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thundara  ·  link  ·  parent  ·  post: Pubski: December 28, 2016

"Hopelash"? Was Cambridge the same for you? My friend who moved to Ithaca for grad school hated it by the first winter I saw him back home.

thundara  ·  link  ·  parent  ·  post: Pubski: December 21, 2016

Got discharged from PT, feels good to not be in pain for two hours a day. Turns out foam rolling your IT is a thing and can alleviate 80% of a half-year's worth of pain within half a week. I'm a little annoyed that the orthopedic physician I saw never mentioned it, but they get a by for being a student trainee I guess...

Been going through a series of drug books, Acid Test, Methland, and now Dreamland. All have been fascinating, but damn if the history of almost every drug hasn't been plagued with social strife. Shit's fucked.

Headed home now, spent the last three weeks holed up in lab trying to get datas. It went okay... culminating in an experiment Monday that showed not just a negative effect, but an inverse effect from what I was expecting. More controls are needed to actually figure out wtf's going on, since cell culture can be pretty easy to mislead when the conditions across different cell lines, like the population density half a week back, vary in subtle ways.

In any case, flying back to California and trying not to think about it for a couple weeks. Time to visit Berkeley + SF and make the rounds of all the friends who I haven't seen in a year.

For sure, I've just seen a couple talks / papers now that describe some (non-cytokine) receptor as being the thing that polarizes cells in one direction or the other and I find it somewhat garbage science, at least in the Alzheimer's field. Especially since there does't seem to be any real consensus on how they're defined.

The microglia you're talking about in this context are with regards to young blood treatments?

Yep yep, realized that after replying and ninja edited.

    I was referring to the microglia activation, but you def answered my question and more.

Microglial "activation" is sort of a misnomer in my opinion. But basically they show a state switch. Whether this is a response to less inflammatory factors secreted by neurons, improved blood flow to the area, magic electrical effects, decrease plaque production, etc is not well understood. They characterize in the paper that there is a state change (morphological, RNA expression), but not how / why.

There's some thought that microglia have 2+ states, a "pro-inflammatory" / "M1" state and an "neuroregenerative" / "M2" state, but in my opinion that's probably a baloney pigeonhole of what's actually going on.

    Wild shit, and hopefully there is some clinical relevance to it.

Indeed, though what'll probably not be mentioned in the press releases is "Extended Data Figure 5: A 40 Hz light flicker does not affect Aβ levels in hippocampus or barrel cortex." ... There is still a lot of work to be done.


Yes, high potential for either breakthrough or years of pseudoscience to come out of this. Much excitement. Wow! They're looking at others models now, but I'm probably not supposed to share that until it's at least being presented publicly.

    Is the paper out? that is kind of a wild result. What was the optogenetics targeting? I'm assuming the neurons responsible for the gamma rhythm, and the microglia activation was unintentional, and that's why the decided to attempt the effect with an external light source?

Yep. Optogenetics targetted parvalbumin interneuron and did not show an effect in excitatory neurons (PV-Cre vs. αCamKII-Cre in fig 1) or at non-40 Hz pulses. Why the microglia get activated is anyone's guess / for follow-up work to determine.

The light source was used after the optogenetics experiments showed an effect because, as one prof put it: "We're more than a decade away from optogenetic therapies in humans". Note they switch the explanation from "hippocampus" to "visual cortex" when they explain that in the video though. In theory, any signal that gets a stimulus at 40 Hz to the hippocampus should be effective, but not all circuits from the eyes / ears / mouth / fingers / nose are as direct.

    Had no one seen that before? Optogenetics and EEG stuff was never on my plate, so I have only a cursory understanding.

The closest is deep brain stimulation for Parkinson's, which sort of works okay but isn't very well understood. This is the first (mouse) therapy of the sort, and the first that I know of that links dysregulated signaling to stimulation to targeted activation of certain cells in a certain region to actual non-invasive therapy.

thundara  ·  link  ·  parent  ·  post: Pubski: December 7, 2016
thundara  ·  link  ·  parent  ·  post: Pubski: December 7, 2016

Long day yesterday. Fifteen hours straight of lab work, but finally replicated my results from last year in another model of Alzheimer's. Pretty decent for tissue that was just lying in the freezer ready to be thrown out. When I look at my lab journal, I'm reminded of people's comments on modern art. Without context, it's a bunch of scribbles, but to me, it's dancing and excitement at 11pm after everyone else has gone home.

Some heavy hitting research should be hitting the journals / university PR machines later today. My collaborator's lab found a novel treatment that appears to heavily clear amyloid. They've had to be very careful about their wording and the scope of their claims, but doubtless it will either catapult the field forward or breed the next decade of pseudoscience and alt-medicine treaments. The procedure is super simple though, and they had an exhibit set up around the Christmas tree on Sunday during the lab's holiday party. It should be linkable by this afternoon.

Should be booking travel info for my first big science conference this week. Will be going to Vienna!

I'm told I shouldn't present my own work though as it's too early / too much potential to be scooped. Hopefully I can turn that assessment around between now and then.

thundara  ·  link  ·  parent  ·  post: Pubski: November 30, 2016

Yep, but only on certain actions (i.e. opening up the app drawer). I'm not sure how much a fan I'd be of my phone feeling like a vibrator on the day to day though. I've found I prefer just not using it as much when I can spare the self control.

thundara  ·  link  ·  parent  ·  post: Pubski: November 30, 2016

Never tried an ergonomic + mechanical keyboard so your mileage may vary. I will say that I feel the same thing on styluses pressing on hard screens, made ~10x worse with fingers on hard screens, fingers on touchpads, and fingers on low depth keyboards (a la mac keyboards). Something about the backpressure just makes the tendons inflamed lightning fast. Vertical mice did wonders for me though.

Let me know if you find a better solution, keyboards and mice are mostly a solved problem for me, but hard glass screens and stiff buttons are still my Achilles heel so to speak.

thundara  ·  link  ·  parent  ·  post: Pubski: November 30, 2016

Echoing kleinbl00, had quiet a few tendon injuries recently. Been two months since my most recent knee tendon injury and I'm just now able to do the 30 minute walk to work without an inflamed ball on my knee.

Wrists are especially annoying because you can't exactly not use them if that's your job. I went heavy on the ergonomics after damaging mine a few summers ago. Wavy keyboard, slanted / vertical mouses galor, and a stylus for the phone. Plus re-organizing my desks to avoid any edges pressing on my forearms.

I'd be lying if I said the pain was completely gone even a year after the ergonomic upgrades. No laptop at the coffee shop. But the wrists are functional / able to work full days at the computer again.

thundara  ·  link  ·  parent  ·  post: Pubski: November 9, 2016

He also started the DEA. But I'm willing to accept that a president can have pros and cons despite being universally hated by liberals in the present.

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