Frontiers in

neuropsychiatry
DR KKR DPM DNB
Sr Asst Prof
PMCH

Connectomics
"Connectomics"has been defined as the
science concerned with assembling and
analyzing connectome data sets.
Aconnectomeis a comprehensive map
ofneural connectionsin thebrain, and
may be thought of as its "wiring diagram".
More broadly, a connectome would
include the mapping of all neural
connections
within
anorganism's
nervous system.

A color coded functional neuronal

cluster

Connectome contd..
Research
has
successfully
constructed the full connectome of
one
animal:
theroundwormC.
elegans
Partial connectomes of a mouse
retinaand mouse primary visual
cortexhave also been successfully
constructed. Bocket al.'s complete
12TB data set is publicly available at
Open Connectome Project.

Human Connectome Project

TheHuman Connectome Project(HCP) is a
five-year
project
sponsored
by
sixteen
components of theNational Institutes of Health
The goal of the Human Connectome Project is
to build a "network map" that will shed light on
the anatomical and functional connectivity
within the healthy human brain, as well as to
produce a body of data that will facilitate
research into brain disorders such asdyslexia,
autism,Alzheimer's disease, andschizophrenia.

Tractography
Inneuroscience,tractographyis a
3D modeling technique used to
visually representneural tractsusing
data
collected
by
difusion tensor imaging(DTI)
Used for mapping long tracts and
various short tracts.

Proteomics
The term"proteome"refers to the
entire complement of proteins,
including the modifications made to
a particular set of proteins, produced
by an organism or a cellular system.
Proteomicsis the large-scale study
ofproteins,
particularly
their
structuresandfunctions.

 One major development to come

from the study of human genes and
proteins has been the identification
of potential new drugs for the
treatment of disease.
For example, if a certain protein is
implicated in a disease, its 3D
structure provides the information to
design drugs to interfere with the
action
of
the
protein.eg

 TheHuman
Proteome
Project
(HPP)
is
a
collaborative efort coordinated by the Human
Proteome Organization(HUPO). Its stated goal is to
experimentally observe all of the proteinsproduced by
the sequences translated from thehuman genome.
TheHuman Liver Proteome Project(HLPP) is a
large-scale
international
collaborativeinitiative
focusing on theproteomic analysisof the human
liver. It aims to generate a comprehensive protein
atlas of the human liver, uncover the proteomic basis
of liver development, physiology and pathology and
develop liver-specific diagnostics and therapeutics.

Proteomics and brain

understand neurodegenerative diseases and
aging.
identify prognostic and diagnostic
biomarkers.
push new diagnostic approaches and
medications.
define needs and guidelines for proteomic
approaches in brain research.
exchange knowledge with other HUPO
projects and national/international projects.

Metabolome
Metabolome refers to the complete set of
small-molecule metabolites (such as metabolic
intermediates, hormones and other signaling
molecules, and secondary metabolites) to be
found within a biological sample
the metabolome is dynamic, changing from
second to second
Metabolomics is the investigative methods to
get a metabolic snapshot of the cellular
physiology at a given time.

 The first metabolite database(calledMETLIN) for searching m/z values

from mass spectrometry data was developed by scientists at
The Scripps Research Institute in 2005.
On 23 January 2007, theHuman Metabolome Project, led by Dr. David
Wishart of theUniversity of Alberta, Canada, completed the first draft
of the human metabolome, consisting of a database of approximately
2500 metabolites, 1200 drugs and 3500 food components.
Human Metabolome Database (www.hmdb.ca)
The chemical data includes 41,514 metabolite structures with detailed
descriptions
The clinical data includes information on >10,000 metabolite-biofluid
concentrations and metabolite concentration,information on more
than 600 diferent humandiseases. The biochemical data includes
5,688protein(andDNA)
sequences
and
more
than
5000
biochemical reactions that are linked to these metabolite entries.

METLIN database
TheMETLIN
Metabolomics
Databaseis
a
repository
of
metaboliteinformation as well as
tandem mass spectrometrydata.
It contains over 64,727 structures. An
annotated list of known metabolites
and their mass, chemical formula,
and structure are available on the
METLIN website.

Nanorobotics(nanobots)
Nanoroboticsis theemerging technologyfield creating machines
orrobotswhose components are at or close to the scale of a
nanometer(109meters)
nanorobotics refers to thenanotechnologyengineering discipline
of designing and buildingnanorobots, with devices ranging in
size from 0.110 micrometers
According toRichard Feynman, it was his former graduate student
and collaboratorAlbert Hibbswho originally suggested to him
(circa 1959) the idea of amedicaluse for Feynman's theoretical
micromachines
Hibbs suggested that certain repair machines might one day be
reduced in size to the point that it would, in theory, be possible to
(as Feynman put it) "swallow the doctor
The idea was incorporated into Feynman's 1959 essayThere's
Plenty of Room at the Bottom.

 By the late 2020s, nanobots in our brain, that will

get there noninvasively, through the capillaries,
will
create
full-immersion
virtual-reality
environments from within the nervous system. So
if you want to go into virtual reality the nanobots
shut down the signals coming from your real
senses and replace them with the signals that
your brain would be receiving if you were actually
in the virtual environment. So this will provide fullimmersion virtual reality incorporating all of the
senses.Ray kurzweil futurologist

 Brain nanobots could just as easily manipulate motor

functions, cognitive processes, memories, emotions,
and basic drives.
But nanobot-mediated virtual reality, virtual emotion,
and modulated cognition are only the beginning.
Kurzweil predicts that by the late 2030s, we will be
able to routinely scan an individual's brain with such
molecular precision and with such a complete
understanding of the rules underlying neuronal
function and plasticity that we will be able to
"upload" our mental life into a vastly powerful and
capacious future computer.--Mind Uploading

 At that point, boundaries between brain,

mind, and machine would fall away. Once
our individual mental selves are instantiated
in machine form, manipulations of mental
function, perception, and action just become
software modules. Want to improve your
mood?
Want
to
preserve
all
your
experiences in memories with perfect
fidelity? Want to have the mother of all
orgasms? There's an app for that.

Carbon nanotube harpoon

catches individual brain-cell
signals
The new brain cell spear is a millimeter long, only a
few nanometers wide and harnesses the superior
electromechanical properties of carbon nanotubes
to capture electrical signals from individual
neurons.
Useful to study signals from individual neurons and
their interactions with other brain cells to better
understand the computational complexity of the
brain.
the probes are useful in a range of applications,
from basic science to human brain-computer
interfaces and brain prostheses.

Brain-machine interface
The brain-machine interface is based on a set of real-time decoding
algorithms that process neural signals by predicting their targeted
movements.
When paralyzed patients imagine or plan a movement, neurons in the
brain's motor cortical areas still activate even though the
communication link between the brain and muscles is broken. By
implanting sensors in these brain areas, neural activity can be recorded
and translated to the patient's desired movement using a mathematical
transform called the decoder.
The decoded movement was used to directly control the limb of the
animal by electrically stimulating its spinal cord.
The next step is to advance the development of brain-machine interface
algorithms using the principles of control theory and statistical signal
processing," Shanechi said. "Such brain-machine interface architectures
could enable patients to generate complex movements using robotic
arms or paralyzed limbs."

First human brain-to-brain interface allows remote

control over the internet, telepathy coming soon

The first human-to-human, brain-to-brain noninvasive

interface has been created by researchers at the University
of Washington.
The first human brain (the sender) is connected to a
computer via an EEG-basedBCI. The second human brain
(the receiver) is connected to another computer via a
Magstim transcranial magnetic stimulation (TMS) machine
When the sender plays a game and thinks about firing a
cannon at a target, the EEG picks it up, sends the signal
across the internet to the second computer, and the TMS
stimulates the region of the receivers motor cortex that
controls hand movement. This causes the receivers index
finger to twitch, firing the cannon and blowing up the target.
This process is almost instantaneous.

MindMind interface.

Passthoughts instead of
passwords
In the future, instead of trying to type your mixed-case, numbersand-punctuation on a painfully small smartphone screen, logging in
might be as simple as thinking of your password
orpassthoughts, if you will.
This finding, which comesfrom UC Berkeley, essentially turns your
brain activity into a biometric identifier. In much the same way that
your DNA or the blood vessels in your retina are unique, your
brainwaves also seem to be unique and can be used to identify you.
To do this, the Berkeley researchers use a $100 commercial EEG
(electroencephalogram). This $100 EEG, made by Neurosky,
basically resembles a Bluetooth headset with a single electrode that
rests your brains left frontal lobe. This electrode measures your
brainwaves, which it then transmits via a Bluetooth link to a nearby
PC. The Berkeley researchers say that they their system has an
error rate of below 1%,

Smartphone app for bipolar

patients wins $100K prize
A smartphone app to assist people with bipolar disorder, conceived by
Cornell researchers, has won the prestigious $100,000 Heritage Open
mHealth Challenge.
The app for iPhone and Android phones, called MoodRhythm, was
developed by a team led by Tanzeem Choudhury,
It uses a phones microphone, light sensors and accelerometer to
monitor sleep and social patterns and combines this information with
what the patient reports about daily activities, food routines and mood
to learn what situations have positive or negative outcomes.
To protect privacy, the phone does not listen in on the content of
speech, but notes variations in pitch, volume, speaking rate and other
characteristics to measure emotional states.
Choudhury directs the People-Aware Computing group at Cornell, which
develops systems that can reason about human activities, interactions
and social networks in everyday environments. The group creates
mobile apps to monitor physical and mental health,

Optogenetics
Optogenetics is the science of using genetically
modified
viruses
to
insert light-responsive channels into the neurons that th
ey infect
. If the virus is introduced early on in development, all
the progeny (ofspring) of that cell can potentially be
light responsive.
If the light opens excitatory channels, the neurons are
typically induced to fire an electric signal. The light
might also be used to inactivate a channel in which case
the neurons temporarily cant fire. Alternatively if the
light opens, in efect, negative channels, activity in the
neuron is generally inhibited and they become
unresponsive in the near term.

 40
years
ago
biologists
knew
that
some
microorganisms produce proteins that directly regulate
the flow of electric charge across cell membranes in
response to visible light. These proteins, which are
produced by a characteristic set of "opsin" genes
bacteriorhodopsin, acts as a single-component ion
pump that can be briefly activated by photons of green
light
Later identification of other members of this family of
proteinsthe halorhodopsins in 1977 and the
channelrhodopsins in 2002continued this original
theme from 1971 of single-gene, all-in-one control.

 It includes the discovery and insertion into cells of genes that confer light
responsiveness; it also includes the associated technologies for delivering
light deep into organisms
What excites neuroscientists about optogenetics is control over defined
events within defined cell types at defined times
channelrhodopsin-2 gene transfected into mammalian neurons in culture
that is, by splicing the gene for ChR2 and a specific kind of on switch, or
promoter, into a vector (like a benign virus) that ferried the added genetic
material into the cells. Promoters can ensure that only selected kinds of
neurons (such as those able to secrete the neurotransmitter glutamate) will
express, or make, the encoded proteins.
Using nothing more than safe pulses of visible light, researchers have
attained reliable, millisecond-precision control over the cells' patterns of
firing of action potentialsthe voltage blips, or impulses, that enable one
neuron to convey information to another.
Optogenetics has also been employed to control a kind of neuron (the
hypocretin cells) thought to be involved in the sleep disorder narcolepsy

 Optogenetics is thus helping to move

psychiatry
toward
a
networkengineering approach, in which the
complex functions of the brain (and
the behaviors it produces) are
interpreted as properties of the
neural system that emerge from the
electrochemical dynamics of the
component cells and circuits.

CLARITY: Hydrogel process developed

at Stanford creates transparent brain
Combining neuroscience and chemical
engineering, researchers at Stanford University
have developed a process that renders a
mouse brain transparent
The process is described in a paper published
online April 10 in Nature by bioengineer and
psychiatrist Karl Deisseroth, MD, PhD,
Researchers have used CLARITY on zebrafish
and on preserved human brain samples with
similar results, establishing a path for future
studies of human

 drew upon chemical engineering to transform biological tissue

into a new state that is intact but optically transparent and
permeable to macromolecules
This new form is created by replacing the brain's lipids with a
hydrogel. The hydrogel is built from within the brain itself in a
process conceptually similar to petrification, using what is
initially a watery suspension of short, individual molecules
known as hydrogel monomers.
The intact, postmortem brain is immersed in the hydrogel
solution, and the monomers infuse the tissue. Then, when
"thermally triggered," or heated slightly to about body
temperature, the monomers begin to congeal into long
molecular chains known as polymers, forming a mesh
throughout the brain. This mesh holds everything together, but,
importantly, it does not bind to the lipids

 With the tissue shored up in this way,

the team is able to vigorously and
rapidly extract lipids through a
process called electrophoresis. What
remains is a 3-D, transparent brain
with all of its important structures
neurons, axons, dendrites, synapses,
proteins, nucleic acids and so forth
intact and in place

 CLARITY not only allows tracing of individual neural

connections over long distances through the brain,
but also provides a way to gather rich, molecular
information describing a cell's function that is not
possible with other methods
remove the lipids nondestructively, we might be
able to get both light and macromolecules to
penetrate deep into tissue, allowing not only
3D imaging, but also 3D molecular analysis of the
intact brain

Human Brain Project

funded by theEuropean Union
aims to simulate the completehuman brainon
supercomputersto better understand how it functions.
The project is based inGeneva,Switzerland.
the project aims to build a full computer model of a
functioning brain to simulate drug treatments.
Henry Markram of cole Polytechnique Fdrale de
Lausanne described the goalsfor the Human Brain
Project in Scientific American in June, saying that the
project would become the most powerful flight
simulator ever built, it is intended to furnish a bigscreen blowup of every cell and connection inside the
human skull.

 The project involves hundreds of researchers,

from 135 partner institutions in 26 countries.
Its total costs are estimated at 1.190 billion
It is funded by theEuropean Commission
through its Future and Emerging
Technologies (FET) Flagship grant. 86
institutions across Europe are now involved
and will receive one billion euro in funding
over ten years.

Brain Research through Advancing

Innovative
NeurotechnologiesSM(BRAIN)
It is a proposed collaborative research initiative
announced by theObama administrationon
April 2, 2013, with the goal of mapping the
activity of everyneuronin thehuman brain.
Based upon theHuman Genome Project, the
initiative has been projected to cost more than
$300 million per year for ten years.
the research would map the dynamics of neuron
activity inmice and other animals and
eventually the tens of billions of neurons in the
human brain.

 They proposed the development of

nanoparticlesthat could be used asvoltage
sensorsthat would detect individual
action potentials, as well asnanoprobesthat
could serve aselectrophysiological
multielectrode arrays.
In particular, they called for the use of
wireless, noninvasive methods of neuronal
activity detection, either utilizing
microelectronicvery-large-scale integration,
or based onsynthetic biology

Allen Brain Atlas

TheAllen Mouse and Human Brain Atlasesare
projects within theAllen Institute for Brain Sciencewhich
seek to combinegenomicswithneuroanatomyby creating
gene expressionmaps for the mouse and human brain.
As of May 2012, sevenbrain atlaseshave been published:
Mouse Brain Atlas, Human Brain Atlas, Developing Mouse
Brain Atlas, Developing Human Brain Atlas, Mouse
Connectivity Atlas, Non-Human Primate Atlas, and Mouse
Spinal Cord Atlas.
They aim to advance the research and knowledge about
neurobiological conditions such asParkinson's,Alzheimer's
, andAutismwith their mapping of gene expression
throughout the brain.

 The Allen Brain Atlas website contains a

downloadable 3-D interactive Brain explorer. The
explorer is essentially a search engine for locations of
gene expression; this is particularly useful in finding
regions that express similar genes.
The Allen Human Brain Atlas was made public in May
2010. It was the first anatomically and genomically
comprehensive three-dimensional human brain map.
The atlas is also geared toward furthering research
into mental health disorders and brain injuries such
asAlzheimer's disease, autism,schizophreniaand
drug addiction.

Brain Implant Could Restore Memory

The Defense Advanced Research Projects Agency
(DARPA) is forging ahead with a four-year plan to
build a sophisticated memory stimulator, as part
of President Barack Obama's $100 million BRAIN
initiative to better understand the human brain.
"We think that we can develop neuroprosthetic
devices that can directly interface with the
hippocampus, and can restore the first type of
memories we are looking at, the declarative
memories,Declarative memories are
recollections of people, events, facts and figures,

The Forgetting Pill Erases Painful Memories Forever

When a memory is first formed a number of proteins become active within participating
neurons. These proteins help reshape the neurons thus making the memory permanent.
Once this reshaping is complete the proteins involved in the process once again become
inactive.
Researchers have uncovered a protein (PKMZeta) which, unlike others involved in memory
formation, remains active in cells long after the initial memory forming eventperhaps
indefinitely. This discovery led scientists to question whether PKMZeta may hold the key to
maintaining memory
Researchers have erased recently stored memories in the brains of rats by injecting them
with ZIP, a chemical that neutralises PKMzeta.
Boosting old memories by loading rats withextraPKMzeta. They injected the rodents with
viruses carrying the protein, before teaching them to avoid the taste of sweetener. With extra
copies of PKMzeta in their brains, the rats were morelikely to remember their distaste.
PKMzeta works by increasing the levels ofAMPAR, a protein that sits at synapses and allows
fast signals to travel across them.
In humans, the distressing memories underpinningpost-traumatic stress disorder (PTSD)
can occur following experiences of life-threatening incidents such as military combat, assault,
serious accidents or terrorist attacks.
Disruption of memory reconsolidation may provide the magic bullet to erase these
damaging memories.

Brain-to-Brain Mind Meld

a non-invasive telepathic interface between two humans
brains.
By wearing an EEG cap that read his brains electrical signals,
UW computer scientist Rajesh Rao was able to use his
thoughts to control the actions of assistant professor Andrea
Stucco, who wore a transcranial magnetic stimulation coil that
stimulates brain activity. A code was used to translate brain
signals from EEG readings into brain commands.
With both hands on his chairs arm rests, Rao envisioned his
right hand moving, as if he was clicking a fire button on a
cannon shooting video game. Across campus, Stucco had his
back to the computer screen where the video game was
playing out. Still, he involuntary moved his right hand and
pushed his keyboards space bar to fire the cannon.

Neural engineering
Neural engineering(also known as
Neuroengineering) is a discipline within
biomedical engineeringthat uses engineering
techniques to understand, repair, replace, enhance, or
otherwise exploit the properties of neural systems.
The field of neural engineering draws on the fields of
computational neuroscience, experimental
neuroscience, clinicalneurology,electrical engineering
andsignal processingof living neural tissue, and
encompasses elements fromrobotics,cybernetics,
computer engineering,neural tissue engineering,
materials science, andnanotechnology.

 Prominent goals in the field include

restoration andaugmentationof
human function via direct
interactions between the nervous
system andartificial devices.
Neuromechanics
Neuromechanicsis the coupling of
neurobiology, biomechanics,
sensation and perception, and
robotics

 Neuromodulation
Neuromodulationaims to treat disease or injury by
employing medical device technologies that would
enhance or suppress activity of the nervous system
with the delivery of pharmaceutical agents,
electrical signals, or other forms of energy stimulus
to re-establish balance in impaired regions of the
brain.
Neuromodulator devices can correct nervous system
dysfunction related to Parkinson's disease, dystonia,
tremor, Tourette's, chronic pain, OCD, severe
depression, and eventually epilepsy.

 Artificial neural networkscan be built

from theoretical and computational
models and implemented on
computers from theoretically devices
equations or experimental results of
observed behavior of neuronal
systems. Models might represent ion
concentration dynamics, channel
kinetics, synaptic transmission,
single neuron computation, oxygen

 Neural interfacesare a major element used for

studying neural systems and enhancing or
replacing neuronal function with engineered
devices.
Optical neural interfaces involveoptical recordings
andoptogeneticsstimulation that makes brain
cells light sensitive. Fiber optics can be implanted
in the brain to stimulate and record this photon
activity instead of electrodes.
Two-photon excitation microscopycan study living
neuronal networks and the communicatory events
among neurons

 Brain computer interfaces

Microelectrode arraysare specific tools used to
detect the sharp changes in voltage in the
extracellular environments that occur from
propagation of an action potential down an axon.
Dr. Mark Allen and Dr. LaPlaca have microfabricated
3D electrodes out of cytocompatible materials such
as SU-8 and SLA polymers which have led to the
development of in vitro and in vivo microelectrode
systems with the characteristics of high compliance
and flexibility to minimize tissue disruption.

What is CRISPR?
CRISPR, which stands for Clustered Regularly
Interspaced Short Palindromic Repeats, is the latest
in a long line of genome editing techniques.
The technology, can be used to make specific
changes in the DNA of plants and animals, has
become instrumental to studying disease systems in
the lab because of its low cost, precision, and ease
of use.
Unlike other genome editing methods, scientists can
use it to change any stretch of DNA in a genome, as
long as they know the sequence to target. They can
make multiple changes in one fell swoop.

 The CRISPR system has two parts: 1) a protein

borrowed from bacteria thatcuts DNA, and
2) aguide RNAthat tells the protein where to cut.
Once the DNA of the gene being targeted is cut,
the cell will try to repair the DNA but will often
make a mistake, causing the gene to be disrupted
and no longer function.
3:DNA template tells the cell how to repair the
cut DNA and introduce a very specific mutation that
changes the gene in some way. Either way,
scientists can use CRISPR to alter the DNA inside
cells.

How CRISPR works. A guide RNA that matches the genomic DNA
sequence of interest helps direct a CRISPR protein toward this site in the
DNA. The protein cuts the strands of DNA. The cell will try to repair this
break, but during this process may introduce random mutations that
render the gene non-functional the gene is thus silenced. However, if
scientists introduce a DNA template that is slightly diferent from the
original DNA sequence, the cell can use it to guide the repair and
introduce a specific mutation into the gene sequence.

The advent of CRISPR has been timed perfectly with the recent
neuroscience research boom. Over the past few years, scientists
have been using gene sequencing to uncover genes that are
important in brain development and in neurological diseases,
like Alzheimers disease andschizophrenia. Whereas some
neurodevelopmental disorders, likeFragile X Syndrome, are
known to be caused by mutations in a single gene, diseases like
schizophrenia involve many genes and are very complicated, so
thousands of people had to be sequenced before scientists
could figure out which genetic diferences might be linked to the
disease.
Today, there are clues to the genes that might afect a number
of disorders, like OCD, autism, and major depression. The next
step is to figure out if disrupting these genes can cause any of
these diseases.
CRISPR seems to be the perfect technology to make this happen
.
Because the brain is the product of
millions of connections between neurons, its important to see
what these genetic changes do in an actual animal brain. If we
think that a specific mutation in the Huntingtin gene causes
Huntingtons disease, we can introduce that mutation into the
embryo of a mouse via the CRISPR system. These mice and
their ofspring will contain this mutation and we can study their
behavior and physical changes and see if they have the mouse
version of Huntingtons disease. These mice can then be given
potential drugs to see if those drugs help relieve symptoms

CRISPR and neuroscience

Using CRISPR to study neurological diseases in model organisms. Once a possible genetic link has been
found to a neurological disease like Huntingtons disease, Alzheimers disease, or Parkinsons disease,
scientists can use the CRISPR system to introduce the relevant genetic mutations into model organisms
like mice. By understanding the diferences between mice with the genetic mutation and mice without it,
scientists can paint a clearer picture of how the disease might be afecting a human body. Then, the mice
can be given potential drugs or treatments that can help to alleviate their symptoms or even help cure the
disease.

Timeline of CRISPR compared to a traditional genome editing technique. For diseases like OCD that
are known to be caused by more than one genetic mutation, making model organisms with multiple
genetic mutations is crucial to understanding the disease. With traditional genome editing
methods, it might take up to three years to create a mouse model with two genetic mutations, with
CRISPR, scientists can create a mouse model with one, two, or even more genetic mutations in as
little as six weeks!

With CRISPR, dozens of mouse models and other animal

models have been made to study neuroscience. For
example, the Zhang lab at the Broad Institute in
Cambridge, MA have used CRISPR to make mouse models
ofOCD and autism.
Mice with OCD-related genetic mutations groom
themselves more and seem to be anxious about their
environmental cleanliness and mice with autism-related
genetic mutations are generally less sociable than other
mice.
The Zhang lab is currently working on making mouse
models with particular mutations in a gene calledShank3
which might be important in both autism and
schizophrenia.
Many scientists are also using CRISPR in human induced
pluripotent stem cells or in neurons derived from these
stem cells to study the efects of genetic changes on
human neurons in a dish. As neuroscientists create more
animal and cell models with CRISPR, we will be able to
unravel more about what makes the brain tick and how to
fix it if it breaks.

CRISPR and
Stem cells
Disease in a Dish: Using Stem Cell-Derived Neurons
to Understand the Brain

Organoids: Brains in a Dish?

Stem cells, the forefathers of each of the 3.72 trillion cells
that make up the adult human body, have the unique ability
to become any kind of cell, much like the potential we begin
with in life. They slowly make choices that propel them down
certain paths, toward certain fates, until ultimately they
mature and end up as a neuron in your brain, or a skin cell in
your toe, or a muscle cell in your heart.
Throughout human development, the fate of most stem cells
becomes narrower and more specific until they reach a fully
mature state, a process known asdifferentiation.Within the
body, the process of diferentiation is generally irreversible:
once a mature cell is formed, it no longer has unlimited
potential, orpluripotency.

Reprogramming and directed

diferentiation

Successful reprogramming of diferentiated human somatic cells into a

pluripotent state would allow creation of patient- and disease-specific
stem cells. We previously reported generation of induced pluripotent
stem (iPS) cells, capable of germline transmission, from mouse
somatic cells by transduction of four defined transcription factors.
Here, we demonstrate the generation of iPS cells from adult human
dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and
c-Myc. Human iPS cells were similar to human embryonic stem (ES)
cells in morphology, proliferation, surface antigens, gene expression,
epigenetic status of pluripotent cell-specific genes, and telomerase
activity.
Furthermore, these cells could diferentiate into cell types of the three
germ layers in vitro and in teratomas. These findings demonstrate that
iPS cells can be generated from adult human fibroblasts.--Takahashi

 130 scientists, entrepreneurs and policy leaders held an

invitation-only,
closed-door
meeting
at
Harvard
University to discuss an ambitious plan to create
synthetic human genomes.
After a flurry of criticism over the secrecy of the efort,
the participants have published their idea, declaring that
they're launching a project to radically reduce the cost of
synthesizing genomes a potentially revolutionary
development in biotechnology that could enable
technicians to grow human organs for transplantation.
The announcement, published in the journal Science, is
the latest sign that biotechnology is going through a
rapidly advancing but ethically fraught period.

Human Genome Project

Write
The promoters of synthetic genomes envision a
project that would eventually be on the same scale
as the Human Genome Project of the 1990s, which
led to the sequencing of the first human genomes.
The diference this time would be that, instead of
reading genetic codes, which is what sequencing
does, the scientists would be writing them. They
have dubbed this the Genome Project-write.
The goal of HGP-write is to reduce the costs of
engineering and testing large genomes, including a
human genome, in cell lines, more than 1,000-fold
within ten years.

 The Science paper gives a number of examples of

what could emerge from cheaper synthesized
genomes: "growing transplantable human organs;
engineering immunity to viruses in cell lines via
genome-wide
recoding;
engineering
cancer
resistance into new therapeutic cell lines; and
accelerating
high-productivity,
cost-efficient
vaccine and pharmaceutical development using
human cells and organoids.
The synthetic genome plan emerged from two
closed-door meetings, one in New York City last
year, and the second on May 10 at Harvard.

 Doctors have always recognized that every

patient is unique, and doctors have always
tried to tailor their treatments as best they
can to individuals. You can match a blood
transfusion to a blood type that was an
important discovery. What if matching a
cancer cure to our genetic code was just as
easy, just as standard? What if figuring out
the right dose of medicine was as simple as
taking our temperature?
- President Obama, January 30, 2015

Mission Statement
The future of precision medicine will enable health care
providers to tailor treatment and prevention strategies to
peoples unique characteristics, including their genome
sequence, microbiome composition, health history, lifestyle,
and diet.
To get there, we need to incorporate many diferent types of
data, from metabolomics (the chemicals in the body at a
certain point in time), the microbiome (the collection of
microorganisms in or on the body), and data about the
patient collected by health care providers and the patients
themselves.
Success will require that health data is portable, that it can
be easily shared between providers, researchers, and most
importantly, patients and research participants.

 Most medical treatments have been designed for the average patient. As
a result of this one-size-fits-all-approach, treatments can be very
successful for some patients but not for others.
This is changing with the emergence of precision medicine, an innovative
approach to disease prevention and treatment that takes into account
individual diferences in peoples genes, environments, and lifestyles.
Precision medicine gives clinicians tools to better understand the complex
mechanisms underlying a patients health, disease, or condition, and to
better predict which treatments will be most efective.
Patients with breast, lung, and colorectal cancers, as well as melanomas
and leukemias, for instance, routinely undergo molecular testing as part of
patient care, enabling physicians to select treatments that improve chances
of survival and reduce exposure to adverse efects.
The Presidents 2016 Budget will provide a $215 million investment for the
National Institutes of Health (NIH), together with the Food and Drug
Administration (FDA), and the Office of the National Coordinator for Health
Information Technology (ONC) to support this efort.

Single molecule electronic DNA nanopore

sequencing advanced
Researchers from Columbia University, with
colleagues at Genia Technologies (Roche),
Harvard University and the National Institute of
Standards and Technology (NIST) report
achieving real-time single molecule electronic
DNA sequencing at single-base resolution using
a protein nanopore array.
revolutionary, cost-efective genetic diagnostic
platforms with unprecedented potential for
precision medicine
reaching read-lengths of over 1000 bases of
DNA has recently been achieved.

single-molecule nanopore DNA sequencing by

synthesis data from a template with homopolymer
sequences.

INTERNET OF CARING THINGS

consumers will embrace connected objects with a
clear mission: to actively care for them.
All too often, the Internet of Things looks likethis.
The Samsung T9000 is a wifi-enabled smart fridge
that allows users to Tweet via a touchscreen
embedded on the door. It retails for USD 4,000.
INTERNET OF CARING THINGS | A network of
connected objects brought to life by a clear
mission: to actively care for consumers their
physical and mental wellbeing, homes, loved ones,
and more.

 Cuptime a Chinese smart cup that monitors hydration for

the user. The user enters their height and weight, and
Cuptime will monitor if they are drinking enough and award
the user a hydration performance score on their
smartphone.
Athos a smart fitness suit that monitors muscle function,
heart rate, breathing, cadence, balance, and form. The suit
allows wearers to track how they are using their muscle
groups and if they are exercising properly.
Stir Kinetic Desk a smart desk that monitors health and
encourages productivity. The user enters personal data and
selects a preferred height for the desk. In Active Mode, the
desk will move up and down to encourage the user to
move at appropriate times.

 INTERNET OF MINDFUL THINGS

Mindful products are designed to help stressed, overstimulated, and time-poor individuals balance their work
and mental health.
NeuroOn a sleep mask that monitors brain waves, eye
movement, and muscle tension to help the user get the
most out of their nap. Forget the nap pods at Google, you
can have your own powernap this July for $250!
Vigo a device worn around the ear that uses an
infrared sensor to detect the users levels of alertness.
When Vigo detects the wearer is growing tired, an alert is
sent to the users smartphone to energize them.

And the Revolution

Continues

Exponential medicine
Liquid Biopsy
Stereology/Blue histology
Wearable tech
Lipidomics
DNA microarrays
Caspase inhibitorsto stop apoptosis
neurogenesis stimulators
glia-proliferation enhancers to rebuild white matter
Orexin modulators
Targetted neurostimulation
Precision pharmaco genomics
Electroporation
SLENDR --SLENDR provides a valuable means to determine subcellular localization of proteins, and will help researchers to
determine the function of the proteins.
Digital distributism and Peer to peer healthcare
Big data initiatives
Self healing Bio prosthetics
Biosimilars
Organs in Dishes to Diseases in Dish
molecular engineering,, electronics and data science
Human Animal Chimeras.
Neural electronics
Neural dust
Neuromorphic computing