THEME
Irene Adler

itsspooderman:

When you finish a tv sho, that you have invested months of your personal time to carries and indescribable darkness that hangs on your shoulders for days.

50shadesofwhy:

E.L. loves her ‘quickly’ and ‘slowly’. How about some more evocative verbs instead?

50shadesofwhy:

E.L. loves her ‘quickly’ and ‘slowly’. How about some more evocative verbs instead?

madhatter-in-training:

PSAT: what religion are you
*looks at list, sees 50 shades of Cristian*

neurosciencestuff:

Novel culture system replicates course of Alzheimer’s disease, confirms amyloid hypothesis
An innovative laboratory culture system has succeeded, for the first time, in reproducing the full course of events underlying the development of Alzheimer’s disease. Using the system they developed, investigators from the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease. They also identify the essential role in that process of an enzyme, inhibition of which could be a therapeutic target.
"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events – the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death," says Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research Unit and co-senior author of the report receiving advance online publication in Nature. “One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call ‘Alzheimer’s-in-a-dish,’ we’ve been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death.”
While the mouse models of Alzheimer’s disease that express the gene variants causing the inherited early-onset form of the disease do develop amyloid plaques in their brains and memory deficits, the neurofibrillary tangles that cause most of the damage do not appear. Other models succeed in producing tangles but not plaques. Cultured neurons from human patients with Alzheimer’s exhibit elevated levels of the toxic form of amyloid found in plaques and the abnormal version of the tau protein that makes up tangles, but not actual plaques and tangles.
Genetics and Aging Research Unit investigator Doo Yeon Kim, PhD, co-senior author of the Nature paper, realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the MGH team used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes – the amyloid precursor protein and presenilin 1 – known to underlie early-onset familial Alzheimer’s Disease (FAD). Both of those genes were co-discovered in Tanzi’s laboratory.
After growing for six weeks, the FAD-variant cells were found to have significant increases in both the typical form of beta-amyloid and the toxic form associated with Alzheimer’s. The variant cells also contained the neurofibrillary tangles that choke the inside of nerve cells causing cell death. Blocking steps known to be essential for the formation of amyloid plaques also prevented the formation of the tangles, confirming amyloid’s role in initiating the process. The version of tau found in tangles is characterized by the presence of excess phosphate molecules, and when the team investigated possible ways of blocking tau production, they found that inhibiting the action of an enzyme called GSK3-beta – known to phosphorylate tau in human neurons – prevented the formation of tau aggregates and tangles even in the presence of abundant beta-amyloid and amyloid plaques
"This new system – which can be adapted to other neurodegenerative disorders – should revolutionize drug discovery in terms of speed, costs and physiologic relevance to disease," says Tanzi. "Testing drugs in mouse models that typically have brain deposits of either plaques or tangles, but not both, takes more than a year and is very costly. With our three-dimensional model that recapitulates both plaques and tangles, we now can screen hundreds of thousands of drugs in a matter of months without using animals in a system that is considerably more relevant to the events occurring in the brains of Alzheimer’s patients."

neurosciencestuff:

Novel culture system replicates course of Alzheimer’s disease, confirms amyloid hypothesis

An innovative laboratory culture system has succeeded, for the first time, in reproducing the full course of events underlying the development of Alzheimer’s disease. Using the system they developed, investigators from the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease. They also identify the essential role in that process of an enzyme, inhibition of which could be a therapeutic target.

"Originally put forth in the mid-1980s, the amyloid hypothesis maintained that beta-amyloid deposits in the brain set off all subsequent events – the neurofibrillary tangles that choke the insides of neurons, neuronal cell death, and inflammation leading to a vicious cycle of massive cell death," says Rudolph Tanzi, PhD, director of the MGH Genetics and Aging Research Unit and co-senior author of the report receiving advance online publication in Nature. “One of the biggest questions since then has been whether beta-amyloid actually triggers the formation of the tangles that kill neurons. In this new system that we call ‘Alzheimer’s-in-a-dish,’ we’ve been able to show for the first time that amyloid deposition is sufficient to lead to tangles and subsequent cell death.”

While the mouse models of Alzheimer’s disease that express the gene variants causing the inherited early-onset form of the disease do develop amyloid plaques in their brains and memory deficits, the neurofibrillary tangles that cause most of the damage do not appear. Other models succeed in producing tangles but not plaques. Cultured neurons from human patients with Alzheimer’s exhibit elevated levels of the toxic form of amyloid found in plaques and the abnormal version of the tau protein that makes up tangles, but not actual plaques and tangles.

Genetics and Aging Research Unit investigator Doo Yeon Kim, PhD, co-senior author of the Nature paper, realized that the liquid two-dimensional systems usually used to grow cultured cells poorly represent the gelatinous three-dimensional environment within the brain. Instead the MGH team used a gel-based, three-dimensional culture system to grow human neural stem cells that carried variants in two genes – the amyloid precursor protein and presenilin 1 – known to underlie early-onset familial Alzheimer’s Disease (FAD). Both of those genes were co-discovered in Tanzi’s laboratory.

After growing for six weeks, the FAD-variant cells were found to have significant increases in both the typical form of beta-amyloid and the toxic form associated with Alzheimer’s. The variant cells also contained the neurofibrillary tangles that choke the inside of nerve cells causing cell death. Blocking steps known to be essential for the formation of amyloid plaques also prevented the formation of the tangles, confirming amyloid’s role in initiating the process. The version of tau found in tangles is characterized by the presence of excess phosphate molecules, and when the team investigated possible ways of blocking tau production, they found that inhibiting the action of an enzyme called GSK3-beta – known to phosphorylate tau in human neurons – prevented the formation of tau aggregates and tangles even in the presence of abundant beta-amyloid and amyloid plaques

"This new system – which can be adapted to other neurodegenerative disorders – should revolutionize drug discovery in terms of speed, costs and physiologic relevance to disease," says Tanzi. "Testing drugs in mouse models that typically have brain deposits of either plaques or tangles, but not both, takes more than a year and is very costly. With our three-dimensional model that recapitulates both plaques and tangles, we now can screen hundreds of thousands of drugs in a matter of months without using animals in a system that is considerably more relevant to the events occurring in the brains of Alzheimer’s patients."

feaqu:

ask any teenager what type of music they listen to and 99 percent of the time they’ll say ‘anything but country’

How to finish that last minute assignment

elovers:

leetakeuchi:

imageimageimageimageimage

I can not count the number of times this trick has saved my ass.

durnesque-esque:

moonblossom:

steverogershelmethair:

the-goddamazon:

sugaryleopard:

aculturedpearl:

Louboutins are redefining the “nude” pump— now available in five shades.  Great initiative!

Thank you Christian Louboutin. 

This is so important.

Yes, thank you for making more shoes literally none of us will ever be able to afford.

Fashion trickles down though. When a high-end designer like Christian Louboutin acknowledges that there should be variety in “nude” pumps, it will invariably be copied by cheaper and more accessible brands. This is a huge, positive thing.

durnesque-esque:

moonblossom:

steverogershelmethair:

the-goddamazon:

sugaryleopard:

aculturedpearl:

Louboutins are redefining the “nude” pump— now available in five shades.  Great initiative!

Thank you Christian Louboutin. 

This is so important.

Yes, thank you for making more shoes literally none of us will ever be able to afford.

Fashion trickles down though. When a high-end designer like Christian Louboutin acknowledges that there should be variety in “nude” pumps, it will invariably be copied by cheaper and more accessible brands. This is a huge, positive thing.

mrchrismad:

beaumarbre:

random-homestuck-things:

bishounen-jake-english:

jackadiddlediddle:

bishounen-jake-english:

FOR THOSE OF YOU WHO DO NOT KNOW

THIS IS A TRUMPET

image

THIS IS A TROMBONE

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THIS IS A TUBA

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AND THIS IS A FRENCH HORN

image

THANK YOU FOR YOUR TIME

You mean trumpet

image

Slidey Trumpet

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Big ass trumpet

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Drunk Trumpet

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I’M GONNA PUNCH YOU

My sides

AT LEAST YOUR INSTRUMENTS LOOK DIFFERENT 

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those are some fancy guitars

hm

hm

thestreethippie:

TheStreetHippie.tumblr.com

thestreethippie:

TheStreetHippie.tumblr.com

Way to go yahoo people - little mistake i think

Way to go yahoo people - little mistake i think

accioheadcanons:

lmaoalien:

plot twist: JK rowling writes a series on voldemorts point of view

"i looked in the mirror and cried. i look like an egg"

So someone actually tried to sell strongsville high school

…?

btw since AP scores are now online

tubachan27:

everyone repeat after me:

  • I am not my test scores
  • My test scores do not show what I learned
  • A bad score is not the end of the world
  • this education system is bullshit and your intelligence should not be measured on how well you take a 3 hour test

if you took an AP test then good job!! really they’re scary tests and it can take a lot of courage to even sign up for one

okay now have a nice day

rockmebradfordbadboy:

*runs to California to check AP scores*