One of the more uncomfortable symptoms of a cold and one of the most common is a sore throat. What starts as an annoying scratch can worsen overnight, making simple tasks such as eating, drinking water and talking really painful. While you might not be able to rid yourself of pain entirely, there are a few things you can do to ease your discomfort.

Is It a Cold or the Flu? How to Tell the Difference

Gargle with salt waterGargling with salt water might seem like it would make things worse, but it could really help you feel better. The saltwater solution helps to reduce inflammation by drawing mucus out from your throat and calming swelling. To make the solution, simply combine a half-teaspoon of table salt in 8 ounces of warm water and stir until the salt dissolves. Then, gargle the solution for several seconds before spitting it out. You can repeat this throughout the day as needed.

Suck on a menthol-flavored lozengeThroat lozenges can help, too, for a few reasons. They contain menthol, which partially numbs the tissue in your throat. Additionally, they increase the amount of saliva in your mouth, which keeps your throat lubricated to prevent scraping.

Stay hydratedAbove all, when youre sick it is crucial to stay hydrated. When youre dehydrated, in addition to the other side effects of dehydration, your body cant produce enough saliva and mucus to keep your throat lubricated. This can worsen inflammation. Sip on water and other hydrating beverages all day long. In particular, you may want to try loading up on the best drinks to help fight the flu, which also work on fighting the common cold.

Drink warm tea with honeyDrinking a cup of warm tea mixed with honey can help to temporarily ease pain. The tea keeps you hydrated while also providing antioxidants, which can be anti-inflammatory and work to protect against damage from free radicals. Chamomile tea in particular, according to a review in Molecular Medicine Reports, helps to lubricate the throat and reduce inflammation. Adding a spoonful of honey can make this even more of an effective pain reliever. According to research published by Canadian Family Physician, honey can reduce throat discomfort in both children and adults. However, its crucial that you drink the tea warm, not hot. Drinking tea while its too hot will further irritate the area.

Hopefully with one of these remedies, you can feel a little better during your cold. After all, a sore throat is just one of the first symptoms youre likely to experience when you catch a cold.

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The Best Ways to Soothe a Sore Throat - Yahoo Lifestyle

CIL Management Consultants has enjoyed rapid growth in the US since it established its US team in Chicago a year ago. The growth has been driven by new mandates for market reviews, commercial due diligence, and corporate strategy engagements to support private equity and management teams across a range of sectors.

The team has trebled in size over the past year and as a result has moved to new offices at the Citadel Center in Chicago, which provides room to grow as the firm continues to recruit experienced consultants across all sectors.

Recent projects include vendor commercial due diligence to support Leeds Equity Partners (New York) sale of Project Management Academy to Morgan Stanley Capital Partners. Project Management Academy is a provider of training and exam preparation services for project management professionals.

CIL also provided commercial due diligence to support Five Arrows Capital Partners' (New York) investment in Virginia-based Averhealth, which provides drug testing and laboratory services. Averhealth serves more than 1,800 courts and probation services across 26 states in the US.

CIL also supported Fishawack Group's acquisition of Dudnyk, providing commercial due diligence. Fishawack, backed by LDC, provides communications services to the global pharmaceutical industry. Philadelphia-based Dudnyk is an advertising agency focused on rare disease, oncology, and molecular medicine.

The consulting firm hasalso supported clients with market studies and growth strategy support across a range of other areas, including gyms, testing and inspection services, and smart building technology.

Rebecca Pigula, Principal at CIL Management Consultants, commented: CIL has enjoyed an extremely successful first 12 months in the US, providing advice to clients across a range of sectors. As a result, we are building the team to ensure that we continue to deliver the excellent service and advice that is at the heart of our business.

In a market environment where competition for prize assets is increasingly fierce, our focus on private equity, understanding of investment considerations, evidence-driven approach, and deep sector insight are all aspects that have been well-received in the US. Were looking forward to supporting our growing number of US clients to acquire and maximize the success of their portfolio companies in the years to come.

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CIL Management Consultants enjoys growth in the US - Consulting.us

09 November 2019

Much of the news from the annual National Cancer Research Institute (NCRI) conference, held in Glasgow this week, was about being able to diagnose cancer through blood tests a liquid biopsy - and the role of AI in assisting with this. To get a full overview of what was new at conference have a lookherehowever the piece most relevant to our community is the development of anAI blood test that can spot signs of brain tumour to speed up diagnosis.

Scientific updates from Sweden and Germany below

Pharmaceutical updates from the US and Israel now;

Immunologically cold tumours, are cancers that contain few infiltrating T cells and do not provoke a strong response by the immune system. Immunologically hot tumours contain high levels of infiltrating T cells and more antigens, making them more recognizable by the immune system and more likely to trigger a strong immune response.Cancers that are classically immunologically cold include glioblastomas.

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Weekly pick of Neuroscience news from around the world - Brain Tumour Research

Dr. Nancy Brown

Dr. Nancy J. Brown, recently appointed as the C.N.H. Long Professor of Internal Medicine, is an internationally renowned educator, investigator, and clinician. Her appointment will be effective Feb. 1, pending approval by the School of Medicine Board of Permanent Officers.

In September, Brown was named the next dean of the Yale School of Medicine. She will assume that post on Feb. 1.

A Yale College graduate, Brown is currently the Hugh Jackson Morgan Professor and chair of the Department of Medicine at Vanderbilt University.

Brown majored in molecular biophysics and biochemistry at Yale and earned her medical degree at Harvard University. After completing internship and residency programs at Vanderbilt University, she joined its faculty, engaging in both clinical care and research.

While taking on increased leadership responsibilities and mentoring scores of Vanderbilt students, residents, and fellows, Brown has led a research program in cardiovascular pharmacology, which has been continuously funded by the National Institutes of Health since 1993. Among her research contributions, she has defined the molecular mechanisms through which commonly prescribed blood pressure and diabetes drugs affect the risk of cardiovascular and kidney disease. She has continued to care for patients, especially those with resistant and secondary forms of hypertension, and to mentor the next generation of physician-scientists.

Since becoming leader of Vanderbilts Department of Medicine in 2010, Brown expanded mentorship resources for trainees and faculty members who concentrate on research and established a career development program for faculty members who focus on clinical work. During her tenure, there was an increase in the number of women and members of underrepresented groups in medicine, both on the faculty and in leadership positions.

Throughout her career, Brown has focused on medical education and mentoring career development. She founded and directed the Vanderbilt Master of Science in Clinical Investigation program to promote the advancement of patient-oriented researchers. She also developed the Elliot Newman Society to shorten time-to-independence for physician-scientists. She is an elected member of the Vanderbilt Academy for Excellence in Teaching and has received many mentorship awards.

Brown serves on a number of editorial boards and national and international scientific advisory committees, providing guidance on the development of research programs and educational initiatives. She has received numerous awards for her achievements, including election to the American Society for Clinical Investigation, the Association of American Physicians, and the National Academy of Medicine.

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Dr. Nancy Brown named the Long Professor of Internal Medicine - Yale News

Handheld electrochemical sensors are part of the daily routine for millions of people with diabetes around the globe who monitor their blood sugar levels with electric glucometers. While such sensors have revolutionized at-home medical testing for diabetics, they have not yet been successfully applied to diagnosing other conditions. Sensors like glucometers detect glucose in blood based on the activity of an enzyme, and there are only a limited number of enzymes that can be used to sense biomarkers of human disease. An alternative detection strategy based on binding events between antibodies and their molecular targets have been investigated to expand the use of electrochemical sensors for medicine, but these sensors fall victim to the rapid accumulation of "fouling" substances from biological fluids on their conductive surfaces, which deactivate them. Existing antifouling coatings are difficult to mass-manufacture, suffer from quality and consistency issues, and are not very effective.

Now, a new diagnostic platform technology developed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University known as "eRapid" enables the creation of low-cost, handheld electrochemical devices that can simultaneously detect a broad range of biomarkers with high sensitivity and selectivity in complex biological fluids, using as little as a single drop of blood. The technology is described in the newest issue of Nature Nanotechnology.

"As long as an antibody exists for a given target molecule, eRapid can detect it," said co-author Pawan Jolly, Ph.D., a Senior Research Scientist at the Wyss Institute. "By solving the biofouling problem with a simple yet robust design, we are now able to easily mass-produce biochemical sensors for a wide variety of applications at low-cost."

The challenge in developing the antifouling coating was to prevent accumulation of off-target substances on the sensor's metal electrodes while still maintaining their conductivity to allow sensing of the target. After experimenting with a variety of recipes, the research team developed a simple, porous, 3D matrix consisting of bovine serum albumin (BSA) crosslinked with glutaraldehyde and supported by a network of conducting nanomaterials, such as gold nanowires or carbon nanotubes. The small pore size of the BSA matrix size-excludes proteins found in blood and plasma, and the BSA's weak negative charge prevents the strong adhesion of positively charged biomolecules onto the sensor.

When the researchers tested their nanomaterial-coated sensors in human blood serum and plasma, they retained more than 90% of their ability to detect signal even after being stored for one month in those biofluids, whereas sensors coated with best previously published anti-fouling coatings lost significant signal sensitivity when incubated for one hour, and were completely inactivated after one day.

To functionalize the coated sensors, the researchers attached antibodies to the surface of the nanomaterial coating on top of the electrode, and used a "sandwich assay" to convert the antibody binding event into a chemical signal that precipitates onto the electrode surface, thereby generating an electric signal. The magnitude of the electrical signal directly correlates to the amount of the precipitate produced, and thus to the number of target molecules bound to the antibodies, allowing the concentration of the target to be measured.

The team demonstrated the commercial utility of this approach by creating a multiplexed sensor with three separate electrodes, each coated with the BSA/gold nanowire matrix and a layer of antibodies against a specific clinically relevant target molecule: interleukin 6 (IL6), insulin, or glucagon. When they incubated the sensor with the respective target molecules in undiluted human plasma, they observed excellent electrical signals with picogram-per-mL sensitivity. Conversely, electrodes coated with a published "PEG-SAM" anti-fouling coating failed to produce distinct signals, indicating that they had been irreversibly fouled by off-target molecules in human plasma samples. In addition, the BSA/gold-nanowire-coated sensors can be washed and reused multiple times with minimal signal loss, allowing serial monitoring of biomarkers easily and at low cost.

Since then, the Wyss team has been able to detect more than a dozen different biomarkers ranging from 100 Da to 150,000 Da in size with eRapid, and they are continuing to experiment with conductive nanomaterials to optimize the electrode coating and the system's performance, as well as reduce the cost even further. They are actively exploring commercialization options for eRapid in the handheld point-of-care diagnostics space, but also hope to extend the coating and sensor technology platform to other targets and contexts, including in-hospital diagnostics, environmental toxin sensing, small molecule detection, and implantable medical devices.

Interestingly, the team - led by the Wyss Institute's Founding Director Donald Ingber, M.D., Ph.D. - did not originally set out with this goal in mind. This work began because they needed to simultaneously detect multiple biomolecules produced by various types of tissue cells growing within human Organs-on-Chips to non-invasively assess their function and inflammatory status over time. The tiny volume of liquid outflows from the chips' channels necessitated highly sensitive sensors that could also be multiplexed, which led to the creation of the current technology.

"eRapid emerged from pursuing one innovation that led to another that has the potential to transform medical diagnostics. Hopefully, this simple technology will enable great advances in our ability to develop handheld diagnostic devices that can be used at home, as well as in pharmacies, ambulances, doctor's offices, and emergency departments in the near future," said Ingber who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at Harvard's John A. Paulson School of Engineering and Applied Sciences.

Reference:Sabat del Ro, J., Henry, O. Y. F., Jolly, P., & Ingber, D. E. (2019). An antifouling coating that enables affinity-based electrochemical biosensing in complex biological fluids. Nature Nanotechnology. https://doi.org/10.1038/s41565-019-0566-z

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Moving Diagnostics Out of the Lab and Into Your Hand - Technology Networks

Some gastrointestinal viruses need calcium. They need calcium ions to carry out several essential aspects of viral life, such as entry into host cells, genome replication and building new viruses to invade other cells. The cells invaded by viruses also use calcium. They use it as signals to regulate many of the cells own processes, but viruses can takeover cellular calcium signaling to satisfy their own needs.

This viral takeover involves, in many cases, the production of a viral protein called viroporin that acts like an ion channel redirecting cellular calcium signaling to serve viral functions. Medically important gastrointestinal viruses, such as rotavirus, require calcium for replication and use viroporins to gain control over cellular calcium signaling, but it has not been investigated whether other viruses that also cause severe gastrointestinal problems in people and animals, such as norovirus, do the same.

While she was working on her doctorate degree in the Graduate Program in Integrative Molecular and Biomedical Sciences at Baylor College of Medicine, Dr. Alicia Strtak took on the project to investigate whether Tulane virus, a calicivirus that is biologically similar to human noroviruses, required calcium for its replication. If so, how does it take over cellular calcium signaling?

Human noroviruses are the leading cause of acute gastroenteritis, a potentially life-threatening illness in every age group, said Strtak. There is great interest in developing effective therapies, but many aspects of how calicivirus, including norovirus, cause disease have not been made clear yet.

Studying norovirus has posed quite a challenge to researchers and, although much progress has been made to successfully culture it in the laboratory using human intestinal enteroid cultures, there is still much to be gained from studying other caliciviruses, such as Tulane virus, that are closely related to norovirus and are easier to study in the lab.

During this project, Strtak worked in the laboratory of Dr. Joseph Hyser, assistant professor of molecular virology & microbiology at Baylor, and used Tulane virus as a model system for norovirus.

We think that Tulane virus has features that make it a good candidate for a model of human norovirus. These viruses share biologic and genetic characteristics, for instance, both organize their genomes in the same manner, infect the same type of cells (intestinal epithelia) and cause a disease the presents in a similar way, Strtak said. In addition, Tulane virus can be grown in the lab in systems that facilitate investigation into the pathways it takes over during infection.

Strtak, Hyser and their colleagues combined cell culture, biochemistry and calcium imaging techniques to answer the following question, what are the key factors Tulane virus needs to achieve robust and efficient replication? To address the question, they focused on how Tulane virus reshaped the hosts calcium signaling during infection.

First, we discovered that Tulane virus does need intracellular calcium to replicate. Without it, the virus replicates poorly, Strtak said. We also found that the calcium came from cellular storage in the endoplasmic reticulum and, to gain access to this source of calcium, Tulane virus seemed to use its protein NS1-2.

The researchers found evidence that Tulane virus NS1-2 protein acted as a viroporin, an ion channel that disrupted cellular calcium signaling by triggering its flow from the endoplasmic reticulum, where it was stored, to the cytoplasm where viral replication took place.

Looking to determine whether norovirus might be using a similar strategy to infect epithelial cells, Strtak and her colleagues compared Tulane virus NS1-2 protein and the human norovirus protein in their ability to disrupt calcium signaling. They found that norovirus NS1-2 protein induced changes in cellular calcium signaling that were similar to those triggered by Tulane virus NS1-2 protein. (see video above)

This is the first piece of functional evidence suggesting that the function that we identified in the Tulane virus may also exist in human norovirus, Strtak said.

Viral ion channels are very difficult to identify. Strtaks work shows that with a little bit of innovation, ingenuity and willingness to explore outside the clinically relevant system, it is possible to find a suitable experimental model that enables researchers to achieve the initial broad characterization and find relevant information about complex biological systems. We hope that the information we have found here also helps other researchers who study other aspects of viral infection, said Hyser, a member of theAlkek Center for Metagenomics and Microbiome Researchand theDan L Duncan Comprehensive Cancer CenteratBaylor.

Learn all the details of this work in the journal mSphere.

Other contributing authors include Jacob L. Perry, Mark N. Sharp, Alexandra L. Chang-Graham and Tibor Farkas. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Louisiana State University School of Veterinary Medicine, Louisiana Animal Disease Diagnostic Laboratory and Augustana College.

Financial support was provided by National Institutes of Health grants (R01DK115507, R21AI137710, F30DK112563, DK56338 and CA125123) and Baylor College of Medicines Medical Scientist Training Program. Additional support came from the Integrative Molecular and Biomedical Sciences Graduate Program (T32GM008231), CPRIT (RP150578 and RP170719), the Dan L. Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.

By Ana Mara Rodrguez, Ph.D.

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'Give me the calcium!' Tulane virus takes over cellular calcium signaling to replicate - Baylor College of Medicine News

Next, the team tested 78 approved or investigational cancer drugs against each of the cell lines, selecting the compounds based on their effectiveness in other solid-tumor cancers. After a series of initial experiments to gauge their effectiveness, 12 of the drugs were prioritized for deeper analysis.

Among these, the research group found six drugs that showed promising results against tumors with particular molecular features suggesting the approach is a solid first step toward developing robust biomarkers of drug response in triple-negative breast cancer.

Many other breast cancer subtypes are defined by the pathways that you would use to target them for example, youd treat HER2-positive breast cancer with a HER-2 inhibitor, says senior study author Sofia Merajver, M.D., Ph.D., a professor of internal medicine and epidemiology at the U-M. Triple-negative breast cancer is defined by its lack of hormone receptors and HER2 expression, which makes it much more difficult to target. We needed to do better.

Since cancer often quickly develops resistances against individual drugs, the researchers also wanted to use their multi-omic approach to look for ideal combinations of drugs.

The idea is that if we find a marker that is particularly high in drug-resistant cells, we might be able to make the cells more responsive to treatment by adding a drug that also targets that marker, says senior study author Matthew Soellner, Ph.D., an assistant professor of internal medicine and chemistry at U-M, and an affiliate faculty member of the U-M Life Sciences Institute. Ultimately, we found we could make most of the cell lines more sensitive to our target drug it worked better than we had hoped for.

The research was supported by the National Institutes of Health (1R21CA218498), the Breast Cancer Research Foundation, Tempting Tables, The Rose Run, and the Kathy Bruk Pearce Research Fund of the U-M Rogel Cancer Center.

Additional authors include Eric J. Lachacz, Nathalie M. Vandecan, Peter J. Ulintz, Liwei Bao, John P. Lloyd, Joel A. Yates and Aki Morikawa, all of U-M.

Paper cited: Molecular determinants of drug response in TNBC cell lines, Breast Cancer Research and Treatment. DOI: 10.1007/s10549-019-05473-9

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Approach to Personalizing Treatment of Triple-Negative Breast Cancer Shows Promise in Cell Lines - Michigan Medicine

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Newswise New Brunswick, N.J., November 11, 2019 Rutgers Cancer Institute of New Jersey researcher Hossein Khiabanian, PhD, has received a $600,000 Translational Award from the V Foundation for Cancer Research to study chronic lymphocytic leukemia (CLL) with the aim of developing research models that may help investigators better understand how CLL cells are influenced by new therapies.

The most common leukemia in the Western world, CLL starts in the bone marrow in a type of white blood cell known as B-lymphocytes. Standard chemotherapy has been successful in treating most patients; however, it is not effective for some patients with specific DNA changes in their leukemia cells. In previous work by Dr. Khiabanian and colleagues, advanced DNA sequencing uncovered mutations that changed the function of a gene called TP53. These mutations could be detected in only a few leukemia cells at initial CLL diagnosis, but would be present in a majority of cells in patients whose CLL returned after treatment with chemotherapy.

To treat such high-risk patients, new drugs have been developed that disrupt processes used by leukemia cells to interact with their environment. One of these drugs, which has shown significant activity in CLL, is ibrutinib. Similar to resistance against chemotherapy, some cells may have alterations that stop this drug from working. As a result, these cells are not killed and can result in the recurrence of CLL. As such, there is a need to better understand these mutations as well as changes in gene expression so that better treatment strategies can be developed. notes Khiabanian, who is part of Rutgers Cancer Institutes Genome Instability and Cancer Genetics Research Program and an assistant professor of pathology and laboratory medicine at Rutgers Robert Wood Johnson Medical School.

He adds, I am grateful for the V Foundation for Cancer Research in its support of this project, which is in line with our labs goal of designing experimental and computational methods that help characterize molecular diversity in small population of cells early in their evolution and transformation.

In this project, the Khiabanian lab will work with the Institute of Oncology Research (Bellinzona, Switzerland) as well as Rutgers Cancer Institute of New Jerseys Hematologic Malignancies Program to analyze patient samples collected during treatment in a clinical trial. Highly sensitive experimental approaches will be applied to thousands of single leukemia cells to develop models that may help describe how CLL cells behave and change under new therapies.

The project period runs through October 2022.

About Rutgers Cancer Institute of New Jersey

As New Jerseys only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute, along with its partner RWJBarnabas Health, offers the most advanced cancer treatment options including bone marrow transplantation, proton therapy, CAR T-cell therapy and complex robotic surgery. Along with clinical trials and novel therapeutics such as precision medicine and immunotherapy many of which are not widely available patients have access to these cutting-edge therapies at Rutgers Cancer Institute of New Jersey in New Brunswick, Rutgers Cancer Institute of New Jersey at University Hospital in Newark, as well as through RWJBarnabas Health facilities.

Along with world-class treatment, which is often fueled by on-site research conducted in Rutgers Cancer Institute laboratories, patients and their families also can seek cancer preventative services and education resources throughout the Rutgers Cancer Institute and RWJBarnabas Health footprint statewide. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-8013 or visit http://www.cinj.org/giving.

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Examining Molecular Evolution and Impact of Treatment in a Common Form of Leukemia - Newswise

Before the Second World War, Max and Gertrud Hahn of Gttingen, Germany had a Judaica collection that was considered one of the most significant private collections in pre-war Europe, rivalling those of the Rothschild and Sassoon families.

Handout

For about 20 years, the boxes sat in the storage room of Michael Haydens Vancouver home, unopened. He had found them in a basement room behind the garden of his fathers home in Cape Town, South Africa after his sudden death in 1984. They had been shipped there, originally from Germany and had never been opened by his father either, not since the boxes had arrived after the Second World War. There were about 15 of them, all from the 1940s. The information inside would give Hayden one of the worlds foremost geneticists a new purpose in life.

I could feel the gravity of what was in there, Hayden, 67, says. I knew there was going to be a big burden and an obligation to come from opening them. And I wasnt ready. I think I was fearful too. I knew this was going to be a burden, and a very personal burden.

Gertrud and Max Raphael Hahn, Haydens grandparents, were wealthy residents of Gottingen, Germany, a university city that has been home to dozens of Nobel Prize laureates. Max ran a successful business that included a leather factory and a real estate empire; the Hahns owned about 40 per cent of the buildings in the town. They were prominent members of the Jewish community Max was president of the synagogue and deeply patriotic Germans: Max had been a senior procurement official for the German army during the First World War. And they were great collectors of art, fine furniture, antiques and a collection of Judaica that is said to have rivalled those of the Rothschilds and Sassoons.

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At about 2 a.m. on Nov. 10, 1938, Nazis armed with axes broke into the Hahn home, smashing doors and windows, destroying their belongings and forcing Max and Gertrud half-naked into the street, while bystanders hissed and yelled, calling them filthy Jews and pig Jews. Their home was ransacked and many of their possessions were stolen.

This horrific night became known as Kristallnacht the night of broken glass a government-sanctioned series of Nazi pogroms in Germany and Austria that saw hundreds of synagogues burned, Jewish businesses destroyed and Jewish cemeteries desecrated. There were dozens or hundreds of deaths (the number is disputed) and some 30,000 Jewish men sent to prisons and concentration camps.

Max was one of them.

He was sent to jail for nearly nine months, during which much of his property, including his silver Judaica collection, was confiscated. The family also sold possessions to the local museum, under duress, as they were stripped of their wealth and livelihood.

Even while in prison, Max worked for the return of his prized Judaica items, thinking they could help fund the familys future life somewhere outside Germany. He was not successful.

There were more pressing concerns. In 1939, the Hahns managed to get their children, Rudolf and Hanni, 19 and 17, to safety in England. In early 1941, they shipped some precious items that remained, including a piano and violin, and many documents to Sweden and Switzerland for safe storage in neutral countries.

By the time Max and Gertrud tried to leave Germany themselves, later that year, it was too late. In December, 1941, they were deported by train to a concentration camp in Riga, Latvia. Gertrud, who was diabetic and without her medication, may have died on the way in the cattle cars. Its believed Max was shot in the Bikernieki Forest in March, 1942, and buried in a mass grave, like thousands of other murder victims. No records of their deaths exist.

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In three-dimensional silver, Jacob's Cup depicts three scenes from the biblical story of Jacob. The date of its carving, 1757, is engraved on the base.

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Michael Hayden grew up without grandparents. He had a vague notion that they had been killed during the Second World War, but he knew no details about their deaths and very little about them.

Those boxes, left unopened for all those years, held answers to questions he didnt know he had. One night in the mid-2000s, at around 3 a.m., he went down the stairs of his Vancouver home and started opening them. Hes not sure what compelled him that night. Was it his state of mind? Was he ready to confront the past? Did his curiosity finally win out over his fear? In any case, he felt ready to know more.

The containers held thousands of documents that painted a rare and urgent picture of life in Nazi Germany for a prominent Jewish family his own.

Inside, Hayden found about 50 letters sent during the war between Max and Rudolf; petitions that Max had submitted in response to anti-Semitic laws enacted by the Nazis; and photographs and lists of the art and other objects that had been stolen from the Hahns or sold under duress while under Nazi rule.

Hayden, who doesnt speak German, hired a historian who is fluent in the language to help him deal with the contents. The documents were a treasure trove of information about his family, but they also contained clues and evidence about his grandparents stolen property.

Thats when he decided he would search for it.

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The first time Hayden visited Gottingen, it was long before he knew about the boxes or much of anything about his fathers life. He was in his 30s, travelling with his father. They visited a childhood friend of Rudolfs, who was very welcoming. It was the first time Michael had ever heard his father speak German. The man brought out a photo album from their shared childhoods. There they were as kids. Then, a few pages in, there was a photo of his fathers friend, in an SS uniform.

Since opening the boxes, Hayden has been working with the Gottingen Museum and other German institutions for several years, looking for what is left of his familys treasures. There have been a lot of obstacles restitution can be a fraught endeavour but a few dozen items have been identified as having belonged to the Hahns. Last year, in a moving ceremony, the first of these treasures was returned a remarkable silver gilt kiddush cup one of very few items of Judaica seized by the Nazis that had not been melted down for the precious metal. The cup was discovered in a basement vault at a Hamburg museum in 2018 and returned to the family last November.

I felt a sense of great triumph and justice, Hayden says. It was a great occasion to restore that and to give some respect to [my grandfather] and an item that I knew he loved and he must have handled.

In three-dimensional silver, the cup depicts three scenes from the biblical story of Jacob. The date of its carving, 1757, is engraved on the base. Theres a rude red number splashed next to it, assigned by one of its Nazi thieves.

This is one of the items being displayed for the first time at an exhibition that opened on Friday at the Vancouver Holocaust Education Centre. Treasured Belongings: The Hahn Family and the Search for a Stolen Legacy includes many extraordinary items that belonged to the Hahns, including a 17th-century Passover Haggadah and precious secular art, such as an original work by the artist Max Liebermann.

The museum was interested in creating the exhibition not just because of the Hahns compelling, tragic story, but also because of the contemporary resonance. Their story is a lens through which to view reconciliation and repatriation in the aftermath of catastrophic injustice.

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The show also includes historical context, as well as family photographs and original letters. In one, written right after Kristallnacht Nov. 11, 1938 Rudolf, writing from Hamburg, tries to comfort and encourage his mother back in Gottingen. He ends it with a quote. We will not let this get us down!

Michael Hayden is a world-renowned medical researcher who has accumulated many titles and accolades over the course of his career. He is the founder and director emeritus of the Centre for Molecular Medicine and Therapeutics at the Department of Medical Genetics at BC Childrens Hospital and the University of British Columbia, and Killam Professor and Canada Research Chair in Human Genetics and Molecular Medicine. He is one of the worlds leading experts on Huntingtons disease. He has been named to the Order of Canada, the Order of British Columbia and the Canadian Medical Hall of Fame, as well as many other honours. When I asked him about if he has unwittingly inherited characteristics from the grandparents he never knew, he paused and then said yes.

And some of it is deeply comforting. Because Im a deep collector and partly what Ive done, in the eighties I started collecting DNA and body parts from patients who died of certain genetic diseases. And I did it very methodically. Today we have the largest DNA bank and organ bank in the world that is supporting global research into Huntington disease.

He also collects other things including, similar to his grandfather, Haggadot (the books used during the Passover Seder).

What motivates Haydens quest for his familys belongings is not financial restitution or even the lost items themselves. He was eager to learn about Max and Gertrud and illuminate their identities, their individuality.

Im really driven from a perspective of wanting to rescue my grandparents from obscurity and wanting to restore them to their particularity and distinctiveness and to rescue them from complete anonymity, he says.

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These were just two of six million, my grandparents, but for me I wanted to get away from generalizations. Im really just trying to understand: Whats the genetic legacy? Whats the legacy of courage and personality? Who were these people? And giving them a face.

Thats whats driving me. And somehow its also a search for who I am.

Treasured Belongings: The Hahn Family and the Search for a Stolen Legacy is at the Vancouver Holocaust Education Centre until Nov 27, 2020.

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Family treasures looted during Germanys Kristallnacht on display for the first time at Vancouver exhibition - The Globe and Mail

One of the worlds most pre-eminent molecular diagnostics specialists has boosted the board of Cambridge digital health company Congenica.

Dr Heiner Dreismann has accepted roles as non-executive director and senior independent director. He has over 35 years experience in the global leadership of high-growth life sciences and healthcare businesses.

Dr Dreismann was previously president and CEO of Roche Molecular Systems, the world leader in molecular diagnostics, where he made significant contributions to the organisational and financial growth of the companys molecular business area.

Other senior positions he held in Roche included head of global business development, Roche Diagnostics and member of Roches global diagnostic executive committee.

Since leaving Roche he has served on the board of a number of private and public biotech and healthcare companies.

Dr Dreismann said: I am excited to join the board of Congenica, a company at the forefront of healthcare innovation that is bringing medical meaning to genomic data.

I look forward to helping the company in its next stage of growth and in supporting healthcare professionals with its technologies to expedite the diagnosis and treatment of conditions affecting millions of people worldwide.

Congenica enables genomic medicine with what it markets as the worlds leading clinical decision support platform for the interpretation of complex genomic data.

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Molecular diagnostics supernova on board at Congenica - Business Weekly

Perth researchers discover way to enhance immune response and drug treatment of stiff, difficult-to-treat solid cancers

Some solid tumours are so stiff they make a cracking noise when they are cut by researchers on the laboratory bench.

The fibrous nature of liver, pancreatic and some breast cancers make them difficult to treat. However, five years of research by a team of Perth scientists has resulted in the development of a novel, non-toxic agent that can deliver drugs to the cancer cells embedded in the fibrous matrix.

Research published in EMBO Molecular Medicine showed a non-toxic therapeutic agent boosted immune cells to selectively remove the fibrous scar tissue allowing cancer treatments to reach their target.

Dr Juliana Hamzah, head of the Targeted Drug Delivery, Imaging and Therapy Laboratory at the Harry Perkins Institute of Medical Research said by breaking down the fibrous matrix of stiff tumours the patients own immune system paved the way for drug treatments to take effect.

The cancer is like a wound, and a way that our body tries to repair the wound is to grow a scar tissue around it, but that scar tissue makes it very difficult to get to the cancer cells to destroy them.

It is stiff, non-cellular, has very few blood vessels and impenetrable. The scar tissue is not only a physical barrier but it constricts blood vessels which are key pathways for delivering cancer treatment.

The barrier around some cancers, such as liver cancer, pancreatic cancer and some breast cancers is like barbed wire.

We have developed a non-toxic agent that does not affect surrounding healthy tissue.

The agent activates immune cells to release enzymes that digest the scar tissue. This allows more cancer killing immune cells to enter the tumour. Our results show that removal of the fibrous tissue dramatically eliminates the drug delivery barrier.

Tumours treated with the drug weve developed are more permeable to anti-tumour immune cells and cancer treatments, Dr Hamzah said.

The research data have been validated in four laboratories including the Harry Perkins Institute of Medical Research in Perth, the School of Engineering at The University of Western Australia, Sanford Burnham Prebys Medical Discovery Institute, California, USA, and the University California Davis, California, USA.

Dr Hamzah says that now the drug has been proven to have a positive impact on fibrosis, or scar tissue, she is investigating whether it can be used to prevent malignant cancer by treating the early stages of fibrosis in liver cancer.

If you take liver cancer, it doesnt start immediately as cancer, it starts as fibrosis, cirrhosis, which then develops into liver cancer.

Because chronic tissue fibrosis can lead to cancer we aim to investigate whether early treatment with our drug of the pre-cancerous stage, such as liver fibrosis, could prevent development of malignant cancer.

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Press Release: New drug that breaks down the 'barbed wire' around some cancers - PRWire

CHF 32 Million in Milestone Revenues

Multiple Upcoming Catalysts

Execution Across Clinical and Preclinical Neurodegenerative Development Pipeline

LAUSANNE, Switzerland, Nov. 13, 2019 (GLOBE NEWSWIRE) -- AC Immune SA (ACIU), a Swiss-based biopharmaceutical company with a broad clinical-stage pipeline focused on neurodegenerative diseases, today provided a business and clinical update and reported its consolidated financial results for the third quarter of 2019.

Prof. Andrea Pfeifer, Ph.D., CEO of AC Immune, commented: AC Immune, together with our leading pharmaceutical partners, is advancing one of the industrys broadest, most diversified development pipelines targeting neurodegenerative diseases. This quarter, we continued to demonstrate strong progress across our pipeline of potentially best-in-class small molecule, antibody, and vaccine therapeutics, as well as our cutting-edge diagnostic agents. This resulted in milestones achieved totaling CHF 32 million which were comprised of CHF 30 million from Eli Lilly and Company and EUR 2 million (CHF 2.2 million) from Life Molecular Imaging.

Prof. Pfeifer continued, We anticipate multiple catalysts in 2019 and 2020, highlighted by expected Phase 2 data for semorinemab, our anti-Tau antibody partnered with Genentech/Roche, which we anticipate will be the first Phase 2 data available for a Tau-targeted therapy in Alzheimers disease (AD). We also anticipate achieving further progress across our development pipeline with both early and late stage data readouts that we believe will build substantial value for the Company.

AC Immunes unique, multi-pronged approach is designed to address the full spectrum of neurodegenerative diseases. By selectively targeting misfolded pathological proteins both intracellularly and extracellularly, and by creating state-of-the-art diagnostic imaging agents that enable early detection of multiple disease pathologies and tracking of disease progression, AC Immune is pioneering a personalized medicine approach to deliver the right therapy to the right patient at the right time.

Research & Development Highlights

Analysis of Financial Statements for the Three and Nine Months Ended September 30, 2019

About AC ImmuneAC Immune SA is a Nasdaq-listed clinical-stage biopharmaceutical company, which aims to become a global leader in Precision Medicine for neurodegenerative diseases. The Company is utilizing two proprietary discovery platforms, SupraAntigenTMand MorphomerTM, to design, discover and develop small molecule and biological therapeutics as well as diagnostic products intended to diagnose, prevent and modify neurodegenerative diseases caused by misfolding proteins. The Company's pipeline features nine therapeutic and three diagnostic product candidates, with five currently in clinical trials. It has collaborations with major pharmaceutical companies including Roche/Genentech, Lilly and Janssen Pharmaceuticals Inc.

As a strategic leader in the field of neurodegenerative diseases, AC Immune has developed a five-point Roadmap to Successful Therapies for Neurodegenerative Diseases that recognizes the importance of treating earlier, targeting Tau, focusing on more homogeneous patient populations, precision medicine and exploring neuroinflammation as a target.

For further information, please contact:

Forward-looking statementsThis press release contains statements that constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical fact and may include statements that address future operating, financial or business performance or AC Immunes strategies or expectations. In some cases, you can identify these statements by forward-looking words such as may, might, will, should, expects, plans, anticipates, believes, estimates, predicts, projects, potential, outlook or continue, and other comparable terminology. Forward-looking statements are based on managements current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include those described under the captions Item 3. Key InformationRisk Factors and Item 5. Operating and Financial Review and Prospects in AC Immunes Annual Report on Form 20-F and other filings with the Securities and Exchange Commission. Forward-looking statements speak only as of the date they are made, and AC Immune does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law. All forward-looking statements are qualified in their entirety by this cautionary statement.

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Balance Sheets

Statements of Income/(Loss)

Statements of Comprehensive Income/(Loss)

Reconciliation of Income/(Loss) to Adjusted Income/(Loss) and Earnings/(Loss) Per Share to Adjusted Earnings/(Loss) Per Share

(a) Reflects non-cash expenses associated with share-based compensation for equity awards issued to Directors, Management and employees of the Company. This expense reflects the awards fair value recognized for the portion of the equity award which is vesting over the period.

(b) Reflects foreign currency remeasurement gains and losses for the period, predominantly impacted by the change in the exchange rate between the US Dollar and the Swiss Franc.

(c) Effective interest expense for the period relates to the accretion of the Companys convertible loan in accordance with the effective interest method.

(d) Change in fair value of conversion feature that is bifurcated from the convertible loan host debt with Lilly.

For the three and nine months ended September 30, 2019, adjustments increased net income and decreased net income by CHF 0.6 million and CHF 0.9 million compared with decreases to the net losses by CHF 1.9 million and CHF 3.0 million for the comparable periods in 2018, respectively. The Company recorded CHF 0.9 million and CHF 2.0 million for the three and nine months, respectively, for share-based compensation expenses. There were foreign currency remeasurement gains of CHF 0.3 million and remeasurement losses of CHF 0.3 million, respectively, related to foreign currency fluctuations. The Company recorded nil and CHF 1.4 million for amortization of effective interest for the three and nine months ended September 30, 2019, respectively. Finally, the Company recognized nil and a CHF 4.5 million gain for the change in fair value of the liability related to the conversion feature.

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AC Immune Q3 2019 Financial Results and Business Update - Yahoo Finance

Scientists have discovered a new bacteria-killing toxin that can prove beneficial in combatting diseases infected by superbugs, a study has revealed. According to the new study, this growth inhibiting enzyme is injected by bacteria into rival bacteria to gain a competitive advantage.

A team of researchers led by author John Whitney, assistant professor of the Department of Biochemistry and Biomedical Sciences at McMaster University, and co-author Mike Laub, professor of biology at the Massachusetts Institute of Technology (MIT), explained that bacteria secreted antibacterial molecules when they came across a toxin, and the new toxin was an antibacterial enzyme that scientists had never seen before.

Whitney and Ahmad after determining the molecular structure of this toxin realized that it resembled enzymes that synthesized a well-known bacterial signaling molecule called (p)ppGpp, which helps bacteria survive under stressful conditions such as exposure to antibiotics. Ahmad stressed the 3-D structure of this toxin was at first puzzling because no known toxins looked like enzymes that made (p)ppGpp, and (p)ppGpp itself was not a toxin.

The authors earlier thought the toxin might kill bacteria by overproducing harmful quantities of (p)ppGpp. The findings published in the journal Nature suggested Boyuan Wang, a postdoctoral researcher in the Laub lab who specializes in (p)ppGpp signalling and examined the activity of the newly discovered enzyme, as concluding the toxin instead produced a poorly understood but related molecule called (p)ppApp, which is somehow harmful to bacteria.

The researchers found that the rapid production of (p)ppApp by this enzyme toxin depleted cells of a molecule called ATP -- the energy currency of the cell -- whose exhaustion killed pathogen Pseudomonas aeruginosa. "This discovery has potential implications for developing alternatives to antibiotics, a global priority in the fight against antimicrobial resistance," stressed Charu Kaushic, scientific director of the CIHR-III and a professor of pathology and molecular medicine at McMaster.

The research concluded that it would be exciting to see whether other examples of this toxin were found across the bacterial domain or perhaps even in bacteriumhost interactions.

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Antibiotic resistance: Scientists discover new toxin that promises to fight it out finally - International Business Times, Singapore Edition

This Global Fluoroscopy & C Arms Market byData Bridge Market Researchbrings all the figures needed to corner the Global fluoroscopy and C-arms market by showing all the recent developments, product launches, joint ventures, mergers and accusations done by the key players and brands that are making a mark in the market. Besides it also pinpoints the market drivers and restraints with the help of SWOT analysis.

Global fluoroscopy and C Arms marketis expected to reach at a CAGR of 4.3% in the forecast period of 2018 to 2025.

The main perspective of the Fluoroscopy and Mobile C-Arms report is to support companies comprehend the customer in terms of approach, cultural trends, routine factors and how social framework impacts product selection and usage. It evaluates the quality of service that has been provided to the customer or to provide information about various operational aspects. The Fluoroscopy and Mobile C-Arms report serves with all inclusive, highly effective and thoroughly analyzed information in a well-organized manner, based on actual facts, the information of the market trends is mentioned in the report. The Fluoroscopy and Mobile C-Arms report presents the market competitive landscape and a corresponding detailed analysis of the major vendor/key players in the market.

Get Sample copy of this Report @https://databridgemarketresearch.com/request-a-sample/?dbmr=global-fluoroscopy-c-arms-market

Some of the prominent participants operating in this market are GE Healthcare, Koninklijke Philips N.V., Siemens AG, Canon Medical Systems Corporation, Shimadzu Corporation, Carestream Health, EcoRay, Eurocolumbus s.r.l., GEMSS Co., Ltd., Hitachi, Ltd., Hologic Inc., INTERMEDICAL S.r.l., ITALYRAY, PAUSCH Medical GmbH, Varex Imaging Corporation, Whale Imaging, and Ziehm Imaging GmbH among others.

Study Highlights

Request ForTOC@https://databridgemarketresearch.com/toc/?dbmr=global-fluoroscopy-c-arms-market

GE Healthcare founded in 1918, headquarters in New York, U.S., and focuses towards the manufacturing and developer of medical imaging, digital solutions, patient monitoring and diagnostics, drug discovery, biopharmaceutical manufacturing technologies and performance improvement solutions.

Access Full Report:https://databridgemarketresearch.com/reports/global-fluoroscopy-c-arms-market/

The company has its presence in U.S, Europe, Asia, Americas, Middle East and Africa.

Koninklijke Philips N.V.:

Koninklijke Philips N.V., founded in 1891 and based in Amsterdam, Netherlands. The company focuses on improving peoples health and enabling better outcomes across the health continuum from healthy living and prevention to diagnosis, treatment and home care.

The company has its presence in Netherland, United states, China, Germany, Japan, France, India and Others.

Siemens AG:

Siemens AG, founded in 1896 and based in Munich, Germany. The company provides manufacturing, distributing and services of medical devices and pharma Services. Company is engaged in providing precision medicines, transforming care delivery, innovative technology in area of diagnostics, molecular medicine and many others. The company has its presence in Europe, C.I.S., Africa, Middle East, Americas , Asia, Australia.

Market Developments:

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Data Bridge Market Researchset forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

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Fluoroscopy and Mobile C-Arms Market to reach USD 3,051.4 million by 2026 | Technology Development Trends, Business Growth Opportunities, Competitive...

TUCSON, Ariz.--(BUSINESS WIRE)--Sunquest Information Systems Inc., the leader in laboratory information solutions, announced today it has recognized Henry Ford Health System as a Center of Excellence for its superior commitment to laboratory innovation and for using Sunquest solutions to improve care for the patient community and drive greater efficiency for the organization.

The Center of Excellence program recognizes world-class health systems that utilize Sunquest solutions to support the strategic direction of their organization. This includes establishing and promoting best practices that improve patient safety, decrease the cost of healthcare, streamline provider care, and provide thought leadership and recommendations on new and existing Sunquest products. The Sunquest Center of Excellence program identifies those organizations that are committed to the Institute for Healthcare Improvements quadruple aim, which calls for the pursuit of lower costs, better outcomes and improved patient and provider experiences.

Our collaboration with Henry Ford Health System has demonstrated that the value of a strategically developed laboratory solution extends far beyond the four walls of the lab, said Paul Stinson, Chief Growth Officer for Sunquest. Henry Fords commitment to laboratory innovation along with the use of the Sunquest clinical and anatomic pathology laboratory information solutions platform allows them to efficiently deliver valuable laboratory data to stakeholders within the enterprise, as well as manage a complex core lab with outreach to physician offices and the community.

Henry Ford Health System, founded in 1915 by auto pioneer Henry Ford and now one of the nation's leading healthcare providers, is a not-for-profit corporation comprising six hospitals, 30 medical centers and one of the nation's largest group practices, the Henry Ford Medical Group, with more than 1,500 physicians practicing in over 40 specialties. The System's flagship, Henry Ford Hospital in Detroit, is a Level 1 Trauma Center recognized for clinical excellence in cardiology, cardiovascular surgery, neurology and neurosurgery, orthopedics, sports medicine, multi-organ transplants and cancer treatment.

Just as the auto pioneer Henry Ford exemplified innovation, we too are committed to continuous improvement, both today and for the future, stated J. Mark Tuthill, MD, Division Head of Pathology Informatics at Henry Ford Health System. Partnerships enable us to support the strategic direction of the Henry Ford Health System, our physicians, and provide us the opportunity to drive greater efficiency and collaboration throughout the enterprise, using laboratory data and resources that are supported by Sunquest technology.

Henry Ford Health System has been a Sunquest customer for more than 30 years and uses the following Sunquest solutions: Sunquest Laboratory, Sunquest CoPathPlus, Sunquest VUE, Sunquest Analytics, Sunquest Physician Portal, and Sunquest Advanced EMR Connectivity. These solutions are tightly integrated with Data Innovations for instrument connectivity, Epic EHR for registration and order capture, as well as numerous physician office EMRs to support the organizations large outreach program.

About Sunquest

Sunquest Information Systems Inc. provides diagnostic informatics solutions to laboratories worldwide. With our wide-ranging technical and cross-discipline expertise, and equally deep business acumen, no one is better equipped than Sunquest to transform your lab to meet todays complex healthcare challenges and deliver next-level performance. Since 1979, Sunquest has helped laboratories and healthcare organizations enhance efficiency, improve patient care, and optimize financial results. Our capabilities include multi-site, multi-disciplinary support for complex anatomic, molecular and genetic testing, and support engagement with physicians and patients outside the hospitals at the point-of-care. Headquartered in Tucson, AZ with offices in Calabasas, London, Dubai, Bangalore and Brisbane, Sunquest is a global leader in healthcare information technology. Visit http://www.sunquestinfo.com to learn more.

About Henry Ford Health System

Henry Ford Health System is a six-hospital system headquartered in Detroit, Michigan. It is one of the nations leading comprehensive, integrated health systems, recognized for clinical excellence and innovation. Henry Ford provides both health insurance and health care delivery, including acute, specialty, primary and preventive care services backed by excellence in research and education. Henry Ford Medical Group physicians and researchers are involved in more than 2,000 ongoing clinical research projects. Henry Ford Health System is led by President & CEO Wright Lassiter III. Visit HenryFord.com to learn more.

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Henry Ford Health System Recognized as Center of Excellence by Sunquest Information Systems - Business Wire

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Could lead to universal flu vaccine, better flu therapies

A human antibody that protects mice against a wide range of lethal flu viruses could be the key to a universal vaccine and better treatments for severe flu disease, according to a new study from Washington University School of Medicine in St. Louis, Icahn School of Medicine at Mount Sinai in New York City, and Scripps Research in La Jolla, Calif.

Researchers have found an antibody that protects mice against a wide range of lethal influenza viruses, according to a study from Washington University School of Medicine in St. Louis, Icahn School of Medicine at Mount Sinai in New York City, and Scripps Research in La Jolla, Calif. The antibody could serve as a template to aid in design of a universal vaccine that protects against all strains of the virus, and a drug to treat and protect against severe cases of flu, including pandemics.

The research is published Oct. 25 in Science.

There are many strains of influenza virus that circulate, so every year we have to design and produce a new vaccine to match the most common strains of that year, said co-senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. Now imagine if we could have one vaccine that protected against all influenza strains, including human, swine and highly lethal avian influenza viruses. This antibody could be the key to the design of a truly universal vaccine.

Ellebedy discovered the antibody an immune protein that recognizes and attaches to a foreign molecule in blood taken from a patient hospitalized with flu at Barnes-Jewish Hospital in St. Louis in the winter of 2017. Ellebedy was working on a study analyzing the immune response to flu infection in humans, in collaboration with the Washington University Emergency Care and Research Core, which was sending him blood samples from consenting flu patients. He quickly noticed that this particular blood sample was unusual: In addition to containing antibodies against hemagglutinin, the major protein on the surface of the virus, it contained other antibodies that were clearly targeting something else.

At the time we were just starting, and I was setting up my lab so we didnt have the tools to look at what else the antibodies could be targeting, said Ellebedy, who is also an assistant professor of medicine and of molecular microbiology, and a scholar at Washington Universitys Bursky Center for Human Immunology & Immunotherapy Programs.

He sent three of the antibodies with unknown targets to co-senior author Florian Krammer, PhD, a microbiology professor at the Icahn School of Medicine at Mount Sinai. An expert on neuraminidase the other protein on the surface of the influenza virus Krammer tested the antibodies against his extensive library of neuraminidase proteins. At least one of the three antibodies blocked neuraminidase activity in all known types of neuraminidase in flu viruses, representing a variety of human and nonhuman strains.

The breadth of the antibodies really came as a surprise to us, Krammer said. Typically, anti-neuraminidase antibodies can be broad within a subtype, like H1N1, but an antibody with potent activity across subtypes was unheard of. At first, we did not believe our results. Especially the ability of the antibodies to cross between influenza A and influenza B viruses is just mind-boggling. It is amazing what the human immune system is capable of if presented with the right antigens.

Neuraminidase is essential to flu virus replication. The protein cuts newly formed viruses free of infected cells so they can move on and infect new cells. Tamiflu, the most widely used drug for severe flu infection, works by inactivating neuraminidase.

To find out whether the antibodies could be used to treat severe cases of flu, Krammer and colleagues tested them in mice given a lethal dose of influenza virus. All three were effective against many strains, and one antibody called 1G01 protected mice against all 12 strains tested, representing all three groups of human flu virus, as well as avian and other nonhuman strains.

All the mice survived, even if they were given the antibody 72 hours after infection, Ellebedy said. They definitely got sick and lost weight, but we still saved them. It was remarkable. It made us think that you might be able to use this antibody in an intensive care scenario when you have someone sick with flu and its too late to use Tamiflu.

Tamiflu should be administered within 48 hours of symptoms. A drug that could be used later would help many people diagnosed after the Tamiflu window has closed. But before the researchers could even think of designing such a drug based on the antibody, they needed to understand how it was interfering with neuraminidase.

They turned to co-senior author Ian Wilson, DPhil, a noted structural biologist at Scripps Research. Wilson and Xueyong Zhu, PhD, a staff scientist in his lab, mapped the structures of the antibodies while they were bound to neuraminidase. They found that the antibodies each had a loop that slid inside the active site of neuraminidase like a stick between gears. The loops prevented neuraminidase from releasing new virus particles from the surface of cells, thereby breaking the cycle of viral production in cells.

We were surprised how these antibodies managed to insert a single loop into the conserved active site without contacting the surrounding hypervariable regions, thereby achieving much greater breadth against the neuraminidase of different influenza viruses than we have seen before, Wilson said.

The structures showed that the antibodies provide such broad protection because they target parts of the active site of the neuraminidase protein that is much the same across distantly related flu strains. Even minor changes to that part of the protein could abolish its ability to do its job, thereby preventing the virus from replicating.

The researchers are working on developing new and improved treatments and vaccines for influenza based on antibody 1G01, which has been patented by Washington University.

Neuraminidase has been ignored as a vaccine candidate for a long time, Ellebedy said. These antibodies tell us that it should not have been overlooked. Now that we know what a broadly protective antibody to neuraminidase looks like, we now have an alternative approach to start designing novel vaccines that induce antibodies like this. And that could be really important if we are going to figure out how to design a truly universal vaccine.

Stadlbauer D, Zhu X, McMahon M, Turner JS, Wohlbold TJ, Schmitz AJ, Strohmeier S, Yu W, Nachbagauer R, Mudd PA, Wilson IA, Ellebedy IA, Krammer F. Broadly protective human antibodies that target the active site of influenza virus neuraminidase. Science. Oct. 25, 2019. DOI: science.aay0678

The study was supported by the National Institute of Allergy and Infectious Diseases, contract number HHSN272201400008C and HHSN272201400006C and grant numbers R01 AI117287, R21 AI139813, and U01 AI141990; and the National Institutes of Health (NIH), grant number R56 AI117675.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Flu antibody protects against numerous and wide-ranging strains - Washington University School of Medicine in St. Louis

People with pancreatic cancer and a specific type of change or mutation in their DNA live longer when treated with platinum-based chemotherapy, compared to those who received the same treatment but didnt have the same mutation type. This study is out today in Journal of Clinical Oncology (JCO) Precision Oncology and draws on data from the Pancreatic Cancer Action Networks (PanCAN) Know Your Tumor precision medicine service.

Being able to define subsets of patients who should be treated a certain way, based on their tumors biology, underscores the value of molecular profiling to improve patient outcomes in this challenging disease, said Lynn Matrisian, PhD, MBA, chief science officer at PanCAN and a co-author of the study. These are the types of results we hoped to see when we launched Know Your Tumor in 2014.

Looking at Know Your Tumor reports and follow-up patient outcomes, the study authors, led by researchers at Perthera, Inc., examined data on 820 pancreatic cancer patients who either had advanced disease or who had their tumors partially or completely removed by surgery. They then looked at whether the study participants had a specific type of mutation that impaired a DNA repair process known as homologous recombination (HR).

A persons DNA gets damaged daily, which is why the cell is designed to repair errors in DNA through many ways, including HR. But when some genes, like the BRCA genes (BRCA1 and BRCA2), become mutated, they can no longer repair DNA by HR. Mutations in other genes can impair HR also, including PALB2, ATM, ATR, ATRX, BAP1, BARD1, BRIP1, CHEK1/2 and several others.

When HR is not functioning, certain conditions may develop, like cancer.

The patients evaluated in the study could have been born with mutations in HR genes (germline mutations) or could have mutations present only in their tumor tissue (somatic mutations). PanCANs Know Your Tumor is able to test patients tumor tissue and saliva to identify both types of mutations.

For patients with metastatic disease, those with HR-related mutations lived an average of 11 months longer when treated with platinum-based chemotherapy, as compared to patients who underwent the same treatment but didnt have HR-related mutations.

The new study supports other research suggesting that cancers with HR-related mutations are especially vulnerable to platinum-based chemotherapy. Further, this study follows promising phase III clinical trial results showing that pancreatic cancer patients who responded to this chemotherapy type also responded well to a PARP inhibitor called Lynparza (olaparib).

Lynparza is an FDA-approved treatment for ovarian cancer, but not yet for pancreatic cancer. Published phase III clinical trial results suggest it may have the potential to extend the good results seen by some patients undergoing platinum-based chemotherapy.

While platinum-based chemotherapy is shown to be effective for certain patients, many patients may not have the chance to benefit from this treatment type. The study authors noted that while its estimated that 17 to 25 percent of pancreatic cancers have HR-related mutations, about half of all patients do not receive platinum-based therapy as their first line of treatment. This highlights the importance of patients undergoing molecular profiling to identify mutations, such as those disrupting the HR pathway, or other alterations that may impact their treatment options.

One theory in the field was that pancreatic cancer patients with HR-related mutations naturally ended up living longer than patients without such mutations, Matrisian said. But our study shows thats not true. Unless they underwent platinum-based treatment, these patients did not see any survival benefit.

Every pancreatic tumor is different. Patients who receive treatment based on their tumors biological characteristics have better outcomes. PanCAN strongly recommends molecular profiling to help determine best treatment options.

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Matched Therapy Increases Pancreatic Cancer Survival - Pancreatic Cancer News & Stories

The flu virus (above) has frustrated scientists with its constant shapeshifting, eluding many vaccines and drugs.

By Kai KupferschmidtOct. 23, 2019 , 2:00 PM

Scientists often warn about the dangers of pandemic pathogens spreading quickly around the globe. But one virus already sweeps across the world every year, causing tens of millions of infections and hundreds of thousands of deaths: influenza. Now, a new drug that has shown promise in ferrets may help drive down that toll, researchers report today. The drug appears to be more effective than the most commonly used treatment, oseltamivir, and there are hints that it wont prompt easy resistance in the virus.

Scientists have long been frustrated by the constant shapeshifting of the flu virus, which necessitates an annual reformulation of flu vaccines to reflect commonly circulating strains. When that match is bad, vaccine protection can be low, especially for elderly people who are most at risk. Meanwhile, new influenza drugs have been slow to develop, and those that exist are often inadequate. Oseltamivir, for instance, provides a moderate benefit at best, and only when given early in the infection; whether it prevents hospitalizations and deaths is controversial.

Whats more, the flu virus has developed resistance to oseltamivir and to an older drug, amantadine. And there are already reports of flu strains resistant to baloxavir, a drug approved by the U.S. Food and Drug Administration just last year.

To come up with an alternative, scientists at Georgia State University and Emory University, both in Atlanta, investigated a compound named N-hydroxycytidine (NHC), which has been known for years to inhibit a broad range of RNA viruses like the flu. Previously, the researchers had shown that NHC is active against influenza; but in tests on macaques, they found the drug is not taken up well by the body, a potential deal breaker for human use, says Georgia State molecular virologist Richard Plemper, one of the researchers leading the new work.

The researchers tweaked NHCs structure to create a new compound named EIDD-2801, which converts back into NHC inside the body. They then tested it in ferrets, the most widely used animal model for influenza. If the ferrets received the compound 12 hours after infection, they did not develop disease at all. Those that received it after 24 hours, when fever had started, produced less virus than control animals that received oseltamivir or no treatment at all. The fever also ended faster in treated animals, the researchers write in Science Translational Medicine.

Its important that they showed a reduction in symptoms in ferrets, because it gets much closer to predicting what happens in people, says Andrew Pavia, an infectious disease expert at the University of Utah in Salt Lake City. Its a major step towards developing a drug for humans.

The scientists also investigated how NHC blocks influenza by sequencing the genomes of flu viruses exposed to the compound. They found that the virus incorporates the drug into its RNA when it replicates, instead of a molecule named cytosine, leading to a cascade of mistakes that virologists call error catastropheessentially overwhelming the virus with mutations.

To test how easily flu becomes resistant to EIDD-2801, the researchers also grew the virus while keeping it exposed to sublethal doses of NHC or slowly increasing the concentration of NHCmethods that typically dont kill the virus, but give it a chance to evolve resistance. Even though sequencing clearly shows the virus trying to resist the drug, no resistant strains developed. That bodes well, Pavia says, because oseltamivir and other older drugs all eventually fail the test.

Still, it doesnt mean resistance cannot develop, says Albert Osterhaus, a virologist at the University of Veterinary Medicine in Hanover, Germany. Favipiravir, a drug approved in 2014 in Japan for pandemic flu viruses resistant to all other drugs, was thought to have a similarly high barrier to resistance before resistant strains developed.

Plemper says additional toxicity tests in animals have not thrown up any red flags, and the first trials of EIDD-2801 in humans are likely to start next spring. Pavia says the new drug could eventually be used in combination with other drugs to stave off resistance, a strategy already in use for HIV and hepatitis B treatments.

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New drug forces flu virus into 'error catastrophe,' overwhelming it with mutations - Science Magazine

CAMBRIDGE, Mass.--(BUSINESS WIRE)--CAMP4 Therapeutics, a biotechnology company unraveling transcriptional machinery and the network of signaling pathways to accelerate drug discovery and development across therapeutic areas, announced that Richard Young, Ph.D., one of the companys founders, has been elected to the National Academy of Medicine (NAM). Dr. Young, a Member of the Whitehead Institute and Professor of Biology at the Massachusetts Institute of Technology (MIT), was one of 90 regular members and 10 international members elected to NAM earlier this week. Election to NAM is considered one of the highest honors in the fields of health and medicine, recognizing individuals who have made major contributions to the advancement of the medical sciences, health care and public health. Dr. Young was elected to the National Academy of Sciences in 2012 as well.

Dr. Youngs research focuses on mapping the regulatory circuitry that controls cell state and differentiationusing experimental and computational technologies to determine how signaling pathways, transcription factors, chromatin regulators, and small RNAs control gene expression.

CAMP4 was founded based on the seminal discoveries made by Dr. Young, along with Leonard Zon, M.D., Grousbeck Professor of Pediatric Medicine at Harvard Medical School, Investigator at Howard Hughes Medical Institute, and Director of the Stem Cell Program at Boston Childrens Hospital.

Based on Drs. Young and Zons discoveries, CAMP4 has built its proprietary Gene Circuitry Platform, with which it is pioneering a systematic and scalable approach to discover new, druggable targets to control gene expression to treat diseases across all therapeutic areas.

On behalf of the entire CAMP4 team, I want to congratulate Rick on this tremendous and well-deserved honor, said Josh Mandel-Brehm, President and Chief Executive Officer of CAMP4. In addition to all of his remarkable scientific accomplishments that have the potential to impact peoples lives around the world, and the numerous resulting accolades bestowed on him, I am continually struck by Ricks incredible humility and humanity. We are grateful to have the opportunity to work with and advance Ricks science and vision.

Dr. Young received his Ph.D. in Molecular Biophysics and Biochemistry at Yale University, conducted postdoctoral research at Stanford University and joined Whitehead Institute and MIT in 1984. He has served as an advisor to the National Institutes of Health, the World Health Organization, the Vatican and numerous scientific societies and journals. Dr. Young has founded and advised companies in the biotechnology and pharmaceutical industry and is currently a member of the Board of Directors of CAMP4, Syros Pharmaceuticals and Omega Therapeutics. His honors include Membership in the National Academy of Sciences, the Chiron Corporation Biotechnology Research Award, Yales Wilbur Cross Medal, and in 2006 Scientific American recognized him as one of the top 50 leaders in science, technology and business.

The National Academy of Medicine, established in 1970 as the Institute of Medicine, is an independent organization of eminent professionals from diverse fields including health and medicine; the natural, social, and behavioral sciences; and beyond. It serves alongside the National Academy of Sciences and the National Academy of Engineering as an adviser to the nation and the international community. Through its domestic and global initiatives, the NAM works to address critical issues in health, medicine, and related policy and inspire positive action across sectors. The NAM collaborates closely with its peer academies and other divisions within the National Academies of Sciences, Engineering, and Medicine.

View the Whitehead Institutes statement on Dr. Youngs election to NAM.

About CAMP4 Therapeutics

At CAMP4 Therapeutics, we are revolutionizing drug discovery and development to be faster, smarter and better. With our Gene Circuitry Platform, we have discovered how to dial up or dial down the expression of any gene. Using the foundational insights enabled by our platform, we are pioneering a systematic and scalable approach to discover new, druggable targets to control gene expression to treat diseases across all therapeutic areas. This approach involves creating tissue-specific Gene Circuitry Maps that comprehensively reveal the transcriptional machinery and its connected network of signaling pathways governing gene expression. Each map serves as its own therapeutic area discovery engine, revealing dozens, sometimes even hundreds of disease-solving opportunities. Our goal is to decipher the transcriptional machinery and signaling networks controlling gene expression for all cell types central to disease, ultimately delivering druggable targets for a multitude of undruggable diseases. Our vision is to create a world where a treatment for every disease is possible. Learn more about us at http://www.camp4tx.com.

Original post:

Richard Young, Ph.D., Founder of CAMP4 Therapeutics, Elected to National Academy of Medicine - Business Wire

25 Oct 2019

Too much salty food wreaks havoc on the cardiovascular system, raising blood pressure, damaging small blood vessels, and limiting perfusion into the brain. But is this why salt increases the chances of cognitive impairment? Not so fast. At this years Society for Neuroscience meeting, held October 1923 in Chicago, Giuseppe Faraco from Costantino Iadecolas lab at Feil Family Brain and Mind Research Institute of Weill Cornell Medicine, New York, reported that learning and memory deficits in mice chowing on a high-salt diet correlated with phosphorylation of tau, not with damage to the brains blood vessels. The study, published October 23 in Nature, links reduced nitric oxide in blood vessel walls to activation of kinases that modify tau. The findings present a new twist in the well-known link between cardiovascular disease and risk for cognitive decline.

Admittedly, at eight to16 times the norm, the amount of salt the mice consumed exceeds all but the very highest equivalents in which people might indulge. Still, researchers found the results thought-provoking. However artificial the diet, this highlights that salt has effects independent of high blood pressure and that salt is a risk factor in its own right, said Joanna Wardlaw, University of Edinburgh. Wardlaw thinks the mechanism may explain some clinical observations. Weve seen in studies of small stroke that despite treating high blood pressure, people continue to get worse clinically and on their brain scans, she told Alzforum. We need to think about the role of other common risk factors, including dietary salt.

Li-Huei Tsai and Joel Blanchard, Massachusetts Institute of Technology, found the Columbia groups work fascinating. They illustrate that neuronal cells and the cerebrovasculature have dynamic molecular and biochemical interactions that clearly influence neurodegenerative pathologies, they wrote to Alzforum (full comment below). Faraco found the salt-induced reduction in nitric oxide (NO) boosted levels of p25, which activates the kinase Cdk5. Tsai has linked p25/Cdk5 to neurodegeneration (Dec 1999 news).

Pickled. AT8 immunostaining detects phosphorylated tau in the brains of mice fed a high-salt diet (right), but not in brains of mice on normal chow (left). [Courtesy of Giuseppe Faraco et al., Nature.]

The NO link most intrigued Zvonimir Katusic, Mayo Clinic, Rochester, Minnesota, as well. Susan Austin in Katusics lab found that knocking out endothelial nitric oxide synthase (eNOS) increases processing of A precursor protein and impairs learning and memory, and most recently that it boosts p25 and phosphorylation of tau (Austin et al., 2010; Austin et al., 2013; Katusic and Austin et al., 2016). In Chicago, Austin reported that microglia from eNOS knockouts ramp up production of ADAM17, the primary sheddase for TREM2, and tone down production of the anti-inflammatory cytokine IL-10. It appears release of NO by the endothelium is an important control mechanism for the brain, said Katusic.

The plot gets thicker. The effect of high salt may not start in the endothelial cells of the brain, but in immune cells of the gut. Last year Faraco reported that a high-salt diet elicits a flood of interleukin-17 from T helper cells in the intestine. That IL-17 lead to a dearth of endothelial NO and impaired memory (Jan 2018 news). The IL-17 reduced cerebral blood flow by about 25 percent, but Faraco considers this insufficient to cause the memory impairment. Since tau pathology has been linked to cerebrovascular disease, he decided to see if a high-salt diet affected the microtubule binding protein.

Faraco put normal C56/Bl6 mice on a diet comprising 8 percent NaCl. This is 16 times the normal amount of salt in mouse chow; seawater is about 3.5 percent NaCl. The mice ate as much food as usual, but over the next 36 weeks, levels of phosphorylated tau rose. AT8 immunoreactivity peaked after 24 weeks, RZ3 immunoreactivity after 36 weeks. These antibodies recognize tau phosphorylation at serine 202/threonine 205 and threonine 231, respectively. Hyperphosphorylation of tau was detected in both male and female mice, and in mice on a 4 percent NaCl diet, albeit only AT8 staining in that case. Faraco found similar tau changes when he fed 8 percent salt to Tg2576 mice, which model amyloidosis. Levels of A were unaffected.

What about neurofibrillary tangles? Faraco found none in any of the mice, but levels of insoluble tau released by formic acid did increase slightly in the cortices and hippocampi of mice on the high-salt diet.

In parallel with the tau phosphorylation, C57/Bl6 mice began having learning and memory problems. They struggled to recognize novel objects in their cages and had trouble finding the escape route in the Barnes maze. The deficits modestly correlated with AT8 binding in the cortex and hippocampus.

Was hyperphosphorylation of tau to blame? The authors tested this in two ways. They administered anti-tau antibodies to wild-type mice on high salt, and they fed high salt to tau knockouts. In both cases the animals performed as well as mice on normal chow, despite hypoperfusion of the brain, suggesting that indeed it was the tau that drove the cognitive decline due to the salt and not reduced blood flow.

Given Katusics prior data suggesting links between endothelial NO and tau phosphorylation, Faraco tested if he could stop the protein modification with L-arginine, a precursor in NO production. This suppressed both tau phosphorylation and the learning and memory deficits. In addition, elevated p-tau in eNOS knockouts could not be boosted further by high salt, supporting the idea that suppression of endothelial NO was behind the tau modification.

Delving more deeply into the mechanism, Faraco found that the salty food elevated calpain activity in the brain. Calpain cleaves p35 to p25; in keeping with this, the levels of the smaller peptide rose, as did activity of Cdk5, the tau kinase. All told, the data suggest that by triggering IL-17 production in the gut, high salt triggers loss of endothelial NO, which in turn leads to phosphorylation of tau and cognitive impairment.

Precisely how NO is suppressed remains to be seen. Katusic emphasized that the gas easily diffuses. Since cells in the brain are rarely more than 15 micrometers away from a blood vessel, NO could be an important signaling molecule. Faraco found no gross changes in astrocytes, microglia, or neurons in mice on high salt, as judged by GFAP, Iba1, and NeuN staining, but agreed it would be important to study downstream effects on these cells.

In her SfN talk, Austin reported that NO affected on microglia more profoundly. In cultures of the cells from eNOS knockout mice, she found not only an increase in ADAM17, but also decrease in cell surface TREM2. Mutations in this microglial receptor increase risk for Alzheimers and frontotemporal dementia. The sensor plays a central role in microglial homeostasis (Nov 2012 news; Oct 2012 news; Aug 2019 news). Austin also found that eNOS-/- microglia, either cultured or isolated from brain by cell sorting, make less TNF and IL-10, pro- and anti-inflammatory cytokines, respectively, while at the same time ramping up phospholipase A2, which mobilizes arachidonic acid, a precursor for inflammatory molecules.

We are slowly developing this concept that vascular mechanisms independent of perfusion affect cognitive impairment, said Katusic. Tsai and Blanchard agreed. Further unraveling these mechanisms will undoubtedly be a promising endeavor that will strengthen our understanding of how dietary habits influence susceptibility to age-related cognitive decline, they wrote.

For his part, Faraco is using RNA-Seq to study what happens in the endothelial cells to reduce NO. It will be interesting to examine interactions with other genetic and dietary risk factors, such as high-fructose or high-fat diets, he said. He thinks it will be important to identify the tau species responsible for the effects on cognition. We need to go much more deeply into the mechanism of neuronal dysfunction.Tom Fagan

No Available Further Reading

Originally posted here:

Not Just Blood PressureDietary Salt Linked to Tau Phosphorylation - Alzforum