Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 33,991 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label listening on neurons. Show all posts
Showing posts with label listening on neurons. Show all posts
With ANY BRAINS AT ALL in stroke leadership,
this would have immediately started research using this to listen in on
neuron signalling in neuroplasticity. We need to know why and how a
neighboring neuron gives up its current task and takes on a neighboring
task. Without that knowledge neuroplasticity will never be made
repeatable and made into a stroke protocol. Hell, this has been out
since October 2016 so more proof that the stroke medical world is
completely incompetent.
First in vivo electrophysiological recordings with neural dust motes
•
Passive, wireless, and battery-less EMG and ENG recording with mm-scale devices
•
Recorded signals transmitted via ultrasonic backscatter from implanted neural dust motes
•
Ultrasound as a scalable means of providing wireless power and communication
Summary
The
emerging field of bioelectronic medicine seeks methods for deciphering
and modulating electrophysiological activity in the body to attain
therapeutic effects at target organs. Current approaches to interfacing
with peripheral nerves and muscles rely heavily on wires, creating
problems for chronic use, while emerging wireless approaches lack the
size scalability necessary to interrogate small-diameter nerves.
Furthermore, conventional electrode-based technologies lack the
capability to record from nerves with high spatial resolution or to
record independently from many discrete sites within a nerve bundle.
Here, we demonstrate neural dust, a wireless and scalable ultrasonic
backscatter system for powering and communicating with implanted
bioelectronics. We show that ultrasound is effective at delivering power
to mm-scale devices in tissue; likewise, passive, battery-less
communication using backscatter enables high-fidelity transmission of
electromyogram (EMG) and electroneurogram (ENG) signals from
anesthetized rats. These results highlight the potential for an
ultrasound-based neural interface system for advancing future
bioelectronics-based therapies.
)
have renewed interest in implantable systems for interfacing with the
peripheral nervous system. Early clinical successes with peripheral
neurostimulation devices, such as those used to treat sleep apnea (
).
A recently proposed roadmap for the field of bioelectronic medicines
highlights the need for new electrode-based recording technologies that
can detect abnormalities in physiological signals and be used to update
stimulation parameters in real time. Key features of such technologies
include high-density, stable recordings of up to 100 channels in single
nerves, wireless and implantable modules to enable characterization of
functionally specific neural and electromyographic signals, and scalable
device platforms that can interface with small nerves of 100 μm
diameter or less (
)
as well as specific muscle fibers. Current approaches to recording
peripheral nerve activity fall short of this goal; for example, cuff
electrodes provide stable chronic performance but are limited to
recording compound activity from the entire nerve. Single-lead
intrafascicular electrodes can record from multiple sites within a
single fascicle but do not enable high-density recording from discrete
sites in multiple fascicles (
).
However, most wireless systems use electromagnetic (EM) energy coupling
and communication, which becomes extremely inefficient in systems
smaller than ∼5 mm due to the inefficiency of coupling radio waves at
these scales within tissue (
; see also Size Scaling and Electromagnetics in the Supplemental Information).
Further miniaturization of wireless electronics platforms that can
effectively interface with small-diameter nerves will require new
approaches.
In contrast to EM,
ultrasound offers an attractive alternative for wirelessly powering and
communicating with sub-mm implantable devices (
). Ultrasound has two advantages. First, the speed of sound is 105
× lower than the speed of light in water, leading to much smaller
wavelengths at similar frequencies; this yields excellent spatial
resolution at these lower frequencies as compared to radio waves.
Second, ultrasonic energy attenuates far less in tissue than EM
radiation; this not only results in much higher penetration depths for a
given power, but also significantly decreases the amount of unwanted
power introduced into tissue due to scattering or absorption. In fact,
for most frequencies and power levels, ultrasound is safe in the human
body. These limits are well defined, and ultrasound technologies have
long been used for diagnostic and therapeutic purposes. As a rough
guide, about 72× more power is allowable into the human body when using
ultrasound as compared to radio waves (
We previously introduced the neural dust
ultrasonic backscattering concept to harness the potential advantages
of ultrasound and showed that, theoretically, such a system could be
scaled well below the mm-scale when used for wireless
electrophysiological neural recording (
).
Here, we present the first experimental validation of a neural dust
system in vivo in the rat peripheral nervous system (PNS) and skeletal
muscle, reporting both electroneurogram (ENG) recordings from the
sciatic nerve and electromyographic (EMG) recordings from the
gastrocnemius muscle. The neural dust system consists of an external
ultrasonic transceiver board which powers and communicates with a
millimeter-scale sensor implanted into either a nerve or muscle (Figure 1A). The implanted mote consists of a piezoelectric crystal, a single custom transistor, and a pair of recording electrodes (Figures 1B, 1C, and S1).
With ANY BRAINS AT ALL in stroke leadership, this would have immediately started research using this to listen in on neuron signalling in neuroplasticity. We need to know why and how a neighboring neuron gives up its current task and takes on a neighboring task. Without that knowledge neuroplasticity will never be made repeatable and made into a stroke protocol. Hell, this has been out since July 2015 so more proof that the stroke medical world is completely incompetent.
Seamless
and minimally-invasive three-dimensional (3D) interpenetration of
electronics within artificial or natural structures could allow for
continuous monitoring and manipulation of their properties. Flexible
electronics provide a means for conforming electronics to non-planar
surfaces, yet targeted delivery of flexible electronics to internal
regions remains difficult. Here, we overcome this challenge by
demonstrating syringe injection and subsequent unfolding of
submicrometer-thick, centimeter-scale macroporous mesh electronics
through needles with a diameter as small as 100 micrometers. Our results
show that electronic components can be injected into man-made and
biological cavities, as well as dense gels and tissue, with > 90%
device yield. We demonstrate several applications of syringe injectable
electronics as a general approach for interpenetrating flexible
electronics with 3D structures, including (i) monitoring of internal
mechanical strains in polymer cavities, (ii) tight integration and low
chronic immunoreactivity with several distinct regions of the brain, and
(iii) in vivo multiplexed neural recording. Moreover, syringe
injection enables delivery of flexible electronics through a rigid
shell, delivery of large volume flexible electronics that can fill
internal cavities and co-injection of electronics with other materials
into host structures, opening up unique applications for flexible
electronics.
The
emergence of flexible electronics has significantly extended the
applications of electronics by allowing intimate interfaces between
electronic units and non-planar surfaces for better monitoring and
manipulation of their properties1-3. A variety of electronic devices1-8 has been integrated on flexible and stretchable substrates to enable applications from foldable display to electronic skin3-8.
3D interpenetration of flexible electronics within existing structures
could further broaden and open up new applications by directly
interfacing devices with the internal structures of man-made and
biological materials.
Recent work has shown that flexible electronics can be placed into 3D structures through surgical processes9-12 or by being attached to and subsequently released from a rigid delivery substrates13-14
for biological and biomedical applications. However, direct 3D
interpenetration of electronics within these structures is limited by
the intrinsic thin-film 14
supporting substrates. We have introduced a macroporous mesh paradigm
that allow electronics to be combined, for example, with polymer
precursors and cells to yield 3D interpenetration15, 16,
although controlled delivery and/or non-surgical placement of these
ultraflexible open electronic networks into structures with seamless 3D
integration and interpenetration has not been possible.
Here,
we describe the design and demonstration of macroporous flexible mesh
electronics that allow electronics to be precisely delivered into 3D
structures by syringe injection and subsequently relax and
interpenetrate within the internal space of man-made and biological
materials. Distinct from previous reports3, 17, 18,
syringe injection requires complete release of the mesh electronics
from a substrate so that the electronics can be driven by solution
through a needle. The syringe injectable electronics concept involves
(i) loading the mesh electronics into a syringe and needle, (ii)
insertion of the needle into the material or internal cavity and
initiation of mesh injection (Fig. 1a), (iii) simultaneous mesh injection and needle withdrawal to place the electronics through the targeted region (Fig. 1b), and (iv) delivery of the input/output (I/O) region of the mesh outside of the material (Fig. 1c) for subsequent bonding and measurements.
a to c,
Schematics of injectable electronics. The red-orange lines highlight
the overall mesh structure and indicate the regions of supporting and
passivating polymer mesh layers; the yellow lines indicate metal
interconnects between I/O pads (green filled circles) and recording
devices (blue filled circles). d, Schematic of the mesh
electronics design (upper image), where the orange and red lines
represent polymer encapsulated metal interconnects and supporting
polymer elements, respectively, and W is the total width of the
mesh. The dashed black box (lower image) highlights the structure of
one unit cell (white dashed lines), where α is the angle deviation from rectangular. e, Longitudinal mesh bending stiffness, DL, and transverse mesh bending stiffness, DT, as a function of α defined in d. f and g, Images of mesh electronics injection through a glass needle, ID = 95 μm, into 1x PBS solution. Bright-field microscopy image f
of the mesh electronics immediately prior to injection into solution;
the red arrow indicates the end of the mesh inside the glass needle. 3D
reconstructed confocal fluorescence image g recorded
following injection of ca. 0.5 cm mesh electronics into 1x PBS solution.
The blue and white dashed boxes correspond to regions shown in Supplementary Fig. 3a and b. h, Optical image of an injectable mesh electronics structure unfolded on a glass substrate. W
is the total width of the mesh electronics. The red dashed polygon
highlights the position of electrochemical devices or FET devices. Green
and black dashed boxes highlighted metal interconnect lines and metal
I/O pads, respectively. i and j,
Yields and change with ±1 standard deviation (±1SD) in properties
post-injection for single-terminal electrochemical and two-terminal
field-effect transistor (FET) devices. i, Yield (blue)
and impedance change (red) of the metal electrodes from the mesh
electronics injected through 32, 26 and 22 gauge metal needles. Inset:
bright field image of a representative metal electrode on mesh
electronics, where the sensing electrode is highlighted by a red arrow.
Scale Bar: 20 μm. j, Yield (blue) and conductance
change (red) of silicon nanowire FETs following injection through 32,
26, 24, 22 and 20 gauge needles. Inset: scanning electron microscopy
(SEM) image of a representative nanowire FET device in the mesh
electronics; the nanowire is highlighted by the red arrow. Scale bar: 2
μm.
Design and implementation of electronics for syringe injection
The
mechanical properties of the free-standing mesh electronics are
important to the injection process. The basic mesh structure (Fig. 1d and Supplementary Fig. 1, a and b)
consists of longitudinal polymer/metal/polymer elements, which function
as interconnects between exposed electronic devices and I/O pads, and
transverse polymer elements. The mesh longitudinal and transverse
bending stiffness, DL and DT,
are determined by the mesh unit cell and corresponding widths and
thickness of the longitudinal and transverse elements, and the angle, α, 15, 16. Simulations of DT and DL versus α(Fig. 1e) show that DT (DL) decreases (increases) for increasing α. Hence, increasing α facilitates bending along the transverse direction (reduced DT) and should allow for rolling-up of the mesh electronics within a needle constriction, while at the same time increasing DL, which should reduce bending and potential buckling along the injection direction.
The mesh electronics were fabricated, fully-released from substrates using reported methods15, 16 and loaded into glass needles connected to a microinjector (details see, Supplementary Information Sections 2 and 3 and Supplementary Figs. 2 and 3).
Images of injection of a 2 mm wide sample through a 95 μm inner
diameter (ID) glass needle show the compressed mesh ca. 250 μm from the
needle opening (Fig. 1f), and then injected ca. 0.5 cm into 1x phosphate-buffered saline (PBS) solution (Fig. 1g),
where the 3D image highlights the unfolding of the mesh structure from
the point of the needle constriction (blue dashed box). Higher
resolution images (Supplementary Fig. 4, a and b)
show that the mesh structure is continuous as it unfolds. Similar
results were obtained for injection of a 1.5 cm width sample through a
20 gauge (600 μm ID) metal needle (Supplementary Fig. 4c) demonstrating the generality of this injection through common glass and metal syringe needles.
To
test further electrical continuity and functionality of the mesh
electronics post-injection, we used anisotropic conductive film (ACF)19 to connect the I/O pads of theelectronics post-injection to flexible cables that are interfaced to measurement electronics (Supplementary Fig. 5, a-d).
Studies of the electrical performance and yield of devices following
injection into 1x PBS solution through 100-600 μm ID needles (Fig. 1, i and j)
highlight several points. First, metal electrochemical devices had an
average device >94% and an average device impedance change, which
represents an important characteristic for voltage sensing applications20, 21, of <7% post injection (Fig. 1i).
Second, silicon nanowire field-effect transistor (FET) devices had a
yield > 90% for needle IDs from 260 to 600 μm, only dropped to 83%
for the smallest 100 μm ID needles, and exhibited < 12% conductance
change on average post injection (Fig. 1j).
Together these results demonstrate the robustness of our mesh
electronics design and the capability of maintaining good device
performance following injection through a wide-range of needle IDs.
We
have characterized the structures of different mesh electronics within
glass needle-like constrictions to understand design parameters for
successful injection (Fig. 2, a and b).
Bright field microscopy images of mesh electronics with different
structural parameters recorded from the central region of different ID
glass channels (Fig. 2c) highlight two important features. First, mesh electronics with α
= 45° and widths substantially larger than the constriction ID can be
smoothly injected. Relatively straight longitudinal elements are seen in
Fig. 2c, I and II,
where the 5 mm 2D mesh widths are 11- and 20-times larger than the
respective 450 and 250 μm ID needle constrictions. Second, even 1.5 cm
width mesh electronics (Fig. 2c, III) can be injected smoothly through a 33-times smaller ID (450 μm) constriction.
We should be able to use this to listen in as neuroplasticity occurs. Where a neuron gives up its current task and takes on a neighboring neurons task. Then if we can artificially create those signals we can speed up and make neuroplasticity repeatable.
The cells that make up heart muscles are generally squishy
things, structured so that they can squeeze tight when they get the
right signal and release otherwise. Yet to study how those cells work
researchers have relied for years on rigid electrodes that sit flat
against the cell's surface.
Now, a team of chemists, bioengineers and chemical engineers has come
up with something much better: a soft, thin electrode that can track
electrical activity in a cardiac muscle cell without interfering with
its contractions and other movements, as rigid electrodes are likely to
do.
Their work appears in Proceedings of the National Academy of Sciences.
"We want to have a measurement [tool] that does not change what we're measuring," said Yuxin Liu, a graduate student in bioengineering who, with Allister McGuire,
a graduate student in chemistry, is co-lead author of the paper. With
the new soft electrodes, which are built out of water-absorbing polymers
called hydrogels, that goal appears to be in reach.
The project originated when McGuire and his advisor, Bianxiao Cui,
PhD, an associate professor of chemistry, wanted a way to study how
cardiac muscle cells move in response to the electrical signals that
cause them to contract. Cui's lab had already developed thin and
vertical electrodes that did a better job of embedding themselves in a
heart cell's outer membrane than existing electrodes, which are
relatively large and flat compared to the cells they aim to monitor.
But to do what they really wanted to do, they knew they needed
something soft as well, and for that they turned to Liu and his advisor,
Zhenan Bao,
PhD, a professor of chemical engineering who has been designing and
making electrically conductive soft materials for years. With help from a
seed grant from Stanford Bio-X that supported Liu and a Bio-X Bowes Fellowship that supported McGuire, the two labs began collaborating.
What they came up with was a "micropillar" that starts out as small
dots of an electrically conductive polymer and then, through a mix of
chemical solutions, heating, and rehydrating grows taller by roughly a
factor of ten without increasing in width. The resulting hydrogel
micropillars, which were fabricated through the Stanford Nano Shared Facilities and the Stanford Nanofabrication Facility,
bend around much more easily than conventional electrodes and are
better electrical conductors as well. Tests in mouse-derived heart cell
lines showed soft micropillars also interfered less with the function
and mechanical behavior of the cells.
Although the new devices do not fully address McGuire's original goal
— measuring both the electrical activity and movement of cardiac muscle
cells at the same time — Cui said that the results are promising. In
the future, the team plans to use their new device to better understand
how cardiac muscle cells work and, in particular, the differences
between several different kinds of those cells.
How will your doctor use this knowledge to improve neuroplasticity? Or will your doctor DO NOTHING like usual? https://www.quantamagazine.org/cells-talk-in-a-language-that-looks-like-viruses-20180502/
or cells, communication is a matter of life and death. The ability to
tell other members of your species — or other parts of the body — that
food supplies are running low or that an invading pathogen is near can
be the difference between survival and extinction. Scientists have known
for decades that cells can secrete chemicals into their surroundings,
releasing a free-floating message for all to read. More recently,
however, scientists discovered that cells could package their molecular
information in what are known as extracellular vesicles. Like notes
passed by children in class, the information packaged in an
extracellular vesicle is folded and delivered to the recipient.
The past five years have seen an explosion of research into
extracellular vesicles. As scientists uncovered the secrets about how
the vesicles are made, how they package their information and how
they’re released, it became clear that there are powerful similarities
between vesicles and viruses.
A small group of researchers, led by Leonid Margolis, a Russian-born virologist at the National Institute of Child Health and Human Development (NICHD), and Robert Gallo,
the HIV pioneer at the University of Maryland School of Medicine, has
proposed that this similarity is more than mere coincidence. It’s not
just that viruses appear to hijack the cellular pathways used to make
extracellular vesicles for their own production — or that cells have
also taken on some viral components to use in their vesicles.
Extracellular vesicles and viruses, Margolis argues, are part of a
continuum of membranous particles produced by cells. Between these two
extremes are lipid-lined sacs filled with a variety of genetic material
and proteins — some from hosts, some from viruses — that cells can use
to send messages to one another.
“There are fundamental differences between viruses and vesicles:
Viruses can replicate and vesicles cannot,” Margolis said. “But there
are many variants in between. Where do viruses start, and where do
extracellular vesicles start?”
Whether cells started using vesicles for communication first and
viruses copied them, or cells stole the idea from viruses, or both
evolved the strategy in tandem is currently impossible to determine:
Sending information in extracellular vesicles must have first appeared
billions of years ago because even bacteria do it. “This idea of using a
membrane-bound sac of information to transport between cells has been
around a long time,” said David Meckes, Jr., a virologist at Florida State University.
One of the most striking pieces of evidence supporting Margolis and
Gallo’s hypothesis is the recent discovery, widely reported in January,
that a mammalian protein called Arc, which is implicated in learning and
memory, is actually a repurposed retroviral protein. More important,
Arc appears to be secreted from the synapses of neurons in extracellular
vesicles. “These vesicles may be acting like a viral envelope,” said Cedric Feschotte, a retrotransposon expert at Cornell University.
Now that humans are aware of this shared membranous medium for
transporting information between cells, the idea is paving the way for
new discoveries and the development of new therapeutics for cancer and
viral diseases.
Bad News Wrapped in Protein Coats
When scientists first started gazing at cells under powerful light
microscopes, they noticed a “dust” of minuscule particles surrounding
the otherwise crisp edges of the cell’s plasma membrane. Researchers
generally chalked up the debris to the cellular equivalent of dandruff
and didn’t pay much attention. Over time, scientists noticed that these
membranous flakes appeared in a wide range of cell cultures and body
fluids, such as plasma and blood. Some formed by budding directly from
the cell membrane itself and were first dubbed microvesicles, and later,
extracellular vesicles. Other, typically smaller ones were assembled
within the cell before being released through the plasma membrane and
became known as exosomes. Extracellular vesicles and exosomes range
tremendously in size, from 30 nanometers — approximately the diameter of
a small virus — to as large as one micron.
The quantity of these vesicles is extraordinary: Every day, a cell
produces the equivalent of its own plasma membrane in extracellular
vesicles and exosomes, according to D. Michiel Pegtel, a vesicle expert at VU University Medical Center in Amsterdam.
The field took off in 2006–2007 when a Swedish team and a joint American-European group
independently discovered that exosomes and extracellular vesicles could
carry several types of RNA. These included the messenger RNAs (mRNAs)
that are intermediaries in the translation of DNA into proteins, as well
as the small molecules called microRNAs that affect gene expression.
After the initial discovery of extracellular vesicles and exosomes in
blood, scientists found them in nearly every type of body fluid they
tested, including saliva, urine, amniotic fluid, breast milk and seminal
fluid. Although researchers have begun to classify extracellular
vesicles and exosomes into different subtypes, they struggle with
finding ways to sort and identify those categories.
The realization that vesicles can carry RNAs also invites comparisons
to viruses. Some of the vesicles that cells shed are similar in size to
viruses, but their molecular cargo and their capabilities are of course
different. “What inherently separates vesicles and exosomes from
viruses is that exosomes are not infectious,” Pegtel said. Even so, the
reasons for the similarities are significant.
The pioneering immunologist Peter Medawar once asserted that viruses
are “bad news wrapped in a protein coat” — but retroviruses also drape a
second layer over their protein shell by wrapping themselves in pieces
of their host’s cell membrane. The host-derived membrane protects the
virus from discovery by the immune system. When virologists probed the
cellular pathways hijacked by these minuscule pathogens, they discovered
that viruses get their envelopes by tapping into cells’ preexisting
pathway for making exosomes and extracellular vesicles.
Not all the viruses encased in cell-derived envelopes are fully
intact and functional. Many are the equivalent of lemons in a used car
lot: secondhand and not operational. These viral trash heaps covered in
membrane can’t infect other cells or perpetuate disease outbreaks. Yet
in some cases, on the surface, these vesicles carrying viral junk look
nearly identical to those carrying cellular RNA.
The similarity was so striking that Margolis realized that some
viruses — like HIV and other small RNA viruses — and exosomes and
extracellular vesicles fall on two different extremes of the same
continuum. The defective viruses and viruslike particles extruded from
infected cells form the vast middle ground on this field, Margolis says.
Lucy Reading-Ikkanda/Quanta Magazine
“Cell-cell communication is one of the most ancient mechanisms that
makes us who we are,” Margolis said. “Since vesicles resemble viruses,
the question of course is whether the first extracellular vesicles were
primitive viruses and the viruses learned from extracellular vesicles or
vice versa.”
Margolis and his colleagues at the NICHD and abroad weren’t the first
to notice the similarities between vesicles and viruses, but their 2016
paper in the Proceedings of the National Academy of Sciences was the first to hypothesize that they were two extremes of the same phenomenon. The idea was provocative, said Dirk Dittmer,
a virologist at the University of North Carolina at Chapel Hill,
because people really weren’t thinking in that way. “But those are the
kinds of things we like to debate late at night, and no one has an
answer.”
What Margolis’s idea needed was more evidence supporting the close
relationship between viruses and exosomes. This support eventually came
from two independent labs that weren’t even studying this relationship.
Raw Materials for Evolution
When the neuroscientist Jason Shepherd and his postdoc Elissa Pastuzyn
at the University of Utah began trying to decode the detailed structure
of the Arc protein, they knew nothing about extracellular vesicles.
What they did know was that mice lacking the Arc gene were
unable to learn from scary situations—a deadly defect for an animal
that’s a snack-size morsel for many predators. What’s more, another lab
had already forged ahead with a less-detailed structure of the protein,
and they were strongly motivated to publish a more detailed paper on
Arc.
As Pastuzyn repeatedly tried to purify Arc, however, the single
protein kept self-assembling into a more complex structure. At first,
everyone thought it was a mistake. But when it kept happening, Shepherd
and Pastuzyn took a peek under the electron microscope. The protein
structure looked familiar.
“It looked like a virus,” she said. “It was a double-ringed
structure, and the resemblance was uncanny. I had no idea that’s what it
was.”
When Pastuzyn looked up the DNA sequence of Arc in GenBank
(the NIH’s depository for all gene sequences), she discovered that the
predicted structure of Arc most closely resembled that of Gag, a protein
that forms a retrovirus’s capsid shell, which is subsequently encased
in a host-derived lipid membrane. Gag isn’t the only culprit, either. What researchers have
come to realize is that sometime millions of years ago, part of a
retrovirus genome inserted itself into its host’s DNA, and that sequence
was then passed on to countless generations of offspring. Around 8
percent of the human genome is ultimately derived from viruses. Although
some of this DNA is, in fact, “junk,” scientists are learning that much
of it plays a role in our biology.
For the host, these viral genes provide a genetic junk drawer full of
nuts and bolts for evolution to play with. Evolution, Shepherd says, is
the ultimate MacGyver, referring to the 1980s TV hero who could defuse a
bomb with bubble gum and a paper clip. It doesn’t invent things
outright in an insomnia-fueled burst of creativity. Instead, evolution
tinkers, cobbling together inventive solutions out of the spare parts at
hand.
“Although these viruses aren’t good for individuals, they provide the
raw materials for new genes,” Shepherd says. “They’re a potential gold
mine.”
In the case of Arc, the Gag-derived viral gene gave mammals a
ready-made delivery device that could be packaged in an extracellular
vesicle. A retrovirus packages RNA and moves it out of the cell,
Feschotte said. “Arc has preserved many of these same functions.”
About two thousand miles east of Shepherd’s lab in Salt Lake City, Vivian Budnik
was also working on Arc in her lab at the University of Massachusetts
Medical School. Unlike Shepherd, whose interest in memory and learning
spurred his interest in Arc, Budnik became interested in the protein
through her studies of extracellular vesicles at the synapse of neurons.
In 2009, Budnik and her colleagues generated the first animal model
that showed how fruit flies use extracellular vesicles to ferry a
protein called Wnt across the synapse. When Budnik read a paper that
showed extracellular vesicles could carry microRNA, it made her wonder
if the vesicles could also carry messenger RNA. She began looking in the
fly version of the Arc protein.
Then Travis Thomson arrived in her lab as a postdoc after completing
another postdoc in a lab that studied the mobile genetic elements called
transposons, many of which resemble viruses. As soon as he saw the mRNA
from the Arc gene, he noted that it looked like RNA from a virus and
wondered if it also behaved like a capsid.
Budnik presented her initial findings on Arc at a closed conference
two years ago; Shepherd was sitting in the back and realized Budnik had
independently reached the same conclusions about Arc. He approached her
afterward and explained his identical findings from a different
approach. Budnik and Shepherd soon determined that animals had
repurposed a retroviral Gag protein twice: once in flies and once in
mammals. In both groups of animals, Arc acts to move RNA across
synapses.
“They look very similar. The mechanism on a molecular level is very
similar, even though they come from different retrotransposons,”
Feschotte said. Shepherd and Budnik agreed to publish their papers in parallel, and did so in January 2018 in Cell.
Budnik’s experience with Arc led her to look for other transposons and
viral elements transported by extracellular vesicles. Thus far, she has
found several, and one of them behaves like Arc. “We have viruslike
sequences throughout our genome, but we have mostly no idea what they
do,” Budnik said.
This work bolsters the close links between extracellular vesicles and
viruses. Meanwhile, Shepherd and his colleagues have been scouring the
human genome for other genes similar to Arc. Like Budnik, they’ve found several (their results, too, have yet to be published).
The recent explosion of research on extracellular vesicles — from 135
studies published in 2013 to 1,087 studies in 2017 — testifies to
scientists’ new appreciation of their centrality to cellular
functioning. Because extracellular vesicles and exosomes can pass
information between cells, scientists have begun to implicate them in
everything from cancer to viral infections to basic neural functioning.
To Lynne Maquat,
an expert on retrotransposons at the University of Rochester, this
process shows how parts of the genome we used to think of as junk
actually have important functions.
“You could say that the host domesticated a viral sequence for its
own purposes,” Maquat said. “That’s the beauty of our complexity —
[these elements] allow tinkering or fine-tuning of genes.”
Although it’s now clear that extracellular vesicles are far from
simple cellular debris, and the viral genes littering our DNA aren’t
exactly junk, researchers have only just begun to crack the mystery of
what they can do. Correction: The article was updated on May 4 to specify that
Leonid Margolis is affiliated with the NICHD within the National
Institutes of Health. This article was reprinted on TheAtlantic.com.
A new type of
electrode for recording brain cell activity is set to revolutionize our
understanding of decision making in the brain.
The findings of a global collaborative effort are published today in the journal Nature.
The paper describes a new recording probe, Neuropixels, 10mm long and
thinner than the width of a human hair. Each Neuropixels probe uses
technology identical to that found in your smart phone to enable
recording from 384 channels that line the shank of the electrode. Seeing neuronal activity in hi-def.
The
Neuropixels probes enable observation of the activity of hundreds of
neurons simultaneously at a level of resolution previously unachievable.
The
densely packed recording channels allow researchers to see brain
activity in higher resolution because they can now pick out activity in
the small processes, like dendrites or axons, that they may have missed
with the current wire electrodes in use, which are limited to dozens of
recording sites.
The Neuropixels probe. Courtesy of imec.
The
design is also a big improvement on the current technology, in that the
headstage, the part of the set-up that amplifies the millivolt signals
recorded from the neurons so they can be seen on a screen, is directly
connected to the electrode. Also, the recorded analog signal is
digitized at the level of the headstage. This limits the amount of
signal interference from external electrical sources, electrical noise
which is a frustration for any electrophysiologist.
Improving
the fidelity of the electrical signal improves the resolution of the
electrical activity recorded. Meaning the researchers are not only able
to record from more neurons in one go, they also get cleaner signals
from the neurons as well. Deep brain activity
The
long 10mm shank means scientists can delve deeper into the brain and
record from the multiple brain areas that the shank passes through,
simultaneously. The set-up allows researchers to record up to 384
channels at any one time from the 960 channels available. This means
researchers can group their recording sites around areas of interest. The product of international collaboration
The
probes were developed by an international team who received $5.5
million from the Howard Hughes Medical Institute (HHMI), the Allen
Institute for Brain Science, the Gatsby Charitable Foundation and
Wellcome. Scientists at HHMI’s Janelia Research Campus, the Allen
Institute and University College London (UCL) worked together with
engineers at nanotechnology company imec to build and test the probes.
Lead author Dr Timothy Harris,
Senior Fellow at HHMI’s Janelia Research Campus, was speaking with
Wellcome about the power of the Neuropixels probes: “Every action and
decision you take involves the interactions of millions of neurons
spread across your brain. This new technology enables us to detect the
activity of large numbers of neurons from multiple brain regions with
much less difficulty. I believe they will be transformational and will
greatly accelerate the pace of neuroscience research”.
Prof. Matteo Carandini,
Wellcome Investigator and joint head of the Cortex lab at UCL, was also
speaking to Wellcome about the impact the probes will have on the field
of neuroscience: “To understand the brain we need to understand how a
lot of neurons spread all over the brain work together. Until recently,
it was possible to measure the activity of individual neurons within a
specific spot in the brain or to reveal larger, regional patterns of
activity—but not to do both at the same time. These probes are a game
changer. If you place them appropriately, you can really study how
different parts of the brain work together at the neuronal level.”
In
their paper, the researchers describe how the Neuropixels work. They
also present data obtained from 700 well-isolated single neurons from
five brain structures in a mouse. The researchers have also shown that
the probes can be used in long-duration experiments with freely moving
animals, in experiments with mice lasting up to 150 days. Long-term
experiments enable researchers to study changes in the brain resulting
from development, experience and learning, as well as the effects of
neurodegenerative processes in disease. This
video from Wellcome describes the power of the Neuropixel probes and
how they are being utilized by the International Brain Lab to increase
our understanding of the brain. Credit: Wellcome Neuropixels at the heart of a large coordinated neuroscience effort
In September, the International Brain Laboratory was
launched. The research groups involved in this coordinated approach, to
understand decision making, have been working with the prototype
Neuropixels probes and helping guide their development.
The
different groups will use Neuropixels probes to study many different
areas in the brain of a mouse, as it forages for food. The collaboration
will involve data sharing between the groups involved, to enhance
understanding of neural activity and to build a functional map of
neuronal activity throughout the brain as the animal performs a foraging
task.
Collaboration is at the heart of the development of these
probes which were developed and tested between labs in America, UK and
the nanofabrication company, imec, in Belgium. The probes will shortly
be made available to researchers across the world at cost-price. The
authors hope this will encourage uptake of these probes among academic
researchers and contribute to advancing our understanding of the brain.
The probes are already enabling a concerted and collaborative effort in
the form of the International Brain Lab.
You'll have to make sure your doctors follow this research and apply it to your 100% recovery protocols. With the monitoring capabilities they are using it would be goddamned easy to figure out EXACTLY how neuroplasticity works. Now we could have that great stroke association write up an RFP to solve why a neuron gives up its function and takes on neighboring duties. http://www.nature.com/news/researchers-unite-in-quest-for-standard-model-of-the-brain-
Leading
neuroscientists are joining forces to study the brain — in much the same
way that physicists team up in mega-projects to hunt for new
particles.
The International Brain Lab (IBL),
launched on 19 September, combines 21 of the foremost neuroscience
laboratories in the United States and Europe into a giant collaboration
that will develop theories of how the brain works by focusing on a
single behaviour shared by all animals: foraging. The Wellcome Trust in
London, and the Simons Foundation in Washington DC have together
committed more than US$13 million over five years to kick-start the
IBL.
The pilot effort is an attempt to shake
up cellular neuroscience, conventionally done by individual labs
studying the role of a limited number of brain circuits during simple
behaviours. The ‘virtual’ IBL lab will instead ask how a mouse brain, in
its entirety, generates complex behaviours in constantly changing
environments that mirror natural conditions.
The
project will use chips that can record the electrical signals of
thousands of neurons at once. It will also use other emerging
technologies, such as optogenetics toolkits that control neurons with
light. “It’s a new approach that will likely yield important new
insights into brain and behaviour,” says Tobias Bonhoeffer, a director
of the Max Planck Institute for Neurobiology in Martinsried, Germany,
who is also a Wellcome Trust governing-board member.
Large-scale
neuroscience projects are hardly rare. In 2013, the European Commission
announced the 10-year Human Brain Project, which will cost more than €1
billion ($1.1 billion); and in 2014, US president Barack Obama launched
the US Brain Initiative to develop neuro-technologies, with $110
million of funding that year. The Allen Institute for Brain Science, in
Seattle, Washington, has been creating comprehensive maps of brain
anatomy and neural circuitry since 2003. Japan, China, Canada and other
countries also have, or are planning, their own big neuroscience
initiatives.
But none operates quite like the
IBL, which will be governed in a similar way to large-scale physics
projects such as ATLAS and CMS, at Europe’s particle-physics lab CERN,
which reported evidence for the Higgs boson in 2012. The two
collaborations, at CERN’s Large Hadron Collider near Geneva,
Switzerland, brought together experimentalists and theoreticians from
hundreds of labs worldwide to test the predictions of particle physics’
standard model.
Like the massive CERN teams,
the IBL has created a flat hierarchy and a collaborative decision-making
process with near-daily web meetings. Instead of acting only when group
consensus is reached, teams will make decisions by simple consent. “No
one will be able to stop a proposed experiment being carried out without
a very convincing proposal of why it would be a disaster,” says
Alexandre Pouget, an IBL member and a theoretician at the University of
Geneva in Switzerland.
So far, says Andreas
Herz, a theoretical neuroscientist at the Ludwig Maximilian University
of Munich, Germany, "neuroscience has been stuck in an exploratory
phase". The IBL will aim to generate and test unifying theories about
how the brain encodes and computes information – seeking to come up with
the equivalent of physicists’ standard model.
But
the IBL is hardly unique among big neuroscience projects in melding
theory and practice, points out neuroanatomist Katrin Amunts at the
Jülich Research Centre in Germany. Amunts also chairs the scientific
board of Europe’s Human Brain Project, an initiative that is taking a
more conventional approach to collaboration in its own attempts to
understand how the brain works. “The future will show which is the
best,” she says.
The IBL’s principal
investigators, who include data-analysis experts as well as experimental
and theoretical neuroscientists, will dedicate around 20% of their time
to the effort. During its first two years, the IBL will build
informatics tools for automatic data-sharing and establish a reliable
experimental protocol for a basic foraging task in mice. Members will be
required to register their experiments before they start, and results
will be instantly visible to the whole collaboration.
“It
is a big challenge — and it’s not the way the field works at the
moment,” says Anne Churchland, an IBL member at Cold Spring Harbor
Laboratory, New York.
In experimental
neuroscience, the slightest parameter change can alter the outcomes of
the experiment. The IBL’s standard protocol attempts to address all
possible sources of variability, from the mice’s diets to the timing and
quantity of light they are exposed to each day and the type of bedding
they sleep on. Every experiment will be replicated in at least one
separate lab, using identical protocols, before its results and data are
made public.
“This sort of approach will
help solve the reproducibility crisis,” says Christof Koch, president of
the Allen Institute for Brain Science.
Expanding
the IBL beyond its pilot phase will require much more than $13 million,
Pouget acknowledges. After the foraging protocol is established, the
project’s second phase will test specific theories relating to how the
brain integrates diverse information to make moment-by-moment decisions.
He also hopes to enrol many more labs and broaden the suite of
behaviours studied.
For Herz, a theoretician
who is part of an influential computational-neuroscience network, it’s
about time neuroscience adopted such rigour. “A hundred years from now,”
he says, “people will look back and wonder why it hadn’t, until now,
been possible to do a more physics-based approach of designing
experiments to consolidate or disprove theories.”
Joining this with the nanorobots we could listen in on neuroplasticity signals and duplicate the signals to make neuroplasticity completely repeatable. Also used to deliver stem cells or TPA to the correct locations. Doesn't anyone in stroke have two neurons they can rub together to get a spark of intelligence?
Imagers, gastric pacemakers
and other diagnostic and therapeutic tools could someday transform the
way diseases of the gastrointestinal tract are measured and treated. But
in order for these electronic devices to work, they need a power
source. Traditional power sources, such as batteries, can be
incompatible with the mucosal lining of the gastrointestinal tract and
have a limited lifespan within the body. A more promising possibility is
to power electronic devices from outside the body.
In a new study published in the journal Scientific Reports,
investigators from Brigham and Women’s Hospital, Massachusetts Institute
of Technology and The Charles Stark Draper Laboratory report that an
ingestible electronic capsule, complete with a capsule–sized antenna
capable of receiving a radio signal wirelessly, can safely power a
device in the gastrointestinal tract in preclinical models. The new work
makes wireless medical electronics for treating the gastrointestinal
tract one step closer to reality.
“Electronic devices that can be placed in the gastrointestinal tract for
prolonged periods of time have the potential to transform how we
evaluate and treat patients. This work describes the first example of
remote, wireless transfer of power to a system in the stomach in a large
preclinical animal model – a critical step toward bringing these
devices into the clinic,” said co–corresponding author Carlo “Gio”
Traverso, MD, PhD, a gastroenterologist and biomedical engineer at BWH.
Other medical devices – such as cochlear implants or neural probes – use
a well–established technique known as near–field coupling to deliver
power wirelessly. But ingestible devices must be small enough to be
swallowed and, moreover, lie a significant distance from the surface of
the body, making this technique unattainable for most gastrointestinal
electronics. A new technique known as mid–field coupling provides an
alternative way to deliver power to deeply implanted devices. Mid–field
coupling operates at higher frequencies to deliver power two to three
times more efficiently.
To test whether mid–field coupling could help deliver power from outside
the body into the gastrointestinal tract, the research team designed
antennas capable of operating efficiently in tissue. They then placed
one antenna outside of the body and the other in the esophagus, stomach
and colon of a swine model. They were able to transmit power levels of
37.5 uW, 123 uW and 173 uW, respectively, all of which are sufficient to
wirelessly power a range of medical devices from outside of the body.
"We are very excited about this work which we feel can someday offer
many new opportunities for oral drug delivery of different molecules,"
said co–corresponding author Robert Langer, Institute Professor from the
Harvard–MIT Division of Health Sciences and Technology.
“In further work, we would like to expand on these measurements by
characterizing the effects of animal size, antenna depth, orientation
and more on transmission efficiency, and focus on propagating fields –
or the way power travels – to make transmission even more efficient,”
said Traverso.
With this we could listen in to the signals being sent between neurons as neuroplasticity occurs. That could then be analyzed and made into a consistently repeatable process, rather than the current knowledge of neuroplasticity. Which is, exercise, but we don't know how many times or what actually triggers neuroplasticity to take place. http://mcgovern.mit.edu/news/news/tiny-fibers-open-new-windows-into-the-brain/
For the first time ever, a single flexible fiber no bigger than a
human hair has successfully delivered a combination of optical,
electrical, and chemical signals back and forth into the brain, putting
into practice an idea first proposed two years ago. With some tweaking
to further improve its biocompatibility, the new approach could provide a
dramatically improved way to learn about the functions and
interconnections of different brain regions.
The new fibers were developed through a collaboration among material
scientists, chemists, biologists, and other specialists. The results are
reported in the journal Nature Neuroscience, in a paper by
Seongjun Park, an MIT graduate student; Polina Anikeeva, the Class of
1942 Career Development Professor in the Department of Materials Science
and Engineering; Yoel Fink, a professor in the departments of Materials
Science and Engineering, and Electrical Engineering and Computer
Science; Gloria Choi,
the Samuel A. Goldblith Career Development Professor in the Department
of Brain and Cognitive Sciences, and 10 others at MIT and elsewhere.
The fibers are designed to mimic the softness and flexibility of
brain tissue. This could make it possible to leave implants in place and
have them retain their functions over much longer periods than is
currently possible with typical stiff, metallic fibers, thus enabling
much more extensive data collection. For example, in tests with lab
mice, the researchers were able to inject viral vectors that carried
genes called opsins, which sensitize neurons to light, through one of
two fluid channels in the fiber. They waited for the opsins to take
effect, then sent a pulse of light through the optical waveguide in the
center, and recorded the resulting neuronal activity, using six
electrodes to pinpoint specific reactions. All of this was done through a
single flexible fiber just 200 micrometers across — comparable to the
width of a human hair.
Previous research efforts in neuroscience have generally relied on
separate devices: needles to inject viral vectors for optogenetics,
optical fibers for light delivery, and arrays of electrodes for
recording, adding a great deal of complication and the need for tricky
alignments among the different devices. Getting that alignment right in
practice was “somewhat probabilistic,” Anikeeva says. “We said, wouldn’t
it be nice if we had a device that could just do it all.”
After years of effort, that’s what the team has now successfully
demonstrated. “It can deliver the virus [containing the opsins] straight
to the cell, and then stimulate the response and record the activity —
and [the fiber] is sufficiently small and biocompatible so it can be
kept in for a long time,” Anikeeva says.
Since each fiber is so small, “potentially, we could use many of them
to observe different regions of activity,” she says. In their initial
tests, the researchers placed probes in two different brain regions at
once, varying which regions they used from one experiment to the next,
and measuring how long it took for responses to travel between them.
The key ingredient that made this multifunctional fiber possible was
the development of conductive “wires” that maintained the needed
flexibility while also carrying electrical signals well. After much
work, the team was able to engineer a composite of conductive
polyethylene doped with graphite flakes. The polyethylene was initially
formed into layers, sprinkled with graphite flakes, then compressed;
then another pair of layers was added and compressed, and then another,
and so on. A member of the team, Benjamin Grena, a recent graduate in
materials science and engineering, referred to it as making “mille
feuille,” (literally, “a thousand leaves,” the French name for a
Napoleon pastry). That method increased the conductivity of the polymer
by a factor of four or five, Park says. “That allowed us to reduce the
size of the electrodes by the same amount.”
One immediate question that could be addressed through such fibers is
that of exactly how long it takes for the neurons to become
light-sensitized after injection of the genetic material. Such
determinations could only be made by crude approximations before, but
now could be pinpointed more clearly, the team says. The specific
sensitizing agent used in their initial tests turned out to produce
effects after about 11 days.
The team aims to reduce the width of the fibers further, to make
their properties even closer to those of the neural tissue. “The next
engineering challenge is to use material that is even softer, to really
match” the adjacent tissue, Park says. Already, though, dozens of
research teams around the world have been requesting samples of the new
fibers to test in their own research.
The research team included members of MIT’s Research Laboratory of
Electronics, Department of Electrical Engineering and Computer Science,
McGovern Institute for Brain Research, Department of Chemical
Engineering, and Department of Mechanical Engineering, as well as
researchers at Tohuku University in Japan and Virginia Polytechnic
Institute. It was supported by the National Institute of Neurological
Disorders and Stroke, the National Science Foundation, the MIT Center
for Materials Science and Engineering, the Center for Sensorimotor
Neural Engineering, and the McGovern Institute for Brain Research.
