October 30, 2017

Boyce Thompson Institute

For some, pumpkins conjure carved Halloween decorations, but for many people around the world, these gourds provide nutrition. Scientists have sequenced the genomes of two important pumpkin species, Cucurbita maxima and Cucurbita moschata.


Group of assorted pumpkins, gourds and squash.
Credit: © stevecuk / Fotolia



For some, pumpkins conjure carved Halloween decorations, but for many people around the world, these gourds provide nutrition. Scientists at Boyce Thompson Institute (BTI) and the National Engineering Research Center for Vegetables in Beijing have sequenced the genomes of two important pumpkin species, Cucurbita maxima and Cucurbita moschata.

The finished genomes appear in the October issue of Molecular Plant, which highlights the work on its cover.

“Pumpkins are used as a staple food in many developing countries and are cultivated all over the world for their culinary and ornamental uses,” said Zhangjun Fei, associate professor at BTI, Cornell adjunct associate professor of plant pathology and a senior author of the paper. Over two-thirds of the world’s pumpkins, squash and gourds are produced in Asia alone.

The researchers sequenced the two different pumpkin species to better understand their contrasting desirable traits: Cucurbita moschata is known for its resistance to disease and other stresses, such as extreme temperatures, while C. maxima is better known for its fruit quality and nutrition.

Additionally, the hybrid of these two species, called ‘Shintosa’ has even greater stress tolerance than C. moschata, and is often used as a rootstock for other cucurbit crops, such as watermelon, cucumber, and melon. Growers will cut the pumpkin seedling from its roots, and fuse the stems of other cucurbits onto it, giving them strong, resistant roots to grow from.

Once deciphered, the genome sequences are an important resource for further scientific research and breeding of Cucurbita crops. By analyzing the genomes, researchers will be able to identify many genes associated with the pumpkin’s desirable traits, and better understand the genetics behind the extreme phenotypes of the ‘Shintosa’ hybrid.

“The high-quality pumpkin genome sequences will lead to more efficient dissection of the genetics underlying important agronomic traits, thus accelerating the breeding process for pumpkin improvement,” said Fei.

In the cucurbit world, this means faster breeding for resistance to diseases such as fusarium wilt or powdery mildew — that white film many gardeners might find killing their squash leaves, or enhancing production of carotenoids — the orange pigments associated with eye health, among other benefits.

While the ultimate goal for genome sequencing is to be able to link specific genes to the traits they control, the pumpkin sequencing results also revealed an interesting evolutionary history for Cucurbita species.

Cucurbitas have large genomes with 20 pairs of chromosomes, compared to watermelon’s 11 or cucumber’s 7. This was the first clue that the pumpkin’s genome had expanded a long time ago. By comparing the Curcurbita genome sequences to those of other cucurbits, the researchers discovered that the pumpkin genome is actually a combination of two ancient genomes, making it a paleotetraploid.

Although the pumpkin is considered a diploid today, meaning that it has only two copies of each chromosome, the genome sequence analysis revealed that between 3-20 million years ago, two different ancestral species combined their genomes to create an allotetraploid — a new species with four (tetra-) copies of each chromosome, from two different (allo-) species.

Typically after an allotetraploid is formed, the genome will experience downsizing and gene loss, eventually transforming the new species back into a diploid. Sometimes, one of the contributing genomes will dominate over the others to retain more genes, a phenomenon observed in maize and cotton.

Interestingly, for pumpkins this was not the case. The ancient Cucurbita allotetraploid lost its duplicated genes randomly from both of the contributing diploids. Furthermore, the ancestral chromosome remained largely intact, leaving the modern pumpkin with two subgenomes representing the ancient species that contributed to the paleotetraploid.

“We were excited to find out that the current two subgenomes in pumpkin largely maintain the chromosome structures of the two progenitors despite sharing the same nucleus for at least three million years,” said Shan Wu, first author of the paper and BTI postdoc.

The next time you carve a pumpkin, take a moment to think about the curious evolutionary path it took to get here, and how breeders, now armed with the genome sequence, will be better able to improve the pumpkin to help feed millions around the world.

Story Source:

Materials provided by Boyce Thompson InstituteNote: Content may be edited for style and length.

Journal Reference:

  1. Honghe Sun, Shan Wu, Guoyu Zhang, Chen Jiao, Shaogui Guo, Yi Ren, Jie Zhang, Haiying Zhang, Guoyi Gong, Zhangcai Jia, Fan Zhang, Jiaxing Tian, William J. Lucas, Jeff J. Doyle, Haizhen Li, Zhangjun Fei, Yong Xu. Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita GenomesMolecular Plant, 2017; 10 (10): 1293 DOI: 10.1016/j.molp.2017.09.003


Source: Boyce Thompson Institute. “Pumpkin genomes sequenced, revealing uncommon evolutionary history.” ScienceDaily. ScienceDaily, 30 October 2017. <>.

Who is Target Health and What Do We Do?


From time to time we are asked “What is Target Health and What Do You Do?“ So those of you not familiar with our services, here they are.


Target Health Inc., a full-service e*CRO, is committed, through creative collaboration, to serve the pharmaceutical community with knowledge, experience, technology and connectivity. Our goal is to get products to the market to help those in need. Our pledge is to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. We provide superior, consistent performance with a cutting edge, diverse team with the highest standards of ethical conduct and integrity.


Our team is both home-grown and from the Industry, with many of our employees have been with us for 10, 15 and yes, some just about 20 years. Our industry-based employees come from Amgen, Boehringer Ingelheim, Certara, Eisai, Microsoft, NY Blood Center, Pfizer, Quintiles, Regeneron, Sanofi, Siemans, Wyeth, etc.


We have been inspected twice by FDA as part of 2 pre-approval inspections with no 483 findings.  Here is an excerpt: “This inspection is a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to ensure that the rights, safety, and welfare of the human subjects of those studies have been protected.“ “From our evaluation of the establishment inspection report and the documents submitted with that report, we conclude that you adhered to the applicable statutory requirements and FDA regulations governing the monitoring practices of clinical investigations and the protection of human subjects.“


Our services, in alphabetical order, include:


Biostatistics: Led by Leigh Ren, we provide full Biostatistical services including statistical planning, randomization codes, protocol statistical sections, SAPs, TLF’s, statistical reports, etc.


Clinical Research: Led by Dave Luke, we manage full paperless clinical programs using top PMs from the industry. We also prepare clinical study reports (CSRs) and prepare manuscripts. Examples of current and past programs include, autism, ADHD, epilepsy, psychiatry, male health, emergency contraception, head lice, periodontal disease, studies in the newborn, etc.


Data Management: Led by Yong Joong Kim, we provide full DM services, fully integrated with Target e*CRF®, Data Management plans, DM review during the clinical trial, clean file meetings, CRF annotation, integration with external labs, SDTM mapping, etc.


EDC: Led by Joonhyuk Choi, we provide full EDC application services at one website and no required devices. We use Target e*Studio® to build Target e*CRF applications, including on line randomization, direct data entry at the time of patient encounter (Target e*CTR® ; eClincal Trial Record), ePRO, eCOA, management and risk-based monitoring reports, drug supply management, SAE management, onsite and remote monitoring reports, etc.


Regulatory Affairs: Led by Mary Shatzoff, we provide strategic planning and regulatory operations services for more than 55 companies. We initiate, coordinate and manage FDA meetings and interactions, and provide paperless regulatory submissions via FDA’s Gateway. Examples of key FDA approvals where we made a difference include, Gaucher Disease, Emergency Contraception, Head Lice, In Vitro Fertilization, Prostate Cancer, Periodontal Disease, Adhesion Prevention in Cardiac Surgery in the Newborn, Urology, Hair Loss in Cancer Chemotherapy, Bone Fracture Healing, etc.


Software Development: Led by Les Jordan, the next version of Target e*Studio will allow almost anyone with clinical research experience, to rapidly create and deploy the cost-effective clinical trial of the future, including but not limited to, online randomization, eSource, and full integration with the EHR, mobile devices, telemedicine, etc.


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



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ATP: Biological Transfer of Energy

Diagram of a typical animal cell. Organelles are labelled as follows: Nucleolus Nucleus Ribosomes (dots on rough reticulum walls) Vesicle Rough endoplasmic reticulum Golgi apparatus (or “Golgi body“) Cytoskeleton Smooth endoplasmic reticulum Mitochondrion Vacuole Cytosol Lysosome Centriole Cell membrane. By Kelvinsong – Own work, CC0,


Diagram of a mitochondrion – Source: By Kelvinsong – Own work, CC0,


Electron transport chain in the mitochondrial intermembrane space

Graphic credit: By T-Fork –, Public Domain,



Bioenergetics is a field in biochemistry and cell biology that concerns energy flow through living systems. This is an active area of biological research that includes the study of the transformation of energy in living organisms and the study of thousands of different cellular processes such as cellular respiration and the many other metabolic and enzymatic processes that lead to production and utilization of energy in forms such as 1) ___ ___, or ATP molecules. The goal of bioenergetics is to describe how living organisms acquire and transform 2) ___ in order to perform biological work. The study of metabolic pathways is thus essential to bioenergetics.


Energy homeostasis is the homeostatic control of energy 3) ___ – the difference between energy obtained through food consumption and energy expenditure – in living systems. Bioenergetics is the part of biochemistry concerned with the energy involved in making and breaking of chemical bonds in the 4) ___ found in biological organisms. It can also be defined as the study of energy relationships and energy transformations and transductions in living organisms. The ability to harness energy from a variety of metabolic pathways is a property of all living 5) ___. Growth, development, anabolism and catabolism are some of the central processes in the study of biological organisms, because the role of energy is fundamental to such biological processes. Life is dependent on energy transformations. Living organisms survive because of exchange of energy between living tissues/ cells and the outside environment. Some organisms, such as autotrophs, can acquire energy from 6) ___ (through photosynthesis) without needing to consume nutrients and break them down. Other organisms, like heterotrophs, must intake nutrients from food to be able to sustain energy by breaking down chemical bonds in nutrients during metabolic processes such as glycolysis and the citric acid cycle. Importantly, as a direct consequence of the First Law of Thermodynamics, autotrophs and heterotrophs participate in a universal metabolic network. By eating autotrophs, or 7) ___, heterotrophs harness energy that was initially transformed by the plants during photosynthesis.


In a living organism, chemical bonds are broken and made as part of the exchange and transformation of energy. Energy is available for work (such as mechanical work) or for other processes (such as chemical synthesis and anabolic processes in growth), when weak bonds are broken and stronger bonds are made. The production of stronger bonds allows release of usable energy. Adenosine triphosphate (ATP) is the main “energy currency“ for organisms; the goal of metabolic and catabolic processes is to synthesize ATP from available starting materials (from the environment), and to break down ATP (into adenosine diphosphate (ADP) an inorganic phosphate) by utilizing it in biological processes. In a cell, the ratio of ATP to ADP concentrations is known as the “energy charge“ of the cell. A cell can use this energy charge to relay information about cellular needs; if there is more ATP than ADP available, the cell can use ATP to do work, but if there is more ADP than ATP available, the cell must synthesize ATP via oxidative phosphorylation. Living organisms produce ATP from energy sources via oxidative phosphorylation. The terminal phosphate bonds of ATP are relatively weak compared with the stronger bonds formed when ATP is hydrolyzed (broken down by water) to adenosine diphosphate and inorganic phosphate. Here it is the thermodynamically favorable free energy of hydrolysis that results in energy release; the phosphoanhydride bond between the terminal phosphate group and the rest of the ATP molecule does not itself contain this energy. An organism’s stockpile of ATP is used as a battery to store energy in 8) ___. Utilization of chemical energy from such molecular bond rearrangement powers biological processes in every biological organism.


Living organisms obtain energy from organic and inorganic materials; i.e. ATP can be synthesized from a variety of biochemical precursors. For example, lithotrophs can oxidize minerals such as nitrates or forms of sulfur, such as elemental sulfur, sulfites, and hydrogen sulfide to produce ATP. In photosynthesis, autotrophs produce ATP using light energy, whereas heterotrophs must consume organic compounds, mostly including carbohydrates, fats, and proteins. The amount of energy actually obtained by the organism is lower than the amount present in the food; there are losses in digestion, metabolism, and thermogenesis. Environmental materials that an organism intakes are generally combined with oxygen to release energy, although some can also be oxidized anaerobically by various organisms. The bonds holding the molecules of nutrients together and in particular the bonds holding molecules of free oxygen together are relatively weak compared with the chemical 9) ___ holding carbon dioxide and water together. The utilization of these materials is a form of slow combustion because the nutrients are reacted with 10) ___ (the materials are oxidized slowly enough that the organisms do not actually produce fire). The oxidation releases energy because stronger bonds (bonds within water and carbon dioxide) have been formed. This net energy may evolve as heat, which may be used by the organism for other purposes, such as breaking other bonds to do chemistry required for survival.


ANSWERS: 1) adenosine triphosphate; 2) energy; 3) balance; 4) molecules; 5) organisms; 6) sunlight; 7) plants; 8) cells; 9) bonds; 10) oxygen


Dr. Peter Dennis Mitchell, British Biochemist


The Nobel Prize in Chemistry 1978 was awarded to Peter Mitchell “for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory“.

Peter Dennis Mitchell (29 September 1920-10 April 1992), British biochemist

Sources: Nobel Prize Foundation: MLA style: “The Nobel Prize in Chemistry 1978“. Nobel Media AB 2014. Web. 24 Oct 2017.; Wikipedia: By Source, Fair use,


The Thesis – The rates of synthesis and proportions by weight of the nucleic acid components of a Micrococcus during growth in normal and in penicillin containing media with reference to the bactericidal action of penicillin.


Peter Dennis Mitchell was born in Mitcham, Surrey on 29 September 1920. His parents were Christopher Gibbs Mitchell, a civil servant, and Kate Beatrice Dorothy (nee) Taplin. His uncle was Sir Godfrey Way Mitchell, chairman of George Wimpey. He was educated at Queen’s College, Taunton and Jesus College, Cambridge where he studied the Natural Sciences Tripos specializing in Biochemistry. He was appointed a research post in the Department of Biochemistry, Cambridge, in 1942, and was awarded a Ph.D. in early 1951 for work on the mode of action of penicillin.


In 1955 Mitchell was invited by Professor Michael Swann to set up a biochemical research unit, called the Chemical Biology Unit, in the Department of Zoology, at the University of Edinburgh, where he was appointed a Senior Lecturer in 1961 and then Reader in 1962. From 1963 to 1965, he supervised the restoration of a Regency-fronted Mansion, known as Glynn House, at Cardinham near Bodmin, Cornwall – adapting a major part of it for use as a research laboratory. He and his former research colleague, Jennifer Moyle founded a charitable company, known as Glynn Research Ltd., to promote fundamental biological research at Glynn House and they embarked on a program of research on chemiosmotic reactions and reaction systems.


In the 1960s, ATP was known to be the energy currency of life, but the mechanism by which ATP was created in the mitochondria was assumed to be by substrate-level phosphorylation. Mitchell’s chemiosmotic hypothesis was the basis for understanding the actual process of oxidative phosphorylation. At the time, the biochemical mechanism of ATP synthesis by oxidative phosphorylation was unknown. Mitchell realized that the movement of ions across an electrochemical potential difference could provide the energy needed to produce ATP. His hypothesis was derived from information that was well known in the 1960s. He knew that living cells had a membrane potential; interior negative to the environment. The movement of charged ions across a membrane is thus affected by the electrical forces (the attraction of positive to negative charges). Their movement is also affected by thermodynamic forces, the tendency of substances to diffuse from regions of higher concentration. He went on to show that ATP synthesis was coupled to this electrochemical gradient.


His hypothesis was confirmed by the discovery of ATP synthase, a membrane-bound protein that uses the potential energy of the electrochemical gradient to make ATP; and by the discovery by Andre Jagendorf that a pH difference across the thylakoid membrane in the chloroplast results in ATP synthesis. Later, Mitchell also hypothesized some of the complex details of electron transport chains. He conceived of the coupling of proton pumping to quinone-based electron bifurcation, which contributes to the proton motive force and thus, ATP synthesis. In 1978 he was awarded the Nobel Prize in Chemistry “for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory.“ He was elected a Fellow of the Royal Society (FRS) in 1974. Mitchell could not have achieved all that he did, without standing on the shoulders of at least two other great researchers (among many), Dr. Friedrich Miescher and Dr. Richard Altmann.


Friedrich Miescher (1844-1895)

Photo credit: copied from, Public Domain,



Miescher isolated various phosphate-rich chemicals, which he called nuclein (now nucleic acids), from the nuclei of white blood cells. This took place in 1869 in Felix Hoppe-Seyler’s laboratory at the University of Tubingen, Germany, paving the way for the identification of DNA as the carrier of inheritance. The significance of the discovery, first published in 1871, was not at first apparent, and it was Albrecht Kossel who made the initial inquiries into its chemical structure. Later, Friedrich Miescher raised the idea that the nucleic acids could be involved in heredity.


Richard Altmann (12 March 1852 – 8 December 1900) was a German pathologist and histologist from Deutsch Eylau in the Province of Prussia. Altmann studied medicine in Greifswald, Konigsberg, Marburg, and Giessen, obtaining a doctorate at the University of Giessen in 1877. He then worked as a prosector at Leipzig, and in 1887 became an anatomy professor (extraordinary). He died in Hubertusburg in 1900 from a nervous disorder. Altmann improved fixation methods, for instance, his solution of potassium dichromate and osmium tetroxide. Using that along with a new staining technique of applying acid-fuchsin contrasted by picric acid amid delicate heating, he observed filaments in the nearly all cell types, developed from granules. He named the granules “bioblasts“, and explained them as the elementary living units, having metabolic and genetic autonomy, in his 1890 book “Die Elementarorganismen“ (“The Elementary Organism“). His explanation drew much skepticism and harsh criticism. Altmann’s granules are now believed to be mitochondria. He is credited with coining the term “nucleic acid“, replacing Friedrich Miescher’s term “nuclein“ when it was demonstrated that nuclein was acidic.


Role for Parkinson’s Gene in the Brain


A new study published online in the journal Neuron (19 October 2017) provides new evidence on the normal function of LRRK2, the most common genetic cause for late-onset Parkinson’s disease. According to the NIH, for more than 10 years, it has been known that mutations in the LRRK2 gene can lead to Parkinson’s disease, yet both its role in the disease and its normal function in the brain have remained unclear. In this new study in the mouse, it was demonstrated that LRRK is necessary for the survival of dopamine-containing neurons in the brain, the cells most affected by Parkinson’s. Importantly, this finding could alter the design of treatments against the disease.


LRRK2 is found along with a closely related protein, LRRK1, in the brain. A mutation in LRRK2 alone can eventually produce Parkinson’s disease symptoms and brain pathology in humans as they age. In mice, however, LRRK2 loss or mutation does not lead to the death of dopamine-producing neurons, possibly because LRRK1 plays a complementary or compensatory role during the relatively short, two-year mouse lifespan.


To better understand the roles of these related proteins in brain function using animal models, the authors created mice lacking both LRRK1 and LRRK2. Results showed that a loss of dopamine-containing neurons in areas of the brain consistent with PD beginning around 15 months of age. When the authors looked at the affected brain cells more closely, they saw the buildup of a protein called a-synuclein, a hallmark of Parkinson’s, and defects in pathways that clear cellular “garbage.“ At the same time, more dopamine-containing neurons also began to show signs of apoptosis, the cells’ “self-destruct“ mechanism.


While the deletion of both LRRK1 and LRRK2 did not affect overall brain size or cells in such areas of the brain as the cerebral cortex and cerebellum, the mice showed other significant effects such as a decrease in body weight and a lifespan of only 15 to 16 months. Thus, the authors were unable to study other Parkinson’s-related effects such as changes in behavior and movement nor were they able to conduct a long-term analysis of how LRRK’s absence affects the brain.


Interestingly, the most common disease-linked mutation in LRRK2 is thought to make the protein more active. As a result, most efforts to develop a treatment against that mutation have focused on inhibiting LRRK2 activity. Therefore, according to the authors, the fact that the absence of LRRK leads to the death of dopamine-containing neurons suggests that the use of inhibitory drugs as a treatment for Parkinson’s disease might not be the best treatment approach. The authors are now developing mice that have LRRK1 and 2 removed only in the dopamine-containing neurons of the brain. This specific deletion will allow for the ability to study longer-term and behavioral changes while avoiding the other consequences that lead to a shortened lifespan.


New Targets For Anti-Malaria Drugs


Plasmodium falciparum, the species of parasite that causes the most malaria deaths worldwide, has developed drug-resistance in five countries in Southeast Asia. According to an article published on line in Science (27 October 2017), this parasite needs two proteins to infect red blood cells and exit the cells after it multiplies, a finding that may provide new targets for drug development.


In the current study, the authors sought to uncover the role of plasmepsins IX and X, two of the 10 types of plasmepsin proteins produced by P. falciparum for metabolic and other processes. To do this, the authors created malaria parasites that lacked plasmepsin IX or X under experimental conditions and compared them to those that had the two proteins. The authors found plasmepsin IX in rhoptries, specialized cell structures inside the parasite, which help it invade red blood cells. Parasites lacking plasmepsin IX had defective rhoptries. In addition, the authors observed plasmepsin X in exonemes-small vesicles (balloon-like structures) that help malaria parasites exit infected cells. The authors also discovered that plasmepsin X processes an important protein called SUB1. When deprived of plasmepsin X, the parasites couldn’t process SUB1 and couldn’t infect red blood cells or exit these cells after multiplying.


The authors also identified three experimental malaria drugs that may work by targeting plasmepsin X. One drug, called CWHM-117, has already been tested in a mouse model of malaria. The new findings may help researchers modify CWHM-117 to make it more effective. Furthermore, parasites lacking the plasmepsins could potentially be used to screen candidate drugs to identify additional anti-malaria compounds.


Robotic Surgery Clearance


The FDA has cleared the Senhance System, a new robotically-assisted surgical device (RASD) that can help facilitate minimally invasive surgery. RASD, sometimes referred to as robotic surgery, is one type of computer-assisted surgical system. RASD enables the surgeon to use computer and software technology to control and move surgical instruments through one or more tiny incisions in the patient’s body (laparoscopic surgery) in a variety of surgical procedures or operations. The benefits of RASD technology may include its ability to facilitate minimally invasive surgery and assist with complex tasks in confined areas of the body. The device, however, is not actually a true robot because it cannot perform surgery without direct human control.


The design of the Senhance System allows surgeons to sit at a console unit or cockpit that provides a 3-D high-definition view of the surgical field and allows them to control three separate robotic arms remotely. The end of each arm is equipped with surgical instruments that are based on traditional laparoscopic instrument designs. The system also includes unique technological characteristics: force feedback, which helps the surgeon “feel“ the stiffness of tissue being grasped by the robotic arm; eye-tracking, which helps control movement of the surgical tools and laparoscopic-type controls similar to traditional surgical equipment.


The Senhance System is intended to assist in the accurate control of laparoscopic instruments for visualization and endoscopic manipulation of tissue including grasping, cutting, blunt and sharp dissection, approximation, ligation, electrocautery, suturing, mobilization and retraction in laparoscopic colorectal surgery and laparoscopic gynecological surgery. The system is for use on adult patients by trained physicians in an operating room environment.


The manufacturer conducted a clinical study of 150 patients undergoing various gynecological operations with the Senhance System. Clinical outcomes were compared to those described in eight peer-reviewed research publications involving more than 8,000 gynecological operations performed in real-world settings (real-world evidence) using another RASD. In addition, the manufacturer submitted Senhance System operative results involving 45 patients undergoing colorectal procedures in a real-world setting and compared the results to those from peer-reviewed research publications describing the real-world device experience. The FDA concluded that these study data, supported by real-world evidence, along with performance testing under simulated use and worst-case scenario conditions, demonstrated the substantial equivalence of the Senhance System to the da Vinci Si IS3000 device for gynecological and colorectal procedures.


The Senhance System was reviewed through the premarket clearance (510(k)) pathway. A 510(k) notification is a premarket submission made by device manufacturers to the FDA to demonstrate that the new device is substantially equivalent to a legally marketed predicate device.


The FDA granted clearance of the Senhance System to TransEnterix Surgical Inc.


Italian Veggie Balls, Served Over Pasta & Your Favorite Sauce

If you like to include a meatless Monday (or additional veggie dinners) in your weekly menus, here is one of my most delicious veggie recipes. It has evolved over a period of two or three years to what I now call Italian Veggie Balls. The sauce I recommend is not my marinara sauce, published in our newsletter many years ago, but a more recent tomato sauce, published recently to serve with seafood. This sauce has rich depth and is also perfect for meat or meatless recipes. Whenever Jules travels, he takes with him a large container of these Italian Veggie Balls, which he gives a score of A+. We both love this dish and have it about once a week. ©Joyce Hays, Target Health Inc.





1 cup chickpea flour, to roll the balls in

1 cup quinoa

3 boxes mushrooms (cremini or Bella or white), well chopped

2 cups chicken stock or broth, or more if needed

4 eggs, whisked

1 cup Parmesan cheese, freshly grated

4 scallions, chopped

25 cloves garlic, minced

Pinch Kosher or sea salt

2 Tablespoons DRY oregano

2 Tablespoons fresh basil, very well chopped

2 Tablespoons fresh parsley, very well chopped

1 red chili, seeds removed, then chopped very well

4 cups steamed kale, chopped

1.5 cup Panko crumbs

1 Tablespoon olive oil

Make your favorite marinara or tomato sauce

Make capellini or your favorite pasta

Freshly grate extra parmesan for the table


Healthy and Easy to Find Ingredients.  ©Joyce Hays, Target Health Inc.


1. Make your marinara or tomato sauce first or the night before.

2. Get a pot with salted water, out to make your pasta, later, after you make the veggie balls.  You want the pasta to be freshly cooked and nice and warm, before serving.

3. Rinse the kale leaves three times, before steaming, to get all the sand and grit out.  After all the work cooking this wonderful recipe, it’s terrible to sit down, take a bite, and have your teeth crunch down on even one grain of sand.  So, rinse, drain; rinse, drain; rinse, drain.

4. While you’re rinsing the kale three times, do all of the cutting, chopping, grating, you need to do, so everything is ready for mixing, later.


Do all your cutting, slicing and chopping at the same time and on the same cutting board.  ©Joyce Hays, Target Health Inc.


Chopping the cilantro.  ©Joyce Hays, Target Health Inc.


5. After kale is rinsed and drained 3 times, steam it until it wilts and is reduced in volume.  Let it drain well before you use it.  In fact, before combining the kale with anything, after it drains well, give it a squeeze with paper towel so there’s not too much liquid in the veggie ball mixture.


Steaming the kale.  ©Joyce Hays, Target Health Inc.


6. Rinse 1 cup of quinoa thoroughly and place the grains in a medium sauce pan with 2 cups of chicken stock or broth. Allow quinoa to soak for 15 minutes. Then, with the lid on the pan, bring the broth to a boil and reduce to a simmer. Cook until quinoa is tender and has absorbed the liquid – about 20 minutes. Let cool to room temp.


Cooked the quinoa.  ©Joyce Hays, Target Health Inc.


7. While the quinoa is cooking, get out a nice looking pan that you will bring to the table and serve from. In this pan, sautee the chopped mushrooms, minced garlic, chili flakes, oregano and basil, in a mixture of olive oil and chicken broth or stock.  Sautee for about 5 minutes, stirring the whole time.


Sautee the mushrooms, onion, garlic, scallions, herbs and spices.  ©Joyce Hays, Target Health Inc.


8. When mushrooms & garlic are done, use a spatula to scrape every bit of the mushroom mixture out of the pan and onto a cutting board.

9. With a large knife, chop the mushroom mixture into very small pieces, as small as you can.  I did not want to use a food processor here, because by making a paste in the processor, you will lose a certain texture, that adds to the flavor.


Above is in the middle of chopping the mushroom mixture.  The pieces need to get just a little smaller.  ©Joyce Hays, Target Health Inc.


10. Into the same mixing bowl, add the cooked quinoa, eggs, 1 cup of parmesan, red chili chopped, salt, steamed kale, Panko crumbs and anything that you might have forgotten to add earlier. Let everything sit for a few minutes to absorb the liquid. You want the batter to be moist, but not runny.


Starting to make the batter; adding egg to the cooked quinoa in a large bowl.  ©Joyce Hays, Target Health Inc.


Here is what the batter should look like, done.  Now, you’re ready to start making the Italian Veggie Balls. ©Joyce Hays, Target Health Inc. 


11. Get a large pan out to cook the veggie meatballs.

12. Sprinkle a little chickpea flour on a plate.

13. With your hands, form little balls and roll them in the chickpea flour.


With your hands, take a fingerfull of the batter and roll balls about the size of golf balls.  Then roll those balls in the chickpea flour until they’re completely covered with a thin film of the flour.  Then fry them in batches in a skillet with enough room to move them around, without breaking them. ©Joyce Hays, Target Health Inc.


14. Heat 1 Tablespoon olive oil in a large skillet over medium-low heat. Cook about 6 veggie balls at the same time. Cover the pan and let the veggie balls cook for about 5 minutes, then roll them around so more of the sides get a nice brown color.  Cook another 5 minutes until the other-sides are a deep rich brown.


Cook the Italian Veggie Balls in extra virgin olive oil with enough room in the pan to move them around.  ©Joyce Hays, Target Health Inc.


15. When each batch is done, put them on a plate, while you finish the next rest.

16. When all the veggie meatballs are done and on a plate or in a serving bowl, fill the skillet with marinara sauce or other tomato sauce, over low flame. When sauce begins to simmer, put veggie balls in and warm everything up, so ready to serve over the pasta.


These Veggie Balls are done now and about to go into a pre-warmed serving bowl. ©Joyce Hays, Target Health Inc.


Into a pre-warmed serving bowl.  ©Joyce Hays, Target Health Inc.


17. On the table, set a trivet out and bring the pan with veggie meatballs to the table to serve (over the pasta).  Garnish the veggie balls with some of the chopped basil or parsley.


Getting hungry just looking at these photos. Such a yummy, flavorful meal ! We love this and hope you do too. ©Joyce Hays, Target Health Inc.


Good to the last bite.  Have your favorite bread with this meal, so you can sop up the wonderful sauce  ©Joyce Hays, Target Health Inc.


Relatives came over for dinner this weekend.  We started with a variety of appetizers (shrimp cocktail, mushroom deviled eggs, stuffed mushrooms, baked cauliflower/potato tiny nibbles).  We were drinking nicely chilled Bellini’s, they chose red. First course was a simple garden salad (my recipe published several years ago), with fresh lemon juice & olive oil, warm French baguette and European butter. Next, my recipe for spinach pie (published several years ago). The entree was Italian Veggie Balls with Capellini and an extraordinarily rich tomato sauce. (My recipe for this sauce was published recently). We had two desserts made at home: my apple cheese cake recipe (published recently in the newsletter) and a chocolate cake (recipe by the great London chef, Yotam Ottolenghi, from Israel).  Our son, Alex, gave me a book of his recipes. We all had a wonderful time!


We saw the play, Junk, at the Vivian Beaumont Theater at Lincoln Center. If you liked the Oliver Stone movie with Michael Douglas about Wall Street greed, called, Wall Street, you will probably like, Junk.  Junk is by playwright, Ayad Akhtar, the Pakistani-American, who won a Pulitzer Prize-for his memorable Broadway play (debut), “Disgraced,“ which we saw and liked immensely.  Watch for more works by this extremely talented writer.


Hope your weekend was stimulating, yet relaxing.  Note to the whole east coast for the next few days: watch out for unusually strong wind.  We’ve heard that New Hampshire may get 120 mile an hour, hurricane force wind, so stay indoors if you can.  Be careful.


We actually drank Bellini’s from start of evening to finish, but don’t necessarily, recommend that. Because of the earthiness of the Italian Veggie Balls and the richness of the sauce, you could easily pair a full-bodied cabernet sauvignon or a chilled white, which you see in the photo above.  ©Joyce Hays, Target Health Inc.


From Our Table to Yours

Bon Appetit!


October 26, 2017

University of Basel

Although bacteria have no sensory organs in the classical sense, they are still masters in perceiving their environment. A research group has now discovered that bacteria not only respond to chemical signals, but also possess a sense of touch. The researchers demonstrate how bacteria recognize surfaces and respond to this mechanical stimulus within seconds. This mechanism is also used by pathogens to colonize and attack their host cells.


Sense of touch: Swimming bacteria can sense surfaces with the flagellum.
Credit: University of Basel, Biozentrum



Although bacteria have no sensory organs in the classical sense, they are still masters in perceiving their environment. A research group at the University of Basel’s Biozentrum has now discovered that bacteria not only respond to chemical signals, but also possess a sense of touch. In their recent publication in Science, the researchers demonstrate how bacteria recognize surfaces and respond to this mechanical stimulus within seconds. This mechanism is also used by pathogens to colonize and attack their host cells.

Be it through mucosa or the intestinal lining, different tissues and surfaces of our body are entry gates for bacterial pathogens. The first few seconds — the moment of touch — are often critical for successful infections. Some pathogens use mechanical stimulation as a trigger to induce their virulence and to acquire the ability to damage host tissue. The research group led by Prof. Urs Jenal, at the Biozentrum of the University of Basel, has recently discovered how bacteria sense that they are on a surface and what exactly happens in these crucial first few seconds.

Research focused only on chemical signals

In recent decades, research has made enormous progress in exploring how bacteria perceive and process chemical signals. “However, we have little knowledge of how bacteria read out mechanical stimuli and how they change their behavior in response to these cues,” says Jenal. “Using the non-pathogenic Caulobacter as a model, our group was able to show for the first time that bacteria have a ‘sense of touch’. This mechanism helps them to recognize surfaces and to induce the production of the cell’s own instant adhesive.”

How bacteria recognize surfaces and adhere to them

Swimming Caulobacter bacteria have a rotating motor in their cell envelope with a long protrusion, the flagellum. The rotation of the flagellum enables the bacteria to move in liquids. Much to the surprise of the researchers, the rotor is also used as a mechano-sensing organ. Motor rotation is powered by proton flow into the cell via ion channels. When swimming cells touch surfaces, the motor is disturbed and the proton flux interrupted.

The researchers assume that this is the signal that sparks off the response: The bacterial cell now boosts the synthesis of a second messenger, which in turn stimulates the production of an adhesin that firmly anchors the bacteria on the surface within a few seconds. “This is an impressive example of how rapidly and specifically bacteria can change their behavior when they encounter surfaces,” says Jenal.

Better understanding of infectious diseases

“Even though Caulobacter is a harmless environmental bacterium, our findings are highly relevant for the understanding of infectious diseases. What we discovered in Caulobacter also applies to important human pathogens,” says Jenal. In order to better control and treat infections, it is mandatory to better understand processes that occur during these very first few seconds after surface contact.

Story Source:

Materials provided by University of BaselNote: Content may be edited for style and length.

Journal Reference:

  1. Isabelle Hug, Siddharth Deshpande, Kathrin S. Sprecher, Thomas Pfohl, Urs Jenal. Second messenger–mediated tactile response by a bacterial rotary motorScience, 2017; 358 (6362): 531 DOI: 10.1126/science.aan5353


Source: University of Basel. “Bacteria have a sense of touch.” ScienceDaily. ScienceDaily, 26 October 2017. <>.

October 25, 2017

Howard Hughes Medical Institute

A new type of DNA editing enzyme lets scientists directly and permanently change single base pairs of DNA from A*T to G*C. The process could one day enable precise DNA surgery to correct mutations that cause human diseases.


A newly created DNA base editor contains an atom-rearranging enzyme (red) that can change adenine into inosine (read and copied as guanine), guide RNA (green) which directs the molecule to the right spot, and Cas9 nickase (blue), which snips the opposing strand of DNA and tricks the cell into swapping the complementary base.
Credit: Gaudelli et al./ Nature 2017



DNA editing just got a sharp, new pencil. Researchers have built an enzyme that can perform a previously impossible DNA swap, directly changing the DNA base pair from an A●T to a G●C. The new enzyme, known as a base editor, may one day enable genome surgery that erases harmful mutations and writes in helpful ones, Howard Hughes Medical Institute (HHMI) Investigator David Liu and colleagues report October 25, 2017, in Nature.

The new system is a “really exciting addition to the genome engineering toolbox,” says Feng Zhang, an HHMI-Simons Faculty Scholar and molecular biologist at the Broad Institute of MIT and Harvard, who was not involved in the study. “It’s a great example of how we can harness natural enzymes and processes to accelerate scientific research.”

Some genome editing tools, such as the method known as CRISPR/Cas9, cut both strands of DNA and rely on the cell’s own molecular machinery to fill in the gap with the desired DNA sequence. Base editors are, in a sense, more precise tools. “CRISPR is like scissors, and base editors are like pencils,” says Liu, a chemical and molecular biologist at Harvard University and the Broad Institute.

Those pencils can rewrite the individual chemical units of DNA, known as bases. Each base on one strand of DNA joins its partner base on an opposing strand, so that the base adenine pairs with thymine (A●T), and guanine pairs with cytosine (G●C). Last year, Liu and colleagues described a base editor that could change C●G base pairs into T●A. But researchers didn’t have the ability to convert A●T to G●C, until now.

Going in, Liu and his team knew that the project was risky, because the first step involved creating an enzyme that didn’t yet exist. Postdoctoral researcher Nicole Gaudelli took on the challenge, relying in part on evolution to create an enzyme that could do the job. Gaudelli started with an enzyme called TadA that’s able to convert adenine to a molecule called inosine (which cells treat as guanine), but in transfer RNA rather than in DNA. She made larger libraries of TadA mutants into bacterial cells and required them to convert A to inosine in antibiotic resistance genes in order to survive in the presence of antibiotics. Surviving bacteria encoded TadA mutations that imparted the ability to perform the adenine-to-inosine conversion on DNA.

This evolution in the lab paid off. Soon enough, the researchers saw that some bacterial colonies were able to fix their own mutations with chemical surgery and survive the antibiotic challenge. Along with other tweaks, the researchers attached the enzyme to a molecule called Cas9 nickase. That add-on allows the base editor to find the right spot to cut along a DNA strand and snip the opposing strand of DNA — a nick that prompts the cell to insert the correct partner base pair to match the new one, thereby completing the swap of A●T to G●C.

Along with several related enzymes, the most tricked-out version, called ABE7.10, is an efficient chemical surgeon, turning A●T into G●C in both human and bacterial genomes. The enzyme operates with more than 50 percent efficiency and few, if any, byproducts such as undesired mutations.

Mutations in which a G●C mutates into an A●T account for nearly half of the roughly 32,000 single point mutations associated with human diseases. Experiments in the new study hint at the promise of the new genome pencil. ABE7.10 reversed a G-to-A mutation associated with a genetic iron-storage disease known as hemochromatosis in cells taken from patients. In a different experiment, ABE7.10 added a mutation that restored the function of a hemoglobin gene in human cells. That mutation is known to confer protection against blood diseases including sickle cell anemia.

The results are an early step. “We are hard at work trying to translate base editing technology into human therapeutics,” Liu says, but many hurdles remain. Safety, efficiency, and base editor delivery methods still need to be answered before base editing can be used to tweak the human genome. “Having a machine that can make the change you want to make is only the start,” Liu says. “You still need to do all this other work, but having the machine really helps.”

Story Source:

Materials provided by Howard Hughes Medical InstituteNote: Content may be edited for style and length.

Journal Reference:

  1. Nicole M. Gaudelli, Alexis C. Komor, Holly A. Rees, Michael S. Packer, Ahmed H. Badran, David I. Bryson, David R. Liu. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavageNature, 2017; DOI: 10.1038/nature24644


Source: Howard Hughes Medical Institute. “Precise DNA editing made easy: New enzyme to rewrite the genome.” ScienceDaily. ScienceDaily, 25 October 2017. <>.

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