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Category Archives: Transhuman News

Researchers develop new tool for making genetic engineering of microbial circuits reliably predictable

Posted: October 10, 2012 at 3:13 am

Fluorescence microscopy images of cells containing various plasmid pairs which were constructed with the help of a tna element adaptor and logic gates driven by two, three or four RNA inputs that linked to ribosome binding sites.

(Phys.org)Synthetic biology is the latest and most advanced phase of genetic engineering, holding great promise for helping to solve some of the world's most intractable problems, including the sustainable production of energy fuels and critical medical drugs, and the safe removal of toxic and radioactive waste from the environment. However, for synthetic biology to reach its promise, the design and construction of biological systems must be as predictable as the assembly of computer hardware.

An important step towards attaining a higher degree of predictability in synthetic biology has been taken by a group of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) under the leadership of computational biologist Adam Arkin. Arkin and his team have developed an "adaptor" that makes the genetic engineering of microbial components substantially easier and more predictable by converting regulators of translation into regulators of transcription in Escherichia coli. Transcription and translation make up the two-step process by which the coded instructions of genes are used to synthesize proteins.

"Application of our adaptor should produce large collections of transcriptional regulators whose inherent composability can facilitate the predictable engineering of complex biological circuits in microorganisms," Arkin says. "This in turn should allow for safer and more efficient constructions of increasingly complex functions in microorganisms."

Arkin is the director of Berkeley Lab's Physical Biosciences Division and the corresponding author of a paper describing this work in Nature Methods. The paper is titled "An adaptor from translational to transcriptional control enables predictable assembly of complex regulation. Co-authoring this paper were Chang Liu, Lei Qi, Julius Lucks, Thomas Segall-Shapiro, Denise Wang and Vivek Mutalik.

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When a bacterial translational regulator is fused to a tna element adaptor, it is able to also regulate transcriptional elongation.

"Much of the regulatory potential of a bacterium is contained in the five-prime untranslated regions (UTRs), which control the expression of physically adjacent downstream genes and have become attractive platforms for a parts-based approach to synthetic biology," Arkin says. "This approach, in which integrated engineered regulatory parts respond to custom inputs by changing the expression of desired genes, must satisfy two criteria if it is to have long-term success. First, the regulatory parts must be easily engineered in a way that yields large homogenous sets of variants that respond to different custom inputs, and second, the parts must be composable such that they can be easily and predictably assembled into useful higher-order functions."

In the five prime UTRs of bacteria, two primary types of regulators can serve as starting points for designing new parts those that regulate transcriptional elongation, in which cellular inputs are linked to the process by which a sequence of DNA nucleotides is transcribed into a complementary sequence of RNA; and those that regulate translation, in which a ribosome translates the RNA message into a protein. Transcriptional elongation regulators meet the second criterion by featuring versatility and composability that makes them ideal for building custom regulatory functions. Translational regulators meet the first criterion by being easier to engineer and relatively common to all bacteria.

"Our solution for meeting both criteria was to develop an adaptor based on tryptophanase, the catabolic operon for tryptophan that converts regulators of translational initiation into regulators of transcriptional elongation," Arkin says. "Because our adaptor strategy bypasses the otherwise restrictive tradeoff between criterion one and criterion two, we believe it will have a crucial role in the long-term development of five prime UTRs as platforms for the design and integration of custom regulatory parts."

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Researchers develop new tool for making genetic engineering of microbial circuits reliably predictable

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New tool for making genetic engineering of microbial circuits reliably predictable

Posted: at 3:13 am

ScienceDaily (Oct. 8, 2012) Synthetic biology is the latest and most advanced phase of genetic engineering, holding great promise for helping to solve some of the world's most intractable problems, including the sustainable production of energy fuels and critical medical drugs, and the safe removal of toxic and radioactive waste from the environment. However, for synthetic biology to reach its promise, the design and construction of biological systems must be as predictable as the assembly of computer hardware.

An important step towards attaining a higher degree of predictability in synthetic biology has been taken by a group of researchers with the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab) under the leadership of computational biologist Adam Arkin. Arkin and his team have developed an "adaptor" that makes the genetic engineering of microbial components substantially easier and more predictable by converting regulators of translation into regulators of transcription in Escherichia coli. Transcription and translation make up the two-step process by which the coded instructions of genes are used to synthesize proteins.

"Application of our adaptor should produce large collections of transcriptional regulators whose inherent composability can facilitate the predictable engineering of complex biological circuits in microorganisms," Arkin says. "This in turn should allow for safer and more efficient constructions of increasingly complex functions in microorganisms."

Arkin is the director of Berkeley Lab's Physical Biosciences Division and the corresponding author of a paper describing this work in Nature Methods. The paper is titled "An adaptor from translational to transcriptional control enables predictable assembly of complex regulation. Co-authoring this paper were Chang Liu, Lei Qi, Julius Lucks, Thomas Segall-Shapiro, Denise Wang and Vivek Mutalik.

Synthetic biology combines modern principles of science and engineering to develop novel biological functions and systems that can tackle problems natural systems cannot. The focus is on bacteria and other microbes that can metabolize a wide variety of valuable chemicals and molecules, and play a critical role in the global cycles of carbon and other important elements. One of the keys to success in synthetic biology is the design and construction of customized genetic switches in microbes that can control the expression of both coding and non-coding RNA, act on operons (small groups of genes with related functions that are co-transcribed in a single strand of messenger RNA), and be tethered to higher-order regulatory functions (a property called composability).

"Much of the regulatory potential of a bacterium is contained in the five-prime untranslated regions (UTRs), which control the expression of physically adjacent downstream genes and have become attractive platforms for a parts-based approach to synthetic biology," Arkin says. "This approach, in which integrated engineered regulatory parts respond to custom inputs by changing the expression of desired genes, must satisfy two criteria if it is to have long-term success. First, the regulatory parts must be easily engineered in a way that yields large homogenous sets of variants that respond to different custom inputs, and second, the parts must be composable such that they can be easily and predictably assembled into useful higher-order functions."

In the five prime UTRs of bacteria, two primary types of regulators can serve as starting points for designing new parts -- those that regulate transcriptional elongation, in which cellular inputs are linked to the process by which a sequence of DNA nucleotides is transcribed into a complementary sequence of RNA; and those that regulate translation, in which a ribosome translates the RNA message into a protein. Transcriptional elongation regulators meet the second criterion by featuring versatility and composability that makes them ideal for building custom regulatory functions. Translational regulators meet the first criterion by being easier to engineer and relatively common to all bacteria.

"Our solution for meeting both criteria was to develop an adaptor based on tryptophanase, the catabolic operon for tryptophan that converts regulators of translational initiation into regulators of transcriptional elongation," Arkin says. "Because our adaptor strategy bypasses the otherwise restrictive tradeoff between criterion one and criterion two, we believe it will have a crucial role in the long-term development of five prime UTRs as platforms for the design and integration of custom regulatory parts."

When an E.coli translational regulator was fused to the adaptor created by Arkin and his colleagues, it was also able to control transcriptional elongation. The team applied their adaptor to the construction of several transcriptional elongation regulators that respond to RNA and small-molecule inputs. Included were five mutually orthogonal RNA-triggered attenuators (meaning they can terminate transcription), which the team assembled into logic gates driven by two, three or four RNA inputs that linked to ribosome binding sites. Because their adaptor is so easily linked to ribosome binding sites, a common mechanism in bacteria, the team believes the adaptor will be widely applicable.

"Continued application of our adaptor should produce large collections of transcriptional regulators whose inherent composability can facilitate the predictable engineering of complex synthetic circuits," Arkin says.

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Outsmarting breast cancer

Posted: at 3:13 am

In a groundbreaking study hailed as a roadmap for new targeted treatments, Professor Charles Perou and his colleagues collected DNA and tumor samples from 825 breast cancer patients for the first comprehensive look at the underlying genetics behind the deadly disease.

The researchers conducted an exhaustive examination of all 20,000 or so genes in the human body for each sample. They were looking for patterns of genetic mutations that promote the tumors and can potentially be counteracted with new or even existing drugs.

Its a mountain of data, but Perou never forgets those samples came from real human beings grappling with a terrifying diagnosis.

Its what drives him.

Dozens of those women will likely die of the disease. Some surely already have in just the few years since the samples were collected.

I think about that all the time. Personally, its a huge motivation for me. These studies are dealing with real human beings and every death is a tragedy, said Perou, a professor of genetics at the University of North Carolina and the lead author on the study which was published in the journal Nature and is part of a large federal project, the Cancer Genome Atlas, looking at genetic mutations associated with various types of cancer.

Perou said the term genetics can be confusing. Whats at issue is not the so-called breast cancer genes, by which a person inherits a susceptibility to breast cancer. About 10 percent of women with breast cancer fall into that category.

We are talking about the other 90 percent of women who are presumably born with no particular tendency to develop the disease. For those women, one in eight will develop breast cancer and seven in eight will not.

In all those cases, there are genetic mutations that cause the disease, Perou said.

The genome study does not address the vital but murky question of what causes those mutations.

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This Week in PNAS

Posted: at 3:13 am

An international team led by investigators at the French National Institute for Agricultural Research, the US Department of Energy's Joint Genome Institute, and the Wellcome Trust Centre for Human Genetics presents results from a genome sequencing study of the button mushroom, Agaricus bisporus, in the early, online issue of the Proceedings of the National Academy of Sciences. The team generated draft genome sequences for two A. bisporus representatives a cultivated European strain from the A. bisporus variety bisporus and a California strain from the burnetti variety that makes it home in the leaf litter around woody plants. By folding in transcriptome data for different mushroom developmental stages and for mushrooms grown on different substrates, the group uncovered clues about the fungal adaptations that the mushroom uses for growth in humic acid-rich environments, including genes coding for enzymes involved in the decomposition of leaves and other plant materials.

Adult stress levels and socio-economic status during childhood appear to influence some DNA methylation differences that exist between individuals within a community, according to a study by researchers at the University of British Columbia, Simon Fraser University, and Stanford University. The researchers performed array-based DNA methylation profiling on peripheral mononuclear white blood cells from 92 individuals between the ages of 24 and 45 from a community in and around Vancouver, Canada. When they looked at how methylation patterns at the promoters of nearly 14,500 human genes corresponded to individuals' gene expression profiles, blood composition, early-life socio-economic status and so on, the researchers found several factors that seemed to coincide with inter-individual methylation differences. These included the proportion of different white blood cell types present in the individuals' sample, their stress hormone output sex, age, and ethnicity as well as experiences such as childhood poverty and stress during adulthood. Even so, the DNA methylation differences detected often did not coincide with gene expression shifts at nearby genes, the researchers reported, "suggesting a more complex relationship than anticipated."

Another PNAS study looks at the bacterioplankton communities present in ocean samples collected in the Antarctic and the Arctic. By sequencing the V6 region of the 16S ribosomal RNA gene, Desert Research Institute investigators Alison Murray and colleagues from several centers around the world catalogued the bacteria found in surface or deep water bacterioplankton communities in the Southern and Arctic Oceans. The researchers then looked at how deep-water and shallow-water communities in the 20 Southern Ocean samples and the 24 Arctic Ocean samples tested compared with one another and with four-dozen samples collected at lower latitude ocean sites. "Our results suggest differences in environmental conditions at the poles and different selection mechanisms controlling surface and deep ocean community structure and diversity," the study's authors say. "Surface bacterioplankton may be subjected to more short-term variable conditions, whereas deep communities appear to be structured by longer water-mass residence times and connectivity through ocean circulation."

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DNA from cigarette solves 1998 rape

Posted: at 3:12 am

Steve Wisbauer/Getty Images

DNA from a cigarette butt left near a rape scene in 2011 links a Staten Island man to a brutal 1998 rape.

A Staten Island man who raped and robbed a college professor nearly 14 years ago, holding a piece of broken glass to her neck, pleaded guilty to the heinous crime on Tuesday, after being busted by DNA from a cigarette he discarded near the scene of another sexual assault.

Lerio Guerrero, 34, tossed a cigarette butt near the scene of a 2011 sexual assault in Brooklyn. While he was never charged in that rape, police arrested him for trespassing and matched his DNA to the cigarette.

A search of the state DNA database came up with a hit from the rape on Orchard St. on a chilly November night back in 1998.

A masked Guerrero pushed a 28-year-old professor as she stepped into her apartment building, then raped and sodomized her.

Not satisfied with just brutalizing her and taking what was left in her wallet, the sicko dragged her to an ATM to steal her money.

"He held a piece of broken glass against her neck. He said there was not enough money in her wallet," said Assistant District Attorney Martha Bashford. The prosecutor said he made her call her credit card company to allow him to steal more money out of her account.

He robbed her of $800, but as he forced her to a second ATM, the victim was able to break free and get help.

Without having the name of a suspect, in 2005 prosecutors indicted just the DNA extracted from the blood he left behind on the victim's coat when he cut his hand on the jagged piece of glass.

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Glowing DNA invention points towards high speed disease detection

Posted: at 3:12 am

ScienceDaily (Oct. 9, 2012) Many diseases, including cancers, leave genetic clues in the body just as criminals leave DNA at the scene of a crime. But tools to detect the DNA-like sickness clues known as miRNAs, tend to be slow and expensive. Now a chemist and a biologist from University of Copenhagen have invented a method that promises to shave days off the lab work done to reveal diseases, using cheap methods and easy to use analytical apparatuses.

Chemistry researcher Tom Vosch and plant molecular biologist Seong Wook Yang invented a DNA sensor, coupling genetic material to a luminous molecule which goes dark only in the presence of a specific target. Details on their invention, Silver Nano cluster DNA-probes, are published in the high profile scientific journal ACS Nano, and Tom Vosch is understandably proud of the invention.

"We invented a probe that emits light only as long as the sample is clean. That is an unusually elegant and easy way to screen for a particular genetic target," says Vosch of the Department of Chemistry's Nano Science Centre.

DNA clues help detect disease

You could say that the inventors took their cue from crime detection. In murder cases police technicians use DNA to identify the killer. Similarly Individuals with disease are likely to have a unique miRNA profile. Any disease that is attacking a patient leaves this genetic clue all over the victim. And because the profiles of miRNAs vary by type of cancer, finding it proves beyond a reasonable doubt what made the patient sick.

Gene magnets stick to opposites

The new detection method exploits a natural quality of genetic material. A single DNA strand is made up of molecules, so called bases, ordered in a unique combination. When two strands join to form their famous double helix, they do so by sticking to complementary copies of themselves. Likewise strands tailored to match particular miRNAs will stick to the real thing with uncanny precision. But detecting this union of the strands was only made possible when Vosch and Yang paired their skills.

A real kill switch

Tom Vosch is specialized in studying molecules that light up. Seong Wook Yang is specialized in miRNA. Together they figured out how to attach the light emitting molecules to DNA sensors for miRNA detection. Vosch and Yang discovered, that when these luminous DNA-strands stick with microRNA-strands, their light is snuffed out, giving a very visible indication that the target miRNA is present in the sample. In other words: When the light goes out, the killer is in the house.

Likely to lead to high speed cancer diagnostics

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Rayney trial: London expert's DNA tests proved nothing

Posted: at 3:12 am

HAPPIER TIMES: Lloyd and Corryn Rayney on a family holiday in Canada in late 2003-early 2004. Source: PerthNow

A DNA expert based in London was called in to investigate whether Lloyd Rayney or another, unidentified "person of interest" were involved in the 2007 death of Mr Rayney's estranged wife, Supreme Court registrar Corryn Rayney.

But tests by forensic scientist Rosalyn Treliving did not shed any light on who may have been responsible for Mrs Rayney's death.

Ms Treliving, who specialises in the analysis of body fluids and the interpretation of DNA profiles, was asked by Major Crime Squad officers to examine hairs, DNA extracts and a handkerchief collected from crime scenes related to the case.

In a written statement tendered to the Supreme Court in Perth, she said her DNA tests were to "assist in addressing the issue" of whether Mr Rayney or a second person - whose name has been withheld - were involved in Mrs Rayney's death on August 7, 2007.

She said she understood Mr Rayney and the second individual were both "persons of interest" in the investigation.

The prominent Perth barrister has been on trial for three months charged with wilfully murdering his wife at the family home in Como on the night of August 7, 2007.

Prosecutors have alleged that Mr Rayney killed Mrs Rayney at their home before placing her body in the back of her State-issued car and driving to Kings Park where he buried her in a clandestine bush grave.

He has pleaded not guilty.

Ms Treliving said she examined hair and DNA extracts from Mrs Rayney's car; hair samples from outside the Rayneys' Como home; a handkerchief found in Mrs Rayney's grave; DNA from a tree branch near the gravesite and DNA extracts from hairs found at the grave, on Mrs Rayney's clothing and in the body bag in which she was placed after being removed from the grave.

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Mystery of DNA decay unravelled

Posted: at 3:12 am

A new study is finally laying to rest the debate over whether DNA from the age of the dinosaurs could survive to the present day.

Scientists at Murdoch University led a study which shows the rate of DNA degradation and calculates that all bonds in a DNA strand preserved at the ideal temperature of minus five degrees centigrade would be completely destroyed in bone after approximately 6.8 million years.

This figure is incompatible with the idea of finding intact DNA in an 80 million year old dinosaur remnant, as was famously alluded to in the Steven Spielberg film Jurassic Park, but is much older than the currently accepted record of 450,000 to 800,000-year-old DNA from Greenlandic ice cores.

Dr Mike Bunce and Dr Morten Allentoft from Murdoch Universitys Ancient DNA lab came to their conclusions after studying 158 fossilised leg bones belonging to three species of the moa, an extinct group of birds that once roamed New Zealand.

It has been agonisingly difficult to estimate the rate of DNA decay before now because finding a large set of DNA-containing fossils with which to make meaningful comparisons are exceedingly rare, said Dr Bunce.

Environmental conditions like temperature, degree of microbial attack and oxygenation, can affect the DNA decay process and make it hard to detect a basic rate of degradation.

The moa bones however have allowed us to study the comparative DNA degradation because they come from different ages from a region where they have all experienced the same environmental conditions.

The fossil bone specimens were carbon dated as being between 600 and 8000 years old and looking at the varying degrees of DNA degradation in each specimen, the team were able to calculate a DNA half-life of 521 years. The half-life is the amount of time taken for an amount of DNA to reach 50 per cent of the starting amount.

The scientists found that the estimated decay rate in the specimens was almost 400 times slower than predicted from simulation experiments carried out in the lab.

Based on these calculations and other investigations, the team were able to make their predictions of DNA survival deeper into time.

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DNA has a 521-year half-life

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Palaeogeneticist Morten Allentoft used the bones of extinct moa birds to calculate the half-life of DNA.

M. Mhl

Few researchers have given credence to claims that samples of dinosaur DNA have survived to the present day, but no one knew just how long it would take for genetic material to fall apart. Now, a study of fossils found in New Zealand is laying the matter to rest and putting paid to hopes of cloning a Tyrannosaurus rex.

After cell death, enzymes start to break down the bonds between the nucleotides that form the backbone of DNA, and micro-organisms speed the decay. In the long run, however, reactions with water are thought to be responsible for most bond degradation. Groundwater is almost ubiquitous, so DNA in buried bone samples should, in theory, degrade at a set rate.

Determining that rate has been difficult because it is rare to find large sets of DNA-containing fossils with which to make meaningful comparisons. To make matters worse, variable environmental conditions such as temperature, degree of microbial attack and oxygenation alter the speed of the decay process.

But palaeogeneticists led by Morten Allentoft at the University of Copenhagen and Michael Bunce at Murdoch University in Perth, Australia, examined 158 DNA-containing leg bones belonging to three species of extinct giant birds called moa. The bones, which were between 600 and 8,000 years old, had been recovered from three sites within 5 kilometres of each other, with nearly identical preservation conditions including a temperature of 13.1 C. The findings are published today in Proceedings of the Royal Society B1.

By comparing the specimens' ages and degrees of DNA degradation, the researchers calculated that DNA has a half-life of 521 years. That means that after 521 years, half of the bonds between nucleotides in the backbone of a sample would have broken; after another 521 years half of the remaining bonds would have gone; and so on.

The team predicts that even in a bone at an ideal preservation temperature of 5 C, effectively every bond would be destroyed after a maximum of 6.8 million years. The DNA would cease to be readable much earlier perhaps after roughly 1.5 million years, when the remaining strands would be too short to give meaningful information.

This confirms the widely held suspicion that claims of DNA from dinosaurs and ancient insects trapped in amber are incorrect, says Simon Ho, a computational evolutionary biologist at the University of Sydney in Australia. However, although 6.8 million years is nowhere near the age of a dinosaur bone which would be at least 65 million years old We might be able to break the record for the oldest authentic DNA sequence, which currently stands at about half a million years, says Ho.

The calculations in the latest study were quite straightforward, but many questions remain.

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DNA has a 521-year half-life

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Applied DNA Sciences and 3SI Use DNA to Protect Teller Stations

Posted: at 3:12 am

STONY BROOK, NY--(Marketwire - Oct 9, 2012) - Applied DNA Sciences, Inc. ( OTCBB : APDN ), (Twitter: @APDN), a provider of DNA-based anti-counterfeiting technology and product authentication solutions, announced today that 3SI Security Systems is expanding its use of APDN's SigNature DNA evidence marking product into 3SI smoke and dye cash protection systems used across Europe. First orders, to the banking sector, are already being processed.

3SI Security Systems is a world leader in cash protection systems designed to recover stolen cash and high-value assets, apprehend criminals and deter crime.

The smoke and dye system, called Thinpac, is already in use in over 130,000 locations worldwide, with great success at deterring crime. 3SI called the addition of SigNature DNA marking to the Thinpac "a unique and leading edge security feature which we are happy to be able to offer to our customers." The company points out that "SigNature-DNA-tagged items can be identified unequivocally with a marker unique to a specific Thinpac, and hence unique to a particular crime. Any item, cash or person that comes in contact with the smoke will be marked by the SigNature DNA."

Police forces across Europe are becoming more familiar with the use of unique SigNature DNA markers in cash-protection systems, placing them in a much better position to catch and convict criminals. SigNature DNA provides police with a welcome additional investigative tool, which often reduces the amount of time it takes the police to undertake such investigations.

James Hayward, Chairman and CEO of Applied DNA Sciences, said, "Our SigNature DNA product is now used in many countries across Europe and is increasingly popular with police. One of our best examples of how the police make excellent use of our DNA to catch criminals is in the United Kingdom where 48 criminals have already been convicted and jailed for over 242 years, providing a great deterrent that has helped to significantly reduce the number of Cash in Transit robberies."

SigNature DNA is used to protect approximately 26% of cash movements in the United Kingdom.

Protection of bank tellers adds to APDN's portfolio of cash protection products. 3SI already uses APDN SigNature DNA marks to protect nearly 5,000 ATMs, using a DNA liquid which is placed in ink tanks that are fitted inside individual ATM cassettes. The cassette activates when triggered, marking all the cash inside the ATM and the criminals.

David Stanks, CEO of 3SI Corporation noted, "We have proven that we can significantly extend the value of our solutions by including the SigNature DNA products. This is a logical continuation of our strategy to deter crime and protect people."

About Applied DNA Sciences

APDN is a provider of botanical-DNA based security and authentication solutions that can help protect products, brands and intellectual property of companies, governments and consumers from theft, counterfeiting, fraud and diversion. SigNature DNA and smartDNA, our principal anti-counterfeiting and product authentication solutions that essentially cannot be copied, provide a forensic chain of evidence and can be used to prosecute perpetrators.

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