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Chemo-boosting drug discovered for leukaemia – Drug Target Review – Drug Target Review

Drugs developed to treat heart and blood vessel problems could be used to treat leukaemia

Drugs developed to treat heart and blood vessel problems could be used in combination with chemotherapy to treat an aggressive form of adult leukaemia.

Researchers at the Francis Crick Institute, Kings College London and Barts Cancer Institute discovered that acute myeloid leukaemia (AML) causes bone marrow to leak blood, preventing chemotherapy from being delivered properly.

Drugs that reversed bone marrow leakiness boosted the effect of chemotherapy in mice and human tissue, providing a possible new combination therapy for AML patients.

To study how AML affects bone marrow, the researchers injected mice with bone marrow from AML patients. Later, they compared their bone marrow with healthy mice using a technique called intravital microscopy that allows you to see biological processes in live animals. They found that pre-loaded fluorescent dyes leaked out of the bone marrow blood vessels in AML mice, but not healthy mice.

Next, the team tried to understand what caused the bone marrow in AML mice to become leaky by studying molecular changes in the cells lining the blood vessels. They found that they were oxygen-starved compared to healthy mice, likely because AML cells use up a lot of oxygen in the surrounding tissue. In response to a reduction in oxygen, there was an increase in nitric oxide (NO) production a molecule that usually alerts the body to areas of low oxygen.

As NO is a muscle relaxant, the team suspected that it might be causing bone marrow leakiness by loosening the tight seams between cells, allowing blood to escape through the gaps. By blocking the production of NO using drugs, the team were able to restore bone marrow blood vessels in AML mice, preventing blood from leaking out. Mice given NO blockers in combination with chemotherapy had much slower leukaemia progression and stayed in remission much longer than mice given chemotherapy alone.

When the vessels are leaky, bone marrow blood flow becomes irregular and leukaemia cells can easily find places to hide and escape chemotherapy drugs, said researcher Dr Diana Passaro. Leaky vessels also prevent oxygen reaching parts of the bone marrow, which contributes to more NO production and leakiness.

By restoring normal blood flow with NO blockers, we ensure that chemotherapy actually reaches the leukaemia cells, so that therapy works properly, she added.

In addition to ensuring that chemotherapy drugs reach their targets, the team also found that NO blockers boosted the number of stem cells in the bone marrow. This may also improve treatment outcomes by helping healthy cells to out-compete cancerous cells.

The team also found that bone marrow biopsies from AML patients had higher NO levels than those from healthy donors, and failure to reduce NO levels was associated with chemotherapy failure.

Our findings suggest that it might be possible to predict how well people with AML will respond to chemotherapy, said Dr Dominique Bonnet, senior author of the paper and Group Leader at the Francis Crick Institute.

Weve uncovered a biological marker for this type of leukaemia as well as a possible drug target. The next step will be clinical trials to see if NO blockers can help AML patients as much as our pre-clinical experiments suggest.

We found that the cancer was damaging the walls of blood vessels responsible for delivering oxygen, nutrients, and chemotherapy. When we used drugs to stop the leaks in mice, we were able to kill the cancer using conventional chemotherapy, said Dr Passaro. As the drugs are already in clinical trials for other conditions, it is hoped that they could be given the green light for AML patients in the future.

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Chemo-boosting drug discovered for leukaemia – Drug Target Review – Drug Target Review

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Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack – The New Indian Express

Bishnupriya Nayak at BMT unit after bone marrow transplantation | Express

BHUBANESWAR: The Haematology Department of SCB Medical College and Hospital (SCBMCH) at Cuttack has notched up a record of sorts and achieved a new milestone in the country by performing 50 bone marrow transplantations in just over three years.

The special Bone Marrow Transplant (BMT) unit started in February 2014 has conducted its 50th procedure on Bishnupriya Nayak (40), a cancer patient from Koelnagar in Rourkela, on Sunday.Head of the department Prof Rabindra Kumar Jena said it is a significant achievement as SCBMCH having all state-of-the-art facilities is the only State-run hospital in the country to complete 50 cases and provide BMT services completely free of cost.

We have a great record of survival rate of patients than other such units elsewhere in the country. Of 50 cases conducted so far, 47 patients are healthy and doing normal activities. Two died due to infection within a month after BMT procedure, another succumbed to brain stroke (not related to BMT or disease) on 178th day, he said.

The BMT unit at SCBMCH has also established a few international and national distinctions. The eldest transplant conducted so far in Asia and Europe region belonged to the unit. Zabar Khan (74), who was suffering from multiple myeloma (a type of blood cancer) is doing fine after the procedure was performed.Similarly, five patients, aged over 65, have been transplanted successfully which is first-of-its-kind in India, Asia and Europe. The first BMT, also known as stem cell transplant, was performed on Sakuntala Sahoo (54) from Kendrapara district on April 23, 2014.

The unit has also mobilised the stem cell adequately in many complicated blood cancer patients who had very low stem cell blood level of 8.7 per micro litre, besides multiple chemotherapy treated cases and successfully performed BMT procedures.

Stating that the priority is being given on adequate stem cell mobilization, collection and engraftment (proper functioning of new bone marrow graft), Prof Jena said the unit is going to start allogenic BMT soon.

We have been doing autologous transplants so far. Our next plan is to start allogenic transplants. We are poised to take complicated cancer patients for BMT. Besides, plans are afoot to expand the unit to a 20-room ward to accommodate huge waiting lists patients, including thalassemia, sickle sell disease and various cancer patients, he added.

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Bone marrow transplant on record run in SCB Medical College and Hospital at Cuttack – The New Indian Express

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Irish researcher bags 150000 to make 3D-printed knee implant – Siliconrepublic.com

Irish researcher Prof Daniel Kelly has secured 150,000 in funding to develop a novel implant for treating cartilage damage.

As a recipient of one of the European Research Councils Proof of Concept grants, Prof Daniel Kelly will now spend the next 18 months developing his 3D-printed project entitled Anchor.

Using the 150,000, Kelly will look to develop and commercialise his new medicinal product for cartilage regeneration, employing a postdoctoral researcher to help.

Those active in many sports would be familiar with cartilage damage as a result of injury, of which many cases occur in the knee joint. If left untreated, it can lead to difficulties such as osteoarthritis (OA).

OA can be a debilitating condition, with 80pc of those over the age of 60 experiencing limitations in movement and 25pc saying they cannot perform their major daily activities, according to the World Health Organisation.

Kellys product uses 3D-printed, biodegradable polymer components to make a scaffold, which acts as a template to guide the growth of new tissue by recruiting endogenous bone marrow derived from stem cells.

This, Kelly believes, gives it a competitive edge over similar implants, as standard ones are designed with a finite lifespan, making them unsuitable for younger patients with OA.

Kelly, a principal investigator at AMBER the Trinity College Dublin materials science research centre explained why it could be a major breakthrough for other conditions, such as arthritis.

Our 3D-printed polymer posts will anchor the implant into the bone and will be porous to stimulate the migration of stem cells from the bone marrow into the body of the scaffold, he said.

While various scaffolds like this have been available for some time, they have had limited success, partly because scaffolds need to be anchored securely due to the high forces experienced within the joint. Our 3D-printed posts overcome this problem.

Prior to Anchor, Kelly had worked on this technology in previous projects, such as the ERC-funded StemRepair project to develop a range of porous cartilage-derived scaffolds, and JointPrint.

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Irish researcher bags 150000 to make 3D-printed knee implant – Siliconrepublic.com

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How animal genes go into battle to dominate their offspring – Gears Of Biz

Authors

Director of the Ecology Institute, Universidad Nacional Autnoma de Mxico (UNAM)

Professor of Evolutionary Biology and Speciation, University of St Andrews

University of St Andrews

The burdens of becoming parents are often shared unequally between male and female animals. This is particularly true of species that give birth to live young, where male duties such as defending the breeding territory and building dens or nests rarely compare with the ordeals of pregnancy and labour.

You might have thought that animals just accept this imbalance and get on with it. But actually, they compete over how much each parent contributes. This isnt like the competition to win a mate, with locking horns or displays of plumage. Instead this remarkable battle takes place at the level of the genes.

It now appears it may have evolved very early in animal evolution, perhaps among the first child-bearing animals. What is more, it may even help to explain why animals diversified into different lineages.

One arena in which this battle plays out is over the size of offspring. In principle its in both a mothers and fathers interests to produce bigger newborns, since they are more likely to prevail in the struggle for food and survival.

Yet live-bearing females are more likely to die giving birth to larger offspring or become unable to reproduce again. Their mates neednt care unless they are likely to sire more broods together, as with humans and certain gibbons, wolves and mice. Otherwise, the males only concern is that their mate invests as much as possible in the offspring they produce together.

This common conflict of interests manifests itself in various ways in nature. Males often desert pregnant females from birds to humans, for example thereby leaving them with the burden of bringing up the young. More rarely, in some normally biparental species females desert males. We see this in some beetles, for example.

The genetic battle mentioned previously is another manifestation of this conflict. The males of many species can manipulate the genes that they pass on to their offspring so that they induce extra growth at the expense of the mother. As with desertion, this effectively hands the female a greater share of the child-bearing burden than is in her interests.

It works as follows. When an embryo grows inside its mother, it consumes resources from her, signalling its metabolic needs along the way. These signals are influenced by certain hormones which either come from the growth genes of the mother or father. The males manipulate the females to deliver more resources by increasing the extent to which these hormones are produced through a chemical modification of their growth genes during sperm formation.

Females have evolved mechanisms to resist this. They can, for instance, pass on to their offspring what is known as a silenced copy of their own growth gene. This can counterbalance the male genes influence by making the embryo grow less than it otherwise would.

This battle is far less prevalent in truly monogamous species, including humans. This goes back to the fact that it becomes less genetically necessary where the two parents have a common interest in the female producing more offspring in future.

British microbiologist David Haig first proposed in 2003 that this battle was more likely in organisms where one sex disproportionately contributes to the offspring, such as live-bearing species, particularly polygamous ones. This was used to explain the puzzling size of the offspring of crosses between oldfield mice and deer mice.

Separately, these species produce similar sized offspring. Yet crosses between male deer mice and female oldfield mice produce offspring that are larger, while the offspring from female deer mice and oldfield males are smaller. Oldfield mice are monogamous while deer mice are polyandrous, meaning one female mates with several males.

Mimicking nature by artificially manipulating a growth gene called igf2, researchers showed that these smaller and larger offspring were due to genetics. In further support of the theory, placental mammals and marsupials including kangaroos and opossums have since been found to have signs of female resistance to such male manipulation.

How early did this mechanism evolve? Researchers have previously suggested it arose in live-born mammals, and would therefore be absent in egg-laying mammals such as the platypus and other vertibrates.

But that raises questions about all the reptiles, amphibians and fish which produce live young, since the same genetic manipulation would equally be in their males interests. To see if it was present, we looked at a Mexican fish called the amarillo or dark-edged splitfin (see lead image).

Along with co-researchers Yolitzi Saldvar and Jean Philippe Vielle Calzada, we crossed males and females from two distant populations of these fish, since they would not have evolved mechanisms which cancel one another out in the way that a single population is likely to have. Sure enough, the size of the embryos was influenced by the specific combination of father and mother. We found signs of male manipulation and probable resistance from the females.

Though based on a small sample size, this suggests that these mechanisms evolved much earlier than previously believed: fish split from other vertebrates some 200m years before live-bearing mammals appeared, dating back about 370m years in total. Whether it comes from a single evolution or from several in different lineages, we cannot yet tell.

One consequence of these genetic battles is the effect on reproductive compatibility within a species. The genetic mutations aimed at manipulating offspring that take place among males and females within a certain group of a species are like a sort of arms race. The genes continually adapt and counter-adapt to one another to try and further their reproductive interests.

If they then mate with an animal from a different group of the same species, their genetic mutations can have made them sufficiently unmatched over time that they are unable to reproduce thus they are now two species. If this started happening much earlier in evolution than was previously thought, it is likely to have influenced how different groups of live-born animals diverged, including lizards, sharks and mammals. From little acorns, these are the kinds of big oak trees that can grow.

This article was originally published on The Conversation. Read the original article.

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How animal genes go into battle to dominate their offspring – Gears Of Biz

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A Fourth-Generation DNA Base Editor Could Replace CRISPR – Futurism

CRISPR: The Next Generation

The latest news in genetic science has been dominated by the CRISPR/Cas9 technique over the past fiveyears. But a new fourth-generation DNA base editor could see CRISPR dethroned, according to a recent study published in Science Advances.

The fourth-generation base editor a tool used to modify the building blocks of genetic code, only now with an inhibitor added to protect DNA from accidental changes heightens editing accuracy and reduces unintentional DNA changes, which occur with current base-editing technologies.

DNA is a series of base pairs, or nucleotides: adenine, thymine, guanine and cytosine, called A-T-G-C for short. When CRISPR converts a C:G base pair to a T:A pair, sometimes it inadvertently changes the C:G base pair to a G:C or A:T base pair. Thismight seem like an insignificant mess of letters, but on the genetic level, even a single mistaken nucleotide can have devastating consequences for an organism.

Approximately two-thirds of known human genetic variants associated with disease are point mutations, said study co-author David R. Liu, Harvard University Professor of Chemistry and Chemical Biology and Howard Hughes Medical Institute Investigator, in an email interview with Futurism.The fourth-generation base editors to my knowledge are the most effective forms of these molecular machines that can directly correct certain types of point mutations.

Liu, co-author Alexis Komor, and their colleagues found that the number of undesired editing products depends on the level of a cutting enzyme called uracil N-glycosylase (UNG). Uracil is one of the four base pairs found in RNA, which is involved in the process of transcribing DNA so that its code is physically expressed by the organism.

Mechanistically, it made sense that [this]was leading to the undesired products we would occasionally observe, Liu explained. The teamhad a hunch that UNG, which initiates base excision repair at uracils, might be the culprit. Indeed, when we performed base editing in cells lacking UNG, essentially all undesired product formation went away.

Komoret al. then designed a fourth-generation base editor combined with an inhibitor, called BE4, which blocks UNG from cutting and altering DNA inadvertently. BE4 shuts down the cellular troublemaker (UNG) more effectively than our previous base editors, which results in higher efficiency of C to T base editing, and also fewer undesired products, said Liu.

Using BE4 formed with the bacteriaStreptococcus pyogenes, this base editing procedure increased the efficiency of swapping C:G to T:A by 50 percent, while halving the frequency of undesired byproducts. Click to View Full Infographic

This comes at a time when the number of incredible things CRISPR is doing extends beyond the medical field: into ecology, with the possibility of artificially designing algae to create a more efficient biofuel, and national security, with the U.S. Advanced Research Projects Agency (DARPA) investing $65 million in a project called Safe Genes.The DARPA Safe Genes program is very forward-thinking and focused on important issues including safest practices for genome editing, as well as helping to advance these technologies to realize their full potential, commented Liu.

Ultimately, the optimum balance lies in protecting the public with restrictions on gene editing technology, but not implementing so many that it decreases the number and diversity of efforts to use these technologies for the public good, Liu said.

For a nominal charge, Lius team has made the base editor available ona nonprofit genetic repository called Addgene: We definitely want the scientific community to use these tools.

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A Fourth-Generation DNA Base Editor Could Replace CRISPR – Futurism

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Workshop Next Week On Public Interest And CRISPR Gene Editing, CAR T Cancer Treatment – Intellectual Property Watch

Experts at a one-day workshop in Washington DC next week will discuss public interest aspects of patents and two breakthrough new medical technologies related to gene editing (CRISPR) and cancer treatment (CAR T).

The 15 September event, entitled, Patents, the Public Interest and Two New Medical Technologies: CRISPR and CAR T, will feature a unique mix of key health advocates, academics, licensing and standards experts, congressional staff and others.

A live webcast on YouTube will be available here.

Event moderators include William New of Intellectual Property Watch and Sarah Karlin-Smith of Politico.

The full KEI event announcement is reprinted below:

Workshop: Patents, the Public Interest and Two New Medical Technologies: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), Chimeric Antigen Receptors (CAR) technologiesOn September 15th, 2017, Knowledge Ecology International will be hosting a workshop on: Patents, the Public Interest and Two New Medical Technologies: CRISPR and CAR T.

CRISPR related inventions include breakthrough technologies to modify genes, which have broad applications for innovations in medicine, agriculture and other fields.

CAR T therapies are an exciting new approach to treating cancer and other diseases, including previously incurable cancers.

Both technologies were developed with significant funding from the U.S. federal government.

There are controversies over the licensing of several CRISPR related inventions, and over the pricing of new CAR Treatments, including most recently the decision by Novartis to charge $475,000 for Kymriah, a CAR T treatment for leukemia.

The workshop will bring feature a diverse group of experts and stakeholders to discuss the public policy challenges appropriate governance of CRISPR and CAR Ts intellectual property.

Date: Friday, September 15, 2017Location: Kaiser Permanente Center for Total Health, 700 Second St. NE (near Union Station), Washington, DC 20002

To Register: use this form.

A PDF version of the program is available here.

Related

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Workshop Next Week On Public Interest And CRISPR Gene Editing, CAR T Cancer Treatment – Intellectual Property Watch

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New genetic testing lab development to improve DNA test turnaround – Sheep Central

Processing time for sheep DNA tests is set to improve through Neogens new genomic testing laboratory in Queensland.

AUSTRALIAN sheep DNA testing turnaround times are expected to be more reliable and up to 40 percent faster with Neogen Corporations decision to establish a genomic testing laboratory in Queensland.

GeneSeek Australasia, a wholly owned subsidiary of United States-based parent company Neogen, has acquired the assets of the Animal Genetics Laboratory, based at the Gatton campus of the University of Queensland.

The Neogen facility in Australia will be its fourth animal genomics laboratory, joining locations in the US, Scotland, and Brazil.

Chief executive officer of the Cooperative Research Centre for Sheep Industry Innovation (Sheep CRC) Professor James Rower expected reliable turnaround times for DNA could be reduced from four to three weeks.

Todays announcement is a major development which will help consolidate the use of DNA technologies and support accelerated genetic improvement in our flocks.

The Cooperative Research Centre for Sheep Industry Innovation (Sheep CRC) has led the development of DNA testing within the Australian sheep industry and has worked in collaboration with Neogens GeneSeek laboratories since the start of the Information Nucleus program in 2007.

GeneSeek has always provided competitive pricing and excellent quality control but until now all tests had to be shipped to the US for processing, Sheep CRC chief executive James Rowe said.

While the range of DNA test products we have developed has proven to be immensely valuable to sheep breeders, the turnaround time from taking blood samples to receiving results has been the biggest single factor limiting wider uptake of genomic technologies within the Australian sheep industry.

Professor Rowe didnt expect the development would change the price of DNA testing initially.

The real story is that we wont need to send our samples to the United States in the future, which is one step that has been variable and quite frustrating.

Every now and then you get a batch that is held up in US Customs or goes walkabout with the courier system, and when that happens it pushes our turnaround time out to about 10 weeks.

Prof. Rowe said the new lab would result in faster and more consistent turnaround time and combined with the new GeneSeek technical platform would also mean fewer repeat analyses.

At the moment we are operating pretty much on a 4-5 week turnaround, unless you get a glitch, which throws everyone into turmoil, he said.

But Professor Rowe said there would be a transition period while Neogens new Queensland laboratory is set up, but within six months, DNA test turnaround times could drop to three weeks.

Thats a game-changer.

Quicker turnaround would be particularly valuable for terminal ram breeders wanting to make earlier selection decisions after taking weaning weight, muscle and fat scan measurements, he said.

Neogens vice president of corporate development and cirector of GeneSeek AustralAsia, Dr Jason Lilly, said that as Neogens business in Australia had grown, the company had recognized the importance of improving its presence in the local market and its service to strategic partners such as the Sheep CRC.

Combining AGLs complementary expertise and local support with GeneSeeks animal genomic capabilities, will provide Australian sheep producers with the utmost in local service, turnaround time, and technical support, Dr Lilly said.

The lab will feature the latest equipment and will be compatible with the recent developments in the parentage and 15k multi-trait genotyping tests for the Australian sheep industry.

This will mean that breeders will be able to plan their genotyping around the best possible combination of parentage and multi-trait genotyping testing to minimise the costs of double testing and maximise the information from multi-trait genomic predictions, Prof. Rowe said.

GeneSeek has always provided excellent technical support in the design and development of the Sheep CRCs DNA testing systems and being based in Australia is likely to further enhance what has been a very productive working relationship.

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New genetic testing lab development to improve DNA test turnaround – Sheep Central

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Genetic testing may benefit this population – ModernMedicine

In the Ashkenazi Jewish population, the mutation profile ofBRCA1andBRCA2is distinctive, with three ancient founder mutations in these two genes. Combined, these three mutations are responsible for 10% of invasive breast cancer among Ashkenazi Jewish women.

The relatively high frequency of the Ashkenazi Jewish founder mutations inBRCA1 andBRCA2has enabled the effective use of cancer genetics services by Jewish women, according to research published online July 20, 2017, in JAMA Oncology.

For Ashkenazi Jewish patients with breast cancer who do not carry one of these three founder mutations, the chance of carrying some other pathogenic mutation inBRCA1orBRCA2, or a pathogenic mutation in a different breast cancer gene, is not known. This information, however, would be valuable to patients and their families for cancer prevention and treatment.

King

A group of researchers, led by Mary-Claire King, PhD, Department of Medicine, University of Washington in Seattle, conducted a study to determine the frequency of cancer-predisposing mutations other than theBRCA1andBRCA2founder mutations among patients of Ashkenazi Jewish ancestry with breast cancer.

Should Ashkenazi Jewish women with breast or ovarian cancer who have negative results for the three founder mutations obtain complete sequencing ofBRCA1andBRCA2so as not to miss some other mutation? Should these patients also be tested for mutations in other breast cancer genes?

We addressed these questions by sequencing all known breast and ovarian cancer genes in genomic DNA, which was provided by participants of the New York Breast Cancer Study (NYBCS), a longstanding cohort of Ashkenazi Jewish women with a primary diagnosis of invasive breast cancer, the authors said.

The result, they said, is that Ashkenazi Jewish patients with breast cancer can benefit from genetic testing for all breast cancer genes. Comprehensive sequencing would provide complete relevant genetic information.

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Genetic testing may benefit this population – ModernMedicine

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This Company Freezes Your Body So That You Could One Day Be Resurrected – Billionaire BLLNR | Singapore (registration)

An estimated 2,500 bodies around the world have been frozen in the hope of some future resurrection.

Robert Ettinger, the father of cryogenics, who introduced the concept in 1962.

If you have around US$90,000 to spare and are of a gambling disposition, perhaps your final journey should be to Australia. A company called Southern Cryonics is looking to open a facility in New South Wales this year that will allow its customers to freeze their bodies after death in the hope of one day being resurrected. If it goes ahead, it will make Australia only the third country, after the US and Russia, where such a service is available.

But, especially for those of a futurist bent perhaps, its as valid a thing to do with ones body as burial or cremation. Last year, a terminally ill 14-year-old girl in the UK became the first and only child so far to undergo the cryonic process. This is technically not freezing but vitrification, in which the body is treated with chemicals and chilled to super-cold temperatures so that molecules are locked in place and a solid is formed. An estimated 2,500 bodies around the world are now stored in this condition.

Supporters concede that the technology to revive the infinitely complex interactions between those molecules may never exist, but are nonetheless hopeful, pointing to shifting conceptions of what irreversible death actually is. If, for example, cessation of a heartbeat used to define it, now hearts can be re-started todays corpse may be tomorrows patient. They point to experiments such as that announced last year by 21st Century Medicine, which claimed to have successfully vitrified and recovered an entire mammalian brain for the first time, with the thawed rabbits brain found to have all of its synapses, cell membranes and intracellular structures intact.

Its not just cryonics. Stem-cell research, nano-tech, cloning, the science just keeps plugging away towards a future [of reanimating] that may or may not come to exist, says an upfront Dennis Kowalski, president of the Michigan-based Cryonics Institute. His company was launched just over 40 years ago to provide cryostasis services. Lots of things considered impossible not long ago are possible today, so we just dont know how cryonics will work out. For people who use the service its really a case of theres nothing to lose.

Naturally, not everyone is hopeful that such processes will ever work out for those in the chiller. The problem with cryonics is that the perception of it is largely shaped by companies offering a service based on something completely unproven, says Joo Pedro De Magalhes, biologist and principal investigator into life extension at the University of Liverpool, UK, and co-founder of the UK Cryonics and Cryopreservation Network. Youre talking about a fairly eccentric procedure that only a few people have signed up to and into which little reported research is being done. That said, I think the people providing these services do believe theres a chance it may work one day, although I would have to say theyre optimistic.

But this is not to say that living longer wont, in time, prove possible as a result of some other method; just that arguably this is more likely to be based around preserving a life that has not experienced death, rather than the promise of reanimating one after its demise. The chasm between the two is all the more pronounced given neurosciences still scant ideas as to what consciousness or mind is, let alone how it might be saved and rebooted; would the warmed and reanimated you be the you that died, or a mere simulacrum? Your body may well not be the same: many of those opting for cryo-preservation go for the freezing of just their brains.

Certainly while cryonics specifically may remain a largely unexplored field, Google is now investing in anti-ageing science, an area that, as De Magalhes puts it, now has fewer crackpots and more reputable scientists working in it, with stronger science behind it too. Indeed, as Yuval Noah Harari argues in his best-selling book Homo Deus, humanisms status as contemporary societys new religion of choice, combined with technological advances, makes some form of greatly extended lifespan inevitable for some generation to come. Whether this will be by melding man and machine, by genetic manipulation, by a form of existence in cyberspace or some other fix can only be speculated at, but everything about our civilisations recent development points to it becoming a reality.

Advances in medicine, after all, have greatly extended average longevity over the last century alone. With this has come a shift in perspective that sees death less as the natural end point to a life so much as a process of disease that could, and perhaps should, be tackled like any other disease that threatens existence. De Magalhes points out that for many working in the field it is less about the pursuit of immortality as of improved health.

After all, its not self-evident that we all want to live forever, and there are philosophical arguments for the idea that death is good, that its necessary to appreciate life, he says. But it is self-evident that nobody wants Alzheimers, for example. If you focus on retarding the problems of ageing then inevitably were going to live longer. The longevity we have now isnt normal; its already better than what we had not long ago. Extrapolate that to the future and in a century the length of time we live now might be considered pretty bad. One can envisage a time when we might live, if not forever, then perhaps thousands of years so much longer than we live now that it might feel like forever.

That, naturally, would bring with it profound changes to the way in which we perceive ourselves and to how the world operates and all the more so if living considerably longer became a possibility faster than society was able to inculcate the notion. How would such a long lifespan affect our sense of self? Would institutions and mores such as lifelong marriage and monogamy remain the norm? When would we retire? How would our relationships with the many subsequent generations of our family be shaped? How would population growth be managed? How would such long lives be funded?

Such questions are, for sure, of no concern to those currently in cryostasis. These people tend to be into sci-fi, and into science too, suggests Kowalski, who has signed up himself, his wife and children for cryonic services when the time comes. I think for a lot of them its not necessarily about the fear of death. Its more a fascination with the future. Theyre optimistic about what it will bring. Theyre more Star Trek than Terminator.

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This Company Freezes Your Body So That You Could One Day Be Resurrected – Billionaire BLLNR | Singapore (registration)

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Controversial Genetic Testing Company in Receivership – Pain News Network

In June, FBI agents raided the companys headquarters in Irvine, California. Former and current employees who were interviewed by STAT said the agents were focused on possible kickbacks to doctors who encouraged patients to take Prooves DNA tests. Physicians reportedly could make $144,000 a year in kickbacks that were called research fees.

In July, PNN reported that Proove was linked to a Medicare fraud case, in which three Indiana healthcare providers allegedly caused Proove Bioscience to falsely and fraudulently bill various health care programs for genetic tests… that were not medically necessary and never interpreted.”

Proove was not named as a defendant in the Indiana case. In an email to PNN, Meshkin said Proove had cooperated with investigators.

Proove has cooperated with both the FBI and US Attorneys office on this case,” said Meshkin. “With regards to tests being ‘medically necessary’, Proove received written and signed determinations of medical necessity supporting the tests ordered and billed to insurance carriers just like every other laboratory which requires such a determination on a test requisition form. Thus Proove operated appropriately and consistent with usual and customary practices.”

Meshkin also defended Proove research, published in the Journal of Addiction Research & Therapy, which claimed to show the effectiveness of its genetic tests.The publisher of the journal, OMICS International, has been accused by the Federal Trade Commission (FTC) of deceiving researchers and readers about the true nature of its publications and peer review process.

“Proove can only speak to its experience with this particular journal, Meshkin said in an email to PNN. “Specifically for papers submitted to this journal, our R&D team and academic collaborators engaged in documented, extensive peer-review, received suggested edits and provided responses to the suggested edits to the manuscripts submitted for review and publication. Thus, Proove would certainly consider the publications accepted from Proove-affiliated authors in that journal to be ‘peer-reviewed’.”

According to the FTC complaint filed last August, OMICS has created hundreds of “open access” online medical journals that publish articles with little or no peer review. Researchers are also charged significant fees to get their articles published by OMICS, a “pay to play” policy that some consider unethical because it diminishes the quality of academic journals and the peer review process.

Proove has aggressively promoted its genetic tests with healthcare providers around the country. A pain clinic in Montana, for example, had a Proove patient engagement representative employed on site at the Benefis Pain Management Center in Great Falls.

We had a meeting one day and here are these people from Proove Biosciences. They told us they were doing a research project, said Rodney Lutes, a physician assistant who was later fired by Benefis. They wanted to come to Benefis, into the pain department, and test our patients. We were told this would be at no cost to the patient. My understanding was that they werent going to charge anybody, but I found out afterwards they were charging insurance companies.

They said providers who participated in this would get some form of payment for participating in the program and for filling out all the paperwork.

Lutes supervising physician at the clinic was Katrina Lewis, MD, a pain management specialist at Benefis who is listed as a member of Prooves Medical Advisory Board. Lewis apparently plays a significant role at the clinic, even though she only works there part time. Benefis has denied that Lewis or any of its employees received kickbacks from Proove for referring business to them.

STAT reported that Prooves restructuring was apparently ordered by Mike Leavitt, a Proove board member, who also served as Utah governor and secretary of the Department of Health and Human Services. Leavitts investment firm, Leavitt Equity Partners, provided about $7 million in funding to Proove, according to Meshkin.

A former Proove manager told STAT that she initially felt good about going to work for the company, but soon had misgivings about Proove’s research and billing practices.

It sucked the life out of me, on an integrity level, said Rhonda Frantz-Smith. It got more and more corrupt.

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Controversial Genetic Testing Company in Receivership – Pain News Network

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Open Longevity Project: a Scientific Approach to Conquer Aging – Blockchain News

A new project in the field of biotechnology, telemedicine, clinical research and medical services is completing preparations for pre-ICO. Open Longevity is organizing research of anti-aging therapies in humans by providing online advisory services. Their ultimate goal is to find and introduce effective methods of radical life extension into clinical practice. Therefore, the tokens are called YEAR.

The project claims they will combine the capabilities of modern IT-systems, the expertise of leading scientific analysts and the energy of the patients themselves. Another driving force they emphasize is openness and rejection of commercial benefits in those matters where this can affect the objectivity of scientific research.

One of the common concerns, when antiaging drugs are being mentioned, is that, once proven effective, anti-aging medicine will become available only to the elite. The fact that the trials results will belong to the patients community, might be a possible solution to this potential problem.

Mikhail Batin, the CEO of Open Longevity, states he is sure that effective ways to delay the onset of aging will be foundit is only a matter of time. He and his colleagues just want to accelerate the research.

The project consists of two parts: clinical trials and online service. Part of the funds raised through ICO will be spent on the first three studies: Longevity Diet-1 (a variant of a fasting mimicking diet); Alzheimers disease therapy (vitamin B12) and atherosclerosis therapy (sartans + statins). One can even find documents for the first trial in progress, though just in Russian yet. As the trial is planned to be submitted to NIHs https://clinicaltrials.gov, the documents will be translated into English at some point.

All the subsequent studies will later be also funded: life extension projects are expected to be submitted for voting on a general basis, voting will be conducted among all the YEAR token holders.

All clinical trials will be carried out in strict accordance with existing norms. Thus CROs (contract research organizations), laboratories, and clinical institutions that traditionally carry out similar research, will be involved. But OL team is already talking about making all paperwork more automated.

Another part of the funds will be spent on creating an online platform. By uploading biomedical data, users will be able to monitor their health and aging status in dynamics; receive recommendations from specialists and expert system based on AI; and also become volunteers in trials.

The service will be accessible to everyone. But payment with YEAR tokens is promised to be more favorable than paying with fiat currencies due to 50% discount. This, among other points mentioned in projects WP, has to maintain a constant token flow within the system and ensure the stability of its exchange rate.

The first three days of pre-ICO is going to be in the format of Private Placement. The registration has started already, but the date of preICO launch itself will be announced in advance in projects channels in Telegram.

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Texas relief funds benefit farmers and ranchers – Kotatv

RAPID CITY, S.D. (KOTA TV) – Hurricane Harvey is still wreaking havoc in Texas, and South Dakota farmers and ranchers are no stranger to the affects of Mother Nature.

“What the country did for South Dakota ranchers and particularly those ranchers in our neck of the woods was awesome, said Kadee Handee, marketing manager of the Black Hills Stock Show and Central States Fair. We want to make sure that your donation will go to an organization that will truly use it.”

Hurricane Harvey has displaced many families from their home, but also cattle from their pastures.

According to the U.S. Department of Agriculture, about 1.2 million beef cows are registered in the 54 counties that have been declared as disaster areas.

Hundreds of pets have been rescued from the rising waters as well. If you are interested in donating to that cause, seek out local shelters in Houston and San Antonio.

But there are other ways to donate as well. Tangible donations like hay, resources and even animals can be made to the Agri-Life Extension.

“It is an arm of the Extension Agency in Texas that will be able to facilitate those demands and facilitate those resources to those ranchers that are affected, said Handee

The Texas FFA Association and the Texas A&M Veterinary Emergency Team are some more reputable organizations that are accepting donations for relief funds.

Donations can also be mailed to: Cattleraisers Relief1600 Gindy St. Ft. Worth, TX 76107

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Regulating Bone Marrow Protein can Improve Stem Cell Transplants – CMFE News (press release) (blog)

A recent study has identified a key protein capable of regulating the process of new blood cells, including immune cells, which can potentially improve bone and stem cell transplants for donors as well as recipients. The researchers at Technical University of Dresden, Germany, led by the University of Pennsylvania, USA, found that a protein known as Del-1 occupies a key role in the process of hematopoiesis. In addition, researchers inferred that the protein regulator may be modulated to act as potential drug targets in patients affected by certain blood cancers types.

The findings were reported this week (August 28 September 1, 2017) in The Journal of Clinical Investigation.

Del-1 Expression in Hematopoetic Malignancy Key to Boost Myelopoesis in Bone Marrow Transplants

Initially, some of the researchers discovered that Del-1 was the soluble protein that acted as a powerful drug target in gum diseases. Further investigating the role of the protein in hematopoetic malignancy, they inferred that it played a more global role by establishing its expression in a variety of cell types in bone marrow, most notable of them being endothelial cells, CAR cells, and osteoblasts.

The scientists observed that hematopoietic stem cells plays an increasingly important role in various stressful conditions such as bone marrow injury, stem cell transplantation, or systemic infection. These cells affect the production of myeloid cells that forms the core of bone marrow transplants.

Modulating Protein Regulator may Prove Promising in Some Chemotherapies

The team found that the presence of Del-1 in recipient bone marrow facilitated the process of engrafting in recipients by greatly influencing myelopoesis and consequently boosting the formation of new blood cells. The results were observed in experiments conducted in mice suffering with systemic infection. Whereas, in donors, limiting the interaction between the protein and hematopoetic stem cells could boost donor cell numbers in the blood stream, inferred scientists.

Furthermore, the research team observed that the protein regulator also boosts the production of immune-related blood cells. Thus, this may prove to benefit patients suffering with febrile neutropenia who are undergoing chemotherapy.

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Regulating Bone Marrow Protein can Improve Stem Cell Transplants – CMFE News (press release) (blog)

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SCB conducts 50th bone marrow transplant – Times of India

CUTTACK: The bone marrow transplant unit of SCB Medical College and Hospital achieved a feat on Sunday by successfully conducting its 50th bone marrow transplant (BMT)surgery.

The 50th patient to be operated on Sunday was Bishnupriya Nayak, 40, a cancer patient from Rourkela in Sundargarh district.

The BMT wing was started at SCB in 2014 and in three years the department has operated 50 patients. Besides, it has managed to conduct BMT surgery on a 74-year-old patient Zabar Khan. Hospital authorities claimed that he is the oldest person to undergo bone marrow transplant in the country. “Zabar Khan, a patient of multiple myeloma, was operated in 2015 and he is doing fine. He is the oldest patient to undergo BMT in Asia. Adding to it, we have done BMT on five patients who are above 65 years of age. In elderly patients, the risk factor is quite high,” said head of the BMT unit, Dr R K Jena.

Jena highlighted that so far only three patients out of the 50 have died. “Two patients died due to infection while one succumbed to brain stroke,” added Jena.

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SCB conducts 50th bone marrow transplant – Times of India

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Our Community: Firm pitches in for Woodwynn Farms – Times Colonist

An event-rental business haspartnered with a therapeutic community to introduce altruism into its business model, producing a new kind of accountable commerce.

The Wise Co. has announced it will offer a collection of rental furniture designed and produced by the therapeutic community at Woodwynn Farms.

I had often worked with people who were incredibly generous, and wanted to do good for their communities, said Niecia Dunn, CEO and founder. But due to the hastiness of [the] Western lifestyle, [they] lacked the network or ability to source the right target for the resources they had to offer.

People can now support the farm through renting reasonably priced furniture produced by the farms residents.

Half of all rental costs for the lifetime of the products will return to the 193-acre farm to fund the Believe in People program established by social pioneer Richard Leblanc.

The goal of the program is to raise $30,000 what it costs to sponsor a participant to live at the farm for a year.

The unveiling of the first piece of furniture from the new rental partnership line will take place at a four-course Fall Harvest Dinner, hosted by the Greater Victoria Chamber of Commerce, Sept.7 at Woodwynn Farms, 7789West Saanich Rd.

For more information, go to woodwynnfarms.org.

Donating blood saves lives. Last week, a Vancouver Island woman got to celebrate her 55th birthday and to meet the person whose blood donation made it possible.

Ann Radelet was diagnosed with non-Hodgkins lymphoma in 2003 and underwent three years of chemotherapy. By 2006, the cancer had returned and had transformed into a secondary cancer. The only hope left for her was a bone-marrow transplant.

Her doctor suggested they try a stem-cell transplant instead of a marrow transplant.

But they needed a donor.

The doctors look at antigens in the blood, which they rate out of 10. They tested Radelets two siblings, but found only a five-out-of-10 match, which was not good enough. So they went further afield, looking for donors in a worldwide registry.

Just as she was undergoing her seventh round of chemotherapy, Radelet got the news that they found a nine-out-of-10 match, which translates into a 70per cent success rate.

She received the donated stem cells in February 2007.

She has been cancer-free since then.

Donors are protected by privacy regulations. Radelet was told she would have to wait two years before she could inquire about the donor and only if the donor would allow it.

She eventually found out the donor was a woman named Nicole from Duisburg, Germany. The two corresponded and have talked frequently since then.

When Nicole and Radelet spoke for the first time, they said: We are blood sisters, and that name has stuck for the pair.

In August, Nicole and her sister (an eight-out-of-10 match) visited Vancouver Island for their first meeting in person.

We are all so very excited. I cant ever thank her enough, but I will honour her any way I can, said Radelet. I am so grateful for the team at Vancouver General Hospital and the Canadian Blood Services. They save so many lives in more ways than one.

I am forever eternally grateful to Nicki; she donated blood and stem cells and saved my life. Thank you to all the blood donors out there. I needed lots of it during all my chemotherapy.

My family is still whole. My mother still has her daughter, my brothers still have their sister, my children still have their mom, my husband still has his wife, and now I am a grandma to three adorable babies. I am the most fortunate woman in the world.

Canadian Blood Services maintains the OneMatch Stem Cell and Marrow Network. It is responsible for finding and matching volunteer donors to patients who require stem-cell transplants.

For more information on the network, what it entails and how it saves lives, go to blood.ca.

Need2 Suicide Prevention and Education Support is hosting a public gathering to mark World Suicide Prevention Day, Sunday, Sept. 10 in Centennial Square.

This marks the 15th year of the event. The gathering aims to bring awareness to the efforts to prevent deaths by suicide and the devastating effects of suicide.

The gathering is an open forum where everyone can share. Educational information will be available, along with Need2 support staff.

Suicide is difficult to talk about. It is emotionally charged and carries a great deal of associated shame and stigma.

When persons who are feeling suicidal try to talk about their feelings of desperation, hopelessness and alienation, there is often no one who can really hear their pain.

Need2 provides assistance (urgent or general), runs suicide-prevention programs, puts on workshops and provides information.

The event runs 2 to 4 p.m. Sept. 10 in Centennial Square. For more information, go to need2.ca.

Kane Mercer has just completed a cycle tour across Canada in memory of his father and to raise awareness and funds for Victoria Hospice and palliative care.

Like life, long journeys can be challenging and full of unexpected difficulties, said Mercer. But through a positive attitude, support from friendly people and a consistent effort, these hurdles can be overcome.

In honour of the fifth year since his passing, Mercer is keeping the memory of his father alive with this epic cycling tour across Canada called Ride for Rand.

I decided to make this ride in support of Victoria Hospice in acknowledgment of the support they gave my father and my family, he said. Hospice is a chronically underfunded and neglected area, which I feel deserves attention.

Donations fund almost half of Victoria Hospices annual operating costs. Funds enable it to provide the best possible end-of-life care. For more information, or to donate, go to victoriahospice.org.

The Cook Street Village Activity Centre has just published its Fall Program Guide, listing the many fun and interesting events for the entire family.

Cribbage Tournament Everyone is welcome to this social tournament. It costs $5 to join. It runs 1 to 3:30 p.m. on Sept.13.

Welcome Back to Fall New and seasoned friends are invited to learn about new programs, events and activities. Enjoy a Syrian meal, and watch a play about Emily Carr at this family-friendly event.

Tickets are $12 (or $10 for members) and $6 for children. The event runs 12:20 to 2:30 p.m., Sept. 14 Please purchase tickets by Sept. 8.

International Day of Older Persons Celebrate the United Nations International Day of Older Persons with free activities. This event is free to attend. It runs 8:30 a.m. to 4 p.m. Sept. 30.

Other activities taking place at the centre include yoga, Pilates, Tai Chi, learning different languages, workshops, music, art, listening to guest speakers, learning about computers and seasonal events.

Membership includes discounted rates for courses and daily drop-in programs.

Volunteers are always welcome.

All events take place at the Cook Street Village Activity Centre, 380 Cook St.

For more information, go to cookstreetvillageactivitycentre.com.

Seniors Serving Seniors is recruiting volunteers for its Return to Health Program, as well as candidates for its October training session.

Training for volunteers, funded by the United Way of Greater Victoria, consists of a comprehensive course on seniors concerns and services.

Graduates also attend monthly, two-hour support meetings throughout the year.

Return to Health volunteers provide companionship and social support for frail seniors returning home after a hospital stay.

Volunteers visit clients and offer assistance to help them connect to services and regain self-confidence. The goal of the program is to assist clients in finding practical services they might need following hospitalization, re-socializing and making new friends at seniors social programs in the area.

Training includes: Effective communication skills, nutrition, the effects of disease on normal aging, navigating the health-care system, and how to get access to community programs.

Training for new volunteers takes place from 1 to 4 p.m. every Thursday over five weeks beginning on Oct. 19.

Please call the Return to Health education co-ordinator, Donna Ross, at 250-655-1327 to register for the information session on Oct. 12.

For more information, go to seniorsservingseniors.bc.ca.

Deconstructing Comfort, an interdisciplinary arts exhibition presenting the work of seven contemporary Indigenous artists and artists of colour, opens Friday at Open Space.

Artists include Luli Eshraghi, Jamelie Hassan, Syrus Marcus Ware, Lisa Myers, Nadia Myre, Haruko Okano and Philip Kevin Paul.

The exhibition co-curators, Michelle Jacques, Doug Jarvis and France Trpanier, examine: Decolonization and Indigenization; issues raised by Black Lives Matter; calls to action from the Truth and Reconciliation Commission; Islamophobia; unsettling settlers; and Canada 150 celebrations.

Deconstructing Comfort runs to Oct. 14. A public reception will take place on Sept. 25 as part of the public program for the Primary Colours/Couleurs primaires gathering.

This three-year initiative seeks to place Indigenous art practices at the centre of the Canadian art system. It also asserts that art practices by people of colour, which have roots around the world, play a critical role in any discussion that imagines Canadas future.

The initiative includes a major multidisciplinary, trilingual Lekwungen, French and English gathering at the Songhees Wellness Centre, on Lekwungen territories.

For more information, go to primary-colours.ca.

More than a dozen survivors of Japanese-Canadian internment during the Second World War will speak of their experiences at a luncheon commemorating the 75th anniversary of the saga, Sept. 10.

The Victoria Nikkei Cultural Society is hosting the event, which tells the tragedy of the relocation and internment of Japanese-Canadians during the conflict.

Because its so hard to imagine this happening today, its critical that all Canadians whether they have Japanese heritage or not remember what happened with the internments during the Second World War, said Tsugio Kurushima, president of the society. We are fortunate to still have first-hand witnesses who can share their stories with the generations who followed them.

From 1942 until 1949 (four years after the end of the war), Japanese-Canadians living in coastal British Columbia were detained by the government. They were relocated to camps and farms in the Interior and in the rest of Canada, restricted in their movement and stripped of their businesses and homes.

To add insult to injury, the sale of their personal property was used to fund the internments.

People who never committed a crime were treated like criminals simply because of their heritage, said Kurushima. Its a wrong the Canadian government apologized for in 1988, along with the launch of a redress program.

There will also be a presentation by Jordan Stanger-Ross, director of the Landscapes of Injustice project, housed at the University of Victoria.

He will give an update on the project, which explores the forced dispossession of Japanese-Canadians.

The event includes a buffet lunch with two hot entres, including a vegetarian lasagna option.

Tickets are $15 adults, $7.50 for children 5 to 12. The event runs 1 to 4:30 p.m. Sept. 10 at the Ambrosia Event Centre, 638 Fisgard St.

Tickets available from Patti Ayukawa, Real English Victoria, #301 1111 Blanshard St. or 250-858-8445. For more information, go to vncs.ca.

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Our Community: Firm pitches in for Woodwynn Farms – Times Colonist

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Center for Embryonic Cell and Gene Therapy | Center for …

Mitalipov successfully repairs genes in human embryos

A ground breaking discovery by Shoukhrat Mitalipov, Ph.D.,was reported in Nature the successful removal of a lethal geneticdefect in human embryos. The breakthrough is the initial confirmation that adangerous genetic defect can in theory be erased.

Scientific success in embryo editing re-opens reg debate. BioWorld

Study in Nature demonstrates method for repairing genes in human embryos that prevents inherited diseases. OHSU News

Gene Editing Breakthrough. Charlie Rose Show

A Promising And Still Uncertain Future For Human Gene Editing. Science Friday

In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos. NY Times

First human embryo editing experiment in U.S.’corrects’ gene for heart condition. The Washington Post.

Scientists Precisely Edit DNA In Human Embryos To Fix A Disease Gene. NPR

Human embryos edited to stop disease. BBC

A Gene Editing Breakthrough. On Point with Tom Ashbrook.

First U.S.-based group to edit human embryos brings practice closer to clinic. Science

In breakthrough, OHSU corrects defective gene in embryo. Oregonlive.

First Safe Repair of Gene in Human Embryos. Associated Press.

A new discovery may unlock the answer to a vexing scientificquestion: How to conduct mitochondrial replacement therapy, a new gene-therapytechnique, in such a way that safely prevents the transmission of harmful mitochondrialgene mutations from mothers to their children.

For women with mitochondrial diseases, a step closer to preventing transmission. STAT

Human embryo experiment shows progress toward ‘three-parent’ babies. The Washington Post

Families struggling with infertility or a genetic predisposition for debilitating mitochondrial diseases may someday benefit from a new breakthrough led by scientists at OHSU and the Salk Institute for Biological Studies.

Egg ‘nobbles’ can be used to create embryos, say scientists in fertility breakthrough

Fertility success may get boost from new research

First he pioneered a new way of making life. Now he wants to try it in people

Shoukhrat Mitalipov: The cloning chief.

Researchers announced they had derived stem cells fromcloned human embryos, a long-awaited research coup that Science’s editors choseas a runner-up for Breakthrough of the Year.Read the article on Science

#4. Finally, We’re Just Like Dolly

#5. Functioning Organs Made From Stem Cells

#2. Human embryonic stem cells cloned

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Center for Embryonic Cell and Gene Therapy | Center for …

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iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson’s – ReliaWire

Monkeys with Parkinsons disease symptoms show significant improvement over two years after being transplanted neurons prepared from human induced pluropontent stem cells, scientists at the Center for iPS Cell Research and Application (CiRA), Kyoto University, report. One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

Parkinsons disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons.

Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease.

The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin.

Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy,

said Professor Jun Takahashi, a neurosurgeon specializing in Parkinsons disease, who plans to use DA neurons made from iPS cells to treat patients.

To test the safety and effectiveness of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.

We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinsons disease patients,

said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.

It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survive, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.

Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival, Kikuchi said.

To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.

Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications.

Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery.

MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred,

said Takahashi.

The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year. The study is the teams answer to bring iPS cells to clinical settings, said Takahashi.

Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun TakahashiHuman iPS cell-derived dopaminergic neurons function in a primate Parkinsons disease modelNature, 2017; 548 (7669): 592 DOI: 10.1038/nature23664

Image: Annie Cavanagh / Wellcome Images

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iPS Cell-based Neuron Therapy Benefits Monkeys With Parkinson’s – ReliaWire

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Monkeys With Parkinson’s Disease Successfully Treated With Human Stem Cell Transplants – Technology Networks

Monkeys show reduced Parkinsonian symptoms following a donor-matched iPS cell-based therapy. Misaki Ouchida, Center for iPS Cell Research and Application, Kyoto University

One of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys. In its latest study, the Jun Takahashi lab shows monkeys with Parkinson’s disease symptoms show significant improvement over two years after being transplanted neurons prepared from human iPS cells. The study, which can be read in Nature, is expected to be a final step before the first iPS cell-based therapy for a neurodegenerative disease.

Parkinson’s disease degenerates a specific type of cells in the brain known as dopaminergic (DA) neurons. It has been reported that when symptoms are first detected, a patient will have already lost more than half of his or her DA neurons. Several studies have shown the transplantation of DA neurons made from fetal cells can mitigate the disease. The use of fetal tissues is controversial, however. On the other hand, iPS cells can be made from blood or skin, which is why Professor Takahashi, who is also a neurosurgeon specializing in Parkinson’s disease, plans to use DA neurons made from iPS cells to treat patients.

“Our research has shown that DA neurons made from iPS cells are just as good as DA neurons made from fetal midbrain. Because iPS cells are easy to obtain, we can standardize them to only use the best iPS cells for therapy, ” he said.

To test the safety and effectiveness of DA neurons made from human iPS cells, Tetsuhiro Kikuchi, a neurosurgeon working in the Takahashi lab, transplanted the cells into the brains of monkeys.

“We made DA neurons from different iPS cells lines. Some were made with iPS cells from healthy donors. Others were made from Parkinson’s disease patients,” said Kikuchi, who added that the differentiation method used to convert iPS cells into neurons is suitable for clinical trials.

It is generally assumed that the outcome of a cell therapy will depend on the number of transplanted cells that survived, but Kikuchi found this was not the case. More important than the number of cells was the quality of the cells.

“Each animal received cells prepared from a different iPS cell donor. We found the quality of donor cells had a large effect on the DA neuron survival,” Kikuchi said.

To understand why, he looked for genes that showed different expression levels, finding 11 genes that could mark the quality of the progenitors. One of those genes was Dlk1.

“Dlk1 is one of the predictive markers of cell quality for DA neurons made from embryonic stem cells and transplanted into rat. We found Dlk1 in DA neurons transplanted into monkey. We are investigating Dlk1 to evaluate the quality of the cells for clinical applications.”

Another feature of the study that is expected to extend to clinical study is the method used to evaluate cell survival in the host brains. The study demonstrated that magnetic resonance imaging (MRI) and position electron tomography (PET) are options for evaluating the patient post surgery.

“MRI and PET are non-invasive imaging modalities. Following cell transplantation, we must regularly observe the patient. A non-invasive method is preferred,” said Takahashi.

The group is hopeful that it can begin recruiting patients for this iPS cell-based therapy before the end of next year. “This study is our answer to bring iPS cells to clinical settings,” said Takahashi.

This article has been republished frommaterialsprovided byCIRA, Kyoto University. Note: material may have been edited for length and content. For further information, please contact the cited source.

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This Week In Neuroscience News 8/31/17 – ReliaWire

This weeks roundup of recent developments in neuroscience kicks off with a study from MIT, where engineers have devised a way to automate the process of monitoring neurons in a living brain using a computer algorithm that analyzes microscope images and guides a robotic arm to the target cell. In the above image, a pipette guided by a robotic arm approaches a neuron identified with a fluorescent stain.

Neurosurgeons at the Center for iPS Cell Research and Application, Kyoto University. They report two new ways to improve outcomes of induced pluropontent stem cell-based therapies for Parkinsons disease in monkey brains. The findings are a key step for patient recruitment of the first iPS cell-based therapy to treat neurodegenerative diseases, since one of the last steps before treating patients with an experimental cell therapy for the brain is confirmation that the therapy works in monkeys.

In other Parkinsons news, the FDA has denied Acorda Therapeutics New Drug Application filing for Inbrija. Inbrija is an inhaled, self-administered, form of levodopa for treating Parkinsons disease. According to the FDA, reason for the denial were the date when the manufacturing site would be ready for inspection, and a question regarding submission of the drug master production record. FDA also requested additional information at resubmission, which was not part of the basis for the refusal.

At the University of Turku, in Finland, researchers have revealed how eating stimulates the brains endogenous opioid system to signal pleasure and satiety. Interestingly, eating both bland and delicious meals triggered significant opioid release in the brain.

A young New York woman with severe headaches represented a never-before-seen case for neurosurgeons at New York Presbyterian. She was diagnosed with an unusual form of hydrocephalus/Chiari malformation, in which the skull is too small and restricted the brain. More about her in the video below:

Tinnitus, a chronic ringing or buzzing in the ears, has eluded medical treatment and scientific understanding. A new University of Illinois at Urbana-Champaign study found that chronic tinnitus is associated with changes in certain networks in the brain, and furthermore, those changes cause the brain to stay more at attention and less at rest. The finding provides patients with validation of their experiences and hope for future treatment options.

In social media news, research by BuzzFeed found more than half of the most-shared scientific stories about autism published in the last five years promote unevidenced or disproven treatments, or purported causes. More disturbingly, families in the autism community are excessively targeted by purveyors of bad information, making them more vulnerable to harmful, unproven so-called treatments.

Top Image: Ho-Jun Suk

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This Week In Neuroscience News 8/31/17 – ReliaWire

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Scientists Upload a Galloping Horse GIF Into Bacteria With …

E. coli might best be known for giving street food connoisseurs occasional bouts of gastric regret. But the humble microbial workhorse, with its easy-to-edit genome, has given humankind so much moreinsulin, antibiotics, cancer drugs, biofuels, synthetic rubber, and now: a place to keep your selfies safe for the next millennium.

Scientists have already used plain old DNA to encode and store all 587,287 words of War and Peace, a list of all the plant material archived in the Svalbard Seed Vault, and an OK Go music video. But now, researchers have created for the first time a living library, embedded within, you guessed it: E. coli. In a paper published today in Nature, Harvard researchers1 describe using a Crispr system to insert bits of DNA encoded with photos and a GIF of a galloping horse into live bacteria. When the scientists retrieved and reconstructed the images by sequencing the bacterial genomes, they got back the same images they put in with about 90 percent accuracy.

The study is an interestingif slightly gimmickyway to show off Crispr’s power to turn living cells into digital data warehouses. (As if E. coli didnt already have enough on its plate, what with securing global insulin supplies and weaning the world off fossil fuels.) But the real question: Why would anyone want to do this?

To the left are a series of frames from Eadweard Muybridges Human and Animal Locomotion. To the right are the frames after multiple generations of bacterial growth, recovered by sequencing bacterial genomes.

Seth Shipman

If youre Jeff Nivala, its not to preserve visual messages for people in the far-off future. Its so he can turn human cells like neurons into biological recording devices. The E. coli is just a proof of concept to show what cool things you can do with this Crispr system, says Nivala, a coauthor on the paper and geneticist at Harvard. Our real goal is to enable cells to gather information about themselves and to store it in their genome for us to look at later. That concept is called the molecular ticker tape. Its something George Church thought up before Nivala, a postdoc, arrived in his lab. But its a challenge Nivala thinks is uniquely suited to Crispr.

In case youve been living in a bunker, Crispr-Cas9 is a revolutionary molecular tool that combines special proteins and RNA molecules to precisely cut and edit DNA. It was discovered in bacteria, which use it as a sort of ancient immune system to fend off viral attackers. Cas9 is the protein that does all the cutting, i.e. gene editings heavy lifting. Lesser known are Cas1 and Cas2. Theyre the ones that tell Cas9 where to do the cutting.

Church’s lab plans to leverage that system to get human brain cells to show how exactly they develop into neurons. Nivala thinks theyll be able to do that because of how Cas1 and Cas2 work. During a viral invasion, the proteins go out and grab a piece of the attackers DNA, which they slip into the bacterial genome for another enzyme to turn into a matching guide RNA. Thats what helps Cas9 find (and then chop up) copies of the virus in the cell. The really cool bit is that Cas1 and Cas2 dont just insert viral DNA into the genome at random. As they encounter new threats, they add DNA in the order in which it arrives. That turns a cells genome into a temporal recordthink ice cores for molecular historyof whatever the cell encounters.

To the left is an image of a human hand, which was encoded into nucleotides and captured by the Crispr-Cas adaptation system in living bacteria. To the right is the image after multiple generations of bacterial growth, recovered by sequencing bacterial genomes.

Seth Shipman

One day, Nivala thinks scientists will be able to use that system to record synaptic activity. Like a guest book at a wedding, embedded signals in the genome could tell researchers exactly which neurons were talking to each other at different times, in response to different stimuli.

If you think of a cell as a processor, this adds a thumb drive, which stores information for later processing, says Karin Strauss, lead researcher on Microsoft’s own DNA storage project. Last year the company set a new record200 megabytesand has plans to get a DNA storage system up and running by the end of this decade. As for DNA data storage in the IT industry, it is more well served by standard DNA synthesis and sequencing at the moment because they are easier to control and a lot denser than whole cells, says Strauss, who is unconnected to the Harvard research.

Companies that make custom DNA, such as Twist Biosciences, are already selling to customers using it for storage purposes. But its still only a small piece of their businessabout 5 percent. Costs have to come down by a factor of about 10,000 before DNA becomes competitive with traditional storage methods. But the long-term benefits will be huge: Properly stored in a cold, dry place, DNA can keep data intact for at least 100,000 years.

Thats why scientists such as Ewan Birney, director of the European Bioinformatics Institute, are working on better tools and methods to make DNA storage truly scalable. In that endeavor he doesnt see a place for live cells, which start out at less than 100 percent accuracy and are susceptible to mutations over time that could further degrade data integrity. Its cute, and I wish Id done it, Birney says of the Nature paper. But it doesnt add much on the DNA storage side of things. What did impress me was the amount of edits they achieved with high fidelity. Its a real tour de force of Crispr.

So, at least for now, theres no reason to think your family photo albums will one day be backed up on an E. coli drive. More likely, the memories cells store will be their own.

1Disclosure: One of these researchers is married to a WIRED editor.

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Scientists Upload a Galloping Horse GIF Into Bacteria With …

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Skepticism surfaces over CRISPR human embryo editing claims … – Science Magazine

Newly fertilized (left) and later-stage (right) human embryos that have had a disease mutation corrected by the CRISPR editing system.

OHSU

By Kelly ServickAug. 31, 2017 , 12:28 PM

When the first U.S. team to edit human embryos with CRISPR revealed their success earlier this month, the field reeled with the possibility that the gene-editing technique might soon produce children free of their parents genetic defects. But the way CRISPR repaired the paternal mutation targeted in the embryos was also a surprise. Instead of replacing the gene defect with strands of DNA that the researchers inserted, theembryos appeared to use the mothers healthy gene as a template for repairing the cut made by CRISPRs enzyme.

But such a feat has not been observed in previous CRISPR experiments, and some scientists are now questioning whether the repairs really happened that way. In a paper published online this week on the preprint server bioRxiv, a group of six geneticists, developmental biologists, and stem cell researchers offers alternative explanations for the results. And uncertainty about exactly how the embryos DNA changed after editing leaves many questions about the techniques safety, they argue. (The authors declined to discuss the paper while its being reviewed for publication.)

Embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, who led the now-disputed experiments, released a statement saying that his team stands by its explanation. We based our finding and conclusions on careful experimental design involving hundreds of human embryos, it says.

In the 2 August Nature paper, Mitalipov and his collaborators showed they could bump up the efficiency of human embryo editing by inserting the CRISPR machinery earlier in development than previous experiments. When they combined healthy eggs with sperm bearing a disease-causing mutation and immediately added CRISPR, they found that 72% of the resulting embryos were free of the mutationrather than the expected 50% that would have avoided inheriting the harmful gene anyway.

Although the researchers inserted short strands of DNA as templates for repair, the cells didnt seem to take them up; those specific sequences were absent from the embryos. The cells must have relied instead on the nonmutated sequence in the egg donors DNA when making the repairs, the team concluded.

The bioRxiv response, led by developmental biologist Maria Jasin of Memorial Sloan Kettering Cancer Center in New York City and Columbia University stem cell biologist Dieter Egli, challenges that interpretation. The authors, which also include well-known CRISPR researcher and Harvard University geneticist George Church, say that the Nature paper goes against conventional wisdom about how embryos are organized early in development. Right after an egg is fertilized, the DNA from the sperm and the egg arent believed to be in close enough proximity to interact or share genes, they explain.

Stem cell researcher Junjiu Huang of Sun Yat-Sen University in Guangzhou, China, who led the first published study of CRISPR editing of a human embryo, isnt on the bioRxiv paper, but shares that concern. Its not unexpected for a cell to use its own sequences to guide repair, he notes. In his groups study, which used nonviable embryos, a gene related to the CRISPR-targeted gene seemed to function as a template. But that gene was on the same chromosome as CRISPRs edits. Here, the sperm and egg nuclei are seemingly too far apart to cooperate in the repairs, he says.

The preprint authors lay out two other scenarios for what Mitalipovs team saw. Its possible that some of the embryos didnt take up paternal DNA at all, and thus never inherited the mutation to begin with. In some in vitro fertilization procedures, embryos can occasionally start to develop from maternal DNA alone, and the study didnt rule out this phenomenon for every embryo, they say.

They also suggest that mutated paternal gene could have been snipped out of young embryos but never actually replaced with a healthy version. CRISPRs cuts can sometimes cause chunks of DNA to be removed from the strand before the two cut ends are rejoined, they note. That would mean no detectable mutationbut it could also mean missing sections of DNA that could have unknown consequences for the embryo.

This possibility of allele dropout has been the subject of discussion in the field ever since the Nature paper was published, says developmental biologist Robin Lovell-Badge of the Francis Crick Institute in London. Many scientists are now waiting for a response from Mitalipov, he says.

In his statement, Mitalipov promised to respond to [the] critiques point by point in the form of a formal peer-reviewed response in a matter of weeks. He also urged follow-up to resolve the matter. We encourage other scientists to reproduce our findings by conducting their own experiments on human embryos and publishing their results.

*Update, 1 September, 1:30 p.m.: The new version of this story has additional comments from several researchers and clarifies the authorship of the preprint.

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Skepticism surfaces over CRISPR human embryo editing claims … – Science Magazine

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Video gamers tasked with helping develop new molecule for controlling CRISPR – New Atlas

A few years ago, a team of researchers at Stanford University launched a video game called Eterna. The game was designed to harness the brain power of thousands of gamers, challenging them to design new chemical sequences of RNA. A new follow-up game has just been launched, and this time players are challenged to create a new RNA molecule that can essentially function as an on/off switch for the CRISPR/Cas9 gene editing process.

When Eterna was first launched in 2011 it was a bit of an experiment. Half-intended to simply educate people in an entertaining way, researchers hoped once the game scaled up to enough players the results would start to become clinically significant. And significant they became.

As players refined their RNA molecule-making skills, the game grew in complexity. Up to 100,000 registered players were engaging with the game at its peak, and in early 2016 a paper, co-authored by the game players, was published in the peer-reviewed Journal of Molecular Biology. The paper established a set of rules developed by the game players determining the difficulty of designing appropriate RNA molecular structures.

Earlier in 2016 Eterna players were tasked with designing a novel molecule to assist with the creation of a simple and accurate blood test for tuberculosis. Now researchers are turning their sights on CRISPR, hoping this gaggle of game players can inspire a new molecular structure that will help focus the gene-editing technology.

“Great ideas can come from anywhere, so this is also an experiment in the democratization of science,” says Stanford’s Professor Howard Chang. “A lot of people have hidden talents that they don’t even know about. This could be their calling. Maybe there’s somebody out there who is a security guard and a fantastic RNA biochemist, and they don’t even know it.”

The new Eterna challenge asks players to design a unique RNA molecule that can do several things, from being recognized by the CRISPR-associated enzyme to guiding it to a targeted gene. The researchers suspect that this new challenge may be slightly easier than other, more mathematically orientated Eterna challenges, but they are looking for thousands of diverse solutions that could be applied into laboratory outcomes.

“We’re not sure yet if there will be unforeseen problems with the Cas9 protein experimentally,” says Rhiju Das, the principle investigator for Eterna. “That’s partially why we want as many diverse solutions as possible for the Greenleaf and Chang labs to test, even in this pilot round. We’re hoping for 10,000 to 100,000 players to contribute 10 solutions each. If we get that many, we’ll indeed work to get that many synthesized and tested.”

This real-life laboratory outcome makes the Eterna game unique as it gives game players the possibility of having their designs actually created and tested in the lab. And anyone can play the game as long as they have access to the internet and an interest in learning how to play.

“There is a misconception of science as something that happens in an ivory tower by someone in a white coat with a long beard,” says Das. “And they are saying things and drawing things that nobody understands. But it’s not like that! It’s really like a puzzle that anybody can get engaged with.”

Learn more about the Eterna CRISPR challenge in the video below and join the Eterna community and play the game here.

Source: Stanford University

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Video gamers tasked with helping develop new molecule for controlling CRISPR – New Atlas

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‘Gentler’ CRISPR sheds light on autoimmune disease | FierceBiotech – FierceBiotech

CRISPR is typically used to edit disease-causing gene mutations, but is increasingly being tapped for broader applications. The latest? Identifying sequences that activate genes, which could help unravel the causes of autoimmune disease.

While CRISPR shows great promise in the treatment of genetic disease, the genes it cuts outthose that code directly for proteinsonly make up 2% of the human genome. The other 98% consists of regulatory gene sequences, including promoters, which switch on genes next to them, and enhancers, which activate genes that may sit far away from them in the genome.

When the balance of promoters and enhancers is out of whack, it can lead to disease. But its difficult to pinpoint just which regulators have a hand in causing disease, as specific regulators play a role in specific cells, under specific conditions.

Jacob Corn and Alexander Marson at the University of California, San Francisco, focused on T cells and the IL2RA protein, which tells T cells if they should step up or dampen an inflammatory response. If the enhancers that switch on IL2RA are faulty, the T cells dont suppress inflammation, which could cause autoimmune disorders, such as Crohns and inflammatory bowel disease (IBD).

Corn and Marson usedCRISPR activation, or CRISPRa, to homein on the IL2RA gene. This methoduses a guide RNA to target sections of the genome, much like regular CRISPR, but instead of cutting them, it activates those sequences to see how they affect gene expression.

They created 20,000 guide RNAs for use with CRISPRa: “We essentially performed 20,000 experiments in parallel to find all the sequences that turn on this gene,” said Marson, an assistant professor of microbiology and immunology at UC San Francisco, in a statement.

The teamturned up several sequences that might be important for ILR2A expression, including a common genetic variant that was already linked to increased IBD riskbut was not well understood. The findings are published in Nature.

“This starts to unlock the fundamental circuitry of immune cell regulation, which will dramatically increase our understanding of disease,” Marson said.

The utility of CRISPR is growing by the day. Recently, UC San Diego researchers created a new version of CRISPR that targets RNA rather than DNA, which could be used to treat diseases caused by errant repeats in RNA sequences, including Huntington disease and a type of amyotrophic lateral sclerosis.

And scientists at eGenesis have deployed the gene-editing tool in the organ transplant field. By snipping out a family of viruses in the pig genome, they have overcome one obstacle in xenotransplantation, or using animal organs for human transplant.

The next step forthe UCSF researchers isto modify their method so that it can screen for enhancers of many different genes at once.

“Not only can we now find these regulatory regions, but we can do it so quickly and easily that it’s mind-blowing,” said Corn, assistant adjunct professor of molecular and cell biology at Berkeley. “It would have taken years to find just one before, but now it takes a single person just a few months to find several.”

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‘Gentler’ CRISPR sheds light on autoimmune disease | FierceBiotech – FierceBiotech

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Physician Experts Highlight Research Ahead of Otolaryngology’s Annual Meeting – Sleep Review

The latest research on patient preferences, quality-of-life, ear health, thyroidectomy, and other topics related to the specialty of otolaryngology will be presented in Chicago Sept 10-13, during the AAO-HNSF 2017 Annual Meeting & OTO Experience.

The 2017 Annual Meeting includes hundreds of research presentations. All abstracts to be presented are now available online as a PDF.

Nineteen studies have been selected to be presented during the Best of Orals session on Sunday, Sept 10, at 10 am, CDT, in room E450A of the McCormick Place Convention Center. These studies, identified by the Annual Meeting Program Committee, comprised of physician members, are recognized for outstanding scientific merit and innovation.

What role does the Internet and social media play in patient perception of physicians? This study looks at the physicians age and online/social media presence in relation to positive ratings and comments from patients.

What drives patients decisions, and what are their preferences of care? Where do factors like cost, timely appointments, experience, and thorough physical exam fall in a patients list of priorities?

This study reviewed 906 patient charts to identify significant factors predicting hypocalcemia after total thyroidectomy. After extensive analysis of patient demographics and surgical characteristics, only parathyroid hormone (PTH) was found to have significantly predicted hypocalcemia postoperatively. Further findings suggest that early, standardized supplementation can significantly reduce hypocalcemia-related extended stays and associated costs.

This is the first population-level analysis focusing on quality metrics for parathyroidectomy. The study identified independent, potentially modifiable perioperative factors that may assist in appropriate risk stratification for patients susceptible for readmission and reoperation.

What are the outcomes and complications after rhinoplasty with either autologous rib graft (ARG) or cadaveric rib graft (CRG)? This meta-analysis demonstrates that further research is needed to determine the complication rates and outcomes of ARG versus CRG in rhinoplasty.

Is advanced age an independent risk factor for complications following free flap surgery of the head and neck? Are such patients likely to have a longer hospital stay or be discharged to a skilled nursing facility? This study analyzes the effects of increasing age on outcomes of microvascular reconstructive surgery of the head and neck.

This study assesses the sustainability of clinical benefit with balloon dilation of the Eustachian tube (BDET) using the Eustachian tube balloon catheter (ETBC) in conjunction with medical management at 12 months follow-up in adult patients aged 22 years and older with drug-refractory Eustachian tube dilatory dysfunction (ETDD).

Do ototopical quinolones delay tympanic membrane healing in a drug-specific manner? This study compared the effect of both ciprofloxacin + dexamethasone and ofloxacin on tympanic membrane perforation healing in rats, with reported results.

The study population consisted of 8,281 individuals diagnosed with HNSCC, with 537 (6.4%) surviving to 5 years with the purpose to estimate the prevalence of comorbidity in HNSCC survivors at diagnosis and evaluate changes in prevalence of comorbidity over time.

This review analyzed the effect of adjuvant radiation on survival in pathologic N1 oropharyngeal squamous cell carcinoma (OPSCC) and if these findings apply to HPV+ tumors.

Laryngotracheal stenosis (LTS) is a fibroinflammatory disorder that causes narrowing of the airway. This study analyzed the effects of macrophage polarization on LTS-derived and normal airway fibroblasts (FBs) in vitro.

This study assessed patient decision making in subglottic stenosis treatment with findings that predict that most patients will prefer voice-sparing, low-risk procedures, consistent with an endoscopic approach, even if they require multiple procedures.

Is there a significant difference in postoperative complications in tympanoplasty with or without concurrent therapeutic mastoidectomy? This study addressed this question in the management of chronic ear disease alone.

Is the human middle ear inhabited by more diverse microbial communities than was previously thought? The aim of this prospective multicenter cohort study was to profile and compare the middle ear microbiomes of human individuals with and without chronic otitis media.

Does gender, age, nasal trauma, prior nasal surgery, allergic rhinitis, or additional surgeries (at the time of procedure) affect postoperative Nasal Obstruction Symptom Evaluation (NOSE) scores? This study analyzed disease specific quality-of-life in patients undergoing septoplasty and functional septorhinoplasty.

Is the modified Swallowing Quality of Life instrument a valid measure of dysphagia-specific QOL in children? Does it demonstrate a significant association with videofluoroscopic swallow studies and moderate-to-strong correlations with multiple domains of generic QOL measure?

Is balloon catheter dilation (BCD) an effective treatment for sinus pressure headaches? In this study, participants were recruited who reported sinus pressure headaches, localizing to either unilateral or bilateral maxillary and/or frontal sinuses, and were blinded and randomized to receive either BCD of the affected sinus ostia or a sham procedure.

This study explored whether single-nucleotide polymorphisms (SNPs) in the Thymic Stromal Lymphopoietin gene are associated with chronic rhinosinusitis and can predict TSLP activity.

This study analyzed cranial nerve XII (CNXII) stimulation 5-year outcomes and assessed effects of stimulation and body mass index (BMI). The study found that cranial nerve stimulation demonstrates significant clinical improvements at one year, but was it maintained at 5years?

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Physician Experts Highlight Research Ahead of Otolaryngology’s Annual Meeting – Sleep Review

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Pneumonia ventolin inhaler – Albuterol aerosol inhaler – Laughlin Entertainer

When an experiment turns into a tradition in Laughlin, it means there was a show worth taking a chance on at one timethen consistently that same show proved itself time after time to be one audiences didnt want to miss. The Memorial Day Comedy Festival at the Riverside Resort was that show. Experiencing comedy served up as a variety show with veteran comedian Gabe Lopez as the shows producer, performer and emcee was like discovering a hidden gem on the entertainment landscapemore along the lines of one of those underground clubs in Vegas, known only to a lucky few. But now the word is out and the Comedy Festival is coming back to the Riverside Resort over the Labor Day weekend this time.

If you are a local, or a regular visitor to Laughlinespecially if your visits are on holiday weekendsyou are aware that the Avi Resort & Casino doesnt simply wait for the Fourth of July to set off a major fireworks display. Nope. Beginning in 1996, and continuing every year since, they have been filling the skies above the Colorado River with the amped-up creations of Zambelli Internationale Fireworks on Memorial Day weekend, the Fourth of July and Labor Day weekend.

The Colorado Belle is home to a multitude of outdoor festivals that embrace particular themes and for the Labor Day Riverwalk Festival, its a celebration of the end of summer and the cooler temperatures just starting to take hold of the Colorado River regionthink of it as one big neighborhood block party.

Theres a lot to be said for being in the right place at the right time, but could Air Supplys long-time success be the result or a chance meeting or was the cosmos working overtime on a little something called destiny? Maybe, but one thing is for surenone of it would have been possible at all without their hard work and tenacity to make it happen.The two Russells, Graham Russell and Russell Hitchcock, happened to be cast in the same Sydney, Australian production of Jesus Christ Superstar in 1975, and everything changed after that.

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Pneumonia ventolin inhaler – Albuterol aerosol inhaler – Laughlin Entertainer

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