The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.
i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich
how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"
If you buy a AAA game, you are supporting capitalism.
im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin
but I'm totes down with abolishing capitalism where do I sign
I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc
well those properties have been around a long time at least
this seemed to spring up as soon as overwatch existed
it confused me
A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.
"""unrelated"""
there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
definitely a subtle visual storytelling
The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.
They do talk about this a little, in a purely speculative manner, admittedly.
Here, we have not addressed how P. gingivalis infection might relate to apolipoprotein E4 (APOE4), the greatest genetic risk factor for sporadic AD (77). Studies in mice deficient in APOE proteins demonstrated an impaired innate immune response to the bacterial pathogen Listeria monocytogenes (78), implicating APOE in normal innate immune function in vivo. It was recently reported that human APOE is a target of gingipain proteolysis, and the authors suggested that this mechanism could generate neurotoxic APOE fragments in the AD brain (79). We propose that APOE4 may be more susceptible to gingipain cleavage than APOE3 or APOE2 due to the presence of more arginine residues, resulting in decreased innate immune function and the generation of neurotoxic fragments (80). The distinct role of APOE in relation to P. gingivalis infection and targeting by gingipains remains a focus of future studies.
I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc
well those properties have been around a long time at least
this seemed to spring up as soon as overwatch existed
it confused me
A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.
"""unrelated"""
there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
definitely a subtle visual storytelling
Pokemon but it is a game designed to be somewhat challenging for adults rather than being designed to be easily beatable by young children.
honestly this is pokemon, but with no motherfucking hyper potions
as a kid, the one and only approach to a fight was grind the fuck out of those pokeymans
as an adult, I can't be arsed to do that, so now I'm using strategies and expending every pokemon I have to reduce stats a little and barely eke out a chance at victory and I have tons of fun in the battles because they're hard
and then the gym leader goes haha nope hyper potion
What pokemon game would this be?
The modern ones require absolutely none of that.
the latter GBA ones, last time
I also barely pay attention to having the right types or the right pokemon, just have a bunch I like and work with that
Ahh. Yea I mean I always just pick the pokemon I think are the cutest/coolest as well. I don't remember the GBA ones at this point but on the DS ones even that is enough to just steamroll on through.
Heck people playing nuzlocke rules on those ones can even steamroll through all the way to the elite 4 (where things do tend to actually get rough).
i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich
how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"
If you buy a AAA game, you are supporting capitalism.
im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin
but I'm totes down with abolishing capitalism where do I sign
Except for BMX XXX on the Gamecube, Hentai games are all indies.
The periodontal strep hypothesis is very enticing in that it doesn't involve tau or abeta at all which would be novel. There is 0 mechanism for how the strep bacteria infiltrate the brain and I suspect that it will turn out that general cerebrovascular breakdown that is 100% concomitant with alzheimer's progression will be responsible for the post-mortem correlation and it won't be causative. I could be pleasantly surprised though! But also a periodontal mechanism doesn't explain familial Alzheimer's in the slightest. But since AD and PD and ALS and FTLD are all on a spectrum, it could help explain sporadic AD to some degree since it is obvious that there could just be environmental hits regardless of denovo mutations in sporadic patients.
They do talk about this a little, in a purely speculative manner, admittedly.
Here, we have not addressed how P. gingivalis infection might relate to apolipoprotein E4 (APOE4), the greatest genetic risk factor for sporadic AD (77). Studies in mice deficient in APOE proteins demonstrated an impaired innate immune response to the bacterial pathogen Listeria monocytogenes (78), implicating APOE in normal innate immune function in vivo. It was recently reported that human APOE is a target of gingipain proteolysis, and the authors suggested that this mechanism could generate neurotoxic APOE fragments in the AD brain (79). We propose that APOE4 may be more susceptible to gingipain cleavage than APOE3 or APOE2 due to the presence of more arginine residues, resulting in decreased innate immune function and the generation of neurotoxic fragments (80). The distinct role of APOE in relation to P. gingivalis infection and targeting by gingipains remains a focus of future studies.
APOE4 is the only known SNP associated with AD but familial AD is mutations to the precursor of A-beta, APP. I've read the paper several times.
0
The Escape Goatincorrigible ruminantthey/themRegistered Userregular
I don't see much difference between fans of Overwatch and fans of Zelda/Smash/etc
well those properties have been around a long time at least
this seemed to spring up as soon as overwatch existed
it confused me
A big part of this was just how well designed and animated all the characters are. For reasons COMPLETELY unrelated to the discussion further up this page I immediately fell in love with both Roadhog and Junkrat because you could play them for ten minutes and have a very strong idea of who they are as characters; they did a fantastic job with subtle visual storytelling. And that's a very good way to inspire fan artists to pick up and run with those characters.
"""unrelated"""
there is one on GIS where junkrat is giving roadhog the old 1-2 with his peg leg and he's using vegemite as lube
definitely a subtle visual storytelling
And it still invokes tau/Abeta as the direct cause of neurodegeneration, it just provides a trigger to explain why they might start accumulating other than time/genetics/bad luck.
I love dragon's dogma, I love my derpy pawn who comments about the existence of harpies while being carried off into the clouds and dropped, managing to utter "It seems all roads lead to gran soren master" before their brains paint the rocks
override367 on
+2
TL DRNot at all confident in his reflexive opinions of thingsRegistered Userregular
I'm really concerned and mad at Pinecone's work; it's whiteout conditions outside and everyone knew there'd be a storm today starting around noon, and their job decided to still have people come in and work until 2:30!!! >:((((
Our car sucks for snow driving and our street hasn't been plowed at all and it's already snowed almost two inches and Pinecone's gotta come home in this
@Blameless Cleric I just got dismissed myself and if it's half as bad as it is here holy shit anyone without 4wd is screwed.
not a doctor, not a lawyer, examples I use may not be fully researched so don't take out of context plz, don't @ me
Sorry its been my field on and off for 10 years. I am basically kept up at night by what mechanisms actually and legitimately drive neurodegeneration. You are totally right that it still involves tau and a-beta.
+1
The Escape Goatincorrigible ruminantthey/themRegistered Userregular
Pokemon but it is a game designed to be somewhat challenging for adults rather than being designed to be easily beatable by young children.
honestly this is pokemon, but with no motherfucking hyper potions
as a kid, the one and only approach to a fight was grind the fuck out of those pokeymans
as an adult, I can't be arsed to do that, so now I'm using strategies and expending every pokemon I have to reduce stats a little and barely eke out a chance at victory and I have tons of fun in the battles because they're hard
and then the gym leader goes haha nope hyper potion
What pokemon game would this be?
The modern ones require absolutely none of that.
the latter GBA ones, last time
I also barely pay attention to having the right types or the right pokemon, just have a bunch I like and work with that
Ahh. Yea I mean I always just pick the pokemon I think are the cutest/coolest as well. I don't remember the GBA ones at this point but on the DS ones even that is enough to just steamroll on through.
Heck people playing nuzlocke rules on those ones can even steamroll through all the way to the elite 4 (where things do tend to actually get rough).
If your favorites happen to have decent type coverage you're good. I had a friend try to go through Moon with a six water type team (bc Alola is full of awesome water types) and that was rough. But that's a very specific hoop to jump through to make the game anymore more than "pretty easy".
i hadnt actually watched sterling's video but activision's CEO is gross all these CEOs are gross eat the rich
how can any intelligent sane animal person have a business plan of "Make exponentially more money every year or declare utter disaster"
If you buy a AAA game, you are supporting capitalism.
im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin
but I'm totes down with abolishing capitalism where do I sign
Except for BMX XXX on the Gamecube, Hentai games are all indies.
I would love a party-based action game where all your companions are Dragon's Dogma style learning AIs, but they're explicitly barely living homunculi and you have to train them to get past any difficult fights
Sorry its been my field on and off for 10 years. I am basically kept up at night by what mechanisms actually and legitimately drive neurodegeneration. You are totally right that it still involves tau and a-beta.
Posts
im pretty sure im supporting capitalism when I buy a hentai game about anime girls as different houseplants or whatever as well, but I doubt their developer is upset when their games only have a 1000% profit margin
but I'm totes down with abolishing capitalism where do I sign
definitely a subtle visual storytelling
They do talk about this a little, in a purely speculative manner, admittedly.
i asked him do you speak-a my language
"wolves hunt in packs, arisen"
holy shit they do hunt in packs
Ahh. Yea I mean I always just pick the pokemon I think are the cutest/coolest as well. I don't remember the GBA ones at this point but on the DS ones even that is enough to just steamroll on through.
Heck people playing nuzlocke rules on those ones can even steamroll through all the way to the elite 4 (where things do tend to actually get rough).
really any three letter acronym that starts with a C can go
Except for BMX XXX on the Gamecube, Hentai games are all indies.
https://www.penny-arcade.com/comic/2002/10/18/now-you-know
just watch this video ya perverts
https://youtu.be/7Dga-UqdBR8
TIS A GOBLIN MASTER!
Except CBD
Bad boyz
Tell the higher-ups this one needs to be updated for streamers in 2019.
@Blameless Cleric I just got dismissed myself and if it's half as bad as it is here holy shit anyone without 4wd is screwed.
the "no true scotch man" fallacy.
If your favorites happen to have decent type coverage you're good. I had a friend try to go through Moon with a six water type team (bc Alola is full of awesome water types) and that was rough. But that's a very specific hoop to jump through to make the game anymore more than "pretty easy".
It's still capitalism when you're buying it from a small company
thats basically the expansion right?
I started reading the patents, then I remembered how much reading patents sucks.
All good
:bro:
you can make it grindy
I liked 12 because it was basically Final Fantasy Star Wars with some fairly heavy inspiration from KOTOR. First FF I enjoyed post 8.
edit: and honestly the last one I enjoyed at all.
Let's play Mario Kart or something...
also i love the galaxy brain turn the last act of the story takes
No one mentions FF13 or FF15 here at all anymore. They must have been duds with no staying power.
12 is v good and if they hadn't completely flubbed the last third and finished out Vayne's character arc properly, it could've been the best.
Switch - SW-7373-3669-3011
Fuck Joe Manchin
FF15 is on my list