Category Archives: Transhuman News

Long before cats became the darlings of Facebook and YouTube, they spread through the ancient human world.

A DNA study reached back thousands of years to track that conquest and found evidence of two major dispersals from the Middle East, in which people evidently took cats with them. Genetic signatures the felines had on those journeys are still seen in most modern-day breeds.

Researchers analyzed DNA from 209 ancient cats as old as 9,000 years from Europe, Africa and Asia, including some ancient Egyptian cat mummies.

"They are direct witnesses of the situation in the past," said Eva-Maria Geigl of the Jacques Monod Institute in Paris. She and colleagues also looked at 28 modern feral cats from Bulgaria and east Africa.

It's the latest glimpse into the complicated story of domesticated cats. They are descendants of wild ancestors that learned to live with people and became relatively tame though some cat owners would say that nowadays, they don't always seem enthusiastic about our company.

The domestication process may have begun around 10,000 years ago when people settled in the Fertile Crescent, the arch-shaped region that includes the eastern shore of the Mediterranean Sea and land around the Tigris and Euphrates rivers. They stored grain, which drew rodents, which in turn attracted wild cats. Animal remains in trash heaps might have attracted them too. Over time, these wild felines adapted to this man-made environment and got used to hanging around people.

Previous study had found a cat buried alongside a human some 9,500 years ago in Cyprus, an island without any native population of felines. That indicates the cat was brought by boat and it had some special relationship to that person, researchers say.

Cats were clearly tame by about 3,500 years ago in Egypt, where paintings often placed them beneath chairs. That shows by that time, "the cat makes its way to the household," said Geigl.

But the overall domestication process has been hard for scientists to track, in part because fossils skeletons don't reveal whether a cat was wild or domesticated.

It's easier to distinguish dogs, our first domesticated animal, from their wolf ancestors. Dogs evolved from wolves that had begun to associate with people even before farming began, perhaps drawn by the food the humans left behind.

The new study tracked the spread of specific cat DNA markers over long distances through time, a sign that people had taken cats with them. Results were released Monday by the journal Nature Ecology & Evolution.

The study "strengthens and refines previous work," said Carlos Driscoll of the Wildlife Institute of India. The extensive sampling of cat DNA going back so far in time is unprecedented, he said.

Researchers also looked for a genetic variant that produces the blotchy coat pattern typical of modern-day domestic cats, rather than the tiger-like stripes seen in their wild cousins. It showed up more often in samples from after the year 1300 than earlier ones, which fits with other evidence that the tabby cat markings became common by the 1700s and that people started breeding cats for their appearance in the 1800s.

That's late in the domestication of cats, in contrast to horses, which were bred for their appearance early on, Geigl said.

Most of the study focused on the ancient dispersals of cats. In the DNA samples analyzed, one genetic signature found first in the Asian portion of Turkey and perhaps once carried by some Fertile Crescent cats showed up more than 6,000 years ago in Bulgaria.

That indicates cats had been taken there by boat with the first farmers colonizing Europe, Geigl said. It also appeared more than 5,000 years ago in Romania, as well as around 3,000 years ago in Greece.

A second genetic signature, first seen in Egypt, had reached Europe between the first and fifth centuries, as shown by a sample from Bulgaria. It was found in a seventh-century sample from a Viking trading port in northern Europe, and an eighth-century sample from Iran.

The dispersal of the cats across the Mediterranean was probably encouraged by their usefulness in controlling rodents and other pests on ships, the researchers said.

Follow Malcolm Ritter on Twitter: @MalcolmRitter. His recent work can be found here .

This Associated Press series was produced in partnership with the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.

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Science Says: DNA shows early spread of cats in human world - ABC News

In brief

DNA-encoded libraries let researchers screen millions, billions, and even trillions of chemical compounds in a single, simple experiment, thanks to a DNA tag that encodes how each component in the library was made. Although the technology was invented 25 years ago, its only within the past five years that its become a mainstay of drug discovery. Read on to learn about how the technology works and to read some recent success stories that pharmaceutical companies, biotechs, and academics have achieved using the technology.

Forty trillion is the kind of number that gives one pause. Consider it written out with its 13 zeros: 40,000,000,000,000. Assembling and maintaining a collection of 40 trillion of anything seems like a mind-bogglingly massive task. But in February the Danish biopharmaceutical company Nuevolution announced that it had created a library of 40 trillion unique moleculesquite possibly the largest collection of synthetic compounds in the world.

You might think it would require every building in Copenhagen to store batches of 40 trillion different compounds. Not so, says Alex Haahr Gouliaev, Nuevolutions chief executive officer. All of that fits into an Eppendorf tube and is handled by one person for screening, he says.

The substance that makes it possible to maintain this multitudinous mixture of molecules is the same substance that contains the code of lifeDNA. Nuevolution covalently attaches a short, unique strand of DNA to each of its 40 trillion compounds. Instead of holding the directions for life, though, these DNA strands encode the recipe used to synthesize each linked molecule. This trick enables the firm to store all the compounds as a mixture in a small volume and later sequence, or read, them out. As the cost for DNA sequencing plummets and the repertoire of DNA-compatible chemical reactions grows, these so-called DNA-encoded libraries are becoming a go-to resource for finding new drug candidates and research tools for large pharmaceutical companies, small biotechs, and academics alike.

DNA-encoded libraries are revolutionary, says Roger D. Kornberg, a biochemist at Stanford University School of Medicine and winner of the 2006 Nobel Prize in Chemistry. I think they represent the most innovative and broadly significant advance in chemistry in the past decade or more. Some of my chemical colleagues who develop beautiful new chemistry might be offended by the breadth of that remark, but suffice it to say, this is a major advance.

A dizzying number of deals in the DNA-encoded library space over the past year demonstrate the pharmaceutical industrys growing excitement over the technology. Last October, Amgen and Nuevolution inked a collaboration for the former to use the latters DNA-encoded libraries to search for drug candidates against multiple targets in oncology and neuroscience. GlaxoSmithKline, a world leader in DNA-encoded library technologies, established a partnership with Warp Drive Bio in March to create a library aimed at targets previously considered undruggable. HitGen, a Chinese company that specializes in DNA-encoded libraries, has set up partnerships with Johnson & Johnson, Merck & Co., Pfizer, and the California Institute for Biomedical Research over the past nine months. And just last month X-Chem Pharmaceuticals, another company that specializes in DNA-encoded libraries, announced it would be collaborating with Vertex Pharmaceuticals.

Companies are also expanding their in-house efforts with DNA-encoded libraries. In February, Novartis announced that it would use the technology to ramp up its compound collection from 3 million molecules to 300 million over the next three years.

The reason for all this activity is obvious, Kornberg says. The standard for testing compounds in the pharmaceutical industry has for a long time been the high-throughput screen, in which scientists interrogate a library of a couple million compounds one by one to see if they affect the function of a target of interest. To do all of that costs on the order of a billion dollars and requires instrumentation that occupies space the size of the building I am sitting in at the moment, Kornberg says from his office at Stanfords three-story Fairchild building.

By comparison, a DNA-encoded library of billions or even trillions of compounds can fit into a space the size of an Eppendorf tube and costs just tens to hundreds of thousands of dollars to create and use. Thats because the DNA-encoded library is made, stored, and screened as a mixture.

Since we can screen them as a mixture, theres really no limit to the number of molecules we can put into the mixture, explains Matthew A. Clark, senior vice president of research at X-Chem.

Credit: C&EN/Adapted from The Scientist

Constructing and reading the library

Although scientists can use a few different methods to make a DNA-encoded library, the one they use most often treats the DNA like a bar code. They start by attaching a short piece of DNA to a small organic functional groupan aliphatic amine, for example. That basic building block is then split into wells in a plate, where it undergoes a chemical reaction with a different building block in each well. Then researchers add a unique bit of DNA, anywhere from seven to 15 base pairs long, to each well and connect, or ligate, it to the existing DNA, creating a code for the reaction that just took place. The contents of all the wells are then pooled and split up again. The process is repeated. In this manner, its possible to build a library of considerable size in just a few iterations.

To screen a DNA-encoded library, researchers combine the mix of compounds with a biological target such as an enzyme. Anything that doesnt bind to the target washes away. The scientists then denature the target, collect the resulting batch of hits, and incubate them with a fresh target to ensure the best binders remain. This process gets repeated for a third time. Only vanishingly small amounts of the compounds that bind the target remain after these repeated screenings, so to determine their identities, the DNA on each compound must be amplified and sequenced. By analyzing the sequences, scientists can read the DNA bar code and tell which reactions and building blocks were used to make the compounds that bind best. Chemists then resynthesize those compounds without the DNA tag and test them with the target again to see if they have any biological effects.

DNA-encoded libraries are a rejuvenation of the combinatorial chemistry concepts of the 1990s propelled into the 21st century, says Frdric Berst, a scientist who works on DNA-encoded libraries at Novartis. You can deeply and routinely sample huge chemical collections in a comparatively easy-to-run experiment.

If you have 3 million compounds, to screen them all with high-throughput screening is really a lot of work, says Robert A. Goodnow Jr., a scientist with Pharmaron and editor of A Handbook for DNA-Encoded Chemistry: Theory and Applications for Exploring Chemical Space and Drug Discovery. But with DNA-encoded chemistry, you can put hundreds of millions, billions, or even trillions of compounds in front of a target. You simply could not assay a billion compounds in a high-throughput screening format, Goodnow says. Its just not possible in terms of time and money.

Besides the leap in the number of compounds that can be screened in a single experiment, the technology offers an additional advantage. Its possible to do many screenings in parallel with DNA-encoded libraries, says Johannes Ottl, another Novartis scientist who works with the technology. That cant be said for high-throughput screening.

For example, its relatively easy to find kinase inhibitors but challenging to find inhibitors that are specific for a particular kinase. If you wanted to test a high-throughput screening collection of 1 million compounds against 50 specific kinases, youd need to conduct 50 million experiments. To do the same type of screening with a DNA-encoded library would take only 50 experiments and could potentially identify compounds that bind to a specific kinase.

We dont want to make it sound too simple because there is a lot of due diligence you need to do to run such a project, Ottl says. But the up-front workthe assay developmentis quite simple compared to many other approaches in lead finding. Basically, he says, scientists are just fishing for binders and dont need to create an assay that measures a targets biological function.

The concept of DNA-encoded libraries was introduced 25 years ago by Richard Lerner, a chemist at Scripps Research Institute California, and his colleague Sydney Brenner, cowinner of the 2002 Nobel Prize in Physiology or Medicine. The pair published a paper thats often described as a thought experiment (Proc. Natl. Acad. Sci. USA 1992, DOI: 10.1073/pnas.89.12.5381). They also put their pipettes into action to make a small DNA-encoded library and patented the idea around the same time (U.S. Patent No. 5573905).

Lerner recalls that the two came up with the concept when discussing the difference between chemistry and biology. They reasoned that small molecules, such as drugs and natural products, differ from biological molecules in that they do not carry information in the form of a code. They dont tell you who they are, Lerner explains, and secondly, they dont replicate. Lerner and Brenner reckoned that they could give molecules a replicable identity by putting a piece of DNA on them after each step in a chemical synthesis.

Typically, Lerner says, large numbers are the enemy of identification in organic chemistry. But with DNA-encoded library technology, scientists can take large numbers of molecules and give each one an identifying marker that carries information, Lerner points out. That information can be replicated, he says, adding, Its hard to beat that sort of power.

The idea, however, languished for at least a decade.

For a long time I think the technology was not readily available for people to try, nor did they understand it well enough to say I want to apply it, Goodnow says. But, he adds, that attitude has changed in the past five years. People have become much more aware that this presents a real opportunity to find hits. Its another tool in the toolbox.

Its remarkable that it works so well, says Barry A. Morgan, HitGens chief scientific officer. The reason that it works is really a tribute to the fundamental developments over the last 30 years in our ability to manipulate and sequence DNA.

In the early 2000s, Morgan worked for Praecis Pharmaceuticals (which was acquired by GSK in 2007), one of the first companies to explore DNA-encoded libraries. When the firm started working on the technology, he recalls, current high-throughput DNA-sequencing methods werent available. But about six months into the project, he and his Praecis colleagues found a company called 454 Life Sciences that had sequencing methods perfectly suited to DNA-encoded libraries.

We wouldnt be able to make such large libraries and deconvolute them if the current sequencing methods were not available, Morgan says.

Gouliaev says that when Nuevolution was getting started in the early 2000s, pharma companies and venture capitalists would tell him that it didnt make sense to synthesize such big libraries. They were put off by previous efforts in combinatorial chemistry, wherein chemists prepared tens of thousands to millions of small molecules as a mixture and screened them for useful properties. They would say, Dont you know combinatorial chemistry failed? And, Having DNA will limit your chemistry so much that you cant make the molecules wed be interested in.

We needed to prove ourselves, Gouliaev continues, and it took us quite a few years to get something that was robust, reliable, and would have high diversity of truly druglike small molecules.

X-Chems Clark agrees that many were skeptical about DNA-encoded libraries because of the failure of combinatorial chemistry in the 1990s. The best way to overcome skepticism is with data, and theres been enough data reported in the last five years that it would be very difficult to maintain that sort of skepticism, Clark says.

Several DNA-encoded library success stories have emerged just this year. GSK advanced its compound GSK2982772which came about from DNA-encoded library workto Phase IIa clinical trials in patients with psoriasis, rheumatoid arthritis, and ulcerative colitis. GSK2982772 inhibits receptor interacting protein 1 kinase, or RIP1 kinase, an enzyme thats been linked to inflammation.

Looking to develop an inhibitor for RIP1 kinase, scientists at GSK first screened the companys set of known kinase inhibitors, but they were unable to find molecules that had the druglike properties they were looking for, and they also found that hits from this set of compounds werent selective for RIP1; they inhibited other kinases as well.

They also screened GSKs high-throughput collection of roughly 2 million compounds and identified a RIP1 inhibitor, but that compound had challenges. In particular, it didnt get into the bloodstream of rodents when given orally. By far the most promising lead, a compound known as GSK481, was obtained by screening a DNA-encoded library of approximately 7.7 billion compounds against RIP1 kinase. GSK481 turned out to be extremely potent as well as highly specific to RIP1 kinase (J. Med. Chem. 2016, DOI: 10.1021/acs.jmedchem.5b01898).

But the scientists thought they could improve GSK481s pharmacokinetics. Using a traditional medicinal chemistry approach, they eventually wound up swapping GSK481s isoxazole for a triazole to get their clinical candidate GSK2982772 (J. Med. Chem. 2017, DOI: 10.1021/acs.jmedchem.6b01751).

On paper it looks like it was just a tweak in a few atoms, says Christopher P. Davie, manager of discovery chemistry at GSK who leads its efforts on DNA-compatible reaction development and encoded library synthesis. But a ton of medicinal chemistry work went into it.

In another recent success story, just last month, researchers at AstraZeneca, Heptares Therapeutics, and X-Chem published the crystal structure of two allosteric ligands bound to a G protein-coupled receptor (GPCR) called protease-activated receptor 2, or PAR2. One of those allosteric ligandsAZ3451was identified using DNA-encoded libraries from X-Chem (Nature 2017, DOI: 10.1038/nature22309).

PAR2 has been implicated in a wide range of diseases, including cancer and inflammation. Allosteric binders of this target could prevent the structural rearrangements PAR2 needs to undergo to become active and participate in signaling. The researchers hope AZ3451 will help guide them in the development of selective PAR2 antagonists for a range of therapeutic uses.

This years success stories arent just limited to the pharmaceutical industry. Every academic whos a biologist and has a target would like to do chemistry, but they have no access to chemical matter, Scrippss Lerner points out. DNA-encoded libraries now make it possible for academics to access compounds that pharmaceutical companies struggled for many years to develop, he says.

One recent academic success comes from 2012 Chemistry Nobel Laureate Robert J. Lefkowitzs lab at Duke University. Lefkowitzs team used a 190 million-compound DNA-encoded library from Nuevolution to find an allosteric modulator for the 2-adrenergic receptor, another GPCR. Screening for ligands of GPCRs has, in the past, been a cumbersome and labor-intensive process. The method developed by the Lefkowitz lab using DNA-encoded libraries is broadly applicable, the researchers note, and could potentially lead to more therapeutics that target these receptors (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1620645114).

Along with the recent success stories, many DNA-encoded library makers point to the economic advantage their technology provides. You can make from scratch DNA-encoded libraries for a relatively small investment compared with accruing a high-throughput screening collection, HitGens Morgan points out. And then you can interrogate those libraries very efficiently and effectively within a period of a few weeks.

With DNA-encoded chemistry, because youre making such large numbers of compounds in very small quantities, the cost of production of that mixture of compounds is orders of magnitude smaller than previous methods, says Pharmarons Goodnow, who broke down the cost savings in a recent paper in Nature Reviews Drug Discovery (2016, DOI: 10.1038/nrd.2016.213).

To create and interrogate a conventional high-throughput screening collection of 1 million compounds costs between $400 million and $2 billion, roughly $1,100 per compound, by Goodnows estimate. A DNA-encoded library of 800 million compounds, on the other hand, costs about $150,000 for materials to create and screenapproximately $0.0002 per compound.

This makes DNA-encoded libraries a good starting point for small companies, start-ups, or academics who dont already have a large high-throughput screening collection at their disposal, Novartiss Ottl says. You dont need to invest much in automation, and you dont need to invest a lot in compounds up front.

But even with the cost savings and massive expansion of chemical space to explore, scientists who work with DNA-encoded libraries say the technologys not a panacea. Its a complement to other existing methods. Its not better than high-throughput screening, Goodnow says. Its just a different way to go about it. Ideally people would want to do both.

Despite their revolutionary stature, DNA-encoded libraries are not without their challenges. Often chemists wonder if the large DNA bar code attached to a compound will interfere with how it binds to a target. Ideally, the DNA tag would face away from where the compound is binding to a target, explains GSKs Davie. Thats always observed in crystal structures of library ligands that have successfully bound to their target. Of course, thats not always going to happen for unsuccessful ligands, he says, but while the DNA tag is a natural constraint of DNA-encoded library technology, its not a showstopper.

Another constraint is that any chemistry used to construct a DNA-encoded library must be able to tolerate water because DNA requires an aqueous solution. The reaction conditions also have to keep the DNA intact; damaged DNA cant be amplified or sequenced.

DNA is quite robustafter all, we are still digging out DNA from dinosaursbut it is still fragile with respect to pH and temperature, Novartiss Berst says. Heating DNA in xylenes at 200 C in the presence of a metal catalyst is not something I would recommend to a budding DNA-encoded library chemist, he jokes.

But this limitation also makes developing new DNA-compatible reactions exciting for synthetic chemists. You put that kind of challenge before a synthetic chemist and its like a red cape to a bull, Scrippss Lerner says.

GSKs Davie says that his group has managed to construct components of DNA-encoded libraries in solutions that contain just 20% water. Theyve done ring-closing metathesis reactions as well as cross-couplings, he says, although he admits sometimes they have to use large amounts of catalysts. The reactions arent particularly elegant, but they work, he says.

Davie thinks the real bottleneck when it comes to DNA-encoded library chemistry comes after library synthesis and screening. He points out that when screening a DNA-encoded library, you turn up only compounds that bind a target. But thats no guarantee that those hits will have the activity youre looking for.

And then theres the matter of deciding which hits to resynthesize. There are always more compounds to make than we have resources to make, so we have to prioritize them, Davie says. Right now, he says, about half the molecules they choose to resynthesize dont show any activity when screened against their target.

Also, Berst notes, while you might need only 5 mg of a building block when constructing a DNA-encoded library, you will need more than that if you need to resynthesize that hit. When rare building blocks are in hits it can set back the timeline of a resynthesis.

Despite these challenges, DNA-encoded libraries are gaining ground in drug discovery, and scientists see them becoming even more integral to research efforts in the future. It is truly one of the most profound and original ideas in chemistry, and the consequences are only just beginning to be felt, Stanfords Kornberg says. Once a leap forward in technology takes place, then people begin to think of all kinds of ingenious ways of putting it to use. Were just at the beginning.

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How DNA-encoded libraries are revolutionizing drug discovery ... - The Biological SCENE

Here's proof of how far we've come in science - in a world-first, researchers have recorded up-close footage of a single DNA molecule replicating itself, and it's raising questions about how we assumed the process played out.

The real-time footage has revealed that this fundamental part of life incorporates an unexpected amount of 'randomness', and it could force a major rethink into how genetic replication occurs without mutations.

"It's a real paradigm shift, and undermines a great deal of what's in the textbooks," says one of the team, Stephen Kowalczykowski from the University of California, Davis.

"It's a different way of thinking about replication that raises new questions."

The DNA double helix consists of two intertwining strands of genetic material made up of four different bases - guanine, thymine, cytosine, and adenine (G, T, C and A).

Replication occurs when an enzyme called helicase unwinds and unzips the double helix into two single strands.

A second enzyme called primase attaches a 'primer' to each of these unravelled strands, and a third enzyme called DNA polymerase attaches at this primer, and adds additional bases to form a whole new double helix.

You can watch that process in the new footage below:

The fact that double helices are formed from two stands running in opposite directions means that one of these strands is known as the 'leading strand', which winds around first, and the other is the 'lagging strand', which follows the leader.

The new genetic material that's attached to each one during the replication process is an exact match to what was on its original partner.

So as the leading strand detaches, the enzymes add bases that are identical to those on the original lagging stand, and as the lagging strand detaches, we get material that's identical to the original leading strand.

Scientists have long assumed that the DNA polymerases on the leading and lagging strands somehow coordinate with each other throughout the replication process, so that one does not get ahead of the other during the unravelling process and cause mutations.

But this new footage reveals that there's no coordination at play here at all - somehow, each strand acts independently of the other, and still results in a perfect match each time.

The team extracted single DNA molecules from E. coli bacteria, and observed them on a glass slide. They then applied a dye that would stick to a completed double helix, but not a single strand, which means they could follow the progress of one double helix as it formed two new double helices.

While bacterial DNA and human DNA are different, they both use the same replication process, so the footage can reveal a lot about what goes on in our own bodies.

The team found that on average, the speed at which the two strands replicated was about equal, but throughout the process, there were surprising stops and starts as they acted like two separate entities on their own timelines.

Sometimes the lagging strand stopped synthesising, but the leading strand continued to grow. Other times, one strand could start replicating at 10 times its regular speed - and for seemingly no reason.

"We've shown that there is no coordination between the strands. They are completely autonomous," Kowalczykowski says.

The researchers also found that because of this lack of coordination, the DNA double helix has had to incorporate a 'dead man's switch', which would kick in and stop the helicase from unzipping any further so that the polymerase can catch up.

The question now is that if these two strands "function independently" as this footage suggests, how does the unravelling double helix know how to keep things on track and minimise mutations by hitting the brakes or speeding up at the right time?

Hopefully that's something more real-time footage like this can help scientists figure out. And it's also an important reminder that while we humans love to assume that nature has a 'plan' or a system, in reality, it's often a whole lot messier.

The research has been published in Cell.

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DNA Replication Has Been Filmed For The First Time, and it's not ... - ScienceAlert

A Jacksonville man is charged in the shooting death of another man caught in a crossfire when a gun deal near Edward Waters College was interrupted last summer by a robbery, authorities said.

Detectives got a warrant last week for the arrest of Devin Roshaun Bartley, 21, after state lab tests of a bullet fragment collected at the scene tested positive for his DNA and that of the victim, according to the Sheriffs Office.

Facing a murder charge, Bartley turned himself in Monday and was booked into the Duval County jail, where he remains in custody in lieu of $500,000 bail.

Anthony Carl Whitley, 37, was found slumped inside a Chevrolet Impala that crashed into a fence near 4th and Grunthal streets about 11 p.m. Sept. 4, 2016. Shot several times in the head and wrist, he was pronounced dead at the scene.

There was an open passenger door that indicated to officers, because of the blood trail leading away from it, that there was another occupant in the vehicle, Lt. Steve Gallaher said Monday. But they were no longer at the scene.

Gallaher said detectives determined the shooting actually took place a couple blocks away near Dot and Grunthal streets and the victims were able to drive away before crashing the Impala. At that location, they found shell casings and bullet fragments.

Shortly after, detectives were notified Marcus Treynard Glover, 20, had shown up at the hospital with multiple gunshot wounds, Gallaher said. Then, he said, Bartley came into the emergency room, shot in the hand.

Glover told detectives he and Whitley had arranged for a gun deal to take place at the Dot Street location, but that during the deal, a masked gunman confronted and robbed them.

During that robbery attempt, Marcus said that he pulled his handgun and there was a gunfight between he and the robber, and thats when Whitley was shot and killed, the lieutenant said.

Bartley, meanwhile, told detectives he had been walking down the sidewalk several blocks away when he heard gunshots and then noticed hed been struck in the hand. He said he sought help from a friend, who gave him a ride to the ER.

Gallaher said detectives collected a DNA sample from Bartley with his consent and then released him due to a lack of information linking him to the shooting. He said police tracked down the gun buyer, who backed up Glovers account.

Detectives were able to loosely link the individual in the car buying the guns and Bartley as associates; however, at this time they are not able to prove that that subject set up this robbery, Gallaher said.

A bullet fragment recovered at the scene was sent to the state police crime lab for processing, which later found both Whitleys and Bartleys DNA on it. An analyst determined it must have traveled through Whitley before striking Bartley.

Reached Monday, the victims younger cousin, Devin Alexander, said the arrest brought him a little closure because he had made peace with Whitleys passing. He was a good guy who found himself in the wrong spot at the wrong time because somebody put him in a bad situation, he said.

Alexander, 23, said Whitley, described as a gentle giant and teddy bear known to loved ones as Amp, had been a mentor to him since his father passed away more than a decade ago.

He was a great dad, a great guy and the best cousin I could ask for.

Staff writer Dan Scanlan contributed to this report.

Garrett Pelican: (904) 359-4385

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DNA from bullet fragment links suspect to Jacksonville man's shooting death - Florida Times-Union

During the past 20 years or so, DNA testing has become a household phrase. Television shows about tracing one's heritage and medical discoveries into the genetic links to illness have fed into this need to find one's origins or one's DNA pattern.

Now that is a possibility.

Sometimes people search their lineage out of curiosity. Family lore often carries untruths that people have believed for a few generations, and then they find out that the information was not accurate. Sometimes the curiosity stems from another desire.

"I have found that many people just want the information so that they can go on a trip and visit the geographic areas from which their ancestors came," said Marsha Peterson-Maass, a professional genealogist.

Whether it is an interest in ethnicity, lineage or medical predispositions, there is a commercial DNA test for finding out the answers.

"DNA testing technology is available for everyone, but first you need to figure out what test you want to take because there is usually a reason for why you are testing," said Peterson-Maass, during an "Understanding Commercial DNA Test Results" seminar at the Kankakee Public Library.

Peterson-Maass explained there are three different types of DNA, which include Autosomal DNA, mtDNA and Y-DNA. Each type tells something a little bit different about oneself and one's heritage.

1. Autosomal DNA offers the most extensive answers. It provides both kinship and medical results. It traces back six or possibly seven generations. Once tested, the testing company can identify other people already in its database, called cousins, who share long strings of matching DNA. (The matches are labeled cousins because somewhere back in the lineage, the two people came from a common couple pairing.)

In addition to lineage, this type of DNA also can identify physical traits and medical predispositions.

But, "I'd like to provide a word of caution here," Peterson-Maass said. "A predisposition does not mean that someone will definitely develop the condition, but if something in the report is scary, hiring a forensic genealogist through The Council for the Advancement of Forensic Genealogy to help understand the results can be a benefit."

2. mtDNA (mitochondrial DNA) offers deep ancestry information through the female line. Mitochondria are found in the cytoplasm of human cells, and while a mother passes it to every child, only daughters pass it on to the next generation. The mutation rate for mtDNA is only every 450 years or 22 generations, so having one person in a family tested is usually enough. Information found with a test for mtDNA would be able to tell a person what geographic area in which the matrilineal family line originated. It also is possible to find out what other family lines stemmed from the same origin and branched out elsewhere.

3. Y-DNA offers information passed only through males. It is the DNA on the Y-chromosome. Similar to mtDNA, Y-DNA also has a slow mutation rate. The mutation rate is about 150 to 200 years, so again, having one person tested in a family line is often enough to gather the results needed. Information about the origins of the patrilineal line can be found with a test for Y-DNA.

Commercial tests are available for each DNA type. At the moment, five companies offer commercial DNA testing: FamilyTreeDNA, DNA.Ancestry.com, 23andMe.com, Nat Geo and DNA Tribes.com. All of the companies offer some type of ethnicity report, but only 23andMe will give a chromosomal view, showing physical traits and medical predispositions.

Worried about a blood test? These testing companies use saliva samples swabbed at home and mailed in to the companies.

"It should be noted that DNA testing is not a magic solution and doesn't provide an instantaneous family tree," Peterson-Maass said. These tools work best in conjunction with traditional documentary research, she added.

It can get pricey. In general, costs for FamilyTreeDNA, DNA.Ancestry.com and 23andMe range from $59 to $99. FamilyTreeDNA offers mtDNA for $79 (for the full sequence, $199) and Y-DNA testing for $169 to $359. National Geographic offers mtDNA for $149. DNA Tribes testing starts at about $119.

And sometimes the results found can lead to further questions, as Al Mikel, a seminar attendee stated: "I just got my results from Ancestry.com, and they are something that I think I need to study."

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Thinking about testing your DNA? Here's what to know - Kankakee Daily Journal

June 19, 2017 Credit: Tel Aviv University

Antimicrobial resistance is one of the biggest threats to global health, affecting anyone, at any age, in any country, according to the World Health Organization. Currently, 700,000 deaths each year are attributed to antimicrobial resistance, a figure which could increase to 10 million a year by 2050 save further intervention.

New breakthrough technology from Tel Aviv University facilitates DNA delivery into drug-resistant bacterial pathogens, enabling their manipulation. The research expands the range of bacteriophages, which are the primary tool for introducing DNA into pathogenic bacteria to neutralize their lethal activity. A single type of bacteriophage can be adapted to a wide range of bacteria, an innovation which will likely accelerate the development of potential drugs based on this principle.

Prof. Udi Qimron of the Department of Clinical Microbiology and Immunology at TAU's Sackler Faculty of Medicine led the research team, which also included Dr. Ido Yosef, Dr. Moran Goren, Rea Globus and Shahar Molshanski, all of Prof. Qimron's lab. The study was recently published in Molecular Cell and featured on its cover.

For the research, the team genetically engineered bacteriophages to contain the desired DNA rather than their own genome. They also designed combinations of nanoparticles from different bacteriophages, resulting in hybrids that are able to recognize new bacteria, including pathogenic bacteria. The researchers further used directed evolution to select hybrid particles able to transfer DNA with optimal efficiency.

"DNA manipulation of pathogens includes sensitization to antibiotics, killing of pathogens, disabling pathogens' virulence factors and more," Prof. Qimron said. "We've developed a technology that significantly expands DNA delivery into bacterial pathogens. This may indeed be a milestone, because it opens up many opportunities for DNA manipulations of bacteria that were impossible to accomplish before.

"This could pave the way to changing the human microbiomethe combined genetic material of the microorganisms in humansby replacing virulent bacteria with a-virulent bacteria and replacing antibiotic-resistant bacteria with antibiotic-sensitive bacteria, as well as changing environmental pathogens," Prof. Qimron continued.

"We have applied for a patent on this technology and are developing products that would use this technology to deliver DNA into bacterial pathogens, rendering them a-virulent and sensitive to antibiotics," Prof. Qimron said.

Explore further: Programming DNA to reverse antibiotic resistance in bacteria

More information: Ido Yosef et al, Extending the Host Range of Bacteriophage Particles for DNA Transduction, Molecular Cell (2017). DOI: 10.1016/j.molcel.2017.04.025

Journal reference: Molecular Cell

Provided by: Tel Aviv University

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DNA delivery technology joins battle against drug-resistant bacteria - Phys.Org

June 19, 2017 by Stuart Mason Dambrot feature Fig. 1. Spontaneous formation of aligned DNA nanowires. (A) Schematic illustrations of the spontaneous formation of an array of DNA nanowires by the skin folding induced by water filaments containing DNA molecules. (B) Sequential optical microscope images of a droplet of DNA solution spreading over wrinkles (t = 5 min, 0.03); the wrinkle-to-fold transition occurs at the boundary and propagates with the edge of the droplet. (C) AFM image of an array of DNA nanowires extending from the boundary (t = 2 min, 0.02). The line profiles for each region are shown next to the image. (Scale bars: B, 50 m and C, 4 m.). Credit: Nagashimaa S, Haa HD, Kima DH, Komrljb A, Stone HA, Moon M-W (2017) Spontaneous formation of aligned DNA nanowires by capillarity-induced skin folding. Proc Natl Acad Sci USA 114:24 6233-6237.

(Phys.org)Nanowires fashioned from DNA (deoxyribonucleic acid)one of several type of molecular nanowires incorporating repeating molecular unitsare exactly that: Geometrically wire-like DNA-based nanostructures defined variously as having a 1~10 nm (109 m) diameter or a length-to-diameter ratio >1000. While nanowires can be made from several organic and inorganic materials, DNA nanowires have been shown to provide a range of valuable applications in programmed self-assembly1,2 of functional materialsincluding metallic and semiconductor nanowires for use in electronic devicesas well as biological, medical, and genetic analysis applications3,4,5. That being said, DNA nanowire adoption has been limited due to historical limitations in the ability to control their structural parametersspecifically, size, geometry and alignment. Recently, however, scientists at Korea Institute of Science and Technology and Princeton University leveraged the capillary forces of water containing DNA molecules to demonstrate size-controllable straight or undulated aligned DNA nanowires that were spontaneously formed by water entering wrinkled channels of a compressed thin skin on a soft substrate, which subsequently induced a wrinkle-to-fold transition.

Assistant Professor and lead author So Nagashima, Assistant Professor Andrej Komrlj, Donald R. Dixon '69 and Elizabeth W. Dixon Professor Howard A. Stone, and Principal Research Scientist Myoung-Woon Moon discussed the paper they and their co-authors published in Proceedings of the National Academy of Sciences. "I think that the most challenging aspect of devising our method for utilizing a thin skin template that responds to water by dynamically changing its surface morphology was finding the conditions where the wrinkle-to-fold transition occurs," Moon tells Phys.org. "The critical conditions as a function of the applied strain, initial wrinkle geometries, and thickness of the skin layer determined by oxygen plasma treatment duration were difficult to find." Moon adds that the observation technique for the dynamic transition was limited to only optical microscopes whose highest optical resolution falls between 100 to 1000 nm in the width of nanowires, this being due to the dynamic transition taking place at the submicron scale.

When inducing a template surface wrinkle-to-fold transition by exploiting the capillary forces of water containing DNA molecules, Stone points out, the observation that water changes the wrinkle-to-fold transition is new. "As far as we know, ours is the first study to show this effect, as is demonstrating one use of such folds for the alignment of DNA. Moreover, control of surface tension or resultant capillary forces and the area for fold formation is relatively hardand by adding DNA molecules to water, it appears that the surface tension is changed, so the fold transition length was shorter."

Template preparation used an oxygen plasma treatment of prestretched polydimethylsiloxane (or PDMS, a polymeric organosilicon compound) substrates for varying durations. "In fact," Moon explains, "the manipulation of PDMS with prestretching strain is a relatively well-developed method as is the oxygen plasma treatment: both have been discussed in the literature. We can make the samples with various sizes of a few millimeters to a few centimeters, which can be also made on much larger area." Moon notes that the researchers can also vary polydimethylsiloxane's mechanical propertiesto make it more stretchable, soft or flexibleby changing the ratio of elastomer and cross-linker for PDMS preparation.

A key aspect of the study was confirming that the new method reliably manipulates DNA nanowire size, geometry, and alignment. "By adjusting the conditions for stretching strain, plasma treatment duration, and post-compression of the stretched PDMS, DNA nanowires can be a half cylinder, a perfect cylinder, or undulated wire shape," Moon tells Phys.org. "By changing the wrinkle geometries such as the amplitudewhich is governed by the strainone can control the distance between wires in the fold channel." Wider distances between wires, he continues, can be accomplished by compressing the PDMS less, while compressing the substrate more yields smaller distances.

To address these challenges, the scientists discovered a transformation resulting from capillary forces that act at the edge of a water droplet that can, with only 1% compression, transform wrinkles into folds, which in the absence of a liquid drop form only at very high (~30%) compression. In addition, Moon adds, smaller substances such as biomolecules or nanoparticles can follow the water channel to form aligned 1-dimensional nanostructures. "Smaller is better. Less is more. We've found that the wrinkle-to-fold transition takes place more easily when the following factors become smaller: compression level, skin thickness, droplet volume, size of the sample surface, and static contact angles of droplets."

Based on their findings, the authors stated that their approach could lead to new ways of fabricating functional materials. "Our key finding is that one can change wrinkles into localized folds by simply exploiting the capillary forces of water on wrinkled surfaces under very small strain of about 1% in compression," Nagashima tells Phys.org. "Recent studies reported in the literature have demonstrated that such wrinkle-to-fold transitions can help develop systems that dynamically change their properties according to the surface morphology. However, inducing the transition in the absence of water is difficult to achieve in practice because, in general, large compression needs to be applied to the skin-substrate system, which hinders wider applications. Our study reveals that even 1% of compression, which is the critical level for creating wrinkles in our case, is large enough to trigger the transition to folds locally when water is present." Nagashima notes that while the compression level required to induce the transition might differ according to the skin-film system used, only a small compression level would be necessary in combination with water.

"This phenomenon can be considered a lithography-free method that allows for ready fabrication of arrays of nanomaterials, where their size, length, and periodicity could robustly be tuned," he continues. "Moreover, not only water but other liquids could be used to carry nanomaterials and to induce the wrinkle-to-fold transition."

Moon describes several examples of potential de novo fabrication and analysis techniques, including nanoscale lithography, nanoimprint, growth by chemical vapor deposition, and chemical reaction. "Our method can potentially be used for the fabrication of 1-dimensional nanowires or nanoarrays for application to DNA analysis with very dilute or small amounts of DNA; DNA templates as new metal or ceramic nanostructures; and DNA treatment devices for healing modified DNA. In addition, one can adopt this technique to handle protein, blood, or nanoparticles at nanoscale."

Komrlj and Stone tell Phys.org that one area of planned research is focused on nonlinear analysis and modeling for improved quantitative understanding of the capillarity-induced wrinkle-to-fold transition. "Since our system is composed of the mechanical behavior of the fold transition triggered by liquid surface tension, the wrinkle-to-fold transition that we've found is associated with large deformations where conventional linear elasticity theory does not apply. While the basic mechanisms can be explained within the linear theory, quantitative comparison with experiments can only be achieved by taking into account geometrical and material nonlinearities. We are therefore performing numerical simulations by coupling liquid surface tension and solid deformation, as well as performing analysis with perturbation series, where nonlinearities of elastic structures can be studied systematically."

"I also think that the challenges ahead are to find how to achieve larger areas for DNA pattern formation," Moon says. "In fact, our latest resultsobtained after this PNAS article was acceptedshows some impressive progress for the region with wrinkle-to-fold transition in larger areas, such as the entire area underneath a water droplet. Another area to be studied, Moon continues, concerns the fact that biological morphogenesis of skinsubstrate systems are ubiquitous in organisms where water is a major constituent. "We're trying to find situations where our findings are applicable. Active collaborations with experts in the field would be helpful."

The researchers might also investigate materials other than PDMS. "Yes. other polymers can work if they possess the basic factors to govern the fold transition, these being the thinness of the nano-skin and soft body materials, and surface hydrophilicity to ensure sufficient surface reaction with liquid," Moon notes.

Other possible future research interests and additional innovations mentioned by the authors include:

- theoretical analysis to elucidate the underlying physics related to the water-induced surface folding

- exploit the underlying physics to develop a robust and mass fabrication method for inducing the wrinkle-to-fold transition

- find and discuss morphological changes in nature where water is likely a key factor

- apply the current study's results to DNA analysis or DNA drug devices

- 2-D/3-D sensors, diagnostic tools, and drug-release systems

- templates for fabricating 1-dimensional nanomaterials

- methods for local patterning

"I believe that this work is beneficial to materials science for nanowire templates, mechanics for fluidic channels, and biology for quantitative analysis of DNA or other biomolecules," Moon concludes.

Explore further: Observation of the phase transition of liquid crystal defects for the first time

More information: Spontaneous formation of aligned DNA nanowires by capillarity-induced skin folding, PNAS (2017) 114:24 6233-6237, doi:10.1073/pnas.1700003114

Related:

1DNA nanowire fabrication, Nanotechnology (2006) 17:R14m https://core.ac.uk/download/pdf/1559975.pdf

2DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires, Science (2003) 301:5641 1882-1884, doi:10.1126/science.1089389

3Nanowire-Based Sensors for Biological and Medical Applications, IEEE Transactions on NanoBioscience (2016) 15:3 186-199, doi:10.1109/TNB.2016.2528258

4DNA-Based Applications in Nanobiotechnology, Journal of Biomedicine and Biotechnology (2010) Article ID 715295, doi:10.1155/2010/715295

5Nanowire nanosensors, Materials Today (2005) 8:5, doi:10.1016/S1369-7021(05)00791-1

2017 Phys.org

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Of wrinkles and wires: Capillarity-induced skin folding spontaneously forms aligned DNA nanowire - Phys.Org