Welcome to 2016! We start this year off with articles on:
- “Science for All,” Penn’s postdoc-run science outreach group
- Researchers at Penn looking the effects of bisphenol A (BPA) across generations
- Career Capsule: Patent Law
You can access the PDF here: goo.gl/fFTPtv
By Chris Edwards, Ph.D.
What happens if you submerge candy in a mixture of water and baking soda? Depends on the candy. M&Ms do nothing, but Sour Patches fizzle like fireworks due to their acidity! From the acids in foods to the circuits in smartphones, the footprints of science are all around us. Yet widespread doubts regarding climate change and vaccine safety illustrate that many people do not fully understand science or its benefits to society. Maintaining a scientifically literate and engaged public is thus important, not just to prevent the propagation of bad science, but also to ensure that taxpayer-funded research and the resulting rewards are understood and appreciated.
To support this cause, Dr. Zenobia Cofer, a postdoctoral researcher at the Children’s Hospital of Philadelphia (CHOP), created Science for All. Formed in 2015, this organization holds local science outreach events with the help of volunteer postdocs from CHOP, The University of Pennsylvania (UPenn), and the Monell Chemical Senses Center. As Dr. Cofer explained, through these events, this group aims to educate the public, generate excitement about science, and give lay people an opportunity to meet and interact with scientists. Additionally, these efforts give scientists a chance to learn how to explain their research, and science in general, to a lay audience. Science for All held three such events this past fall at the Free Library of Philadelphia’s Fumo Family Branch.
The first event brought science to children on Halloween with a trio of interactive demonstrations. Participants saw the effects of submerging dry ice in water in a demo led by Dr. Cofer. In another activity led by myself and inspired by demos at candyexperiments.com, participants learned about the acidic content of candies by dropping Halloween treats into a baking soda solution. A particularly notable activity led by Dr. Gautami Das demonstrated DNA extraction from blueberries using alcohol and detergent. As explained to participants, releasing DNA from the fruit via detergent followed by precipitating it with alcohol is the method used by scientists in a laboratory. Thus, although these demos appeared to be merely simple and fun activities, they gave audience members insights into laboratory procedures and showed that scientific phenomena are present all around us, even in everyday items found in our kitchens.
In November, Science for All held its next event, “Scientists Talk Science.” This was the group’s first event aimed at teens and adults and consisted of presentations by researchers outlining the significance of their work. Dr. Amanda Zacharias highlighted the importance of intergenic DNA, the “dark matter” of the genome, and its role in regulating gene expression. Dr. Jessica Chacon outlined her strategy to improve melanoma therapy by culturing patient-derived T cells, to make them more aggressive, followed by reintroducing them to the patient. A talk concerning the circadian rhythm by research associate Dr. Sarah McLoughlin concluded the event.
Communicating research to a lay audience is no easy task. To accomplish this, the presenters focused on the underlying concepts motivating their studies rather than technical details. Importantly, they utilized real-world examples to emphasize their work’s significance to society. Dr. McLoughlin, for example, highlighted the importance of circadian rhythm research by noting that the Chernobyl accident occurred at night, when workers are least alert. The presentations were well received by the audience. As library branch manager and audience member Renee Pokorny mentioned, it “…was fascinating to hear what kind of research people are currently conducting…. What I loved about [the] presentation[s] was they made it…really easy for me to grasp as a layman…. Science actually intimidates me, and [the presentations] made me really comfortable and interested in what the scientists are doing.”
Science for All’s most recent event, “The Science of Baking,” was held in mid-December. Directed towards children and families, it was the most hands-on event of the three and explained the chemistry behind converting butter, sugar, and flour into cookies and cakes. Participants baked a pound cake after calculating the required amounts of ingredients, a tomato soup cake after determining the needed amount of leavening agents, and cookies using a variety of sugars. Each baking session was preceded by an explanation of the underlying science by Drs. Cofer and Zacharias, Dr. Keeley Mui, and myself. The bakers gained much from these activities beyond just a hearty meal. They learned to see a recipe as scientists do, as a protocol where reagent types and amounts can be adjusted as needed to change the outcome of the procedure.
Given the hectic lives that scientists live, why did these researchers take the time to volunteer? As Dr. McLoughlin pointed out, being largely government-funded, scientists have an obligation to communicate their endeavors to the public. “We don’t need to live separate from society, we’re part of society and we should tell people what we do, cause we’re dealing with taxpayers’ money….” Importantly, these outreach activities were also an opportunity to develop valuable communication skills. “A lot of people don’t realize how challenging it is to explain your research to a non-scientist,” explained Dr. Chacon. “[These skills are] really critical because not everybody you meet is going to be a scientist — such as donors, your spouses, your children, your family…this kind of practice helps you to become a better scientist by allowing you to gain expertise in talking [with] non-scientific terms….”
Since its creation early last year, Science for All’s popularity has grown, with “The Science of Baking” having particularly strong turnout. The participants have benefited by meeting scientists and learning to see science in everyday life. Likewise, the volunteering postdocs have honed their communication skills and given back to the public that financially supports them. As Dr. Cofer noted, it is also particularly rewarding to see that more and more people are attending these events after hearing about them simply by word of mouth. Science for All will continue its mission of bringing science to the people of Philadelphia with additional events in the upcoming year. For more information, contact Dr. Cofer
By Amita Bansal, Ph.D. @amita_bansal
Every day we are exposed to a compound, Bisphenol A (BPA), a manmade chemical commonly used in many types of consumable goods, from the linings of canned and packaged foods to plastic bottles, and even baby pacifiers, paper receipts and eyeglasses. Our exposure to BPA is ubiquitous; we are exposed through what we eat, drink and touch. BPA can even be found on unwashed hands. Detectable amounts of BPA are found in urine of >90% of the United States population (1). Recently, BPA has captured even more attention because of its association with increased risk of diabetes and obesity in humans and animals. BPA is believed to disrupt the normal hormonal activity in the body, and is therefore scientifically categorized as an endocrine disrupting chemical.
In our laboratory, using a mouse model, we have demonstrated that offspring (first generation progeny, or the mouse’s “children,” and second generation progeny, or the mouse’s “grandchildren”) of mothers who were exposed to BPA (lower BPA group: 10 micrograms per kilogram of body weight per day, and upper BPA group: 10 milligrams per kilogram of body weight per day) in their food throughout pregnancy and the nursing period were significantly fatter and had reduced ability to metabolize glucose compared to first and second generation progeny of mothers who were not exposed to BPA (control group) (1). Male offspring were mostly affected and female offspring unaffected (1). Most frightening, the BPA doses used in this study were within the current safe human exposure levels. How the effects of BPA are transmitted from one generation to the next remains unknown. One possible effect of BPA is its effect on glucose metabolism.
We know that in order to metabolize glucose, beta cells of the pancreas produce a hormone called insulin. Insulin acts on target tissues such as liver, muscle, and fat, where glucose is processed. The body fails to metabolize glucose when either beta cells do not produce enough insulin (insulin secretory failure), or insulin fails to affect the target tissue (insulin resistance). To see which of these mechanisms might be at work, we performed physiological tests in our animals. We found that first and second generation progeny of mothers exposed to lower doses of BPA, especially males, had reduced insulin secretion, while those from mothers exposed to high doses of BPA were insulin resistant compared to mice that were never exposed to BPA. In BPA-exposed male animals we also observed defects in beta-cell mitochondrial function. Healthy mitochondria are essential to meet the energy demands for insulin secretion. We wanted to know what mechanisms caused these inter-generational changes.
To see if BPA was affecting how genes are turned on and off, we screened expression levels of genes that play an important role in insulin secretion in pancreas and insulin action in liver. Using a high throughput next-generation whole transcriptome sequencing technique, RNA Seq, we found that both lower and upper doses of BPA exposure in mothers alter expression of several pancreatic genes in male offspring. We have also used a real-time measure of gene expression levels, called qPCR, to measure gene expression changes in pancreas and liver. Our qPCR findings indicate that expression levels of several pancreatic and liver genes are altered in children and grandchildren of lower and upper dose BPA exposed mothers. Currently, we are investigating whether epigenetic alterations, i.e. changes where expression of a gene is altered without changing the DNA sequence, are involved in the transmission of the observed gene expression changes from one generation to the next.
Our findings using a mouse model suggest that exposure to BPA in the womb and throughout nursing has deleterious effects on the metabolic health of the first and second generation progeny, especially in male mice. Although we don’t know if BPA affects humans in the same way it affects mice, we suggest that, to be safe, people should make informed decisions while shopping for groceries, adapt a healthy lifestyle and choose fresh fruits and vegetables as opposed to canned and packaged foods. Importantly, policy makers should also consider strictly regulating overall use of BPA in manufacturing products, which might otherwise have severe public health consequences.
- Susiarjo M et al. Bisphenol a exposure disrupts metabolic health across multiple generations in the mouse. Endocrinology. 2015;156(6):2049-2058. doi: 2010.1210/en.2014-2027. Epub 2015 Mar 2025.
- Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Perspect. 2008;116(1):39-44. doi: 10.1289/ehp.10753.
By Jocelyn Lippman-Bell, Ph.D.
Has a recent query into what you want to be when you grow up thrown you into a state of panic? Do you want to leave academia but have been on the path for so long that you don’t know if other paths exist? Do you want to learn about jobs other Ph.D.’s perform? Then sit back and enjoy our next installment of the BPC Newsletter’s continuing series, Career Capsule, where we take a look at what’s beyond the ivory tower to help you decide which career suits you best.
Last time, we discussed Life Science Consulting (https://bpcnewsletter.wordpress.com/2015/07/11/career-capsule-life-sciences-consulting/), a career ideal for scientists interested in business. If you are business-minded, but also fascinated about how ideas move beyond research to become products, therapeutics, or machines, intellectual property (IP) and patent law might be for you. Luckily, I happen to know someone in the field who was willing to teach me all about it.
Even before completing his Ph.D. in neuroscience, Mark Bell, a third-year patent agent at the law firm Pepper Hamilton LLC, knew he would not take the typical academic track. Though he loves science, he has a mind for business. Therefore, he began a venture capital internship to learn how applications from labs spin off into companies and real-world products. After receiving his Ph.D., Bell moved straight to working with biotechnology start-ups, and in the process, met several IP lawyers, as IP is crucial for the development of these small companies. Soon Bell realized that IP might be the field for him. In his words, IP/patent law “is where science meets law meets business, and that’s a great place to be. I’m always learning something new. Most people appreciate the speed [with which] science and technology change, but business and law change too, more than you might expect.”
So what does a patent agent do? Patent agents create patent applications and defend those applications to the United States Patent and Trademark Office (USPTO) in a process called patent prosecution. Not all applications are successfully issued as patents. Unlike patent attorneys, patent agents focus solely on patents, and cannot deal with other forms of IP, such as trademarks or copyrights, or litigate the use of patents. Bell says his typical day involves speaking with clients (especially inventors), writing new patent applications, and assisting attorneys with patents and other analysis and diligence projects such as mergers and acquisitions involving biotech companies. Although Bell works at a law firm, patent agents can also find jobs in technology transfer offices at universities or directly working for companies. Regardless of the setting, they have the same primary function: writing and prosecuting patents and assisting with the process of moving scientific and technological ideas into the business sphere. Bell particularly loves working with inventors and new ideas in a broad range of applications, as patent law by its nature deals with cutting edge technology in many fields. One downside, for those who continue on to become patent attorneys, as Bell plans to do, is that they will likely work long hours, but in return they are better compensated and can perform a wider variety of tasks.
A normal career arc in patent law is to get a science Ph.D., do a postdoctoral fellowship, and then become a technical specialist. One can also get to this point with a masters degree in something such as engineering. The next steps are passing the USPTO registration exam, commonly known as the “patent bar” to become a patent agent, and then if one so chooses, to attend law school and become a patent attorney. Not all patent attorneys take this track. For example, if you know you want to go into patent law, you can take the patent bar on your own before getting a law job. Bell explains that while passing the patent bar exam prior to your job search will make getting a job easier, “what I learned while working made passing the patent bar exam much easier. Either way, take a training course before you take the test!” Also consider that if you take the patent bar while working as a technical specialist, your employer may cover many of the associated costs.
How do you know if you would be a good fit for patent law? Bell described three main characteristics needed to succeed in the field. First, you need an analytical mind with a love of fine details, especially technical details. “Most postdocs already know that accurate details matter, and have honed their critical thinking skills,” Bell says. Second, because of the strong financial component – patents cost money to make and enforce – if you don’t inherently like business, patent law will not be the best fit for you. Finally, communication skills are key to understanding and translating ideas between the diverse vernaculars of technology, law, and business. Bell explains, “Most postdocs have written grants and papers. In a career dealing with patents, you are similarly writing to communicate … not for a general audience, but for the audience of the patent. For example, a biochemistry patent describes something in a manner that will allow it to be replicated by another biochemist, but not necessarily by a mechanical engineer.”
If this sounds like you, start learning more. The USPTO website and sciencecareers.com are good places to start, with articles such as this: http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2011_10_14/caredit.a1100113. Bell also recommends, “look up patents in your scientific area of specialization using Google Patents and see if you have any interest. They read like science papers but with law in them. If you read it and … think it’s an interesting way to describe a new product or invention, that’s a good indicator that you might enjoy a career in patent law.”
So how do you get started on your path to patent law? We have an amazing network as part of the UPenn community. Take advantage of it! Do alumni searches on LinkedIn or contact the career office to help you locate alumni who are in patent law. Bell says, “Write to them nicely to ask for an informational interview. Face time is really important. That person can point you in the right direction, and provide you with contacts or information. Get to know people.” You can also join business events involving startup companies, as patent attorneys often attend. Bell emphasizes that “once you move past being someone just looking for a job to someone who has taken the time to learn and meet with people, your chances go up dramatically.”
The WordPress.com stats helper monkeys prepared a 2015 annual report for this blog.
Here’s an excerpt:
A San Francisco cable car holds 60 people. This blog was viewed about 2,200 times in 2015. If it were a cable car, it would take about 37 trips to carry that many people.
Letter from the Editor
In this special issue of the BPC Newsletter, we present the three winners selected in the inaugural University of Pennsylvania BPC Science Writing Competition. The competition was organized as a joint effort between the University of Pennsylvania BPC Newsletter and Postdoctoral Editors Association, and drew applications from postdoctoral fellows across the University of Pennsylvania, including the School of Medicine, Veterinary Medicine, as well as Wistar and CHOP. The writers’ task? To explain a recent finding in scientific research that’s relevant and interesting, describing the background, findings, and most importantly, relevance to human health. Entries were judged on factors including an engaging writing style, scientific accuracy, and compelling scientific storytelling. Guest judging was provided by Bethany Brookshire, Ph.D., an award-winning science writer with Science News. Dr. Brookshire provided invaluable comments to the finalists, who used her feedback to hone their writing. Additional editorial assistance was provided by Daphne Avgousti, Ph.D., Editor in Chief of the Postdoctoral Editors Association. The top three finalists were recognized at the 2015 Biomedical Postdoctoral Research Symposium; their winning entries are published in this special issue of the BPC Newsletter. We hope that you enjoy these pieces of science writing. I would like to thank Dr. Brookshire for her impeccable and constructive critiques. I would also like to thank Dr. Avgousti for her enthusiasm and collaboration style which made orchestrating this competition so enjoyable. We are excited about this year’s winning entries, and hope to see even more great entries next year.
-Liisa Hantsoo, Ph.D., Editor in Chief, BPC Newsletter
Please access the PDF here: _BPC_Vol_4_Issue_4_10.25.15
1st Place: “Turning Back Time: It’s Never Too Late to Learn Like A Child,” by Jocelyn Lippman-Bell
2nd Place: “A Sexy New Way to Fight Malaria,” by Charitha Gowda
3rd Place: “AMPed and Dangerous,” by Kimberly Malecka
BPC Science Writing Competition 1st Place: “Turning Back Time: It’s Never Too Late to Learn Like a Child”
By Jocelyn Lippman-Bell
If you could take a pill to restore your mind to the flexible state of childhood learning, would you do it?
This is not as far out of the realm of possibility as one might imagine. Children possess an enhanced capacity for learning compared to adults, in part due to the high level of neuronal plasticity, or adaptability, that enables neurons to be especially sensitive and reactive to incoming messages. These periods of high neuronal responsiveness, remodeling, and refinement are called critical periods, and allow environmental cues to mold the developing brain and optimize neural functioning. Critical periods exist for many different forms of learning, including acquiring language and motor skills, developing sharp vision (visual acuity), and learning how to interpret sounds. A mounting body of research aimed at controlling the opening and closing of critical periods is rapidly making the possibility of reestablishing neuronal flexibility in adulthood a reality.
The idea that critical periods can be manipulated emerged largely through research in the developing visual system. Starting with the seminal studies of Hubel and Wiesel, evidence began to build demonstrating that if one eye of an animal remains closed throughout its visual critical period, the deprived eye had forever lost the ability to develop perfect acuity, and connections to the non-deprived eye were persistently much stronger than those to the deprived eye [1-4]. However, raising an animal in complete darkness (i.e. no visual stimulation to either eye) essentially shifted the critical period so that when the lights came back on, regardless of how long the animal had been in the dark, they were able to recover function and normal neural connectivity for both eyes [5, 6]. Because of these observations, scientists realized that the critical period was not an absolute; it could be altered. Thus began the race to uncover the mechanisms governing critical period regulation.
Using clues from the light deprivation experiments, scientists theorized that the key element controlling the critical period time course was the precise balance of excitatory and inhibitory activity at developing local neural circuits. Therefore, researchers began looking to the major mode for neuronal inhibition in the brain, the neurotransmitter gamma-aminobutyric acid, or GABA. Inhibitory circuits come on line later in development than excitatory circuits, and dampen excitation. When Huang and colleagues at MIT examined mice with accelerated onset of inhibitory circuit development, they found not only that the mice developed visual acuity sooner than their unaffected siblings, but also that the critical period for vision closed prematurely in these mice . Conversely, in mice that had genetic modifications that decreased GABA release and therefore inhibition, the critical period never closed throughout the lifespan of the mouse, likely because the neural circuits in these mice never reach the required peak inhibition .
Risk and benefits
It is now clear that critical periods can be experimentally altered, but what is the cost of such manipulation? One must consider that there is an evolutionary advantage underlying the loss of brain flexibility. In the first years of life, an overabundance of neuronal connections is formed, then refined in response to experience and environmental cues to optimize neural circuit function and our perception of our surroundings. What would it be like to be in the throes of a critical period? Imagine being three again. Young children absorb everything around them, everything they see, everything they hear. However, in absorbing everything, the child cannot focus as readily as an adult. They have trouble letting go of unimportant things. Recreating child-like brain flexibility to allow the brain to rewire could result in a loss of memories at best, or loss of sensory mapping or outright brain damage at worse. So for, say, a 50-year-old who wants to master windsurfing, this many not be a viable shortcut.
In contrast to the science fiction-esque idea of creating mind-expanding drugs for personal gain, the real promise of this research lies in its medical implications. Exploiting critical period reopening can open new avenues for cognitive recovery from stroke, enhanced acquisition of motor control of a prosthetic, and reversal of early childhood disorders such as amblyopia (or “lazy eye”, in which vision in one eye is weak despite the eye being perfectly healthy) . Emerging work over the past year from Krishnan, He, and colleagues now also links shifted critical periods to autism and autistic-like disorders such as Rett Syndrome [10, 11], a debilitating neurological disease of early childhood that affects 1 in 10,000 girls worldwide.
While reopening critical periods in humans offers theoretical usefulness, how can we actually accomplish this? Genetically decreasing overall inhibition in the brain tends not to be a viable treatment option. Without inhibition to keep it in check, excitation would overrun the brain, leading to massive seizures and likely death. Thus, therapeutic targeting requires a greater understanding of the specific molecules involved in critical period regulation, and of how to direct therapies only to the desired brain circuits. Though removing inhibition from the brain would be lethal, targeting specific GABA receptors has proven feasible. Luckily, not all GABA receptors regulate critical period closure. Only one subtype of GABA receptor, the GABAA receptor, seems to significantly modify plasticity, but not all the GABAA receptors are the same. GABAA receptors can be made up of different subunits, and the specific combinations of these subunits provide varying levels of influence on critical period closure .
Another promising line of research comes out of the studies of Rett Syndrome, an autistic-like neurodevelopmental disorder. Altered expression of a single gene, MeCP2, causes Rett Syndrome , and the mouse model replicates the human disorder fairly well, providing a straightforward approach for examining functional changes relevant to the disorder. Recent research in a Rett Syndrome mouse model discovered that the main inhibitory neurons involved in critical period plasticity maturated earlier than normal in the visual cortex of animals with MeCP2 gene mutations . Further, the visual critical period opened and closed earlier than normal in these mice, and could be restored by dampening inhibition , reminiscent of the foundational studies of critical period manipulation. Taken together, these data strongly implicate MeCP2 expression, and probably regulation, as a major molecular influence on the visual critical period.
Though the GABAA and MeCP2 pathways are only two of many possible candidates currently emerging as regulators of critical period, a major hurdle remains. Controlling the time course of critical periods depends on more than just altering the molecular pathways. Once the inhibitory circuitry matures, the inhibitory cells (parvalbumin (PV) cells) regulating critical period plasticity become enwrapped in a mesh of extracellular matrix proteins and adhesion molecules that basically form nets around the PV cells [14, 15]. These nets may physically constrict further plasticity of the inhibitory cells, holding the critical period window closed tightly in place. While molecular targets such as GABAA receptors and MeCP2 may represent promising targets for chemically restoring critical period plasticity, research into reversing the structural constraint has proven less fruitful.
Old brain, new tricks
The realization that critical periods could be manipulated and thus reopened brings to the table a new discussion of the mature and immature brain. A child’s brain differs so radically from that of the adult, for example, in receptor expression, in the balance of excitation and inhibition, and in the neuronal capacity for plasticity, that it can never be taken for granted that therapies successful for neuronal conditions in adults would be either safe or effective in children. However, understanding how the brain transitions from immaturity to maturity may blur these lines, holding the key to the possibility of turning back neural time and reopening our minds to cognitive malleability.
- Wiesel, T.N. and D.H. Hubel, Single-cell responses in striate cortex of kittens deprived of vision in one eye. . J Neurophysiol, 1963. 26: p. 1003-17.
- Timney, B., The effects of early and late monocular deprivation on binocular depth perception in cats. Brain Res, 1983. 283(2-3): p. 235-43.
- Guire, E.S., M.E. Lickey and B. Gordon, Critical period for the monocular deprivation effect in rats: assessment with sweep visually evoked potentials. J Neurophysiol, 1999. 81(1): p. 121-8.
- Gordon, J.A. and M.P. Stryker, Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J Neurosci, 1996. 16(10): p. 3274-86.
- Timney, B., D.E. Mitchell and F. Giffin, The development of vision in cats after extended periods of dark-rearing. Exp Brain Res, 1978. 31(4): p. 547-60.
- Fagiolini, M., T. Pizzorusso, N. Berardi, L. Domenici and L. Maffei, Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation. Vision Res, 1994. 34(6): p. 709-20.
- Huang, Z.J., A. Kirkwood, T. Pizzorusso, V. Porciatti, B. Morales, M.F. Bear, L. Maffei and S. Tonegawa, BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell, 1999. 98(6): p. 739-55.
- Fagiolini, M., & Hensch, Inhibitory threshold for critical-period activation in primary visual cortex. Nature, 2000. 404(6774): p. 183-186.
- Hensch, T.K. and P.M. Bilimoria, Re-opening Windows: Manipulating Critical Periods for Brain Development. Cerebrum, 2012. 2012: p. 11.
- Krishnan, K., B.S. Wang, J. Lu, L. Wang, A. Maffei, J. Cang and Z.J. Huang, MeCP2 regulates the timing of critical period plasticity that shapes functional connectivity in primary visual cortex. Proc Natl Acad Sci U S A, 2015. 112(34): p. E4782-91.
- He, L.J., N. Liu, T.L. Cheng, X.J. Chen, Y.D. Li, Y.S. Shu, Z.L. Qiu and X.H. Zhang, Conditional deletion of Mecp2 in parvalbumin-expressing GABAergic cells results in the absence of critical period plasticity. Nat Commun, 2014. 5: p. 5036.
- Hensch, T.K., Critical period plasticity in local cortical circuits. Nat Rev Neurosci, 2005. 6(11): p. 877-888.
- Amir, R.E., I.B. Van den Veyver, M. Wan, C.Q. Tran, U. Francke and H.Y. Zoghbi, Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet, 1999. 23(2): p. 185-8.
- Beurdeley, M., J. Spatazza, H.H. Lee, S. Sugiyama, C. Bernard, A.A. Di Nardo, T.K. Hensch and A. Prochiantz, Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci, 2012. 32(27): p. 9429-37.
- Mix, A., K. Hoppenrath and K. Funke, Reduction in cortical parvalbumin expression due to intermittent theta-burst stimulation correlates with maturation of the perineuronal nets in young rats. Dev Neurobiol, 2015. 75(1): p. 1-11.