The EndoPil: A potential solution in the fight against the global obesity epidemic

By Patrycja Sztachelski

Scientists have developed a self-inflating capsule that could help fight against obesity. The EndoPil contains a balloon that can be self-inflated using a handheld magnet once the capsule reaches the stomach to create a sense of fullness.

Nowadays, patients can decide to undergo surgery to insert an intragastric balloon into the stomach via endoscopy under sedation, but this option is rather invasive, and side effects, such as nausea and vomiting, are quite common, affecting up to 20 percent of patients and necessitating early balloon removal as a result.

The capsule, which was designed by a team led by Professor Louis Phee, the Dean of Engineering at Nanyang Technological University, and Professor Lawrence Ho, a clinician-innovator at the National University Health System, avoids such problems by providing an orally-administered option to battle obesity. The EndoPil should be removed within a month to ensure that the stomach does not completely adapt to the balloon’s presence—by increasing the space-occupying effect in the stomach gradually, side effects such as nausea or vomiting can be avoided.

Currently, once the capsule is swallowed with a glass of water, it enters the stomach, where the acid breaks the outer gelatine casing. The location of the capsule in the stomach is identified using a magnetic sensor, which can attract the magnet attached to the inflation valve on the capsule. This attractive force between magnets causes the valve to open, which allows the acid and salt stored in compartments in the capsule to be released, producing carbon dioxide to fill up the balloon.

The team of scientists is working on programming the capsule to automatically biodegrade and deflate after a certain time period before passing through the body’s digestive system naturally.

Nanyang Technological University. (2019, April 24). Scientists develop swallowable self-inflating capsule to help tackle obesity. ScienceDaily. Retrieved April 27, 2019 from www.sciencedaily.com/releases/2019/04/190424102215.htm

The Beneficial Effects of Regular Exercise within Pregnant Mice

By Alec Tyminski

Jun Seok Son , a doctoral student at at the Washington State University, recently published results which display the great beneficial effects of regular exercise in pregnant individuals. The study examined both the offspring of mice that performed 60 minutes of moderate intensity exercise every morning during pregnancy, and offspring born to mice that did not exercise. The studies which preceded this only applied to exercise within obese female mice.  By applying many of the same techniques used previously, the study held that regular exercise in non-obese females demonstrated the same beneficial effect. Son specifically sites to “exercise regularly during pregnancy because it benefits their children's metabolic health." This assertion stems from the specific finding that within the exercise group, the brown adipose tissue examined was found to have higher thermogenic function, or better efficiency. This increased efficiency has been shown to prevent obesity and metabolic problems. Although further studies are sure to follow, these results are proper evidence that regular exercise during pregnancy benefits offspring.

Experimental Biology. (2019, April 7). Exercise during pregnancy protects offspring from obesity: Mouse study suggests exercise by normal-weight pregnant mothers boosts brown fat, metabolic health of children. ScienceDaily. Retrieved April 27, 2019 from www.sciencedaily.com/releases/2019/04/190407144210.htm

Hope Found in New Drug Rapastinel to Treat Opioid Addiction

By Duru Cosar

Current medications that are available to relieve withdrawal symptoms in people recovering from opioid use may cause side effects and keep the brain changes that led to the addiction initially, which may lead to relapse. However, new research gives hope that a better solution is out there.

Rapastinel, which is an experimental drug that was initially an antidepressant, may be useful in helping to manage withdrawal during the first days after entering treatment. According to Julia Ferrante, an undergraduate at Villanova University, Rapastinel did not show any negative side effects. Ferrante worked with Cynthia M. Kuhn, PhD, who is a professor of pharmacology and cancer biology at Duke University, to study this new drug. Current drugs, buprenorphine and methadone, are dangerous because they are also opioids and thus may cause the patient to have side effects and become dependent on them. Ketamine, which is a non-opioid option for treatment, may cause hallucinations and other side effects. Rapastinel binds to the same receptor that ketamine does, but at a different site where the effect is milder. Kuhn and Ferrante looked at opioid dependence in rats by giving groups of rats rapastinel, ketamine, or a saline solution. After three days, rats given rapastinel showed less signs of withdrawal than the other rats. The drug has not been tested on in humans yet because it is not fully developed. Researchers will investigate its effects more closely. If approved for treatment, rapastinel would probably be given intravenously in an outpatient setting. It is still unknown how long patients would need to take rapastinel to recover from opioid addiction.

 

Experimental Biology. (2019, April 7). Experimental drug shows promise for opioid withdrawal symptoms: In rats, rapastinel reverses signs of withdrawal with no side effects. ScienceDaily. Retrieved April 20, 2019 fromwww.sciencedaily.com/releases/2019/04/190407144228.htm

Research Highlight: Dr. Sergei Mirkin

By Kurtis Chien-Young

Dr. Sergei Mirkin is the Chair of the Biology Department at Tufts. He serves as principal investigator of the Mirkin Laboratory, which researches the mechanisms of diseases caused by expandable DNA repeats. I had the privilege of interviewing him on his work and experiences.

Dr. Sergei Mirkin, The Mirkin Laboratory

Dr. Sergei Mirkin, The Mirkin Laboratory

1. Can you give some background on your research with trinucleotide repeats?

Let’s consider, for example, a pedigree for the human genetic disease, called myotonic dystrophy type 1. In three generations: the grandmother is basically not affected, her daughter got mildly affected in her adulthood, while the grandson has a very severe form of the disease from birth. This phenomenon is called genetic anticipation, and even though this disease is caused by an autosomal dominant mutation, its inheritance is non-Mendelian in a sense that the manifestation of the disease gets worse as a mutant allele passes through generations.

The phenomenon of genetic anticipation was described in 1918, but it was substantiated, in a molecular sense, many years thereafter, when in the early nineties scientists cloned the genes responsible for those diseases. The first success was cloning of the fragile X syndrome gene. That was done by Steve Warren and his group at Emory University. The myotonic dystrophy gene was cloned by Bob Korneluk in Canada and by David Housman here in MIT.

What they found was that in all those cases, the disease is caused by the expansion of a very simple repeat. In the case of myotonic dystrophy, this is the CTG repeat located in the 3’ untranslated region of the DMPK gene, while in the fragile X case it’s the CGG repeat in the 5’ UTR of the FMR1 gene. The rule they found out was very clear-cut. When the number of repeats is between 6 and 50, the individual is healthy. When it’s somewhere between 50 and 200, the person is a carrier. In the disease state, it’s over 200 and up to 3,500 repeats. In other words, the molecular mechanism of genetic anticipation is that the longer the repeat, the more likely it is to lengthen further, the more severe the disease manifestation, and the earlier the onset.

In the DM1 pedigree discussed above, the number of repeats increased tenfold in just three generations. This is what my lab studies. How can a repeat expand so profoundly, and what are the mechanisms of these expansions? Specifically, we concentrate on how the carrier size repeat becomes a disease-size.

All these repeats can form unusual DNA structures that are strikingly different from regular B-DNA. Their individual strands can form imperfect hairpins or even four-stranded G-quartets if they are sufficiently G-C rich. They can also form what’s called slipped-strand DNA, when their complementary strands are annealed out of register. Last but not least, they can form a structure called a DNA triplex, or H-DNA, which I co-discovered in course of my postdoctoral studies. Very early on, back in 1995,  Bob Wells had proposed that the formation of these structures during DNA synthesis may account for the repeat instability. His reasoning was as such. If there is a hairpin on the nascent strand during DNA synthesis, then after a round of replication this would result in an expansion. If, in contrast, the same hairpin is on the template strand, then it would end-up in contraction.

So that’s essentially when my lab has jumped in. We first wanted to see whether replication through expandable repeats inside the cell proceeds abnormally. In order to do this, we used a technique called 2-dimensional gel electrophoresis of replication intermediates. One can isolate from a cell all of its DNA, including molecules that are in the process of replication. This DNA is then digested with restriction enzymes and run on the gel across two dimensions, so they are separated by size and shape. This separates DNA molecules at various stages of replication from linear DNA that is not being replicated. If the replication fork is stalled at an abnormal DNA structure, one would observe an accumulation of a particular replication intermediate. Using this approach, we were able to demonstrate that expandable DNA repeats do stall replication in every experimental system studied, including bacterial, yeast and mammalian cells!

After that, we developed a new experimental system to study repeat expansions in baker’s yeast, S. cerevisiae. We took a reporter gene, artificially split it and inserted a carrier-size repeat into the intron. Yeast can not splice out very long introns. Thus, when we inserted 100 repeats, the intron was still short enough to be spliced. When repeats expand, however, the intron gets too longs to be spliced, and we can easily detect this event by the reporter’s inactivation.

Using this system, we were able to carry out genome-wide analysis of the genes that affect the rate of repeat expansions in our system. By the end, we identified roughly 40 genes that are important for the expansion process. As we expected, the majority of them encode the components of DNA replication machinery. Thus, repeat expansions occur during DNA replication! Other genes affect transcription and chromosome maintenance, and we are currently investigating their mechanisms of action.

2. Can you tell me a bit about the courses that you teach? Does the material overlap with your research?

Yeah, there is significant overlap with my Bio 190 course. This is an advanced course called DNA Structure to Function, which is 50% lectures, 50% paper presentations by students. There, we talk a lot about unusual DNA structures, including the structures involved in repeat expansion diseases. We also talk about the problems that they cause for DNA replication, transcription, and recombination. That’s actually directly related to my science.

The second course, which I co-teach with Catherine Freudenreich, is Bio 188. There, we talk about papers that are so important that they were chosen to be awarded with the Nobel Prize. These are really the key papers in modern biology. We give the background to the students and then they present original papers. We then discuss what is so special about these papers, and what makes them worth the highest prize in the natural sciences.

3. What first pulled you toward the study of genetics?

So that has to do with an ancient history. I grew up in the Soviet Union, and for the reasons, which would be too long to describe, genetics was outlawed in the Soviet Union from 1948 on. In 1948, the state made the decision that genetics is a bourgeois science, and as such it should not be taught. And then it was not taught for the next 20 years. So, this ban started when Joseph Stalin was in power, continued through the next country leader Nikita Khrushchev, and ended only when Leonid Brezhnev came to power . Now, you know that DNA structure was unraveled in 1953, so all reasonable people realized right away that not only is genetics a great science, but that there is actually a material carrier of genetic information. Yet this notwithstanding, genetics continued to be outlawed in the Soviet Union.

Anyhow, the state finally allowed genetics to be taught and the first textbook was published sometime around 1968. At the time, I was in the middle school. And I was totally fascinated that this textbook was published and I can read about genetics without worrying for the state repercussions. It was sort of like finally trying the forbidden fruit. I bought myself this college textbook in genetics, and I’m like 12 or 13 years old, so it was very hard for me to comprehend it. But I decided that I’ll read it as many times as needed to before I understand everything it says. So this is how it all started. Then I went to a high school which had a specialization in biology, and afterwards to the Biology Department of the Moscow State University. But the decision was made very early on, when I was essentially still in the middle school.

You grew up here in the US, and you grew up in a different era, so it’s probably hard for you to comprehend how it is to live in a system which is repressive by nature. It prevents you from doing certain things, it prevents you from reading certain books, watching certain movies, or studying certain scientific topics. It’s almost impossible for someone who grew up in this country to comprehend it. But such a system has a fundamental flaw, as people always try to do things that are forbidden: to read the forbidden books, watch the forbidden movies, do the forbidden science. And ultimately, when a critical mass of people is doing forbidden stuff, the system collapses. That’s what happened with the Soviet Union. But in my particular case, this repressive Soviet system made me a geneticist, which I’m kind of grateful for. That said, it required a lot of drive and resilience on my part.

When I teach my course, I always tell my students “there is science, and there is life.” Scientists do not live in an ivory tower. Life intervenes, and sometimes in a very brutal ways. Whether it’s like with genetics, which was not allowed to be taught in the Soviet Union, or before that during the Nazi years in Germany, when top German scientists of Jewish descent immigrated to the United States, which ultimately made US science great. The interplay between science and life is certainly worth discussing. In my case, as I said, this interplay made me study genetics. Were it not forbidden, who knows?


You can read more about Dr. Mirkin’s research at http://ase.tufts.edu/biology/labs/mirkin/, or register for one of the courses he teaches, Biology 188: Seminar in Molecular Biology & Genetics (Fall) and Biology 190: DNA: Structure to Function (Spring). If you would like to have your own research featured on the TuftScope blog, you can reach Kurtis at kurtis.chien_young@tufts.edu

City dangers: the correlation between asthma and traffic-related pollution in urban areas

By Patrycja Sztachelski 

According to a study published by researchers at the George Washington University Milken Institute School of Public Health, approximately 4 million children globally develop asthma each year because of inhaling nitrogen dioxide air pollution. The findings suggest that an overwhelming number of cases of pediatric asthma could be prevented in cities by reducing air pollution.

As Susan C. Anenberg, PhD, the senior author of the study and an associate professor of environmental and occupational health at Milken Institute SPH states, “improving access to cleaner forms of transportation, like electrified public transport and active commuting by cycling and walking, would not only bring down NO2 levels, but would also reduce asthma, enhance physical fitness, and cut greenhouse gas emissions”. Some key findings from the study include that an estimated 4 million children acquired asthma each year between 2010 and 2015 as a result of exposure to nitrogen dioxide pollution, which mainly comes from motor vehicle exhaust, and for cities in the US specifically, the top five places with the highest percentage of pediatric asthma cases linked to polluted air include Los Angeles, New York, Chicago, Las Vegas, and Milwaukee.

In response to these findings, the World Health Organization has recognized that guidelines for nitrogen dioxide levels may have to be reassessed. Unfortunately, they found that approximately 92 percent of the new pediatric asthma cases that could be attributed to nitrogen dioxide presented in areas that sufficiently meet the WHO guideline, which thereby emphasizes the need for reforming the current policies.

 

George Washington University. (2019, April 10). Millions of children worldwide develop asthma annually due to traffic-related pollution. ScienceDaily. Retrieved April 15, 2019 from www.sciencedaily.com/releases/2019/04/190410210003.htm

Traffic-Related Pollution Making Its Way into Pediatric Lungs

By Eliana Rosenzweig

            A comprehensive study done by the George Washington University Milken Institute School of Public Health estimates 4 million children worldwide are developing asthma each year. Research collected from 2010 to 2015 concluded that approximately 64% of new asthma cases were diagnosed in urban areas. This study is the first of its kind to quantify the incidence of pediatric asthma related to nitrogen dioxide exposure from traffic-related pollution. This correlation was established in 125 major cities around the world. Cities in the United States found to be the most affected by nitrogen dioxide pollution were Los Angeles, New York, Chicago, Las Vegas, and Milwaukee. In fact, the United States came in third for the largest burden of air pollution, behind China and India, with 240,000 cases of asthma per year.

            The study suggests environmental efforts concentrated on reducing air pollution may not be a waste of a time. In fact, the correlation between pediatric asthma and nitrogen dioxide supports the urgent need for a reduction in air pollution, specifically with regard to nitrogen dioxide. Increasing physical activity by biking or walking as well as using electric powered alternatives to public transportation may not only help get people in shape, but also help reduce the threat of pollution on pediatric asthma as well as climate change as a whole. The study also suggests a focus on asthma prevention among the pediatric population around the world; researchers propose creating stricter air pollution guidelines related to nitrogen dioxide emissions. Future studies will focus on identifying the specific element of traffic-related pollution that is actually inducing asthma in children worldwide.

 

George Washington University. (2019, April 10). Millions of children worldwide develop asthma annually due to traffic-related pollution. ScienceDaily. Retrieved April 11, 2019 from www.sciencedaily.com/releases/2019/04/190410210003.htm

Environmental consequences on the human genome: study shows that poverty is correlated with epigenetic processes

By Patrycja Sztachelski

A study at Northwestern University has found that lower socioeconomic status is associated with high levels of DNA methylation—specifically, at more than 2,500 sites, across more than 1,500 genes. The results of the study are particularly relevant in the nature vs. nurture debate, since research suggests that the environment shapes the structure and function of the human genome.

In the past, studies have shown that socioeconomic status (SES) is strongly correlated to human health and disease, since social inequality is undeniably a stressor for the human population. For example, lower educational attainment or income can place a person at higher risk for conditions including heart disease, diabetes, and many cancers and infectious diseases. Lower SES is also associated with physiological processes that intensify the development of disease.

In the study, researchers found that poverty affects nearly 10 percent of the genes in the genome, which is significant because the underlying mechanism that evolves gene expression in DNA is better understood, and there is irrefutable evidence that life experience shapes the human genome.

In the future, follow-up studies will be necessary to determine the exact health impacts of methylation at the sites the researchers identified. Many of the genes that have been studied are associated with responses to infection from the immune system, skeletal development, and development of the nervous system.

 

Northwestern University. (2019, April 4). Poverty leaves a mark on our genes: Study's findings challenge understandings of genes as fixed features of our biology. ScienceDaily. Retrieved April 7, 2019 from www.sciencedaily.com/releases/2019/04/190404135433.htm

“Hearing” Pictures: Exploring the Visual-Ear Phenomenon

By Annmarie Hoch

At City University of London, researchers have been investigating the phenomenon of “visual ear,” in which visual cues evoke an auditory sensation of the brain. This phenomenon is present in 20% of the population and can be experienced when looking at “noisy gifs” or flashing neon signs. Some researchers think it is a type of synesthesia, an uncommon condition where seeing or hearing music notes, numbers, or letters create the perception of color in the brains of those affected. The researchers found that musicians were more likely to experience visual-ear than non-musicians. The researchers tested subjects by showing them audio and visual stimuli that could lead to the visual-ear phenomenon, asking whether they “heard” the visual stimulus, and observing their brain patterns while the participants observed the stimulus. The researchers found that for participants without visual-ear, the visual and auditory parts of their brains inhibited each other, depending on the type of stimulus. For visual-ear participants, these areas of the brain cooperated with each other to create the visual-ear phenomenon. This research supports the idea that visual-ear and synesthesia are caused by cross-wiring of different neural areas. Those participants also had better performance on both the audio and visual components than those without, which the researchers connected to improved musical ability, hypothesizing that this was why many musicians had visual-ear.

 

City University London. (2019, March 27). People 'hear' flashes due to disinhibited flow of signals around the brain, suggests study: Study sheds light on why some people hear the 'skipping pylon' and other 'noisy GIFs'. ScienceDaily. Retrieved April 2, 2019 from www.sciencedaily.com/releases/2019/03/190327112710.htm

Could Your Medicine and Personal Care Products be Polluting Waterways?

By Duru Cosar

Scientists from Rutgers University have determined that bacteria in sewage treatment plants could be making new contaminants that have not been tested for personal risks, and they may be harming the aquatic environments. The scientists tested how well the bacteria from the sewage treatment plants could break down two common pharmaceutical products, naproxen and guaifenesin. Naproxen is a non-steroidal anti-inflammatory drug and guaifenesin is an expectorant in many cough and cold medicines. They also looked at two common compounds from personal care products, oxybenzone which is found in sunscreen, and methylparaben, a preservative in cosmetics. They found that bacteria that don’t require oxygen to grow in the sewer sludge broke down methylparaben, but they only broke down the three other chemicals partially, creating new contaminants in the process. Abigail W. Porter, an author and teaching instructor in the Department of Environmental sciences at Rutgers University-New Brunswick, claims that the partial breakdown of pharmaceuticals and personal care products is important because it leads to contaminants clogging up the water ways and affecting certain environments.

The scientists also looked at how bacteria that thrive in conditions with no oxygen can break down the chemicals found in pharmaceuticals and personal care products. They studied a sludge bacterial community from a sewage treatment plant and the other in a low oxygen subsurface sediment from a clean environment in Tuckerton, New Jersey. They determined that the communities had different kinds of bacteria, but both communities were able to transform the four chemicals in the same way. In the future, the researchers hope to look at sediment samples from different locations to study the long-term persistence of transformed chemicals.

 

Rutgers University. "Medicine and personal care products may lead to new pollutants in waterways: Bacteria in wastewater plants transform widely used chemicals." ScienceDaily. ScienceDaily, 21 March 2019. <www.sciencedaily.com/releases/2019/03/190321092212.htm>.

Inheritance of Obesity-Related Cardiac Conditions

By Yasaman Khorsandian

Diets high in fat and sugar have long been recognized as the culprit for causing various heart problems. However, a recent study conducted by researchers at Washington University School of Medicine shows that these medical conditions can be passed down for at least three generations, even if the following generations maintain a healthy diet. The inheritance of such cardiac conditions has been linked to changes in the epigenome of the fertilized egg; the epigenome is a crucial portion of the genetic material that determines how the rest of the DNA is read and executed. The epigenetic changes can lead to structural abnormalities in the cardiac mitochondria, which in turn does not allow them to consume as much oxygen as their normal counterparts, resulting in conditions such as insulin resistance. Moreover, the researchers observed an increase in the mass of the left ventricle in the mice produced by obese mothers, which often times leads to cardiac failure.

Another main finding of this study was that the cardiac mitochondrial abnormalities were passed down by both the male and female offspring. Many scientists previously thought that only the female offspring would continue to pass down these genes, but the results of the study prove that the offspring of fathers who had obese mothers also developed cardiac conditions. The researchers plan to continue working with these mice to find out why these cardiac conditions do not stop with a single generation. Although the heart problems caused by maternal obesity were passed down, if the following generations maintained a healthy diet throughout their lives, the inherited medical conditions somewhat dissipated over time. For this reason, the researchers recommend exercise and a healthy diet to all individuals, regardless of their family history with obesity.

         

Washington University School of Medicine. (2019, March 22). Obese mouse mothers trigger heart problems in offspring. ScienceDaily. Retrieved March 31, 2019 from www.sciencedaily.com/releases/2019/03/190322140528.htm

Taking “Eat Your Greens” to Heart (or Limb?): New Algae-Based Treatment for Patients with Critical Limb Ischemia Reduces Need for Amputation

By Jacqueline Katz

Until now, surgical revascularization has been the cornerstone of critical limb ischemia (CLI) therapy, but Professor Bijan Modarai, M.D. and his team’s findings offer the promise of noninvasive treatment. CLI is a condition in which blood flow is restricted by plaque buildup. This generally hinders the transport of oxygen and nutrients to the extremities, which limits cell metabolism and can result in severe tissue damage and the need for amputation or, in more serious cases, death.

As surgical intervention is unsuccessful in approximately one-third of patients with CLI, researchers everywhere are looking for an alternative. After significant projects experimenting with cells to grow and repair arteries failed, this group of investigators at St Thomas' Hospital and King's College London found that macrophages, a type of white blood cell from brown algae, stimulated the formation of new blood vessels in the afflicted region of subjects with CLI. In mice, this algae-containing capsule has been successful in reestablishing the circulation of oxygen and other life-supporting compounds, although human clinical trials are not yet underway.

While we expect this new treatment will greatly reduce the CLI burden, we must also explore potential interventions to address the underlying causes of the condition. CLI is heavily associated with poor health indicators, such smoking and obesity. To make a more significant impact on the disease burden, we must also look toward prevention.

 

British Heart Foundation. (2019, March 20). Algae could prevent limb amputation: Researchers develop new algae-based treatment which could reduce the need of leg amputation in people with severely limited blood flow. ScienceDaily. Retrieved March 31, 2019 from www.sciencedaily.com/releases/2019/03/190320101943.htm

The relationship between the gut and brain: adverse life experiences affect microbes in the gastrointestinal system and are linked to changes in brain function

By Patrycja Sztachelski

A study at Columbia University found that adverse life experiences have a correlation with increased gastrointestinal symptoms in children that might impact the manner in which their brain and behavior evolve as they reach maturity. Scientists are aware that there is a strong connection between the gut and brain—research has shown that in the cases of up to half of adults with irritable bowel syndrome, a history of trauma or abuse has been reported.

While there has been research on this relationship in adults, there is a lack of research performed in childhood. Although animal studies have indicated that adversity-induced changes in the gut microbiome affect neurological development, this study is “among the first to link disruption of a child’s gastrointestinal microbiome triggered by early-life adversity with brain activity in regions associated with emotional health.”

Researchers focused on development in children who were exposed to institutional care before international adoption, since they had experienced extreme psychosocial deprivation. Children who had succumbed to this adversity showed higher levels of stomach aches, constipation, and vomiting and nausea. Researchers also used gene sequencing to identify microbes in stool samples of these children and compare them to those in the stool of children who had been raised by their biological parents. A significant finding was that the children raised by parents had increased gut microbiome diversity. Since this is linked to the functions of the prefrontal cortex, this served as an advantage to their abilities to regulate emotions.

Researchers recognize that more research has to be performed to reach a sufficient conclusion on the relationship between adverse experiences and brain and gut function.

 

Columbia University. (2019, March 29). Gastrointestinal complaints in children could signal future mental health problem: Adversity-induced disruptions in the body's gut microbes influence are linked to changes in brain function. ScienceDaily. Retrieved March 31, 2019 from www.sciencedaily.com/releases/2019/03/190329171417.htm

Researchers discover novel anti-inflammatory transcription factors

By Sanjana Puri

Researchers have discovered two proteins, transcription factors SIX1 and SIX2, that work to reduce inflammation in the adult immune system. Transcription factors are proteins that bind to DNA sequences and either induce or repress transcription of the sequence into protein. SIX1 and SIX2 play critical roles in fetal development through their induction of the synthesis of key tissues and organs. Its role change into a suppressor in an adult is of particular interest to researchers as it provides insight into an entirely new pathway for controlling inflammation. These transcription factors are closely associated with a condition called a cytokine storm in which the immune system provides an excessive response after stimulation (such as the flu). SIX1 and SIX2 work to curb this response and prevent its signalling cascade. Further study of these transcription factors could also demonstrate why certain cancer cells are resistant to chemotherapy. Disruption of the anti-inflammation pathway (due to the dysfunction of SIX1 and SIX2) could cause the proliferation of cancer cells.


Zixu Liu, Katrina B. Mar, Natasha W. Hanners, Sofya S. Perelman, Mohammed Kanchwala, Chao Xing, John W. Schoggins, Neal M. Alto. A NIK–SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB. Nature, 2019; DOI: 10.1038/s41586-019-1041-6

Neurological changes for children in team sports

By Emily Taketa

This study associates children’s participation in team sports to larger hippocampal volumes and decreased rates of depression in boys. Previous research has correlated a smaller hippocampus, the region in the brain thought to influence memory and stress responses, with adult depression, but the researchers at Washington University in St. Louis recently published pioneering data suggesting the same relationship in preteen children.

This paper, published in the Biological Psychiatry: Cognitive Neuroscience and Neuroimaging journal, analyzed the parental reports of their children’s sports and behavior with supplemental brain scans to observe hippocampal volume of over four thousand children between the ages of 9-11 years. The findings reveal that involvement in sports is correlated with an increase in the volume of the hippocampal region and team sports will generally lead to a more significant increase. The researchers also found that for boys specifically, team sports appeared to have an antidepressant effect that follows the known trend of increased hippocampal volume with decreased adult depression. However, this trend was not observed in girls from this sample which researchers suggest may indicate that other factors contribute to their depression or that associate in team sports may influence girls in later years.

These findings support positive impact team sports have on neurological development and mood and urge more children to participate in these activities. Furthermore, the differences between the preteen female and males suggests the role of gender in cognitive and behavioral development. Overall, these fascinating association between team sports and increased hippocampal region and decreased male depression hold important implications for further memory research and future treatment of childhood depression.

 

Washington University in St. Louis. (2019, March 21). How team sports change a child's brain: Team sports associated with less depression in boys as young as 9. ScienceDaily. Retrieved March 27, 2019.

Does Sugar Intake Directly Increase Risk of Cancer?

By Eliana Rosenzweig

A study conducted by researchers at Baylor College of Medicine and Weill Cornell Medicine found that daily consumption of a modest amount of high-fructose corn syrup increases the rate of growth of intestinal tumors in mouse. Previously, sugar has been considered to be an indirect correlate of cancer. Sugar was thought to lead to a direct increase in obesity, which then put people at higher risk of developing cancer. However, this study supports a causal relationship between sugar and increasing risk for cancer, independent of obesity.

This study created a model of early-stage colon cancer in a mouse using the method of deleting the APC gene, which essentially halts the growth and death of intestinal cells, allowing early stage tumors, or polyps, to form. In fact, over 90% of people affected by colon cancer have a mutation in the APC gene. The team of researchers gave the mice sugar-sweetened water, which contained 25% high-fructose corn syrup, a sugar sweetener that contains mostly sugars glucose and fructose. In order to mimic daily consumption of one can of soda per day and to avoid causing obesity in the mice, the mice were given the sugary water in a special syringe once a day. In just two months, researchers noticed that the mice were not becoming obese, instead they were developing tumors that were greater in size and more advanced than the control mice given regular water.

The mechanisms of the tumor growth with sugary water were also explored in the mice. Using technology to trace the fructose and glucose sugars in the mice, researchers found that the fructose was chemically broken down to enable to the glucose sugars to better form fatty acids, which effectively bolstered tumor growth.

Although this research has not been tested in humans, the results of the study support the notion that chronic consumption of sugary drinks may accelerate the progression of colorectal cancer and leads to new understanding of the mechanisms by which sugar can accelerate intestinal tumor growth at the molecular level.

            

Baylor College of Medicine. (2019, March 21). High-fructose corn syrup boosts intestinal tumor growth in mice. ScienceDaily. Retrieved March 24, 2019 from www.sciencedaily.com/releases/2019/03/190321141924.htm

A dog, bacteria and electricity, oh my!

By Grace Perry

A recent study at Ohio State University highlighted the innerworkings of bandages infused with electricity and their ability to destroy infection and heal wounds. Sometimes biofilms within bacterial infections create a protective barrier that renders antibiotics useless, highlighting the need for another approach to treatment. Enter electroceutical bandages! While the use of these bandages goes back to 2013, the study at Ohio State was the first study to look more closely at how the bandages work. The researchers used bandages made of Japanese silk with small devices attached that provided an electric current. They tested the bandages on bacteria and biofilms in a petri dish and found that the biofilms were disrupted by the electricity and the bacteria even continued to die two days after the current had been delivered. Other instances have provided promising results regarding the bandages’ ability to fight infection. In 2018, a dog with a sore that had persisted despite attempts to address it through antibiotic medications was treated with one of these electroceutical bandages and the infection was healed within 11 days. The researchers at Ohio State asserted that the way in which the bandages heal wounds involves the production of hypochlorous acid. They theorized that this antimicrobial chemical is produced from the interaction between the electric current and the bandage, and while it kills bacteria, it does not hurt the healthy skin surrounding the wound. While these findings are exciting, further research is needed to better understand why these bandages work to heal wounds when other treatment don’t in order to further inform the design of electroceutical bandages and expand their applications to human wounds.

Ohio State University. "Electrifying wound care: Better bandages to destroy bacteria: New study offers fundamental clues about electroceutical wound care." ScienceDaily. ScienceDaily, 6 March 2019. <www.sciencedaily.com/releases/2019/03/190306110645.htm>.

An unexpected finding: hormone deficiencies seem to be a consequence of long-term opioid use 

By Patrycja Sztachelski

Research has found that many people who use opioid medications for a long time fail to produce enough testosterone or cortisol. Amir Zamanipoor Najafabadi, M.D./Ph.D. student at Leiden University Medical Center, and colleagues observed which hormones opioids may impact and what percentage of patients have a hormone deficit.

A systematic review of 52 studies was published before May 2018, in which patients were receiving opioids to relieve persistent pain in approximately half of the studies. Afterwards, the researchers focused on the number of studies that involved patients dealing with long-term opioid use, which was defined as drug use for longer than six months.

They found evidence of hypogonadism, an insufficient production of testosterone, as well as hypocortisolism, in which the body fails to produce enough cortisol. According to the results of the study, up to 65 percent of men using opioids long-term had hypogonadism, which may lead to erectile dysfunction, infertility, decreased body hair and muscle mass, and the development of breasts. Additionally, researchers discovered that up to 19 percent of 207 men and women who had taken opioids in the long-term had hypocortisolism—this was observed in five studies and is problematic since cortisol is crucial to many functions in the body. With low levels of the hormone, symptoms experienced by the patient can include fatigue, weight loss, and mood changes.

Above all, researchers are trying to raise awareness of the endocrinological issues that can likely result from taking opioid medications long-term, so they suggest regular endocrine checkups for these patients.

 

The Endocrine Society. (2019, March 23). Another possible consequence of the opioid epidemic: hormone deficiencies. ScienceDaily. Retrieved March 24, 2019 from www.sciencedaily.com/releases/2019/03/190323145152.htm

Protein Before Bed for Larger Muscles?

By Duru Cosar

Reportedly, a casein shake increases muscle mass and strength in response to resistance exercise if drank just before overnight sleep. However, currently there are no studies that have directly addressed if this effect is a result of total protein intake or if a bedtime beverage is better. A review from Frontiers in Nutrition claims that current findings suggest that overnight sleep is a nutritional window for increasing muscle gains. According to Dr. Tim Snijders, an Assistant Professor at Maastricht University, one-night studies have demonstrated that having protein before sleep increases muscle protein synthesis during sleep, and this has brought the idea that over a longer period, having protein supplement before bed “can maximize the strength and muscle mass gains during regular resistance exercise training.” Snijders did a study on this in which he put 44 healthy young men on a 12-week lifting program. Half of them were given a protein shake before sleep each night with 30g of casein and 15g of carbs, whereas the other half just got an energy-free drink. Both groups ended with a bigger squat and larger quads, but the group that was given protein before bed gained more muscle strength and size.

However, there is still a question of whether muscle gains are boosted by protein before sleep or just higher intake overall of protein and calories. One study tried to test this question but did not get statistically significant results because of the low number of participants (26). There are still indirect indicators that protein before sleep is beneficial for healthy young lifters because it can be used to improve protein intake distribution over the day. Muscles only grow and repair when amino acids from protein are available in the blood. A survey conducted among 500 athletes found that they typically consumed more than 1.2g of protein per kilo of their bodyweight across three main meals, but only 7g of protein in the evening, so lower levels of amino acids would be available for muscle growth during sleep. Studies have found that adding protein at bedtime does not affect appetite the next morning. Furthermore, there is concern that intaking calories right before a long period of inactivity may cause fat gain, but according to Snijders, in the study he conducted with casein, the additional consumption of protein did not result in any fat gain. In fact, another study done with a group of 11 young men found that a casein shake before sleep increased the rate of fat burning the next day, most likely because ingesting casein lowers the insulin response to later meals, pushing the body to use more fat. So, overall, although there is not conclusive evidence for adding a protein supplement before bed, it may be worth a try and certainly worth more research.

 

Frontiers. (2019, March 6). Bedtime protein for bigger gains? Here's the scoop. ScienceDaily. Retrieved March 18, 2019 from www.sciencedaily.com/releases/2019/03/190306081832.htm

Protecting the lymphatic system: preventing cancer from becoming more dangerous by diagnosing cancer cells inside lymph nodes

By Patrycja Sztachelski

Researchers at Tohoku University have developed a method to detect cancers in lymph nodes prior to the disease spreading to other parts of the body. Most cancer deaths occur as a result of the disease traveling across many organs, either through the blood or through the lymphatic system, so this diagnostic approach could save the lives of many.

Currently, there are not many imaging techniques that could detect tumors in lymph nodes while they are still small, and biopsies in lymph nodes can be falsely negative. The new method takes advantage of a technique known as x-ray microcomputed tomography (micro-CT). Tested on mice, breast cancer cells were inserted into their lymph nodes, followed by a contrast agent that allowed researchers to track its movement as it crossed the lymphatic system. After 28 days of this initial injection of cancer cells into the lymph nodes, the cells had divided and grown so that they blocked the movements of the contrast agent, thereby creating areas in the scan that did not indicate the presence of any contrast agent.

Future efforts to improve this technique would involve discovering better contrast agents that would offer clearer pictures of how cancer cells migrate through the lymphatic system.

 

Tohoku University. (2019, March 14). A new method to diagnose cancer cells inside lymph nodes. ScienceDaily. Retrieved March 18, 2019 from www.sciencedaily.com/releases/2019/03/190314101315.htm

Research Highlight: Yassi Khorsandian

By Kurtis Chien-Young

Yassi Khorsandian, Myocardial Regeneration Lab at Worcester Polytechnic Institute

Yassi Khorsandian, Myocardial Regeneration Lab at Worcester Polytechnic Institute

Yassi Khorsandian is a freshman pursuing a Biomedical Engineering degree at Tufts University. She worked with the Myocardial Regeneration Lab at Worcester Polytechnic Institute to study stem cell regeneration of heart tissue.

1. How did you get involved with research at the Myocardial Regeneration Lab? What got you interested in researching cardiology?

I have always been fascinated by the heart and the way it fuels our bodies as the source of life, so when it was time for me to pick a science fair project to work on back in high school, I decided to pick a topic pertaining to the field of cardiology. I talked to a number of researchers working in this field, and I was introduced to Professor Gaudette’s research at the Myocardial Regeneration lab by one of his colleagues. I was instantly captivated. I knew at that moment that I simply had to find out more about the ongoing projects in this lab and get involved in them. Eventually, I ended up working on a number of projects at the Myocardial Regeneration Lab over the course of the next two years.

2. Can you tell me about what you did in your research project?

The main goal of the project was to bioengineer a blood vessel using stem cells. Because heart attacks are the leading cause of death in both the US and the rest of the world, many scientists have tried to approach this problem from a bioengineering angle. However, blood vessels are really the root of the problem, so I decided that for this project, I would try to bioengineer blood vessels that could then be transplanted into individuals with myocardial infarction to deliver blood and stem cells to damaged portions of the heart. All of the plant cellular material was removed from spinach stems in a thorough decellularization process, leaving only their extracellular matrices that were used as fast and inexpensive bioscaffolds for the stem cells to grow on. A novel fibrin-based mechanism was also developed to adhere the cells to the scaffold. The technique that I developed in my project seems to be a promising solution that could permanently treat heart attacks.

3. Why did you choose spinach as a medium to grow on?

Other than being accessible and inexpensive, spinach leaves have very large petioles (leafstalks) compared to other leaves that are easily available worldwide. Due to this large petiole size, spinach is the best candidate to become a scaffold for the stem cells to grow on because it most accurately resembles the size of our blood vessels.

4. What are some of the challenges that you faced when designing your methodology?

One of the major challenges was finding the right decellularization technique to use on the spinach stems. A commonly used technique that had previously been proven to be effective on other plant species was adapted for this project, but an endless number of trials had to be run to find the right ratio of decellularizing solutions to get rid of all of the plant cellular material without disrupting the extracellular matrix. Adapting the known method of creating fibrin strands to best suit the purposes of this project was also tedious at times, but very rewarding in the end.

5. How do you think the findings of your project will be applied to real life therapeutic techniques?

The low cost and international accessibility of spinach allows bioengineers all around the world to use the method developed in my study as a novel tissue regeneration technique. Fibrin also has an extensive potential as a cell delivery technique because of its natural adherence quality as well as its degradation in the cells’ waste products. This protein can be easily produced in vitro and it does not cause complications if transplanted into a patient because it degrades over time. This method can be easily adapted to various organs. By varying the type of decellularized plant and the kind of stem cells used, researchers can use this novel technique to bioengineer other organs throughout the body.  

6. In a broad sense, what do you think biomedical engineering research, such as your own work, has to offer to the field of medicine?

I think the future of the field of medicine lies in the hands of bioengineers today because the technologies that are currently available to researchers have such an abundance of applications, many of which have not even yet been thought of. All of the new discoveries and advances that are being made today, particularly in the fields of genetics and stem cell regeneration, will steer the field of medicine towards a more personalized discipline. They will improve the quality of screenings and overall care offered to individuals across the globe.

7. How do you think your research experiences will impact your career?

Although I was previously interested in the field of cardiology, the technical aspects of this project helped me narrow down my career choices and decide to pursue a career as a cardiothoracic surgeon. Furthermore, this research opportunity allowed me to explore the overlap of various fields and realize my passion for surgery, as well as stem cell research. By combining my previous knowledge and newly learned skills, my experience working in the lab made me more excited about discovering the great unknowns of science every day.

8. Do you have any advice for other undergraduates who are looking to pursue research in bioengineering?

I would recommend finding topics that you are interested in and then searching for researchers and labs that conduct research in that field. By applying to as many positions as possible in your desired field, you can ensure that you will earn a spot in a lab that you will enjoy working in. And once you begin your work in a lab, be sure to always be prepared and well-informed on the subject, but remain eager to learn more.

You can read Yassi’s original article, titled “Fixing a Broken Heart.” If you would like to have your own research featured on the TuftScope blog, you can reach Kurtis at kurtis.chien_young@tufts.edu