First human trials of gas-sensing capsule reveal potential new immune system

January 8, 2018

RMIT University

Findings from the first human trials of a breakthrough gas-sensing swallowable capsule could revolutionize the way that gut disorders and diseases are prevented and diagnosed.


This is a close up of the ingestible gas-sensing capsule developed by researchers at RMIT University.
Credit: RMIT University/Peter Clarke (Creative Commons License)



Findings from the first human trials of a breakthrough gas-sensing swallowable capsule could revolutionise the way that gut disorders and diseases are prevented and diagnosed.


The trials by researchers at RMIT University in Melbourne, Australia have uncovered mechanisms in the human body that have never been seen before, including a potentially new immune system.

The new technology and discoveries offer a game-changer for the one-in-five people worldwide who will suffer from a gastrointestinal disorder in their lifetime. They could also lead to fewer invasive procedures like colonoscopies.

The ingestible capsule (the size of a vitamin pill) detects and measures gut gases — hydrogen, carbon dioxides and oxygen — in real time. This data can be sent to a mobile phone.

Professor Kourosh Kalantar-zadeh, study lead and capsule co-inventor, said the trials showed that the human stomach uses an oxidiser to fight foreign bodies in the gut.

“We found that the stomach releases oxidising chemicals to break down and beat foreign compounds that are staying in the stomach for longer than usual,” Kalantar-zadeh said.

“This could represent a gastric protection system against foreign bodies. Such an immune mechanism has never been reported before.”

Another never before seen observation from the trial was that the colon may contain oxygen.

“Trials showed the presence of high concentrations of oxygen in the colon under an extremely high-fibre diet,” Kalantar-zadeh said. “This contradicts the old belief that the colon is always oxygen free.

“This new information could help us better understand how debilitating diseases like colon cancer occur.”

The trials were conducted on seven healthy individuals on low- and high-fibre diets. Results showed that the capsule accurately shows the onset of food fermentation, highlighting their potential to clinically monitor digestion and normal gut health.

The trials also demonstrated that the capsule could offer a much more effective way of measuring microbiome activities in the stomach, a critical way of determining gut health.

“Previously, we have had to rely on faecal samples or surgery to sample and analyse microbes in the gut,” Kalantar-zadeh said.

“But this meant measuring them when they are not a true reflection of the gut microbiota at that time. Our capsule will offer a non-invasive method to measure microbiome activity.”

Now that the capsule has successfully passed human trials, the research team is seeking to commercialise the technology.

Co-inventor Dr Kyle Berean said: “The trials show that the capsules are perfectly safe, with no retention.

“Our ingestible sensors offer a potential diagnostic tool for many disorders of the gut from food nutrient malabsorption to colon cancer. It is good news that a less invasive procedure will now be an option for so many people in the future.

“We have partnered with Planet Innovation to establish a company called Atmo Biosiences and bring the product to market.

“This will lead to Phase II human trials, and help raise the funds needed place this safe and revolutionary gut monitoring and diagnostic device into the hands of patients and medical professionals.”

Story Source:

Materials provided by RMIT University. Original written by James Giggacher. Note: Content may be edited for style and length.

Journal Reference:

  1. Kourosh Kalantar-Zadeh, Kyle J. Berean, Nam Ha, Adam F. Chrimes, Kai Xu, Danilla Grando, Jian Zhen Ou, Naresh Pillai, Jos L. Campbell, Robert Brkljača, Kirstin M. Taylor, Rebecca E. Burgell, Chu K. Yao, Stephanie A. Ward, Chris S. McSweeney, Jane G. Muir, Peter R. Gibson. A human pilot trial of ingestible electronic capsules capable of sensing different gases in the gutNature Electronics, 2018; 1 (1): 79 DOI: 10.1038/s41928-017-0004-x


Source: RMIT University. “Swallowable sensors reveal mysteries of human gut health: First human trials of gas-sensing capsule reveal potential new immune system.” ScienceDaily. ScienceDaily, 8 January 2018. <>.

Target Health Inc. Welcomes All to 2018


Target Health begins the New Year with new clinical programs in psychiatry, neurology and diabetes, and more to come. Our regulatory group now represents over 55 companies at FDA with a pre-IND meeting in neurology planned for next month. Biostatistics is completing an analysis of a major Phase 3 program, in addition to analyses in oncology, urology and other multiple indications. Data management continues to support multiple Target e*CRF® programs, including an ongoing major phase 3 program in Alzheimer’s disease. Application development continues to build EDC studies including a new study starting soon in Hong Kong which will use Target e*CTR® (eSource; eClinical Trial Record), as well as a new study just started in diabetes which is using both Target e*ICF™ (eInformed Consent) and Target e*CTR®. Finally, software development continues on the cutting edge with the next version of Target e*Studio®. This user-friendly version will be transformational for the industry as the entire clinical trial will be at one website, there will be full integration with mobile devices and there will be a sophisticated user management schema. Of course, this is just the tip of the iceberg.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. 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


Antonio Damasio MD, PhD (1944 to present)

Antonio Damasio giving a talk at the Universidade de Sao Paulo, in Brazil in 2013.

Photo credit: Fronteiras do Pensamento – This file has been extracted from another file: Antonio Damasio no Fronteiras do Pensamento Porto Alegre 2013 original file, CC BY-SA 2.0,



Antonio Damasio is a Portuguese-American neuroscientist who is currently the David Dornsife Professor of Neuroscience, Psychology and Philosophy at the University of Southern California, and an adjunct professor at the Salk Institute. Damasio heads the Brain and Creativity Institute, and has authored several books including, Self Comes to Mind: Constructing the Conscious Brain (2010), which explores the relationship between the brain and consciousness. His most recent book, about to be released in February 2018 is The Strange Order of Things: Life, Feeling, and the Making of Cultures. Damasio’s research in neuroscience has shown that emotions play a central role in social cognition and decision-making. Damasio continues his quest for a theory of human consciousness, in his latest book he links feelings and culture with homeostasis and evolution. His ideas are exciting, his explanations tend to be abstract, as might be expected when describing consciousness. He writes that “the constructions that inhabit our minds can well be imagined as ephemeral musical performances, played by several hidden orchestras.“ Attempting to explain “the biological underpinnings of the human cultural mind,“ Damasio begins with the Cambrian unicellular organism and shows how the mapping of internal and external images led to the development of nervous systems, which in turn laid the groundwork for verbal language, consciousness, subjectivity, and feeling. Damasio posits that feelings in humans “arose from a series of gradual, body-related processes accumulated and maintained over evolution.“ He then explores the biological roots of culture, particularly the role homeostasis played in generating behavioral strategies. Damasio extends his thinking on homeostasis to the shaping of moral codes and the emergence of religious and political systems, and even to the internet and what he dubs “the current crisis of the human condition.“ Wide in scope, Damasio’s book contains moments of genius but feels like a work in progress. As expected from a scientist whose life has been dedicated to a constant search for difficult solutions.


Damasio studied medicine at the University of Lisbon Medical School, where he also did his neurological residency and completed his doctorate. For part of his studies, he researched behavioral neurology under the supervision of Norman Geschwind of the Aphasia Research Center in Boston. Damasio’s main field is neurobiology, especially the neural systems which underlie emotion, decision-making, memory, language and consciousness. Damasio believes that emotions play a critical role in high-level cognition – an idea counter to dominant views in psychology, neuroscience and philosophy. Damasio formulated the somatic marker hypothesis, a theory about how emotions and their biological underpinnings are involved in decision-making (both positively and negatively, and often non-consciously). Emotions provide the scaffolding for the construction of social cognition and are required for the self processes which undergird consciousness. “Damasio provides a contemporary scientific validation of the linkage between feelings and the body by highlighting the connection between mind and nerve cells, this personalized embodiment of mind.“


The somatic marker hypothesis has inspired many neuroscience experiments carried out in laboratories in the U.S. and Europe, and has had a major impact in contemporary science and philosophy. Damasio has been named by the Institute for Scientific Information as one of the most highly cited researchers in the past decade. Current work on the biology of moral decisions, neuro-economics, social communication, and drug-addiction, has been strongly influenced by Damasio’s hypothesis. An article published in the Archives of Scientific Psychology in 2014 named Damasio one of the 100 most eminent psychologist of the modern era. (Diener et al. Archives of Scientific Psychology, 2014, 2, 20-32). The June-July issue of Sciences Humaines included Damasio in its list of 50 key thinkers in the human sciences of the past two centuries.


Damasio also proposed that emotions are part of homeostatic regulation and are rooted in reward/punishment mechanisms. He recovered William James’ perspective on feelings as a read-out of body states, but expanded it with an “as-if-body-loop“ device which allows for the substrate of feelings to be simulated rather than actual (foreshadowing the simulation process later uncovered by mirror neurons). He demonstrated experimentally that the insular cortex is a critical platform for feelings, a finding that has been widely replicated, and he uncovered cortical and subcortical induction sites for human emotions, e.g. in ventromedial prefrontal cortex and amygdala. He also demonstrated that while the insular cortex plays a major role in feelings, it is not necessary for feelings to occur, suggesting that brain stem structures play a basic role in the feeling process. He has continued to investigate the neural basis of feelings and demonstrated that although the insular cortex is a major substrate for this process it is not exclusive, suggesting that brain stem nuclei are critical platforms as well. He regards feelings as the necessary foundation of sentience.


In another development, Damasio proposed that the cortical architecture on which learning and recall depend involves multiple, hierarchically organized loops of axonal projections that converge on certain nodes out of which projections diverge to the points of origin of convergence (the convergence-divergence zones). This architecture is applicable to the understanding of memory processes and of aspects of consciousness related to the access of mental contents. In The Feeling of What Happens, Damasio laid the foundations of the “enchainment of precedences“: “the nonconscious neural signaling of an individual organism begets the proto-self which permits core self and core consciousness, which allow for an autobiographical self, which permits extended consciousness. At the end of the chain, extended consciousness permits conscience.


Damasio’s research depended significantly on establishing the modern human lesion method, an enterprise made possible by Hanna Damasio’s structural neuroimaging/neuroanatomy work complemented by experimental neuroanatomy (with Gary Van Hoesen and Josef Parvizi), experimental neuropsychology (with Antoine Bechara, Ralph Adolphs, and Dan Tranel) and functional neuroimaging (with Kaspar Meyer, Jonas Kaplan, and Mary Helen Immordino-Yang). The experimental neuroanatomy work with Van Hoesen and Bradley Hyman led to the discovery of the disconnection of the hippocampus caused by neurofibrillary tangles in the entorhinal cortex of patients with Alzheimer’s disease. Damasio’s books deal with the relationship between emotions and their brain substrates. His 1994 book, Descartes’ Error: Emotion, Reason and the Human Brain, won the Science et Vie prize, was a finalist for the Los Angeles Times Book Award, and is translated in over 30 languages. It is regarded as one of the most influential books of the past two decades. His second book, The Feeling of What Happens: Body and Emotion in the Making of Consciousness, was named as one of the ten best books of 2001 by the New York Times Book Review, a Publishers Weekly Best Book of the Year, a Library Journal Best Book of the Year, and has over 30 foreign editions. Damasio’s Looking for Spinoza: Joy, Sorrow, and the Feeling Brain, was published in 2003. In it, Damasio suggested that Spinoza’s thinking foreshadowed discoveries in biology and neuroscience views on the mind-body problem and that Spinoza was a proto-biologist. In Damasio’s book, Self Comes to Mind: Constructing the Conscious Brain. Damasio suggests that the self is the key to conscious minds and that feelings, from the kind he designates as primordial to the well-known feelings of emotion, are the basic elements in the construction of the proto-self and core self. The book received the Corinne International Book Prize.


Damasio is a member of the American Academy of Arts and Sciences, the National Academy of Medicine, the European Academy of Sciences and Arts. He is the recipient of several prizes, amongst them the Grawemeyer Award, the Honda Prize, the Prince of Asturias Award in Science and Technology and the Beaumont Medal from the American Medical Association, as well as honorary degrees from, most recently, the Sorbonne (Universit? Paris Descartes), shared with his wife Hanna Damasio. He has also received doctorates from the Universities of Aachen, Copenhagen, Leiden, Barcelona, Coimbra, Leuven and numerous others. In 2013, the Escola Secundaria Antonio Damasio was dedicated in Lisbon. He says he writes in the belief that “scientific knowledge can be a pillar to help humans endure and prevail.“ Damasio additionally serves on the board of directors of the Berggruen Institute, and sits on the jury for the Berggruen Prize for Philosophy.


Stem Cell Transplant for Severe Scleroderma


Scleroderma is characterized by hardening of the skin and connective tissues. Diffuse systemic sclerosis is a severe, often fatal form of the disease that also involves the internal organs. Treatment options are limited. People with the disease may take antirheumatic drugs and immune-suppressing drugs like cyclophosphamide to help manage symptoms, but none of these medications has been proven to provide long-term benefit.


New clinical trial findings, published in the New England Journal of Medicine (4 January 2018) show that a therapeutic regimen involving transplantation of a person’s own blood-forming stem cells can improve survival and quality of life for people with severe scleroderma. The regimen, known as myeloablative autologous hematopoietic stem cell transplant (HSCT), includes chemotherapy and total body radiation to destroy the bone marrow followed by transplantation of the person’s own blood-forming stem cells to reconstitute the marrow and immune system. The study, funded by the National Institutes of Health, found myeloablative HSCT to be superior to treatment with the immune-suppressing drug cyclophosphamide.


The clinical trial, called Scleroderma: Cyclophosphamide or Transplantation (SCOT), compared the safety and potential benefits of the two treatment regimens among 75 people with diffuse systemic sclerosis who had lung or kidney involvement. Compared with cyclophosphamide, stem cell transplantation offered significantly greater long-term benefits, but also carried known short-term risks, such as infections and low blood cell counts.


Two previous clinical trials suggested HSCT benefited people with severe scleroderma. Participants in these earlier trials received non-myeloablative HSCT, a less intensive procedure using lower doses of chemotherapy that does not completely destroy the bone marrow. However, neither trial changed clinical practice in the United States, in part because of concerns about the durability of responses to treatment and the safety of these transplant regimens. The SCOT trial assessed a myeloablative transplant regimen, which was thought to offer better long-term outcomes. Investigators followed the participants for up to six years to assess safety and durability of remission.


Participants in the SCOT trial, conducted at 26 clinical research sites in the United States and Canada, were randomly assigned to receive either myeloablative autologous HSCT or one year of treatment with monthly doses of intravenous cyclophosphamide. Of the 36 participants assigned to the transplant arm, 33 received a transplant. The procedure began with the collection of a participant’s blood-forming stem cells, after which the participant received chemotherapy and radiation to eliminate the bone marrow. Finally, the participant’s own blood stem cells were reinfused to rebuild the bone marrow and a normally functioning immune system. Of the 39 participants assigned to the cyclophosphamide arm, 34 received at least nine of the 12 prescribed monthly doses.


The study investigators used an analytic approach based on a hierarchy of clinical outcomes specific for severe systemic sclerosis to compare every participant in the study with every other participant. These outcomes included death, survival without scleroderma-related organ damage, progression of lung and skin disease, and quality of life. At four and a half years of follow up, participants who received a transplant experienced significantly better outcomes overall than those who received cyclophosphamide. In addition, 44% of participants who received cyclophosphamide had begun taking antirheumatic drugs for progression of their scleroderma, compared to only 9% of those who received a transplant. During the study, seven participants in the transplant arm died, compared to 14 in the cyclophosphamide arm. Of these deaths, three in each arm were among participants who did not complete their assigned treatment by either receiving the transplant or an adequate regimen of cyclophosphamide. Participants who received transplants were much less likely to die from progression of their scleroderma compared to those who received cyclophosphamide. Only two participants who received a transplant died due to disease progression, while 11 such deaths occurred among those who received an adequate regimen of cyclophosphamide. The two other deaths in the transplant arm were attributed to the treatment, which is a lower rate of transplant-related death than previously reported for HSCT. No deaths were attributed to cyclophosphamide.


Participants in both study arms experienced treatment side effects, such as infections. Most serious adverse events among transplant recipients occurred during the first 26 months after transplant. Overall infection rates in the two study arms were similar, although more transplant recipients developed infections with varicella zoster, the virus that causes chickenpox and shingles.


The study continues to follow many of the SCOT participants to further assess their long-term health outcomes.


Data from the SCOT study are freely available through the NIAID-sponsored ImmPort database.


Hibernating Ground Squirrels Provide Clues to Stroke Treatments


An ischemic stroke occurs when a clot cuts off blood flow to part of the brain, depriving those cells of oxygen and nutrients like the blood sugar glucose that they need to survive. Nearly 800,000 Americans experience a stroke every year and 87% of those are ischemic strokes. Currently, the only way to minimize stroke-induced cell death is to remove the clot as soon as possible. A treatment to help brain cells survive a stroke-induced lack of oxygen and glucose could dramatically improve patient outcomes, but no such neuroprotective agents for stroke patients exist.


Now, in the fight against brain damage caused by stroke, hibernating ground squirrels may provide some key insights and answers. While ground squirrel brains experience dramatically reduced blood flow during hibernation, just like human patients after a certain type of stroke, the squirrels emerge from their extended naps suffering no ill effects. Now, according to an article published in The FASEB Journal (16 November 2017), a potential drug has been identified that could grant the same resilience to the brains of ischemic stroke patients by mimicking the cellular changes that protect the brains of ground squirrels. The study found that a cellular process called SUMOylation goes into overdrive in a certain species of ground squirrel during hibernation. The authors suspected this was how the animals’ brains survived the reduced blood flow caused by hibernation, and subsequent experiments in cells and mice confirmed this hypothesis.


SUMOylation occurs when an enzyme attaches a molecular tag called a Small Ubiquitin-like Modifier (SUMO) to a protein, altering its activity and location in the cell. Other enzymes called SUMO-specific proteases (SENPs) can then detach those tags, thereby decreasing SUMOylation. In the current study, the authors examined whether any of over 4,000 molecules from the NCATS small molecule collections could boost SUMOylation by blocking a SENP called SENP2, which would theoretically protect cells from a shortage of life-sustaining substances. The authors first used an automated process to examine whether the compounds prevented SENP2 from severing the connection between a tiny metal bead and an artificial SUMO protein. This system, along with computer modeling and further tests performed both in and outside of cells, whittled the thousands of candidate molecules down to eight that could bind to SENP2 in cells and were non-toxic. Two of those – ebselen and 6-thioguanine – were then found to both boost SUMOylation in rat cells and keep them alive in the absence of oxygen and glucose. A final experiment showed that ebselen boosted SUMOylation in the brains of healthy mice more than a control injection. 6-thioguanine was not tested because it is a chemotherapy drug with side effects that make it unsuitable as a potential stroke treatment. The authors now plan to test whether ebselen can protect the brains of animal models of stroke. Because SUMOylation affects a variety of molecules, the authors believe that their approach could inspire similar attempts to treat neurological conditions by targeting pathways with wide-ranging effects.


New Patient Engagement Collaborative


The following was excerpted from FDA Voice, posted December 20, 2017 by By: Nina L. Hunter, Ph.D., and Rachel E. Sherman, M.D, M.P.H.


According to FDA Voice, the FDA is committed to collaborating with patients, caregivers, and advocates, as well as incorporating the various perspectives from these groups into the FDA’s regulatory decision-making processes. In fact, members of the patient and stakeholder communities commented in public feedback on Section 1137, Patient Participation in Medical Product Discussions, of the Food and Drug Administration Safety and Innovation Act (FDASIA). Stakeholders recommended that the FDA create an outside group to provide input on patient engagement across the agency. FDA has announced that in response to that feedback and to accelerate the FDA’s efforts in this area, it has published a request for nominations to join the FDA’s Patient Engagement Collaborative (PEC). The PEC will be coordinated by the FDA and the public-private partnership, the Clinical Trials Transformation Initiative. FDA is seeking a group of diverse representatives from the patient community to participate in the PEC including:


1. Patients who have personal disease experience

2. Caregivers who support patients, such as a parent, child, partner, other family member, or friend, and who have personal disease experience through this caregiver role

3. Representatives from patient groups who, through their role in the patient group, have direct or indirect disease experience


The PEC will provide an ongoing forum to discuss how to achieve more meaningful patient engagement in medical product development and other regulatory discussions. Topics to be discussed may include making patient engagement more systematic; how to improve transparency, education and communication; new strategies for enhancing patient engagement; and new models for patients to collaborate as partners in the medical product development and FDA review process. The PEC builds on the agency’s existing patient engagement efforts, such as the Patient Focused Drug Development meetings (for drugs and biologic products) and the Patient Preference Initiative (for medical devices).


The new collaborative will be modeled after the European Medicines Agency’s Patients’ and Consumers’ Working Party (PCWP) which “has enabled the Agency to build upon its existing interactions with patients and consumers.“ Examples of PCWP accomplishments include having patients review information on medicines ahead of publication to ensure that the information is “clear and relevant,“ deciding on the eligibility criteria for patient and consumer groups who will be working with EMA, and involving patients as experts in EMA regulatory activities. The PEC will be spearheaded by the FDA’s new Patient Affairs Staff (PAS) in the Office of Medical Products and Tobacco (OMPT), which is responsible for the coordination of agency-wide and cross-center projects related to patient engagement. The PAS will work closely with the medical product centers, the Office of External Affairs (OEA), and other offices across the agency to complement and support ongoing patient engagement efforts. Specifically, the PAS will focus on the following key areas:


1. Creating and assisting with public and private collaborations and partnerships with external groups of patients to discuss topics around medical product development and regulatory policies

2. Coordinating cross-cutting programs and activities to leverage best practices and enhance patient engagement

3. Facilitating consistent cross-center policy-making and common standards to enhance integration of patient perspectives into the regulatory and scientific process

4. Building a framework for hosting and maintaining a shared database of patient engagement information

5. Providing navigation services to triage inquiries from patients and patient organizations

6. Establishing a centralized point of entry into the FDA for patients and their advocates (existing FDA interactions will not be affected)

7. Enhancing our external communication platform to create awareness of the FDA’s patient engagement activities and regulatory processes


This new Collaborative is also facilitated by provisions in both the 21st Century Cures Act of 2016 and the Food and Drug Administration Reauthorization Act of 2017. Both sought to foster patient participation and incorporate patient experiences in the regulatory process. The goal of the nomination process announced today is to identify individuals interested in serving as members of the PEC.


Persian Pomegranate-Pistachio Lamb Meatballs



1 onion, chopped well

2 stalks scallions, chopped well

10 garlic cloves, chopped

1 1/2 cups raw pistachios

1/4 cup almond flour

2 cups fresh parsley, chopped

1 cup fresh tarragon, chopped

1 cup fresh cilantro, chopped

Zest of 1 fresh lime

1 Tablespoon fresh lime juice

1 jalapeno, seeds removed, chopped well

1 pinch black pepper

1 teaspoon cumin

1 teaspoon turmeric

1 pinch salt

2 pounds ground lamb

1 egg

1/2 cup olive oil




3/4 cup pomegranate molasses (I got it from

1/4 cup honey

1 pinch salt

1 pinch black pepper

1 pinch chili flakes



2 Tablespoons chopped pistachios

1 sprig basil

mint leaves

1 cup fresh pomegranate arils




1. To make the meatballs: Pulse all the ingredients, except the meat and egg, in a food processor until you have a grainy paste.

2. Transfer the paste, to a large mixing bowl add the meat and egg. Lightly knead with your hands for a few minutes (do not over mix).

3. Cover and place in the refrigerator overnight.

4. Preheat the oven to 500F.

5. With extra virgin olive oil, grease a baking dish, large enough to hold 24 meatballs, and set aside. Use a baking dish that goes from oven to trivets on the table.

6. Remove the paste from the refrigerator and scoop out of bowl with a Tablespoon and shape into bite-sized balls, the size of the 1 Tablespoon.

7. Put the meatballs in the baking dish and brush with olive oil. Bake in the oven for 10 minutes.



1. In a mixing bowl combine all the ingredients for the glaze.

2. Taste and decide whether it’s too sour. If so, just add more honey.

3. Reduce the oven to 400 degrees.

4. Brush the glaze over each meatball and bake for another 5 minutes, so the flavor of the glaze becomes incorporated. to infuse them with the flavor of the pomegranate. Keep warm in the oven until ready to serve.

5. Just before bringing to table, garnish the meatballs with chopped herbs and more arils.


Serve these delicious meatballs with Basmati or Jasmine rice, or your favorite Daal recipe; a simple tossed salad, warm pita bread and one of the following wines: red Cabernet Sauvignon, Shiraz, Merlot, Pinot Noir, or an excellent Chardonnay, plus many more.


My dear husband was the guinea pig for this recipe, as he is for all of them. After he helped himself to the dinner spread, laid out, there was a pause, and great suspense, waiting for a reaction as he raised his fork. Before I could say one word, he let out sounds of high satisfaction. Happily, he loved the lamb meatballs and I hope you will too! This was definitely one way to my husband’s heart!


Try this excellent wine with lamb. ©Joyce Hays, Target Health Inc.


With the lamb we had Stag’s Leap Wine Cellars, “Artemis“ Cabernet. If you haven’t tried any of the wines (red and white) from this reliable vineyard, we urge you to do so. This vineyard has a very wide range of wines and prices to pick from and it’s fun to experiment. We have never been disappointed. One of our favorites is the “Artemis“ above.


We stayed in this weekend, relaxing, reading and just generally chilling. Maybe, that’s not exactly the right word to use when it was 5 degrees here in Manhattan, last night. Luckily, we could curl up with a good red wine, delicious food and the best company there is.



Have a great week everyone!


From Our Table to Yours

Bon Appetit!


DNA mutations found to be biased toward favoring ‘G-C’ content

January 3, 2018

Arizona State University

DNA rules specify that G always pairs with C, and A with T. But, when it’s all added up, the amount of G+C vs A+T content among species is not a simple fixed percentage or, standard one-to-one ratio. Biologists have now experimentally demonstrated that G+C composition is generally strongly favored by natural selection, regardless of the class of DNA, size of a species’ genome, or where the species is found on the evolutionary tree of life.


Rendering of DNA.
Credit: © DigitalGenetics / Fotolia



To make the iconic, twisted double helix that accounts for the diversity of life, DNA rules specify that G always pairs with C, and A with T.

But, when it’s all added up, the amount of G+C vs A+T content among species is not a simple fixed percentage or, standard one-to-one ratio.

For example, within single-celled organisms, the amount of G+C content can vary from 72 percent in a bacteria like Streptomyces coelicolor while the protozoan parasite that causes malaria, Plasmondium falciparum, has as little as 20 percent.

In single-celled eukaryotes, yeast contain 38 percent G+C content, plants like corn have 47 percent, and humans contain about 41 percent.

The big question is, why?

“This has been one of the long-standing problems in genome evolution, and prior attempts to explain it have involved considerable arm waving,” said Michael Lynch, who leads a new Center for Mechanisms of Evolution at Arizona State University’s Biodesign Institute.

Is there something within the chemical nature of DNA itself that favors one nucleotide over the other, or does the bias of mutation pressure vary, and if so, why would this be different among species?

“In the absence of key observations on the mutation process, there has been a struggle to fathom what the mechanism is,” said Lynch.

Michael Lynch’s group has now experimentally demonstrated that G+C composition is generally strongly favored, whereas this is often opposed by mutational pressure of various strengths in the opposite direction.

“On average, natural selection or some other factor (possibly associated with recombinational forces) favors G+C content, regardless of the class of DNA, size of a species’ genome, or where the species is found on the evolutionary tree of life,” said Lynch.

The study was published in the journal Nature Ecology and Evolution.

To err is universal

Driving evolution are DNA mutations, errors in the genome that are introduced and passed along to the next generation, so that over time, providing the fuel for the invention of new adaptations or traits.

To get to the heart of the matter, the scientists wanted a way to quantify the full spectrum of DNA mutations in the lab across a wide swath of species.

This can now be done due in part by new technologies to make DNA sequencing faster and cheaper. It has fueled a golden age of evolutionary experimental biology.

“We started with knowledge of the mutational spectrum that occurs at the genome level in about 40 species examined in my lab,” said Lynch. “You can use such information to calculate what the GC composition would be in the absence of selection. And then we can compare this null expectation with the the actual genome content, the difference being due to selection.”

In a tour de force experiment that is the largest survey to date, they examined every single DNA mutation across different species, sequencing billions of DNA chemical bases.

“This represented a very substantial work load, effort and cost that was necessary to test different evolutionary models with high statistical power,” said Hongan Long, a postdoctoral researcher who led the experiments.

They also took advantage of an analysis of 25 current datasets of mutations and 12 new mutation-accumulation (MA) experiments (many from their own lab), including bacteria and a menagerie of multicellular organisms including yeast, worms, fruit flies, chimpanzees and humans.

During each MA experiment, they performed complete genome sequencing of about 50 different bacterial lines that had been passaged through severe, single-cell bottlenecks for thousands of cell divisions.

“This single-cell passage of each line acts like a filter, eliminating the ability of natural selection to modify the accumulation of all but the most severe and deleterious mutations, giving us an effectively unbiased view of the mutation process,” said Long.

With each generation, they carefully measured the mutation rate, or every occurrence of when just a single DNA letter is changed.

This can happen in two ways: a single G or C DNA base pair being converted to the A+T direction; or the opposite can happen, with an A or T base switching in the G+C direction.

After all the number and data crunching, a striking pattern emerged between G+C content and the expectations based on DNA mutations.

“It turns out, they are correlated,” said Lynch.. “The G+C composition is always higher than you expect, based on neutrality. That tells us that there is pervasive selection. So mutation drives the overall pattern, but selection for G’s and C’s over A’s and T’s boosts the genome content above the neutral mutational expectation.

This seems to be almost universally true.”

The end of the beginning

Now that they’ve shown the G+C composition correlation, it has opened up the door to many more questions, and answers that remain elusive.

“One question is, ‘why does the mutation spectrum change so dramatically across species'”? asked Lynch. “Species don’t have the same mutation spectrum. There are species whose mutation profiles are more AT rich and others more GC rich. We still don’t know the mechanisms behind such divergence in the mutational spectrum.”

They may be due to simple differences in chemistry and biophysics.

One general force that may be of relevance is DNA stability, driven by the chemistry of the DNA letters. The forces that keep the DNA ladder intact are called hydrogen bonds. G:C pairs involve three hydrogen bonds, whereas, A:T pairs involve only two.

“The prevailing thought is that more G:C content adds to genome stability,” said Lynch.

Another possibility is during reproduction, when the DNA strands intertwine from each parent to make a fertilized egg, mismatches can occur in the base pairing, leading to mistakes that DNA proofreading enzymes have to fix later on. Sometimes, a G can get changed to an A, or a T becomes a C, converting genes during this mismatch repair process.

“That’s generally thought to be biased towards Gs and Cs,” said Lynch.

Now, with their experimental setup in place, Lynch’s team is poised to further explore the mechanisms of evolution and fundamental forces behind this great mystery.

Story Source:

Materials provided by Arizona State UniversityNote: Content may be edited for style and length.

Journal Reference:

  1. Hongan Long, Way Sung, Sibel Kucukyildirim, Emily Williams, Samuel F. Miller, Wanfeng Guo, Caitlyn Patterson, Colin Gregory, Chloe Strauss, Casey Stone, Cécile Berne, David Kysela, William R. Shoemaker, Mario E. Muscarella, Haiwei Luo, Jay T. Lennon, Yves V. Brun, Michael Lynch. Evolutionary determinants of genome-wide nucleotide compositionNature Ecology & Evolution, 2018; DOI: 10.1038/s41559-017-0425-y


Source: Arizona State University. “Scientists explore mysteries behind diversity of DNA composition among species: DNA mutations found to be biased toward favoring ‘G-C’ content.” ScienceDaily. ScienceDaily, 3 January 2018. <>.

Study suggests new approach to treating cancers with this gene fusion

January 3, 2018

Columbia University Medical Center

Researchers have discovered that a common fusion of two adjacent genes can cause cancer by kicking mitochondria into overdrive, increasing the amount of fuel available for rampant cell growth.


Central nervous system cells expressing the FGFR3-TACC3 fusion protein.
Credit: Iavarone Lab, Columbia University Medical Center



The fusion of two adjacent genes can cause cancer by kicking mitochondria into overdrive and increasing the amount of fuel available for rampant cell growth, researchers at Columbia University Medical Center (CUMC) have discovered. They also found that drugs that target this newly identified cancer pathway can prevent tumor growth, both in human cancer cells and mice with a form of brain cancer.

The study was published online today in the journal Nature.

In a 2012 study published in Science, the CUMC team found that some cases of glioblastoma, the most common and aggressive form of primary brain cancer, are caused by the fusion of two genes, FGFR3 and TACC3. At the time, it was thought that this gene fusion was limited to a fraction of brain tumors, affecting about 300 patients in the U.S. per year.

Since then, however, other researchers have observed the same gene fusion in a percentage of lung, esophageal, breast, head and neck, cervical, and bladder cancers, affecting tens of thousands of cancer patients overall. “It’s probably the single most common gene fusion in human cancer,” said study co-leader Antonio Iavarone, MD, professor of neurology and of pathology and cell biology (in the Institute for Cancer Genetics) at CUMC. “We wanted to determine how FGFR3-TACC3 fusion induces and maintains cancer so that we could identify novel targets for drug therapy.”

Changes in mitochondria — the ‘powerhouse’ of the cell — have been observed in cancer for a long time, but researchers have found only recently that mitochondrial activity and cellular metabolism are linked to certain cancers. However, the mechanism by which genetic mutations alter mitochondrial activity and promote tumor growth was unknown.

In the current study, the CUMC researchers compared the activity of thousands of genes in cancer cells with and without FGFR3-TACC3. They discovered that the fusion greatly increases the number and accelerates the activity of mitochondria. Cancer cells, which require huge amounts of energy to rapidly divide and grow, can thrive when mitochondrial activity has been amped up.

Using a variety of experimental techniques, the researchers determined that the gene fusion initiates a cascade of events that increases mitochondrial activity. First, FGFR3-TACC3 activates a protein called PIN4. Once activated, PIN4 travels to peroxisomes, cellular structures that break down fats into substances that fuel mitochondrial activity. Activated PIN4 triggers a four-to-five-fold increase in the production of peroxisomes, which release a flood of oxidants. Finally, these oxidants induce PGC1alpha, a key regulator of mitochondrial metabolism, to increase mitochondrial activity and energy production.

“Our study offers the first clues as to how cancer genes activate mitochondrial metabolism, a crucial and longstanding question in cancer research, and provides the first direct evidence that peroxisomes are involved in cancer,” said study co-leader Anna Lasorella, MD, professor of cell biology (in the Institute for Cancer Genetics) and of pediatrics at CUMC. “This gives us new insights into how we may be able to disrupt cancer’s fuel supply.”

In another experiment, treating human brain cancer cells containing FGFR3-TACC3 with mitochondrial inhibitors interrupted the production of energy inside cancer cells and significantly slowed tumor growth. The same effect was seen in a mouse model of human brain cancer containing this gene fusion.

Dr. Iavarone suspects that a dual-treatment approach may be needed for patients with FGFR3-TACC3 tumors. In their previous study, the researchers found that drugs that inhibit FGFR3 kinase, an enzyme that helps the protein produced by this fusion gene do its work, increased survival when tested in mice with glioblastoma.

These drugs are now being tested in patients with recurrent glioblastoma that contains the gene fusion by one of the paper’s co-authors, Marc Sanson, MD, of Pitié Salpêtrière Hospital in Paris. “Drugs that inhibit active kinases have been tried with encouraging results in some cancers,” said Dr. Iavarone. “But invariably, they become resistant to the drugs, and the tumors come back. However, it may be possible to prevent resistance and tumor recurrence by targeting both mitochondrial metabolism and FGFR3-TACC3 directly.”

Based on the findings in this study, the team is now considering the possibility of adding mitochondrial inhibitors into the therapeutic mix for patients in this trial.

The CUMC team is currently testing this dual approach in human cancer cells and animals models.

The study is titled, “A metabolic function of FGFR3-TACC3 gene fusions in cancer.” The other contributors from CUMC are: Véronique Frattini, Stefano M. Pagnotta, Tala FNU, Marco V. Russo, Sang Bae Lee, Luciano Garofano, Jing Zhang, Peiguo Shi, Genevieve Lewis, Heloise Sanson, Vanessa Frederick, and Angelica M. Castano, Additional contributors are listed in the paper.

The study was supported by grants from the National Institutes of Health (R01CA101644, U54CA193313, R01CA131126, R01CA178546, U54CA193313, R01CA179044, R01CA190891, R01NS061776), Chemotherapy Foundation, SickKids Garron Family Cancer Centre, Ontario Institute for Cancer Research Brain Translational Research Initiative, and American Brain Tumor Association.

Drs. Iavarone and Lasorella received research funds from AstraZeneca and Tahio Pharmaceutical Co. Ltd. Dr. Marc Sanson MS is investigator of two clinical trials using anti-FGFR therapies: AZD4547 (NCT02824133, funded by AstraZeneca) and TAS-120 (NCT02052778, funded by Tahio Pharmaceutical Co., Ltd). The remaining authors declare no financial or other conflicts of interest.

Story Source:

Materials provided by Columbia University Medical CenterNote: Content may be edited for style and length.

Journal Reference:

  1. Véronique Frattini, Stefano M. Pagnotta, Tala, Jerry J. Fan, Marco V. Russo, Sang Bae Lee, Luciano Garofano, Jing Zhang, Peiguo Shi, Genevieve Lewis, Heloise Sanson, Vanessa Frederick, Angelica M. Castano, Luigi Cerulo, Delphine C. M. Rolland, Raghvendra Mall, Karima Mokhtari, Kojo S. J. Elenitoba-Johnson, Marc Sanson, Xi Huang, Michele Ceccarelli, Anna Lasorella, Antonio Iavarone. A metabolic function of FGFR3-TACC3 gene fusions in cancerNature, 2018; DOI: 10.1038/nature25171


Source: Columbia University Medical Center. “Gene fusion shifts cell activity into high gear, causing some cancer: Study suggests new approach to treating cancers with this gene fusion.” ScienceDaily. ScienceDaily, 3 January 2018. <>.

Pioneering new technology set to accelerate the global quest for crop improvement

January 1, 2018

John Innes Centre

A new technology, speed breeding, allows plants to be grown more rapidly. The technology produced wheat, from seed-to-seed in 8 weeks.


Speed breeding means that it is now possible to grow as many as 6 generations of wheat every year — a threefold increase on the techniques currently used by breeders and researchers.
Credit: John Innes Centre



Pioneering new technology is set to accelerate the global quest for crop improvement in a development which echoes the Green Revolution of the post war period.

The speed breeding platform developed by teams at the John Innes Centre, University of Queensland and University of Sydney, uses a glasshouse or an artificial environment with enhanced lighting to create intense day-long regimes to speed up the search for better performing crops.

Using the technique, the team has achieved wheat generation from seed to seed in just 8 weeks. These results appear today in Nature Plants.

This means that it is now possible to grow as many as 6 generations of wheat every year — a threefold increase on the shuttle-breeding techniques currently used by breeders and researchers.

Dr Brande Wulff of the John Innes Centre, Norwich, a lead author on the paper, explains why speed is of the essence:

“Globally, we face a huge challenge in breeding higher yielding and more resilient crops. Being able to cycle through more generations in less time will allow us to more rapidly create and test genetic combinations, looking for the best combinations for different environments.”

For many years the improvement rates of several staple crops have stalled, leading to a significant impediment in the quest to feed the growing global population and address the impacts of climate change.

Speed breeding, says Dr Wulff, offers a potential new solution to a global challenge for the 21st century.

“People said you may be able to cycle plants fast, but they will look tiny and insignificant, and only set a few seed. In fact, the new technology creates plants that look better and are healthier than those using standard conditions. One colleague could not believe it when he first saw the results.”

The exciting breakthrough has the potential to rank, in terms of impact, alongside the shuttle-breeding techniques introduced after the second world war as part of the green revolution.

Dr Wulff goes on to say: “I would like to think that in 10 years from now you could walk into a field and point to plants whose attributes and traits were developed using this technology.”

This technique uses fully controlled growth environments and can also be scaled up to work in a standard glass house. It uses LED lights optimised to aid photosynthesis in intensive regimes of up to 22 hours per day.

LED lights significantly reduce the cost compared to sodium vapour lamps which have long been in widespread use but are ineffective because they generate much heat and emit poor quality light.

The international team also prove that the speed breeding technique can be used for a range of important crops. They have achieved up to 6 generations per year for bread wheat, durum wheat, barley, pea, and chickpea; and four generations for canola (a form of rapeseed). This is a significant increase compared with widely used commercial breeding techniques.

Speed breeding, when employed alongside conventional field-based techniques, can be an important tool to enable advances in understanding the genetics of crops.

“Speed breeding as a platform can be combined with lots of other technologies such as CRISPR gene editing to get to the end result faster,” explains Dr Lee Hickey from the University of Queensland.

The study shows that traits such as plant pathogen interactions, plant shape and structure, and flowering time can be studied in detail and repeated using the technology.

The speed breeding technology has been welcomed by wheat breeders who have become early adopters.

Ruth Bryant, Wheat Pathologist at RAGT Seeds Ltd, Essex, UK, said: “Breeders are always looking for ways to speed up the process of getting a variety to market so we are really interested in the concept of speed breeding. We are working closely with Dr Wulff’s group at the John Innes Centre to develop this method in a commercial setting.”

Dr Allan Rattey, a wheat crop breeder with Australian company Dow AgroSciences, has used the technology to breed wheat with tolerance to pre-harvest sprouting (PHS) a major problem in Australia.

“Environmental control for effective PHS screening and the long time taken to cycle through several cycles of recurrent selection were major bottle necks. The speed breeding and targeted selection platform have driven major gains for both of these areas of concerns.”

Story Source:

Materials provided by John Innes CentreNote: Content may be edited for style and length.

Journal Reference:

  1. Amy Watson, Sreya Ghosh, Matthew J. Williams, William S. Cuddy, James Simmonds, María-Dolores Rey, M. Asyraf Md Hatta, Alison Hinchliffe, Andrew Steed, Daniel Reynolds, Nikolai M. Adamski, Andy Breakspear, Andrey Korolev, Tracey Rayner, Laura E. Dixon, Adnan Riaz, William Martin, Merrill Ryan, David Edwards, Jacqueline Batley, Harsh Raman, Jeremy Carter, Christian Rogers, Claire Domoney, Graham Moore, Wendy Harwood, Paul Nicholson, Mark J. Dieters, Ian H. DeLacy, Ji Zhou, Cristobal Uauy, Scott A. Boden, Robert F. Park, Brande B. H. Wulff, Lee T. Hickey. Speed breeding is a powerful tool to accelerate crop research and breedingNature Plants, 2018; DOI: 10.1038/s41477-017-0083-8


Source: John Innes Centre. “Speed breeding technique sows seeds of new green revolution: Pioneering new technology set to accelerate the global quest for crop improvement.” ScienceDaily. ScienceDaily, 1 January 2018. <>.

← Previous PageNext Page →