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Category Archives: Transhuman News

Gene editing of human embryos yields early results | Science News – Science News

Posted: March 31, 2017 at 6:38 am

Scientists have long sought a strategy for curing genetic diseases, but with just a few notable exceptions have succeeded only in their dreams. Now, though, researchers in China and Texas have taken a step toward making the fantasies a reality for all inherited diseases.

Using the gene-editing tool known as CRISPR/Cas9, the researchers have successfully edited disease-causing mutations out of viable human embryos. Other Chinese groups had previously reported editing human embryos that could not develop into a baby because they carried extra chromosomes, but this is the first report involving viable embryos (SN Online: 4/8/16; SN Online: 4/23/15).

In the new work, reported March 1 in Molecular Genetics and Genomics, Jianqiao Liu of Guangzhou Medical University in China and colleagues used embryos with a normal number of chromosomes. The embryos were created using eggs and sperm left over from in vitro fertilization treatments. In theory, the embryos could develop into a baby if implanted into a womans uterus.

Researchers in Sweden and England are also conducting gene-editing experiments on viable human embryos (SN: 10/29/16, p. 15), but those groups have not yet reported results.

Human germline editing wasnt realistic until CRISPR/Cas9 and other new gene editors came along, says R. Alta Charo, a bioethicist at the University of Wisconsin Law School in Madison. Weve now gotten to the point where its possible to imagine a day when it would be safe enough to be feasible. Charo was among the experts on a National Academies of Sciences and Medicine panel that in February issued an assessment of human gene editing. Altering human embryos, eggs, sperm or the cells that produce eggs and sperm would be permissible, provided there were no other alternatives and the experiments met other strict criteria, the panel concluded (SN: 3/18/17, p. 7).

Story continues below graphic

CRISPR/Cas9 is a tool for editing genes. A guide RNA shepherds the Cas9 enzyme to a specific stretch of DNA. Cas9 then cleaves the DNA to disable or repair a gene.

Illustrations: E. Otwell

Still, technical hurdles remain before CRISPR/Cas9 can cross into widespread use in treating patients.

CRISPR/Cas9 comes in two parts: a DNA-cutting enzyme called Cas9, and a guide RNA that directs Cas9 to cut at a specified location in DNA. Guide RNAs work a little like a GPS system, says David Edgell, a molecular biologist at Western University in London, Ontario. Given precise coordinates or a truly unique address, a good GPS should take you to the right place every time.

Scientists design guide RNAs so that they will carry Cas9 to only one stretch of about 20 bases (the information-carrying subunits of DNA) out of the entire 6 billion base pairs that make up the human genetic instruction book, or genome. But most 20-base locations in the human genome arent particularly distinctive. They are like Starbucks coffee shops: There are a lot of them and they are often similar enough that a GPS might get confused about which one you want to go to, says Edgell. Similarly, guide RNAs sometimes direct Cas9 to cut alternative, or off-target, sites that are a base or two different from the intended destination. Off-target cutting is a problem because such edits might damage or change genes in unexpected ways.

Its a major issue for sure, says Bruce Korf, a geneticist at the University of Alabama at Birmingham and president of the American College of Medical Genetics and Genomics Foundation. Doctors trying to correct one genetic defect in a patient want to be sure they arent accidentally introducing another.

But CRISPR/Cas9s propensity to cut undesired sites may be exaggerated, says Alasdair MacKenzie, a molecular biologist at the University of Aberdeen in Scotland. In experiments with mice, MacKenzie and colleagues limited how much Cas9 was produced in cells and made sure the enzyme didnt stick around after it made an edit. No off-target cuts were detected in any of the mice resulting from successfully edited embryos, MacKenzie and colleagues reported in November in Neuropeptides.

Other researchers have experimented with assembling the Cas9 and guide RNAs outside of the cell and then putting the preassembled protein-RNA complex into cells. Thats the strategy the Chinese researchers took in the new human embryoediting study. No off-target cuts were detected in that study either, although only one edited embryo was closely examined.

Other researchers have been tinkering with the genetic scissors to produce high-fidelity versions of Cas9 that are far less likely to cut at off-target sites in the first place.

When a guide RNA leads Cas9 to a site that isnt a perfect match, the enzyme can latch onto DNAs phosphate backbone and stabilize itself enough to make a cut, says Benjamin Kleinstiver, a biochemist in J. Keith Joungs lab at Harvard Medical School. By tweaking Cas9, Kleinstiver and colleagues essentially eliminated the enzymes ability to hold on at off-target sites, without greatly harming its on-target cutting ability.

Regular versions of Cas9 cut between two and 25 off-target sites for seven guide RNAs the researchers tested. But the high-fidelity Cas9 worked nearly flawlessly for those guides. For instance, high-fidelity Cas9 reduced off-target cutting from 25 sites to just one for one of the guide RNAs, the researchers reported in January 2016 in Nature. That single stray snip, however, could be a problem if the technology were to be used in patients.

Story continues below graph

Snipping the wrong bit of DNA is a potential problem for gene editing. In recent experiments, researchers modified the Cas9 enzyme in a CRISPR/Cas9 system to create a high-fidelity version that reduced off-target cutting.

Source: B. Kleinstiver et al/Nature 2016

A group led by CRISPR/Cas9 pioneer Feng Zhang of the Broad Institute of MIT and Harvard tinkered with different parts of the Cas9 enzyme. That team also produced a cutter that rarely cleaved DNA at off-target sites, the team reported last year in Science.

Another problem for gene editing has been that it is good at disabling, or knocking out, genes that are causing a problem but not at replacing genes that have gone bad. Knocking out a gene is easy because all Cas9 has to do is cut the DNA. Cells generally respond by gluing the cut ends back together. But, like pieces of a broken vase, they rarely fit perfectly again. Small flaws introduced in the regluing can cause the problem gene to produce nonfunctional proteins. Knocking out genes may help fight Huntingtons disease and other genetic disorders caused by single, rogue versions of genes.

Many genetic diseases, such as cystic fibrosis or Tay-Sachs, are caused when people inherit two mutated, nonfunctional copies of the same gene. Knocking those genes out wont help. Instead, researchers need to insert undamaged versions of the genes to restore health. Inserting a gene starts with cutting the DNA, but instead of gluing the cut ends together, cells use a matching piece of DNA as a template to repair the damage.

In the new human embryo work, Liu and colleagues, including Wei-Hua Wang of the Houston Fertility Institute in Texas, first tested this type of repair on embryos with an extra set of chromosomes. Efficiency was low; about 10 to 20 percent of embryos contained the desired edits. Researchers had previously argued that extra chromosomes could interfere with the editing process, so Lius group also made embryos with the normal two copies of each chromosome (one from the father and one from the mother). Sperm from men that have genetic diseases common in China were used to fertilize eggs. In one experiment, Lius group made 10 embryos, two of which carried a mutation in the G6PD gene. Mutations in that gene can lead to a type of anemia.

Then the team injected Cas9 protein already leashed to its guide RNA, along with a separate piece of DNA that embryos could use as a template for repairing the mutant gene. G6PD mutations were repaired in both embryos. Since both of the two embryos had the repair, the researchers say they achieved 100 percent efficiency. But one embryo was a mosaic: It carried the fix in some but not all of its cells. Another experiment to repair mutations in the HBB gene, linked to blood disorders, worked with 50 percent efficiency, but with some other technical glitches.

Scientists dont know whether editing just some cells in an embryo will be enough to cure genetic diseases. For that reason, some researchers think it may be necessary to step back from embryos to edit the precursor cells that produce eggs and sperm, says Harvard University geneticist George Church. Precursor cells can produce many copies of themselves, so some could be tested to ensure that proper edits have been made with no off-target mutations. Properly edited cells would then be coaxed into forming sperm or eggs in lab dishes. Researchers have already succeeded in making viable sperm and eggs from reprogrammed mouse stem cells (SN: 11/12/16, p. 6). Precursors of human sperm and eggs have also been grown in lab dishes (SN Online: 12/24/14), but researchers have yet to report making viable human embryos from such cells.

The technology to reliably and safely edit human germline cells will probably require several more years of development, researchers say.

Germline editing as altering embryos, eggs and sperm or their precursors is known probably wont be the first way CRISPR/Cas9 is used to tackle genetic diseases. Doctors are already planning experiments to edit genes in body cells of patients. Those experiments come with fewer ethical questions but have their own hurdles, researchers say.

We still have a few years to go, says MacKenzie, but Ive never been so hopeful as I am now of the capacity of this technology to change peoples lives.

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Should your boss get a peek at your DNA? – Chicago Tribune

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Bet you thought the mess that was Trumpcare was about as horrible a piece of legislation that could be concocted for ruining a lot of people's health. Nope. A bill called the Preserving Employee Wellness Programs Act, currently under enthusiastic review by Congress, will allow employers to charge their employees a higher insurance premium if they refuse to provide them with their personal genetic information. It is hard to think of a worse idea.

An individual's genetic code can reveal a vast amount of information. It can show whether you suffer from an existing medical condition, the odds that you will develop a certain disease in your lifetime, information about your kids' genetic health and your ancestry.

Until now, no titan of industry could snoop into your DNA. The Genetic Information Nondiscrimination Act of 2008 prohibits employers from discriminating against employees based on their genetic data. In addition to prohibiting discrimination, GINA also forbids employers from penalizing employees if they refuse to provide genetic information.

Under the ill-advised PEWPA legislation, if an employer hires a company to institute a wellness program to try to create a healthier workforce and if these hired helpers want to require genetic testing, then you either spit in a cup to give a DNA sample or pay up to 30 percent more on your health insurance premium. Permitting huge penalties clearly allows employers to bully their employees into revealing their genetic information in the name of keeping them fit. Under this regressive bill, not only will your boss have access to your DNA profile, but there is also no prohibition about sharing it with third parties.

If PEWPA passes, you or your relatives who have certain genetic traits may face significant hurdles not only in getting a job but also in acquiring life insurance, disability insurance and health care. Employers looking to hire new employees may opt not to hire those with genetic traits that put them at risk for certain diseases even if those diseases do not materialize for decades or at all.

Fretting about the harm of killing genetic privacy is not hypothetical. The Equal Employment Opportunity Commission reported that it received 201 complaints of genetic discrimination in 2010 and 333 complaints 2014. Many complaints involved allegations from workers that knowledge of the genetic risk of getting, say, breast cancer led to their termination.

There is one other huge problem with asking workers to turn over their genetic information to third-party health promoters paid for by their employers. There is little data to show that wellness programs work. Giving up your genetic privacy for an employer-imposed program that is not likely to help you lose weight, lower your blood pressure or manage stress makes no sense at all. But, so far that has not stopped Congress from nudging this bill along.

Congress has shown itself incapable of dealing with health care insurance, and its members are not doing better with genetic testing. Genetic information ought to stay where it is under your control and no one else's.

Arthur L. Caplan is director of medical ethics at the New York University Langone Medical Center's Department of Population Health.

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DNA technology, volcanic ash help pinpoint when bisons …

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The time frame for when bison the most successful mammal in colonizing North America after humans came to the continent from Asia has long been a matter of debate.

But a group of Canadian scientists, using genetic and geologic information, recently were able to pinpoint a time frame of when these beasts came across the Bering Land Bridge.

According to a new study published in the Proceedings of the National Academy of Sciences, Bison came to North America between 135,000 and 195,000 years ago a lot sooner than the 640,000 years ago stipulated in previous estimations.

Bison also apparently fared quite well in their new home, quickly multiplying their number, diversifying and becoming the dominant grazers on the plains of North America. They displaced mammoths, Pleistocene horses and other mammals that arrived on the continent earlier.

"They became very successful very quickly," Duane Froese of the University of Alberta, lead author of the study, told the Alaska Dispatch News. "Outside of humans, it's pretty much the most successful mammal invasion into North America."

The findings rely heavily on DNA extracted from the worlds oldest known bison fossil, which was discovered almost a decade ago near the Gwich'in indigenous village of Old Crow in Canada's Yukon Territory.

The fossil was discovered under a layer of ash from an enormous eruption that happened about 130,000 years ago in southwestern Alaska. The ash basically acted as a time marker in the earth that allowed scientists to figure out the age of the Yukon bison fossil and confirm it as the oldest known bison fossil in North America.

Because radiocarbon dating doesnt work past the ages of about 40,000 to 50,000 years, the DNA analysis was necessary. Using new technology, researchers compared the DNA from the Yukon fossil with that of a younger fossil found near Snowmass, Colorado. Both fossils then were compared with dozens of younger bison fossils.

From their research, scientists were able to determine that all bison shared a common ancestor 135,000 to 195,000 years ago during a period when the Bering Land Bridge was exposed. Scientists were also able to determine that bison migrated over the land bridge in a second wave 21,000 to 45,000 years ago.

"It's been kind of a long puzzle in the world of paleontology and paleobiology," Froese said.

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House committee OKs bill to collect DNA samples in felony arrests … – Greensburg Daily News

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INDIANAPOLIS A bill allowing law enforcement to collect DNA samples from people at the time they are arrested on felony charges advanced to the full House.

On Thursday, Senate Bill 322 passed the House Judicial Committee by a 9-1 vote.

The bills author, Sen. Erin Houchin, R-Salem, told the committee that collecting the DNA sample at the time of the felony arrest will help law enforcement identify perpetrators much earlier in the crime cycle.

Studies have shown that serial criminals will commit seven or eight crimes before they are identified. Houchin said.

Houchin cited the case of John Clements, 82, who was shot and killed last fall outside his Zionsville home. A suspect was identified through DNA that was in a database in Ohio, where samples are collected at the time of arrest.

If the bill becomes law, Indiana would be the 31st state to implement DNA testing at the point of arrest.

DNA samples are removed from the system under three circumstances: the person is acquitted of all felony charges or charges are converted to misdemeanors, all felony charges against the person are dismissed, or no felony charges are filed against the person within 365 days.

A similar bill was filed in the House. House Bill 1577 required that the DNA sample be removed from the database if no charges are filed within 30 days, but Houchin said that was too little time to do any good.

Both the state police and prosecutors thought that 30 days was too short of a time frame, Houchin said. We looked at the national averages and theyre anywhere from one to three years.

Rep. John Young, R-Franklin, argued that collecting DNA at the time of arrest is an invasion of privacy even though the samples might be eventually removed from the database.

To me this is a dragnet sweep to collect peoples DNA, Young said. I cant think of anything more personal then my own DNA.

Houchin said that arrestees will be informed of their right to remove the DNA sample if cleared and be provided a form with instructions on how to do so. Under the law the DNA will not automatically be removed the person who gave the sample will have to petition the court for its removal.

The only time it is sent to the database is if there is an arrest on probable cause or an arrest with a warrant, Houchin said.

Young said the bill is unconstitutional.

Guilty people do walk away free on technicalities, Young said. Thats a price that we pay to live in a free society.

If the bill becomes law, it would take effect on Jan. 1, 2018.

Kayla Walker is a reporter for TheStatehouseFile.com, a news website powered by Franklin College journalism students.

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Inovio Pharmaceutical’s DNA vaccine will be tested in patients with … – Philly.com

Posted: at 6:37 am

Inovio Pharmaceuticals in Plymouth Meeting is collaborating with the University of California San Francisco, which received a $6.95 million grant from the National Institutes of Health, to test the biotech company's DNA-based vaccine to reduce or prevent the HIV virus.

Inovio's immunotherapy, Pennvax GP, will be tested in HIV-positive patients to see if it generates killer T cells in the body's immune system to attack the HIV virus.

Current antiviral drugs work well against HIV, "but people have to take these drugs every day for decades," said Steven Deeks, the grant's principal investigator and professor of medicine at the University of California, San Francisco. For many people around the world the drugs "are just not feasible" due to side effects or costs, he said. "We're trying to find a way to enable the immune system to do what antiretroviral drugs do, which is to prevent the virus from replicating and spreading in the person."

Nearly 36 million people have died from HIV related causes and 35 million are living with HIV, a retrovirus that causes acquired immunodeficiency syndrome, or AIDS.

"Inovio has developed an approach which has worked quite well in other settings, for example HPV infection in women who might be developing cervical cancer," Deeks said. "We want to take their approach, which we think is very exciting, to see if we can generate these powerful CD cells that can recognize and kill HIV. In theory if we are lucky, it will allow us to one day stop antiretroviral drugs and let the immune system to take over."

CD8 is a receptor on the surface of T cells that allows the cell to recognize something foreign, Deeks said.

The vaccine is a strand of DNA that contains the genetic information of the virus. Once in the body - through an inoculation in the arm - the DNA gets into critical immune cells that attack HIV. Inovio's immunotherapy has been tested for HPV and for the Zika virus. "It's the same general approach, but the DNA is quite different," Deeks said.

Inovio's vaccine will be tested alone and in combination with other products in patient trials at the University of California in San Francisco and Los Angeles. "Similar to what we are doing in the cancer field," said Inovio CEO Joseph Kim, "we believe that the one-two punch of generating potent killer T cells with our immunotherapies" could be an important step in finding a cure for these diseases.

Published: March 30, 2017 3:28 PM EDT

Over the past year, the Inquirer, the Daily News and Philly.com have uncovered corruption in local and state public offices, shed light on hidden and dangerous environmental risks, and deeply examined the regions growing heroin epidemic. This is indispensable journalism, brought to you by the largest, most experienced newsroom in the region. Fact-based journalism of this caliber isnt cheap. We need your support to keep our talented reporters, editors and photographers holding government accountable, looking out for the public interest, and separating fact from fiction. If you already subscribe, thank you. If not, please consider doing so by clicking on the button below. Subscriptions can be home delivered in print, or digitally read on nearly any mobile device or computer, and start as low as 25 per day. We're thankful for your support in every way.

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Murder accused’s DNA found on victim’s belt, court hears – BBC News – BBC News

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Murder accused's DNA found on victim's belt, court hears - BBC News
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A court hears forensic evidence at the trial of Philip Morrison who denies murdering Derek Sheerin in Glasgow in 1994.

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A body inside a wall, DNA that freed a lifer all in a day’s work for longtime NJ prosecutor – Philly.com

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Robert Bernardi has seen too many bodies, including one that was wrapped in plastic and sealed behind a wall inside a Philadelphia rowhouse.

That was a scene right out of Edgar Allan Poe, the Burlington County prosecutor said recalling that hot August day in 2001 when he was at the shore and received a call about the discovery of the remains of Kimberly Szumski, a Cinnaminson, N.J., mother of two who had been missing for three months. Later, he watched as investigators removed cinderblocks and then the body.

When Bernardi retired Friday, he was the longest serving county prosecutor in New Jersey. In an interview a week earlier, he reflected on nearly two decades of service as a top law enforcement official.

Over the years he had tangled with the Innocence Project of New York over a murder conviction that was reversed due to DNA evidence and with Amnesty International over two deaths and alleged inhumane conditions at the county jail in Mount Holly. He also fought with courts that decided the law and order prosecutor had gone too far in some cases, and with county politicians who wouldnt give his staff a raise for years, making his assistants the lowest paid in the state.

Bernardi also supervised thousands of criminal cases, which led to an average of 1,200 indictments and about 50 trials a year. Many criminals, including murderers, were locked up on his watch and remain incarcerated, he said.

Its been a great run, 17 years and 10 months, he said, in his Mount Holly office where he had overseen a staff of 150. Im 67, I didnt want to get carried out on my shield, the grandfather of two said, mentioning he was looking forward to more golf. Less than 12 hours earlier, there was a homicide in which a Pemberton man was found shot in the head.

Gov. Christie, in a statement, called Bernardi an extraordinary leader A voice of justice and reason in the state shortly after the governor named his senior deputy chief counsel, Scott A. Coffina, of Marlton, to replace Bernardi.

A Republican from Mount Laurel, Bernardi was first appointed by former Gov. Christie Whitman and was a holdover after his latest five-year term expired in December.

The Kimberly Szumski case was among the most memorable, Bernardi said, recalling how her husband, Thomas, was found dead of an overdose before her body was discovered. Bernardi said Szumski had killed his wife, but luckily an informant had just told detectives about the basement where Szumski had done some construction work.

Also memorable was the single case that Bernardi had tried personally the matter of John Denofa, a Bucks County businessman who was found guilty of killing an exotic dancer and tossing her to her death from the Turnpike Bridge in 2002.

Bernardi remembered how he and the former Bucks County prosecutor had argued over who should handle the sensational case since the attack occurred in Pennsylvania and the body was found along the shoreline in New Jersey.

After he was convicted, Denofa filed several appeals and recently filed another motion to reduce his sentence of 30 years to life in prison. But Bernardi said the sentence has remained intact.

The case of Larry Peterson was thornier. Peterson was exonerated by DNA evidence and freed in 2006 after he served 18 years in prison after he was convicted of murder in the strangling of a Pemberton woman.

Bernardi bristled when asked if he had any regrets about that case. He had opposed the DNA testing and it took Peterson seven years to get a judge to order the tests that opened the door for him to prove his innocence. The tests determined that microscopic hairs and semen found on the body of the murder victim did not belong to Peterson.

We dealt with far too much resistance from Bernardi in terms of getting the DNA testing, said Vanessa Potkin, an attorney with the Innocence Project who handled the Peterson case. Since then Im sure weve had over 100 exonerations if not 200.

She said that more prosecutors are now recognizing they have a role in finding out the truth and in taking an active role in exonerating innocent persons instead of digging in their heels to maintain a conviction.

Potkin said that the jury heard false evidence, that the hairs found on the victim belonged to Peterson, and this was critical since he had not confessed and there was no other forensics placing him at the scene. She said she hoped there was a change in (Bernardis) heart about the Larry Peterson case and that he would do it differently now.

But Bernardi said that, in retrospect, he still believes he was right when he considered retrying the case and fought the DNA testing.

We did everything we were supposed to do in a professional manner to investigate and determine whether we would prosecute Larry Peterson again The DNA didnt 100 percent say he couldnt have done it. The gripe was we left him in jail, but we had an obligation to the victim and the victims family to make sure that Mr. Peterson was not involved, he said.

The other controversy Bernardi faced involved the deaths of two Burlington County Jail inmates, one in December 2013 and the other two months later. The human rights group Amnesty International had asked Bernardi to investigate to see if there was any criminal negligence by jail officials or staff.

Bernardi said he found there was no wrong-doing, but Amnesty International officials later said the details of the report he gave them about the death of a sick, frail homeless man led to more questions and concerns that he was left to die. In the interview, Bernardi said that was not the case.

While most of the convictions obtained by Bernardi's office were upheld on appeal, a few were reversed bythe state Supreme Court for prosecutorial overreach.

In the Marie Hess case, Bernardi said the judges erred when they ruled in 2011 that the prosecutor should not have restricted her right to raise the defense of Battered Woman Syndrome during her sentencing after she confessed to killing her husband, James Hess, a Burlington Township patrolman.

The supreme court got it wrong.. She confessed. We are here to serve victims, people dragged into the system without any choice They are the ones who are forgotten, he said.

Kevin Walker, a public defender who represented Hess, said that Bernardi overall was "tough but fair." But in the Hess case, he said that Hess was "clearly an abused woman...I'm not trying to justify what happened, but the law acknowledges the circumstances with which she had to deal with on a daily basis and these were mitigating factors that had to be considered at sentencing."

Ray Milavsky, who was Bernardis first assistant prosecutor since the beginning, said the office handled many cases that had very fascinating issues and dealt with them in a professional manner. The two met when they were assistant prosecutors in Camden County in the the 1980s and they became longtime friends.

The biggest challenge for Bernardi, Milavsky said, was dealing with inadequate staff. We have a dedicated group of individuals, but to make it work ideally, there has to be more resources, he said.

Bernardi, a past president of the County Prosecutors Association of New Jersey, had pushed to get the county Freeholder Board to hire more staff and also to approve raises for his assistant prosecutors, who at one time were the lowest paid in the state. They had not been granted raises between 2008-2012 and some had left to join the Camden County prosecutors office and other offices that were paying more competitive wages.

During that period, the assistant prosecutors were making nearly $10,000 to $20,000 less than the statewide average of $91,000.

Bernardi, who earned $165,000 a year in his role as prosecutor, said that the "bleeding" of his office and cutbacks reduced his staff, which went from 39 prosecutors to 34. He said 41 assistants are needed to do the job well.

When Bernardi walked through his office, the assistants greeted him with "Hello Sir."

Staffing is an issue, said Bernardi, said, adding that recent bail reforms have also increased the workload. Were treading water.

But that may be a task for the new prosecutor to address. That and a backlog that is growing, he said.

Still, Bernardi said that being prosecutor was wonderful, the best experience of my life, and an honor. When he was appointed to his first five-year term, he had expected it would be just a five-year hitch.

Bernardi said that he plans to offer his services to municipalities that may need to hire hearing officers in police disciplinary matters. "I would like to kick back a little," he said, "but I would like to do this part-time."

Published: March 31, 2017 6:13 AM EDT

Over the past year, the Inquirer, the Daily News and Philly.com have uncovered corruption in local and state public offices, shed light on hidden and dangerous environmental risks, and deeply examined the regions growing heroin epidemic. This is indispensable journalism, brought to you by the largest, most experienced newsroom in the region. Fact-based journalism of this caliber isnt cheap. We need your support to keep our talented reporters, editors and photographers holding government accountable, looking out for the public interest, and separating fact from fiction. If you already subscribe, thank you. If not, please consider doing so by clicking on the button below. Subscriptions can be home delivered in print, or digitally read on nearly any mobile device or computer, and start as low as 25 per day. We're thankful for your support in every way.

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Unique genome architectures after fertilisation in single-cell embryos – Phys.Org

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March 30, 2017 Credit: Institute of Molecular Biotechnology

Using a newly developed method, researchers at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) have been able to shed light on the complexity of genome reorganization occurring during the first hours after fertilization in the single-cell mammalian embryo. Their findings have recently been published in the journal Nature. The team of researchers (from three continents) have discovered that the egg and sperm genomes that co-exist in the single-cell embryo or zygote have a unique structure compared to other interphase cells. Understanding this specialized chromatin "ground state" has the potential to provide insights into the yet mysterious process of epigenetic reprogramming to totipotency, the ability to give rise to all cell types.

Fusion of the egg and sperm, two highly differentiated cell types, leads to formation of the single-cell embryo or zygote. During the first hours after fertilization, the two separate genomes undergo reprogramming events that presumably function to erase the memory of the differentiated cell type and establish a state of totipotency. The mechanisms underlying totipotency remain poorly understood but are essential for generating a new organism from a fertilized egg.

A major advance in single-cell genomics

After fertilization, maternal and paternal genomes erase some of the epigenetic memory of the previously differentiated states in order to facilitate the beginning of new life as the zygote. In the first cell cycle after fertilization the maternal genome inherited from the oocyte (egg) and the paternal genome provided by sperm exist as separate nuclei in the zygote. The two genomes are marked by distinct epigenetic modifications acquired during reprogramming. Whether the 3-D chromatin structure of the maternal and paternal genomes is also distinct was not known.

An international team headed by Kiku Tachibana-Konwalski from IMBA in collaboration with researchers from the Massachusetts Institute of Technology (MIT) in Boston and the Lomonosov Moscow State University (MSU) aimed to uncover how chromatin structure is reorganized during the mammalian oocyte-to-zygote transition. Using next-generation sequencing, bioinformatics analysis and mathematical modeling performed by Maxim Imakaev in Leonid Mirny's lab, the researchers identified specific patterns that emerge during genome reorganization in mouse oocytes and zygotes.

The low availability of starting material made it necessary to develop a new single-nucleus Hi-C (snHi-C) method that made it possible to analyze the chromatin architecture in oocytes and single-cell embryos for the first time. Using this method, features of genomic organization including compartments, topologically associating domains (TADs) and chromatin loops were detected in single cells when averaged over the genome. "Our method allowed us to detect chromatin contacts ten times more efficiently than a previous method. Because of this we were able to find differences in genome folding on the level of single cells: these cell-to-cell variations were missed in conventional Hi-C due to the averaging over millions of cells," says Ilya Flyamer, former Vienna Biocenter (VBC) summer student and then Master student and one of the first authors of the study.

Contrasting behaviour of maternal and paternal chromatin

"Additionally, we found unique differences in the three-dimensional organization of the zygote's chromatin compared to other interphase cells. What was even more interesting is that maternal and paternal genomes of the zygote seem to have different organizations within the same cell. It seems like the chromatin architecture is reorganized after fertilization, and that this reorganization happens differentially for the maternal and the paternal genomes," explained Johanna Gassler, PhD student at IMBA and one of the first authors of the study.

Senior author and IMBA group leader Kiku Tachibana-Konwalski is fascinated by the secrets of the mammalian oocyte-to-zygote transition and has been studying the miracle of life, and in particular the very first molecular steps, for many years. She also hopes the findings will generate new insights for the emerging field of totipotency. "To place the power of the zygote into context: Reprogramming to pluripotency by the Yamanaka factors takes several days with limited efficiency, whilst reprogramming to totipotency occurs in the zygote within hours. How this is achieved remains one of the key unknowns in biology. By studying the chromatin state of zygotes, we aim to gain insights into this mechanism, which could also have applications for regenerative medicine," says Tachibana-Konwalski, underlining her excitement for the potential applications for her favourite research topic.

Explore further: The influence of the mother: Maternal epigenetic inheritance

More information: Ilya M. Flyamer et al. Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition, Nature (2017). DOI: 10.1038/nature21711

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Unique genome architectures after fertilisation in single-cell embryos - Phys.Org

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Genome rivalry – The Straits Times

Posted: at 6:37 am

DINGO

Why is this the most interesting genome in the world?

Charles Darwin stated that the process of domestication can be divided into two steps that we now call unconscious and artificial selection.

Unconscious selection may be defined as non-intentional human selection, while artificial selection is the breeding of desirable traits. This is thought to be the process by which thousands of domestic plants and animals around the world have been produced and continue to be developed.

We aim, for the first time and in a unique case, to test Darwin's hypothesis and differentiate the genomic and genetic processes involved in unconscious and artificial selection. The Australian dingo is the ideal species to explore these questions because it represents an intermediate step along the evolutionary pathway from wild wolves to domestic dogs.

BOMBARDIER BEETLE

Why is this the most interesting genome in the world?

Bombardiers are among the world's most impressive chemists. Their genetic machinery provides for biochemical warfare.

They repel predators with rapid-fire, precisely-aimed explosive discharges of a toxic chemical mix at over 100 deg C, earning them lead roles in media and culture.

Yet the genomic basis of this extraordinary ability remains a mystery. The first bombardier genome will allow us to understand the genetic basis of bombardier chemical production, solving a longstanding evolutionary puzzle. This understanding will elucidate the currently unknown genetic basis of explosive chemical defence in the animal kingdom.

PINK PIGEON

Why is this the most interesting genome in the world?

The pink pigeon would be the first endangered bird species to be sequenced with PacBio's Iso-Seq method, which would make this species a blueprint for future conservation genomic research.

We are in a unique position to find out the reasons for the pink pigeon's continued decline; low genetic diversity reduces reproductive success and makes birds susceptible to infectious disease.

With recent advances in sequencing technology, such as the Iso-Seq method, we aim to identify the causative genetic variants responsible for the decline in population numbers. This is pivotal for the genetic rescue of the population through the reintroduction of beneficial genetic variants still present in captive individuals in zoos, thereby stopping the pink pigeon from becoming the next Dodo.

SOLAR-POWERED SLUG

Why is this the most interesting genome in the world?

The "solar-powered" sea slug Elysia timida is no beast of fiction. It is a real Mediterranean sacoglossan that can "steal" chloroplasts - the little solar panels where photosynthesis takes place - from its algal food source.

These "stolen" plastids are then stored in a still functional state in the slug's digestive gland cells, allowing the slug to endure at least three months of starvation. During this time, the chloroplasts continue photosynthesis and build up a starch reservoir that finally can be used by the slug.

This phenomenon, termed functional kleptoplasty, is unique among animals and, with this extraordinary evolutionary feature, E. timida stands for a climate- and eco-friendly lifestyle. However, the genetic basis enabling this lifestyle remains poorly understood.

See the solar sea slug stealing sustenance at http://www.pacb.com/smrt-science/smrt-grant/ pag2017/solar-powered-slug/

SOURCE: PACBIO

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Genome rivalry - The Straits Times

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An enzyme keeps the parasites of the genome in check and turns them into an evolutionary advantage – Phys.Org

Posted: at 6:37 am

March 30, 2017 Human genes are riddled with a vast amount of DNA sequences which are known as jumping genes (colorful interconnected strings on the left). Without DHX9, these repetitive elements interact with each other to form entangled structures that can be detrimental to decoding the message. DHX9 is a nuclear enzyme that untangles this mess and creates neat mRNAs (thread) that are then used to make proteins (knitwork). Credit: Melica & timquo/ shutterstock.com; montage: MPI of Immunobiology & Epigenetics

Jumping genes are double-edged sword: By copying and integrating themselves into other parts of the genome these so-called transposons can lead to a variety of genetic disorders such as haemophilia or breast cancer. On the other hand the mobile DNA bits can create new genes and new gene expression programs. This is crucial for maintaining high genetic variability and adaptability to environmental changes. Scientists from the Max Planck Institute of Immunobiology and Epigenetics Freiburg in collaboration with the University of Freiburg have now found that an enzyme called DHX9 can neutralize the harmful structures formed by transposons and effectively increase the tolerance of the genome to include these jumping genes. By understanding this process better scientists can devise better therapies for diseases caused by transposons while retaining their evolutionary advantage.

Geneticists have long focused only on a very small part of DNA that contains blueprints for proteins. The non-coding remainder, around 97 percent in humans, was often dismissed as junk. But what was damned as junk before turned out to be the key regulator of genes determining where and how much protein should be synthesized. However, an even closer look into the "junk" revealed that it is also home for many more actors in the genome. One of these are the so-called transposons or jumping genes. Jumping genes are DNA sequences which are able to copy themselves and then insinuate the copies into distant sections of the genome.

"Our work revolves around a family of human transposons called Alu elements, which with more than 1.1 million copies, compose more than ten percent of our entire genome" says Tue Akta, co-first author of the study. To copy themselves, Alu elements are transcribed into RNA, reverse transcribed and then reintegrated into the genomic DNA at a different location. Once reintegrated, the short Alu elements have a vast amount of effects on the genome. "Depending on their site of insertion they can cause problematic mutations if they, for instance, jump into essential genes. Interestingly, Alu elements can cause a variety of genetic disorders such as haemophilia, breast cancer or familial hypercholesterolaemia, thus our work has to be explored further for therapeutic potential," says brahim Avar Ilk, co-first author of the study.

Jumping genes in evolution

Alu elements, are often referred to as "invaders" or "parasites" harming the genome stability. But at the same time Alu elements are also important drivers of evolution. Studies comparing primates and humans showed that more than five thousand Alu elements were newly inserted into the human genome during the past six million years. Scientists suggest that they act as a "creative destroyer" by separating parts of the genome into functional pieces that can be copied, moved around and re-used in other contexts. This ability to modify the DNA by more than 1.1 million Alu elements at the same time increases the possibility to create new genes as well as gene expression programs that probably allowed faster adaptation to the environment.

"We wondered how our genome deals with the outcome of this continuous copy-pasting and still avoids potentially fatal threats. Our discovery that DHX9 as the enzyme responsible for neutralizing harmful RNA structures produced during expression of our genes is very exciting as it opens a new angle to look into the complex biology hidden behind this abundant RNA helicase," says Asifa Akhtar, Max Planck Director and the lead investigator.

Untie the knot

DHX9 has the ability to unwind DNA and RNA duplexes and plays a central role in many processes in the cell like DNA replication, transcription or RNA processing. The Akhtar team in collaboration with Daniel Maticzka and Rolf Backofen from the bioinformatics research group of the University of Freiburg was able to show that in mice and humans DHX9 finds and removes disruptive RNA structures formed by dense Alu insertions. "If the distance between Alu elements in our genome is not large enough they interact with each other and form massive tangled RNA pieces", says brahim Avar Ilk. These huge cluttered structures can have fatal consequences, because essential RNA processing signals can be masked by them. DHX9 resolves the clutter and hands the now-untangled RNA over to further processing. "So without DHX9, our RNA turns into an entangled yarn that is no good for knitting," adds Tue Akta (see Fig. 1).

DHX9 does not do all the work by itself but has a "partner in crime" called ADAR, another enzyme that was previously shown to also be involved in the handling of tangled RNA structures especially during viral infections. "We suggest that this clearing unit evolved originally to fight against viral invasions. Their untangling activities were later reassigned and put into use in cells that are not under viral invasion, but are experiencing a surge in Alu element insertions", explains Asifa Akhtar the evolutionary implications of the data.

The great collaborative effort between the Max Planck Institute and the University of Freiburg leads the team to propose that DHX9 allowed the insertion of excessive amounts of Alu elements in our genome by simply counteracting harmful consequences of having too many of them side-by-side. Even though harboring so many disturbing jumping genes may seem like a waste of our cellular resources it pays for itself in the long run with genomic innovations that would otherwise be impossible. In other words, what is seen as a waste in our genome has never really been a waste, it is essentially a long, expensive road to complexity.

Explore further: A hidden code in our DNA explains how new pieces of genes are made

More information: Tue Akta et al. DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome, Nature (2017). DOI: 10.1038/nature21715

Journal reference: Nature

Provided by: Max Planck Society

We're all here because of mutations. Random changes in genes are what creates variety in a species, and this is what allows it to adapt to new environments and eventually evolve into completely new species. But most random ...

Scientists have discovered a previously unknown wellspring of genetic diversity in humans, chimps and most other primates. This diversity arises from a new component of itinerant sections of genetic code known as jumping ...

For more than 50 years, scientists have known of the existence of "jumping genes," strands of DNA material that can move from one location in the genome to another.

Almost 50 percent of our genome is made up of highly repetitive DNA, which makes it very difficult to be analysed. In fact, repeats are discarded in most genome-wide studies and thus, insights into this part of the genome ...

The human genome shares several peculiarities with the DNA of just about every other plant and animal. Our genetic blueprint contains numerous entities known as transposons, or "jumping genes," which have the ability to move ...

Moving genetic elements from one location to another in a genome makes for a very dynamic situation in terms of development and disease. An EU project has investigated a special type of micro transposable element and its ...

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