July 26, 2017 A microscope image showing glia cells and neurons in the eye's retina. Credit: Tom Reh lab/UW Medicine

Scientists have successfully regenerated cells in the retina of adult mice at the University of Washington School of Medicine in Seattle.

Their results raise the hope that someday it may be possible to repair retinas damaged by trauma, glaucoma and other eye diseases. Their efforts are part of the UW Medicine Institute for Stem Cell and Regenerative Medicine.

Many tissues of our bodies, such as our skin, can heal because they contain stem cells that can divide and differentiate into the type of cells needed to repair damaged tissue. The cells of our retinas, however, lack this ability to regenerate. As a consequence, injury to the retina often leads to permanent vision loss.

This is not the case, however, in zebrafish, which have a remarkable ability to regenerate damaged tissue, including neural tissue like the retina. This is possible because the zebrafish retina contains cells called Mller glia that harbor a gene that allows them to regenerate. When these cells sense that the retina has been injured, they turn on this gene, called Ascl1.

The gene codes for a type of protein called a transcription factor. It can affect the activity of many other genes and, therefore, have a major effect on cell function. In the case of the zebrafish, activation of Ascl1 essentially reprograms the glia into stem cells that can change to become all the cell types needed to repair the retina and restore sight.

The team of researchers in the new study were led by Tom Reh, University of Washington School of Medicine professor of biological structure. The scientists wanted see whether it was possible to use this gene to reprogram Mller glia in adult mice. The researchers hoped to prompt a regeneration that doesn't happen naturally in mammal's retina.

Their research findings appear online July 26 in the journal Nature. The lead author is Nikolas Jorstad, a doctoral student in the Molecular Medicine and Mechanisms of Disease program at the University of Washington.

Like humans, mice cannot repair their retinas. Jorstad said that to conduct their experiment, the team "took a page from the zebrafish playbook." They created a mouse that had a version of the Ascl1 gene in its Mller glia. The gene was then turned on with an injection of the drug tamoxifen.

Earlier studies by the team had shown that when they activated the gene, the Mller glia would differentiated into retinal cells known as interneurons after an injury to the retina of these mice. These cells play a vital role in sight. They receive and process signals from the retina's light-detecting cells, the rods and the cones, and transmit them to another set of cells that, in turn, transfer the information to the brain.

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In their earlier research, however, the researchers found that activating the gene worked only during the first two weeks after birth. Any later, and the mice could no longer repair their retinas. Reh said that at first they thought another transcription factor was involved. Eventually they determined that genes critical to the Mller glia regeneration were being blocked by molecules that bind to chromosomes. This is one way cells "lock up" genes to keep them from being activated. It is a form of epigenetic regulationthe control of how and when parts of the genome operate.

In their new paper, Reh and his colleagues show that, by using a drug that blocks epigenetic regulation called a histone deacetylase inhibitor, activation of Ascl1 allows the Mller glia in adult mice to differentiate into functioning interneurons. The researchers demonstrated that these new interneurons integrate into the existing retina, establish connections with other retinal cells, and react normally to signals from the light-detecting retinal cells.

Reh said his team hopes to find out if there are other factors that can be activated to allow the Mller glia to regenerate into all the different cell types of the retina. If so, it might be possible, he said, to develop treatments that can repair retinal damage, which is responsible for several common causes of vision loss.

Explore further: Study helps explain how zebrafish recover from blinding injuries

More information: Nikolas L. Jorstad et al, Stimulation of functional neuronal regeneration from Mller glia in adult mice, Nature (2017). DOI: 10.1038/nature23283

Journal reference: Nature

Provided by: University of Washington

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Scientists regenerate retinal cells in mice - Medical Xpress

Three Litchfield High School graduates have been chosen for induction into the LHS Hall of Fame later this year.

The former students Dean Urdahl, Samara Reck-Peterson and Dave Kleis followed active high school careers by making their marks in professional lives ranging from politics to biology and education.

The inductees:

Dean Urdahl

Urdahl, who graduated in 1967, has served as a state representative for 15 years. He was first elected to the Minnesota House of Representatives in 2002.

But decades before that political career, Urdahl was a student in Litchfield schools, where he was active in sports and other organizations. He participated in speech, Future Teachers and Dragon newspaper, in addition to playing football, basketball and swimming. He also was manager for the high school baseball team.

Urdahl said current students should have goals and be persistent in striving to achieve them. Dont give up.

Following high school graduation, he attended St. Cloud State University. He went on to a 35-year teaching career in the New London-Spicer school district, where he taught history and coached the cross-country team. His runners earned three consecutive state titles.

Urdahl has served as president of the Meeker County Historical Society, chairman of the 1976 Forest City Stockade Restoration Committee, vice president of the Litchfield Baseball Association, Education Minnesota Local President for New London-Spicer, vice chairman of the Minnesota Republican Party in 1970-1971, and chairman of the Sixth District Republican Party Committee.

Urdahl has authored nine books, including a number of historical fiction novels set around the Dakota-American War.

Samara Samie Reck-Peterson

Reck-Peterson graduated from Litchfield High School in 1989 and went on to earn bachelors and masters degrees in biology at Carleton College in Northfield in 1993. She then earned a doctorate in cell biology from Yale University in 2000, and a National Institutes of Health postdoctoral fellowship at University of California at San Francisco in 2007.

She has been a professor of cellular and molecular medicine at University of California San Diego since 2015, following eight years as an associate professor of cell biology at Harvard Medical School in Boston.

Reck-Peterson served as the senior class president while at Litchfield High School, and was the class salutatorian. In addition, she competed in cross country, basketball and track. She served as captain of the cross country and track teams, and competed at the state meet in both sports. She also was a marching band member for three years.

Todays students should Figure out what you are passionate about, Reck-Peterson said. Then set goals for yourself and pursue them with determination.

During her professional career, Reck-Peterson has served as program chairwoman of The American Society for Cell Biology Annual Meeting, council member of The American Society for Cell Biology, been on the editorial board of the Journal of Cell Biology, board of reviewing editors of eLife, associate editor of Molecular Biology of the Cell, and has served as associate director of Biological and Biomedical Sciences Graduate Program at Harvard Medical School.

Dave Kleis

Kleis has served as mayor of St. Cloud for the past 11 years, following an 11-year career in the Minnesota Senate.

He got his start in Litchfield, however, where he was active in sports and student organizations throughout high school. Kleis played football and ran track, serving as captain of the track team his senior year. He also served on the Student Council, including as class vice president his senior year. He also was a member of the German Club and choir.

He served 9 1/2 years in the U.S. Air Force and Air Force Reserve. Following military service, he joined the American Legion and served as post adjutant for Post 76 in St. Cloud.

Kleis is a small business owner in St. Cloud and he has been a member of the St. Cloud Area Chamber of Commerce and St. Cloud Rotary. He also served as chairman of the St. Cloud Metro Transit Commission and is a founding member and former co-chairman of the Mississippi River City & Towns Initiative.

Kleis said students today should Get involved in your community, get to know others, and contribute in every way you can. Life is an adventure, try not to worry so much about material reward, and invest in the moment.

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Three chosen for LHS Hall of Fame induction - Crow River Media

The Conference will bring together allopathic doctors, Ayurveda practitioners and modern scientists on a common platform.Kochi, July 26, 2017 Indias biggest conference on integrative Ayurveda and modern medicine, with 60 experts and 1,000 delegates from around the world participating, is set to begin at Kochis Amrita Institute of Medical Sciences on August 6, 2017. The two-day event, titled Amrita Samyogam 2017, is being held in collaboration with Amrita Universitys School of Ayurveda. It will be inaugurated by the Union Minister of State for AYUSH, Shripad Yasso Naik.

The Conference will bring together allopathic doctors, Ayurveda practitioners and modern scientists on a common platform. It will identify strategies for integrating Ayurveda with Allopathy in the management of cancer, auto-immune diseases like arthritis, diabetes, neuro-degenerative diseases, and mental health. The event will demonstrate how integrative medicine can be made a reality through examples of clinical integration, basic science studies, and application of new technologies.

Said Prof. Shantikumar Nair, Director, Centre for Nanosciences & Molecular Medicine, Amrita University: Integrating Indias ancient tradition of Ayurveda with evidence-based modern medicine has the potential to revolutionize world healthcare. Integrative medicine is becoming a popular specialty among physicians in Western countries because of the myriad ways in which it can benefit patients. It focuses on healing the person in entirety rather than merely treating the symptoms by investigating the root cause of illness. It is much more patient-centric and can positively impact chronic and lifestyle diseases for which modern medicine has no answer. Western medicine and Indian ancient healing sciences can be a win-win combination to effectively tackle the enormous healthcare challenges facing humanity.

Amrita Samyogam 2017 is expected to trigger important collaborations across the world in the field of integrative medicine, especially academic collaborations and funding opportunities. An International Journal of Integrative Health will be launched at the event and a Society for Integrative Health will be established to promote the development of Integrative Medicine in India.

Eminent medical experts attending the Conference include: Dr. Jeffrey White, Director of National Cancer Institute, USA; Dr. Daniel Furst, Rheumatologist at University of California; Dr. Nereo Bresolin, Neurologist, University of Milan; Dr. Christian Kessler, Internal Medicine Specialist, Charite Medical University, Germany; Dr. Valdis Pirags, Diabetologist, University of Latvia; Dr. Maryam Matar, Genetics Specialist, UAE; Dr. Ravi Mehrotra, Director, National Institute for Cancer Prevention and Research, Noida, Dr. B.N. Gangadhar, Director, NIMHANS, Bengaluru; Dr. Rama Jayasundar, Professor, All India Institute of Medical Sciences, New Delhi, Dr. Ketaki Bapat, Scientific Advisor to the Government of India, and many others.

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India's biggest conference on integrative Ayurveda and Allopathy to ... - ETHealthworld.com

Newswise PHILADELPHIA Benjamin L. Prosser, PhD, an assistant professor of Physiology, in the Perelman School of Medicine at the University of Pennsylvania, has received the Outstanding Early Career Investigator Award from the American Heart Associations (AHA) Council on Basic Cardiovascular Sciences, one of its scientific divisions.

Prossers award was based on his research to date and the originality, quality and impact of an oral abstract he presented at the Councils 2017 Basic Cardiovascular Sciences (BCVS) meeting, held earlier this month in Portland, Oregon. The presentation focused on the Prosser lab discovery that clinicians and researchers, working together, might improve the beating strength of heart cells from patients with heart failure by "softening" the internal cytoskeleton (the network of protein filaments and microtubules) of those cells.

Last year, in a paper published in Science, Prosser and his colleagues described advanced imaging techniques to explore microtubule behavior in beating heart-muscle cells from rodents. They discovered that healthy microtubules long believed to be stiff instead buckle with each contraction and then return to their original configuration. This process provides mechanical resistance for the beating of the heart, enabling the microtubules to serve as what Francis S. Collins, MD, PhD, director of the National Institutes of Health, called molecular shock absorbers in a blog about the findings. But, Prosser and his colleagues found that manipulating heart cells to increase microtubule stiffness impeded contraction, impairing cardiac function. A tentative conclusion is that microtubules provide sufficient, but not excessive resistance in healthy heart muscle.

The visual evidence produced by the Prosser team was a major advance, since it is technically difficult to see parts of heart muscle in operation in real time. Together, the findings and visual documentation have potentially powerful implications for better understanding how microtubules affect the mechanics of the beating heart and what happens when the process goes wrong. Prosser is now examining whether specific drugs can make diseased heart cells isolated from patients with heart failure beat stronger by enabling the microtubules to slide back and forth more smoothly. This would allow the heart to pump blood more efficiently with each contraction. Promising early studies from patient cells were presented at this years BCVS meeting.

Prosser received his BS degree in health and exercise science from Wake Forest University and his PhD in molecular medicine from the University of Maryland School of Medicine.

Under the AHAs criteria, early career investigators are PhDs and/or MDs who are still in training (e.g., residency, fellowship) or have completed training within the last four years; or PhDs and/or MDs who are within in the first four years after their first faculty appointment as of the award application date.

Penn Medicineis one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and theUniversity of Pennsylvania Health System, which together form a $6.7 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2016 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals byU.S. News & World Report-- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2016, Penn Medicine provided $393 million to benefit our community.

SEE ORIGINAL STUDY

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Penn Medicine Cardiology Researcher Wins American Heart Association Outstanding Early Career Investigator Award - Newswise (press release)

July 26, 2017 Medication has different effects on men and women. In recent studies, Jena researchers have once again given concrete indications for the need for a gender-specific medicine. Credit: Jan-Peter Kasper/FSU

One difference between the sexes that medical professionals take seriously is the susceptibility to certain diseases.

"We know, for example, that inflammatory diseases such as asthma, psoriasis or rheumatoid arthritis occur much more frequently in women than in men," says Prof. Oliver Werz of the Friedrich Schiller University Jena. The german pharmacist and his team, together with colleagues from Italy, Denmark and Sweden, have uncovered a significant cause for these sex differences at the molecular level. In two high-profile publications in the Journal of Clinical Investigation and Scientific Reports, they show how the male sex hormone testosterone interferes with the biosynthesis of inflammatory substances, and additionally reduces the effectiveness of anti-inflammatory drugs.

The researchers comprehensively analysed and compared inflammatory processes in diverse animal models and isolated immune cells from the blood of male and female human donors. This was made possible by a cell system developed in Prof. Werz's laboratory, in which the biochemical processes can be observed with high precision through time-resolved microscopy. "We investigated the formation of inflammatory substances, such as leukotrienes and prostaglandins, and looked at whether the effect of anti-inflammatory drugs differs in male and female cells," explains Werz.

As expected, the effect of the drugs under investigation was significantly stronger in the female samples than in the male samplesafter all, the inflammatory process is much more pronounced in women. "However, these differences are completely abolished by the administration of testosterone," says Dr Simona Pace, first author of both papers. Previous studiesincluding work by Prof. Werz's team in Jenahave already shown that testosterone can protect against inflammatory reactions. "However, now we have been able to throw light on the molecular mode of action and show that testosterone also influences the therapeutic effect of drugs," notes the postdoc from the Department for Pharmaceutical and Medical Chemistry of the University of Jena.

The researchers found that the sex hormone directly interferes with leukotriene biosynthesis by blocking the necessary interaction between the "5-Lipoxygenase" and "FLAP" proteins. Secondly, they were able to prove that the reduced leukotriene synthesis leads to increased amounts of prostaglandins, which further promote inflammatory reactions. This means that testosterone plays a key role in the inflammatory process and in modulating the immune response.

With this work, the researchers have once again provided specific evidence supporting the need for gender-specific medicine. "Anti-inflammatory substances that are suitable for women may have only a limited effect in men, and the opposite might also be true," concludes Prof. Werz. Treatment using a single product from the medicine cabinet could therefore lead to very different levels of success. This is a fact that should clearly be considered much more carefully in future in developing new drugsespecially for treating inflammatory diseases. In future, this could even lead to separate 'his' and 'hers' medicine cabinets.

Explore further: How testosterone protects against inflammation

More information: Simona Pace et al. Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males, Journal of Clinical Investigation (2017). DOI: 10.1172/JCI92885

Simona Pace et al. Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation, Scientific Reports (2017). DOI: 10.1038/s41598-017-03696-8

Pharmacists of the University Jena, Germany, and partners have shown that cells from men and women react in a different manner to inflammatory stimuli. They found that in male cells the enzyme phospholipase D is less active ...

Lutein, a nutrient found in several highly coloured vegetables and fruits, can suppress inflammation, according to a new study by researchers at Linkping University, Sweden. The results, published in Atherosclerosis, suggest ...

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Do we need separate his and hers medicine cabinets? - Medical Xpress

The DRILL device is connected to a mass spectrometer to sort charged droplets and improve desolvation of ionized biomolecules for analysis. The device requires no modification of the mass spectrometer, and can be accommodated within the standard work flow now used by researchers. (Credit: Rob Felt, Georgia Tech)

Adding the equivalent of a miniature tornado to the interface between electrospray ionization (ESI) and a mass spectrometer (MS) has allowed researchers to improve the sensitivity and detection capability of the widely-used ESI-MS analytical technique. Among the scientific fields that could benefit from the new technique are proteomics, metabolomics and lipidomics which serve biomedical and health applications ranging from biomarker detection and diagnostics to drug discovery and molecular medicine.

Known as Dry Ion Localization and Locomotion (DRILL), the new device creates a swirling flow that can separate electrospray droplets depending on their size. In this application, one of many potential uses for DRILL, the smaller droplets are directed to enter the mass spectrometer, while the larger ones which still contain solvent remain in the vortex flow until the solvent evaporates. Removing the solvent allows analysis of additional ions that may be lost in current techniques and reduces the chemical noise that inhibits selectivity of the mass spectrometer.

A major challenge for detecting small quantities of biomolecules using mass spectrometry technology is that we cant see everything that is actually in the sample, said Matthew Torres, an assistant professor in Georgia Techs School of Biological Sciences. The DRILL device provides a new way to solve that problem by increasing the number of ions we can get into the mass spec instrument so we can productively detect them. The ions are there now, but not necessarily in a form that the mass spec can handle.

Developed by researchers at the Georgia Institute of Technology with support from North Carolina State University, DRILL can be added to existing electrospray ionization mass spectrometers without modifying them.

The principle is to make the droplets rotate and use inertia to separate them out by size, explained Andrei Fedorov, a professor in Georgia Techs Woodruff School of Mechanical Engineering. We want the droplets to stay in the flow long enough to remove the solvent. In practice, smaller droplets remain in the center, where they are can be removed first for analysis, while the larger ones remain on the edge of the flow until they are dried.

The key idea of DRILL is based on Fedorovs 2007 invention Confining/Focusing Vortex Flow Transmission Structure, Mass Spectrometry Systems, and Methods of Transmitting Particles, Droplets, and Ions." (US Patent No. 7,595,487). In the past three years, the DRILL device has been developed with support from the National Institute of General Medical Sciences of the National Institutes of Health, and its latest version was described June 14 in the American Chemical Society journal Analytical Chemistry.

In electrospray ionization (ESI), an electric potential is applied to a solution inside a capillary, producing a strong electric field at the spray capillary tip. That leads to the expulsion of an aerosol containing charged droplets that carry the molecules to be analyzed. The ejected droplets then break up into smaller droplets, creating a plume that expands spatially beyond the inlet intake capacity of the mass spectrometer, resulting in sample loss. The DRILL device provides an effective interface for collection and transmission of charged analytes from ionization sources, such as ESI, to detection devices, such as mass spectrometers, resulting in significantly improved detection capability.

As much as 80 to 90 percent of large biopolymers (proteins, peptides, and DNA) are currently lost to analysis using existing ESI-MS techniques, which have grown in importance to the life sciences community. Capturing all of the biopolymers could lead to new discoveries, said Torres, whose lab studies post-translational changes in proteins. By allowing analysis of large biomolecules, DRILL could facilitate top-down proteomics in which complete protein molecules could be studied without the need to enzymatically break them up into smaller pieces before MS analysis.

This could allow us to see combinatorial modifications that exist on a single protein molecule, said Torres. Its very important for us to understand how proteins communicate with one another, and DRILL may allow us to do that by more effectively removing the solvent from these types of samples.

The Georgia Tech researchers are using DRILL in their lab to interface between liquid chromatography and the ESI-MS instrument. Multiple electrodes and inlet/outlet ports enable precise control over the flow generation and guiding electric field inside the DRILL, so the device can be configured for a variety of uses, Fedorov noted. In a general sense, DRILL adds a new approach for manipulating the trajectory of charged droplets, which, when combined with hydrodynamic drag forces and electric field forces, provides a rich range of possible operational modes.

DRILL can improve the signal-to-noise ratio by a factor of 10 in the detection of angiotensin I, a peptide hormone, and boost the sensitivity for angiotensin II ten-fold to picomole levels. DRILL demonstrated improved signal strength up to 700-fold for eight of nine peptides included in a test extract of biological tissue.

DRILL could potentially allow the study of entire cell contents, analyzing thousands of different molecule types simultaneously. That could allow researchers to see how these molecules change over time to detect problems in chemical pathways and to determine why drugs work in some people and not others.

This could be a huge advance for biologists and others who are interested in protein biochemistry and cell biology because it enhances the sensitivity of the analytical technical and overcomes a major hurdle in studying large biological molecules, Torres added. We expect to be able to see things we havent been able to see before.

The Georgia Tech researchers have been collaborating with David Muddiman, a professor in the Department of Chemistry at North Carolina State University, on developing DRILL and its analytical characterization using state-of-the-art mass spectrometry experiments. A unique contribution of the North Carolina State University researchers is in using a powerful statistical method called design of experiments to guide the multi-parameter optimization of the DRILL device, resulting in the identification of a sweet spot for optimal operation.

Fedorov and Torres hope to expand use of the DRILL device beyond Georgia Tech laboratories and further enhance its design. Among the near-term improvements planned is the addition of internal heating to accelerate the removal of solvent. We see many additional improvements that will allow DRILL to further enhance the ESI-MS process, said Fedorov. We plan to continue evolving it as more labs start to use the device.

This article has been republished frommaterialsprovided by Georgia Institute of Technology. Note: material may have been edited for length and content. For further information, please contact the cited source. ReferencePeter A. Kottke, et al., DRILL: An ESI-MS interface for improved sensitivity via inertial droplet sorting and electrohydrodynamic focusing in a swirling flow, (Analytical Chemistry, 2017). http://dx.doi.org/10.1021/acs.analchem.7b01555.

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Tiny Tornado Boosts Performance of Electrospray Ionization Mass Spectrometry - Technology Networks

Sorry for the delay, folks a glitch prevented this newsletter from going out earlier this morning.

We finally got a break from the heat. The high might not even make 90 today, and that's all right by us. We've got the full forecast below. Now, the news:

Sales taxes are putting Columbia in a bind. At his annual budget address, city manager Mike Matthes said he's proposing three ballot measures to raise revenues for new initiatives. He's also pitching some budget cuts and creative spending decisions, like hiring civilians instead of trained officers to increase police staffing. Check out all the highlights here.

MU's budget fallout claimed another victim. At the end of June, the International Institute of Nano and Molecular Medicine was shuttered, affecting 17 employees. The institute, led by Frederick Hawthorne, a recipient of the National Medal of Science, did not have enough grant funding to offset its costs, officials said.

The Rise apartment building is nearing completion and affected streets downtown are reopened. Don't be too thrilled, there are still two major downtown projects affecting roads and sidewalks. There's no word yet on when students might start moving in, but the city has cleared the building for occupancy.

Around CoMo this week

5:30 p.m. Monday: Cornerstones of Columbia plaque presentation and celebration. Begins at 10 Hitt St., ends at The Blue Note.

6 p.m. Wednesday: Science on Tap returns to Craft Beer Cellar with presentations by two MU researchers.

All day Thursday Friday: The District hosts its Dog Days Sidewalk Sale at participating shops.

Friday Sunday: The Show-Me State Games continue.

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Sales taxes crimp city's plans; MU shutters biomedical research institute; one downtown project down, more to go - Bonner County Daily Bee

(The Conversation is an independent and nonprofit source of news, analysis and commentary from academic experts.)

Ian Haydon, University of Washington

(THE CONVERSATION) In a factory just outside San Francisco, theres an upright stainless steel vat the size of a small car, and its got something swirling inside.

The vat is studded with gauges, hoses and pipes. Inside, its hot just under 100 degrees Fahrenheit. Sugar and other nutrients are being pumped in because, inside this formidable container, there is life.

Scientists are growing cells in there. Those cells, in turn, are growing medicine. Every two weeks or so, the hot, soupy liquid inside gets strained and processed. The purified molecules that result will eventually be injected into patients with Stage IV cancer.

Drugs that are made this way inside living cells are called biologics. And theyre taking medicine by storm. By 2016, biologics had surged to make up 25 percent of the total pharmaceutical market, bringing in US$232 billion, with few signs their upward trend will slow.

Common medicines such as aspirin, antacids and statins are chemical in nature. Though many were initially discovered in the wild (aspirin is a cousin of a compound in willow bark, the first statin was found in a fungus), these drugs are now made nonbiologically.

To read this article in one of Houston's most-spoken languages, click on the button below.

Conventional medicines are stitched together by chemists in large factories using other chemicals as building blocks. Their molecular structures are well defined and relatively simple. Aspirin, for example, contains just 21 atoms (nine carbons, eight hydrogens and four oxygens) bonded together to form a particular shape. A single aspirin tablet even kid-sized contains trillions of copies of the drug molecule.

Biologic drugs are a different story. This class of medication is not synthesized chemically instead they are harvested directly from biology, as their name suggests. Most modern biologics are assembled inside vats or bioreactors that house genetically engineered microbes or mammalian cell cultures. Efforts are underway to make them in plants.

Biologic drugs can be whole cells, alive or dead. They can be the biomolecules produced by cells, like antibodies, which are normally secreted by our immune systems B cells. Or they can be some of the internal components of cells, like enzymes.

Biologics are typically much larger molecules than those found in conventional pharmaceuticals, and in many cases their exact composition is unknown (or even unknowable). Youre unlikely to find biologic drugs in tablet form they tend to be delicate molecules that are happiest in liquid solution.

While biologics are one of the fastest-growing drug categories in the U.S., they arent exactly new. The Biologics Control Act, passed in 1902, was the first law aimed at ensuring the safety of some of the earliest biologics vaccines. Congress was moved to pass the law after a contaminated batch of diphtheria shots left 13 children dead. Jim, the horse from which the diphtheria antitoxin had been extracted, had contracted tetanus.

Fortunately, scientists have dramatically improved the way they manufacture biologic drugs since then. For starters, the recombinant DNA revolution of the 1970s means that drug makers no longer have to extract many of the most important biologics from whole animals.

The gene that codes for human insulin, for example, can be pasted into a microbe which will happily churn out the drug in bulk. After a multi-million dollar purification process, the injectable insulin that results is indistinguishable from the version a healthy human body would produce. This is how some forms of insulin are made today.

Both conventional and biologic drugs work by interacting with our own biology. Most conventional drugs function as inhibitors theyre just the right size and shape to jam themselves into some molecular cog in our cells. Aspirins pain-reducing power comes from its ability to disrupt an enzyme in the body called cyclooxygenase, an important player in pain signaling.

Conventional drug discovery largely consists of finding new compounds that specifically disrupt only disease-associated processes. Because these drugs are quite small, and because the inside of any cell is a sea of other molecular components, finding a new small drug that blocks only problematic processes is tricky. Off-target interactions can produce side effects of all types.

The large size of biologic drugs can be an asset here. An antibody, for example, has lots of specific points of contact with its target. This enables therapeutic antibody drugs to bind with extreme precision only their target molecule should be an exact match. This binding can lead to inhibitory effects, much like a conventional drug might. In some cases, therapeutic antibodies can also stimulate the immune system in a problem area, like at a tumor, prompting the body to take it out.

Many biologics target molecular processes that no conventional drug can, and they can treat a growing list of diseases. Cancer treatments dominate the list, but since 2011 the U.S. Food and Drug Administration has approved new protein-based biologics for the treatment of Lupus, Crohns disease, rheumatoid arthritis, multiple sclerosis, kidney failure, asthma and high cholesterol.

New types of biologic drugs continue to emerge as well. In late 2015, the FDA approved a first-of-its-kind treatment for patients with advanced melanoma: an engineered herpes virus. Researchers genetically programmed the virus, called T-VEC, to target only cancerous cells, and it can also prompt the immune system to start wiping out cancer. Additional virus-based therapies are currently working their way through the lengthy U.S. drug approval process.

Amgen, the company that produces T-VEC, estimates it will cost an average of $65,000 per patient and that doesnt come close to topping the list of priciest biologic medications. The most expensive drug ever made recently won approval by the FDA. Brineura, a biweekly enzyme replacement therapy produced by BioMarin Pharmaceutical, delays the loss of walking in individuals with a rare genetic disorder. Its price tag? $27,000 per injection, or more than $700,000 for a full years treatment.

The steep prices of biologic drugs are alarming to many patients, physicians and researchers. In an effort to drive costs down, provisions of the Obama administrations Affordable Care Act accelerated the approval process for new biologics intended to compete with already approved medicines. Like generic drugs, so-called biosimilars are designed to be interchangeable with the biologic they seek to replace.

Unlike generic versions of conventional drugs, however, biosimilar drugs are often only similar to not identical with their competition. This means these complex drugs still require lengthy and expensive trials of their own to make sure theyre effective and safe. Because of this, the Federal Trade Commission estimates that biosimilars may only produce an overall 10 to 30 percent discount for patients.

Cost-cutting innovations in the biologic production pipeline are desperately needed. The FDA has called on scientists and drug developers to invent biosimilars that resemble FDA-approved medicines and to develop the tools needed to quickly demonstrate their safety.

As this promising class of drugs continues to grow in number and popularity, their lifesaving power will be limited if costs make them inaccessible to patients who need them.

This article was originally published on The Conversation. Read the original article here: http://theconversation.com/biologics-the-pricey-drugs-transforming-medicine-80258.

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Biologics: The pricey drugs transforming medicine - Houston Chronicle

News - National | 2017-07-24Page no: 7 byDenver Kisting

Bernard Haufiku

LINDA-GAIL Bekker, the president of the International AIDS Society (IAS), yesterday said crucial evidence is needed to inform global policy change on the HIV pandemic.

Bekker was speaking at the start of the ninth IAS conference on HIV science, which started in the French capital early yesterday.

According to her, impending anxiety about funding cuts has necessitated the establishment of how we use what we have in the wisest possible way.

The conference, also attended by health minister Bernard Haufiku and other ministry officials, brought together approximately 6 000 leading scientists, researchers and human immune-deficiency virus professionals from across the globe to take stock of the virus and its continued impact.

In the conference programme, Bekker said: Almost 15 years after Paris last hosted the conference, we return to the city renowned for groundbreaking discoveries in HIV science for the largest open scientific conference on HIV.

This year, it is more critical than ever to highlight the importance and impact of prioritising and investing in research. This will be demonstrated over the next three days, as leading investigators present novel science and new resolutions in HIV prevention, treatment and cure.

Bekker, a South African professor and the deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town, said at the start of a session on HIV and how it relates to young people that the challenges persist to scale up timely HIV testing, treatment and quality care for children and adolescents worldwide.

During the second session, which dealt with the challenges key populations men who have sex with men, sex workers, members of the transgender community, people who inject drugs and people detained in correctional facilities face, Tiffany Lillie, senior technical adviser at an international HIV organisation dealing with these communities emphasised that the care continuum consists of prevention, testing, treatment and viral load suppression.

Lillie said there is an increasing need to focus on key populations in particular in the fight against HIV because they carry a disproportionate burden of HIV as a total of 44% of new infections arise among these communities. In Africa, 25% of new infections are from key populations.

During this same session, Dr Cameron Wolf, an international infectious disease specialist, said key populations remain subjected to pervasive stigma, violence and criminalisation.

In Namibia, consensual anal sexual intercourse between two males remains a criminal offence in terms of the country's common law, despite no successful prosecutions.

This is generally regarded as a benign crime, although human rights activists have criticised it as being unconstitutional.

Other conference objectives include accelerating basic science and clinical innovation for the development and application of new HIV prevention, treatment and care technologies to advance precision medicine, strengthening the implementation science and research agenda to address key barriers and challenges structural, service delivery and policy across HIV to cascade in a variety of epidemic scenarios and amplify the synergies between HIV and co-infections, as well as emerging co-morbidities and other non-communicable diseases.

Furthermore, strengthening research towards cure/treatment remission and vaccine, and demonstrating the links between HIV and other public health and human rights emergencies and identifying strategies for integrated responses, are also on the agenda.

The conference, which ends on Thursday, is organised by IAS, in partnership with France REcherche Nord & sud Sida-hiv Hpatites.

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Global conference on HIV starts - Namibian

To honor the 100th Anniversary of the countrys independence, Visit Finland has launched an exciting new campaign: The Symphony of Extremes Born from Finnish DNA. As Finland is a nation of vast extremes, not only in its weather and seasons, but in its peoples adventurous lifestyles and taste for both headbanging metal and classical music as well, Visit Finland will delve into the nations distinct character by examining its heritage and culture and turning the Finnish genotype into music.

The Symphony of the Extremes Born from Finnish DNA delves deep into the Finnish psyche to introduce Finlandscultural core, by tracking the composition of a new piece by heavy metal band Apocalyptica, who use Finnish DNA samples as raw material for a genre-crossing track which will premiere later this year along with an visually-engaging music video to showcase the work of art globally. The campaign trailer is now available on its official website: http://www.visitfinland.com/symphonyofextremes/.

The campaign closely follows the creative process and highlights a group of noteworthy people behind the genes, each of whom exhibit some extreme and distinctively Finnish trait, such as sisu, their unique grit, or a strong bond with the Arctic.

A number of professionals at the apex of their fields will also be brought together, including Jonathan Middleton, visiting professor at the University of Tampere who has developed a program that can create sounds from the base pairs found in DNA; and Eicca Toppinen, a member of the Finnish cello metal band Apocalyptica formed in 1993, who will then compose a new piece of music based on DNA samples gathered around Finland by geneticists. The campaign starts with the collection of the genes, culminating in the works publication by late 2017.

The Symphony of Extremes will also focus on extreme freediver Johanna Nordblad; Tinja Myllykangas who lives with dozens of dogs in the wilderness of Lapland; and a group of children living in the extreme conditions of outer Finnish Archipelago. Their unique and personal stories will inspire international audiences and also draw attention to the mysterious wonders of Finland, drawing in tourism and visitors around the globe.

This cooperation involves extensive research, product development, and expertise from a number of key academic influencers including Paivi Onkamo, lecturer of genetics in The University of Helsinki; Jonathan Middleton, a composer based in Spokane where he teaches composition at Eastern Washington University; and Janna Saarela, research director of Institute for Molecular Medicine Finland.

Finland appeals to travelers searching for unique and extreme experiences in their destinations. For example, there are 500,000 summer cottages throughout the country, 188,000 lakes, over 3,000,000 saunas (more than the number of cars), 179,000 islands and over 70% of the land covered by forest. Its spectacular nature wonders has attracted travelers and lovers of the outdoors to visit Finland from all over the world.

Besides its stunning landscape wonders, Finlands seasons present extreme conditions that test the strength of its people, with freezing temperatures reaching -51C in the winter when the sun doesnt rise above the horizon for 52 days in Lapland, and 70 days of midnight sun in the summer; and these intense conditions seem to have given birth to an impressive 3,400 Finnish metal bands that rock the country with sound waves.

Over the year, Visit Finland will orchestrate this grand campaign of audio-visual stimulation to showcase the unique and authentic Finland in all its extreme adventure and glory, and to enhance the destinations brand awareness to markets across the globe. Audiences can expect a very real, firsthand look into the nations core DNA, from its peoples ancestry, love of extreme sports, to its rural communities passion for environmental sustainability.

Finland has also been named one of the top countries in the world for travelers, receiving the accolade in Lonely Planets Best in Travel 2017, the highly anticipated collection of the worlds hottest trends, destinations, and experiences for the year ahead

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Finland Tourism: The Symphony of Extremes: Born from Finnish DNA - eTurboNews

SHIVA01 and SHIVA02 are large-scale trials run in France to evaluate the efficacy of precision medicine that have created ripples in the oncology field.

Although molecular alterations are shared among different types of cancer, drug development today is still mainly based on tumor localization. The only recent exception is MSDs Keytruda (pembrolizumab) an antibodyapproved by the FDA in May 2017 for any solid tumor, independently from its location, that expresses MSI-H or dMMR biomarkers of errors in DNA replication.

However, the clinical utility and validity of precision medicine approach remain to be demonstrated.The frequency of molecular alterations that can be targetedusing precision medicine is low you could screen thousands of patients before finding one with the relevant biomarkers. Clinical trials need to include a huge number of patients in order to drawrobust conclusions.

To face these challenges, Institut Curielaunched in 2012 the French precision medicine SHIVA01 trial, led by Prof. Christophe Le Tourneau, senior Medical Oncologist and Head of Clinical Research in the Department of Medical Oncology at Institut Curie.

So far, nobody has demonstrated the concept of precision medicine in oncology, where every single cancer patient would be treated based on its tumor molecular profile. The SHIVA01 trial coordinated by the Institut Curie,however, suggested that this approach is relevant in some cases, says Le Tourneau.

Christophe Le Tourneau discussing precision medicine studies at ASCO 2017

SHIVA01 was a multicentricPhase II trial thatcompared targeted therapy based on tumor molecular profiling versus conventional therapy in patients with any kind of refractory cancer. Molecular profileswere performed on biopsies using high throughput next generation sequencing andestimations of the number of gene copies and expression of hormonal receptors.

Using a predefined algorithm, patients whose tumor harbored a molecular alteration matching one of the 11 targeted therapies available within the trial were randomized between the targeted therapy anda conventional approach. The study managed to include an impressive total of 741 patients at eight sites in France.

The SHIVA01 trialfinishedonly recently, but it has already made noise in the field,producing an impressive amount of publications in major journals besides the principal publication in The Lancet Oncology in 2015. These paperscover everything frombioinformaticstocirculating tumor DNA, biological interpretation of variants, andinterventional radiology.

Results of the primary endpoint of SHIVA01: Progression-free survival in patients with molecular alterations in the hormone receptor RAF/MEK pathway

In the end, this trial can be definitely considered as a major step forward in terms of clinical trial design, even if results were negative for its primary endpoint. In fact,the SHIVA trial did not show that patients treated with targeted therapy had a better outcome, but demonstrated, however, that the administration of targeted therapy outside their indications might be a valid approach in a subgroup of patients with a molecular alteration in the MEK/RAF signaling pathway.

Based on these results and experience gained, a second trial has already started. SHIVA02aims to recruit 400 patients within 2 years using the patient as its own controland will focus on patients with alterations inMEK/RAF,also known as the RasRaf-MEK-ERK pathway.Compared to the first edition, the treatment algorithm for SHIVA02 is more refined. The researchers will use anNGS panel designed in house to capture relevant mutations, amplifications and deletions in the target genes.

In order to run thistrial, the Institut Curie will receivefunding of 1.6M over a period of 5 yearsfrom the MSDAvenir Foundation,an autonomous entity created by MSD in 2015 to foster research and social initiatives in France.

Dominique Blazy (President of the Scientific Council at MSDAvenir); Prof. Christophe Le Tourneau and Pr Thierry Philip (President of the Institut Curie)

What makes the SHIVA trials different is that theyonly evaluate the whole strategy of precision medicine and not the efficacy of each drug separately. In addition, they arealso definitely interesting for biotech industries. The resultingcurated sample databaseopens the door to a broad range of retrospective studies that can be valuable to refine theunderstanding of a disease and improve researchmodels.

Even if there is still a long way to go, Prof. Le Tourneau says, Several precision medicine trials are currently ongoing worldwide, each with a unique design but all aiming to address the main question: does a targeted treatment strategy based on tumor molecular alteration is more efficacious than standard treatment based on tumor localization?Hes already considering aSHIVA03 trial that will include immunotherapies in theprotocol.

Special thanks to Prof. Christophe Le Tourneau and Maud Kamal for their assistance in writing this article.

Images via smart.art / Shutterstock;Institut Curie; Le Tourneau C. et al. The Lancet Oncology (2015).Volume 16, No. 13, p13241334

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SHIVA Trial: France's Big Shot at Precision Medicine for Cancer - Labiotech.eu (blog)

One lady with psoriasis all over the body was under allopathic treatment for over one and a half years. She happened to prepare panchagavya for field use and stir the contents with her forearm. After 15 days, the psoriasis in her forearm got fully cured. Following her own intuition, she smeared panchagavya all over the body and to everyones surprise the psoriasis disappeared in 21 days, the Tamil Nadu Agricultural University (TNAU) website claims.

A claim as tall as they come. And most of the claims about panchagavya fall in the same category. Sample this: According to the TNAU website, the magic potion can cure arthritis within two months and help treat several other diseases and conditions such as epilepsy and Parkinsons. It can reduce blood sugar levels and enable diabetic patients to reduce the dose of anti-diabetic drugs. In the case of TB, it can reduce the duration of treatment by a month. For people with AIDS/HIV, even though the blood tests will be positive, patients will exhibit no symptoms of AIDS and lead a normal healthy life thanks to panchagavya.

Even if we keep the lack of evidence aside, it is beyond me why an agriculture university should be discussing the medicinal benefits of panchagavya.

For its proponents, it doesnt matter that cancer is not a single disease and there is no single cure panchagavya can apparently cure it all. Shankarbhai Vegad, a BJP MP from Gujarat told the Rajya Sabha in March 2015: Cow dung and urine can cure cancer. I am witness to it. Cow dung and urine are a 100 per cent cure for cancer.

For the uninitiated, panchagavya is a concoction of cow dung, cow urine, milk, curd and ghee. Along with the five constituents that come from the cow, it also contains jaggery, banana, tender coconut and water.

Now a 19-member committee has been constituted to select projects that can help scientifically validate the benefits of panchagavya, a report in The Hindu says. It will be headed by Union Science and Technology Minister Dr. Harsh Vardhan and other prominent members such as former CSIR Director R.A. Mashelkar, IIT Delhi director Prof. V. Ramgopal Rao and Prof. V.K. Vijay from IIT Delhi. Of course, the committee will be not influenced by three members who have links to the RSS and the VHP!

Indias National Programme Scientific Validation and Research on Panchagavya (SVAROP) will be coordinated by the Department of Science and Technology (DST), Department of Biotechnology (DBT) and Council of Scientific and Industrial Research (CSIR) in collaboration with IIT Delhi.

At a time when fund crunch at CSIR and ICMR is leaving scientists with little financing for front-line research, a national programme will be trying to validate the benefits of panchagavya for various medical and non-medical purposes. Its a pity that there has not been any scientific laboratory and animal studies carried out with results published in peer-reviewed journals to justify a national programme being launched.

Before launching a large programme such as this, there should be pilot projects and early evidence which shows some benefits. There should be some basis that it would work. Unfortunately, we have not seen any evidence in the form of published work in reputed journals, says Dr. Anant Bhan, a researcher in Global Health Policy. There are five components in panchagavya and one would like to know which of those give benefits for which disease, and in which population and at what dosage and duration. Even the composition of the concoction has not been standardised.

For its proponents, it doesnt matter that cancer is not a single disease and there is no single cure panchagavya can apparently cure it all.

Even if we keep an open mind it has to be conditional on good science being followed, Dr. Bhan adds.

Curcumin, the main ingredient of turmeric, which has been studied for various diseases and conditions has been subjected to tough scientific scrutiny. Unlike curcumin, panchagavya is a mixture of five components. Each component is a complex entity. One is not sure which one is causing what, says Prof. G. Padmanaban, former Director of the Indian Institute of Science (IISc) Bengaluru who has studied curcumin extensively. Each component is a highly variable entity and the time of collection of the components and how it is collected varies. There should be quality control for each component. I am not sure if we can establish that. So it will be very difficult to validate panchagavya.

It is always possible to validate panchagavya but the ratio of the five components has to be carefully measured and the dosing has to be meticulously done. Most of the therapeutic components are metabolites and they vary at different times of the year. For example in the case of tulsi leaves, the active component wont be the same in a tender leaf and a matured leaf. So the results will not be the same, says Prof. Gobardhan Das from the Special Centre for Molecular Medicine, Jawaharlal Nehru University (JNU) Delhi.

As scientists we should have an open mind and not be prejudiced. Discoveries cant be made if we dont have an open mind. But we cant approach it with blind faith either. There should be healthy scepticism, says Dr. Girish Sahni, Director-General of CSIR on how he views CSIRs involvement in the National Programme. According to him, a couple of CSIR labs have got some leads on panchagavya, which have not been followed up.

In place of peer-reviewed studies, what we have are patents (No 6410059 and No. 6896907) granted by the United States Patent Trade mark Office. These patents have been granted to an Indian innovation which has proved that cow urine can make antibiotics, anti-fungal agents and also anti-cancer drugs more effective, The Hindu reported in 2002.

What is often not realised is that patents are granted based on uniqueness of an idea or method and surely not on its translation into reality. In the case of drugs, it is not patents but results from animal studies and clinical trials in humans which will attest the effectiveness. Forget animal studies and human clinical trials, panchagavya has not been rigorously tested even on cells lines (in vitro).

The website of the Central AYUSH Ministry lists out many papers published in journals, but none of the links leads to the original papers. What does become apparent is that only a handful of papers discuss panchagavya while a majority deal with cow urine in isolation.

It also becomes abundantly clear that almost all the papers have been published in predatory journals. For instance, the papers such as Antifungal efficacy of panchagavya; Biochemical characterisation and antibacterial activity of panchagavya; Effect of panchagavya ghrita on some neurological parameters in albino rats; and Panchagavya ghrita, a promising drug in ayurvedic psychiatry; have been published in predatory journals. A paper, Evaluation of in-vitro antioxidant activity of panchagavya a traditional ayurvedic preparation, has been published in the International Journal of Pharmaceutical Science and Research that finds mention in a credible list of predatory journals but is also UGC-approved. UGC has many predatory journals included in its white list.

Now this is a case not only of lack of evidence, but also of questionable work published in bogus or predatory journals being showcased by the Central Ministry as evidence.

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Panchagavya... if cow urine could cure cancer - The Hindu

It is a common problem in a range of areas of great practical importance to have active molecules that possess beneficial properties but are challenging to stabilise for storage Knowles said. A conceptually simple, but powerful, solution is to put these inside tiny capsules. Such capsules are typically made from synthetic polymers, which can have a number of drawbacks, and we have recently been exploring the use of fully natural materials for this purpose. We are particularly excited by the potential to replace plastics with sustainable biological materials for this purpose.

Dr. Ulyana Shimanovich, who performed a major part of the experimental work as a St Johns College Post-Doctoral research associate, and now works at the Weizmann Institute of Science, said: Silk is a fantastic example of a natural structural material. But we had to overcome the challenge of controlling the silk to the extent that we could mould it to our designs which are more than a factor of a thousand smaller than the natural silk cocoons.

Dr. Chris Holland, co-worker and head of the Natural Materials Group in Sheffield added: Silk is amazing because whilst it is stored as a liquid, spinning transforms it into a solid. This is achieved by stretching the silk proteins as they flow down a microscopic tube inside the silkworm.

To imitate this, the researchers created a tiny, artificial spinning duct, which copies the natural spinning process to cause the unspun silk to form into a solid. The researchers then worked out how to control the geometry of this self-assembly in order to create microscopic shells.

Making conventional synthetic capsules can be challenging to achieve in an environmentally friendly manner and from biodegradable and biocompatible materials. Silk is not only easier to produce; it is also biodegradable and requires less energy to manufacture.

Natural silk is already being used in products like surgical materials, so we know that it is safe for human use, Professor Fritz Vollrath head of the Oxford Silk Group said. Importantly, the approach does not change the material, just its shape.

Silk micrococoons could also expand the range and shelf-life of proteins and molecules available for pharmaceutical use. Because the technology can preserve antibodies, which would otherwise degrade, in cocoons with walls that can be designed to dissolve over time, it could enable the development of new treatments against cancer, or neurodegenerative conditions such as Alzheimers and Parkinsons Diseases.

To explore the viability of silk microcapsules in this regard, the researchers successfully tested the micrococoons with an antibody that has been developed to act on alpha-synuclein, the protein that is thought to malfunction at the start of the molecular process leading to Parkinsons Disease. This study was carried out with the support of the Cambridge Centre for Misfolding Diseases, whose research programme is focused on the search for ways of preventing and treating neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Professor Chris Dobson, Director of the Centre and Master of St John's, who is also a co-author of this paper, said: "The results of this study are extremely exciting as they suggest that many potentially therapeutic molecules that could not normally be taken forward into the clinic because of their lack of stability, could become life-changing drugs using these encapsulation techniques."

Some of the most efficacious and largest selling therapeutics are antibodies, Michele Vendruscolo, co-director of the Cambridge Centre of Misfolding diseases, said. However, antibodies tend to be prone to aggregation at the high concentrations needed for delivery, which means that they are often written off for use in treatments, or have to be engineered to promote stability.

By containing such antibodies in micrococoons, as we did here, we could significantly extend not just their longevity, but also the range of antibodies at our disposal, Knowles said. We are very excited by the possibilities of using the power of microfluidics to generate entirely new types of artificial materials from fully natural proteins.

The study, Silk microcooons for protein stabilisation and molecular encapsulation, is published inNature Communications.

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Silk micrococoons could be used in biotechnology and medicine - Bioscience Technology

F

amously, the word vaccine comes from the Latin word for cow a namesake that traces back to the late 1700s.

Now cows are once again at the cutting edge of vaccine science. Thanks to a quirk of how cows make antibodies, they are helping researchers understand human immunity. Someday, cows could serve as testing grounds for whether vaccines are well-designed. And its possible that cow antibodies could treat everything from autoimmunity to infectious disease.

A new study on HIV by scientists at Scripps Research Institute explores these possibilities. Cows dont get HIV, but, when injected with viral proteins, produce antibodies that block HIV infection. The results, which were reported Thursday in Nature, are part of a larger effort to make the first HIV vaccine.

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HIV mutates constantly, creating many strains. Broadly neutralizing antibodies are key to an HIV vaccine because they could protect against these various strains. But theyve proven hard to make in people.

The body in HIV infection either from natural infection or in response to a vaccine does not like to make broadly neutralizing antibodies, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. It just doesnt do it readily, and it doesnt do it very well.

So scientists are keenly interested in other animals that might do it well. Enter cows: Two separate teams of scientists at Scripps made two parallel discoveries in recent years that broadly neutralizing antibodies for HIV are especially long and gangly, and that cows normal antibodies are also long and gangly.

That was the inspiration for this study. It was an alignment of the stars, where we had veterinarians, cow antibody scientists, and HIV scientists all talking and came up with this relatively simple question to test, said Devin Sok, the studys first author and director for antibody discovery and development at the International AIDS Vaccine Initiative.

The scientists injected four cows with a protein that mimics HIVs surface, known as the envelope. They then drew blood samples over the course of a year and isolated antibodies. The antibodies were tested in a dish for their ability to block HIV from infecting cells.

What they found surprised them. Within two months, all the cows made antibodies that blocked a variety of viral strains much faster than in people. And low doses of antibody were enough to block the virus.

We definitely didnt expect to get the [antibody] response that we did. We didnt expect the extent of the response or how quick the response developed, said Sok. That was kind of mind-blowing.

As to why cows are such good antibody factories, it may have to do with their unique stomachs. Dr. Vaughn Smider, professor of molecular medicine at Scripps, points out that cows four-chambered stomachs hold a whopping 20 gallons of digestive microbes. The cow immune system has to deal with keeping in check all these microorganisms, said Smider. Cows extra-long antibodies can potentially bind into grooves, crevices, or areas where a typical antibody from humans or mice may not be able to bind.

The study is the first to reliably elicit broadly neutralizing antibodies. But Dr. John Mascola, director of vaccine research at NIAID, cautions that there are still obstacles to an effective vaccine in humans.

The study doesnt tell us how to make a vaccine for HIV in people, but it does tell us how the virus evades the human immune response, said Mascola.

Mascola believes that HIV vaccine research is at the end of the beginning. To complete the journey, scientists will need to make a vaccine that accurately mimics HIVs envelope and coaxes the immune system to make the right antibodies. Barton Haynes, director of the Duke Human Vaccine Institute, believes cows could help with the first of those two challenges.

There is a debate going on about whether this envelope or that envelope is good, said Haynes. Cows may be a really good model to test that.

Cow HIV antibodies could also be directly given to people. This is not a substitute for a vaccine, which creates long-term immunity to prevent disease. But the antibodies could provide short-term protection or reduce virus levels in those already infected.

To do this, scientists would take antibody-producing cells from cows, isolate their antibody genes, and transfer them into cell lines that grow easily in a lab, such as E. coli or yeast. They would then tinker with the antibodies to make them more human-like. This has already been done with mouse antibodies to create drugs such as alemtuzumab, used to treat leukemia.

Smider hopes that, within five to 10 years, cow antibodies will be used for a variety of diseases. He says that their unusual structures could help treat certain cancers, autoimmune disorders, and infectious diseases such as malaria. Smider is currently working with three different drug companies on this goal.

Another possibility is to milk cows for their antibodies literally. Cows milk is rich in antibodies, and there is evidence that drinking milk from cows immunized against various germs can protect against illness. Immuron, an Australian biotech company, makes a pill prepared with powdered milk from immunized cows to protect against travelers diarrhea. The product is available over-the-counter in multiple countries, including the U.S., Canada, Australia, and China.

AAAS Mass Media Fellow

Jonathan Wosen is STATs 2017 AAAS Mass Media Science & Engineering Fellow.

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July 18, 2017 | :

COLUMBIA, Mo. The University of Missouri System has closed its $10 million medical research institute as part of an effort to cut costs.

The decision to close the International Institute of Nano and Molecular Medicine will affect 17 full-time and part-time employees through layoffs and contract non-renewals, university spokesman Christian Basi told the Columbia Missourian in an email.

The institute was closed June 30 because of its significant operating expenses and its lack of grant funding in recent years, Basi said.

The university broke ground on the institute in 2008. The institute studied how to apply nanotechnology to fighting diseases.

Frederick Hawthorne had been the director of the institute since it opened. He used nanotechnology to manipulate boron to try to find a way to combat cancer, arthritis and other illnesses. He was awarded the National Medal of Science by President Barack Obama in 2012.

The university expects to save about $1.5 million annually with the institutes closing. Basi said the building will likely be used as a research facility and that teams studying biomedical innovations and disease therapeutics will be in the facility next semester.

The school is still recovering from student protests in fall 2015 over the administrations handling of racial issues and the subsequent resignations of the system president and chancellor of the Columbia campus. Freshman enrollment subsequently dropped.

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University of Missouri Research Institute Closes Amid Cuts - Higher ... - Diverse: Issues in Higher Education

July 19, 2017

Infections in surgically implanted heart valves are more common in patients who have been given a biological prosthetic valve than in those with a mechanical one, a study from Karolinska Institutet published today in the journal Circulation shows.

Some 1,500 people undergo aortic valve replacement every year in Sweden, about 75 per cent of whom receive a biological valve (from a pig or calf), the remainder a mechanical one. A complication that carries a high fatality risk is prosthetic valve endocarditis, which occurs when the new valve is infected by bacteria. Until now, there have been no figures on whether the infection frequency differs between the two valve types. It has also been unknown how common infections in an artificial heart valve are. The present study included over 26,500 patients who received a prosthetic heart valve between 1995 and 2012, 940 of whom developed prosthetic valve endocarditis.

The risk of infection in the artificial valve was about 50 per cent higher with a biological prosthesis than with a mechanical. The follow-up time was up to 18 years.

"We hadn't expected this large difference," says Natalie Glaser, doctoral student at Karolinska Institutet's Department of Molecular Medicine and Surgery. "Our results are important as they tell us more about complications following the surgical replacement of aortic valves."

The current European cardiology guidelines state that there is no difference in the incidence of infection between the two types of implant. Dr Glaser argues that this could be because former studies were too small to reveal any difference and were done on patients who were operated on decades ago.

The present study has also provided updated figures on the commonality of the complication, which affected a total of around 0.5 per cent of patients per year. It also shows that the fatality rate was as high as 16 per cent within a month of diagnosed infection and 50 per cent within five years.

"The choice of valve prosthesis is very much decided by the patient's age," says principal investigator Ulrik Sartipy, heart surgeon at Karolinska University Hospital and docent at Karolinska Institutet's Department of Molecular Medicine and Surgery. "Biological valves are usually used for older patients for medical reasons, partly because such valves do not require life-long treatment with anticoagulants. In our study, those who had received biological valves were on average 13 years older than those who were given mechanical ones, but this we've compensated for in our comparison."

Explore further: Mechanical heart valve prosthesis superior to biological

More information: Natalie Glaser et al. Prosthetic Valve Endocarditis After Surgical Aortic Valve Replacement, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.117.028783

Journal reference: Circulation

Provided by: Karolinska Institutet

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Fewer infections in mechanical heart valves - Medical Xpress

COLUMBIA The MU International Institute of Nano and Molecular Medicine was closed June 30 as part of the UM System's cost-cutting measures.

The institute, at 1514 Research Park Drive off Providence Road, has been on campus since 2009.The decision to close the institute was made last month,MU spokesman Christian Basi wrote in an email.

MU broke ground on the $10 million institute in 2008. The future of the building is still to be determined, but it is likely to be used as a research facility, Basi wrote.

Next semester, teams studying biomedical innovations and disease therapeutics will be in the building, Basi wrote.

The closure will affect 17 full and part-time employees through a combination of layoffs and contract non-renewals, Basi said. MU expects to save about $1.5 million annually.

Reasons for the institutes closure included its substantial operating expenses, as well as the lack of grant funding it has received in recent years, Basi wrote.

Frederick Hawthorne, recipient of the prestigiousNational Medal of Science, for his work on the element boron, had been the director since 2008.

He was given the medal in 2012 by President Barack Obama and is the only MU researcher to have ever received the award,according to earlier Missourian reporting.

The institute studied nanotechnology and how to apply it to fight diseases. Nanotechnology is the manipulating of matter on a tiny scale, less than 100 nanometers. A nanometer is one-billionth of a meter or .000000001 meter.

Hawthorne used the technology to manipulate the element boron in an attempt to combat cancer, arthritis and other illnesses.

Theinstitute's webpagedescribes it as "thestrongest research facility for the development of boron neutron capture therapy of cancer in the world."

Hawthorne was lured to MU from UCLA, where he had worked since 1969, in part because of the institute and the reactor it housed, which is among the best in the world for academic research,according to earlier Missourian reporting.

He is still an employee of MU at this time, though his ongoing role is unclear.

Supervising editor isJeanne Abbott.

Read the rest here:

$10 Million Medical Research Institute Closed by MU - KBIA

COLUMBIA, Mo. The University of Missouri System has closed its $10 million medical research institute as part of an effort to cut costs.

The decision to close the International Institute of Nano and Molecular Medicine will affect 17 full-time and part-time employees through layoffs and contract non-renewals, university spokesman Christian Basi told the Columbia Missourian in an email.

The institute was closed June 30 because of its significant operating expenses and its lack of grant funding in recent years, Basi said.

The university broke ground on the institute in 2008. The institute studied how to apply nanotechnology to fighting diseases.

Frederick Hawthorne had been the director of the institute since it opened. He used nanotechnology to manipulate boron to try to find a way to combat cancer, arthritis and other illnesses. He was awarded the National Medal of Science by President Barack Obama in 2012.

The university expects to save about $1.5 million annually with the institute's closing. Basi said the building will likely be used as a research facility and that teams studying biomedical innovations and disease therapeutics will be in the facility next semester.

The school is still recovering from student protests in fall 2015 over the administration's handling of racial issues and the subsequent resignations of the system president and chancellor of the Columbia campus. Freshman enrollment subsequently dropped.

Original post:

University of Missouri research institute closes amid cuts - Manhattan Mercury (subscription)

COLUMBIA The MU International Institute of Nano and Molecular Medicine was closed June 30 as part of the UM System's cost-cutting measures.

The institute, at 1514 Research Park Drive off Providence Road, has been on campus since 2009.The decision to close the institute was made last month,MU spokesman Christian Basi wrote in an email.

MU broke ground on the $10 million institute in 2008. The future of the building is still to be determined, but it is likely to be used as a research facility, Basi wrote.

Next semester, teams studying biomedical innovations and disease therapeutics will be in the building, Basi wrote.

The closure will affect 17 full and part-time employees through a combination of layoffs and contract non-renewals, Basi said. MU expects to save about $1.5 million annually.

Reasons for the institutes closure included its substantial operating expenses, as well as the lack of grant funding it has received in recent years, Basi wrote.

Frederick Hawthorne, recipient of the prestigiousNational Medal of Science, for his work on the element boron, had been the director since 2008.

The institute studied nanotechnology and how to apply it to fight diseases. Nanotechnology is the manipulating of matter on a tiny scale, less than 100 nanometers. A nanometer is one-billionth of a meter or .000000001 meter.

Hawthorne used the technology to manipulate the element boron in an attempt to combat cancer, arthritis and other illnesses.

The institute's webpagedescribes it as "thestrongest research facility for the development of boron neutron capture therapy of cancer in the world."

Hawthorne was lured to MU from UCLA, where he had worked since 1969, in part because of the institute and the *MU Research Reactor it used, which is among the best in the world for academic research, according to earlier Missourian reporting.

He is still an employee of MU at this time, though his ongoing role is unclear.

Read more here:

$10 million medical research institute closed by MU - Columbia Missourian

Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure the disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, researchers have discovered that the molecule CD44s seems to give cancer cells a survival advantage. In the lab, eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib. The study appears in the Proceedings of the National Academy of Sciences.

Treatment with erlotinib attempts to kill cancer cells by inhibiting EGFR signaling, a cellular mechanism that is hyperactive in most cases of glioblastoma multiforme and associated with poor prognosis, said senior author Dr. Chonghui Cheng, associate professor of molecular and human genetics and of molecular and cellular biology at Baylor College of Medicine. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance.

Erlotinib can inhibit EGFR signaling but in time cancer cells become resistant to the treatment, in part because other molecules can compensate for the lack of EGFR activity.

Increasing evidence also suggests that EGFR and related signaling mechanisms do not act alone. Another molecule present in a number of cancers, CD44s, seems to be involved in sustaining those cancer-promoting mechanisms, but how this happens remained a mystery.

CD44s gives cancer cells a survival advantage

In this study, we discovered a mechanism by which CD44s helps maintain the EGFR signaling activated in glioblastoma multiforme, said Cheng, who also is a professor in the Lester and Sue Smith Breast Center at Baylor, part of the NCI-designated Dan L Duncan Comprehensive Cancer Center. Working with a number of cancer cells grown in the lab, we determined that CD44s on the cell surface can enter the cell and prevent the digestion of EGFR, thus sustaining the activity of the signaling cascade that gives the cells a survival advantage.

Cheng and her colleagues have shown that CD44s holds a strategic place from which it can influence not only EGFR, but also a number of other signaling cascades that are important for cancer cell survival.

If we remove CD44s from the cell surface, we also can reduce the appearance of other molecules that could help cancer cells sustain their growth by compensating for the lack of EGFR activity, Cheng said.

Importantly from the therapeutic point of view, the researchers also found that removing CD44s from cancer cells in culture and treating them with erlotinib resulted in higher cancer cell deaths than treating with erlotinib alone. Cheng and colleagues anticipate that CD44s might also play a similar role in other types of cancer in which EGFR signaling is involved. This opens the possibility that targeting CD44s could potentially reduce the growth of many types of cancer, not just glioblastoma.

Researchers have been focused on developing inhibitors of EGRF and related pathways. Instead, we want to find novel approaches to boost the activity of inhibitors already available, and removing CD44s is a good example of how this could be done, said co-author Sali Liu, a graduate student in the Cheng lab. Our work suggests that in the future, physicians and scientists might approach cancer treatment in a different way. For example, instead of deciding on a treatment based on the type of breast cancer a patient has, they might choose a treatment according to the type of mechanism that helps this particular cancer grow, regardless of the type of cancer it is.

Other contributors to this work include Wei Wang, Honghong Zhang, Chung Kwon Kim, Yilin Xu, Lisa Hurley, Ryo Nishikawa, Motoo Nagane, Bo Hu, Alexander Stegh and Shi-Yuan Cheng. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Northwestern University, Saitama Medical University and Kyorin University.

This research was supported in part by grants from the National Institutes of Health, the Northwestern University Brain Tumor Institute and a Brain Cancer Research Award from James S. McDonnell Foundation. Further support was provided by a Zell Scholarship at Northwestern University and the Cancer Prevention Research Institute of Texas.

Originally posted here:

How CD44s gives brain cancer survival advantage - Baylor College of Medicine News (press release)