June 2014, Sample Issue MEDICAL BEAT
May 9, 2014
l
The Science Behind Tomorrow’s Medicine
MITIGATING THE DEADLY EFFECTS OF RADIATION EXPOSURE New Drug Provides Protection against Radiation Sickness pg.11 FORGETFULNESS BEGINS WITH NEW NEURONS
STRATEGIES TO COMBAT THE ROOT OF ASTHMA
Exercise Produces New Neurons to Erase Unused Memories pg. 16
Breathing Better with Early-Life Prevention and New Treatments 1 pg. 22
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.
The Medical Beat
2
THE MEDICAL BEAT The Medical Beat www.themedicalbeat.weebly.com Contact: themedicalbeat@gmail.com Twitter: @themedicalbeat
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.
SUBSCRIPTION & ADVERTISING To subscribe: Download the free The Medical Beat app (for both iOS and Android systems). Find it at http://www.presspadapp.com/digital-magazine/the-medical-beat For advertising inquiries: Contact themedicalbeat@gmail.com
PUBLISHING PressPadApp www.presspadapp.com Presspad Ltd. 5 London Road, SW17 9JR London
The Medical Beat
3
CONTENTS June 2014, Sample Issue
5 9 11 16 22 The Medical Beat
Snapshots-
Wireless device to recharge deeply implanted pacemakers, and 1018 eliminates bacteria biofilm
Editor’s Pick Primitive Viruses Point to a New Cancer Treatment
Mitigating the Deadly Effects of Radiation Exposure New Drug Provides Protection against Radiation Sickness by Protecting the Gut Epithelium from Radiation Damage.
Forgetfulness Begins with New Neurons Exercise Produces New Neurons to Erase Unused Memories
Combating the Root of Asthma Breathing Better with Early-Life Prevention and New Treatments
4
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.
The Medical Beat
5
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.
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 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 powerharvesting device that is implanted into 5cm of tissue.
The size of a rice grain, this miniature powerharvesting device can be safely implanted into In this study, Poon and colleagues designed a the heart. The device can effectively power new wireless power transfer technology that can pacemakers- which only need about 8 successfully charge deeply implanted microwatts of power. The study is published in pacemakers by focusing electromagnetic energy the May 19th 2014 issue of the Proceedings of deep into tissue. The wireless technology the National Academy of Sciences1. consists of a patterned metal plate that uses midfield power transfer to focus 1. Ho J.S. et al. Proceedings of the National Academy of Sciences electromagnetic energy to a specific region deep (2014) in press.
The Medical Beat
6
1018: Bacteria Biofilm Busters Dr. Robert Hancock at the University of British Columbia discovered a peptide, 1018, that could stop bacteria from forming biofilms.
The Medical Beat
7
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.
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)
In a study published in the May 2014 issue of PLOS Pathogens, Dr. Hancock and colleagues
The Medical Beat
8
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. Phages (small particles depicted here) are primitive viruses that
Like a cloak of darkness shielding display specific peptides on their surface. Kwak identified 2 phage invaders from surveillance cameras, peptides (G3 and H6) that can bind specifically to MDSCs. MDSCs are immune suppressive cells that are implicated in helping cancer Kwak faces is the lack of proper tools to evade immune surveillance3,4. Specifically, effectively deplete MDSCs. “We’ve known about MDSCs can inhibit immune surveillance by [MDSCs] for a decade, but haven’t been able to suppressing and killing T cells- an immune cell shut them down for lack of an identified target,” population that can recognize and attack tumor said Kwak. cells5,6. MDSCs can also activate regulatory T cells (Treg)- an immune cell population known to In the study published in the May 28th issue of silence the immune system against the cancer7. Nature Medicine8, Kwak’s team set out to 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.
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
To answer this question, one challenge that The Medical Beat
9
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 cellmediated 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.
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 PepG3 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. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
Dunn GP et al Nat Immunol. 3, 991 - 998 (2002) Sinha P et al J Immunol. 181, 4666-75 (2008) Kusmartsev S. J Immunol. 175, 4583-92 (2005) Kusmartsev S. & Gabrilovich DI. J Immunol. 174, 4880-91 (2005) Rodriguez P.C. et al Blood 109, 1568-1573 (2007) Bingisser R. et al. J. Immunol. 160, 5729-5734 (1998) Huang B et al Cancer Res.66, :1123-31 (2005). Qin H. et al. Nat Med. (2014)- in press Strome S.E. et al. The Oncologist. 12 , 1084-1095 (2007). Review. Ichikawa, M et al. Mol. Cancer Res. 9, 133–148 (2011) Källberg, E. et al. PLoS ONE 7, e34207 (2012)
Kwak further shows that the MDSC depletion is The Medical Beat
10
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
The Medical Beat
Read the full story in the June 2014 issue of the Medical Beat. Purchase your copy today.
11
A
n 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 FDAapproved 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.
A portrait of radiation sickness: An 11-year Japanese girl who survived the nuclear bombing in Hiroshima in World War II.
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.
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.
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.
In a recent study published in the May 14th issue
Read the full story in the June 2014 Issue‌
The Medical Beat
12
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. 16 Purchase your copy today.
The Medical Beat
F
orgetfulness is something that we often face But before we flock to the gym for some memory-boosting exercise, scientists now over the course of our lifetime. It’s very common caution that exercise can also cause to forget about the events in our early lives as forgetfulness. Although exercise can boost infants and toddlers, and we often rely on memory by driving the production of new parents to provide fond recollections of these neurons to build new memories, a recent study early memories. As we begin to age, we face published in the May 9, 2014 issue of Science7 embarrassing moments when we search in vain reveals that exercise-induced neurogenesis can for our lost vehicle in the parking lot, or when cause forgetfulness by impeding the retrieval of we forget the names of familiar faces at a old memories. The study also shows that high cocktail party. levels of neurogenesis in the infant during early brain development can also be the culprit Although precisely what causes forgetfulness behind infantile amnesia, preventing us from remains unclear, decades of research has at least recalling the early events in our infanthood and revealed some insights into how memories are early childhood. formed. We now know that memories are stored in a brain structure called the hippocampus. Exercise-Induced Neurogenesis Promotes Contained in this distinctive structure are Forgetfulness in Adult Mice neuronal circuits that encode memories, as well n the study published in Science,7 Dr. Paul as a neuronal germinal center to produce new Frankland and colleagues at the Toronto’s Sick neurons. The latter is involved in producing Kids Children Hospital (ON, Canada) discover neurons in the adult in the process dubbed adult that exercise can promote forgetfulness. They neurogenesis, and is implicated in memory show this by using a series of behavioral tests to 1 formation . The gradual decline of neurogenesis evaluate how exercise-induced neurogenesis with increasing age2, or in dementia3, is further could influence the retrieval of old memories in implicated in reducing memory. mice. 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.
The Medical Beat
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…
17
Combating the Root of Asthma Breathing Better with Early-Life Prevention and New Treatments By: Jennifer Wong
The Medical Beat Image credit: Тетяна Фіонік/CC-BY-SA-3.0
18 of Read the full story in the June 2014 issue the Medical Beat. Purchase your copy today.
T
he 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.
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 The wheezing during an asthma attack is caused recurrent disease, many asthma sufferers use by an allergic inflammatory reaction that bronchodilators on a regular basis, and its constricts the airway1- a potentially lifeprolonged use could often promote tolerance. threatening condition that asthma sufferers The tolerance could render bronchodilators often face. The allergic inflammation is caused useless against a future asthma attack2. Clearly, by a population of allergic lymphocytes, T helper a more effective treatment is needed to better 2 (TH2) cells1. In response to allergen inhalation, combat asthma. TH2 cells release signals to stimulate the production of IgE antibodies, which in turn With 235 million asthma sufferers worldwide, activate white blood cells (such as eosinophil based on an estimate from the World Health and mast cells) in the airway and lungs. The 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.
The Medical Beat
23
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.
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 th In another study published in the May 20 , 2014 development of the immune system in neonates6, and to shape the immune system in online issue of New England Journal of 7 Medicine5, Canadian researchers from McMaster adults . University show that antibodies suppressing TLSP (thymic stromal lymphoid protein) could be To learn more, read the full story in the June 2014 Issue… a potential treatment to combat the root of
The Medical Beat
24
Thank you for downloading the Medical Beat App. I hope you enjoyed the sample issue.
To access the compelling stories previewed here, purchase your full copy of the June 2014 issue today.
The Medical Beat
25
The Medical Beat
26