Archive for July, 2017

Four months after federal officials declared manatees are no longer endangered, the U.S. Fish and Wildlife Service has announced that it's now reviewing the endangered status of the Florida panther.

The panther, Florida's state animal, has been on the endangered list since the list was first drawn up in 1967.

Federal rules require the agency to review the status of each endangered or threatened species every five years, and it's time for that routine review, explained Larry Williams, South Florida field supervisor for the Fish and Wildlife Service.

But at least one aspect of the review won't be routine at all.

"One of the most interesting things we're going to review is the taxonomy," Williams said Monday.

Questions have been raised for years about whether the Florida panther is really a distinct sub-species of the pumas found out West, and thus deserving of legal protection.

The questions took a different turn after 1995, when state officials tried an unprecedented experiment to save the panther from inbreeding and genetic defects by bringing in eight female mountain lions from Texas to breed with them.

The cross-breeding saved the panthers, and sparked a baby boom. The panther population, estimated to number no more than 20 to 30 in the mid-1990s, now is estimated at around 200.

But there are Floridians who do not believe the scientists who say the animals now prowling the South Florida wilderness are still Florida panthers. Meanwhile others insist that even if they are, they aren't anything special and probably should be managed by allowing hunting.

In 2000, Williams noted, a team of four scientists led by an expert named Melanie Culver published a paper that said genetics show that all the pumas in North America are one species, period. Because pumas are fairly common, that would mean panthers might no longer be considered endangered.

"Obviously, people who want (endangered species) restrictions lifted have latched onto that," said Elizabeth Fleming of the Defenders of Wildlife Florida office in St. Petersburg.

But she said other experts disagree with the findings of the Culver study. She contended there are physical differences, such as the shape of the skull and the thickness of the fur, that mark the Florida panther as distinct.

The fact that this review is being done by an agency under the Trump Administration, though, makes Fleming concerned.

When it comes to environmental issues, she said, "everything undertaken by the Trump Administration gives me pause."

Williams refused to speculate on whether the five-year review could lead to a decision to change the panthers' status similar to the decision his agency made about manatees. In March, the Fish and Wildlife Service announced it was downgrading manatees from endangered to merely threatened. The controversial move was opposed by most of the people who submitted comments in writing and in public hearings, as well as scientists invited to review it.

As with the manatee, the Fish and Wildlife Service is asking the public for information about panthers. The deadline for submitting comments is Aug. 29.

Last year brought a mix of bad and good news for panthers, which for decades had been largely isolated to habitat south of the Caloosahatchee River near Fort Myers. Occasionally male panthers would cross the river looking for mates that didn't exist. Last year, for the first time ever, biologists spotted females and kittens north of the river, proving the animals were expanding their range.

But last year was also the year that drivers set a record for running over the big cats on the state's highways.

In 2012, a new record for road kills was set with 19. Two years later, in 2014, that record was broken and a new one established at 25 kills. In 2015, that record was shattered when 30 were killed. Then came 2016, with 32 run over on the highways.

The total number of panther deaths, 42 from road kills and other causes, tied 2015.

Panthers, sometimes known among Florida's settlers as "lions" and "catamounts," were a terror of the early frontier for attacks on livestock and pets. By 1981, though, schoolchildren had picked the panther as the state animal choosing it over the alligator, the manatee, the Key deer and a few others that got write-in votes, such as the dolphin and the baboon.

They've proven so popular that the cats have become the mascot for dozens of schools, the namesake of the National Hockey League team in South Florida and a figure on tens of thousands of specialty license plates, sold to cover the costs for the state wildlife commission's panther research.

The wide-ranging predators have lost habitat in South Florida not just to suburban sprawl, but also to the creation of Florida Gulf Coast University and the town of Ave Maria. But Williams said the discovery of breeding cats north of the Caloosahatchee shows they now have much more potential habitat available to them than ever before.

Senior news researcher Caryn Baird contributed to this report. Contact Craig Pittman at craig@tampabay.com. Follow @craigtimes.

Federal officials to review endangered status of Florida panther 07/03/17 [Last modified: Tuesday, July 4, 2017 12:25am] Photo reprints | Article reprints

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Federal officials to review endangered status of Florida panther - Tampabay.com

The gene-editing tool known as CRISPR is fast becoming known for its potential to treat disease by snipping genetic mutations from DNA.

But genomic tools like CRISPR also have other possible capabilities, such as the ability to screen people for the presence of viruses, like dengue and Zika, as well as debilitating diseases like Parkinson's.

"I think the public perception of CRISPR is very focused on the idea of using gene editing clinically to cure disease. This is no doubt an exciting possibility, but this is only one small piece," said Neville Sanjana, of the New York Genome Center and an assistant professor of biology, neuroscience and physiology at New York University. [10 Amazing Things Scientists Just Did with CRISPR]

"With CRISPR, I think you'll see many applications in synthetic biology," like sensors for pathogens, Sanjana told Live Science.

At its core, CRISPR is a natural defense system that evolved in single-celled microorganisms to fight against invading viruses. The fight is an all-out war. Scientist estimate that for every cell on Earth, there are about 10 viruses, all launching relentless missions to replicate themselves by inserting their DNA into the machinery in cells.

Bacteria use an arsenal to fight back, including CRISPR, which is an array of short, repeated sequences of DNA that are separated by spacers that have unique sequences.Bacteria use it when they are infected with a virus. As the virus's genetic bits replicate inside the bacteria, CRISPR steps in, guiding the bacterial defenses toward the foreign material.

The protein in CRISPR cuts up the intruder, but also collects a short DNA sequence from the invader, which the protein inserts it into the bacteria's CRISPR as a spacer. Each time a virus invades and is destroyed, a new spacer gets added to the CRISPR.

In a sense, the spacers in CRISPR are an account of the bacteria's battlefield wins, like kill marks in the stock of a rifle barrel. But the spacers provide another function.

When a virus that was previously defeated tries to invade, the bacteria recognizes it and sets about chopping the invader up into tiny bits. And when the bacteria itself multiplies, it passes it's defense system on to its daughter cells.

"It turns out you can actually leverage these properties to potentially develop a very sensitive diagnostic device" that could detect small amounts of molecules from viruses in human blood, such as Zika virus, said biochemist and CRISPR expert Sam Sternberg, the group leader of Technology Development at Berkeley, California-based Caribou Biosciences Inc., which is advancing new applications for CRISPR-based technologies. [5 Amazing Technologies That Are Revolutionizing Biotech]

One of the most recent CRISPR advances in this area is a tool called SHERLOCK (which stands for Specific High Sensitivity Enzymatic Reporter UnLOCKing). In April 2017, a team of researchers led by bioengineer James Collins and CRISPR pioneer Feng Zhang of the Broad Institute of MIT and Harvard reported in Science that they had programmed a CRISPR molecule to seek out strains of Zika and dengue viruses in blood serum, urine and saliva and cut them up.

The researchers programmed the CRISPR molecules to release a fluorescent signal when they were chopping away at the viruses, so that the presence of the virus could be detected. SHERLOCK was so sensitive, it was able to distinguish the American strain of Zika from the African strain and differentiate one strain of dengue from another one.

Collins and his team were able to see the presence of the viruses even in extremely low concentrations, as low as two molecules in a quintillion.

In a separate test, SHERLOCK was able to detect two different strains of the antibiotic-resistant superbug Klebsiella pneumoniae. [6 Superbugs to Watch Out For]

Then, in June 2017, a team at the University of Central Florida reported in the journal Scientific Reports that they had used a CRISPR system to detect the presence of Parkinson's disease. This disorder of the central nervous system causes malfunction and death of nerve cells in the brain, and gets worse over time, causing tremors and problems with movement. The disease affects about 1 million people in the United States, according to the Parkinson's Disease Foundation.

Although the cause is unknown, the amount of a protein called alpha-synuclein, normally found in the brain, rises in people who develop the disease. The researchers used CRISPR to edit the gene that makes the alpha-synuclein protein so that the protein would fluoresce. The larger the amount of the protein, the stronger the fluorescent signal.

The scientists said they think they could use this technique to test out new drugs to treat Parkinson's disease.

"If we take one of these modified cells and treat it with a particular drug, if it doesn't produce light anymore, then this means the drug is a potential treatment for this disease," study co-author Sambuddha Basu, a postdoctoral researcher at Central Florida,said in a statement.

It's still the very early days for these and other CRISPR-related biological tools, and because of the diversity of the immune systems in bacteria, it's quite possible that other tools remain to be discovered, Sternberg said.

"I think it's a really nice example of yet another basic science discovery that has led to a potential breakthrough technology," he said.

Originally published on Live Science.

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Could CRISPR Sniff Out Viruses? - Live Science

With CRISPR being one of the most significant discoveries in genome engineering history, many scientists are now turning towards it as a basic foundation of their research. In response, companies are developing new technologies and products designed to help these very scientists become more effective in their research. One such company is Silicon Valley entity Synthego.

Founded by engineers, Paul and Michael Dabrowski, Synthego has risen from an unknown startup to one of the leading providers of genome engineering solutions today. Having both worked at Elon Musks SpaceX, the Dabrowski brothers seemed like an unlikely pair to create a biotech company focused on CRISPR genome engineering. However, it is their knowledge and experience of precision engineering and automation that has become a key differentiator.

In 2015, Synthego brought on biotech industry veteran Ted Tisch as Chief Operating Officer. In the following years, Ted helped build Synthegos product development, manufacturing and commercial operations, and formally launch the company in 2016.

Eight of the worlds 10 largest biopharma companies are already working with Synthego. Out of the top 25 biology universities in the world, 24 are using its products, and even CRISPR pioneer Jennifer Doudnas interest was sparked she is now an investor in the company.

We caught up with Tisch to talk about how CRISPR is revolutionizing the biotech field and the role Synthego is playing in all of this.

With genetic engineering as a key scientific research area, more and more researchers are using it as a foundation of their studies (source: Shutterstock)

PCR and next-generation sequencing (NGS) have been the two breakthrough technologies of the past 25 years. I call them core platform technologies, because they have been built up and expanded over time. These technologies took 10 to 15 years to reach wide adoption because researchers had to adjust to a technology that was very expensive. This consequently limited the adoption rate.

The cool thing about CRISPR is that it requires only a few pieces of equipment for it to work, so anyone can do it. I have not observed a technology lift like this in the market and this is why I believe that CRISPR will be the third platform technology in life science. Synthego aims to revolutionize CRISPR in two ways: Firstly, it automates the laboratory workflow, and secondly, it focuses on simplifying the workflow.

Biological workflows are extremely complex, as they include many complicated steps, which can lead to errors and wrong assumptions. This is a downward spiral, as many researchers rely on the work of others and subsequently, mistakes might be replicated in other labs. One of the biggest challenges with fast moving technologies is that people start publishing quickly with poor results; Synthego is trying to keep the industry safe from the dissemination of poor results by providing high-quality effective products and ultimately performing the basic research steps themselves.

Synthego is working to revolutionize genetic engineering by offering high-quality synthetic gRNA and a next-generation Design Tool (Source: Shutterstock)

Synthego produces synthetic guide RNA (gRNA) and a next-generation Design Tool. Imagine synthetic gRNA like a shuttle that escorts the enzyme Cas9 to a specific target gene where the Cas9 can cut the DNA. Poor quality gRNA products can lead to off-target events, meaning that the enzyme cuts the wrong part of the DNA strand. Synthegos gRNA has a high on-target efficiency, allowing researchers to work more quickly. Subsequently, there is an increased percentage of edited cells, making research experiments much easier.

The other product is a CRISPR Design Tool, which was launched in May. Synthego developed a software tool that identifies the target gRNA sequence with the highest on-target percentage while reducing off-target events. Researchers can go online, look up over 100,000 genomes and within seconds the tool will present the sequence of the gRNA. Its like shopping on Amazon: users can order it directly online and a receive their product a couple of days later.

The Design Tool coupled with the synthesized gRNA really simplifies the workflow in the lab.

Synthegos main goal is to automate and simplify the laboratory workflow, in order to minimize errors and maximize research success (source: Shutterstock)

There has been a great resonance from the industry. Worldwide, academic institutions and commercial organizations in about 33 countries are working with Synthego. To date, 24 of the 25 top life science universities in the world, and 8 of the worlds 10 largest biopharmaceutical companies are using our technologies.

Following the US, Europe represents one of our largest areas of interest. We have customers in most of the major Western European countries, including the United Kingdom, Germany, France, Spain and the Netherlands. For example, Synthego is working closely with the University of Oxford in the UK, and in Germany, the University of Freiburg.

Well, the first but good problem were facing is that Synthego has a huge customer demand. Helped by the fact that we received series B funding in January, we are now focusing on upscaling our capacities and on the development of new products and solutions.

An automated workflow brings many advantages with it. In the case of CRISPR, off-target events are minimized, whilst on-target events increase dramatically (source: Shutterstock)

One major challenge is to get people to move away from outdated processes. Scientists are notoriously dogmatic and careful about adapting new technologies. However, many researchers are exploring new ways of using genome editing in their processes, whether its therapies, improving the performance of their cell lines, or the development of their drug products. As our products help to deliver good and quick results, we have a high adoption rate.

As a small company that is trying to make noise in a big industry, we have to focus on quality, innovation and quick execution. Our competition are the large multimillion dollar life sciences companies. But these large life science suppliers have tried to address genome editing with old technologies or processes, making their products more expensive, slow to be delivered, and often unclean.

In the near term, we see further simplifying and improving the research workflow by providing easy-to-use kits and tools.

Our long-term strategy is to offer biology as a service. Imagine a scientist who wants to run thousands of experiments, but is lacking the time, budget, or infrastructure. As Synthego continues to develop its platform, any scientist will be able to insert his experimental parameters online via a computer, and Synthego will run the experiment and deliver the results.

Our goal is to make biology research accessible for all scientists worldwide.

Images vianoeldelmar, TarikVision, ibreakstock, science photo, Bloomicon/Shutterstock.com

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Rockets to DNA - How Two SpaceX Engineers became CRISPR ... - Labiotech.eu (blog)

China's State Intellectual Property Office (SIPO) has granted the University of California a patent on CRISPR/Cas9 genome editing technology in the country.

The SIPO patent granted to University of California Berkeley, University of Vienna and researcher Professor Emanuelle Charpentier, will allow them to license CRISPR technologies to firms and researchers in China. It will also allow Professor Charpentier's company CRISPR Therapeutics and that of Professor Jennifer Doudna at Berkeley - Intellia Therapeutics, to market any CRISPR-based therapies they develop in future in the country.

'SIPO's decision further expands our IP portfolio, and is further global recognition that Jennifer Doudna, Emmanuelle Charpentier and their team are the pioneers in the application of CRISPR/Cas9 in all cell types,' said Intellia Therapeutics Chief Executive Officer and President, Dr Nessan Bermingham.

CRISPR intellectual property rights are the subject of an ongoing dispute in the USA between the University of California who were first to file and hold a general patent, and the Broad Institute, whose use of CRISPR in eukaryotic cells was determined to be separately patentable. The University of California argue that Professor Doudna and Professor Charpentier's team were the first to invent the technique, and has since filed an appeal for patent rights to uses of CRISPR in all cell types.

'China is following the lead of the EU and UK in saying that Doudna and Charpentier were the first to invent the CRISPR-Cas9 gene-editing technology,' said University of California Berkeley spokesperson, Robert Sanders, according to The Daily Californian. 'We are arguing that the US Patent and Trademark Office should also recognize Doudna and Charpentier were the first to invent the technology.'

The Broad Institute may yet be granted its own patents in China, as patent applications from the Broad Institute are still being considered by SIPO. 'In China, patents are subject to invalidation proceedings after they are issued,' Lee McGuire, the chief communications officer for the Broad Institute told The Daily Californian.

Continued here:

China sides with Berkeley on CRISPR patent - BioNews

In BriefScientists have developed a tool that can test an entiregenome against a CRISPR molecule to predict potential errors andinteractions. This will allow doctors to ensure treatments aresafer and more effective. Editing The Editor

The CRISPR gene-editing tool is already in use by scientists all over the world who are racing to cure deadly diseases by editing the genomes of patients. However, as human trials for various treatments are slated to begin, we still face the hurdle of ensuring that any errors in CRISPR edits wont causing problems. Scientists from The University of Texas at Austin may have come up with a possible solution. Theyve developedsomething that works like a predictive editor for CRISPR: a method for anticipating and catching the tools mistakes as it works, thereby allowing for the editing ofdisease-causing errors out of genomes.Click to View Full Infographic

Scientists have already learned how to use CRISPR to edit errors in almost any genome and its these errors that can cause a wide range of diseases. Many forms of cancer, Huntingtons disease, and even HIV can be targeted usingCRISPR. That being said, itsnot a perfect solution. Just as the autocorrect on your smartphone can cause you to send an unintentional and embarrassing text message, CRISPR can correct something that was actually right the consequences of which can make it adangerous mistake. One that actually causes a disease as opposed to an embarrassing social gaffe.

The researchers developed a method for quickly testing a CRISPR molecule against a persons entire genome, rather than onlythe target area,in order topredict other segments of DNA the tool might accidentally interact with. This new technique functions like an early warning system, giving doctors a chance to more closely tailor gene therapies to specific patients, while ensuring they are effective andsafe.

If were going to use CRISPR to improve peoples health, we need to make sure we minimize collateral damage, and this work shows a way to do that,Stephen Jones, UT Austin postdoctoral researcher and co-lead author of the study, told the UT News.

This research will also allow scientists to improve their own predictive skills when it comes to CRISPR molecule behaviors even without genome testing. This is because the work is actually revealing the rule book CRISPR molecules follow when they choose targets.

One CRISPR molecule the team tested, Cascade, targets DNA sequences but pays less attention to every third letterin the sequence. So if it were looking for the word shirt and instead found the word short, it might be fine with that, Jones said, explaining the significance of the quirk to the UT News.

As researchers master these rules, they will be able to develop better predictive models for CRISPR therapies. This will make the technique faster and cheaper, which will in turn render personalized gene therapies more accessible to more patients. Most important of all, it will also help make theentire process far safer.

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This New Gene-Editing Technique Can Spot CRISPR's Mistakes - Futurism

The 15 kilometer cross-country ski race at the 1964 Winter Olympics should have been a close race. But in fact Finlands Eero Mntyranta streaked over the line fully 40 seconds ahead of his closest competitor.

His secret? He was born with a mutation of the EPOR gene, which regulates the production of the erythropoietin protein. In turn this determines the production of red blood cells, which are crucial for physical endurance.

Disgraced cyclist Lance Armstrong achieved the same outcome by taking erythropoietin as a drug. But in future if indeed it has not already started athletes may go straight to the root of the matter and mutate their own EPOR gene, to give themselves the same advantage that Mntyranta was born with. How could this possibly be detected?

That athletes will turn to gene editing is, in my view, a certainty. We have the tools to manipulate genes and we know at least some of the genes that code for the sort of physical attributes that athletes crave. Here is a picture of the Belgian bull.

This double muscled specimen has a natural mutation of the gene that codes for the protein myostatin and the result is uninhibited muscle growth. For farmers that means lots of lean meat. But for weight lifters it could be a short cut to an Olympic medal.

A crack in creation

This is just one of the ethical dilemmas unleashed by our newfound ability to edit the genome. As I described last week Jennifer Doudna of UC Berkeley is credited with the discovery of CRISPR, the technique that has made gene editing considerably faster, cheaper, more accurate and accessible, and today I want to tell you a little more about her new book A Crack in Creation.

Much of it covers the voyage of the discovery of CRISPR the hypotheses, the laboratory tests, the international conferences, the chance meetings between researchers and the occasional flashes of inspiration. The book also tells us exactly how CRISPR works.

You may have to read this several times before getting your head around it but essentially CRISPR was adapted from the method that bacteria use to identify and cut the DNA of viruses that are trying to attack them a pair of designer molecular scissors that homes in on a specific twenty-letter DNA sequence and cuts apart both strands of the double helix..

Today we are able to use CRISPR to disable target genes and to add new stretches of DNA. One of the impressive aspects of Doudnas book is her confidence in these techniques.

Scientists tend to be circumspect, but not here. Scientists have succeeded in bringing this primordial process (of the evolution of life) fully under human control. Using powerful biotechnology tools to tinker with DNA inside living cells, scientists can now manipulate and rationally modify the genetic code that defines every species on the planet. And using CRISPR an organisms entire DNA content has become almost as editable as a piece of text.

That is not to say that CRISPR can achieve anything. Many traits are the result of numerous genetic interactions and may be too complicated to affect. And CRISPR is not perfect. DNA does not always get altered as desired, and there are off-target effects that hit other areas of the genome.

Then there is the challenge of delivering the CRISPR mechanism into cells. This is hard enough when the cells are in the laboratory but even harder when the cells are still inside the human body. We are finding ways of making gene editing more accurate, but a certain amount of inaccuracy may not matter anyway.

Most medical treatments have some unforeseen consequences and the judgement is not whether they are perfect but whether the advantages outweigh the disadvantages.

We must though draw an important distinction between the editing of germline cells and of somatic cells. Germline cells contain DNA that is handed down to the next generation. Somatic cells (sometimes called adult cells) are all the others.

Suppose that I have muscular dystrophy, a disease that can be tracked down to specific genetic mutations. If CRISPR is used to correct these mutations then there may be off-target effects that could affect the function of my cells and body in unwelcome ways. But this is my problem alone.

However if in trying to correct a specific gene in germline cells there are off-target effects then these will be passed on. This, it seems to me, is highly problematical.

And yet Doudna believes that germline editing is something that we should accept, arguing that since our genes are constantly and randomly changing as our cells divide and copy, a few extra CRISPR-induced changes wont make much difference.

What this tech can do

What can this new power over the living world do for mankind? First, it can enable us to understand it. The best way to find the function of a gene is to disable it and see the result.

Once we discover the genetic mutation responsible for, say, Huntingdons or cancer we can create cells or laboratory mice with this same mutation as use them as models upon which to test potential therapies. Already we have numerous examples of the potential of gene editing.

In human medicine CRISPR has already been used to develop potential cures for diseases including cystic fibrosis, sickle cell disease, muscular dystrophy, HIV/AIDS and even Alzheimers. Tests have been conducted on laboratory cells and animals and, in some pioneering cases, in humans.

CRISPR is critical to cancer immunotherapy, which sees immune cells engineered to recognize cancer cells. Elsewhere we have made barley that is resistant to powdery mildew, tomatoes that do not rot as soon as they are picked, mosquitoes that are unable to transmit malaria, ultra-muscular police dogs and cows with no horns. On the horizon are pigs that can serve as donors of human organs and even woolly mammoths and unicorns.

This all sounds great and yet Doudna is worried. The availability of CRISPR means that it could fall into villainous hands. She is worried that the same ignorant outcry that has hampered the progress of GM crops could impede the progress of gene editing. And she concedes that CRISPR is forcing us to confront difficult, perhaps unanswerable questions, many of which boil down to conundrums about the relationship between humans and nature.

But mankind has for ever tried to conquer nature and Doudna clearly believes that gene editing is in many ways superior to techniques we have used in the past. In the realm of agriculture historic practice has been to bombard plants with chemicals or radiation in order to cause random genetic changes.

When this has thrown up a plant with superior traits then we have bred from it. Is it not better to identify the desired trait, work out its genetic cause and then deliberately engineer the gene? And if we have hunted the great auk to extinction, should we not use genetic engineering to bring it back?

The most pressing debate concerns germline editing. When allied to established practices like In Vitro Fertilization and pre-implantation testing it is highly likely that we will be able to ensure that babies do not carry the genetic mutations that in some cases virtually guarantee a life of suffering.

Of course these same techniques could be used to create designer babies and yet Doudna favours their approval. I dont believe theres an ethical defence for banning germline modification outright, nor do I think we can justifiably prevent parents from using CRISPR to improve their chances of having a healthy, genetically related child, so long as the methods are safe and offered in an equitable manner.

If we have the tools to prevent suffering, surely we should use them. Doudna argues that some existing practices like PGD (pre-implantation genetic diagnosis) that allow parents to choose the sex of their baby or abort those with Downs syndrome are already facilitating forms of designer baby and that ultimately matters of conception are best left to parental choice.

Finally Doudna dismisses the argument that germline editing should be banned because it unnatural. As she points out natural evolution has not been entirely benign and, in the world of medicine the line between natural and unnatural blurs to the point of disappearing.In my mind the distinction between natural and unnatural is a false dichotomy, and if it prevents us from alleviating human suffering, its also a dangerous one.

So this book is both a description of the extraordinary possibilities of gene editing but also, if indeed the horse has not already bolted, a plea for its acceptance. We should, Doudna believes, be bold and brave. Few technologies are inherently good or bad; what matters is how we use them and in the case of CRISPR it has incredible potential to improve our world.

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CRISPR 'it Has Incredible Potential To Improve Our World - The Daily Reckoning

CRISPR-Cas3 is a subtype of the CRISPR-Cas system, a widely adopted molecular tool for precision gene editing in biomedical research. Aspects of its mechanism of action, however, particularly how it searches for its DNA targets, were unclear, and concerns about unintended off-target effects have raised questions about the safety of CRISPR-Cas for treating human diseases.

Harvard Medical School and Cornell University scientists have now generated near-atomic resolution snapshots of CRISPR that reveal key steps in its mechanism of action. The findings, published in Cell on June 29, provide the structural data necessary for efforts to improve the efficiency and accuracy of CRISPR for biomedical applications.

Through cryo-electron microscopy, the researchers describe for the first time the exact chain of events as the CRISPR complex loads target DNA and prepares it for cutting by the Cas3 enzyme. These structures reveal a process with multiple layers of error detectiona molecular redundancy that prevents unintended genomic damage, the researchers say.

High-resolution details of these structures shed light on ways to ensure accuracy and avert off-target effects when using CRISPR for gene editing.

To solve problems of specificity, we need to understand every step of CRISPR complex formation, said Maofu Liao, assistant professor of cell biology at Harvard Medical School and co-senior author of the study. Our study now shows the precise mechanism for how invading DNA is captured by CRISPR, from initial recognition of target DNA and through a process of conformational changes that make DNA accessible for final cleavage by Cas3.

Target search

Discovered less than a decade ago, CRISPR-Cas is an adaptive defense mechanism that bacteria use to fend off viral invaders. This process involves bacteria capturing snippets of viral DNA, which are then integrated into its genome and which produce short RNA sequences known as crRNA (CRISPR RNA). These crRNA snippets are used to spot enemy presence.

Acting like a barcode, crRNA is loaded onto members of the CRISPR family of enzymes, which perform the function of sentries that roam the bacteria and monitor for foreign code. If these riboprotein complexes encounter genetic material that matches its crRNA, they chop up that DNA to render it harmless. CRISPR-Cas subtypes, notably Cas9, can be programmed with synthetic RNA in order to cut genomes at precise locations, allowing researchers to edit genes with unprecedented ease.

To better understand how CRISPR-Cas functions, Liao partnered with Ailong Ke of Cornell University. Their teams focused on type 1 CRISPR, the most common subtype in bacteria, which utilizes a riboprotein complex known as CRISPR Cascade for DNA capture and the enzyme Cas3 for cutting foreign DNA.

Through a combination of biochemical techniques and cryo-electron microscopy, they reconstituted stable Cascade in different functional states, and further generated snapshots of Cascade as it captured and processed DNA at a resolution of up to 3.3 angstromsor roughly three times the diameter of a carbon atom.

Seeing is believing

In CRISPR-Cas3, crRNA is loaded onto CRISPR Cascade, which searches for a very short DNA sequence known as PAM that indicates the presence of foreign viral DNA.

Liao, Ke and their colleagues discovered that as Cascade detects PAM, it bends DNA at a sharp angle, forcing a small portion of the DNA to unwind. This allows an 11-nucleotide stretch of crRNA to bind with one strand of target DNA, forming a seed bubble.

The seed bubble acts as a fail-safe mechanism to check whether the target DNA matches the crRNA. If they match correctly, the bubble is enlarged and the remainder of the crRNA binds with its corresponding target DNA, forming what is known as an R-loop structure.

Once the R-loop is completely formed, the CRISPR Cascade complex undergoes a conformational change that locks the DNA into place. It also creates a bulge in the second, non-target strand of DNA, which is run through a separate location on the Cascade complex.

Only when a full R-loop state is formed does the Cas3 enzyme bind and cut the DNA at the bulge created in the non-target DNA strand.

The findings reveal an elaborate redundancy to ensure precision and avoid mistakenly chopping up the bacterias own DNA.

To apply CRISPR in human medicine, we must be sure the system is accurate and that it does not target the wrong genes, said Ke, who is co-senior author of the study. Our argument is that the CRISPR-Cas3 subtype has evolved to be a precise system that carries the potential to be a more accurate system to use for gene editing. If there is mistargeting, we know how to manipulate the system because we know the steps involved and where we might need to intervene.

Setting the sights

Structures of CRISPR Cascade without target DNA and in its post-R-loop conformational states have been described, but this study is the first to reveal the full sequence of events from seed bubble formation to R-loop formation at high resolution.

In contrast to the scalpel-like Cas9, CRISPR-Cas3 acts like a shredder that chews DNA up beyond repair. While CRISPR-Cas3 has, thus far, limited utility for precision gene editing, it is being developed as a tool to combat antibiotic-resistant strains of bacteria. A better understanding of its mechanisms may broaden the range of potential applications for CRISPR-Cas3.

In addition, all CRISPR-Cas subtypes utilize some version of an R-loop formation to detect and prepare target DNA for cleavage. The improved structural understanding of this process can now enable researchers to work toward modifying multiple types of CRISPR-Cas systems to improve their accuracy and reduce the chance of off-target effects in biomedical applications.

Scientists hypothesized that these states existed but they were lacking the visual proof of their existence, said co-first author Min Luo, postdoctoral fellow in the Liao lab at HMS. The main obstacles came from stable biochemical reconstitution of these states and high-resolution structural visualization. Now, seeing really is believing.

Weve found that these steps must occur in a precise order, Luo said. Evolutionarily, this mechanism is very stringent and has triple redundancy, to ensure that this complex degrades only invading DNA.

This article has been republished frommaterialsprovided by Harvard Medical School. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Xiao, Y., Luo, M., Hayes, R. P., Kim, J., Ng, S., Ding, F., . . . Ke, A. (2017). Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System. Cell, 170(1). doi:10.1016/j.cell.2017.06.012

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CRISPR Mechanism of Action Imaged Near-atomic Resolution - Technology Networks

Jennifer Doudna: Experiments fail. To have people around that get along with each other is super important. Photograph: Bryan Derballa/Kintzing.com

Jennifer Doudna, 53, is an American biochemist based at the University of California, Berkeley. Together with the French microbiologist Emmanuelle Charpentier, she led the discovery of the revolutionary gene-editing tool, Crispr. The technology has the potential to eradicate previously incurable diseases, but also poses ethical questions about the possible unintended consequences of overwriting the human genome.

Were you nerdy as a child? What got youhooked on science? Yes, I was nerdy. My father was a professor of American literature in Hawaii and he loved books. One day I came home from school and he haddropped a copy of The Double Helixon the bed, by Jim Watson. Onerainy afternoon I read it and Iwasjust stunned. I was blown awaythat you could do experiments about what a molecule looks like. I was probably 12 or 13. I think that wasthebeginning ofstarting to think,Wow, that could be an amazingthing to work on.

Youve spent most of your career uncovering the structure of RNA and never set out to create a tool to copy andpaste human genes. How did you endup working on Crispr? I think you can put scientists into two buckets. One is the type who dives very deeply into one topic for their whole career and they know it better than anybody else in the world. Then theresthe other bucket, where I wouldput myself, where its like youre at a buffet table and you see an interesting thing here and do it for a while, and that connects you to another interesting thing and you take a bit of that. Thats how I came to be working on Crispr it was a total side-project.

But when you first started your collaboration with Emmanuelle Charpentier, did you have a hunch youwere on to something special? We met at a conference in San Juan, Puerto Rico, and took a walk around the old town together. She was so passionate, her excitement was very infectious. I still remember walking down this street with her and she said: Well Im really glad you want to work with us on the mysterious [Cas9 the enzyme that snips DNA at the chosen location in the editing process]. It was this kind of electrifying moment. Even then I just had this gut feeling that this was something really interesting.

I would have loved to continue working with Emmanuelle. Im not blaming her: she had her reasons and I respect her

How important is personal chemistry inscience collaborations? Its essential. Working in a lab is analogous to being in a high-school play: youre rehearsing long hours, itscrowded, there are stressful things that come up. Its the same thing in science. Things never work as you think they will, experiments fail and so to have people around that really get along with each other is super important. Many collaborations dont work out, usually just because peoples interests arent aligned or people dont really like working together.

The real frenzy around your work started in 2012, when you showed that Crispr-Cas9 could be used to slice up DNA at any site [of the DNA molecule] you wanted. Did you realise this was abig deal gradually orimmediately? It wasnt a gradual realisation, it was one of those OMG moments where you look at each other and say holy moly. This was something we hadnt thought about before, but now we could see how it worked, we could see it would be such a fantastic way to do gene editing.

After you demonstrated Crispr could edit bacterial DNA, two rival labs (Harvard and the Broad Institute) got there first in human cells. How come they beat you to it? They were absolutely set up to do that kind of experiment. They had all the tools, the cells growing, everything was there. For us, they were hard experiments to do because its not thekind of science we do. What speaksto the ease of the system was that a lab like mine could even do it.

The Broad Institute won the latest round of an ongoing legal battle over patent rights they claim that it wasnt obvious that Crispr could be used to edit human cells too. Where do you stand? People have asked me over and over again: Did you know it was going to work? But until you do an experiment you dont know thats science. Ive been lambasted for this in the media, but I have to be true to who I am as a scientist. We certainly had a hypothesisand it certainly seemed likea very good guess that it would.

Theres the patent dispute and you and Emmanuelle Charpentier also ended up pursuing rival projects to commercialise the technology. Are you all still friends? If theres a sadness to me about all of this and a lot of its been wonderful and really exciting its that I wouldve loved to continue working with Emmanuelle, scientifically. For multiple reasons that wasnt desirable to her. Im not blaming her at all she had her reasons and I respect her a lot.

The media loves to drive wedges, but we are very cordial. I was just with her in Spain and she was telling me about the challenges [of building her new lab in Berlin]. I hope on her side, certainly on my side, we respect each others work and in the end were all init together.

In your book you describe a nightmare youhad involving Hitler wearing a pig mask, asking to learn more about your amazing technology. Do you still have anxiety dreams about where Crispr mightleave the human race? I had the Hitler dream and Ive had a couple of other very scary dreams, almost like nightmares, which is quite unusual for an adult. Not so much lately, but in the first couple of years after I published my work, the field was moving so fast. I had this incredible feeling that the science was getting out way ahead of any considerations about ethics, societal implications and whether we should be worrying about random people in various parts of the world using this for nefarious purposes.

In 2015, you called for a moratorium on the clinical use of gene editing. Where do you stand on using Crispr to edit embryos these days? It shouldnt be used clinically today, but in the future possibly. Thats a big change for me. At first, I just thought why would you ever do it? Then I started to hear from people with genetic diseases in their family this is now happening every day for me. Alot of them send me pictures of their children. There was one that Icant stop thinking about, just sent to me in the last 10 days or so. A mother who told me that her infant son was diagnosed with a neurodegenerative disease, caused by a sporadic rare mutation. She sent me a picture of thislittle boy. He was this adorable little baby, he was bald, in his little carrier and so cute. I have a son and myheart just broke.

What would you do as a mother? You see your child and hes beautiful, hes perfect and you know hes going to suffer from this horrible disease and theres nothing you can do about it. Its horrible. Getting exposed to that, getting to know some of these people, its not abstract any more, its very personal. And you think, if there were away to help these people, we should do it. It would be wrong not to.

Are people going to start saying I want a child thats 6ft 5in with blue eyes and so on? Do we really want to go there?

What about the spectre of designerbabies? A lot of it will come down to whether the technology is safe and effective, are there alternatives that would be equally effective that we should consider, and what are the broader societal implications of allowing gene editing? Are people going to start saying I want a child thats 6ft 5in and has blue eyes and so on? Do we really want to go there? Would you do things that are not medically necessary but are just nice-to-haves, for some people?Its a hard question. There area lot of grey areas.

Are you worried about cuts to science funding, including to the National Institutes of Health (NIH) budget? I am very concerned. Science funding is not a political football but in fact a down payment on discovery, the seed money to fund a critical step toward ending Alzheimers or curing cancer.

Researchers currently working on projects aimed at improving numerous aspects of our agriculture, environment and health may be forced to abandon their work. The outcome is that people will not receive the medical treatments they need, our struggle to feed our exploding population will deepen, and our efforts to manage climate change will collapse.

Over the long term, the very role of fundamental science as a means to better our society may come into question. History and all evidence points to the fact that when we inspire and support our scientific community we advance our way of life and thrive.

Were you disturbed when Trump tweeted, If U.C. Berkeley does not allow free speech and practices violence on innocent people with a different point of view NO FEDERAL FUNDS? in response to a planned alt-right speaker being cancelled due to violent protests on campus? Yes. It was a confusing tweet since the university was clearly committed to ensuring that the event would proceed safely and first amendment rights were supported. Few expected the awful actions of a few to be met with a willingness from the highest office to deprive more than 38,000 students access to an education.

Youve spoken at Davos, shared the $3m2015 Breakthrough prize, been listedamong the 100 most influential people in the world by Time magazine. Areyou still motivated about heading intothe lab these days? Yesterday I was getting ready to go to a fancy dinner. I was in a cocktail gown and had my makeup on and my hair done, but I wanted to talk to a postdoc in my lab about an experiment he was doing, so I texted him saying can we Skype? It was 8am in California, I was over here [in the UK] in my full evening gown, talking abouttheexperiment.Thats how nerdy I am.

A Crack in Creation: The New Power to Control Evolution by Jennifer Doudna and Sam Sternberg is published by The Bodley Head (20). To order a copy for 17 go to bookshop.theguardian.com or call 0330 333 6846. Free UK p&p over 10, online orders only. Phone orders min p&p of 1.99

Continued here:

Jennifer Doudna: 'I have to be true to who I am as a scientist ... - The Guardian

The UK Governments chief medical adviser has unveiled plans where genome-based personalised medicine could open up for cancer patients within five years.

The genomics dream outlined by Professor Dame Sally Davies would see millions of patients having all their DNA tested as genome sequencing becomes as routine as MRI or CT scans.

Here is everything you need to know about the human genome and the proposed genetic testing to help treat cancer patients:

A genome is the genetic material of an organism.

In humans, it is made up of 23 chromosome pairs. Every persons genome contains 3.2 billion letters of genetic code, amounting to two terabytes of data.

Within the genome are 20,000 genes stretches of DNA that provide the software for making proteins.

Other parts of the genome act as dimmer switches regulating the activity of genes.

Having access to this genetic blueprint can make a huge difference to the diagnosis and treatment of someone with cancer or a rare disease.

In the case of cancer, tumour cells develop a different genome to normal cells. Comparing a patients normal and cancerous DNA can provide valuable clues about the best form of treatment.

However, this information is not set in stone. Cancers evolve rapidly and alter their DNA, which can make them resistant to treatments.

Genome testing at regular intervals can help clinicians keep up in the arms race with cancer and guide ongoing therapy.

It can also help distinguish between aggressive and deadly cancers and slow-growing tumours that may never threaten a patients life.

For adults and children with one of the 7,000 recognised rare diseases, genome testing could lead to far speedier and more effective treatment.

About 3.5 million individuals in the UK has a rare disease, many of them children under the age of five.

Currently having a rare disease identified involves multiple tests and several consultations.

The average patient sees five different doctors and is misdiagnosed three times before the nature of their illness is finally known. Reaching the end of this journey takes four years on average.

By reading a patients DNA rather than relying on the observation of often subtle symptoms, genomics testing can allow much faster diagnosis of rare diseases.

Currently, genetic testing of NHS patients in England is conducted through 25 regional laboratories and a plethora of smaller ones operating along the lines of a cottage industry, according to Dame Sally.

Her chief recommendation is to centralise all the labs and establish a national network providing equal access to the tests across the country.

Within government, a new national genomics board would be set up, chaired by a minister, to oversee the expansion and development of genomic services taking into account new advances within the rapidly evolving technology.

Her report calls for a simplified two-stage consent system and make it easier for patients to get involved in research studies and clinical trials.

Speaking at a news briefing in London, Dame Sally said she hoped to see the new system fully operational within five years.

See the original post here:
Everything you need to know about the Government plan for genetic testing to treat cancer patients - BreakingNews.ie

Ronan is the editor of Life Insurance International. You can reach him at ronan.mccaughey@verdict.co.uk

Would you share your genetic test results with a life or health insurer if it meant a cheaper policy in return?

Its an issue increasingly on the minds of insurers because access to genetic data would allow them to offer more personalised policies, potentially lower costs and assess policyholder risk much better.

And lets not forget, life and health insurers already have access to significant data on consumers medical history, as well as their lifestyle and activity patterns generated by wearable technology and fitness trackers.

Ross Campbell, life and health chief underwriter, research & development at Gen Re, recently wrote for Life Insurance International explaining that genomics, the field of molecular biology focused on mapping the genome, is at the forefront of a technological revolution in bio-medicine and healthcare.

So far, Campbell says the UK insurance industry has voluntarily agreed not to use much of the data that is available.

He explains that when introduced the moratorium acknowledged contemporary concerns that DNA sequencing would allow abnormal patterns in specific genes to be recognised and potentially misused by insurers.

Campbell says:

We now understand medical predictability can only rarely, such as Huntingtons Disease, be based on DNA alone, other risk factors may be more important as an example the combination effect of genes, nutrition, and exercise. But while exercise is linked with genetics, the relationship is too fragile for the results of direct-to-consumer genetic tests to be useful in making lifestyle recommendations.

He adds: Our collective understanding of genomics and its potential relevance to risk assessments has also improved significantly in recent years, and it offers the opportunity for insurers to do things better with individuals consent.

In October 2016 life reinsurer, Gen Re, said its survey of attitudes to genetic testing found that most people are open to being tested for genetic conditions, believing that it will help them to manage their health better.

Many indicated they would have a genetic test if it would give them a better understanding of any health risks they might face, mostly to allow early medical intervention.

Some wanted to understand what risks they might pass along to their children, while others would have a test if there was a good reason such as family history or existing illness.

Those who didnt want to be tested were reluctant about being burdened with knowledge about diseases about which they believe they could do nothing; they felt a test was unlikely to be useful in the absence of a clinical problem or history of genetic conditions in their relatives.

In the UK, at least, it is highly unlikely that life insurers will start using genetic data to set the level of cover anytime soon.

But rapid strides being made by the industry to digitalise and embrace data analytics means its not a question of if, but rather when, life and health insurers lobby the government and public to use genetic testing.

Decoding peoples DNA will be the next frontier for insurance.

More:
DNA insurance: Why genetic testing could revolutionise the industry - Verdict

We are a society obsessed with information. Were constantly connected, click-click-clicking to access a steady stream of news, data, and social-media updates. Curiosity is a powerful motivator, but theres one area in which our thirst for knowledge has been inconsistent: genetic testing.

DNA tests have become du jour in the past decade. Technological advances and access to genomic testing translates into the ability to see whats beneath the hood of our chromosomal cars. Weve become obsessed with ancestry tests like 23andMe and finding out our babies sexes before theyre born, but we often shy away when it comes to more serious curiosities. Even though you can now easily find out if you carry the genetic mutations or changes for recessive diseases like spinal muscular atrophy, we often dont test for these genetic glitches because we just dont want to know. But its important that we find out.

Theres no doubt that genetics is complicated, and maybe its that lack of certainty that deters some people from diving into their DNA. Genetic disease can be confusing, with some mutations definitely resulting in disease and others leading only to increased risk. Some genetic diseases require that both parents have a mutation in order to stand a chance of having an affected child; others can be triggered by just one parent possessing a mutation. Its a bit of a crapshoot.

With so many diseases and conditions transmitted in different ways and identifiable at different stages of pregnancy, its no wonder that some women choose to forego prenatal testing at all; adopting a head-in-the-sand approach can be easier to cope with than grappling with the uncertainties raised by a DNA test.

But when it comes to prenatal testing, information is always a good thing. Knowing ahead of time about a condition can allow parents to set up a support network of family and friends and connect with other parents who have a child with a similar diagnosis. They can learn more about the condition with which their fetus has been diagnosed, seek out medical specialists ahead of time, and choose to deliver at a hospital that has the appropriate level of care for a baby with special needs.

Being surprised by an unexpected diagnosis on the day of delivery turns what should have been a joyous day into a day marked by confusion and fear.I interviewed scores of mothers for my book, The Gene Machine: How Genetic Technologies Are Changing the Way We Have KidsAnd the Kids We Have. In speaking with numerous women who didnt know while pregnant that they would give birth to children with special needs, Ive heard a common theme. Moms say that being surprised by an unexpected diagnosis on the day of delivery turned what should have been a joyous daythe birth of their childinto a day marked by confusion and fear. They wish they would have been aware of their childs diagnosis so that they could have come to terms with it before giving birth. That awareness could have allowed them to educate themselves and to prepare mentally and emotionally. It could have given them a jumpstart on processing and resolving the inevitable feelings of loss that come with learning that the baby youd hoped for is not the baby you have.

Pregnancy is not a perfect science; things can and do go awry. Worldwide, an astounding 8 million babies6% of birthsare born with a birth defect, many of which can be traced to genetics.

But even when the baby you give birth to may not be the perfect baby you expected, arming yourself with information ahead of time can make a big difference in how you process the experience of having a child with special needs. In 1987, Sesame Street writer Emily Perl Kingsley wrote about reconciling reality with expectations after the birth of her son, Jason, who was born in 1974 with Down syndrome.

When youre going to have a baby, its like planning a fabulous vacation trip to Italy. You buy a bunch of guidebooks and make wonderful plans. After months of eager anticipation, the day finally arrives. You pack your bags and off you go. Several hours later, the plane lands. The stewardess comes in and says, Welcome to Holland. Holland?!? you say. What do you mean Holland? I signed up for Italy! Im supposed to be in Italy. All my life Ive dreamed of going to Italy.

Some women decline genetic testing because they say that even if they receive a concerning diagnosis, they wouldnt alter the course of their pregnancy anyway. But thats rarely the case. As one genetic counselor told me, shes never had a couple do absolutely nothing upon learning that their fetus has a health issue. When people say they wouldnt do anything differently, she said, thats simply not true. Do anything differently is often code for abortion, yet ending a pregnancy is just one option upon receiving concerning genetic-test results. Many parents decide to continue an affected pregnancy.

Other women turn down the offer of genetic testing either because theyre overwhelmed by its complexity or because they mistakenly think theyre in the clear because they have no family history of genetic conditions. But family history, while useful, is a poor predictor of potential problems.

Consider autosomal recessive diseases such as cystic fibrosis, which affects one in 2,500 white babies. (Its less common in African American and Asian populations). If both parents carry the same genetic mutation, their children have only a 25% chance of developing the disease. Compare this with autosomal dominant mutations such as BRCA, often called the breast cancer gene. If either parent has a BRCA mutation, theres a 50% chance of passing that same genetic change to a child. Then there are conditions such as Down syndrome, which arent typically inherited and instead occur randomly around the time of conception.

Just because no one in your family suffers from a recessive disease doesnt mean youre not a carrier of it. Think back to those autosomal recessive diseases such as cystic fibrosis that occur only if both parents carry a mutation. Each pregnancy conceived by these carrier couples only has a 25% chance of developing the diseasethat means theres a 75% chance that any child will be disease-free. A mutation for one of these diseases could be unknowingly passed down for generations before two partners with the same mutation find one another and make a baby that has the unfortunate luck to inherit both problematic mutations.

We are no longer living in an era in which women have no choice but to remain in the dark about the health of their unborn children. All parents stand to benefit from knowing about potential problems ahead of time, which allows them to be proactive and take charge. Genetic testing before and during pregnancy can empower parents to make the decisions that are right for them, whether the itinerary of parenting leads them to Italy, Holland, or somewhere in between.

Learn how to write for Quartz Ideas. We welcome your comments at ideas@qz.com.

Originally posted here:
The real reason why all women should get their DNA tested - Quartz

Posted in: History | Comments (0)

A copy of the Declaration of Independence.

Following is the text of the Declaration of Independence in celebration of Independence Day, July 4th, 2017:

IN CONGRESS, July 4, 1776.

The unanimous Declaration of the thirteen united States of America,

When in the Course of human events, it becomes necessary for one people to dissolve the political bands which have connected them with another, and to assume among the powers of the earth, the separate and equal station to which the Laws of Nature and of Natures God entitle them, a decent respect to the opinions of mankind requires that they should declare the causes which impel them to the separation.

We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness.That to secure these rights, Governments are instituted among Men, deriving their just powers from the consent of the governed, That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it, and to institute new Government, laying its foundation on such principles and organizing its powers in such form, as to them shall seem most likely to effect their Safety and Happiness. Prudence, indeed, will dictate that Governments long established should not be changed for light and transient causes; and accordingly all experience hath shewn, that mankind are more disposed to suffer, while evils are sufferable, than to right themselves by abolishing the forms to which they are accustomed. But when a long train of abuses and usurpations, pursuing invariably the same Object evinces a design to reduce them under absolute Despotism, it is their right, it is their duty, to throw off such Government, and to provide new Guards for their future security.Such has been the patient sufferance of these Colonies; and such is now the necessity which constrains them to alter their former Systems of Government. The history of the present King of Great Britain is a history of repeated injuries and usurpations, all having in direct object the establishment of an absolute Tyranny over these States. To prove this, let Facts be submitted to a candid world.

He has refused his Assent to Laws, the most wholesome and necessary for the public good.

He has forbidden his Governors to pass Laws of immediate and pressing importance, unless suspended in their operation till his Assent should be obtained; and when so suspended, he has utterly neglected to attend to them.

He has refused to pass other Laws for the accommodation of large districts of people, unless those people would relinquish the right of Representation in the Legislature, a right inestimable to them and formidable to tyrants only.

He has called together legislative bodies at places unusual, uncomfortable, and distant from the depository of their public Records, for the sole purpose of fatiguing them into compliance with his measures.

He has dissolved Representative Houses repeatedly, for opposing with manly firmness his invasions on the rights of the people.

He has refused for a long time, after such dissolutions, to cause others to be elected; whereby the Legislative powers, incapable of Annihilation, have returned to the People at large for their exercise; the State remaining in the mean time exposed to all the dangers of invasion from without, and convulsions within.

He has endeavoured to prevent the population of these States; for that purpose obstructing the Laws for Naturalization of Foreigners; refusing to pass others to encourage their migrations hither, and raising the conditions of new Appropriations of Lands.

He has obstructed the Administration of Justice, by refusing his Assent to Laws for establishing Judiciary powers.

He has made Judges dependent on his Will alone, for the tenure of their offices, and the amount and payment of their salaries.

He has erected a multitude of New Offices, and sent hither swarms of Officers to harrass our people, and eat out their substance.

He has kept among us, in times of peace, Standing Armies without the Consent of our legislatures.

He has affected to render the Military independent of and superior to the Civil power.

He has combined with others to subject us to a jurisdiction foreign to our constitution, and unacknowledged by our laws; giving his Assent to their Acts of pretended Legislation:

For Quartering large bodies of armed troops among us:

For protecting them, by a mock Trial, from punishment for any Murders which they should commit on the Inhabitants of these States:

For cutting off our Trade with all parts of the world:

For imposing Taxes on us without our Consent:

For depriving us in many cases, of the benefits of Trial by Jury:

For transporting us beyond Seas to be tried for pretended offences

For abolishing the free System of English Laws in a neighbouring Province, establishing therein an Arbitrary government, and enlarging its Boundaries so as to render it at once an example and fit instrument for introducing the same absolute rule into these Colonies:

For taking away our Charters, abolishing our most valuable Laws, and altering fundamentally the Forms of our Governments:

For suspending our own Legislatures, and declaring themselves invested with power to legislate for us in all cases whatsoever.

He has abdicated Government here, by declaring us out of his Protection and waging War against us.

He has plundered our seas, ravaged our Coasts, burnt our towns, and destroyed the lives of our people.

He is at this time transporting large Armies of foreign Mercenaries to compleat the works of death, desolation and tyranny, already begun with circumstances of Cruelty & perfidy scarcely paralleled in the most barbarous ages, and totally unworthy the Head of a civilized nation. He has constrained our fellow Citizens taken Captive on the high Seas to bear Arms against their Country, to become the executioners of their friends and Brethren, or to fall themselves by their Hands. He has excited domestic insurrections amongst us, and has endeavoured to bring on the inhabitants of our frontiers, the merciless Indian Savages, whose known rule of warfare, is an undistinguished destruction of all ages, sexes and conditions.

In every stage of these Oppressions We have Petitioned for Redress in the most humble terms: Our repeated Petitions have been answered only by repeated injury. A Prince whose character is thus marked by every act which may define a Tyrant, is unfit to be the ruler of a free people.

Nor have We been wanting in attentions to our Brittish brethren. We have warned them from time to time of attempts by their legislature to extend an unwarrantable jurisdiction over us. We have reminded them of the circumstances of our emigration and settlement here. We have appealed to their native justice and magnanimity, and we have conjured them by the ties of our common kindred to disavow these usurpations, which, would inevitably interrupt our connections and correspondence. They too have been deaf to the voice of justice and of consanguinity. We must, therefore, acquiesce in the necessity, which denounces our Separation, and hold them, as we hold the rest of mankind, Enemies in War, in Peace Friends.

We, therefore, the Representatives of the united States of America, in General Congress, Assembled, appealing to the Supreme Judge of the world for the rectitude of our intentions, do, in the Name, and by Authority of the good People of these Colonies, solemnly publish and declare, That these United Colonies are, and of Right ought to be Free and Independent States; that they are Absolved from all Allegiance to the British Crown, and that all political connection between them and the State of Great Britain, is and ought to be totally dissolved; and that as Free and Independent States, they have full Power to levy War, conclude Peace, contract Alliances, establish Commerce, and to do all other Acts and Things which Independent States may of right do. And for the support of this Declaration, with a firm reliance on the protection of divine Providence, we mutually pledge to each other our Lives, our Fortunes and our sacred Honor.

The 56 signatures on the Declaration appear in the positions indicated:

Column 1

Georgia:

Button Gwinnett

Lyman Hall

George Walton

Column 2

North Carolina:

William Hooper

Joseph Hewes

John Penn

South Carolina:

Edward Rutledge

Thomas Heyward, Jr.

Thomas Lynch, Jr.

Arthur Middleton

Column 3

Massachusetts:

John Hancock

Maryland:

Samuel Chase

William Paca

Thomas Stone

Charles Carroll of Carrollton

Virginia:

George Wythe

Richard Henry Lee

Thomas Jefferson

Benjamin Harrison

Thomas Nelson, Jr.

Francis Lightfoot Lee

Carter Braxton

Column 4

Pennsylvania: Robert Morris

Benjamin Rush

Benjamin Franklin

John Morton

George Clymer

James Smith

George Taylor

James Wilson

George Ross

Delaware: Caesar Rodney

George Read

Thomas McKean

Column 5

New York:

William Floyd

Philip Livingston

Francis Lewis

Lewis Morris

New Jersey:

Richard Stockton

John Witherspoon

Francis Hopkinson

John Hart

Abraham Clark

Column 6

New Hampshire:

Josiah Bartlett

William Whipple

Massachusetts:

Samuel Adams

John Adams

Robert Treat Paine

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Anti tb drugs side effects pdf - Antioch Herald

Two-year-old Nathan DeAndrea who underwent two stem cell transplants to treat neuroblastoma is free of cancer, according to his mother.

Testing last week that included a CT scan and a full-body scan showed no evidence of cancer, Shannon DeAndrea said during an interview at her home Monday morning.

No more cancer! said Nathans sister, 4-year-old Kailynn.

However, the DeAndreas are awaiting the results of a bone marrow biopsy performed on Nathan last week, Shannon said. Everyone is optimistic.

The doctor said he has never seen a bone marrow biopsy come back positive when everything else is clear, she said.

Results are expected this week, Shannon said.

Nathan was diagnosed with stage 4 neuroblastoma on Aug. 23, 2016. He had a tumor in his abdomen that spread to his bone marrow. He had spots on his skull, ribs and spine. He has had several rounds of chemotherapy, radiation and two stem cell transplants.

Neuroblastomas are cancers that begin in early nerve cells of the sympathetic nervous system, according to the American Cancer Society.

The scans results brought relief to Shannon and her family.

Its like I could breathe, she said.

As Kailynn put it, We said, hooray!

The next phase of treatment will include strengthening Nathans immune system. He will be in the hospital one week a month for six months, Shannon said.

Its to keep it [the cancer] from coming back, she said.

His immune system is still compromised. The genetic makeup of Nathans tumor put him at a higher risk of relapse, Shannon said.

Nathans first transplant included four or five days of chemo. The new stem cells following the chemo that killed off his old stem cells from the transplant were like a rescue, she said.

Its wiping you out and then giving you your cells back to restart your immune system, DeAndrea said.

A second round of heavy chemo was to try to kill what was left of the cancer and replenish cells, she said.

Nathans stem cell transplants were from his own cells, Shannon said.

Two types of stem cell transplants include autologous, which uses stem cells from the patients own body, and allogeneic using stem cells from another person.

The procedure is used for conditions including multiple myeloma, lymphoma, sickle cell anemia and leukemia, and other blood and immune disorders.

Stem cell transplants began in the late 50s/early 60s with the first successful procedure done in an identical twin. However, stem cell transplants were limited until medicines that prevent rejections became available.

The number of procedures increased in the 1980s.

Betsie Letterle, community engagement representative with BeTheMatch in Burlington, North Carolina, said there are more than 14 million bone marrow/stem cell donors in the BeTheMatch registry.

Bone marrow transplants traditionally involved taking the marrow from the back of the donors hip. But since then, weve progressed tremendously, Letterle said.

The newest way is to take stem cells from a vein in the donors arm, Letterle said. The donor receives an injection of medication to help their body manufacture a large amount of stem cells, she said.

Those are taken from the vein, similar to a plasma donation. Letterle said.

Anyone aged 18-44 can join the registry, but commitment is paramount among donors, she said.

Commitment is important because patients depend on us, Letterle said. We dont want anyone whos not really sure they could donate if called.

Only about one in 540 registered donors end up donating, she said. Everyone is an active donor until they turn 61, Letterle said.

Younger donors are healthier and make the most stem cells, she said.

We want to give the patient the optimum opportunity to get the best stem cells they can, she said.

If a donor comes up as a match, they will be asked for about 20-30 hours of their time over several weeks, Letterle said.

We work around the donors schedule, she said.

They get blood work done, and a physical to make sure theyre healthy enough to donate, Letterle said.

The donor never pays for anything, she said.

The doctor determines whether the procedure would be a stem cell or a traditional bone marrow transplant. That depends on the patients or recipients age and condition, Letterle said.

About 80 percent of registered donors are Caucasian, and BeTheMatch is looking for more minority donors, Letterle said. Many minority patients have trouble finding a match, she said.

The recipients blood type becomes whatever blood type the donor has, Letterle said.

Dr. William Clark with the Massey Cancer Center at Virginia Commonwealth University will speak about bone marrow and stem cell transplants from 11:30 a.m. to 1 p.m. July 11 at Ballou Recreation Center. A bone marrow/stem cell donor drive will also be held that day.

For more information on stem cell/bone marrow transplants, call Betsie Letterle at BeTheMatch at (877) 601-1926, ext. 7721.

JohnCrane reports for the Danville Register & Bee. Contact him atjcrane@registerbee.comor(434) 791-7987.

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Tests show no signs of cancer for Danville 2-year-old - GoDanRiver.com

The arthritis in Maureen Munsies ankles was so intense until barely a year ago, she literally had to crawl on hands and knees to get upstairs.

The pain, she recalls now, took my breath away, and played havoc with the avid hikers favourite pastime.

In desperation, Munsie turned to a Toronto-area clinic that provides a treatment many experts consider still experimental, unproven and of questionable safety.

The 63-year-old says the stem cells she received at Regenervate Medical Injection Therapy 18 months ago were transformational, all but eliminating the debilitating soreness and even allowing her to hike Argentinas Patagonia mountains two months ago.

For me its been a life saver, Munsie says. Ive been able to do it all again I dont have any of that pain, at all.

Canadians drawn to the healing promise of stem cells have for years travelled outside the country to such places as Mexico, China or Arizona, taking part in a dubious form of medical tourism.

But Regenervate is one of a handful of clinics in Canada that have begun offering injections of stem cells, satisfying growing demand but raising questions about whether a medical idea with huge potential is ready for routine patient care.

Especially when those patients can pay thousands of dollars for the service.

Clinics in Ontario and Alberta are treating arthritis, joint injuries, disc problems and even skin conditions with stem cells typically taken from patients fat tissue or bone marrow.

The underlying idea is compelling: stem cells can differentiate or transform into many other types of cell, a unique quality that evidence suggests allows them to grow or regenerate tissue damaged by disease or injury.

Researchers including hundreds in Canada alone are examining stem-cell treatments for everything from ailing hearts to severed spinal cords.

With few exceptions, however, the concept is still being studied in the lab or in human trials; virtually none of the treatments have been definitively proven effective by science or approved by regulators like Health Canada.

The fact that Canadian clinics are now offering stem-cell treatments commercially is concerning on a number of levels, not least because of safety issues, says Ubaka Ogbogu, a health law professor at the University of Alberta.

Three U.S. women were blinded after receiving stem-cell injections in their eyes, while other American patients have developed bony masses or tumours at injection sites, Ogbogu said.

Stem cells have to be controlled to act exactly the way you want them to act, and thats why the research takes time, he said. It is simply wrong for these clinics to take a proof of concept and run with it.

Ogbogu says Health Canada must crack down on the burgeoning industry but says the regulator has so far been conspicuous by its inaction.

Other experts say the procedures provided here typically for joint pain are likely relatively safe, but still warn that care must be taken that the stem cells do not develop into the wrong type of tissue, or at the wrong place.

Alberta Health Services convened a workshop on the issue late last year, concluding there is an urgent need to develop a certification system for cell preparation and delivery to avoid spontaneous transformation of (stem cells) into unwanted tissue.

But one of the pioneers of the service in Canada says theres no empirical evidence that such growths can develop, and suggests the treatments only real risk as with an invasive procedure is infection.

Meanwhile, patients at Regenervate have enjoyed impressive outcomes after paying fees from $750 to $3,900, says Dr. Douglas Stoddard, the clinics medical director.

About 80 per cent report less pain, stiffness and weakness within a few months of getting their stem-cell injection, he said.

I believe medical progress is not just limited to the laboratory and randomized double-blind trials, Stoddard said. A lot of progress starts in the clinic, dealing with patients You see something works, you see something has merit, and then its usually the scientists that seem to catch up later.

The Orthopedic Sport Institute in Collingwood, Ont., the Central Alberta Pain and Rehabilitation Institute and Cleveland Clinic in Toronto all advertise similar stem-cell treatments for orthopedic problems.

Edmontons Regen Clinic says it plans to start doing so this fall.

Ottawas Innovo says it also treats a range of back conditions with injections between the vertebrae, and uses stem cells to alleviate nerve damage.

Orthopedic Sport says its doctor focuses on FDA and Health Canada approved stem-cell injection therapy for patient care.

In fact, no treatment of the sort the clinics here provide has ever been authorized.

Health Canada says the vast majority of stem-cell therapies would constitute a drug and therefore need to be authorized after a clinical trial or new drug submission.

A number of stem-cell trials are underway, but only one treatment Prochymal has been approved, said department spokesman Eric Morrissette. Designed to combat graft-versus-host disease where bone marrow transplants for treating cancer essentially attack the patients body its unlike any of the services the stem-cell providers here offer.

But as the U.S. Food and Drug Administration aggressively pursues the hundreds of clinics in America, Health Canada says only that its committed to addressing complaints it receives.

It will take action based on the risk posed to the general public, said Morrissette, who encouraged people to pass on to the department information about possible non-compliant products.

Stoddard said the injections his clinics provide are made up of minimally manipulated tissue from patients own bodies and any attempt to crack down would be regulation for the sake of regulation.

But academic experts remain skeptical about the effectiveness of the treatments.

Scientific evidence suggests the injections may help alleviate joint pain temporarily, but probably just because of anti-inflammatory secretions from the cells not regeneration, said Dr. David Hart, an orthopedic surgery professor at the University of Calgary who headed the Alberta workshop.

Theres a need for understanding whats going on here and theres a need for regulation, he said.

Most of the clinics say they use a centrifuge to concentrate the stem cells after removing them from patients fat tissue or bone marrow. But its unclear if the clinics even know how many cells they are eventually injecting into patients, says Jeff Biernaskie, a stem-cell scientist at the University of Calgary.

Munsie, on the other hand, has no doubts about the value of her own treatment, even with a $3,000 price tag.

The procedure from extraction of fat tissue in her behind to the injection of cells into her ankles took barely over an hour.

Within three months, the retired massage therapist from north of Toronto says she could walk her dogs again. Last week, she was hiking near Banff.

Im a real believer in it, and the possibility of stem cells, says Munsie. I just think Wow, if we can heal with our own body, its pretty amazing.

tblackwell@nationalpost.com

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Canadian clinics begin offering stem-cell treatments experts call unproven, possibly unsafe - National Post

Are you suffering from chronicjoint pain? If so, you may want to ask your doctor whetherstem cellinjections are right for you. If you want to avoid the surgical route of repairing a damaged knee or treating an arthritic shoulder, a stem cell injection may give you the relief you need.

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Stem cells are specialtypes of cells with the ability to self-renew or multiply. They have the potential to replicate any cell in your body. In other words, they canbecome a cartilage cell, a muscle cell or a nerve cell, says orthopedic surgeonAnthony Miniaci, MD.

They have a tremendous capacity to differentiate and form different tissues, so thats the thought behind regenerating cartilage, regenerating nerve cells and healing any injured tissues, he says.

The source of stem cells isfound in your own bone marrow orfat or you can also receive stem cells from donor sources, particularlyamniotic sourcessuch as the placenta or the amniotic fluid and lining surrounding a fetus. These cells are not part of the embryo, Dr. Miniaci says.

The number of stem cells that you have and theirquality and activity diminish as you get older, he says. Amniotic stem cells, on the other hand, are from young tissue, so theoretically these are younger, more active cells.

Thetreatment team harvests stem cells from your bone marrow or fat or uses donor cells . Later on, your treatment team injects the cells preciselyinto your joint, ligament or tendon.

Theoretically, the cells will then divide and duplicate themselves and develop into different types of cells depending on the location into which they have been injected. For example, if you have damagedknee cartilage, stem cells placed near the damaged cartilage can develop into new cartilage tissue.

However, for patients with asevere loss of cartilageor no cartilage at all, a stem cell injection is unlikely to createa new joint, Dr. Miniaci says.

Severe loss of cartilage typically leads to bone erosion or bone deformity, so a stem cell injection is highly unlikely to work in terms of reversing those changes, he says.

It can, however, improve your symptoms of pain and swelling.

The earlier you can treat someones joint pain, the better chance this has of working, making it less painful for thepatient, less inflamed, and improve their function, he says.

The main risk from a stem cell injection is in harvesting the stem cells. When taking the cells from your bone marrow, the treatment team inserts a large needle into your pelvis and removes some blood and the cells.

Any time you make incisions or insert sharp instrument into somebodys pelvis, they can have problems such as acquiring an infection, Dr. Miniaci says.

If youre taking the stem cells from fat, you you can remove some out from under the skin, he says. Again, you have a risk for an infection because were making little nicks into the skin to get to the fat.

While the use of stem cell injections to treatjoint painholds much promise, Dr. Miniaci cautions that this treatment option is still very new. Researchers needto study its effectiveness further.

We dont have a lot of data or proof indicating that stem cell injections actually repair the joint, he says.

He explains that if you have cartilage orbone damage, stem cells candifferentiate and produce bone and cartilage and tissues. So, theoretically, they could heal damaged tissue within a muscle, tendon, bone or cartilage.

Thats the theory behind it, but this type of treatment and research is just in its infancy, he says.

We really dont know whats effective, whats not effective, how many cells are necessary, how many actual injections you need and how often, he says. Nobody knows how well it works yet. But we will eventually.

Anecdotally, Dr. Miniaci finds that some patients can have significant improvement in their symptoms with stem cellinjections. But he has not seen any proof yet that they are regrowing or regenerating a joint.

Many people think that theyre going to come in with their arthritic joint and leave with a newer version of their knee joint. That doesnt happen, he says.

What does occur is a biological reaction which makes the environment in their joints a little healthier, which probably makes it less inflamed, and as result, gives them less pain.

Original post:
Stem Cell Injections: Emerging Option for Joint Pain Relief - Health Essentials from Cleveland Clinic (blog)

Emerald baseball coach Stanley Moss called current College of Charleston infielder Bradley Dixon one of the better players and kids he's ever coached.

The former Emerald standout was a slick-fielding shortstop, according to Moss, who was a cornerstone to the Emerald program.

"He was one of my favorites of all time," Moss said. "He always did what he was asked to do and went above and beyond to try to represent our program."

Dixon shared the field with current Clemson commit Sheldon Reed, who was a year under him at Emerald. Having the two of them play together was a joy and pleasure to be a part of, Moss said.

"(Dixon) and Sheldon hit in the middle of our lineup the whole time," Moss said. "They were big producers for us offensively."

Dixon's dominant play at Emerald earned him an opportunity to play Division I baseball with the Cougars. Dixon's senior season at Emerald, College of Charleston made it to a Super Regional which was just the second appearance in the program's history.

"It's what you grow up dreaming to do, playing Division I baseball," Dixon said. "Whenever you get an opportunity to do it, you take it and make the best of it."

But dreams have sometimes been met with struggles for Dixon. His freshman year in 2015 a week before opening weekend he sprained his MCL, ACL and suffered a bone contusion, forcing him to redshirt.

The following season, though, Dixon's redshirt freshman campaign, everyone got a glimpse of what he could do on the ball field when he's healthy.

Dixon started 45 games and was fourth on the team in batting average hitting .273 with a homer. They weren't the most eye-popping stats, but they proved what he was worth when on the field.

His 2017 season, however, was met with more injuries. Dixon recently had to get stem cells taken from the bone marrow in his hip and injected into the sesamoid bones in both his feet.

All the cartilage had worn down, which meant Dixon didn't have any protection around his bones. He played through the injury the entire season, hitting just .251.

+3

Moss believes he'll be a force again once healthy.

"Bradley's work ethic has always been where you would like to be," he said. "He's that kid in the offseason. Obviously if he can get himself completely healthy he's the kind of kid that can definitely go out and have a big year for College of Charleston."

The recovery time for his injury is 12 weeks, Dixon said, which means he'll be ready for the fall.

The team put together an underwhelming year last season, going just 13-11 in the Colonial Athletic Association, 28-31 overall and losing to Northeastern in the conference tournament.

On top of that, College of Charleston's coach, Matt Heath, was fired on Friday.

Despite the setbacks, Dixon is looking help right the ship.

"I really want to increase some of the numbers I had last year," Dixon said. "And just do better for my teammates, know my role and do whatever I can to help us win."

Contact staff writer Julian McWilliams at 864-223-1814 or on Twitter @JulianMack105

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Former Emerald standout eyes next season - Index-Journal

BAREILLY: Dog owners from across the country, including Delhi and Gujarat, are turning up with their paralytic pets at the Indian Veterinary Research Institute (IVRI) here for stem cell therapy. Scientists treat a paralyzed dog by transplanting stem cells from healthy dogs. IVRI is the second institute in the country to offer this treatment, after Madras Veterinary College, Chennai.

According to scientists, no research has been conducted to determine the number of dogs who suffer from paralysis every year in India. However, the institute receives at least four cases every week of spinal trauma which causes paralysis in dogs. IVRI recorded 143 cases of posterior paralysis in 2016. These were treated with stem cell therapy and medicines.

"If dogs are treated only with medicines, recovery is witnessed only in a few cases," said Amarpal (who goes by his first name), head and principal scientist, division of surgery, IVRI. On an average, 17% recovery rate was noted among dogs administered only medicines.

However, the best response was recorded among severely affected dogs when they were treated using stem cells, where almost all the patients responded to treatment to variable extent, said the scientist. "Though we have cases where recovery was 100%, the average recovery rate is about 50%. The experiment proved the efficacy of stem cell therapy in cases of paralysis due to spinal trauma," said Amarpal. After seven years of research, stem cell therapy was started at IVRI five years ago for clinical purposes on a nominal registration fee of Rs 30.

Due to its success, pet owners from various parts of the country have started visiting the institute.

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Dog owners flock IVRI for pets' cure - Times of India

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UCI-led study to advance understanding of the role of micoglia in Alzheimers disease

Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease. The finding marks an important step in the use of induced pluripotent stem (iPS) cells for targeted approaches to better understand and potentially treat neurological diseases such as Alzheimers. These iPS cells are derived from existing adult skin cells and show increasing utility as a promising approach for studying human disease and developing new therapies. Skin cells were donated from patients at the UCI Alzheimers Disease Research Center. The study, led by Edsel Abud, Wayne Poon and Mathew Blurton Jones of UCI, used a genetic process to reprogram these cells into a pluripotent state capable of developing into any type of cell or tissue of the body.

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Skin Stem Cells Used to Generate New Brain Cells - AANS ...

Scientists have discovered that microscopic 'vampire' amoebae existed hundreds of millions of years ago, and they may have been some of the first predators on Earth. By examining ancient fossils with an electron microscope, paleobiologist Susannah Porter from UC Santa Barbara discovered tiny holes which may have been drilled by vampiric microbes. The tiny creatures are believed to be the ancestors of modern Vampyrellidae amoebae, and punctured holes in their prey before sucking out the contents of their cells

Susannah Porter

An Earth-like planet orbiting a star 1,200 light years away could have conditions suitable for life, say scientists. Kepler 62f is about 40 per cent larger than the Earth and may possess surface oceans. It is the outermost of five planets circling a star that is smaller and cooler than the sun discovered by the American space agency Nasa's Kepler space telescope in 2013

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Scientists have taken a leaf out of the script of The Martian by showing how easy it would be to grow your own veg on the Red Planet. In the hit Ridley Scott film, a stranded astronaut played by Matt Damon uses his botanical skills to cultivate potatoes. Now his success has been emulated by researchers in the Netherlands who harvested tomatoes, peas, rye, rocket, radish and cress raised on simulated Martian soil supplied by Nasa

An ancient Roman estate complete with its own wine press and bathhouse has been unearthed in Jerusalem. A series of buildings dating back at least 1,600 years were discovered underneath the city's famous Schneller Orphanage which operated on the site from 1860 until the end of the Second World War, when it was turned into an army base. The ruins were discovered by archaeologists from the Israel Antiquities Authority who were excavating the site ahead of building new flats for the city's Orthodox Jewish community

Scientists believe they may have found a new species of octopus likened in appearance to Casper, the friendly cartoon ghost. Researchers with the US National Oceanic and Atmospheric Administration made the discovery by chance as they searched the seabed on an unrelated mission collecting geological samples. Teams were operating an unmanned submarine on the Pacific Ocean floor at depths of more than four kilometres (two-and-a-half miles) in the Hawaiian Islands when they spotted the unusual creature

Astronomers have captured a black hole eating a star and then sicking a bit of it back up for the first time ever. The scientists tracked a star about as big as our sun as it was pulled from its normal path and into that of a supermassive black hole before being eaten up. They then saw a high-speed flare get thrust out, escaping from the rim of the black hole. Scientists have seen black holes killing and swallowing stars. And the jets have been seen before.But a new study shows the first time that they have captured the hot flare that comes out just afterwards. And the flare and then swallowed star have not been linked together before

Brains cannot be categorised into female and male, according to the first study to look at sex differences in the whole brain. Specific parts of the brain do show sex differences, but individual brains rarely have all male traits or all female traits. Some characteristics are more common in women, while some are more common in men, and some are common in both men and women, according to the study

A British scientist has uncovered the fossil of a dog-sized horned dinosaur that roamed eastern North America up to 100 million years ago. The fragment of jaw bone provides evidence of an east-west divide in the evolution of dinosaurs on the North American continent. During the Late Cretaceous period, 66 to 100 million years ago, the land mass was split into two continents by a shallow sea. This sea, the Western Interior Seaway, ran from the Gulf of Mexico to the Arctic Ocean. Dinosaurs living in the western continent, called Laramidia, were similar to those found in Asia

A huge asteroid is set to skim by Earth on Halloween, just three weeks after it was first spotted. The rock is travelling through space at 78,000 miles per hour, and will fly past the Earth at a distance of only 300,000 miles only slightly further away than our moon, and easily close enough for Nasa to class it a potentially hazardous object. The asteroid is bigger than a skyscraper

Life may have come to earth 4.1 billion years ago, hundreds of millions of years earlier than we knew. The discovery, made using graphite that was trapped in ancient crystals, could mean that life began "almost instantaneously" after the Earth was formed. The researchers behind it have described the discovery as a potentially transformational scientific advance. Previously, life on Earth was understood to have begun when the inner solar system was hit by a massive bombardment from space, which also formed the moon's craters

Earth could be in danger as our galaxy throws out comets that could hurtle towards us and wipe us out, scientists have warned. Scientists have previously presumed that we are in a relatively safe period for meteor impacts, which are linked with the journey of our sun and its planets, including Earth, through the Milky Way. But some orbits might be more upset than we know, and there is evidence of recent activity, which could mean that we are passing through another meteor shower. Showers of meteors periodically pass through the area where the Earth is, as gravitational disturbances upset the Oort Cloud, which is a shell of icy objects on the edge of the solar system. They happen on a 26-million year cycle, scientists have said, which coincide with mass extinctions over the last 260-million years

Chinese scientists have created genetically-engineered, extra-muscular dogs, after editing the genes of the animals for the first time. The scientists create beagles that have double the amount of muscle mass by deleting a certain gene, reports the MIT Technology Review. The mutant dogs have more muscles and are expected to have stronger running ability, which is good for hunting, police (military) applications, Liangxue Lai, one of the researchers on the project. Now the team hope to go on to create other modified dogs, including those that are engineered to have human diseases like muscular dystrophy or Parkinsons. Since dogs anatomy is similar to those of humans, intentionally creating dogs with certain human genetic traits could allow scientists to further understand how they occur

Nasa has announced that it has found evidence of flowing water on Mars. Scientists have long speculated that Recurring Slope Lineae or dark patches on Mars were made up of briny water but the new findings prove that those patches are caused by liquid water, which it has established by finding hydrated salts.

With warmer summers, flowers in the Rockies have become shallower and more suited to shorter-tongued bees

The titular alien character from 2011's 'Paul' - a poll has found the majority of the public in Britain, Germany and the US believe that intelligent life is out there in the universe

Scientists say that the new dinosaur, known as Ugrunaaluk kuukpikensis, challenges everything we thought about a dinosaurs physiology. Florida State University professor of biological science Greg Erickson said: It creates this natural question. How did they survive up here?

New research has become the first to isolate the particular scent of human death, describing the various chemicals that are emitted by corpses in an attempt to help find them in the future. The researchers hope that the findings are the first step towards working on a synthetic smell that could train cadaver dogs to be able to more accurately find human bodies, or to eventually developing electronic devices that can look for the scent themselves.

Researchers in the Middle East have asked for seeds including those of wheat, barley and grasses, all of which are chosen because especially resistant to dry conditions. It is the first withdrawal from the bank, which was built in 2008. Those researchers would normally request the seeds from a bank in Aleppo. But that centre has been damaged by the war while some of its functions continue, and its cold storage still works, it has been unable to provide the seeds that are needed by the rest of the Middle East, as it once did.

Illustrations of the Earth and moon show the two to be quite close together, Mr Overstreet said. This is inaccurate, the reason being that these images are not to scale.

People lie more convincingly if they have a full bladder, according to research by academics at California State University. Iris Blandn-Gitlin's team asked 22 students to lie to a panel of interviewers. Half were given 700ml to drink before the interview and the other half, just 50ml. The students with the full bladders showed fewer signs that they were lying and their untrue answers were longer and more detailed, meaning interviewers were less able to detect that they were telling porkies. PM David Cameron has previously attested to giving speeches on a full bladder.

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Within 30 years we will no longer use sex to procreate, says Stanford professor - The Independent

Within three decades, we won't be making babies naturally, apparently.

That's the opinion of one Stanford University professor, who believes thatmaking a baby will be carried out in a lab.

Hank Greely, the director of Stanford's Centre of Law and Biosciences claims that the reproductive process will start by parents choosing from a rangeof embryos with their DNA.

Even though this already takes place for people who struggle to conceive, Hank thinks it will become cheaper and the safest option in the long run.

The process would involve taking a female's skin sample to make stem cells, which would then be used to create eggs.

The eggs are then fertilised by sperm cells, which produce the embryos.

"I think one of the hardest things about this will be all the divorces that come about when she wants embryo number 15 and he wants embryo number 64, Hanksaid at Aspen Ideas Festive,Tribunereported.

I think the decision making will be a real challenge for people. How do you weigh a slightly higher chance of diabetes with slightly lower risk of schizophrenia against better musical ability and a much lower risk of colon cancer? Good luck.

Well, it'll certainly be interesting to see.

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In 30 years we won't be having sex to make babies, says science - SHEmazing

Boston Business Journal

After raising $50M, virtual gene therapy startup sets up shop in Cambridge Boston Business Journal LogicBio Therapeutics becomes the latest local entrant to the field of gene therapy, a method of inserting healthy genes into cells to replace missing or faulty ones. ... Research the 3+ year digital archive, and People on the Move leads database download. and more »

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After raising $50M, virtual gene therapy startup sets up shop in Cambridge - Boston Business Journal

July 3, 2017 Credit: CC0 Public Domain

Beta-blocker drugs serve a key role in the treatment of heart failure, preventing bombardment of the heart by catecholamines - substances like epinephrine and norepinephrine - which overexcite and stress the heart. But not all heart failure patients respond to beta-blockers, for reasons that have been unclear. Now, in new work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) show that dysfunction of beta-adrenergic receptor 3 (3AR) - a novel beta-blocker target - and consequent decreases in a critical cardioprotective phospholipid may be to blame.

The cardioprotective molecule, known as sphingosine 1-phosphate 1 (S1P), keeps heart cells from dying following events such as heart attack and heart failure. "The higher the levels of S1P in heart failure, the better the outcome," explains Walter J. Koch, PhD, W.W. Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology and Director of the Center for Translational Medicine at LKSOM, as well as senior investigator on the new study.

According to Dr. Koch, beta-blocker drugs increase S1P levels by attenuating hyperactive beta-adrenergic receptor signaling, with most of the drugs acting selectively on 1ARs. "But the drugs can also have stimulatory effects on 3AR, promoting 3AR activity," he says. "Our new work shows that when 3AR is dysfunctional, the protective effects of S1P are lost."

The findings were published online July 3 in the Journal of the American College of Cardiology.

"Our group has spent more than a decade investigating beta-blocker mechanisms," explains Alessandro Cannavo, PhD, a research associate in the Center for Translational Medicine and Department of Pharmacology at LKSOM and lead author on the new report. "We know that a kinase called GRK2 that is downstream of beta-adrenergic receptor activation is responsible for downregulation (decreased production) of the S1P receptor 1 (S1PR1), which functions in cardioprotective signaling. We have also demonstrated in rats that restoration of S1PR1, via gene-therapy, can correct heart failure."

In their new study, Dr. Koch and colleagues looked more deeply into the mechanisms driving S1PR1 downregulation in heart failure, as well as the effects on S1P of metoprolol, a commonly used beta-blocker drug. Experiments in cells exposed to isoproterenol (to mimic the condition of heart failure) showed that treatment with metoprolol prevented S1PR1 downregulation. Microscopic studies revealed that whereas isoproterenol triggered S1PR1 internalization, with receptors retreating from their active front at the cell surface into the interior of the cell, metoprolol produced the opposite effect.

The researchers further showed in mice that treatment with either metoprolol or S1P effectively halts heart failure progression following heart attack. To determine whether those effects were related to 3AR, Dr. Koch's team performed a series of experiments in 3AR knockout mice. S1P levels remained low in 3AR knockout animals, despite treatment with metoprolol. Moreover, in the absence of 3AR, metoprolol failed to ameliorate cardiac damage suffered post-heart attack, whereas metoprolol improved cardiac function after heart attack in mice with normal 3AR expression.

Analyses of samples from heart failure patients taking 1AR blockers confirmed the clinical relevance of the findings. Compared to untreated patients, circulating levels of S1P were significantly elevated in patients that had been treated with the drugs.

"In the concept of precision medicine, our study suggests that altered 3AR or S1P signaling can be responsible for the diverse response to beta-blockers between human patients usually observed in clinical practice," says Dr. Cannavo.

"Mechanistically, we've identified a novel means by which 1AR blockers prevent the progression of heart failure, whereby 3AR must be active for metoprolol to work," adds Dr. Koch.

The team plans next to explore the effects of beta-blockers that lack activity at 3AR.

Explore further: Some heart attack patients may not benefit from beta blockers

Contracting shingles, a reactivation of the chickenpox virus, increases a person's risk of stroke and heart attack, according to a research letter published today in the Journal of the American College of Cardiology.

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Researchers identify novel mechanism underlying efficacy of common heart failure drug - Medical Xpress

President Donald Trump and Pope Francis have voiced their support for the parents of critically ill British baby Charlie Gard. The pair have been engaged in a long legal battle to take their son to the U.S. for treatment for a rare genetic disease.

Who is Charlie Gard, and why is his case so significant? Here's what you should know.

In September 2016, Charlie Gard, who's now 10 months old, was diagnosed with a rare genetic condition called mitochondrial depletion syndrome, which causes progressive muscle weakness and brain damage. He cannot move his limbs or eat or breathe without assistance.

His parents, Chris Gard and Connie Yates, are both carriers of the faulty gene, but were unaware of it until Charlie turned three months old. According to a fundraising page they set up, Charlie is only the sixteenth known person in the world with the condition.

Charlie's parents believe an experimental medication offered in the U.S. may be able to help the child, who is on life support.

"After endlessly researching and speaking to [doctors] all over the world we found hope in a medication that may help him and a [doctor] in America has accepted him in his hospital," wrote the parents on Charlie's fundraising page. "It hasn't been tried on anyone with his gene before . . . but it's had success with another mitochondrial depletion syndrome called TK2 which is similar."

Gard and Yates added that they "strongly feel . . . Charlie should get a chance to try these medications" and he has "literally has nothing to lose but potentially a healthier, happier life to gain."

The pair set up a GoFundMe page to help raise money to send Charlie to the U.S. They raised 1.3 million ($1.68 million) in five months, with donations from 83,563 people.

Charlie's doctors at London's Great Ormond Street Hospital for Children, or GOSH, believe there is no cure for his condition, which is terminal.

A statement on the hospital's website explains that "GOSH explored various treatment options" including nucleoside therapy, the experimental treatment offered by the U.S. hospital. "GOSH concluded that the experimental treatment, which is not designed to be curative, would not improve Charlies quality of life," the statement says.

After balancing whether the experimental treatment was in Charlie's best interests or not, the GOSH doctors said they thought it would be best to stop providing life support for Charlie and instead move on to a palliative care regime, allowing him to "die with dignity."

"One of the factors that influenced this decision was that Charlies brain was shown to be extensively damaged at a cellular level. The clinician in the U.S. who is offering the treatment agrees that the experimental treatment will not reverse the brain damage that has already occurred," the statement says.

"The entire highly experienced U.K. team, all those who provided second opinions and the consultant instructed by the parents all agreed that further treatment would be futile meaning it would be pointless or of no effective benefit," it adds.

Because Charlie's parents disagreed with the doctors' decision about Charlie's future treatment, the decision went to the Family Division of Britain's High Court in London.

The High Court ruled last April "with the heaviest of hearts" that it was in Charlie's best interests for GOSH to "lawfully withdraw all treatment save for palliative care to permit Charlie to die with dignity.

The judge said his decision not to allow Charlie to go to the U.S. was not related to funding. I dare say that medical science may benefit objectively from the experiment, but experimentation cannot be in Charlies best interests unless there is a prospect of benefit for him," he said, referring to the trial treatment, The Guardian reported at the time.

On May 2, the couple took their fight to the Court of Appeal, asking the judges not to take away the only remaining hope." However, on May 25, three Court of Appeal judges upheld the High Court ruling. Britain's Supreme Court then agreed to review the case, but ruled that Charlie's life support must be switched off.

Charlie's parents took the case to the European Court of Human Rights (ECHR). But on June 27, the ECHR ruled that, in agreement with the domestic courts' ruling, "undergoing experimental treatment with no prospects of success" would offer Gard "no benefit, and continue to cause him significant harm. In a statement acquired by The Guardian, the ECHR declared the decision as "final."

Our thoughts are with Charlies parents on receipt of this news that we know will be very distressing for them," said a spokesperson for GOSH. "Todays decision by the European court of human rights marks the end of what has been a very difficult process and our priority is to provide every possible support to Charlies parents as we prepare for the next steps."

In a Facebook post , Charlie's parents wrote that they are "utterly heartbroken." The post added: "We're not allowed to choose if our son lives and we're not allowed to choose when or where Charlie dies. We and most importantly Charlie have been massively let down throughout this whole process."

Following the ECHR's decision, campaigners gathered at Buckingham Palace to protest the ruling, chanting "save Charlie Gard" and "release Charlie Gard" and holding placards, with one reading, "It's murder."

"If we can help little # CharlieGard, as per our friends in the U.K. and the Pope, we would be delighted to do so," wrote Trump on Twitter Monday morning.

His comment came one day after Pope Francis said in a statement that he was following the case "with affection and sadness," adding that he was praying that Gard's parents' "wish to accompany and treat their child until the end isnt neglected.

Continue reading here:
What to Know About Charlie Gard, the Terminally Ill Baby Trump Wants to Help - TIME

Floyd is a horticulturist with Texas AgriLife Extension Service. He can be reached at 498-4071 in Ector County or 686-4700 in Midland County or by email at Jeff.Floyd@ag.tamu.edu

Floyd is an Agri-Life Extension agent for Ector and Midland counties. To learn more, call the Ector County Extension office at 432-498-4072, or the Midland County Extension office at 432-686-4700, or email jeff.floyd@ag.tamu.edu.

Posted: Sunday, July 2, 2017 3:00 am

GARDENING: Reviving St. Augustine grass By Jeff Floyd Odessa American

Weve discussed a lot of the problems that St. Augustine grass experiences in West Texas lawns but a recent question caused me to realize we havent talked about a basic St. Augustine maintenance schedule for our area.

Question: We have had great success growing Bermuda and St. Augustine, we have mostly shade, and the St. Augustine took over most of the yard. Last year we noticed the St. Augustine was not growing and yellowing and disappearing. It continues to get worse this year. This season I have fertilized, insect and bug killer granules, and Fungicide. No change. Last year I tried Ironite with no change. This month I laid down a strip of dolomite lime, and on the other side of yard a strip of aluminum sulfate. No detectable difference on either side.

Answer: Thank you for the question to Extension. Avoid applying any more amendments or fertilizers until youve gotten on track with a basic maintenance plan and start to see some recovery.

For St. Augustine lawns showing signs of stress, begin with a soil test. Visit http://www.soiltesting.tamu.edu for forms and instructions.

Call the Texas A&M AgriLife Extension office if you are having turf grass problems at 498-4071.

Posted in Gardening on Sunday, July 2, 2017 3:00 am. | Tags: Texas A&m Agrilife Extension Office, Jeff Floyd, Pecans, Pruning, Prune, Soft Landscape Materials, Landscape, Gardening, Gardener, Food, Integra, Repeat Applications, West Texas

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GARDENING: Reviving St. Augustine grass - Odessa American

Visakhapatnam: Lack of awareness on the importance of becoming a blood stem cell donor is hindering the treatment of people suffering from blood cancer and other fatal blood disorders like thalassemia and aplastic anaemia.

Since the only cure is a blood stem cell transplant, the need of the hour is to sensitise people of the city on the necessity of becoming a potential blood stem cell donor to save lives, experts say.

According to oncologists based in Vizag, the cases of blood cancer are increasing and the treatment options are very few. Moreover, patients with blood cancer are sent to Hyderabad and other centres for treatment as neither there are donors nor equipment for stem cell transplant in the port city.

For a successful transplant, patients suffering from fatal blood disorders need blood stem cells from a healthy and genetically matched donor. Unfortunately, the probability of finding a genetically matched donor is one in 10,000 to one in over a million.

Only about 25 per cent of the patients find a donor from within their family. Rest need to wait for a life-saving donor.

"The chances of finding a match for patients suffering from these fatal blood disorders could only widen if there are more number of donors registered," says Ravindranath Chava, co-ordinator of a Chennai-based blood stem cell donors registry- DATRI.

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Lack of stem cell donations plagues patients - Times of India