In two newly published papers, a scientific team at Case Western
Reserve University School of Medicine reports on the discovery and
implementation of a new, more efficient method for generating an
important brain stem cell in the laboratory. The findings pave the way
for greater understanding of the underlying mechanisms of neurological
disorders of myelin and ultimately, possible new treatment and
prevention options. The studies were published in the September issues
of Nature Communications and Stem Cell Reports.
“Making these specialized brain stem cells on a large scale at high
purity from pluripotent stem cells gives us a powerful tool to study
previously inaccessible normal and diseased tissues in the central
nervous system,” said the senior author of the two papers, Paul Tesar,
PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative
Therapeutics and associate professor of genetics and genome sciences at
Case Western Reserve University School of Medicine. “We applied our
technology to genetic models of myelin disease, which resulted in the
discovery of a chemical compound that helps diseased myelin-producing
cells to survive.”
Myelin, a fatty substance produced by cells called oligodendrocytes,
coats nerve fibers and enables electrical signaling in the brain and
facilitates normal neurological function. Induced pluripotent stem
cells are master cells that can potentially produce any cell the body
needs. They are generated directly from existing adult cells. Embryonic
stem cells are also pluripotent.
As reported in Nature Communications,
first author Angela Lager, PhD, and colleagues developed a new
methodology to generate large quantities of oligodendrocytes and their
progenitor cells— known as oligodendrocyte progenitor cells or OPCs—from
mouse embryonic stem cells and induced pluripotent stem cells. Many
genes and cellular processes have been associated with oligodendrocyte
dysfunction, but scientists have typically needed to make mutant mice to
investigate these processes, often involving expensive, multi-year
studies to examine a single aspect of this biology. To address this
problem, the Case Western Reserve team developed a rapid and highly
efficient method for generating OPCs and oligodendrocytes from
pluripotent stem cells from any genetic background—providing new access
to these relatively inaccessible brain cells in healthy and diseased
In Stem Cell Reports,
first author Matthew Elitt, PhD, and colleagues leveraged this OPC
generation technology to provide new insights and therapeutic strategies
for a fatal genetic disorder of myelin, Pelizaeus Merzbacher disease
(PMD). The team found that there was an unexpectedly early critical
phase in PMD-affected cells characterized by endoplasmic reticulum
stress and cell death as OPCs exit their progenitor state. The
endoplasmic reticulum is the part of the cell involved in the processing
of protein. In PMD, which almost exclusively affects male children,
oligodendrocytes are lost and myelin is not properly formed in the brain
and spinal cord. Due to their diseased myelin, children with PMD
exhibit often-debilitating problems of coordination, motor skills,
verbal expression, and learning. Due to the disease’s severity, patients
typically die before adulthood.
To overcome this early cell death in PMD cells, the team screened
thousands of drug-like compounds and found that one, known as Ro
25-6981, was especially successful in rescuing the survival of PMD
oligodendrocytes in mouse and human cells in the laboratory and in PMD
mice. “Our work is an important first step of a multi-phase process,”
said Tesar. “We have achieved survival of oligodendrocytes which
normally die in the disease. The next step is to figure out how to coax
these cells to efficiently myelinate and restore function to patients.”
The Case Western Reserve team’s findings have implications beyond
PMD. Numerous neurological and psychiatric diseases are characterized by
myelin loss or dysfunction, including multiple sclerosis, spinal cord
injury, and schizophrenia. Measures to regenerate or restore myelin
could offer patients hope in these and numerous other disorders
affecting the brain and spinal cord.
Thank you to all the people who posted this so I ended up seeing it. I really needed this right now. Thank you!
Yeah… Not gonna lie… I cried…
We need more people like this
Goddamn it stop making me feel human
The therapist I wanna be.
Text in the image:
“I’m a therapist and keep this poster in my waiting room, apparently it’s saved a few lives.”
I don’t like the phrase “a cry for help.” I just don’t like how it sounds. When somebody says to me, “I’m thinking about suicide. I have a plan: I just need a reason not to do it,” the last thing I see is helplessness.
I think your depression has been beating you up for years. It’s called you ugly, and stupid, and pathetic, and a failure, for so long that you’ve forgotten that it’s wrong. You don’t see any good in yourself, and you don’t have any hope.
But still here you are: you’ve come over to me, banged on my door and said, “HEY! Staying alive is REALLY HARD right now! Just give me something to fight with! I don’t care if it’s a stick! Give me a stick and I can stay alive!”
How is that helpless? I think that’s incredible. You’re like a marine: trapped for years behind enemy lines. Your gun has been taken away, you’re out of ammo, you’re malnourished, and you’ve probably caught some kind of jungle virus that’s making you hallucinate giant spiders.
And you’re still just going, “GIVE ME A STICK. I’M NOT DYING OUT HERE.” “A cry for help” makes it sound like I’m supposed to take pity on you, but you don’t need my pity. This isn’t pathetic. This is the will to survive. This is how humans lived long enough to become the dominant species.
With NO hope, running on NOTHING, you’re ready to cut through a hundred miles of hostile jungle with nothing but a stick, if that’s what it takes to get to safety.
All I’m doing is handing out sticks.
You’re the one saying alive.
I legit cried at this. I’ve needed to hear it put this way. Bless this post.
Every time I see this post I stop to read the whole image. It always helps — even on the good days.
Because it wasn’t weakness. It wasn’t shameful to seek help. It wasn’t pathetic to “cry for help”. I was looking for a stick, be that from myself or from someone else. I was trying to find a way out. I was trying to heal myself.
this is fuckin incredible.
I’m sorry if I repost to many of these, but if it could be someone’s “stick” then it’s worth it
We navigate the world around us by creating maps of the things we see, smell, hear and touch. These ‘maps’ are a collection of cells organised topographically in the brain areas that process sensory cues from our environment. For sounds, cells that respond to a specific frequency are clustered next to cells for similar frequencies. To better understand how these maps are formed, a team of scientists genetically manipulated the auditory neurons of mice. They found that mouse embryos lacking a certain transcription factor didn’t have topographical maps in the cochlea (shown in this image) or inferior colliculus, two of the first sensory organs that relay auditory signals from the ear to the brain. This study presents some of the first evidence that there is a limit to how ‘plastic’ sensory pathways are, and that we rely on molecular cues in early development to create topographical maps of our environment.
When it comes to building barriers, nature comes up trumps with the blood-brain barrier (BBB), a network of blood vessels supplying the brain which only allows select nutrients to pass through, blocking everything else. However, structures in the BBB called circumventricular organs (CVOs) are considerably leakier, allowing the brain to monitor blood changes and respond by triggering sensations such as thirst and hunger. Using mice and zebrafish, researchers investigated what happens when leaky CVO vessels are tightened up. Fluorescent microscopy of zebrafish brain blood vessels (red) revealed low levels of signalling molecules involved in BBB formation (green) in the zebrafish equivalent of the CVO (far left bottom region). Genetically altering mice to produce more of these molecules tightened up leaky CVO vessels but also impaired the ability of brain cells to correctly respond to water deprivation. These insights reveal more about how our most basic needs are controlled.
In a new study, MIT neuroscientists explored how the brain reasons about probable causes of failure after a hierarchy of decisions. They discovered that the brain performs two computations using a distributed network of areas in the frontal cortex. First, the brain computes confidence over the outcome of each decision to figure out the most likely cause of a failure, and second, when it is not easy to discern the cause, the brain makes additional attempts to gain more confidence.
Psychologists at the University of Sussex have confirmed that the
warm glow of kindness is real, even when there’s nothing in it for
you. In their study, published in NeuroImage,
they undertook a major analysis of existing research showing the brain
scans relating to over 1000 people making kind decisions. For the first
time, they split the analysis between what happens in the brain when
people act out of genuine altruism – where there’s nothing in it for
them – and when they act with strategic kindness – when there is
something to be gained as a consequence.
Many individual studies have hinted that generosity activates the
reward network of the brain but this new study from Sussex is the first
that brought these studies together, and then split the results into two
types of kindness – altruistic and strategic. The Sussex scientists
found that reward areas of the brain are more active – i.e. use up more
oxygen – when people act with strategic kindness, when there is an
opportunity for others to return the favour.
But they also found that acts of altruism, with no hope of personal
benefit, activate the reward areas of the brain too, and more than that,
that some brain regions (in the ‘subgenual anterior cingulate cortex’)
were more active during altruistic generosity, indicating that there is
something unique about being altruistic with no hope of gaining
something in return.
Dr Daniel Campbell-Meiklejohn, the study’s lead and Director of the Social Decision Laboratory at the University of Sussex, said:
“This major study sparks questions about people having different
motivations to give to others: clear self-interest versus the warm glow
of altruism. The decision to share resources is a cornerstone of any
cooperative society. We know that people can choose to be kind because
they like feeling like they are a ‘good person’, but also that people
can choose to be kind when they think there might be something ‘in it’
for them such as a returned favour or improved reputation. Some people
might say that ‘why’ we give does not matter, as long as we do. However,
what motivates us to be kind is both fascinating and important. If, for
example, governments can understand why people might give when there’s
nothing in it for them, then they can understand how to encourage people
to volunteer, donate to charity or support others in their community.”
Jo Cutler, the PhD student who co-authored the study at the University of Sussex, added:
“The finding of different motivations for giving raises all sorts of
questions, including what charities and organisations can learn about
what motivates their donors. Some museums, for example, choose to
operate a membership scheme with real strategic benefits for their
customers, such as discounts. Others will ask for a small altruistic
donation on arrival. Organisations looking for contributions should
think about how they want their customers to feel. Do they want them to
feel altruistic, and experience a warm glow, or do they want them to
enter with a transactional mind-set?”
“Given that we know there are these two motivations which overlap in
the brain, charities should be careful not to offer something which
feels like a token gesture, as this might undermine a sense of altruism.
Sending small gifts in return for a monthly donation could change
donors’ perceptions of their motivation from altruistic to
transactional. In doing so, charities might also inadvertently replace
the warm glow feeling with a sense of having had a bad deal.”
“The same issues could also apply when we think about interactions
between family, friends, colleagues or strangers on a one-to-one basis.
For example, if after a long day helping a friend move house, they hand
you a fiver, you could end up feeling undervalued and less likely to
help again. A hug and kind words however might spark a warm glow and
make you feel appreciated. We found some brain regions were more active
during altruistic, compared to strategic, generosity so it seems there
is something special about situations where our only motivation to give
to others is to feel good about being kind.”
Jo Cutler and Dr Campbell-Meiklejohn analysed 36 existing studies
relating to 1,150 participants whose brains were scanned with fMRI scans
over a ten-year period.
If you’ve ever found yourself staring at a lengthy restaurant menu and been completely unable to decide what to order for lunch, you have experienced what psychologists call choice overload. The brain, faced with an overwhelming number of similar options, struggles to make a decision.
A study conducted in California nearly 20 years ago is illustrative
of the effect. In that study, researchers set up a table offering
samples of jams to customers in a grocery store. At times, 24 jam
samples were provided; at other times, only six. It turned out that
although shoppers were more likely to stop and try samples when the
table was jam-packed, they also were much less likely to actually
purchase any jam. Shoppers were somewhat less likely to stop at the
table when it had only six jams, but when they did, they were 10 times
more likely to make a jam purchase than the customers at the fuller
Lunch entrees and fruit preserves might seem trivial, but choice overload can sometimes have serious consequences, says Colin Camerer,
Caltech’s Robert Kirby Professor of Behavioral Economics and the
T&C Chen Center for Social and Decision Neuroscience Leadership
Chair. As an example, he points to Sweden’s partial privatization of its
social security system. The government allowed citizens to move some of
their retirement savings into private funds. The government gave them
hundreds of funds from which to choose, and conducted a large
advertising campaign encouraging them to make their own choice. At
first, nearly 70 percent of the eligible adult population took an active
role in choosing a fund, but the percentage quickly dropped off. After
10 years, only about 1 percent of newly eligible Swedes were making an
active decision about where to put their retirement money.
study conducted at Caltech by Camerer reveals new insights into choice
overload, including the parts of the brain responsible for it, and how
many options the brain actually prefers when it is making a choice.
In the study, volunteers were presented with pictures of scenic
landscapes that they could have printed on a piece of merchandise such
as a coffee mug. Each participant was offered a variety of sets of
images, containing six, 12, or 24 pictures. They were asked to make
their decisions while a functional magnetic resonance imaging (fMRI)
machine recorded activity in their brains. As a control, the volunteers
were asked to browse the images again, but this time their image
selection was made randomly by a computer.
The fMRI scans revealed
brain activity in two regions while the participants were making their
choices: the anterior cingulate cortex (ACC), where the potential costs
and benefits of decisions are weighed, Camerer says; and the striatum, a
part of the brain responsible for determining value.
his colleagues also saw that activity in these two regions was highest
in subjects who had 12 options to pick from, and lowest in those with
either six or 24 items to choose from. Camerer says that pattern of
activity is probably the result of the striatum and the ACC interacting
and weighing the increasing potential for reward (getting a picture they
really like for their mug) against the increasing amount of work the
brain will have to do to evaluate possible outcomes.
As the number
of options increases, the potential reward increases, but then begins
to level off due to diminishing returns. “The idea is that the best out
of 12 is probably rather good, while the jump to the best out of 24 is
not a big improvement,” Camerer says. At the same time, the amount of
effort required to evaluate the options increases. Together, mental
effort and the potential reward result in a sweet spot where the reward
isn’t too low and the effort isn’t too high. This pattern was not seen
when the subjects merely browsed the images because there was no
potential for reward, and thus less effort was required when evaluating
Camerer points out that 12 isn’t some magic number
for human decision-making, but rather an artifact of the experimental
design. He estimates that the ideal number of options for a person is
probably somewhere between 8 and 15, depending on the perceived reward,
the difficulty of evaluating the options, and the person’s individual
Of course, a trip to the nearest grocery store is
likely to reveal that lots of products come in many more than a dozen
varieties. There might be a whole aisle of toothpastes of varying
brands, sizes, flavors, textures, and properties, and on the condiment
aisle, there might be dozens of kinds of mustards to choose from.
says that’s partly because people tend to feel freer and like they have
more control over their lives when they have more options to choose
from, even if having all those options ends up distressing them at
“Essentially, our eyes are bigger than our
stomachs,” he says. “When we think about how many choices we want, we
may not be mentally representing the frustrations of making the
Camerer says future research in this area could explore and attempt to quantify the mental costs of making a decision.
“What is mental effort? What does thinking cost? It’s poorly understood,” he says.
To keep our hearts beating in time the autonomic nervous system carries pulses of electrical activity deep into their muscular walls, causing repeating patterns of contractions. Usually hidden behind layers of fatty molecules, the nerves in this mouse heart are revealed in bright colours under a high-powered microscope after a chemical wash to clear the fats away. Computer algorithms help to spot the ‘circuits’ of nerves, colour-coding them by diameter (left, blue thinnest, red thickest) or by their orientation with the heart (right). These patterns reveal fresh details about how heart rhythm in maintained, but also provide a comparison for future studies – using similar techniques to examine how these patterns are disrupted by cardiovascular diseases and conditions such as myocardial infarction.