November 28, 2016
Ohio State University
A key glacier in Antarctica is breaking apart from the inside out, suggesting that the ocean is weakening ice on the edges of the continent.
A key glacier in Antarctica is breaking apart from the inside out, suggesting that the ocean is weakening ice on the edges of the continent.
The Pine Island Glacier, part of the ice shelf that bounds the West Antarctic Ice Sheet, is one of two glaciers that researchers believe are most likely to undergo rapid retreat, bringing more ice from the interior of the ice sheet to the ocean, where its melting would flood coastlines around the world.
A nearly 225-square-mile iceberg broke off from the glacier in 2015, but it wasn’t until Ohio State University researchers were testing some new image-processing software that they noticed something strange in satellite images taken before the event.
In the images, they saw evidence that a rift formed at the very base of the ice shelf nearly 20 miles inland in 2013. The rift propagated upward over two years, until it broke through the ice surface and set the iceberg adrift over 12 days in late July and early August 2015.
They report their discovery in the journal Geophysical Research Letters.
“It’s generally accepted that it’s no longer a question of whether the West Antarctic Ice Sheet will melt, it’s a question of when,” said study leader Ian Howat, associate professor of earth sciences at Ohio State. “This kind of rifting behavior provides another mechanism for rapid retreat of these glaciers, adding to the probability that we may see significant collapse of West Antarctica in our lifetimes.”
While this is the first time researchers have witnessed a deep subsurface rift opening within Antarctic ice, they have seen similar breakups in the Greenland Ice Sheet — in spots where ocean water has seeped inland along the bedrock and begun to melt the ice from underneath.
Howat said the satellite images provide the first strong evidence that these large Antarctic ice shelves respond to changes at their ocean edge in a similar way as observed in Greenland.
“Rifts usually form at the margins of an ice shelf, where the ice is thin and subject to shearing that rips it apart,” he explained. “However, this latest event in the Pine Island Glacier was due to a rift that originated from the center of the ice shelf and propagated out to the margins. This implies that something weakened the center of the ice shelf, with the most likely explanation being a crevasse melted out at the bedrock level by a warming ocean.”
Another clue: The rift opened in the bottom of a “valley” in the ice shelf where the ice had thinned compared to the surrounding ice shelf.
The valley is likely a sign of something researchers have long suspected: Because the bottom of the West Antarctic Ice Sheet lies below sea level, ocean water can intrude far inland and remain unseen. New valleys forming on the surface would be one outward sign that ice was melting away far below.
The origin of the rift in the Pine Island Glacier would have gone unseen, too, except that the Landsat 8 images Howat and his team were analyzing happened to be taken when the sun was low in the sky. Long shadows cast across the ice drew the team’s attention to the valley that had formed there.
“The really troubling thing is that there are many of these valleys further up-glacier,” Howat added. “If they are actually sites of weakness that are prone to rifting, we could potentially see more accelerated ice loss in Antarctica.”
More than half of the world’s fresh water is frozen in Antarctica. The Pine Island Glacier and its nearby twin, the Thwaites Glacier, sit at the outer edge of one of the most active ice streams on the continent. Like corks in a bottle, they block the ice flow and keep nearly 10 percent of the West Antarctic Ice Sheet from draining into the sea.
Studies have suggested that the West Antarctic Ice Sheet is particularly unstable, and could collapse within the next 100 years. The collapse would lead to a sea-level rise of nearly 10 feet, which would engulf major U.S. cities such as New York and Miami and displace 150 million people living on coasts worldwide.
“We need to understand exactly how these valleys and rifts form, and what they mean for ice shelf stability,” Howat said. “We’re limited in what information we can get from space, so this will mean targeting air and field campaigns to collect more detailed observations. The U.S. and the U.K. are partnering on a large field science program targeted at that area of Antarctica, so this will provide another piece to the puzzle.”
Co-authors on the paper included Seongsu Jeong, a postdoctoral researcher at the Byrd Polar and Climate Research Center at Ohio State, and Jeremy Bassis, a glaciologist at the University of Michigan. This research is funded by NASA and the National Science Foundation.
- Seongsu Jeong, Ian M. Howat, Jeremy N. Bassis. Accelerated ice shelf rifting and retreat at Pine Island Glacier, West Antarctica. Geophysical Research Letters, 2016; DOI: 10.1002/2016GL071360
Source: Ohio State University. “West Antarctic Ice Shelf Breaking Up From the Inside Out.” ScienceDaily. ScienceDaily, 28 November 2016. <www.sciencedaily.com/releases/2016/11/161128085341.htm>.
November 28, 2016
University of Washington
A new study of one of our closest invertebrate relatives, the acorn worm, reveals that regenerating body parts might one day be possible.
What if humans could regrow an amputated arm or leg, or completely restore nervous system function after a spinal cord injury?
A new study of one of our closest invertebrate relatives, the acorn worm, reveals that this feat might one day be possible. Acorn worms burrow in the sand around coral reefs, but their ancestral relationship to chordates means they have a genetic makeup and body plan surprisingly similar to ours.
A study led by the University of Washington and published in the December issue of the journal Developmental Dynamics has shown that acorn worms can regrow every major body part — including the head, nervous system and internal organs — from nothing after being sliced in half. If scientists can unlock the genetic network responsible for this feat, they might be able to regrow limbs in humans through manipulating our own similar genetic heritage.
“We share thousands of genes with these animals, and we have many, if not all, of the same genes they are using to regenerate their body structures,” said lead author Shawn Luttrell, a UW biology doctoral student based at Friday Harbor Laboratories. “This could have implications for central nervous system regeneration in humans if we can figure out the mechanism the worms use to regenerate.”
The new study finds that when an acorn worm — one of the few living species of hemichordates — is cut in half, it regrows head or tail parts on each opposite end in perfect proportion to the existing half. Imagine if you cut a person in half at the waist, the bottom half would grow a new head and the top half would grow new legs.
After three or four days, the worms start growing a proboscis and mouth, and five to 10 days after being cut the heart and kidneys reappear. By day 15, the worms had regrown a completely new neural tube, the researchers showed. In humans, this corresponds to the spinal cord and brain.
After being cut, each half of the worm continues to thrive, and subsequent severings also produce vital, healthy worms once all of the body parts regrow.
“Regeneration gives animals or populations immortality,” said senior author Billie Swalla, director of Friday Harbor Laboratories and a UW biology professor. “Not only are the tissues regrown, but they are regrown exactly the same way and with the same proportions so that at the end of the process, you can’t tell a regenerated animal from one that has never been cut.”
The researchers also analyzed the gene expression patterns of acorn worms as they regrew body parts, which is an important first step in understanding the mechanisms driving regeneration. They suspect that a “master control” gene or set of genes is responsible for activating a pattern of genetic activity that promotes regrowth, because once regeneration begins, the same pattern unfolds in every worm. It’s as if the cells are independently reading road signs that tell them how far the mouth should be from the gill slits, and in what proportion to other body parts and the original worm’s size.
When these gene patterns are known, eventually tissue from a person with an amputation could be collected and the genes in those cells activated to go down a regeneration pathway. Then, a tissue graft could be placed on the end of a severed limb and the arm or leg could regrow to the right size, Swalla explained.
“I really think we as humans have the potential to regenerate, but something isn’t allowing that to happen,” Swalla said. “I believe humans have these same genes, and if we can figure out how to turn on these genes, we can regenerate.”
Regeneration is common in many animal lineages, though among the vertebrates (which includes humans) it is most robust in amphibians and fish. Humans can regrow parts of organs and skin cells to some degree, but we have lost the ability to regenerate complete body parts.
Scientists suspect several reasons for this: Our immune systems — in a frenzy to staunch bleeding or prevent infection — might inhibit regeneration by creating impenetrable scar tissue over wounds, or perhaps our relatively large size compared with other animals might make regeneration too energy intensive. Replacing a limb might not be cost-effective, from an energy perspective, if we can adapt to using nine fingers instead of 10 or one arm instead of two.
The researchers are now trying to decipher which type of cells the worms are using to regenerate. They might be using stem cells to promote regrowth, or they could be reassigning cells to take on the task of regrowing tissue. They also hope to activate genes to stimulate complete regeneration in animals that currently aren’t able to regrow all tissues, such as zebrafish.
- Shawn M. Luttrell, Kirsten Gotting, Eric Ross, Alejandro Sánchez Alvarado, Billie J. Swalla. Head regeneration in hemichordates is not a strict recapitulation of development. Developmental Dynamics, 2016; 245 (12): 1159 DOI: 10.1002/dvdy.24457
Source: University of Washington. “Our closest worm kin regrow body parts, raising hopes of regeneration in humans.” ScienceDaily. ScienceDaily, 28 November 2016. <www.sciencedaily.com/releases/2016/11/161128151055.htm>.
November 25, 2016
Imperial College London
Scientists behind a theory that the speed of light is variable — and not constant as Einstein suggested — have made a prediction that could be tested.
Scientists behind a theory that the speed of light is variable — and not constant as Einstein suggested — have made a prediction that could be tested.
Einstein observed that the speed of light remains the same in any situation, and this meant that space and time could be different in different situations.
The assumption that the speed of light is constant, and always has been, underpins many theories in physics, such as Einstein’s theory of general relativity. In particular, it plays a role in models of what happened in the very early universe, seconds after the Big Bang.
But some researchers have suggested that the speed of light could have been much higher in this early universe. Now, one of this theory’s originators, Professor João Magueijo from Imperial College London, working with Dr Niayesh Afshordi at the Perimeter Institute in Canada, has made a prediction that could be used to test the theory’s validity.
Structures in the universe, for example galaxies, all formed from fluctuations in the early universe — tiny differences in density in certain regions. A record of these early fluctuations is imprinted on the cosmic microwave background — a map of the oldest light in the universe — in the form of a ‘spectral index’.
Working with their theory that the fluctuations were influenced by a varying speed of light in the early universe, Professor Magueijo and Dr Afshordi have now used a model to put an exact figure on the spectral index. The predicted figure and the model it is based on are published in the journal Physical Review D.
Cosmologists are currently getting ever more precise readings of this figure, so that prediction could soon be tested — either confirming or ruling out the team’s model of the early universe. Their figure is a very precise 0.96478. This is close to the current estimate of readings of the cosmic microwave background, which puts it around 0.968, with some margin of error.
Professor Magueijo said: “The theory, which we first proposed in the late-1990s, has now reached a maturity point — it has produced a testable prediction. If observations in the near future do find this number to be accurate, it could lead to a modification of Einstein’s theory of gravity.
“The idea that the speed of light could be variable was radical when first proposed, but with a numerical prediction, it becomes something physicists can actually test. If true, it would mean that the laws of nature were not always the same as they are today.”
The testability of the varying speed of light theory sets it apart from the more mainstream rival theory: inflation. Inflation says that the early universe went through an extremely rapid expansion phase, much faster than the current rate of expansion of the universe.
These theories are necessary to overcome what physicists call the ‘horizon problem’. The universe as we see it today appears to be everywhere broadly the same, for example it has a relatively homogenous density.
This could only be true if all regions of the universe were able to influence each other. However, if the speed of light has always been the same, then not enough time has passed for light to have travelled to the edge of the universe, and ‘even out’ the energy.
As an analogy, to heat up a room evenly, the warm air from radiators at either end has to travel across the room and mix fully. The problem for the universe is that the ‘room’ — the observed size of the universe — appears to be too large for this to have happened in the time since it was formed.
The varying speed of light theory suggests that the speed of light was much higher in the early universe, allowing the distant edges to be connected as the universe expanded. The speed of light would have then dropped in a predictable way as the density of the universe changed. This variability led the team to the prediction published today.
The alternative theory is inflation, which attempts to solve this problem by saying that the very early universe evened out while incredibly small, and then suddenly expanded, with the uniformity already imprinted on it. While this means the speed of light and the other laws of physics as we know them are preserved, it requires the invention of an ‘inflation field’ — a set of conditions that only existed at the time.
- Niayesh Afshordi, João Magueijo. Critical geometry of a thermal big bang. Physical Review D, 2016; 94 (10) DOI: 10.1103/PhysRevD.94.101301
Source: Imperial College London. “Theory that challenges Einstein’s physics could soon be put to the test.” ScienceDaily. ScienceDaily, 25 November 2016. <www.sciencedaily.com/releases/2016/11/161125084229.htm>.
November 24, 2016
Mental disorders and physical diseases frequently go hand in hand. For the first time, psychologists have identified temporal patterns in young people: arthritis and diseases of the digestive system are more common after depression, while anxiety disorders tend to be followed by skin diseases.
Mental disorders and physical diseases frequently go hand in hand. For the first time, psychologists at the University of Basel and Ruhr University Bochum have identified temporal patterns in young people: arthritis and diseases of the digestive system are more common after depression, while anxiety disorders tend to be followed by skin diseases.
Physical diseases and mental disorders affect a person’s quality of life and present a huge challenge for the healthcare system. If physical and mental disorders systematically co-occur from an early age, there is a risk that the sick child or adolescent will suffer from untoward developments.
Data from 6,500 teenagers
In a project financed by the Swiss National Science Foundation, a research group led by PD Dr. Marion Tegethoff in collaboration with Professor Gunther Meinlschmidt from the University of Basel’s Faculty of Psychology has now examined the temporal pattern and relationship between physical diseases and mental disorders in children and young people. In the journal PLOS ONE, they analyzed data from a representative sample of 6,483 teenagers from the US aged between 13 and 18.
The researchers noted that some physical diseases tend to occur more frequently in children and adolescents if they have previously suffered from certain mental disorders. Likewise, certain mental disorders tend to occur more frequently after the onset of particular physical diseases. Affective disorders such as depression were frequently followed by arthritis and diseases of the digestive system, while the same relationship existed between anxiety disorders and skin diseases. Anxiety disorders were more common if the person had already suffered from heart disease. A close association was also established for the first time between epileptic disorders and subsequent eating disorders.
Epilepsy and eating disorders
The results offer important insights into the causal relationship between mental disorders and physical diseases. The newly identified temporal associations draw attention to processes that could be relevant both to the origins of physical diseases and mental disorders and to their treatment. In an earlier study, the same authors had already provided evidence for the relationship between mental disorders and physical diseases in young people.
“For the first time, we have established that epilepsy is followed by an increased risk of eating disorders — a phenomenon, that had previously been described only in single case reports. This suggests that approaches to epilepsy treatment could also have potential in the context of eating disorders,” explains Marion Tegethoff, the study’s lead author. From a health policy perspective, the findings underscore that the treatment of mental disorders and physical diseases should be closely interlinked from an early age on.
- Marion Tegethoff, Esther Stalujanis, Angelo Belardi, Gunther Meinlschmidt. Chronology of Onset of Mental Disorders and Physical Diseases in Mental-Physical Comorbidity – A National Representative Survey of Adolescents. PLOS ONE, 2016; 11 (10): e0165196 DOI: 10.1371/journal.pone.0165196
Source: Universität Basel. “Depression in young people affects the stomach, anxiety the skin.” ScienceDaily. ScienceDaily, 24 November 2016. <www.sciencedaily.com/releases/2016/11/161124081604.htm>
November 22, 2016
Perelman School of Medicine at the University of Pennsylvania
A breathing-based meditation practice known as Sudarshan Kriya yoga helped alleviate severe depression in people who did not fully respond to antidepressant treatments, reports a new study.
A breathing-based meditation practice known as Sudarshan Kriya yoga helped alleviate severe depression in people who did not fully respond to antidepressant treatments, reports a new study published in the Journal of Clinical Psychiatry from researchers in the Perelman School of Medicine at the University of Pennsylvania. The study bolsters the science behind the use of controlled yogic breathing to help battle depression.
In a randomized, controlled pilot study, led by Anup Sharma, MD, PhD, a Neuropsychiatry research fellow in the department of Psychiatry at Penn, researchers found significant improvement in symptoms of depression and anxiety in medicated patients with major depressive disorder (MDD) who participated in the breathing technique compared to medicated patients who did not partake. After two months, the yoga group cut its mean Hamilton Depression Rating Scale (HDRS) score by several points, while the control group showed no improvements. HDRS is the most widely used clinician-administered depression assessment that scores mood, interest in activities, energy, suicidal thoughts, and feelings of guilt, among other symptoms.
More than half of the 41 million Americans who take antidepressants do not fully respond. Add-on therapies are often prescribed to enhance the effects of the drugs in these patients, but they typically offer limited additional benefits and come with side effects that can curb use, prolonging the depressive episode. What’s more, patients who don’t fully respond to antidepressants are especially at risk of relapse.
“With such a large portion of patients who do not fully respond to antidepressants, it’s important we find new avenues that work best for each person to beat their depression,” Sharma said. “Here, we have a promising, lower-cost therapy that could potentially serve as an effective, non-drug approach for patients battling this disease.”
The meditation technique, which is practiced in both a group setting and at home, includes a series of sequential, rhythm-specific breathing exercises that bring people into a deep, restful, and meditative state: slow and calm breaths alternated with fast and stimulating breaths.
“Sudarshan Kriya yoga gives people an active method to experience a deep meditative state that’s easy to learn and incorporate in diverse settings,” Sharma said.
In past studies, the practice has demonstrated a positive response in patients with milder forms of depression, depression due to alcohol dependence, and in patients with MDD; however, there are no clinical studies investigating its use for depression in an outpatient setting. Past studies suggest that yoga and other controlled breathing techniques can potentially adjust the nervous system to reduce stress hormones. Overall, the authors also note, well-designed studies that evaluate the benefits of yoga to treat depression are lacking, despite increased interest in the ancient Indian practice. Millions of Americans participate in some form of yoga every year.
In the study, researchers enrolled 25 patients suffering from MDD who were depressed, despite more than eight weeks of antidepressant medication treatment. The medicated patients were randomized to either the breathing intervention group or the “waitlist” control group for eight weeks. (The waitlist group was offered the yoga intervention after the study). During the first week, participants completed a six-session program, which featured Sudarshan Kriya yoga in addition to yoga postures, sitting meditation, and stress education. For weeks two through eight, participants attended weekly Sudarshan Kriya yoga follow-up sessions and completed a home practice version of the technique.
Patients in the Sudarshan Kriya yoga group showed a significantly greater improvement in HDRS scores compared to patients in the waitlist group. With a mean baseline HDRS score of 22.0 (indicating severe depression at the beginning of the study), the group that completed the breathing technique for the full two months improved scores by 10.27 points on average, compared to the waitlist group, which showed no improvements. Patients in the yoga group also showed significant mean reductions in total scores of the self-reported Beck Depression (15.48 point improvement) and Beck Anxiety Inventories (5.19 point improvement), versus the waitlist control group.
Results of the pilot study suggest the feasibility and promise of Sudarshan Kriya as an add-on intervention for MDD patients who have not responded to antidepressants, the authors wrote. “The next step in this research is to conduct a larger study evaluating how this intervention impacts brain structure and function in patients who have major depression,” Sharma said.
Materials provided by Perelman School of Medicine at the University of Pennsylvania. Note: Content may be edited for style and length.
- Anup Sharma, Marna S. Barrett, Andrew J. Cucchiara, Nalaka S. Gooneratne, Michael E. Thase. A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants. The Journal of Clinical Psychiatry, 2016; DOI: 10.4088/JCP.16m10819
Source: Perelman School of Medicine at the University of Pennsylvania. “Yogic breathing helps fight major depression, study shows.” ScienceDaily. ScienceDaily, 22 November 2016. <www.sciencedaily.com/releases/2016/11/161122182357.htm>.
November 21, 2016
University of Missouri
Studying how gut bacteria affect behavior in zebrafish could lead to a better understanding of how probiotics may affect the central nervous system in humans.
Probiotics, or beneficial live bacteria that are introduced into the body, have become increasingly popular as a way to improve health and well-being. Previous studies have shown a direct correlation between gut microbes and the central nervous system. Now, researchers at the University of Missouri, using a zebrafish model, determined that a common probiotic sold in supplements and yogurt can decrease stress-related behavior and anxiety. Studying how gut bacteria affect behavior in zebrafish could lead to a better understanding of how probiotics may affect the central nervous system in humans. Their results recently were published in Scientific Reports a journal of Nature.
“Zebrafish are an emerging model species for neurobehavioral studies and their use is well-established in drug-screening,” said Aaron Ericsson, director of the MU Metagenomics Center and a research assistant professor in the Department of Veterinary Pathobiology. “Our study has shown that simple probiotics that we normally use to keep our digestive tract in sync, could be beneficial to reducing our stress levels as well.”
In a series of studies, researchers tested how zebrafish behaved after doses of Lactobacillus plantarum, a common bacteria found in yogurt and probiotic supplements. In the first study, scientists added the bacteria to certain tanks housing zebrafish; other tanks of zebrafish received no probiotics. Then, the researchers introduced environmental stressors to both groups, such as draining small amounts of water from the tank and overcrowding.
“Each day we introduced a different stressor — tests that are validated by other researchers and cause higher anxiety among zebrafish,” said Elizabeth Bryda, professor of veterinary pathobiology in the MU College of Veterinary Medicine. “These are common environmental stress patterns, such as isolation stress and temperature change, so it made the tests relevant to humans as well.”
By analyzing the gene pathways of both groups of fish, the research team found that zebrafish that were given the supplements showed a reduction in the metabolic pathways associated with stress.
“By measuring the genes associated with stress and anxiety, our tests were able to predict how this common probiotic is able to benefit behavioral responses in these fish,” said Daniel Davis, assistant director of the MU Animal Modeling Core. “Essentially, bacteria in the gut altered the gene expression associated with stress- and anxiety-related pathways in the fish allowing for increased signaling of particular neurotransmitters.”
To test their theory further, the researchers measured the movements of fish in their tanks using sophisticated computer measuring and imaging tools. Previous studies of fish behavior have found that fish that are stressed tend to spend more time at the bottom of their tanks. Once the fish were administered probiotics, they tended to spend more time toward the top of the tanks — the change in behavior indicating they were less stressed or less anxious.
“Using zebrafish, we’ve developed a relatively inexpensive platform for testing of other species of bacteria and probiotics and their potential benefit on different systems of the body,” Ericsson said.
- Daniel J. Davis, Holly M. Doerr, Agata K. Grzelak, Susheel B. Busi, Eldin Jasarevic, Aaron C. Ericsson, Elizabeth C. Bryda. Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish. Scientific Reports, 2016; 6: 33726 DOI: 10.1038/srep33726
Source: University of Missouri. “Common probiotics can reduce stress levels, lessen anxiety.” ScienceDaily. ScienceDaily, 21 November 2016. <www.sciencedaily.com/releases/2016/11/161121160038.htm>.
November 21, 2016
Cincinnati Children’s Hospital Medical Center
Scientists report using human pluripotent stem cells to grow human intestinal tissues that have functioning nerves in a laboratory, and then using these to recreate and study a severe intestinal nerve disorder called Hirschsprung’s disease.
Scientists report in Nature Medicine using human pluripotent stem cells to grow human intestinal tissues that have functioning nerves in a laboratory, and then using these to recreate and study a severe intestinal nerve disorder called Hirschsprung’s disease.
Published online Nov. 21, the findings describe an unprecedented approach to engineer and study tissues in the intestine — the body’s largest immune organ, its food processor and main interface with the outside world. Study authors at Cincinnati Children’s Hospital Medical Center say the paper puts medical science a step closer to using human pluripotent stem cells (which can become any cell type in the body) for regenerative medicine and growing patient-specific human intestine for transplant.
“One day this technology will allow us to grow a section of healthy intestine for transplant into a patient, but the ability to use it now to test and ask countless new questions will help human health to the greatest extent,” said Michael Helmrath, MD, co-lead study investigator and surgical director of the Intestinal Rehabilitation Program at Cincinnati Children’s.
This ability starts with being able to model and study intestinal disorders in functioning, three-dimensional human organ tissue with genetically-specific patient cells. The technology will also allow researchers to test new therapeutics in functioning lab-engineered human intestine before clinical trials in patients.
“Many oral medications give you diarrhea, cramps and impair intestinal motility. A fairly immediate goal for this technology that would help the largest number of people is as a first-pass screen for new drugs to look for off-target toxicities and prevent side effects in the intestine,” explained Jim Wells, PhD, co-lead investigator and director of the Pluripotent Stem Cell Facility at Cincinnati Children’s.
As science continues to learn more about how important intestinal health is to overall health, Wells and Helmrath said using functioning lab-generated human intestine creates an array of new research opportunities. Some include the ability to conduct deeper studies into nutritional health, diabetes, severe intestinal diseases (like necrotizing enterorcolitis), and biochemical changes in the body from gastric by-pass weight-loss surgery.
Nerves Nature’s Way
Researchers started out by subjecting human pluripotent stem cells to a biochemical bath that triggers their formation into human intestinal tissue in a petri dish. The process was essentially the same as that used by the Wells’ lab in a landmark 2010 Nature study, which reported the first-ever generation of three-dimensional human intestinal organoids in a laboratory.
Intestinal tissues from the initial study lacked an enteric nervous system, which is critical to the movement of waste through the digestive tract and the absorption of nutrients. The gastrointestinal tract contains the second largest number of nerves in the human body, according to Wells. When these nerves fail to work properly it hinders the contraction of intestinal muscles. This contributes to abdominal pain, diarrhea, constipation, and in severe cases creates functional blockages that require surgery.
To engineer a nervous system for the intestinal organoids already growing in one petri dish, researchers generated embryonic-stage nerve cells called neural crest cells in a separate dish. The neural crest cells were manipulated to form precursor cells for enteric nerves. The challenge at this stage was identifying how and when to incorporate the neural crest cells into the developing intestine.
“We tried a few different approaches largely based on the hypothesis that, if you put the right cells together at the right time in the petri dish, they’ll know what do to. It was a longshot, but it worked,” said Wells, who credits Cincinnati Children’s developmental biologist Samantha Brugmann, PhD, (and a study co-author) with providing critical insights into embryonic nerve development.
The appropriate mix caused enteric nerve precursor cells and intestines to grow together in a manner resembling developing fetal intestine. The result was the first evidence for generating complex and functional three-dimensional intestinal organoids in a petri dish, and fully derived from human pluripotent stem cells.
In Vivo Testing
A key test for the engineered intestines and nerves was transplanting them into a living organism — in this case laboratory mice with suppressed immune systems. This allowed researchers to see how well the tissues grow and function. Study data show the tissues work and are structured in a manner remarkably similar to natural human intestine. They grow robustly, process nutrients and demonstrate peristalsis — series of wave-like muscle contractions that in the body move food through the digestive tract.
Researchers then used the technology to study the molecular progression of a rare form of Hirschsprung’s disease — a condition in which the rectum and colon fail to develop a normal nervous system, causing waste to accumulate. A severe form of Hirschsprung’s is caused by a mutation in the gene PHOX2B. Tests in a petri dish and mice demonstrated that mutating PHOX2B causes profound detrimental changes to innervated intestinal tissues.
The current study blends basic research and clinical insight from the Developmental Biology and Endocrinology laboratory staff of Wells and General/Thoracic Surgery research team of Helmrath — who cares for children with a broad spectrum of digestive disorders. Co-first authors include Maxime Mahe, PhD, an instructor in the Helmrath lab, and Michael Workman, PhD, a former a member of the Wells lab.
- Michael J Workman, Maxime M Mahe, Stephen Trisno, Holly M Poling, Carey L Watson, Nambirajan Sundaram, Ching-Fang Chang, Jacqueline Schiesser, Philippe Aubert, Edouard G Stanley, Andrew G Elefanty, Yuichiro Miyaoka, Mohammad A Mandegar, Bruce R Conklin, Michel Neunlist, Samantha A Brugmann, Michael A Helmrath, James M Wells. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nature Medicine, 2016; DOI: 10.1038/nm.4233
Source: Cincinnati Children’s Hospital Medical Center. “Scientists tissue engineer human intestines and functioning nerves.” ScienceDaily. ScienceDaily, 21 November 2016. <www.sciencedaily.com/releases/2016/11/161121130955.htm>.
James Farley Photographs Supermoon Over Winston-Salem, NC.
There will be no ON TARGET next week as we are taking off for the Thanksgiving holiday. Our best to all of our readers. We now have over 6,000 current subscribers to ON TARGET. From time to time we receive newsworthy events and/or photos from our loyal readers.
A Supermoon happens when a Full Moon or New Moon coincides with the Moon’s closest approach to Earth; also called perigee. A Super Full Moon looks around 12% to 14% bigger than its counterpart, the Micromoon. The Supermoon on November 14, 2016, was the closest a Full Moon has been to Earth since January 26, 1948. The next time a Full Moon is even closer to Earth will be on November 25, 2034.
Our friend and colleague James Farley, photographer extraordinaire, took Supermoon photos in Winston-Salem, NC, which were featured by Lanie Pope on WXII 12 Winston-Salem!
Supemoon over the R J Reynolds building, Winston, NC. ©jfarley Photography.
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Copper: The Bacteria-Fighting Super Element is Making a Comeback In Hospitals
This is human coronavirus 229E being inactivated on copper. Credit: University of Southampton, England
Copper is being embraced by some hospitals because of its ability to kill 1) ___ and other microbes on contact, which can help reduce deadly infections. Copper can kill or inactivate a variety of pathogens by interacting with oxygen and modifying oxygen molecules. In bacteria, this disrupts the outer layer, damaging the genetic material and cell machinery, which can lead to cell death. A recent study found that copper also destroys norovirus. There has been only one published clinical trial showing how copper reduces infections in hospitals. The results, however, were striking. The study, which took place between July 2010 and June 2011, showed that copper surfaces reduced infection rates by 58%. The antimicrobial effect of copper-alloy surfaces is a result of the metal stealing electrons from the bacteria when they come into contact with each other. Once the bacteria donate the electrons to the copper metal, this places the organism into a state of electrical-charge deficit. As a consequence, free radicals are generated inside the cell, which ultimately leads to the cell’s death.
Checking into a hospital can boost your chances of infection. That’s a disturbing paradox of modern medical care. And it doesn’t matter where in the world you’re hospitalized. From the finest to the most rudimentary medical facilities, patients are vulnerable to new 2) ___ that have nothing to do with their original medical problem. These are referred to as healthcare-acquired infections, healthcare-associated infections or hospital-acquired infections. These are infections like pneumonia and urinary tract infections. Many of them, like methicillin-resistant Staphylococcus aureus (MRSA), can be deadly. The World Health Organization estimates that each year, hundreds of millions of patients around the world are affected by healthcare-acquired infections. In the United States, the Office of Disease Prevention and Health Promotion in the Health and Human Services Department estimates that 1 in 25 inpatients has a 3) ___-related infection. In developing countries, estimates run higher.
Hospital bed safety railings are a major source of these infections. That’s what Constanza Correa, 33, and her colleagues have found in their research in Santiago, Chile. They’ve taken on the problem by replacing them, since 2013, with railings made of copper, an anti-microbial element. Copper definitely wipes out 4) ___. Bacteria, yeasts and viruses are rapidly killed on metallic copper surfaces, and the term contact killing has been coined for this process, wrote the authors of an article on copper in Applied and Environmental Microbiology. That knowledge has been around a very long time. The journal article cites an Egyptian medical text, written around 2600-2000 BCE, that cites the use of copper to sterilize chest wounds and drinking water. Correa’s startup, Copper BioHealth, has not yet assessed the railings’ impact in Chilean hospitals. But a study of the effects of copper-alloy surfaces in U.S. hospitals’ intensive care units, published last year in Infection Control and Hospital Epidemiology, showed promising results: Their presence reduced the number of healthcare-acquired infections from 8.1% in regular rooms to 3.4% in the copper rooms.
Healthcare-acquired infections are a huge problem. People come to the hospital with a sickness, and they get another one in the hospital. Then they have to stay longer and spend more money on treatment. Sometimes it can cause 5) ___. Eighty percent of these infections come from touching hospital surfaces. In the hospital room, the most contaminated surface is the bed rail. It’s the most manipulated by medical staff and patients. It’s in direct contact with the patient. That’s the most critical surface in the room. A hospital’s objective is to decrease the chance of infection due to surface contact. So if we can replace current bed rails with copper bed rails, there is the potential to kill viruses, fungi and bacteria continuously. The magnitude of the problem is that in industrialized countries, 5% of patients develop these infections and the number is three times more in developing countries. In the United States, the annual direct cost to treat these infections is $40 billion a year. At least 15 hospitals across the country have installed, or are considering installing, copper components on high-touch surfaces easily contaminated with microbes – faucet handles on sinks, cabinet pulls, toilet levers, call buttons and IV poles. We’ve known for a long time that copper and other metals are effective in killing microbes, so it wasn’t a great leap to incorporate copper surfaces into hospitals, said John Lynch, medical director of infection control at Seattle’s Harborview Medical Center, which is redesigning a waste-disposal room to incorporate copper on light switches and door handles. For many hospitals, the death of Ebola patient Thomas Eric Duncan last year at a Dallas hospital heightened concerns – two nurses caring for him caught the 6) ___ because of poor infection control. And even before that, public health officials had identified nearly two dozen dangerous pathogens – many of them resistant to virtually all antibiotics – whose spread in health facilities and elsewhere could result in potentially catastrophic consequences. They include MRSA, a potentially deadly infection that is increasing in community settings; VRE, which can cause a variety of infections; and C. diff, which causes life-threatening diarrhea and sends 250,000 people to the hospital every year.
On any given day, about 1 in 25 patients in acute-care hospitals has at least one health-care-associated infection, according to the CDC or 7) ___ for ___ ___ and ___. Pneumonia and surgical-site infections are among the most common. In 2011, about 75,000 patients with health-care-associated infections died in the hospital. Hospital officials aren’t the only ones interested in copper. Hartsfield-Jackson Atlanta International Airport installed drinking fountains retrofitted with antimicrobial copper surfaces. In Colorado Springs, the U.S. Olympic Committee’s flagship training center uses custom dumbbells with antimicrobial copper grips. So do two professional hockey teams, the Los Angeles Kings and St. Louis Blues. Even a Chick-fil-A in Morganton, N.C., installed antimicrobial copper on restroom door handles.
Now, the CDC is pressing for more research. Recently, it held a roundtable on environmental infection control in preventing Ebola and other health-care-associated infections. Officials, who are exploring copper and other technologies, are working with hospitals, academics and the copper industry. The Defense Department, which funded the first clinical trial on copper and hospital-acquired infections, is researching copper’s effectiveness against one type of bacteria, acinetobacter, which can cause pneumonia or bloodstream infections among critically ill patients, including wounded 8) ___ returning from the battlefield. Many experts have concluded that traditional methods for reducing hospital-acquired infections, such as hand washing, aren’t enough, because people don’t always do what they are supposed to do and many pathogens can survive for long periods on surfaces. That’s why hospitals are experimenting with other ways to destroy them, including using ultraviolet light and hydrogen peroxide vapor to target germs in nooks and crannies not easily reached by cleaning crews. But those measures require actions by human beings – which is not the case with copper. It’s always working, it requires no human intervention, no supervision, and it’s acting continuously, said Michael Schmidt, a microbiology professor at the Medical University of South Carolina and one of the researchers who conducted the first and largest study of copper surfaces in hospitals. Besides the South Carolina hospital, the study involved Memorial Sloan Kettering Cancer Center in New York and the Veterans Affairs hospital in Charleston, S.C. About 600 patients who were admitted to the intensive-care units at the facilities were randomly assigned to receive care in traditional patient rooms or ones in which six frequently touched objects – such as bed rails, tables, IV poles and nurse call buttons – were made from copper alloys. While welcoming the findings, researchers said additional studies are needed to answer many questions. Is there a minimal risk number out there – how many bacteria on a surface to really put people at risk? said L. Clifford McDonald, a medical epidemiologist at the CDC. Right now, there’s not enough data on copper or other technologies to make firm recommendations on what hospitals should do, he said. In the meantime, facilities should continue to thoroughly clean patients’ rooms and supplement that with disinfectants. And everyone, especially health-care workers, should wash their hands with soap and water.
At an American Hospital Association conference in July, Todd Linden, chief executive of Grinnell Regional Medical Center in Iowa, gave a 70-minute presentation on copper items installed in 13 of the hospital’s patient rooms. The 49-bed facility also plans to use copper in renovating its emergency room. Grinnell College biology professor Shannon Hinsa-Leasure is conducting a clinical trial on the hospital’s use of copper. The hospital’s fitness center also has copper components, including on its free weights. Olin Brass and its manufacturing partners donated products for the hospital; community donations paid for the fitness center. A typical U.S. hospital room contains about $100,000 of goods and equipment, experts say. The average cost to outfit a hospital room with antimicrobial copper items is about $5,000, Linden said. But one infection adds $43,000 in patient costs, according to federal data. And under the Affordable Care Act, hospitals with higher infection rates and other patient injuries face decreases in their Medicare reimbursements.
The copper industry, meanwhile, provided financial help to several facilities interested in experimenting with 9) ___surfaces. The Copper Development Association gave $50,000 in grants to four hospitals in 2013 and 2014, said Adam Estelle, a project engineer with the trade group. The association began promoting copper’s antimicrobial properties in 2008, when several groups of copper products met standards of the Environmental Protection Agency to be registered as antimicrobial and effective in killing six types of bacteria, including MRSA, VRE and the deadly E. coli 0157 strain, the culprit in numerous food recalls, illnesses and deaths. Pullman Regional Hospital in Washington State received a $10,000 grant from the copper industry group two years ago. The 26-bed hospital bought more than 1,200 cabinet drawer pulls and 22 handicapped-access buttons on doors. Ed Harrich, chief of surgical services, and his staff have been methodically installing the hardware. He persuaded hospital administrators to approve another $10,000 for more items. More than 150 health-care and other facilities have installed antimicrobial copper alloy surfaces manufactured in the U.S. since 2011, according to the Copper Development Association. Cost is an issue. Adding copper surfaces is about 15 to 20% more expensive than using traditional stainless steel. But the long-term 10) ___are worth it. Sources: The Washington Post, Wall Street Journal, NPR; Medscape; ScienceDaily
ANSWERS: 1) bacteria; 2) infections; 3) hospital; 4) microbes; 5) death; 6) virus; 7) Centers for Disease Control and Prevention; 8) soldiers; 9) copper; 10) benefits
Francis Schlatter (1856-1896), Healer with Copper Rod
Francis Schlatter Credit: Unknown – This image is available from the United States Library of Congress’s Prints and Photographs Division; Public Domain, Wikipedia Commons
Francis Schlatter (1856-1896) was an Alsatian cobbler who, because of miraculous cures attributed to him, became known as the Healer. Schlatter was born in the village of Ebersheim, Bas-Rhin, near Selestat, in Alsace on April 29, 1856. In 1884 he emigrated to the United States, where he worked at his trade in various cities, arriving in Denver, Colorado, in 1892. There, a few months later, he experienced a vision at his cobbler’s bench in which he heard the voice of the Father commanding him to sell his business, give the money to the poor, and devote his life to healing the sick. He then undertook a two-year, 3,000-mile walking pilgrimage around the American West which took him across eastern Colorado, Kansas, and Oklahoma, and then to Hot Springs, Arkansas, where he was arrested and jailed for vagrancy. In early 1894 he escaped and headed west, walking across Texas, New Mexico, and Arizona and into southern California, where he began his first efforts at healing with the Indians of the San Jacinto Valley. After two months, he again took up his pilgrimage and traveled east across the Mohave Desert, living on nothing but flour and water.
In July 1895 he emerged as a Christ-like healer in the Rio Grande villages south of Albuquerque. There, while treating hundreds of sick, suffering, and disabled people who flocked to Albuquerque’s Old Town, he became famous. Crowds gathered about him daily, hoping to be cured of their diseases simply by clasping his hands. The following month he returned to Denver, but did not resume his healings until mid-September. During the next few weeks, his ministry drew tens of thousands of pilgrims to a small home in North Denver. Schlatter is said to have refused all rewards for his services. His manner of living was of the simplest, and he taught no new doctrine. He said only that he obeyed a power which he called Father, and from this power he received his healing virtue.
On the night of November 13, 1895, he suddenly disappeared, leaving behind him a note in which he said that his mission was ended. Then, in 1897 news came out of Mexico that the healer’s bones and possessions had been found on a mountainside in the Sierra Madre. At the same time, a New Mexico woman named Ada Morley published a book called The Life of the Harp in the Hand of the Harper which told of the healer’s three-month retreat on her ranch in Datil, New Mexico, after his disappearance from Denver. The book, which carried the title the healer gave it, also contained a first-person description of his two-year pilgrimage, which he believed held the same significance for mankind as Christ’s forty days in the wilderness. On departing the Morley ranch, Schlatter told Morley that God intended to establish New Jerusalem in the Datil Mountains, and the healer promised to return at that time. In the wake of the healer’s death, several men claiming to be Francis Schlatter made headlines around the country in 1909, 1916, and 1922.
In August Strindberg?s autobiographical novel Inferno, Francis Schlatter is mentioned as a doppelganger of another man Strindberg met in Paris in 1896, the year after Schlatter disappeared. He was afraid of Schlatter. The double turned out to be Paul Herrmann, a German-American painter.
The Healer’s Copper Rod
In 1906 Edgar Lee Hewett, who became a noted archaeologist and museum director, was conducting research near Casas Grandes, Chihuahua, Mexico, when his Mexican guide pointed out an unmarked grave. Ten years before, the guide said, he had come across the body of a dead man following a blizzard. From the guide’s description, Hewett surmised that the dead man the guide had come across was Francis Schlatter, whom Hewett had met and whose healing sessions he observed in 1895. Hewett asked if any of the man’s possessions had survived. The guide led him to the home of the jefe of Casas Grandes, and there Hewett saw Schlatter’s Bible, saddle, and copper rod – which had become a mysterious hallmark of the healer from the time of his disappearance. Years later, in 1922, Hewett returned to Mexico and examined the copper rod again. By now, Edgar Lee Hewett had become the director of the School of American Research (now the School for Advanced Research) and the Museum of New Mexico Hewett showed interest in the rod and made a donation to the village of Casas Grandes to hire a teacher. Back in Santa Fe, a few weeks later, he received a heavy, burlap-wrapped package, and inside was Francis Schlatter’s copper rod. He placed the rod in the collections of the two institutions he directed, which shared space in the Palace of the Governors in Santa Fe, N.M. Today the rod lies in the collections of the New Mexico History Museum in the Palace of the Governors. Almost immediately after reports came out of Mexico announcing the healer’s death, skepticism arose. Ada Morley, who had visited at length with Schlatter during his three-month stay at her ranch in New Mexico in early 1896, had her doubts. The men who found the skeleton declared to have been [Schlatter’s], she said, say it was resting as though it had never been disturbed. I know the coyotes would never have left it, if it had ever lain there bearing flesh. The New York Times expressed doubts as well. It does not appear that the human remains were actually identified as Schlatter’s, the newspaper stated on June 19, 1897, or that any identification was possible. However, the presence of the healer’s possessions at the scene, especially his copper rod, convinced most people otherwise. Over the next twenty-five years, several men arose claiming to be Francis Schlatter. One, a Presbyterian minister named Charles McLean, died in Hastings, Nebraska, in 1909, creating a controversy between skeptics and believers. Two others, August Schrader and Jacob Kunze, who formed a healing team that operated between 1908 and 1917, were arrested and jailed in 1916 for mail fraud. A final so-called imposter died in St. Louis, Missouri, in October 1922.
During the second half of the twentieth century, a renewed interest in Schlatter brought with it speculation about the claim of the healer who had died in St. Louis. Most recently, The Vanishing Messiah: The Life and Resurrections of Francis Schlatter (2016), argues that the healer conspired to stage his death in the mountains of Mexico and returned to the United States to continue healing in the eastern and southern parts of the country until his death in St. Louis in 1922. The Vanishing Messiah claim rests in part on the discovery of a largely forgotten autobiography in the Library of Congress entitled Modern Miracles of Healing: A True Account of the Life, Works and Wanderings of Francis Schlatter, the Healer, attributed to Francis Schlatter, The Alsacian, and published in 1903.