Meet the inflammation and immunity researcher studying the fundamental cellular mechanisms behind uncontrolled inflammatory responses to allergens

As the prevalence of allergic disease continues to rise worldwide, the work of immunologist Dr. Adam MacNeil has never been more important. By identifying novel targets in allergic inflammation to enable the development of innovative therapies, MacNeil and his team are pushing toward a healthier future. Were interested in allergic inflammation from two different branches, firstly, how the cells that contribute to inflammation emerge from the bone marrow, and secondly, how mature mast cells contribute to inflammatory mechanisms at the site of exposure, explains MacNeil, associate professor in the interdisciplinary Health Sciences department at Brock University, Canada.

Dr. Adam J. MacNeil, Associate Professor of Immunologyat Brock University's Department of Health Sciences.Pictured from left to rightare;Melissa Rouillard, Aindriu Maguire, Rob Crozier, Adam MacNeil, Jeremia Coish, Katie Hunter, Colton Watson, and Natalie Hicks. Image courtesy of theMacNeil Lab.

The MacNeil Lab investigates mechanisms in hematopoietic stem cells directing the maturation of the most well-known allergic mediator cellsmature mast cellsthat drive allergic inflammation. A key research goal for the team is to identify how an allergen activates a mast cell to create an inflammatory response.

Seeking to understand the signals that stimulate a progenitor cell to become a mast cell in different tissues, this research looks to determine the signaling pathways directing the epigenetic, and ultimately proteomic, profile of these cells1-3. To do this, cells are isolated and matured from bone marrow to create functional, phenotypical mast cells, which are primed with allergen-specific IgE molecules before addition of the allergen to activate the cells. The inflammatory response to the allergen, and the cell signaling processes that contribute to the inflammatory mechanisms, can then be measured through the secretion of histamines in degranulation mechanisms, or release of pro-inflammatory mediators such as cytokines, chemokines, and lipid metabolites.

Brock University

Being able to identify and sort cells with a specific immune profile requires tools capable of precision sorting of heterogeneous populations of cells. MacNeil expands: Were working with a heterogeneous population of cells in the bone marrow and trying to take only the stem cells out. So, it's a very small population within the total population of cells. Many of the assays that we want to do with that small population of cells are very well-suited to being sorted directly onto a 96-well plate where we can then actually conduct the experiment directly, knowing exactly how many cells are in each well and what the particular profile of those cells is. That makes the Sony SH800S a really strong tool for our lab.

When it comes to optimizing and streamlining the lab's work, Sony technology offers advantages over traditional methods. The traditional flow cytometer or cell sorter in any core lab is operated by a technician, and they're the only one allowed to touch it. That doesn't make for great learning opportunities for graduate students, and it's much better if they can actually interface with the instrument themselves, says MacNeil. The software and automation really allow for that to happen, but also adds to the robustness of the instrument. The way in which it has been designed means that it's pretty difficult to break it.

With an epigenetic approach to understanding how mast cells differentiate, and the effect of inhibiting specific signaling pathways in those cells, the MacNeil Lab uses sorted cells in functional assays such as immune cell profiling and cytokine secretion. Also, the cells can be sorted into plate-based assays for ChIP or RNA-Seq to assess their genetic profile. We're not only interested in sorting. We bought the device because it's robustly dynamic, explains MacNeil, referring to the Sony SH800S. You can look at data acquisition and not have to even use the sorting function at all in certain scenarios. There are many times that were simply interested in looking at the phenotype of our cells and not worried about sorting necessarily. Weve found this instrument to be very easy to use and to give us robust data in terms of the immune profile of our cells.

In addition, the SH800S microfluidic sorting chip helps to automate key stages of instrument setup and demonstrates versatility with a wide range of chip sizes, ranging from 70130 m, for sorting a variety of cells. The chip ultimately gets to the robustness of the instrument, explains MacNeil. Because of the chip, we have such peace of mind about how the instrument functions that we don't even worry about clogging of the instrument and all of the problems that the chip ultimately solves. If we do run into a problem, we can just change the chip. I certainly find the chip technology to be really well suited to our type of lab environment.

For MacNeil, the Sony SH800S Cell Sorter is a great fit for the lab, with a seamless software interface and great overall instrument design and modularity for easy plate-based sorting.MacNeil lab logocourtesy of the MacNeil Lab.

Working within the diverse multidisciplinary department at Brock University opens unique and fascinating research avenues not available to all immunologists and has led MacNeil to interesting collaborations and knowledge exchange on transdisciplinary projects.

As part of these broader research avenues, working with sociologist Prof. Terrance Wade and cardiovascular biologist Prof. Deborah OLeary, MacNeil also studies adverse experiences in childhood. The team is investigating whether such events may set the immunological stage for dysregulated inflammation in later life, through mechanisms involving stress-stimulated cortisol release that can shape how the immune system is responding4.

In another stream of collaborative immunological research, MacNeil collaborates with psychologist Prof. Anthony Bogaert to look at the role of the immune system in shaping sexual orientation as part of the fraternal birth order effect. This research looks at how early pregnancies stimulate the immune system to make antibodies against brain proteins in fetal males that may then affect their social behaviors in later life5. Its something I may not have expected to ever work on, says MacNeil. But when you come to a diverse department with a wide lens on health, these kinds of opportunities emerge. Were now interested in using the SH800S to test hypotheses for particular mechanisms underlying this phenomenon.

Looking ahead, MacNeil expects tissue heterogeneity to be a key issue to tackle in the field of immunology. Cell populations simply aren't uniform, he says. Mast cells in different locations in the body don't have exactly the same phenotype, and so, as our research proceeds and we continue to probe the role of the mast cell in allergic inflammation, we're very conscious that tissue heterogeneity is going to be a factor. But with such challenges come opportunities. Were ultimately interested in going into those tissues and trying to pull mast cells out. To do this, we would require an instrument like a cell sorter. Once the cells are sorted, we can interrogate their functional phenotype, including how they degranulate, secrete cytokines and metabolize lipids etc. toward one day potentially modulating their phenotype for the hundreds of millions affected by this inappropriate immune response, MacNeil concludes.

Originally posted here:
Innovative therapies: Novel targets in allergic inflammation - SelectScience

In one photo, the babys head is turned away from the camera, as someone holds his arm up to show the pink area on his back. In another, a cluster of red bumps ring the area where the babys arm and back meet, and a third, of the childs chest, shows what looks like a bumpy red rash near the belly button.

Hi all does this look like an allergic reaction? asks the poster in a Facebook allergy parent group.

Have you tried a naturopath or chiropractor? And adding probiotics and vitamin D to hid [sic] diet? reads one response.

You might think this social media post, presented by Dr. David Stukus to a room full of experts at the annual meeting of the American College of Allergy, Asthma, and Immunology, would cause an uproar. Why would a parent turn to Facebook with such a severe reaction?Who has the nerve to respond as an expert and give such misguided advice? Instead, the post elicits familiar groans. Every single person I talked to after my presentation has seen this in his or her practice, says Stukus, an associate professor of pediatrics and associate director of the Pediatric Allergy & Immunology Fellowship Program at The Ohio State University College of Medicine. But whats a room full of immunologists to do? Fighting promises of quick fixes with clear science has always been an uphill battle when it comes to the health of kids. Increasingly, parents ofkids with food allergies have seen this first-hand, thanks to the rise of parenting groups who are taking a page from anti-vaxxers and offering medically dubious advice and promoting conspiracies. For worried parents, its disorienting and dangerous. Fortunately, experts are speaking up, looking to nip this trend in the bud before it does real, extensive harm.

Does preschool or preschool-age childcare put a financial strain on your family?

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Yes, but we can handle it

Yes, but were freaking out a bit

Yes. Its a serious problem

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The fact is that there is no cure for food allergies, which affect more than 4 million kids, or 5 percent of children in the U.S.

If parents believed everything they read online about food allergies, theyd worry that smelly feces could signal a gluten intolerance. Theyd shell out $250 for at-home food allergy tests and would ban charcoal briquettes from their grills. Theyd think a detoxifying elixir might cure allergies and that the body can reverse allergies with the help of vitamin B5, probiotics and crystallized sulfur. Theyd make a child having an anaphylactic allergic reaction drink activated charcoal and hope for the best. They would blame the government for the rise of peanut allergies among kids because they started putting peanut oil in vaccines in the 1960s.

Many parents of kids with food allergies correctly understand that theres no scientific evidence supporting the above claims. But a sizable portion missed the lessons and are all too happy to share unsubstantiated clickbait containing dubious health claims via myriad online podiums that offer the misinformed a megaphone. CountlessFacebook groups for allergy parents have cropped up, many of which have tens of thousands of members. People offer anecdotal advice on allergy blogs and YouTube videos, and, to a lesser degree, on allergy-related Instagram accounts (there are more than 50,000 Instagram posts with the tag #allergymom.).

The fact is that there is no cure for food allergies, which affect more than 4 million kids, or 5 percent of children in the U.S., according to the Asthma and Allergy Foundation of America. And although the Food and Drug Administration is close to approving a new peanut allergy treatment, currently, the only available treatments for food allergies are avoiding the allergens and possibly medication and immunotherapy. Sadly, however, many parents get their hopes up chasing spurious and often expensive allergy fixes discouraged by their allergists and that turn out to be useless.

Its not just well-meaning but misinformed parents spreading bad food allergy advice. Irresponsible bloggers and companies selling supplements, herbs, treatment programs, DIY allergy tests and chiropractic services based on junk science prey on parents dealing with the anxiety-inducing new world of severe child food allergies. In addition, even well-informed parents might sometimes click on a promise of some new treatment or remedy that at best is a waste of time and at worst, could lead to dangerous medical decisions affecting their childs health.

One Facebook allergy group member, a father of a 15-month-old son who has an anaphylactic allergic reaction to sesame seeds, peanuts, cashew nuts, and pistachios, offered his story as evidence: Im pretty skeptical, says the man who asked to remain anonymous.He and his wife follow the doctors instructions and do their own research when it comes to allergy treatments or restaurant menu tips they read online. A lot of that research starts for them in Facebook groups for allergy parents which sometimes offer well-cited information that they then verify. But there are also plenty of too-good-to-be-true posts and ads that, he admits, can be hard to resist. I have to say, as a dad with an allergic son, I really wish I could believe the headlines and wish I could think Oh, hes going to be OK, theyve found a cure.Since allergies are still somewhat a science mystery, he says, its ripe territory for clickbait and false information posing as science.

This is what fortune-tellers do: they cast a wide net until they find something that may have some application to somebodys life and go with it.

Its no surprise that parents are vulnerable targets for all sorts of allergy quackery. Its difficult enough to keep kids safe as they navigate the world but can be overwhelming having to worry that a piece of cake containing hidden allergens at a birthday party might kill them. But the volume of targeting this vulnerable population is subject to from modern-day snake-oil salesmen is shocking.

Stukus studied six years worth of allergy-related posts on social media and presented his findings at the American College of Allergy, Asthma & Immunology annual meeting in October. What he saw was alarming, he says, and no surprise to any of his colleagues at the meeting.

There are companies as well as different types of medical providers that deliberately target the food allergy community and peddle pseudoscience as a way to make a profit for their services, such as home food allergy sensitivity testing, which is not an accurate way to diagnose anything, he says.

One branch of quackery aimed at food allergy parents involves dubious means of diagnosing food allergies, such as chiropractic adjustments, muscle testing, and hair analysis, Stukus says. Websites peddling food allergy home tests often are loose with the terms allergy and sensitivity and use them interchangeably, even though food allergies and food intolerances are wildly different things. (Stukus goes so far as to say food sensitivities arent real.)

These bogus online [food intolerance] quizzes basically keep asking about every common symptom until you say yes, Stukus says. This is what fortune-tellers do: they cast a wide net until they find something that may have some application to somebodys life and go with it.

More alarming than persuading someone that they have a nonexistent food allergy, however, is that allergy misinformation can feed a mistrust of mainstream medicine that can endanger kids health. Some Facebook and YouTube videos feature doctors of chiropractic or alternative medicine offering advice that your traditional allergists wont tell you, or point out that avoidance of an allergen isnt a cure and frame their dangerous or useless remedy as more proactive than recommendations from a board-certified allergist.

Scrolling through the comments on some of these videos reveals viewers who enthuse that the advice in the video saved them a trip to the doctor for a diagnosis or ask for a virtual diagnosis of an allergic reaction. Describing big red bleeding bumps, sharp stomach pains and swells around their lips, a sufferer on one video commented, I was just wondering if I should go to the doctor or I should just put cream on it and hope for the best.

The lack of an effective cure means that were a big, ripe target for every medical quack and health scammer out there, including the anti-vaxxers.

The prevalence of food allergies among children has increased, and speculation about the reasons for the spike veers into conspiracy-theory territory with, perhaps unsurprisingly, some crossover from the anti-vaxxer movement.

Heated arguments abound in the parent allergy community over the theory that the government began adding peanut oil to vaccines decades ago and is to blame for the increase in peanut allergies in children. This is a debunked claim that even some anti-vaxxers say is false. Yet many parents believe it and might not vaccinate their children for fear theyll develop a life-threatening peanut allergy.

If not getting vaccinated prevented food allergies then unvaccinated kids should not have food allergies, but they do, says Melanie Carver, vice president of community health services and marketing for the Asthma and Allergy Foundation of America. Delaying vaccination because of a fear of allergies poses health risks to children, she says.

The lack of an effective cure (as opposed to a few treatments still in development), means that were a big, ripe target for every medical quack and health scammer out there, including the anti-vaxxers, says Laurel, an author of an allergy blog and member of several Facebook groups for allergy parents who asked to remain anonymous. Laurel says she recently was kicked out of an allergy group after flagging an anti-vax post to a mod. It turned out that the anti-vax poster was the moderator, and Laurelwas booted.

The hundreds, if not thousands, of Facebook groups for allergy parents, vary widely in terms of the quality of information and how well theyre policed for misleading and dangerous posts, Laurel says. Plenty of good, responsible Facebook groups and blogs help parents understand scientific studies related to allergies. Allergy parents are often anxious and overwhelmed, and the support they can get online from other parents who understand what theyre going through can be invaluable.

But gauging the reliability of Facebook allergy groups is time-consuming. In general, its safer to think of social media as one step in evidence-gathering about allergies and evaluate each article about a study or tip about allergy-free restaurant independently, says Nicole Smith, a longtime allergy parent blogger in Colorado Springs, Colorado.

If anything is claimed to be a cure, run in the opposite direction, Smith says. Parents need to be cautious and discuss even innocuous-seeming herbal supplements with their childs allergist before trying them, she says, because you dont know what else could be in one that could set off the system.

Instead of looking at blogs and less reliable information portals, turn to nonprofit or medical society resources for parents such as FARE, the AAAI and the ACAAI, recommends allergy researcher Thomas Casale, MD, former head of the ACAAI and professor of pediatrics at the University of South Florida.

Remember that allergies are so individual that your childs allergist will always be the most informed source of information.Keep a file of research, remedies, and recommendations you see online and bring the list to appointments to discuss with your allergist. They know your child and are a better source of information than a stranger with a kid whose condition could have little bearing on your childs condition.

Its dangerous to take another persons online anecdote and apply it to your own situation, not recognizing there are many nuances never discussed that can vastly impact whether the anecdote even applies to [your child], Stukus says.

The scariest part of all this is people with a child whos having active symptoms and posts a picture of a rash asking their group, What should I do? And other people with no training whatsoever offer their opinions, he continues. Thats how I see someone might die, and that really scares the hell out of me.

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Food Allergy Treatments and Cures Are Cropping Up Everywhere Online. Parents Beware. - Fatherly

NeoImmuneTechs Chief Business Officer, Samuel Zhang, Ph.D., MBA, will review NeoImmuneTechs recent progress and future directions, including an update on the companys lead drug candidate, Hyleukin-7. NeoImmuneTech is currently conducting several clinical trials of Hyleukin-7 in different types of cancer and multiple pre-IND and non-clinical studies in both solid tumors and hematologic malignancies.

Presentation details:Date: Tuesday, January 14Time: 3:00pm PTTrack: Franciscan B (Ballroom Level)Location: Hilton Hotel, Downtown San Francisco, CA

About Hyleukin-7

Hyleukin-7, the only clinical-stage long-acting human IL-7, is uniquely positioned to address unmet medical needs in immuno-oncology. IL-7 is a fundamental cytokine for T-cell development and for sustaining immune response to chronic antigens (as in cancer). Hyleukin-7's favorable PK/PD and safety profiles make it an ideal combination partner for immunotherapy standard of care (SOC) such as Checkpoint Inhibitor and CAR-T therapies. Hyleukin-7 is being studied in multiple clinical trials in solid tumors, and is being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications.

About NeoImmuneTech

NeoImmuneTech, Inc. (NIT) is a clinical-stage T cell-focused biopharmaceutical company dedicated to expanding the immuno-oncology frontier with Hyleukin-7 and beyond. NIT is partnering with industry and academic leaders to investigate Hyleukin-7 in combination with various immunotherapeutics. For more information, please visit http://www.neoimmunetech.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200103005008/en/

Excerpt from:
NeoImmuneTech to Present at the 2020 Biotech Showcase - BioSpace

Scientists piece together the inflammation mechanism in IgG4-related disease, an autoimmune condition with no current cure, revealing possible therapeutic targets

IgG4-related disease is an autoimmune disorder affecting millions and has no established cure. Previous research indicates that T cells, a major component of the immune system, and the immunoglobulin IgG4 itself are key causative factors, but the mechanism of action of these components is unclear. Now, Scientists from Tokyo University of Science have meticulously explored this pathway in their experiments, and their research brings to light new targets for therapy.

Autoimmune diseases are a medical conundrum. In people with these conditions, the immune system of the body, the designated defense system, starts attacking the cells or organs of its own body, mistaking the self-cells for invading disease-causing cells. Often, the cause for this spontaneous dysfunction is not clear, and hence, treatment of these diseases presents a major and ongoing challenge.

One recently discovered autoimmune disease is the IgG4-related disease (or IgG4-RD), which involves the infiltration of plasma cells that are specific to the immunoglobulin (antibody) IgG4 into the body tissue, resulting in irreversible tissue damage in multiple organs. In most patients with IgG4-RD, the blood levels of IgG4 also tend to be higher than those in healthy individuals. Previous studies show that T cellswhich are white blood cells charged with duties of the immune responseplay a key role in the disease mechanism. In particular, special T cells called cytotoxic T lymphocytes, or CTLs, were found in abundance from the inflamed or affected pancreas of patients, along with IgG4. But what was the exact role of CTLs?

In a new study published in International Immunology, a team of scientists from Tokyo University of Science decided to find the answer to this question. Prof. Masato Kubo, a member of this team, states that their aim was twofold. We planned to explore how IgG4 Abs contributes to the CTL-mediated pancreas tissue damage in IgG4-RD, and also to evaluate the pathogenic function of human IgG4 Abs using the mouse model that we have established. The latter is especially important, as IgG4 is not naturally present in mice, meaning that there is a severe lack of adequate animal models to explore this disease.

With these aims, they selected mice that have been genetically programmed to express a protein called ovalbumin (the major protein in egg white) in their pancreas. Then, they injected IgG4 that specifically targets ovalbumin into the mice. Their assumption was that IgG4 would target the pancreas and bring about IgG-4-RD-like symptoms. However, what they found was surprising. No inflammation or any other symptom typical of IgG4-RD appeared. This convinced the researchers that IgG4 alone was not the causative factor of IgG4-RD.

Next, to check if it was the CTLs that were perhaps the villain of the story, the scientists injected both IgG4 specific against ovalbumin as well as CTLs. Now, the pancreas of the mice showed tissue damage and inflammation. Thus, it was established that the presence of CTLs and IgG4 was necessary for pancreatic inflammation.

When they probed further, they found that another variation of T cells, known as T follicular helper or TFH cells, which develop from the natural T cells of the mice, produce self-reactive antibodies like IgG4, which induce inflammation in combination with CTLs.

Once the puzzle was pieced together, the scientists now had the opportunity to zero in on the target step for intervention; after all, if one of these steps is disrupted, the inflammation can be prevented. After much deliberation, they propose that Janus kinase, or JAK, can be a suitable target. JAK is a key component of the JAK-STAT cellular signaling pathway, and this pathway is an integral step in the conversion of natural T cells of the mice to TFH cells. If this JAK is inhibited, this conversion will not take place, meaning that even the presence of CTLs will not be able to induce inflammation.

Prof. Kubo also suggests a broader outlook, not limited to the therapeutic option explored in the study. He states, based on our findings, the therapeutic targets for IgG4-related diseases can be the reduction of TFH cell responses and the auto-antigen specific CTL responses. These can also provide the fundamental basis for developing new therapeutic applications.

These proposed therapeutic targets need further exploration, but once developed, they have the potential to improve the lives of millions of patients with IgG4-RD worldwide.

###

Reference

Journal:

International Immunology

About The Tokyo University of Science

Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japans development in science through inculcating the love for science in researchers, technicians, and educators.

With a mission of Creating science and technology for the harmonious development of nature, human beings, and society, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of todays most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Masato Kubo from Tokyo University of Science

Dr Masato Kubo is a Professor at the Tokyo University of Science. A respected and senior researcher in his field, he has more than 226 publications to his credit. He is also the corresponding author of this study. His research interests include Immunology and Allergology. He is the team leader at the Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences.

Funding information

This study was supported by grants from JSPS KAKENHI (grant no. 19H03491), Japan Agency for Medical Research and Development (AMED), AMED-CREST, and Toppan Printing CO., LTD.

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Solving the puzzle of IgG4-related disease, the elusive autoimmune disorder - QS WOW News

BEIJING A court in China on Monday sentenced He Jiankui, the researcher who shocked the global scientific community when he claimed that he had created the worlds first genetically edited babies, to three years in prison for carrying out illegal medical practices.

In a surprise announcement from a trial that was closed to the public, the court in the southern city of Shenzhen found Dr. He guilty of forging approval documents from ethics review boards to recruit couples in which the man had H.I.V. and the woman did not, Xinhua, Chinas official news agency, reported. Dr. He had said he was trying to prevent H.I.V. infections in newborns, but the state media on Monday said he deceived the subjects and the medical authorities alike.

Dr. He, 35, sent the scientific world into an uproar last year when he announced at a conference in Hong Kong that he had created the worlds first genetically edited babies twin girls. On Monday, Chinas state media said his work had resulted in a third genetically edited baby, who had been previously undisclosed.

Dr. He pleaded guilty and was also fined $430,000, according to Xinhua. In a brief trial, the court also handed down prison sentences to two other scientists who it said had conspired with him: Zhang Renli, who was sentenced to two years in prison, and Qin Jinzhou, who got a suspended sentence of one and a half years.

The court held that the defendants, in the pursuit of fame and profit, deliberately violated the relevant national regulations on scientific and medical research and crossed the bottom line on scientific and medical ethics, Xinhua said.

Dr. Hes declaration made him a pariah among scientists, cast a harsh light on Chinas scientific ambitions and embroiled other scientists in the United States who were connected to Dr. He. Though Dr. He offered no proof and did not share any evidence or data that definitively proved he had done it, his colleagues had said it was possible that he had succeeded.

American scientists who knew of Dr. Hes plans are now under scrutiny. Dr. Hes former academic adviser, Stephen Quake, a star Stanford bioengineer and inventor, is facing a Stanford investigation into his interaction with his former student. Rice University has been investigating Michael Deem, Dr. Hes Ph.D. adviser, because of allegations that he was actively involved in the project.

Dr. Quake has said he had nothing to do with Dr. Hes work. Mr. Deem has said he was present for parts of Dr. Hes research but his lawyers have denied that he was actively involved.

During the Hong Kong conference, Dr. He said he used in vitro fertilization to create human embryos that were resistant to H.I.V., the virus that causes AIDS. He said he did it by using the Crispr-Cas9 editing technique to deliberately disable a gene, known as CCR, that is used to make a protein H.I.V. needs to enter cells.

The international condemnation from the scientific community that followed Dr. Hes announcement came because many nations, including the United States, had banned such work, fearing it could be misused to create designer babies and alter everything from eye color to I.Q.

Although China lacks laws governing gene editing, the practice is opposed by many researchers there. Dr. Hes work prompted soul-searching among the countrys scientists, who wondered whether many of their peers had overlooked ethical issues in the pursuit of scientific achievement.

Many of them said it was long overdue for China to enact tough laws on gene editing. Chinas vice minister of science and technology said last year that Dr. Hes scientific activities would be suspended, calling his conduct shocking and unacceptable. A group of 122 Chinese scientists called Dr. Hes actions crazy and his claims a huge blow to the global reputation and development of Chinese science.

I think a jail sentence is the proper punishment for him, said Wang Yuedan, a professor of immunology at Peking University. It makes clear our stance on the gene editing of humans that we are opposed to it.

This is a warning effect, signaling that there is a bottom line that cannot be broken.

Despite the outcry, Dr. He was unrepentant. A day after he made his announcement on the genetically edited babies, he defended his actions, saying they were safe and ethical, and he was proud of what he had done.

Dr. He faced a maximum penalty of more than 10 years in prison if his work had resulted in death. In cases that have caused serious damage to the health of the victims, the punishment is three to 10 years in prison.

The court said the trial had to be closed to the public to guard the privacy of the people involved.

Dr. Hes whereabouts had been something of a mystery for the past year. After his announcement, he was placed under guard in a small university guesthouse in Shenzhen and he has made no statements since. But his conviction was a foregone conclusion after the government said its initial investigation had found that Dr. He had seriously violated state regulations.

After Dr. Hes announcement, Bai Hua, the head of Baihualin, an AIDS advocacy group that helped Dr. He recruit the couples, said that he regretted doing so and was deeply worried about the families. In a statement posted on his organizations official WeChat account, Mr. Bai, who uses a pseudonym, said he felt deceived.

When reached by phone, Mr. Bai said he had no idea where the babies were now and declined to say whether he was assisting the government with its investigation.

One H.I.V.-infected man Dr. Hes team tried to recruit said he was not told of the ethical concerns about editing human embryos, according to Sanlian Weekly, a Chinese newsmagazine. The man said a researcher had told him that the probability of his having an unhealthy baby was low and that the team had achieved a high success rate in testing with animals.

The announcement captured the attention of many Chinese people who had not seen or heard from Dr. He in the past year. The hashtag Sentencing in the Genetically Edited Babies Case was trending on Weibo, Chinas version of Twitter.

He violated medical ethics, disrespected life and let three poor children bear the consequences, all for his fame and fortune, one user wrote. I think this punishment is too light.

Elsie Chen contributed research.

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Chinese Scientist Who Genetically Edited Babies Gets 3 Years in Prison - The New York Times

Johnson & Johnson(NYSE:JNJ) enjoyed an excellent run from 2010 to 2017, climbing from $63 to $140 before entering a more volatile period over the past two years. Since then, the stock has bounced between $120 and $147, and it sits closer to the top of that range as 2019 comes to an end. Investors who rode that wave have probably felt frustrated with the ups and downs in recent years, and they're hoping the stock will fare better next year.

The branded company's pharmaceutical segment generates 53% of total company revenue and 67% of its operating profit. This portion of the business currently markets dozens of drugs, but Stelara, Remicade, Imbruvica, Zytiga, Invega, and Darzalex are the current best sellers. Potential regulatory changes and competitionthreatenthe segment, and heavy investments in research and development or acquisitions are required to maintain arobust pipelineto replace drugs with expiring patents. Previous top-seller Remicade is experiencing declining sales due to competition, and pipeline products fromAbbVie(NYSE:ABBV) could threaten Johnson & Johnson's immunology group with pending U.S. Food and Drug Administration approvals.

Image Source: Johnson & Johnson

Medical devices are roughly 30% of total sales and 21% of operating profits. This segment is driven by numerous products for orthopedic, surgical, vision, and interventional applications. The acquisition ofAuris Healthcould hasten Johnson & Johson's entry to the robotic surgery market, which it was already targeting through a partnership withAlphabet. This part of the company has struggled to produce sales growth, with the top line declining nearly 4% year-to-date.

Finally, Johnson & Johnson has a consumer health products segment that contributes 17% of revenue and 12% of total company operating profit. These products include well-known brands such as Neutrogena, Tylenol, Aveeno, Motrin, Zyrtec, Benadryl, Visine, Nicorette, Listerine, and Band-Aid. Johnson & Johnson's consumer division will grow through acquiring and developing promising brands moving forward, but this segment is best characterized as a mature, stable, and slow-moving cash flow generator.

Johnson & Johnson's valuation is somewhat complicated by its combination of businesses because no other health stock offers a direct comparison. Conducting a sum-of-parts analysis and backing into weighted average metrics can be illuminating.

Johnson & Johnson trades at 15.6 times forward earnings, which is somewhat lower than the 18.7 weighted average of major drugmakers, consumer staples companies, and medical device makers. This figure is somewhat less exciting when adjusting for the growth outlook, which results in a relatively high 2.6 PEG ratio. The stock trades at a similar discount based on its 19.6 price-to-free-cash-flow, though the above growth rate caveat is relevant here as well. Finally, Johnson & Johnson's 16.4 EV/EBITDA is roughly in-line with the weighted average, indicating that the company's relatively high financial leverage is partially driving the apparent discount.

For income investors, the stock pays a mediocre 2.6% dividend yield. This number is fine, but there are much higher alternatives elsewhere, and Johnson & Johnson has shown dedication to a buyback program that returns value in the form of anti-dilution to stimulate appreciation rather than income.

Analysts are forecasting below 3% growth for 2020, so the investment community does not seem to recognize massive drivers in the future. Expansion into robotic surgery could help bolster growth in the device segment. Tremfya and Spravato are two drugs that could turn into blockbusters to buoy growth in the medium term. However, Johnson & Johnson is simplyso large and diversifiedthat these positive items are likely only sufficient to maintain a moderately positive growth rate.

Major regulatory changes or issues stemming from its role in theopioid crisiscould certainly send shares tumbling, but there's very little about the current growth prospects or valuation metrics to suggest Johnson & Johnson has a substantial room to the upside. It is likely more prudent to buy this stock when it trades closer to the bottom of its recent range.

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Can Johnson & Johnson Break Out In 2020? - The Motley Fool

This is the fourth of several posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Giny Foudas research focuses oninfant immune responses to infection and vaccination.

Her curiosity about immunology arose during her fourth year of medical school in Camaroon, when she randomly picked up a book on cancer immunotherapy and was captivated. Until then, she conducted research on malaria and connected it to her interest in pediatrics by studying the effects of the parasitic disease on the placentas of mothers.

As a postdoctoral fellow at Duke, shethen linked pediatrics and immunology to begin examining mother to childtransmission of disease and immunity.

Today she is an M.D. and a Ph.D. and amember of the Duke Human Vaccine Institute. Shes an assistant professor inpediatrics and an assistant research professor in the Department of Molecular Geneticsand Microbiology at Duke University School of Medicine.

Based on the recent finding that children of HIV-positive mothers are more susceptible to inheriting the disease, Fouda believes that it is important to understand how to intervene in passive immunity transmissions in order to limit them. Children and adults recover from diseases differently and uncovering these differences is important for vaccine development.

This area of research is personally important to her, because she learned from her service in health campaigns in Central Africa that it is much easier to prevent disease than to treat.

However, she believes that it is important to recognize that research is a collaborative experience with a team of scientists. Each discovery is not that of an individual, but can be accredited to everyones contribution, especially those whose roles may seem small but are vital to the everyday operations of the lab.

At the Duke Human Vaccine Institute, Fouda enjoys collaborating as a team and contributing her time as a mentor and trainer of young scientists in the next generation.

Outside of the lab, Fouda likes to spend time reading books with her daughter, traveling, decorating and gardening. If there was one factor that improve how science in immunology is conducted, she would stress that preventing disease is significantly cheaper than treating those that become infected by it.

Dr. Fouda has made some remarkable progress in the field of disease treatment with her hard working and optimistic personality, and I know that she will continue to excel in her objectives for years to come.

Post by Vandanaa Jayaprakash NCSSM 2020

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Infants, Immunity, Infections and Immunization - Duke Today

This installment is the last of the Marijuana/Hemp CBD series of columns and focuses on the mechanism through which CBD (Cannabidiol Hemp Oil, remember?) works to cure or reduce the magnitude of various ailments.

The ailments that CBD seems to help are arthritis, chronic pain, heart and lung malfunctioning coordinating with the central nervous system. Furthermore, although much more research is needed, it is tentatively concluded that CBD would help reduce autoimmune and inflammatory responses that trigger HIV, cancer and sclerosis.

In terms of dermatological field, CBD is effective in three powerful areas: acne breakouts and redness, preventing excessive oil production and aging over time. Concerning ailments in other animals, such as dogs, cats, horses and birds, we are unaware that their ailments can be reduced or cured by CBD for certain. I have not encountered authoritative literatures on CBD being used to treat animals. However, that is due to my lack of proper literature search. I am convinced there are some solid research literatures available in the field, especially from the research facilities and universities of Israel.

Now we move onto the most important subject of "Why and what does CBD do to cure all that ailments?" Readers, if you are educated through a science class at a college level, you can at least feel that a plant derived chemical would cure or reduce so many wide varieties of ailments as mentioned above can't be real. There has to be some either mistake, misjudgment or worse, a salesman's super hype. Yes, that would be a natural instinct if you had gotten a proper science education in your youth. (Maybe though, you might have slept through it, ha!) So, did I. I said to myself that a chemical extracted from the plant called Hemp, which is available basically everywhere in the world if you look hard, would be so widely effective in treating diseases that seem so remotely connected to each other.

So, I gave myself a mission to dig into this myth. I wanted to find out any credible scientific papers that focus on that question, and that question alone. So, I have gotten some 20 papers of various titles and subjects on CBD. My journey was to find out the very question of why CBD could be so effective for so wide a variety of ailments. My reading these papers started a week ago, and I was nearing the end with no clear conclusion. To read 20 papers in one week is a task I do not want to do again. Finally, I reached the last one, yes, 20th, when my brain got a shot of adrenalin and literally woke up from just a bureaucratic reading to sharply focused excitement. The article title is "Can CBD Really Do All That?" by Moises Velasquez-Manoff, and this paper appeared in New York Time. Due to the limited space and time, I have summarized his description of CBD effect on human body in brief statements.

First, primitive living creatures such as prehistoric fish started to migrate out of the ocean about 460 million years ago. Living on the land gave many advantages to small living creatures than the size-ranked ocean living. One could see farther, and there is less fear of becoming larger foes' lunch. The primitive small living creatures began their journey of evolution to adopt their ability to fit the environment. Today we humans rank as the top dweller of that vast pyramid.

Secondly, in the meanwhile, hemp appeared on the land about 38 million years ago. What hemp brought out into the animal kingdom, including us humans, was a a very effective weapon in immunology. Simply put, hemp produces CBD, which, upon entering human body, produces a material named CB1 Receptor and CB2 Receptors. C 1 ends up in brain, kidney, lungs and liver, while CB2 Receptor ends up in white blood cells of immune system, the gut and the spleen. See Fig 344-1. Without going through a complex and specialized scientific statement, my understanding is that these receptors would then manipulate and guide the human immunological system to better health. As you can see, CB 1 and CB2 combined would cover all the sickness and chronic pain ailments described above. -I would still say that I am amazed that a plant, now called hemp, which showed up on the dry land on the earth 422 million years later than the first primitive animal moved from the ocean to the dry land would know how to fight diseases in the human body and brought forth the very chemical and physiological weapon to do it. Is it just a spectacular coincidence, or God's will and creation?

Nevertheless, we do have this potent weapon called hemp, the most powerful and widely applicable-to-diseases plant on the earth. The plant has been, however, badly mistreated by this nation. In 1937, marijuana was banned nationwide by our country. It does smell of racial prejudice against Mexicans who were entering through the border at that time. I feel that the history may be repeating now. However, I strongly feel that we Americans should positively open up the aggressive research projects on what CBD does for the human health NOW. Israel has been at it, and I am assuming their results would be good. Why are we standing idol and watching the world go by? Hemp produces CBD, which is very widely applicable to many human ailments, and CBD is proven to be positively efficacious with little negative side effects. Let's fund our own research. We have nothing to lose, only much to gain.

This Companion to Aging column appears each week in the Seacoast Sunday features section. You can read earlier installments at http://www.seacoastonline.com. Please send your thoughts about aging to Sasano@umelink.com, Sam Asano, P.O. Box 26, New Castle, NH 03854 or (cell) 781-389-2356 or email Sam at sasano@umelink.com.

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Companion to Aging: The U.S. should fund CBD research - Foster's Daily Democrat

Researchers at the La Jolla Institute for Immunology (LJI), have found definitive evidence that CD4 T cells are not to blame when a mild dengue viral infection morphs into a severe and sometimes deadly dengue hemorrhagic fever/dengue shock syndrome.

This finding is important to both the basic understanding of this disease--the world's most common mosquito-borne illness--and to the hunt for an effective vaccine for dengue.

"We found no evidence to support the common dogma that these T cells are responsible for turning a mild infection to a severe one. This will help us narrow the search for the true culprit," says the study's lead investigator Yuan Tian, Ph.D., an AAI Intersect Fellow, and a Bioinformatics Student at LJI, in the December 24, 2019, issue of Cell Reports.

The goal of the LJI study was to define the molecular pattern of dengue-specific CD4 T cells and to investigate whether there is a difference in the T cell response between patients with mild dengue fever or with severe dengue hemorrhagic fever.

When analyzing dengue-specific CD4 T cells, the researchers realized that the responding CD4 T cells have both a pro-inflammatory function and an anti-inflammatory function which is typically not seen in acute viral infections.

To comprehensively define these dengue-virus specific T cells in hospitalized patients, researchers used whole transcriptome analysis to determine if there was a difference in the quality of the increased response.

This approach allows identifying all RNA transcripts--produced when a gene's DNA sequence is copied, or transcribed--within the transcriptome of dengue-specific CD4 T cells in hospitalized patients being treated for either mild or for severe dengue infection.

These patients were being treated in Sri Lanka, where dengue fever is endemic.

"This is a very powerful approach to detect gene expression activity because all genes upregulated in response to the virus can be identified. It is completely unbiased and does not rely on pre-selected genes," says the study's senior investigator, Daniela Weiskopf, Ph.D., an instructor at LJI, in a related press release.

The research team, to their surprise, detected no difference in the genomic profile of dengue-virus specific CD4 T cells regardless if they isolated them from patients with mild or severe dengue infection.

"The CD4 T cell response in the severe disease does not look different so that cannot be the switch we are all looking for," Tian says.

"In fact, based on some intriguing preliminary findings, we speculate that to counteract the severe immune response occurring in acute cases, these dengue-specific CD4 cells may have gradually acquired the ability to produce more IL-10 by converting IFN. It is as if they are trying to calm themselves, calm the inflammation.

The double-positive CD4 T cells could actually be helping, rather than hurting."

Dr. Tian concluded saying that he hopes these findings will serve to "help guide efforts to develop effective dengue vaccines by improving our understanding of this novel T cell response.

This work was performed as a project of the Human Immunology Project Consortium (HIPC) and supported by the National Institute of Allergy and Infectious Diseases grants U19 AI118626 and P01 AI106695 and NIH contracts HHSN272200900042C and HHSN27220140045C. It was also supported Shared Instrumentation Grants S10 RR027366, S10 OD018499, and S10 OD016262, from the National Institutes of Health.

No conflicts of interest were disclosed.

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases.

Dengue News is published by Precision Vaccinations

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Dengues Progression to a Severe Case Found Not Related to T Cells - PrecisionVaccinations

National Institute of Immunology, an Autonomous Research Institute, Aruna Asaf AliMarg, New Delhi-110067, has invited applications for admission to Ph.D. Programme for the Academic Year 2020-21.

Research at NII encompasses board interdisciplinary areas of Immunology, Infectious and Chronic Disease Biology, Molecular and Cellular Biology and Chemical, Structural and Computational Biology.

Eligibility: Applicants should hold an M.Sc. in any branch of Science, M.Tech., MBBS., M.V.Sc., M.Pharm. or equivalent qualifications as per norms of the Jawaharlal Nehru University (JNU), New Delhi.

Applicant should have at least 60% aggregate score or equivalent grade in Senior Secondary Certificate (10+2) and Bachelor's degree, and 55% aggregate score or equivalent grade in Master's degree in case of General category. Five percent relaxation in aggregate scores in Senior Secondary, Bachelor's and Master's degrees will be applicable for the candidates from reserved categories [OBC (NCL), SC/ST and PwD].

Those who have completed or are likely to complete the required courses in the current academic year can also apply.

Selection to the Ph.D. programme will be through two channels: One will be the Computer based Entrance Examination, NII-2020, to be conducted by NII at multiple centres all over India on 23rd February 2020 (Sunday) and the other will be through the Joint Graduate Entrance Examination in Biology and Interdisciplinary Life Sciences (JGEEBILS-2020).

An applicant must qualify at least one of these two examinations. They will be short-listed for an interview based on either NII Entrance examination or JGEEBILS 2020 marks.

Selected candidates will be enrolled in the Ph.D programme affiliated with Jawaharlal Nehru University, New Delhi.

The online application will be available from December 20, 2019 onwards. The last date for submission of applications is January 31, 2020. Candidates applying through JGEEBILS-2020 must also submit an application through NIl application portal, along with application fees and the JGEEBILS-2020 admit card.

Detailed information, including online application procedure and other information are available at http://www.nii.res.in. Women candidates are encouraged to apply

For more details, visit http://www.nii.res.in

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Research at National Institute of Immunology: Apply by January 31 - Mathrubhumi English