Ghost – Popestar (EP)

Ghost released last week their latest EP named “Polestar”. As they have previously mentioned, this EP has followed the same track then their previous EP “If you have Ghost” and consists of covers. Their previous cover was simply serendipitous, putting a big layer of dark and heavy¬†metal into pop songs, giving that nightmarish and horrific picture. For instance “I’m A Marionette” initially a pop-song by ABBA suddenly became a dark, nightmarish and depressing song. Or listen to “Crucified” bartering the baroque of The Army of Lovers into a mysterious and occult song with the voice of Papa Emeritus.
Altough this dark, doom and gloom is not present in the EP, being more into a progressive metal side, this second EP just reinforce one opinion I have about Ghost: these guys are like the King Midas. They transform any cover they touch into some masterpiece gold.
I will not post any track from the EP, except anything officially on Youtube.

The first track is “Square Hammer” that is the only track not being a cover. Using a thematic inspired by Fritz Lang “Metropolis” and “Nosferatu”, the title is very catchy and maybe suggest a transition of the band into a more progressive metal/rock domain but still much more enjoyable.

The second track is a cover of “Nocturnal Me” by Echo and the Bunnymen. This is the track that gave me some chills down the spine, by giving a mysterious and oppressing atmosphere that was the hallmark of their previous EP. I could even feel like the influence of Fabio Frizzi in that one. Thats in my opinion one of the best cover of that EP that overpass the original song.

The third track is certainly the most bizarre cover because of his clear deviation of the original song. If King Midas could transform some electro-poop into gold, so does Ghost. Instead of having some electro easy-listening song of the original, Ghost did some remarkable work on this one. With an opening sequence that would reminds the early work of Pink Floyd, replacing the electronic beep sounds with a dry guitar and atmospheric sounds. It gives some interesting ambient atmosphere to the song. If you have to compare to the original video, that would something you would illustrate with some kind of refined and zen environment, almost like an Apple advertisement.

The fourth song is taken from Eurythmics “Missionary Man”, giving a strong 70’s progressive rock blended with a touch of blues. It is also the least favorite one.

Finally, the last one. Maybe the most unknown except maybe by Swedes that grew in the 80’s. It is called “Bible” by Imperiet. Dont be surprised if the number of viewers on the Youtube literally explode. Thats certainly THE COVER of that EP. Ghost transformed that new-wave song into something as powerful as “He Is” from their last album “Meliora”. It is so well arranged and produced that you still have the original feel of the 80’s into that song but with the layer of progressive metal of the band. It is so good you could almost sneak it into your Sunday church and bluff the preacher on that as “He Is” was. This is where I give the genius touch to the band that somehow succeed to humanize the beast with many names.

Ghost has some bad rep among metal elitists but indeed I found the band provides this nice escape pod by nicely blending progressive metal and pop songs, transforming with their magic touch into heavy masterpiece.

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[BBB/Sciences] 19th International Symposium on Signal Transduction at the Blood-Brain Barriers

Today marks the third and last day of the 16th International Symposium on Signal Transduction at the Blood-Brain Barriers held this year in Copenhagen, Denmark.
This is typically a conference that is considered as a European Blood-Brain Barrier because it takes place usually in a EU country and has mostly a European audience. Still it attracts few speakers, poster presenters and attendees from the US and from other places. We were few US scientists attending this conferences and also few Japanese scientists.
The Euro-centric did not remove anything to the science presented and the attendance. We estimate about 150 people attended this conference and the scientific programming, the venue and the dinner event was fanatastic.
On the first day (Wednesday), we had some local stars such as Maiken Nedergaard and Kjeld Mollgard (University of Copenhagen) discussing about her latest research in glymphatic system and ABC transporters respectivelly. Furthermore, Joan Abbott (Kings College London, London, UK) provided a very nice and exciting keynote on some evolutionary trait on the brain barriers, discussing about the presence of a glial-based brain barrier and its subsequent evolution into a endothelial-based brain barrier and suggested that it may not be a single evolutionary event but may have happened several times independently in different phylae.
The venue of the first day in the Ceremony Hall at the University of Copenhagen was also giving this formal and colloquial atmosphere, as this room was nicely illlustrated with wall paintings highlighting different periods of Denmark history and the inclusion of the University in such history (the passage of the battalion of 200 students that stood up to Swedish Army in the 18th century was very interesting).
The second and third day took place in the much modern Scandic Hotel located downtown, in one of their ballroom allowing to share the same room with the posters). A lot of very interesting talks were highlighting the conference with Margareta Hammarlund (Uppsala University, Uppsala, Sweden) discussing about the pros and cons of animal models for assessing brain pharmacokinetics and also the need to itemize the different compartments in the brain. Other noteworthy talks were from drug delivery standpoint where a couple of talks on receptor-mediated transcytosis and their impact in neurodegenerative diseases and drug delivery (Claus Piertrizk, University of Mainz, Mainz, Germany), the migration of T cells in multiple sclerosis (Britta Engelhardt, University of Bern, Bern, Switzerland), the protective role of microglial cells following stroke injury (Zena Vexler, UCSF, San Francisco, USA) or cell-cell interactions between brain metastatic cells and the BBB (Imola Wilhelm, Hungarian Academy of Sciences, Szeged, Hungary). Finally the last talk of the day was a keynote by Maria Deli (Hungarian Academy of Sciences) about the current limitations and advances of in vitro models and also the need of BBB expertise in the field of bioengineering. Maria rightly pointed the elegancy of the microfluidics systems for modelling a “BBB on a chip” but also noted that such models fall flat as they use BBB cells with poor barrier properties, far from “the in vivo representation” selling tags in many publications in the field. For me, it clearly emphasize the need of having more bioengineers to come attend BBB conferences as well as the need to have BBB speakers in Bioengineering conferences. Maybe this is something worth considering for the next international meeting.
The conference organizers also included a dinner at the “Skuespilhuset”, a restaurant and theatre located on the shore of Copenhagen, facing Christiana (the famous hippy-turned-hipster village). The food was fantastic and the wine eased the tongues for better social interactions and exchanging ideas.
The third day was as rich as the previous days, with a session on in vitro modelling of the BBB using stem cells with a keynote from Eric Shusta (University of Wisconsin-Madison, Madison, USA), but also an interesting keynote by Ingolf Blassig (Leibnitz Institute, Berlin, Germany) that has done an exhaustive survey on the expression of claudins at the BBB and differences between rodents and human models.
Overall, it was a great conference well organized, short but dense enough to allow interactions, discussion and novel ideas of collaborations to stem.
Last but not at least, the classical photo group of the European (though incomplete) blood-brain barrier community in a nutshell. If you feel like to play “Where’s Waldo?” game, feel free ūüôā

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[Symphonic Metal] Arcadia – Arcadia EP

As you know I like to support young metal bands, especially when these bands are from France and show some potential. The latest discovery is Arcadia, a symphonic metal band from Mulhouse (France). They just released their first EP simply named ‚ÄúArcadia‚ÄĚ.
The EP can be purchased directly from Bandcamp on the band page (see link at the end) and I got my copy via this platform.

The EP contains 4 titles and honestly I liked it. It is heavy, it is loud, it is fast-paced and the keyboards instrumentals are nicely blended without feeling too much invasive or overprocessed.
The only caveat is the front singer is not a mezzo-soprano singer but she is doing a decent performance for a first release.

You can get your hands on their EP through Bandcamp here, there is one track free to listen and you can purchase the EP if you like:
https://arcadia6.bandcamp.com

 

[Symphonic Metal] Delain – Lucidity (10th Anniversary)

Today marked the 10th anniversary of Delain first album “Lucidity”, as it was released on September 4, 2006.
Delain was founded by its core by Martijn Westerholt, former keyboardist Within Temptation, and Charlotte Wessels.¬†This particular bound to Within Temptation¬†(his brother Robert Westerholt is still the guitar of WT) certainly resonates into this first album, as I found heavily influenced by WT but yet at the same time well crafted for a first album. The album is highly symphonic and well crafted, as well as heavy and honestly it was the first and last time I felt a Delain album that would stick to me as long, as I found their drifting into a certain “poppy” sound may works for teenage girls, but not for the old schmuck that I became.
As I said this album is highly regarded in my collection, with the most of the album very enjoyable to listen. Charlotte’s voice is also very enjoyable yet not falling into the category of soprano voices of other Dutch metal singers such as Sharon or Simone. Also the combination of Charlotte and Martijn (clean) on the voices make it enjoyable without saturating your ears.
For instance, “Daylight Lucidity”, “Sever”, “Sleepwalker Dream” and “Shattered” are instant hits. Very well arranged, nicely blending the symphonic and the metal. Tracks featuring Liv Kristine (ex-Leaves Eyes) on “See Me In Shadow” and “Days of Ghosts” or Sharon Den Adel (Within Temptation) “No Compliance” are also damn good. Indeed the number of tracks that I dislike are maybe one or two from a total of eleven tracks.
Surprisingly enough,¬†after listening for Delain for 10 years and 5 albums on the counter, none of them was capable to move “Lucidity” from my playlist. Thats lament me because I really liked their first sound.¬†Paradoxically, this is one of these bands I found better live than on records, as they sound much heavier on stage. Maybe this is the consequence of overproducing and overrating the sounds in studio?
If you don’t know Delain, I strongly suggest to get your hands on this one. This is the golden ticket to the band, certainly their masterpiece even after 10 years.

[BBB/Stem Cells] Do stem cells cross the blood-brain barrier? A quick overview of the literature

This post is related to a recent testimony of Rhonda, a follower of my Facebook page, that asked me whether stem cells can cross the BBB.¬†As a BBB and stem cell scientist, this was a very good question asked. If I have to tell my thought in a sentence, I would it’s complicated. To support my claim, I will use the recent review from Aylenik and colleagues (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4106911/) and Liu and colleagues (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753739/)

First, it is important to remember the reader about what is a stem cell and what are the different types of stem cells. A stem cell is a particular type of undifferentiated cells capable of self-renewal and capable to differentiate into any cell type following the right molecular and environmental triggers.
In the scientific research, we have different types of human stem cells: we have firstly the pluripotent stem cells coming from embryos (human embryonic stem cells or hESCs) or from reprogrammed adult cells (induced pluripotent stem cells or iPSCs). These are the most used in basic research because they have the most potency to differentiate into any cell type. However these are also the type of stem cells that have the most important concerns in terms of safety as such undifferentiated cells rapidly develop aggressive tumors.
The second type of stem cells that are more in use in clinical research are stem cells derived from placental cord blood or from bone marrow (hematopoietic stem cells or HSCs) or from the stroll fraction of adipose tissue (mesenchymal stem cells or MSCs). These cells have a much less pluripotency as these cells are already engaged into a defined lineage. However this lineage restriction make these cells much less prone for developing tumors and are considered safe.

Now let’s get into the details. In this post, we will not talk about stem cell delivery that bypass the BBB such as intranasal, intrathecal or intracerebroventricular injections. We are discussing here about intra-arterial or intra-veinous injection of stem cells and their delivery across the BBB, in particular the delivery of MSCs across the BBB.

One interesting aspect of the MSCs delivery is their particular attraction to sites of injury, including inflammation sites as mentioned in Liu’s review. What we know is that MSCs can cross in vitro models of the BBB (cell culture models) but yet we have a very limited number of studies that have demonstrated similar approaches ¬†in animal models.
The mechanism by which such MSCs may cross the BBB appears to use similar keys used by leukocytes to infiltrate across the BBB but also may include a localized degradation of the basement membrane (a biological mesh lining blood vessels) to allow their infiltration. However, as mentioned by Liu in his review, early clinical trials have shown mixed if not negative results (see Ankrum J et al., Trends in Molecular Medicine 2009; Karp et al., Cell Stem Cells 2009).

Stem cell-based therapies have a important potential to improve regeneration following injury, but yet claims that such stem cells can cross the BBB remains weak and still needed to be demonstrated. Yet, a recent trend observed in the US and in other countries is the emergence of “stem cell clinics” and the subsequent “stem cell tourism”. Such clinics that operates on protocols not approved by the Food & Drug Administration and not published in peer-reviewed journals (to ensure their efficacy and reproducibility) often laud “miraculous claims”, promising patients to cure their diabetes, knee arthritis if not more serious neurological disorders including stroke, Alzheimer’s disease, autism spectrum disorders, lysosomal storage disorders, cerebral palsy or multiple sclerosis.

The main problem with these clinics is not only their claims are not based on science-based medicine, but also until now stem cell therapies in academic settings (including university hospitals) are still in their infancies (Phase I and IIA clinical trials), mostly focusing on the safety of such therapy before we can consider assessing their efficacy.

Such “therapies” are indeed very costly ($30’000+ price tags) but also the nature of such treatment remains shoddy and unclear. Worse, a recent case report recently published by the New England Journal of Medicine (http://www.nejm.org/doi/full/10.1056/NEJMc1600188) reported the case of the growth of a proliferative lesion on the spinal cord of a patient that underwent such “stem cell therapy” following a stroke injury. Indeed, a recent opinion letters written by Turner and Knoepfler in Cell Stem Cell discuss more deeply more about such recent phenomenon (http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(16)30157-6).

In conclusion, stem cell therapies have shown interesting potentials in pre-clinical models and early stages of stem cell therapies are providing optimistic news about the use of certain stem cells to assess their clinical efficacy in a rigorous and reproducible experimental paradigm, especially for aiming to treat neurological diseases.
However, the delivery of such cells remains an important challenge with a weak literature to support the claim that such cells can cross the BBB once injected via IV route.

In addition, because stem cells have an important potential, a recent rise in stem cell clinics promoting unproven treatments raises questions of safety and concern for¬†vulnerable patients to what appears to me as a rise of a new generation of “snake-oil sellers”.