MEDICAL BEAT May 9, 2014
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April-
June 2014
Issue 1
Also in this issue:
The Science Behind Tomorrow’s Medicine
June 2014, Sample Issue
MITIGATING THE DEADLY EFFECTS OF RADIATION EXPOSURE
New Drug Provides Protection against Radiation Sickness pg.11
Issue 1
STRATEGIES TO COMBAT THE
ROOT OF ASTHMA
Breathing Better with Early-Life
Prevention and New Treatments
pg. 22
CATCHING THE HACKERS
BEHIND CANCER
METASTASIS
New approach to stop cancer’s
invasion into the bloodstream
Page 10
FORGETFULNESS BEGINS WITH
NEW NEURONS
Exercise Produces New Neurons to Erase
Unused Memories
pg. 16
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About the Cover
The cover depicts an image of the workers at the
Fukushima nuclear plant following the 2011 nuclear
disaster. Scientists recently discover a new drug that
can protect these workers from the lethal effects of
radiation exposure.
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EDITORIAL Executive Editor- Jennifer WJ Wong (PhD)
ABOUT THE EDITOR
Jennifer received her PhD in Neuroscience in 2010 at the University of British
Columbia in Vancouver, Canada. While working on her postdoctoral fellowship at
the Brain Research Centre (UBC), Jennifer began her career as a scientific writer
by starting her online blog on Science2.0, and has since published in Science
Magazine and the Lancet Oncology. She later joined the Nature Publishing Group
in London (UK) as a temporary scientific editor. Today, Jennifer is the executive
editor of her newly launched magazine The Medical Beat.
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CONTENTS June 2014, Sample Issue
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Forgetfulness Begins with New Neurons Exercise Produces New Neurons to Erase Unused Memories
Mitigating the Deadly Effects of Radiation Exposure New Drug Provides Protection against Radiation Sickness by
Protecting the Gut Epithelium from Radiation Damage.
Snapshots- Wireless device to recharge deeply implanted pacemakers, and 1018 eliminates bacteria biofilm
Editor’s Pick Primitive Viruses Point to a New Cancer Treatment
Combating the Root of Asthma Breathing Better with Early-Life Prevention and New Treatments
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A Wireless Technology to
Recharge Pacemakers
Dr. Ada Poon and colleagues at Stanford University created a miniature
wireless power transfer technology to safely recharge deeply implanted
devices including pacemakers. Credit: Image courtesy of Austin Yee.
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When a pacemaker runs out of power, the
simple act of replacing the pacemaker’s
batteries is an invasive surgical procedure. An
ideal alternative would be to recharge implanted
pacemakers using a wireless power transfer
technology. But the technology that is available
so far is not powerful enough to deliver
sufficient energy to deeply implanted devices, or
small enough to be safely implanted.
In this study, Poon and colleagues designed a
new wireless power transfer technology that can
successfully charge deeply implanted
pacemakers by focusing electromagnetic energy
deep into tissue. The wireless technology
consists of a patterned metal plate that uses
midfield power transfer to focus
electromagnetic energy to a specific region deep
in tissue, where the energy could be taken up by
an implanted power-harvesting device. By
focusing electromagnetic energy, Poon and
colleagues are able to remotely transfer up to
2000 microwatts of power to a miniature power-
harvesting device that is implanted into 5cm of
tissue.
The size of a rice grain, this miniature power-
harvesting device can be safely implanted into
the heart. The device can effectively power
pacemakers- which only need about 8
microwatts of power. The study is published in
the May 19th 2014 issue of the Proceedings of
the National Academy of Sciences1.
1. Ho J.S. et al. Proceedings of the National Academy of Sciences
(2014) in press.
Smaller than the size of a pill, this tiny implantable
device can be remotely charged deep inside the
body using a new wireless power transfer
technology. The device can be used to safely power
deeply implanted devices such as pacemakers.
Credit: Image courtesy of Austin Yee.
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1018: Bacteria Biofilm Busters
Dr. Robert Hancock at the University of British Columbia discovered a
peptide, 1018, that could stop bacteria from forming biofilms.
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Previous page: Bacteria
such as E. coli form
communities called
biofilms in response to
stress.
Right: 1018 stops biofilm
building. Bacteria such as
Pseudomonas aeruginosa
and MRSA can’t form
biofilms in the presence of
1018. (Credit: César de la
Fuente-Núñez)
A biofilm is a community of harmful bacteria
that is implicated in 65% of bacterial infections
in humans. These communities represent a
microbial survival tactic that can help bacteria
resist the host’s anti-microbial defense and even
antibiotics. Often sticking to various surfaces like
human skin and surgical instruments, these
bacterial biofilms are considered a major health
concern worldwide.
The formation of a biofilm is triggered by a
bacterial stress signal known as (p)ppGpp- a
signal that is evolutionarily conserved across all
species of bacteria. As a defense mechanism
against these infectious biofilms, nature has also
created biofilm-inhibiting peptides to stop the
formation of bacteria biofilms.
In a study published in the May 2014 issue of
PLOS Pathogens, Dr. Hancock and colleagues
successfully identified a human peptide with
broad-spectrum biofilm blocking activity- a
peptide known as IDR (innate defense
regulator)-10181. Also known simply as 1018,
this peptide could directly trigger the
degradation of the bacterial stress signal
(p)ppGpp responsible for biofilm formation.
Hancock further shows that 1018 can prevent
biofilm formation in wide range of bacteria,
including E.coli, MRSA, and Pseudomonas. 1018
is also powerful enough to disperse bacteria
biofilms that are at least 2 days old, and to
promote bacterial cell death. The discovery of
1018 could point the way to eliminating biofilms
and minimizing infections.
1. de la Fuente-Nunez C. et al. PLOS Pathogens 10,
e1004152. (2014)
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Primitive Viruses Point
to a New Cancer
Treatment Virus-Derived Peptibodies
Deplete Immune Cells That
Promote Cancer Growth
Our immune system is constantly on
the lookout for cancerous cells in
our bodies, eliminating them before
they become a disease. A prevailing
concept in the late 1990’s suggests
the cancer has the ability to evade
the immune system1. Scientists now
know that cancers release immune
signals to stimulate the recruitment
of a mixed white blood cell
population called myeloid derived
suppressor cells (MDSCs)2.
Like a cloak of darkness shielding
invaders from surveillance cameras,
MDSCs are immune suppressive cells
that are implicated in helping cancer
evade immune surveillance3,4. Specifically,
MDSCs can inhibit immune surveillance by
suppressing and killing T cells- an immune cell
population that can recognize and attack tumor
cells5,6. MDSCs can also activate regulatory T
cells (Treg)- an immune cell population known to
silence the immune system against the cancer7.
Given the well-accepted role of MDSCs in
cancer’s immune evasion, Dr. Larry Kwak and
colleagues at the University of Texas MD
Anderson Cancer (Houston, TX) wondered if
they could thwart the cancer’s ability to evade
the immune system simply by removing MDSCs.
To answer this question, one challenge that
Kwak faces is the lack of proper tools to
effectively deplete MDSCs. “We’ve known about
[MDSCs] for a decade, but haven’t been able to
shut them down for lack of an identified target,”
said Kwak.
In the study published in the May 28th issue of
Nature Medicine8, Kwak’s team set out to
identify an MDSC-specific marker by probing the
surface of MDSCs with a library of primitive
viruses known as phages. Each phage typically
displays a unique array of peptides that can
recognize specific cell surface markers. By
probing the surface of MDSCs with a library of
phages, Kwak discover that phages expressing
either the G3 or H6 peptides can bind
Phages (small particles depicted here) are primitive viruses that
display specific peptides on their surface. Kwak identified 2 phage
peptides (G3 and H6) that can bind specifically to MDSCs.
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specifically to MDSCs.
To create “antibodies” that can specifically
recognize MDSCs, the team designed an
antibody-peptide fusion (peptibody) that
incorporates G3 and H6 peptides into the part of
the antibody that is involved in recognizing
antigens. The idea is to create an “antibody”
version of G3 and H6 peptides, called Pep-G3
and Pep-H6 peptibodies, which can recognize
and bind to MDSCs specifically.
Unlike the G3 and H6 peptides, however the
Pep-G3 and Pep-H6 peptibodies actually behave
like antibodies. Antibodies typically work by
flagging cells for immune destruction- in a
process dubbed antibody-dependent cell-
mediated toxicity (ADCC)9. During ADCC, cells
that are flagged with antibodies could be
recognized by an immune cell population known
as natural killer (NK) cells, which release toxins
to kill the antibody-bound cell. Similar to
antibodies, Pep-G3 and Pep-H6 peptibodies can
flag MDSCs for immune destruction, depleting
MDSCs from the system.
To see if the peptibodies can specifically deplete
tumor-associated MDSCs in mice, Kwak injected
the Pep-G3 or PepH6 into a mouse model of
thymus cancer- a model created by implanting
EL4 thymus cancer cells under the mouse skin.
Following peptibody injections, Kwak discover
that either Pep-H6 or Pep-G3 could deplete
MDSCs over the course of 2 weeks. The
peptibodies did not deplete other immune cells,
demonstrating the incredible cell-type specificity
of these peptibodies.
That’s really exciting because [the peptibodies
are] so specific for MDSCs that we would expect
few, if any, side effects,” said Dr. Kwak.
Kwak further shows that the MDSC depletion is
associated with a significant decline in cancer
growth in mice, suggesting that MDSC-depleting
peptibodies could potentially be a new class of
drug to combat cancer.
Further investigating how the peptibodies affect
cancer growth, Kwak also discovered that Pep-
G3 and Pep-H6 peptibodies appear to recognize
specifically the S100A8 and S100A9 proteins
respectively. S100 proteins are typically
expressed in cancer cells to recruit MDSCs2, to
boost MDSC recruitment.10 The same signals are
also produced by MDSCs to help cancer cells
survive and grow11. Kwak explains that the
peptibodies could sequester these important
survival signals, and consequently hinder cancer
growth in mice.
The question that remains to be answered is
whether MDSC-depleting peptibodies could also
reactivate the immune response against the
cancer. Although further work is needed to
answer this compelling question, Kwak is
optimistic that peptibodies could help unleash
the immune system against the cancer.
The next step is to test whether the peptibodies
could deplete MDSCs in humans, and whether
this approach could successfully combat human
cancers.
By: Jennifer Wong
1. Dunn GP et al Nat Immunol. 3, 991 - 998 (2002)
2. Sinha P et al J Immunol. 181, 4666-75 (2008)
3. Kusmartsev S. J Immunol. 175, 4583-92 (2005)
4. Kusmartsev S. & Gabrilovich DI. J Immunol. 174, 4880-91 (2005)
5. Rodriguez P.C. et al Blood 109, 1568-1573 (2007)
6. Bingisser R. et al. J. Immunol. 160, 5729-5734 (1998)
7. Huang B et al Cancer Res.66, :1123-31 (2005).
8. Qin H. et al. Nat Med. (2014)- in press
9. Strome S.E. et al. The Oncologist. 12 , 1084-1095 (2007). Review.
10. Ichikawa, M et al. Mol. Cancer Res. 9, 133–148 (2011)
11. Källberg, E. et al. PLoS ONE 7, e34207 (2012)
The Medical Beat 11
Mitigating the Deadly Effects
of Radiation Exposure A New Drug Provides Protection against Radiation Sickness
by Protecting the Gut Epithelium from Radiation Damage
By: Jennifer Wong
Read the full story in the June 2014 issue of the Medical
Beat. Purchase your copy today.
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12
A portrait of radiation sickness: An 11-year Japanese girl
who survived the nuclear bombing in Hiroshima in
World War II.
An indelible portrait of the devastating
effects of radiation exposure is the sickly bald
face of an 11-year old Japanese girl from the
Hiroshima nuclear bombing in 1945. This image
depicts radiation sickness- a major health
concern that still haunts today’s society
especially in light of the recent 2011 nuclear
incident in Fukushima Daiichi, Japan, in what
appears to be an unfortunate aftermath of a
tsunami.
With radioactive waste water and debris being
released into the oceans, and travelling
relentlessly towards the pristine west coast
shorelines of Canada and the United States,
radiation is now becoming a global health
concern. Because there are no known FDA-
approved drugs to mitigate the harmful effects
of radiation, scientists are keen to understand
precisely how radiation kills, and what could be
done to reduce the deadly effects of radiation
exposure.
Although precisely how radiation causes death
remains unclear to this day, scientists now know
that radiation causes cell death by inflicting
damage to DNA, the genetic material of the cell
that is replicated during the process of cell
division. Rapidly dividing cells in the bone
marrow, hair follicles and the gut, in particular,
are the most susceptible to radiation damage
and are often the first to be eliminated upon
radiation exposure. Among the battery of
symptoms that define radiation sickness, the
destruction of the gut lining is considered one of
the major causes of death1,2.
In a recent study published in the May 14th issue
of Science Translational Medicine3, scientists at
Stanford University discover an intrinsic cell
stress signal that can protect the body from
radiation sickness, especially by protecting the
gut lining from radiation-induced damage. The
discovery can open a new avenue to mitigate
the life-threatening consequences of radiation.
Harnessing the Gut’s Protective Mechanism
against Radiation Damage
The gut lining, also known as the gut epithelium,
consists of epithelial cells that form a brush-like
barrier between the bloodstream and the gut
environment. This barrier helps the body absorb
nutrients and water from the food we eat, while
preventing gut bacteria from invading the
bloodstream. The destruction of the gut
epithelium from radiation exposure puts the
body at risk of severe dehydration and
electrolyte imbalance, intestinal defects causing
diarrhea and vomiting, as well as life-threatening
sepsis caused by the invasion of gut bacteria1,2.
Read the full story in the June 2014 Issue…
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Forgetfulness Begins with New Neurons
Exercise Produces New Neurons to Erase Unused Memories
By: Jennifer Wong
Read the full story in the June 2014 issue of the Medical Beat.
Purchase your copy today.
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Forgetfulness is something that we often face
over the course of our lifetime. It’s very common
to forget about the events in our early lives as
infants and toddlers, and we often rely on
parents to provide fond recollections of these
early memories. As we begin to age, we face
embarrassing moments when we search in vain
for our lost vehicle in the parking lot, or when
we forget the names of familiar faces at a
cocktail party.
Although precisely what causes forgetfulness
remains unclear, decades of research has at least
revealed some insights into how memories are
formed. We now know that memories are stored
in a brain structure called the hippocampus.
Contained in this distinctive structure are
neuronal circuits that encode memories, as well
as a neuronal germinal center to produce new
neurons. The latter is involved in producing
neurons in the adult in the process dubbed adult
neurogenesis, and is implicated in memory
formation1. The gradual decline of neurogenesis
with increasing age2, or in dementia3, is further
implicated in reducing memory.
Interestingly, scientists also discovered that
regular exercise can actually boost
neurogenesis, specifically by turning on genes
that can stimulate the neuronal germinal centers
in the hippocampus to produce new neurons4. A
body of work reveals that exercise can drive the
expression of growth factors and
neurotransmitters (serotonin) that can boost the
production of neurons4,5,6. Particularly in the
elderly, exercise appears to be an effective way
to boost neurogenesis and learning2, suggesting
that regular exercise could improve the
development of new memories as we age.
But before we flock to the gym for some
memory-boosting exercise, scientists now
caution that exercise can also cause
forgetfulness. Although exercise can boost
memory by driving the production of new
neurons to build new memories, a recent study
published in the May 9, 2014 issue of Science7
reveals that exercise-induced neurogenesis can
cause forgetfulness by impeding the retrieval of
old memories. The study also shows that high
levels of neurogenesis in the infant during early
brain development can also be the culprit
behind infantile amnesia, preventing us from
recalling the early events in our infanthood and
early childhood.
Exercise-Induced Neurogenesis Promotes
Forgetfulness in Adult Mice
n the study published in Science,7 Dr. Paul
Frankland and colleagues at the Toronto’s Sick
Kids Children Hospital (ON, Canada) discover
that exercise can promote forgetfulness. They
show this by using a series of behavioral tests to
evaluate how exercise-induced neurogenesis
could influence the retrieval of old memories in
mice.
The behavioral study involves testing mice that
are trained to associate a specific context with a
foot shock- in a behavioral paradigm called
contextual fear conditioning. Several weeks after
this training, the team evaluated whether
exercise could influence how well the mice could
remember the context (ex: a designated cage)
associated with foot shock, and whether they
could demonstrate contextual fear by showing a
“freeze” response to this context.
Read the full story in the June 2014 Issue…
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Combating the Root of Asthma Breathing Better with Early-Life Prevention and New Treatments
By: Jennifer Wong
Image credit: Тетяна Фіонік/CC-BY-SA-3.0
Read the full story in the June 2014 issue of
the Medical Beat. Purchase your copy today.
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The breath of life is something that we take
for granted. But for someone who has asthma,
breathing can be an everyday struggle, where
simple triggers like dust mites, pollen or even
physical exertions can cause a fit of wheezing
and coughing. Often diagnosed in childhood, this
recurrent disease threatens to take away the
ease of breathing at any moment, and could be
an impediment to everyday sports and activities
throughout life.
The wheezing during an asthma attack is caused
by an allergic inflammatory reaction that
constricts the airway1- a potentially life-
threatening condition that asthma sufferers
often face. The allergic inflammation is caused
by a population of allergic lymphocytes, T helper
2 (TH2) cells1. In response to allergen inhalation,
TH2 cells release signals to stimulate the
production of IgE antibodies, which in turn
activate white blood cells (such as eosinophil
and mast cells) in the airway and lungs. The
white blood cells respond by releasing
inflammatory signals such as histamine- a signal
that stimulates smooth muscles in the
respiratory tract to contract. The contraction
constricts the airway, causing an asthma attack.
The most common treatment for asthma is an
inhalable muscle relaxant, known as
bronchodilators, which can re-open the airway.
Although this inhalant could serve as an
immediate relief for asthma sufferers during an
asthma attack, it does very little to combat the
root of the inflammatory reaction that causes
asthma in the first place. Because asthma is a
recurrent disease, many asthma sufferers use
bronchodilators on a regular basis, and its
prolonged use could often promote tolerance.
The tolerance could render bronchodilators
useless against a future asthma attack2. Clearly,
a more effective treatment is needed to better
combat asthma.
With 235 million asthma sufferers worldwide,
based on an estimate from the World Health
Organization, there is an urgent need to better
An asthma attack is an
allergic inflammatory
reaction that constricts
the airway. The
constriction is caused by
the activation of
immune cells that
produce histamine- a
chemical that stimulates
muscles in the airway to
contract.
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understand what causes of asthma and what
could be done to mitigate the root of this
disease. Although scientists today are still not
sure what causes asthma, a prevalent
hypothesis in the last decade suggests that good
hygiene especially in today’s health-conscious
society could be a potential cause. According to
a 2002 review published in Nature Immunology3,
scientists show clinical evidence suggesting that
children who are exposed to good commensal
bacteria early in life- the bacteria lost to good
hygiene- are less likely to develop asthma. The
bacterial exposure is thought to promote
immune tolerance to allergens- specifically by
suppressing the development of TH2 cells, and
by promoting the development of regulatory T
cells (Treg) to inhibit allergic inflammation in
asthma.
In support of the hygiene hypothesis, Dr.
Benjamin Marsland from the University Hospital
in Lausanne shows for the first time that the
mother’s commensal microbes can colonize the
lungs of neonatal mice. The bacterial
colonization of the lung, especially in the first 2
weeks of life, is crucial for suppressing asthma
later in life. In his paper published in the May
11th, 2014 online issue of Nature Medicine4,
Marsland suggests that factors influencing
microbial exposure early in life, including
antibiotic use or the mother’s diet, could have
implications on whether infants will develop
asthma.
In another study published in the May 20th, 2014
online issue of New England Journal of
Medicine5, Canadian researchers from McMaster
University show that antibodies suppressing
TLSP (thymic stromal lymphoid protein) could be
a potential treatment to combat the root of
asthma in human clinical trials. The clinical study
shows that TLSP is continuously produced in
individuals with asthma, and that TLSP-blocking
antibodies not only reduce baseline
inflammation in the lungs, but could also protect
asthma sufferers from developing an asthma
attack in response to inhaled allergens. The
study points to a potential treatment to combat
the root of asthma, and can be especially useful
for asthma suffers who may have become
tolerant to bronchodilators.
Overall, May 2014 marks two important
discoveries in asthma research, revealing the
neonatal origin of asthma early in life, and the
precise molecular mechanism behind the root of
the disease later in life. The discoveries can
point the way to early-life preventive strategies
and new treatments to combat the
immunological basis of asthma.
Preventing Asthma Early in Life- Mom’s
Microbes
One of the first things that newborns contact
during their early life in this world is their
mothers. Assailing the newborns is not only their
mothers’ scent, but also to their mother’s
microbes- commensal bacteria that colonize
various surfaces of the body including the skin,
the intestinal tract, the airway, and even the
lungs. While these microbes are initially thought
to simply provide protection against foreign
pathogens, a body of work suggests that
commensal bacteria can help orchestrate the
development of the immune system in
neonates6, and to shape the immune system in
adults7.
To learn more, read the full story in the June
2014 Issue…
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