowodowało to zakłócenie BBB.
Do chwili obecnej sprawdzenia poprawności tej tezy podjęto się tylko dwa razy, ponad 40 lat temu, w dziennikach medycznych z Brazylii i Egiptu, które raczej nie są wiodącymi pismami w swojej dziedzinie. Zobaczmy zatem, jaka jest reakcja immunologiczna, w odpowiedzi na uwalnienie dużej ilości histaminy:
https://www.sciencedirect.com/science/article/pii/S0091674900321704?via%3Dihub#aep-table-id22
Mierzony był poziomy histaminy u pacjentów z szokiem alergicznym, jednak żaden z nich nie wykazał zakłócenia BBB. Najwyższy osiągnięty poziom histaminy wynosił około 30 nmoli / L (warto zapamiętać tę liczbę!). Czy zatem możliwe jest, że w przeciwieństwie do szoku, ząbkowanie mogłoby otworzyć barierę krew- mózg? Nie. Od razu zaznaczę, że rozwój BBB następuje u płodu w drugim trymestrze, więc nie ma tu zastosowania argument, o niedojrzałości bariery krew- mózg ( https://www.frontiersin.org/articles/10.3389/fnins.2014.00404/full )
Pojęcie “przeciekania lub niedojrzałości BBB” u niemowląt jest przestarzałe i nie jest już podtrzymywane przez społeczność naukową

Po trzecie, w badaniach potwierdzających możliwość otwarcia BBB przez histaminę jej stężenie było na poziomie między 10 mikromoli / L, a 100 mikromoli / L
( https://www.ncbi.nlm.nih.gov/pubmed/1611469
https://www.ncbi.nlm.nih.gov/pubmed/9379415 ).
Ponieważ 1 mikromol / L jest równy 1000 nmoli / L, prosta matematyka daje nam wniosek, że potrzebna do naruszenia bariery krew- mózg reakcja jest 300- 3000 razy silniejsza niż reakcja wywołana u osób z reakcją alergiczną na histaminę.

Nie daj się zwieść memom, zawsze sprawdzaj źródło użyte do poparcia roszczeń. Teraz możesz śmiać się z tego głupiego mema i głupiej osoby, która udostępniła mój link bez czytania oryginalnego posta na blogu. Ten meme został stworzony przez polskie antyszczepionkowe stowarzyszenie StopNop. Informacja na tym memie jest nieprawidłowa i nie zgadza się z treścią cytowanego artykułu.

 

[SciFi/Star Wars] Star Wars: The Last Jedi (Episode 8) (80%)

Star Wars: The Last Jedi came out about a month ago and I think that now after two views (distanced by about two weeks),  I can finally write down a final opinion on it. What I can tell, it created some serious divide between the critics and fans. Just look at the difference in scores in Rotten Tomatoes between critics (that lauded it) and fans (that some claims is even worse than Attack of The Clones).
So far, the best and most interesting fan review came from Kevin Smith. A very good hour in which he goes through details, highlighting the good and underlining the bad things about.
I decided to give it a few weeks before making my comments for one reason: the Jedi mind trick that hit me 15 years ago when Attack of the Clones came in screen. At first, I was “Oh yeah, it was awesome! One of the best Star Wars!” and still remember the diatribe from Rafic Djoumni, a former journalist in “Mad-Movies” (a well-respected French magazine about Sci-Fi and horror movies that was my favorite movies magazine). Looking back, the movie honestly did not survived the tides of time and is needed not as good as I remember (please someone remove Anakin meadow scene from my brain!).
ATTENTION————————SPOILERS AHEAD! YOU ARE WARNED!———————————-
So, there is the deal: the movie is good, better that was fans try to make you believe. But it is also not the masterpiece sold by critics. No, it is not “The Empire Strikes Back” quality (still awesome after thousands of watching and almost 40 years in the odometer). There are some good moments, and there are also just scenes I would have cut and I would not even notice I was missing something in the story plot. I feel Rian Johnson wanted to not follow the same steps than JJ Abrams and thought probably it was time for  his own vision of a trilogy. Although this can be a laudable move, it also meant that a lot of things brought by JJ went under the rug.
The movie starts with a bang, right where we kind of left it “The Force Awakens” and it is very intense. Imagine a WW2 bombing operation transposed in a galaxy far far away a long time ago. It was starting very well, but then started to stall at some point. The Rebels try to escape from the Imperial Fleet, only to be caught up a few hours after jumping out from Hyperspace. If you are accustomed to the reboot of “Battlestar Galactica” aka “BSG”, the plot of the first episodes named “33”. I don’t want to spoil much (because this is one of the most awesome Sci-Fi franchise from the mid-2000s I wished was aired in FrenchTV back then) as the Cylons are capable to track “the 12 colonies of Kobol” surviving fleet each time they jump from their FTL (faster than light) drive. Each time after 33 minutes.
This creates a plot in which the Rebels are in a sort of face-off, running out of fuel. Thats sounds a good plot but then you realize it runs on a paper thin. The Imperial fleet has a formidable firepower that would zap the fleet. No, they just stand waiting them to run out of fuel. Kylo Ren is keeping on the rage, only to be disciplined by Snokes. Enough to have Kylo to pick a Tie fighter and attempt a suicide mission on the main fleet vessel carrying General Leia Organa. He literally blew the ships deck with Admiral Ackbar in it sending Leia floating in space. This is where we have another ridiculous scene with CGI as good as “The Matrix Reloaded” (the infamous Playstation2 CGI). One of the sequence I liked however was the appearance of Laura Dern as Admiral Hodo. I was waiting for the “Fuck You, Poe!”, as I am still in all my Twin Peaks mindset and seeing Laura Dern playing the Diane tulpa. Her last move was a last kind of bravado act, going down with her ship as any respectable Captain do after ordering the crew to abandon ship (I almost felt Star Wars was getting inspiration from Trek). The whole sequence was simply a shock and awe, with a complete silence during the scene (remember…….in space nobody hear you scream!).
This scene is enough to questioning where Johnson wants to bring us. I guess it was meant to ramp into the sub-plot of the “Casino planet” that I thought was 45 minutes of major meaning. So I will skip this and go to Lukes plot. We left that with Rey finding Luke and handing him over his lightsaber, the same one he lost on Bespin in the Empire Strikes Back. Here comes the funny part that I liked about, seeing Mark Hamill throwing away the lightsaber and basically saying “enough of this BS”. I liked this whole sub-plot except the Porgs and the nuns. I felt seeing this part of the story was very good and show how the Jedi Council behind his allure of virtue and nobility are not as clean as they want to make things look like. They have sinned in their own way by their overconfidence and maybe also their inability to evolve. Seeing Yoda as a puppet was also a touching moment.
Rey rejoins the whole group and decide to confront Snoke. This is just bringing the second anti-climatic phase of the movie. Snoke dies like an idiot, Captain Phasma dies like an idiot. Both getting the Bobba Fett Mary Sue treatment. Both flattened out as a missed souffle. So we have been waiting two years for something that felt flat like a deflated balloon?
The last quarter of the movie was kind of awesome. It was somehow replaying the plot of the Battle of the Hott system. Seeing the evolved AT-AT and seeing the Rebels cornered brought in this level of stress that was initially here. Then came Luke (sort of), almost coming as a Messiah. And Hell he looked like the Chosen One in a scene reminding us of “The Matrix” Neo final scene, resurrected within the Matrix and capable to stop the  agents bullets and move faster than their moves. Seeing Luke being blasted with all the firepower and stood still made us feel Luke reached the uber-jedi  Rank and was appearing as the Jedi. Only to realize he was transposing himself from a distant galaxy, with the sunset on him. This final scene had some profound meaning for me because it was a direct call to my childhood heroes and it was also meaning that the sun is set on our childhood heroes. Han Solo was gone, Luke is gone and Leia is also gone.
My son loved it, but me I stood at the end of the credits sequence and thought. Maybe I am getting old, maybe I am becoming an old shmuck thats mind is stiffening overtime and incapable to show flexibility. I thought to myself that Episode IX will likely be my last one. I don’t see myself piling up another trilogy and I feel somehow sad to see that Star Wars is becoming a cash cow for Disney, milking it ad nauseam (we are not yet having Star Wars condom but I would not be surprised to have some). Maybe it is time, that as Luke, Han and Leia, I close my eyes on Star Wars.

[SciFi/Star Trek] Star Trek: Deep Space Nine (25th Anniversary)

Today marks the 25th anniversary of Star Trek: Deep Space Nine (aka DS9). It marks the branching out of the Trek Universe, five years after the launch of Star Trek: The Next Generation and was running in parallel to the latter one.
It first aired on January 3rd 1993 and in my opinion constitutes the best of the Trek Universe and follows the life of the Deep Space Nine station under the command of Benjamin Sisko. Some people claims DS9 took the idea from Babylon 5, indeed DS9 preceded Babylon 5 by a year roughly.
The series starts chronologically right by the end of TNG Season 2/beginning Season 3 “Best Of Both Worlds”  when Capt. Picard is captured by the Borg collective and became Locutus of Borg. Under his command, the Borg lead the massacre of Wolf 359. The DS9 pilot starts here in which Benjamin Sisko (played by Avery Brooks) serving on a Federation ship amongst his wife. As they try to evacuate the ship, Benjamin lost his wife from collateral damage and constrained to abandon ship in an escape pod. Back in Earth and a couple of years following the Borg encounter, Benjamin is offered the command of the Deep Space Nine station (also referred as Tevok Nor), recently recovered from the Cardassians following their retreat from the Bajor planet, ending their occupation of the planet.
For any means, getting command of the Deep Space Nine is not the most enjoyable assignment: located in the deep end of the Alpha Quadrant, near a planet that remains primitive (Bajorans lack spaceship transportations) and a highly mystical civilization (Bajorans share many similarities with Bhuddism). In order words, this station is considered as being assigned at the frontier of the Federation.
Benjamin comes in with his son Jake, in a dirty, rusty and isolated station and get command of the station under the Federation mandate. As we discover Benjamin Sisko exploring the station, we get introduced to newcomers of the Federation. We have some familiar faces in the person of Senior Chief Petty Officer Miles O’Brien (played by Colm Meaney) transferring from USS Enterprise (we have seen O’Brien in several TNG episodes) amongst his wife Keiko (played by Rosalind Chao) and their daughter Molly. We also have newcomers in the persons of Dr. Julian Bashir (played by Alexander Siddig) and Lt. Jadzia Dax (played by Terry Farrell). Bashir is this young and prodigious doctor eager to discover new horizons. For him, assigned to the frontier of the Federation is a boon and considers it as an formidable opportunity. But behind his joyful and prodigy hides an important family secret that comes in later to haunt him.
Dax is the second time we got introduced to the Trill alien race, a race that is involving a symbiont as corporal support. It is a very interesting character as Trills carry over memories of their previous hosts and often change their gender through the circumstance. Jadzia (female) is the 8th host, following the transfer from Curzon (male) Dax. Benjamin knows Curzon very well and gently refers as “old man” and keep that friendly relationship with Jadzia. It is an interesting concept by bringing the discussion of transgender and LGBT into the Trek Universe.
Amongst the members of the Federation, we also discover the “locals” of the station. We have firstly Major Kira Nerys (played by Nana Visitor), commander from the Bajorian Forces and representing Bajor in the station. We get introduced to Odo (played by Rene Auberjournois), a “changeling” alien that is a fluid-like alien capable to morph into any shape and structure. He was the Chief of Security under the Cardassian occupation and remains as is in the current station. We also get introduced to the Ferengi in more details by the presence of Quark (played by Armin Shimerman) owner of the bar. Quark hold the bar business with the help of his brother Rom (played by Max Grodenshik) and his nephew Nog (played by Aron Eisenberg). In addition to serving alcholic beverages, Quark also maintain some Dabo tables (a complicated gambling game looking like a roulette game) animated by the presence of Leeta (Chase Masterson) and by the presence of Morn  (Mark Allen Shepherd). Finally, the last but very important protagonist is Elim Garak (played by Andrew Robinson), the owner of a tailor shop. Behind his jovial and very warm character, Garak hide a heavy and dark secret that we only learn later in the series.
Early on, the discovery of a wormhole leading to a brand new uncharted Quadrant (the Gamma Quadrant), transform this remote space station as a formidable frontier hub for those traveling to this Quadrant and coming from it.
This congregation of different characters coming from different horizons and different species make this melting-pot that made the DS9 station unique. It look like a Babel tower in space, in which different cultures and aliens cross their way through. The first two seasons are sure campy and make the rides bumpy but by the end of Season 2, the magic formula slowly started to take in and take some radical different directions than the utopia set of Gene Roddenberry. DS9 shows us that the future is full of shades of grey, with characters fighting their own demons and depicting that the Federation is not as shiny as it is.
We get into very interesting story arcs: the Federation-Cardassian treaty that surely ended up the bloody war (we learnt about Miles past as a soldier) but failed to consider the impact of setting DMZs on the population (creating the splinter cell known as the Maquis, taking the name of the French Resistance during WWII). We also get introduced to the Bajoran-Cardassian relationship and the relationship between an occupier belligerant and the occupied, shattering through the idyll of the David versus Goliath. Both camps shed blood and blind terrorism in the name of a cause. But also both camps knew to fell in love (thats really speak to me, as I see it as a metaphor of the occupation of France by German Nazis, with the French population). We also get introduced to the Dominion, a metaphor of the Pax Romana that offers you peace with the condition that you surrender your authority to the Roman Empire) and his army of the Jem’Hadar. An army genetically conceived with one mission: “Born to kill” and maintained in check by the use of a drug referred as Ketracel White (we can see similarities with soldiers given wine and liquors before giving the charge). I also see the Jem’Hadar as a metaphor for the child soldiers that were actively involved in various civil wars in Africa.
Things really starts to kick in when Worf (played by Michael Dorn) join the series by Season 4 (right after Star Trek: First Contact) and when Sisko takes on the “Samuel L. Jackson” goatee look. This exponentially increased the awesomeness of the show by deeply exploring the whole Klingon folklore superficially explored in TNG.
In addition to the story arcs, we have important topics discussed through different two-series episodes with some of the best Star Trek episodes ever created in the whole Trekverse. Look at the “In the Pale Moonlight”, “Assault on AR-558” and many others.
If you have not seen DS9, you have been missing big time. I would however recommend to skip some episodes in Season 1 and 2, especially those that are not associated with the main story line (Bajor or Maquis).