[Metal/Gothic] The Gathering – Nighttime Birds (20th Anniversary Review)

Yesterday marked the 20th anniversary of the Gathering fourth album “Nighttime Birds”. In my opinion this is the last best album from the album, right before they achieved their  transition into some more acoustic and trip-hop album. It has the vibes and the heaviness of “Mandylion” and yet also explored some new sounds. It is a 9-song album lasting 49 minutes.
If I had to go to a desert album and have to choose three albums of the band, this one will make it into the top 3 with “Always” and “Mandylion” (I guess by now you get the point that I am obsessed with the latter, no?)
We get introduced into it with “On Most Surfaces” directly a continuation of “Mandylion” with a lot of similarities with “Sand and Mercury”, in other words some musical delight. “Confusion” downplays the heaviness but still keep on the melodics we got accustomed to  in their previous album, allowing us to enjoy Anneke’s voice, having this kind of melancholic tone. Thats one of my favorite that’s acting as a tag when someone ask me “how The Gathering sounds like?”.
“The May Song” is already investing more into a more progressive sound, more trip-hop sounds clearly cueing us on how the band was envisioning themselves with their next albums. “The Earth Is My Witness” brings us the “Mandylion” feels, with Anneke’s lyrics and vocals making a prime example of the melodic style of this album: a transition from gothic metal into something more progressive. Another favorite.
“New Moon, Different Days” gives this chilling and relaxing feels, slowly swung by Anneke. Almost feels like a lullaby for a metalhead. “Third Chance” brings on the guitars and the gothic metal sounds, giving this extra kick, whereas “Kevin’s Telescope” brings us as a farewell note from “Mandylion” by its melodics and musical arrangement. “Nighttime Birds” indeed marks the blends of the past (“Mandylion”) and the upcoming future (“If Then Else”) artistic direction of the band, giving this surrealistic track, like a seal on a whole epoch.
Finally, the last title of the album “Shrink” a mostly acoustic (piano solo) with Anneke’s solo is just an amazing song to listen and enjoy. This was a time in which very few female voices were heard on the metal scene and really before the scene got populated by Tarja, Cristina and Sharon. I still remember this song, as it was part of the playlist of their gig in town, somewhere in 2003. Anneke performed it live with the lead singer of Pale Forest (the band that provided the opening act).
This album is in my opinion the epitaph of the band. This is where I felt the most comfortable with the band before moving away to other sounds. Other albums came such as “If Then Else”, “Souvenirs”, “How To Measure A Planet” but none of them had this attraction that I had with the previous ones. By then, the band sailed away into other shores.
If you are not a metalhead by heart and want to get introduced to the band, pick this one. It is a great primer and I would definitely recommend to swim upstream and explore their gothic/doom roots.

[Metal] Lacuna Coil – You Love Me ‘Cause I Hate You (Official Video)

You have to stop what you are doing right now and watch this official video of Lacuna Coil “You Love Me ‘Cause I Hate You” from their album “Delirium”. It’s an amazing videoclip formatted as a short giallo.


Rarely a videoclip from a metal band looked so sleek and carefully crafted, with an amazing photography (it feels like straight from an Dario Argento movieset), a good acting from the band members and an interesting story plot to follow.

 

[Sciences/BBB] Endothelial TLR4 and the microbiome drive cerebral cavernous malformations (Tang et al., Nature 2017)

You may have heard about this study that showed how your gut bacteria were responsible for stroke. Of course headline news always love to stretch scientific findings as much as I use to stretch my Stretch Armstrong when I was a kid. However, the paper cited was indeed published in Nature and can be found here:
https://www.nature.com/nature/journal/vaop/ncurrent/full/nature22075.html

It is a very interesting paper to read, because a lot of it sounds like a serendipity and lucky strikes. This paper investigated changes in two mouse models of cerebral cavernoma (Ccms). Ccms are a particular type of hemorrhagic stroke because they are mostly genetics (there are three Ccm genes described, in this study they focused on Krit1 and Ccm2) and most of the time go unnoticed. Mutations in those genes result in some alterations in brain microvessels, making some tiny anatomical abnormalities resulting in a higher susceptibility in some of these micro vessels to spontaneously burst and bleed.

The authors of this study have been developing Cre/Lox mice colonies for Ccm2 and Krit1 to better understand the pathology of this disease. The advantage of Cre/Lox is you can knockout a gene in a specific place at a specific time, just by injecting or providing a molecule (usually tamoxifen) that will induce it.

They have been breeding mice that were deficient in Ccm2 or Krit1 and were as expected developing brain micro bleeds (usually around their first two weeks of postnatal age). Following some changes in the animal facility, they observed that a small fraction of their mice colonies suddenly became resistant to cerebral micro bleeds: they still carried the mutations but they fail to develop these microbleeds. Therefore some non-genetic factors were influencing this resistance pattern.
Things became even more interesting as they found that among some of these resistant mice, some developed again the microbleeds within a same littler. The only difference between those developing the microbleeds and those which did not were apparently related to the intraperitoneal (i.p.) injection of tamoxifen. Have the authors provided the tamoxifen through the drinking water, that would have ended the story here.
The authors indeed found that those who reversed their phenotype from resistant to susceptible developed a bacterial infection at the site of the i.p. injection suggesting that such micro bleed was driven by some bacterial factor. They showed that similar results were obtained if they injected LPS (a common Gram-negative antigen) to these mice.

They identified two receptors known to play a role in cellular response to pathogens (we refer such signaling pathways as Pathogen Associated Molecular Patterns or PAMPs): TLR4 (toll-like receptor 4) and CD14 (TLR4 co-receptor). By knocking down these receptors in their Ccm-resistant animals, they were capable to block such bacteria-induced response. The possible interactions of Gram-negative bacteria with these two receptors at the blood-brain barrier maybe enough to trigger the cerebral micro bleeds.

What is also interesting is that mutations in these two genes (some single nucleotide polymorphism or SNP) in patients known to have an history of Ccm also resulted in a higher probability to have brain microbleeds.

I will not spoil the rest of the story but it confirms the presence of a brain-gut axis in Ccm, suggesting the possible effect of the gut microbiota as a risk factor to increased microbleeds in Ccm patients. Let it be clear, these bacteria WILL NOT induce Ccm in normal invididuals. It increase the risk of bleeds in patients already at risk of Ccm.

Another limitation is that in vitro data to confirm the presence of TLR4/CD14 at the BBB and fails to explain how these receptors are triggered by the gut microbiota. The authors suggested a bacteremia (circulating bacteria from gut to the brain via bloodstream) but I remain skeptical about it.

Nevertheless it is a very good paper that worth being read.

 

[Music/Punk] The Offspring’s Dexter Holland Receives Ph.D In Molecular Biology – Blabbermouth.net

Ok thats certainly gonna make me younger (or any GenXer either) but in other news…..Dexter Holland (The Offspring) got his PhD in molecular biology from USC. Congrats Dr. Holland and welcome to the club, glad to count you as a peer 🙂

Source: http://www.blabbermouth.net/news/the-offsprings-dexter-holland-receives-ph-d-in-molecular-biology/

[Science/Neurosciences] Mole rats running on…..fructose!

You may have heard about this paper from Park TJ and colleagues (Park TJ et al., Science 2017) on how mole rats were showing extreme compliance to anoxic (0% oxygen) level, no? It made the news these last couple of weeks and finally was able to put my hand on. You can access to it here (need to have a Science subscription though) but I read it and it is really interesting for many reasons, especially because I try to think how can we translate it as a therapeutical strategies for hypoxemic pre-terms babies or even as a stroke fighting-drug.

First, mole rats. Oh mole rats! Not the prettiest mammals out there. They are naked, they have long teeth and look all wrinkled. But they are underground dwelling animals like moles. Underneath, oxygenation is scarce and these animals have developed formidable adaption to hypoxia. We as humans can barely survive 8% oxygen (thats about the Mount Everest). At 6% oxygen (thats what would happen if a aircraft cabin undergo a depressurization), you die within minutes.

In this experiment, they went fairly extreme, they put the animals into anoxia (0% O2) and looked how long the animals would survive. They used a common mouse strain as a control. Mice rapidly died at 100% rate at 5% O2 and died twice faster (based on the number of breaths) at 0% O2. In opposite, mole rats went 30 times longer than mice and still were doing fine (0% deaths). Were mice died within 60 seconds, molerats died over 1000 seconds of anoxia. One possible reason is their ability of their heart to beat much longer than mice.

Now what is interesting is how the authors came to fructose. Mammalian cells run on glucose through the following biochemical pathway (see below):

glycolysis-10-steps-explained-steps-by-steps-with-diagram

I will spare you the Krebs cycle but this is what every since healthcare and life scientist have to learn. Glucose is broken down into many intermediates and at the end becomes pyruvate. From pyruvate, you can enter the Krebs Cycle and produce a significant amount of ATP (the fuel cell of every living organism) needed to provide energy for any biological process. Krebs cycle is very good at it and provides an ATP yield of 36ATP/glucose consumed. However, the Krebs cycle stall under hypoxia and forces the cell to adapt. In particular, it needs to regenerate NAD+ (from NADH) in order to keep the system flowing and producing energy. One way mammalian cells solved it is by converting pyruvate into lactate. Thats allow cells to produce some energy (2ATP/glucose) and regenerate its NAD+. However lactate has tendency to accumulate and develop adverse effect (the famous muscle cramps any runners have experienced).

Fructose is not much different from glucose, it has the same composition but just a little difference in the molecular structure.  We get fructose from our daily diet made of fruits and vegetables, but also from refined sugar (sucrose or HFCS, same deal).

17693

Now fructose can bypass and feed the glycolysis at different steps:
fructolysis-pic-ca333

Fructose can produce glyceraldehyde-3-P (GA3P) and dihydroxyacetone-P (DHAP) and enter the rest of the glycolysis. Now like glucose, fructose needs a transporter to enter inside the cells. Glucose has a myriad of glucose transporters (GLUTs and SGLTs) that can provide glucose inside the cells. But not fructose. These transporters have very poor affinity for fructose. In that case, fructose has one transporter called GLUT5 that prefers fructose over glucose.
Now this is where it becomes interesting, mole rats show much higher levels of fructose than mice during anoxia in many organs and in blood. Now the interesting fact is the high prevalence of it as fructose-1-P in the brain, only this form. How it goes in? I don’t know but mole rat brains have a higher GLUT5 expression than mice. Where this transporter is expressed? I don’t know either but it would interesting to look at this transporter at the BBB.

What is interesting is the difference in how mole rats  brain and heart differ from mice in terms of fructose activity. When administered fructose over glucose, mole rats organs know to switch between the two sugars to gets its energy. In the other hand, mice organs fail to switch and result in decrease their activity.

Now the question I have (since I am working on glucose transport across the BBB and its impact in kids suffering from GLUT1 deficiency) is: does human express GLUT5? If yes, which brain cells express it and if these cells can adopt fructose as a source of energy?

[Metal/Powermetal] Seven Kingdoms – Decennium (90%)

Getting my hand on Seven Kingdoms latest album “Decennium” was kind of the wanderlust on betting on a band you don’t know much about and give a small helping hand with crowdfunding. The album was teasing me for the last few months (to be honest since January) and what I can tell it worth all that wait.
Seven Kingdoms is a FF Power Metal band from Florida, USA. Little I knew that once I pressed the “play” button on my iPod Classic that it would take me into a full-speed roller coaster through 14 tracks and lasting 72 minutes.
It is fast-paced, heavy riffs, fully pumped on energy making you to want to ride over a battle cat (armed with eye-lasers of course) and slash some demons and dragons with a legendary Bat’leth. But lets get back to the essential and go through the album.
It is a 72 minutes of damn good of power metal fueled by lyrics heavily inspired by heroic fantasy.
It starts with “Stargazer”, an engaging power metal melodics, transitioning into “Undying” (one of my favorite) and “In The Walls” into a perfect suite, giving little space to breath into your legendary battle. “The Tale Of Deathface Ginny” brings into  some of the best time of heavy metal from the 80s with its storytelling. “Castles in the Snow” continues into the heroic-fantasy, a good one but kind of feel a bit setback. Then comes one of the piece de resistance. “Kingslayer”, bringing the cannons of Navaronne, the Stalin’s Organ. That stuff that makes you get up from your chair, take a sword and rush to the battle.

You think you are done? Wait the call for the battle is still going one with “The Faceless Hero”. Things starts slowly to settle down with “Never-ending” bringing on some good heavy metal vibe but kind of setting the fervor on the back burner, just for this song.  “Hollow” brings you back in the heart of action and finishes with “Awakened from Nothing”, slowing on the pace but keeping on the powerful melodic ballads.

The rest of the album provides an alternative version of “In The Walls” that I found have this small extra-punch and “Undying” bringing you an extra-dose of adrenaline rush. Finally, we have  a remaster of “The Bloody Meadow” and “Stormborn”. I don’t know these titles as they maybe from previous releases but enough to make me dig in deeper into the troll cave and discover the previous albums.

As they are releasing the album, so are they also starting their US tour, if you have a chance to, check them out, they surely blow on stage.
My final word? Buy this album! This is my album of the month without hesitation. Take your cloak and run get this album.

[Metal/Powermetal] Seven Kingdoms – Kingslayer (Official Video)

The US power metal band Seven Kingdoms new album “Decennium” is due to release tomorrow ahead of their North American tour. To mark the release of their album, they released a official video for “Kingslayer”, one track of their album. Well, what I can say: “ca poutre pas mal!” and eager to review that album.
Want to see and hear what it sounds like? Listen below: