June 30, 2015
University of Washington
Researchers have produced cell-to-cell communication in baker’s yeast — a first step in learning to build multicellular organisms or artificial organs from scratch.
For centuries, humans have been playing with yeast. But these simple fungal cells usually do their jobs — making bread rise or converting sugar into alcohol — without having to communicate or work together.
Now, a team of University of Washington researchers has engineered yeast cells (Saccharomyces cerevisiae) that can “talk” to one another, using a versatile plant hormone called auxin.
In a paper published June 23 in the American Chemical Society’s journal ACS Synthetic Biology, the researchers describe a novel cell-to-cell communication system that enables one yeast cell to regulate the expression of genes and influence the behavior of an entirely separate yeast cell.
It’s a basic step in understanding the communication and cooperative processes that might lead to synthetic stem cells that could grow into artificial organs or organisms that require different types of cells to work together.
“Until you can actually build a multicellular organism that starts from a single cell, you don’t really understand it. And until we can do that, it’s going to be hard to do things like regrow a kidney for someone who needs it,” said senior author Eric Klavins, a UW associate professor of electrical engineering and of bioengineering.
It might also enable engineered yeast to perform complicated behaviors that coordinated multicellular systems such as our immune system can pull off, like recognizing an invading pathogen and mounting a response. If so, one might program those cells to collaboratively diagnose the flu or malaria: just add saliva to a packet of yeast and see if it changes color.
For now, though, the team spearheaded by lead authors Arjun Khakhar, a UW doctoral student in bioengineering, and Nicholas J. Bolten, a UW doctoral student in electrical engineering, simply wanted to see if it could induce one yeast cell to send a signal that sets off a cascade of changes in another cell.
In the initial experiment, they used the plant hormone auxin — which yeast cells don’t normally recognize or respond to — to “turn off” a target gene in another cell. In this case, the gene that was switched off was an inserted jellyfish gene that turned the yeast fluorescent green.
“This project was to find out whether we could use auxin to make the cells talk to each other in a really simple way,” said Klavins. “We’re not sending complicated messages yet. One cell is saying ‘hello?’ and the other cell says ‘I can hear you.’ Eventually they’ll say ‘I’m this kind of cell. What are you? Let’s work together.’ But for now it’s pretty much ‘hi.'”
Synthetic biologists, who assemble genetic parts in new ways with the goal of popping them into an organism to produce reliable behaviors, have struggled to build modules that enable cell-to-cell communication in organisms that don’t naturally do it.
The UW team overcame this hurdle by engineering a suite of novel transcription factors — proteins that control whether a specific gene inside a cell’s DNA is expressed or not — with varying sensitivities to auxin. That “tunability” offers important control in regulating cell behavior.
With co-author and UW associate biology professor Jennifer Nemhauser, the UW team figured out how to make a “sender” yeast cell produce auxin, a versatile hormone that controls everything from where a plant’s roots develop to how effectively they fight off pathogens. Through trial and error, the team learned an enzyme borrowed from a soil bacterium can induce yeast to convert a commonly available chemical into auxin.
In the “receiver” yeast cells, the researchers inserted the new transcription factor — which was assembled from so many different genetic parts that they call it the “Frankenfactor” — and engineered it to activate the jellyfish gene that turned the cell green.
When the sender cell released auxin, additional proteins that the researchers introduced in the receiver cell were able to degrade the Frankenfactor and switch off the gene that turned the receiver cell green.
That type of simple communication forms the bedrock of multicellular organisms in which different types of cells collaborate to carry out complicated tasks. As a next step, the UW team plans to test whether auxin can induce more complex behaviors in yeast cells, such as forming patterns or cooperatively computing basic functions.
Since auxin is a plant hormone, mammalian cells also ignore it, making auxin a potentially useful tool in designing gene therapies or other applications without adverse reactions in humans. The UW method, which uses a “guide RNA” to target the gene of interest, could be adapted to produce a number of genetic or behavior changes.
“If you ask someone in computer science what they can do with a programming language, they’ll laugh and say they can do anything with it,” Klavins said. “If we can figure out the programming language of life, we can do anything that life does — except in a more controllable, reliable way.”
The research was funded by the National Science Foundation and the Paul Allen Family Foundation.
- Arjun Khakhar, Nicholas J. Bolten, Jennifer Nemhauser, Eric Klavins.Cell-cell communication in yeast using auxin biosynthesis and auxin responsive CRISPR transcription factors. ACS Synthetic Biology, 2015; 150623113028004 DOI: 10.1021/acssynbio.5b00064
Source: University of Washington. “Scientists program solitary yeast cells to say ‘hello’ to one another.” ScienceDaily. ScienceDaily, 30 June 2015. <www.sciencedaily.com/releases/2015/06/150630141710.htm>.
June 29, 2015
University of Maryland Medical Center/School of Medicine
As the South Korean MERS outbreak continues, researchers have discovered and validated two therapeutics that show early promise in preventing and treating the disease, which can cause severe respiratory symptoms, and has a death rate of 40 percent.
As the South Korean epidemic of Middle East Respiratory Syndrome (MERS) continues unabated, researchers have raced to find treatments for the deadly virus, which has killed more than 400 people since it was first discovered three years ago in Saudi Arabia.
Now, scientists at the University of Maryland School of Medicine and Regeneron Pharmaceuticals, Inc., have discovered and validated two therapeutics that show early promise in preventing and treating the disease, which can cause severe respiratory symptoms, and has a death rate of 40 percent. These therapeutics are the first to succeed in protecting and treating animal models of the MERS virus. The study appears in the journalProceedings of the National Academy of Sciences (PNAS).
“While early, this is very exciting, and has real potential to help MERS patients,” says a lead researcher on the study, Matthew B. Frieman, PhD, an assistant professor of microbiology and immunology at the University of Maryland School of Medicine (UM SOM). “We hope that clinical study will progress on these two antibodies to see whether they can eventually be used to help humans infected with the virus.”
The two antibodies, REGN3051 and REGN3048, showed an ability to neutralize the virus. This research, done in collaboration with Regeneron, a biopharmaceutical company based in Tarrytown, New York, used several of the company’s proprietary technologies to search for and validate effective antibodies targeting the virus.
MERS was first discovered in 2012 in Saudi Arabia. It appears that the disease spread to humans from camels, who may themselves been infected by bats. Research has shown that it is similar to Severe acute respiratory syndrome (SARS); both are caused by Coronaviruses, both cause respiratory problems, and both are often fatal.
The paper also announced the development a novel strain of mice, which will help scientists understand the disease and look for treatments. This work relied on Regeneron’s VelociGene technology to create partially humanized mice that can be infected with MERS.
“Mice are typically not susceptible to MERS,” said Prof. Frieman, who is an expert on both MERS and SARS, as well as other emerging viruses. “This new mouse model will significantly boost our ability to study potential treatments and help scientists to understand how the virus causes disease in people.”
The South Korean outbreak began last month when a traveler returned from Saudi Arabia, and infected many people before officials realized he had the disease. So far, around 180 people have been infected in South Korea, and nearly 30 have died.
“Prof. Frieman’s work provides the first glimmer of hope that we can treat and cure this threatening virus,” said Dean E. Albert Reece, MD, PhD, MBA, who is also the vice president for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the School of Medicine. “I know that they will continue to work hard to see whether these compounds can take the next steps to clinical trials.”
The above post is reprinted from materials provided by University of Maryland Medical Center/School of Medicine. Note: Materials may be edited for content and length.
- Kristen E. Pascal, Christopher M. Coleman, Alejandro O. Mujica, Vishal Kamat, Ashok Badithe, Jeanette Fairhurst, Charleen Hunt, John Strein, Alexander Berrebi, Jeanne M. Sisk, Krystal L. Matthews, Robert Babb, Gang Chen, Ka-Man V. Lai, Tammy T. Huang, William Olson, George D. Yancopoulos, Neil Stahl, Matthew B. Frieman, and Christos A. Kyratsous.Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. PNAS, June 2015 DOI: 10.1073/pnas.1510830112
Source: University of Maryland Medical Center/School of Medicine. “First-ever possible treatments for MERS; two promising candidates.” ScienceDaily. ScienceDaily, 29 June 2015. <www.sciencedaily.com/releases/2015/06/150629162650.htm>.
Target Health Featured in Profile Magazine
Below is an extract of an article in Profile Magazine that featured Target Health. The article in its entirety can be found at (http://profilemagazine.com/2015/target-health/). Notice Malcom Furlow’s Armani Indian in the background picture of the article.
Champion of Paperless Health Care: Independent thinking has paid off for Target Health’s Jules Mitchel, whose company has revolutionized the clinical trial process –By Amy Martino in Profile Magazine
Target Health is not your average contract research organization. In fact, it’s an e-CRO. Key to becoming a player in the brave new e-world was Target Health’s development of its own suite of patented software and its championing of the paperless clinical trial. I was always an independent thinker, but it was not always appreciated within large organizations, says president and cofounder Jules Mitchel. No matter where I worked, even in smaller companies, I had a gut feeling I could do it better.
Mitchel’s pharmaceutical industry experience includes work at Wyeth and Pfizer, as well as a background in research, which has informed his current role. Basic research allowed me to express my passion for learning and to develop problem-solving and analytical skills, no matter what the problem, Mitchel says. It also taught me how to experiment and to appreciate serendipitous findings, and not to be fearful of new knowledge and changing direction once there is an ?aha’ moment.
The most important skill Mitchel honed in his early years, however, was patience. I used to do aging studies that took three years to do, he says. Things take time. A lot of people in business are not patient enough, so they make silly decisions.
Patience came in handy when Target Health was cofounded in 1993 by Mitchel and his wife and CEO, Joyce Hays. I have an MBA and a PhD and all that stuff, but it’s not the same as the real world of actually running a company, Mitchel says of the reality check involved in guiding a company. In addition to generating business and hiring the right people, Mitchel had to adapt his leadership style. When you have your own company, you have to balance empathy and concern about your employees, but also demonstrate a level of firmness, and you have to develop that, Mitchel says. Not easy.
Glorious Roan Sunset – Another Masterpiece by James Farley
From James: Sunset from Jane Bald, facing Round Bald, with blooming Rhododendrons in view. This photo is a dream come true for me!
©JFarley Photography 2015
ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Ancient Man Had a Neanderthal Great-Great Grandfather and You Have Neanderthal DNA
Analysis of the jawbone of a man who lived about 40,000 years ago reveals the closest direct descendant of a Neanderthal who mated with a modern 1) ___. Scientists know that modern humans and Neanderthals lived together in Europe and occasionally 2) ___. A modern human who lived in eastern Europe between 37,000 and 42,000 years ago had at least one Neanderthal ancestor as little as four generations back – which is to say, a great-great-grandparent.
Scientists have known for at least half a decade that living humans bear traces of Neanderthal blood – or more specifically, Neanderthal DNA. Just when and where our ancestors bred with their now-extinct cousins, however, has been tricky to pin down until now. A new study published last week in the journal Nature has the highest percentage of Neanderthal 3) ___ of any modern human ever studied. We were lucky to hit upon an individual like this, says study co-author Svante Paabo of the Max Planck Institute for Evolutionary Anthropology in Leipzig. The specimen, known as Oase 1, consists only of a male jawbone, and from the moment it was discovered in 2002 its shape suggested that it might belong to a hybrid between Homo 4) ___ and Neanderthal. Those claims have remained controversial, but the new analysis lays the controversy to rest. It’s really stunning, says Oxford’s Tom Higham, an expert on the Neanderthal-human transition who was not involved in this research. Part of what stuns Higham is the genomic artistry it took to tease useful genetic information out of the tiny DNA samples lead author Qiaomei Fu of Harvard Medical School and her team were able to extract from the 5) ___. We tried to do this in 2009 and failed, says Paabo. His lab has been working since then to improve their techniques, with resounding success. The genome they sequenced from the samples was incomplete, but it was enough for the scientists to conclude that between 6% and 9% of Oase 1’s genome is Neanderthal in origin. People living today have 4% at most. That difference is more significant than it might seem. We found seven huge pieces of chromosomes that seemed to be purely of 6) ___ origin, says Paabo. That means pieces had to come from a relatively recent ancestor, since they hadn’t yet been broken up by the reshuffling that happens in each generation as parents’ chromosomes combine.
This jawbone from a 40,000-year-old modern human shows some Neanderthal features – and DNA now confirms he had a Neanderthal ancestor as few as four generations back. Photograph By Svante Paabo, Max Planck Institute For Evolutionary Anthropology
The non-Neanderthal genome sequences, meanwhile, show that Oase 1 isn’t related to humans living today. His genealogical line died out at some point. This analysis represents a biotechnological tour de force, but it also puts paleoanthropologists a step closer to fully answering to what Higham calls the $64,000 question: What happened to wipe out the Neanderthals, and when? Genomic analysis of a 45,000-year-old human thigh bone last year suggested that humans and Neanderthals interbred in what is now Siberia sometime between 50,000 and 60,000 years ago – an extremely imprecise number, and a very broad conclusion. The great breakthrough here, Higham says, is the ability to say ?this specific person had a Neanderthal great-great-grandfather.’ That puts a human timescale on it. If scientists can figure out when 7) ___ took place in different parts of Europe and the Middle East, they’ll be able to say in detail just how rapidly humans spread across these regions, how long they were in contact with Neanderthals. An analysis of a first draft of the Neanderthal genome by the Max Planck Institute team, led by Svante Paabo, released in May 2010, indicates interbreeding probably occurred.Those of us who live outside 8) ___ carry a little Neanderthal DNA in us, said Paabo, who led the study. The proportion of Neanderthal-inherited genetic material is about 1 to 4%. It is a small but very real proportion of ancestry in non-Africans today, says Dr. David Reich of Harvard Medical School, who worked on the study. This research compared the 9) ___ of the Neanderthals to five modern humans from China, France, sub-Saharan Africa, and Papua New Guinea. The finding is that about 1 to 4 percent of the genes of the non-Africans came from Neanderthals, compared to the baseline defined by the two Africans. This indicates a gene flow from Neanderthals to modern humans, i.e., interbreeding between the two populations. Since the three non-African genomes show a similar proportion of Neanderthal sequences, the interbreeding must have occurred early in the migration of modern humans out of Africa, perhaps in the 10) ___ East. No evidence for gene flow in the direction from modern humans to Neanderthals was found. Gene flow from modern humans to Neanderthals would not be expected if contact occurred between a small colonizing population of modern humans and a much larger resident population of Neanderthals. A very limited amount of interbreeding could explain the findings, if it occurred early enough in the colonization process. Sources; National Geographic; Wikipedia; Nature; Wall Street Journal
ANSWERS: 1) human; 2) mated; 3) DNA; 4) sapiens; 5) jawbone; 6) Neanderthal; 7) interbreeding; 8) Africa; 9) genome; 10) Middle
Paleogenetics – Svante Paabo (1955 to Present)
Svante Paabo (born 20 April 1955) is a Swedish biologist specializing in evolutionary genetics. One of the founders of paleogenetics, a discipline that uses the methods of genetics to study early humans and other ancient populations, he has worked extensively on the Neanderthal genome. Paabo was born in Stockholm and grew up with his mother, Estonian chemist Karin Paabo. His father, biochemist Sune Bergstrom, who shared the Nobel Prize in Physiology or Medicine with Bengt I. Samuelsson and John R. Vane in 1982.
Paabo earned his PhD from Uppsala University in 1986. Since 1997, he has been director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. In 1997, Paabo and colleagues reported their successful sequencing of Neanderthal mitochondrial DNA (mtDNA), originating from a specimen found in Feldhofer grotto in the Neander valley. In August 2002, Paabo’s department published findings about the language gene, FOXP2, which is lacking or damaged in some individuals with language disabilities, and in 2006, Paabo announced a plan to reconstruct the entire genome of Neanderthals. In 2007, he was named one of Time magazine’s 100 most influential people of the year.
In February 2009, at the Annual Meeting of the American Association for the Advancement of Science (AAAS) in Chicago, it was announced that the Max Planck Institute for Evolutionary Anthropology had completed the first draft version of the Neanderthal genome. Over 3 billion base pairs were sequenced in collaboration with the 454 Life Sciences Corporation. This project, led by Paabo, has shed new light on the recent evolutionary history of modern humans. Paabo and his coworkers also published a report in 2010 about the DNA analysis of a finger bone found in the Denisova Cave in Siberia; the results suggest that the bone belonged to an extinct member of the genus Homo that had not yet been recognized, the Denisova hominin. In May 2010, Paabo and his colleagues published a draft sequence of the Neanderthal genome in the journal Science. He and his team also concluded that there was probably interbreeding between Neanderthals and Eurasian (but not African) humans. There is growing support in the scientific community for this theory of admixture between archaic and anatomically-modern humans, though some archeologists remain skeptical about this conclusion.
In 2014, Paabo published the book Neanderthal Man: In Search of Lost Genomes where he, in the mixed form of a memoir and popular science, tells the story of the research effort to map the Neanderthal genome combined with thought on human evolution.
In terms of awards, in 1992, Paabo received the Gottfried Wilhelm Leibniz Prize of the Deutsche Forschungsgemeinschaft, which is the highest honor awarded in German research. Paabo was also elected a member of the Royal Swedish Academy of Sciences in 2000. In October 2009 the Foundation For the Future announced that Paabo had been awarded the 2009 Kistler Prize for his work isolating and sequencing ancient DNA, beginning in 1984 with a 2,400-year-old mummy. Also, in June 2010 the Federation of European Biochemical Societies awarded him the Theodor Bucher Medal for outstanding achievements in Biochemistry and Molecular Biology, and in 2013, he received Gruber Prize in Genetics for ground breaking research in evolutionary genetics. In June 2015 he was awarded an honorary doctor of science degree from NUI Galway.
Study of Ebola Survivors Opens in Liberia to Examine Long-Term Health Effects of Ebola Virus Disease
Congratulations to our colleagues at NIAID.
The Liberia-U.S. clinical research partnership known as PREVAIL has launched a study of people in Liberia who have survived Ebola virus disease (EVD) within the past two years. The study investigators hope to better understand the long-term health consequences of EVD, determine if survivors develop immunity that will protect them from future Ebola infection, and assess whether previously EVD-infected individuals can transmit infection to close contacts and sexual partners. The study, sponsored by the Ministry of Health of Liberia and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, will take place at various sites in Liberia and is expected to enroll approximately 7,500 people, including 1,500 people of any age who survived EVD and 6,000 of their close contacts. Participants who test positive for HIV infection during the course of the study will be counseled and referred to treatment in accordance with standard medical practice in Liberia.
Study participants will undergo a medical history and physical and vision examination and have blood samples collected so researchers can identify and track any health issues, monitor organ and ocular function and record Ebola antibody levels. Some participants may also be asked to provide samples of bodily fluids, such as sweat, tears, and for adults, semen or cervical secretions. Participants will be asked if they would like to identify up to five close contacts (household members at the time of Ebola diagnosis and sexual partners after recovery from Ebola virus disease). Close contacts who agree to participate in the study will undergo a physical examination, have blood samples taken, and asked to complete a questionnaire detailing their contact with the Ebola survivor, such as touching, sleeping in the same bed and intimate relations. Staff from the NIH’s National Eye Institute have helped establish a new eye clinic at John F. Kennedy Medical Hospital, where ophthalmologists from NEI and Johns Hopkins will be evaluating study participants and their identified close contacts for visual problems. Treatment will be provided by Liberian ophthalmologists partnering in the study. There have been reports of inflammatory eye disease and vision loss among Ebola survivors and one goal of the study is to determine the incidence and extent of Ebola-related eye disease among survivors, risk factors contributing to its development, and optimal treatment strategies.
The research team will follow the Ebola survivors and their close contacts for up to five years with study visits occurring every six months. At each follow-up visit, participants will undergo a physical examination and additional blood draws, to allow study physicians to monitor and characterize any changes in Ebola antibody levels and to detect the presence of select medical conditions. This information will help to determine the evolution of Ebola antibodies and will provide insight on whether survivors can still transmit the virus and if so, whether these people get sick with Ebola virus disease. Using data collected at these site visits, the researchers will calculate the incidence, prevalence and risk factors for various health issues experienced by survivors, such as vision problems; immune system changes; mental disorders; joint pain; diabetes; hypertension; and pregnancy complications. Close contacts will be used as a control group to assess whether the risks of these conditions are the same or different from those who have not had Ebola virus disease.
PREVAIL, or the Partnership for Research on Ebola Virus in Liberia, is a clinical research partnership between the U.S. Department of Health and Human Services and the Liberian Ministry of Health. The new study, an Ebola natural history study known as PREVAIL III, is one of three research projects launched by the partnership. In February 2015, PREVAIL initiated two other Ebola clinical studies. PREVAIL I is a clinical trial to assess the safety and efficacy of two experimental vaccines to prevent Ebola virus infection. A total of 1,500 participants continue to be followed in the Phase 2 segment of this study. PREVAIL II is a clinical trial designed to obtain safety and efficacy data on various investigational drugs for the treatment of Ebola virus disease. The trial is ongoing in Liberia, Sierra Leone and the United States Additional information about the PREVAIL III Ebola natural history study is available at ClinicalTrials.gov using the identifier NCT02431923. For more information about NIAID’s Ebola research, visit the NIAID Ebola webpage.
Efficacy of Handwashing with Soap and Nail Clipping on Intestinal Parasitic Infections in School-Aged Children
Intestinal parasitic infections are highly endemic among school-aged children in resource-limited settings. To lower their impact, preventive measures should be implemented that are sustainable with available resources. As a result, a study, published online in Pols Medicine (9 June 2015), was performed to assess the impact of handwashing with soap and nail clipping on the prevention of intestinal parasite reinfections.
In this trial, 367 parasite-negative school-aged children (aged 6-15 years of age) were randomly assigned to receive both, one or the other, or neither of the interventions in a 2×2 factorial design. Assignment sequence was concealed. After 6 months of follow-up, stool samples were examined using direct, concentration, and Kato-Katz methods. Hemoglobin levels were determined using a HemoCue spectrometer. The primary study outcomes were prevalence of intestinal parasite reinfection and infection intensity. The secondary outcome was anemia prevalence. Analysis was by intention to treat. Main effects were adjusted for gender, age, drinking water source, latrine use, pre-treatment parasites, handwashing with soap and nail clipping at baseline, and the other factor in the additive model.
Results showed that 14% of the children in the handwashing with soap intervention group were reinfected versus 29% in the groups with no handwashing with soap. Similarly, 17% of the children in the nail clipping intervention group were reinfected versus 26% in the groups with no nail clipping. Also, following the intervention, 13% of the children in the handwashing group were anemic versus 23% in the groups with no handwashing with soap. The prevalence of anemia did not differ significantly between children in the nail clipping group and those in the groups with no nail clipping.
According to the authors, handwashing with soap at key times and weekly nail clipping significantly decreased intestinal parasite reinfection rates. Furthermore, the handwashing intervention significantly reduced anemia prevalence in children. The authors noted that the intensive follow-up and monitoring during this study made it such that the assessment of the observed intervention benefits was under rather ideal circumstances, and hence the study could possibly overestimate the effects when compared to usual conditions. It was proposed that the next step should be implementing pragmatic studies and developing more effective approaches to promote and implement handwashing with soap and nail clipping at larger scales.
FDA Approves New Antiplatelet Drug Used During Heart Procedure
According to the Centers for Disease Control and Prevention, percutaneous coronary intervention (PCI) is performed on approximately 500,000 people in the United States each year. For this procedure, the coronary arteries are opened by inflating a balloon at the site of the narrowing, usually followed by placement of a small mesh tube, called a stent, to keep the artery open.
The FDA has approved Kengreal (cangrelor), an intravenous antiplatelet drug that prevents formation of harmful blood clots in the coronary arteries, the blood vessels that supply blood to the heart. It is approved for adult patients undergoing PCI. By preventing platelets from accumulating, Kengreal reduces the risk of serious clotting complications related to the procedure, including heart attack and clotting of the stent (stent thrombosis). As with other FDA-approved anti-platelet drugs, bleeding, including life-threatening bleeding, is the most serious risk of Kengreal.
In a clinical trial that compared Kengreal to Plavix (clopidogrel) in more than 10,000 participants, Kengreal significantly reduced the occurrence of heart attack, the need for further procedures to open the artery and stent thrombosis. However, the overall occurrence of serious bleeding was low but more common with Kengreal than with clopidogrel. Approximately one in every 170 Kengreal patients had a serious bleed versus approximately one in every 275 clopidogrel patients.
Kengreal is manufactured by The Medicines Company based in Parsippany, New Jersey.
Baked Cauliflower Stuffed with Turkey & Cheese Topping
something a little different for dinner ©Joyce Hays, Target Health Inc.
Surprise in the Center – and smells so-o good ©Joyce Hays, Target Health Inc.
2 medium heads cauliflower
8 ounces freshly chopped turkey
2 garlic cloves, minced
1 cup fresh parsley, chopped
1 Tablespoon sour cream
2 Tablespoons freshly grated parmesan cheese, for garnish
Pinch black pepper
2 Pinches chili flakes
Ingredients for Cheese Sauce
2 Tablespoons butter (or olive oil, optional)
2 Tablespoons almond flour
1 cup almond milk
1/4 cup shredded mozzarella
Pinch black pepper
Pinch chili flakes
Delicious, fresh ingredients from Whole Foods ©Joyce Hays, Target Health Inc.
Preheat oven to 350o F.
Remove leaves from cauliflower and clean it. Boil each of the whole heads of cauliflower in salted water for 7 to 8 minutes. Let the cauliflower drain on paper towels.
Create a cavity in the whole cauliflower ©Joyce Hays, Target Health Inc.
Place one head of cauliflower into a round baking dish, with the stem side facing up. With a sharp knife, carve the stem area and pull it out. This will be the area that you will fill with the turkey, so scoop out enough cauliflower, so you have a little nest for the turkey mixture. Throw the stem out, but save useable cauliflower.
Part of the second cauliflower, plus what was scooped out of the first. Will be used to cover the turkey. ©Joyce Hays, Target Health Inc.
Part of the second cauliflower, the top part, will be cut out and used to cover the turkey, after you fill the carved out section of the first cauliflower, with the turkey mixture.
Easy to make the turkey mixture. ©Joyce Hays, Target Health Inc.
To make the turkey mixture: in a large bowl, add the 8 ounces of freshly chopped turkey meat, the minced garlic, sour cream, chopped parsley, salt, pepper, chili flakes. Mix all ingredients together, well.
Then fill the hollowed out space of the first cauliflower, with the turkey mixture, and cover the turkey, with the cooked top of the second cauliflower.
Here’s the first experiment with this recipe, showing the scooped out cavity, filled with the turkey mixture. The bowl I used the first time, was a bit too small, so some of the cheese sauce leaked out. ©Joyce Hays, Target Health Inc.
After you fill the cavity with the turkey mixture, cover the top of the cauliflower with the cooked pieces from the second head, and/or what you scooped out of the first, if there’s enough to cover the turkey. ©Joyce Hays, Target Health Inc.
Easy to make cheese sauce ©Joyce Hays, Target Health Inc.
To make the cheese sauce:
In a medium fry pan add the butter (or olive oil), over a medium flame, when the butter melts, add the almond flour and stir the roux until the two ingredients are well combined. Next, add the almond milk and blend these ingredients together. Now, add the shredded mozzarella, salt, pepper, chili flakes and stir until the cheese is completely melted and mixed into the other ingredients.
Lovely gooey cheese sauce, poured over the top of the cauliflower. ©Joyce Hays, Target Health Inc.
Finally, pour the cheese sauce over the cauliflower, covering the entire top. Then cover the cauliflower with a foil tent (that means very loosely, so the cheese doesn’t stick to the foil), and bake for 40 minutes.
Cover your baking dish with a foil tent and bake in 350 oven for 40 minutes. ©Joyce Hays, Target Health Inc.
Here, it’s out of the oven, and I’ve sprinkled freshly grated parmesan cheese over the top. It goes back in oven for 10 more minutes without foil and without any cover. ©Joyce Hays, Target Health Inc.
Take the dish out of the oven, and 10 minutes before you plan to serve this, remove the foil and sprinkle the Parmesan cheese all over the top. Put back in the oven at the same temperature of 350, for 10 more minutes, then serve.
One serving won’t be enough. ©Joyce Hays, Target Health Inc.
Friday turned out to be a highly charged political day, with a long string of significant events. No matter which political party you belong to, we haven’t run into anyone who was not deeply stirred by President Obama’s moving delivery of Amazing Grace. We were struck by this scene of racial unity. If nothing else, Friday was a day that held up, for the world to see, the torch of democracy renewed in the United States. Isn’t everyone aching for peace? Here it was, poetry and prose, in action; harmony at last.
We started Friday dinner, raising our glasses, with icy Orvieto wine and a veggie salad shared about a month ago, with raw apples, the secret ingredient. Then the new recipe (second time served) of baked cauliflower, turkey center and cheese-y sauce, which was even more delicious the second time; we nearly finished it. If you wanted to serve a starch along with the cauliflower dish, there are lots of options. A low calorie baked sweet potato would be the healthiest, but we also like mini red baked potatoes. If you don’t mind the calories, pasta is now made with veggies like spinach, artichoke, etc. and much, much more. For dessert we had a fresh fruit mix of peaches, mangos and organic strawberries – red to the core. In addition another new recipe: fresh rhubarb/blueberry (in season now) & cake, with a little rum added later; will share this in the future.
We went to a play at one of our theater clubs (Manhattan Theater Club, now a Broadway entity). I love this theater. The play, Good Stock, had excellent acting, beautifully done dialogue by the playwright, Melissa Ross, and a gorgeous ever-changing set. We liked this play a lot and stayed for the talk-back afterwards.
Chilled Italian Orvieto, is a delicate wine, perfect for summer. ©Joyce Hays, Target Health Inc.
From Our Table to Yours!
June 25, 2015
University of Michigan
The relentless flow of a glacier may seem unstoppable, but a team of researchers from the United Kingdom and the U.S. has shown that during some calving events — when an iceberg breaks off into the ocean — the glacier moves rapidly backward and downward, causing the characteristic glacial earthquakes which until now have been poorly understood.
The relentless flow of a glacier may seem unstoppable, but a team of researchers from the United Kingdom and the U.S. has shown that during some calving events — when an iceberg breaks off into the ocean — the glacier moves rapidly backward and downward, causing the characteristic glacial earthquakes which until now have been poorly understood.
This new insight into glacier behavior, gained by combining field observations in Greenland with laboratory calving experiments, should enable scientists to measure glacier calving remotely and will improve the reliability of models that predict future sea-level rise in a warming climate.
The research is scheduled for publication in Science Express on June 25. The lead author is Tavi Murray of Swansea University. Co-authors include U-M’s L. Mac Cathles, an assistant professor in the Department of Earth and Environmental Sciences and the Department of Atmospheric, Oceanic and Space Sciences and a postdoctoral fellow in the Michigan Society of Fellows.
The Greenland ice sheet is an important contributor to global sea level, and nearly half of the ice sheet’s annual mass loss occurs through the calving of icebergs to the ocean. Glacial earthquakes have increased sevenfold in the last two decades and have been migrating north, suggesting an increase in rates of mass loss from the ice sheet through calving.
“Our new understanding is a crucial step toward developing tools to remotely measure the mass loss that occurs when icebergs break off ice sheets,” Cathles said. “Combining field observations with laboratory measurements from scaled-model calving experiments provided insights into the dynamics of calving and glacial earthquakes that would not have otherwise been possible.”
Helheim Glacier is one of the largest glaciers in southeast Greenland. At 6 kilometers (3.7 miles) wide and more than 200 kilometers (124.3 miles) long, it can flow as fast as 30 meters (98 feet) a day. Icebergs calving from Helheim Glacier have been measured at up to 4 kilometers (2.5 miles) across, with a volume of about 1.25 cubic kilometers (0.3 cubic miles).
During summer 2013, researchers from Swansea, Newcastle and Sheffield universities installed a robust wireless network of Global Positioning System devices on the chaotic surface of Helheim to measure velocity and displacement of the glacier surface.
With U.S. collaborators from U-M, Columbia University and Emory University, earthquake data from the Global Seismographic Network and scaled-down models in water tanks were used to explain the unexpected movements of the glacier in the minutes surrounding the calving events.
“We were really surprised to see the glacier flowing backward in our GPS data. The motion happens every time a large iceberg is calved and a glacial earthquake is produced,” said Swansea’s Murray. “A theoretical model for the earthquakes and the laboratory experiments has allowed us to explain the backward and downward movement.”
U-M’s Cathles helped design and run the laboratory experiments of iceberg calving presented in the paper. The international collaboration grew out of a conversation that Cathles and Murray had at an International Glaciological Society meeting in Chamonix, France, last summer.
“We both presented in the same session and realized that I was measuring in the lab a very similar signal to what Professor Murray was observing in the field,” Cathles said. “That started a year-long collaboration in which the paper’s co-authors talked regularly and collectively developed a model to explain the GPS observations and a deeper understanding of how glacial earthquakes are generated during an iceberg calving event.”
Understanding this glacier behavior and the associated glacial earthquakes is a crucial step toward remote measurement of calving events and their contribution to sea-level change. This tool has the potential to provide unprecedented global, near-real-time estimates of iceberg loss from the ice sheet.
The research was supported by the U.K. Natural Environment Research Council, the U.S. National Science Foundation and the Climate Change Consortium of Wales and Thales U.K.
- T. Murray, M. Nettles, N. Selmes, L. M. Cathles, J. C. Burton, T. D. James, S. Edwards, I. Martin, T. O’farrell, R. Aspey, I. Rutt, T. Baug�. Reverse glacier motion during iceberg calving and the cause of glacial earthquakes. Science, 2015 DOI:10.1126/science.aab0460
Source: University of Michigan. “Backward-moving glacier helps scientists explain glacial earthquakes.” ScienceDaily. ScienceDaily, 25 June 2015. <www.sciencedaily.com/releases/2015/06/150625143926.htm>.