Monthly Archives: April 2017

In Brief DNA protects itself from damage naturally, and scientists are hoping to gain insight into how the process works in order to achieve breakthrough treatments for cancer and other diseases that arise from the breakage and mutation of DNA. Simple Parameters, Complex Possibilities

DNA protects itself from damage naturally, and scientists are hoping to gain insight into how the process works. When DNA is bathed in ultraviolet light, it can eject a single proton from a hydrogen atom to rid itself of excess energy, ensuring other chemical bonds remain intact. This protective mechanism is called an excited state proton transfer, and it is the focus of new research by a team of scientists.

The researchers used the Linac Coherent Light Source (LCLS) at the SLAC National Accelerator Laboratory to generate X-ray laser pulses capable ofprobing the nitrogen molecule in the simple molecule 2-thiopyridone for quadrillionths of a second. The short period of time matters because when molecules are exposed to this kind of light they react incredibly quickly. The brightness of the light is equally important, because only very brilliant illumination renders these ultrafast changes visible to the researchers.

The researchers confirmed that optical light breaks nitrogen-hydrogen bonds, but the X-rays did not. This was important to the researchers because they wanted to confirm that any changes they were examining were related to the nitrogen atom or the area immediately surrounding it. The signature showing that the X-rays had been transformed into energy was the confirming resonance effect that they were looking for. On-resonance studies like this one allow researchers to clearly see how X-rays interact with samples because they amplify the signals for observation.

In future research, the team hopes to gain more insight into the greater class of photochemical reactions using the same approach to study more complex molecules. Knowing more about how molecules of all kinds protect themselves from radiation can help scientists achieve breakthrough treatments for cancer and other diseases that arise from the breakage and mutation of DNA.

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Scientists Witnessed DNA Protecting Itself From Radiation - Futurism

Millions of years ago, our ancestors bodies may have waged an epic battle against a virus. Through a sneaky DNA swap, the hosts would have gotten the upper hand, and turned the virus defenses against themselves. Researchers think theyve unearthed the whole ordeal, left like a Dead Sea scroll in our genes.

We know very little about ancient and extinct viruses, since they (mostly) cant form real fossils. But retroviruses, the type of viruses that include HIV, plug their own genetic material into the cells they infect. If a retrovirus infects cells that get passed to offspring, then we can potentially see exactly where and when it was around by looking at ancient and modern DNA. A team of researchers from Rockefeller University did just that, and found what looked like a cunning act of bodily revenge where our extinct hominid cousins used a viruses DNA against itself.

So the whole story is very exciting to me (with a little bit of bias of course since it was my PhD thesis work), first author Daniel Blanco Melo told Gizmodo in an email. From one side we were able to reconstruct a very old [viral] gene from destroyed sequences in primate genomes. And on the other hand we encounter that our ancestors were able to take some information of this virus and used it to drive its own extinction.

Viral archaeology is forensic game. The researchers were interested in studying whether there were any examples in history of hosts evolving protection against viruses, and came across HERV-T, a virus that probably left its genetic mark in germline cells, those that get passed from generation to generation including fetal cells, sperm cells and egg cells. That means the researchers were able to look at the DNA of ancient hominids to see whether or not they had HERV, checking out more and more distant cousins until they found one without the viral DNA. The number of years ago that an infected cousin and our ancestors split off on the evolutionary tree tells us about how old the virus is.

The researchers also investigated how HERV-T DNA mutated over time, by comparing data previously collected from several old world monkey species genomes, like gibbons and bonobos. Like trying to get two different cultures to remember a myth over a very long period of time, minor details change, and differences accumulate between species. The team knew the approximate DNA mutation rates in different species, and used the differences to approximate age of the virus.

HERV-T probably emerged between 30 and 40 million years ago, embedding its DNA into the cells of our ancestors. But where is it today? Thats where our cells may have performed a cunning evolutionary act. Based on their primate analysis, the researchers reconstructed the protein described by the HERV-T gene remnants in the DNA of modern humans. This ancient protein embedded itself in the envelope that encapsulated the virus DNA. The host used that protein to evolve a derivative of it that can essentially block the receptor from the cell surface, Paul D Bieniasz, the papers principle investigator from The Rockefeller University in New York, told Gizmodo, thereby inhibiting the infection by the replicating virus.

Basically, the viral intruder had a copy of the key to the house, but left it inside. Armed with that knowledge, our ancestors cells changed all the locks. Or, more accurately, they got rid of the doorknobs. The primates with the viral gene would have won the survival-of-the-fittest game, and the virus probably went extinct around ten million years ago. However, it is important to note that one anonymous reviewer of the paper, published today in the journal eLife, had some concerns with the evidence that the hsaHTenv ORF, the genetic sequence coding the resurrected protein, was maintained due to selective pressure. The researcher didnt think the evidence that natural selection caused us to continue producing the protein was convincing.

Despite this caveat, the researchers findings could be a first in viral archaeology. Weve known its possible for hosts to co-opt envelope proteins to protect themselves from retrovirus infection, but this is the first time its been demonstrated in hominids, our direct ancestors, said Bieniasz. Its also the first time an extinct virus protein has been resurrected.

Its important to note that this is just one study about one protein, and a many million year look into the past requires some degree of speculationwe werent around to observe the virus or its effects, after all.

The researchers think they might be able to use the protein in cancer research. They think they could make their own viruses stuffed with the ancient viral protein to target and kill cancer cells. Its unlikely that wed be able to cure ourselves of other retroviruses, though, like HIV, since most of them dont infect the germline cellswe wouldnt be able to pass resistance on to our children, or get all of our cells to develop resistance.

Regardless, just think, your DNA essentially contains ancient scrolls with evolutionary epics waiting to be read.

[eLife]

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Scientists Unearth Ancient DNA Depicting a Battle Between Viruses ... - Gizmodo

A state commission overseeing forensic science in New York is scheduled to take a key vote Wednesday that could pave the way for local law enforcement to begin using this summer the emerging technique of familial DNA searching to solve homicide and sex crimes.

The vote by the New York State Commission on Forensic Science is slated for Wednesday morning. The consent of at least seven members of the 14-person body is needed to approve regulations governing the use of the technique by DNA labs in the state, said a spokeswoman for the state Division of Criminal Justice Services.

A special DNA subcommittee last month approved the measure by a vote of 6-0, with one member absent. If the full commission approves the regulations, they would be published in the State Register and the public would have 45 days to comment before they take effect, DCJS spokeswoman Janine Kava said.

Familial searching is in use in 10 states, including California and Colorado. Law enforcement officials in Britain and the Netherlands also use it.

Law enforcement officials in New York City, including NYPD Commissioner James ONeill and Queens District Attorney Richard Brown, pushed for the procedure after a story last November in Newsday highlighted its potential use in the case of slain Howard Beach jogger Karina Vetrano.

Although the Vetrano probe led to an arrest using conventional methods, the family still supports familial searching.

This has to be done for other people, Vetranos father, Philip, told Newsday recently.

The searching method is called upon in cases where an unknown crime scene DNA sample as occurred in the Vetrano case has failed to match any genetic profiles in the state databases. The unknown sample is put through a two-step process that uses special software to produce a list of persons in the database who are likely close relatives of the person whose DNA was left at the crime scene. In the second step, a lineage test is done, usually involving the Y chromosome, to confirm the relationship.

Armed with the test results, police would question the identified relatives of the person under scrutiny to try and locate and obtain a DNA sample from the person of interest. In about 36 percent of cases the investigations lead to the identification of a suspect, according to a 2015 report by the National Institute of Justice.

Under the New York proposal, crimes for which the technique can be used include homicide, first-degree rape, sexual assault, arson, first-degree kidnapping and crimes involving a significant threat to public safety. Strict privacy controls are required.

Civil libertarians and some defense attorneys have criticized the technique. At a February public hearing, Erin Murphy, a professor at New York University School of Law, said it can put relatives of somebody with a criminal record unfairly under suspicion as a possible suspect simply because of a blood relationship.

Murphy also said that there was racial bias at play since people of color are convicted in numbers proportionately greater than their population sizes and have their DNA on file.

But proponents stress that the technique is race-neutral, can clear innocent people and that people of color are overrepresented in the population of both crime victims and suspects. A police source said of the 11 unsolved homicides in New York in 2016 with unknown DNA samples, nine involved black victims, one Hispanic and one white.

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State panel to consider new DNA technique to ID crime suspects ... - Newsday

April 11, 2017 In the original CRISPR-Cas9 technique (top), the guide RNA (green) binds to the target DNA and the cleavage enzyme Cas9 (scissors) cuts out a small DNA sequence (red). A modified version of Cas9 called nCas9 (bottom) is different as it cuts off only one strand of DNA and the cytidine deaminase (pink) transforms a single cytosine (C) into uracil (U). Uracil (U) is then converted to thymine (T) by DNA replication. Credit: IBS

Researchers at the Institute of Basic Science (IBS) proved the accuracy of a recently developed gene editing method. This works as "DNA scissors" designed to identify and substitute just one nucleotide among the 3 billion. "It is the first time that the accuracy of this base editor has been verified at the whole genome level," explains KIM Jin-Soo, leading author of the study. Published in Nature Biotechnology, this validation will help to expand the use of this method in agriculture, livestock, and gene therapy.

Rapid advances in gene editing tools have created excitement in the biology community. The primary third-generation DNA editing technology is CRISPRa tool that is quicker and cheaper than its predecessors. By cutting out a small DNA sequence, CRISPR-Cas9 and CRISPR-Cpf1 are used to silence or reduce the expression of faulty genes. However, last year, biologists discovered a new base editor method that does not cause random DNA deletions and insertions, but instead replaces only one DNA base. These types of gene corrections are critical, as several diseases are caused by the misspelling of one of the four basic components of DNA; adenine (A), cytosine (C), guanine (G), and thymine (T). Single-nucleotide errors in DNA are referred to as point mutations. Examples of conditions caused by point mutations include cystic fibrosis, sickle cell anemia and color blindness.

Unlike the existing technologies, the base editor method consists of a variation of CRISPR-Cas9 (nCas9, nickase) fused with another enzyme called cytosine deaminase, which replaces the DNA component C with T. The scissors are directed to the correct position on the DNA by a guide RNA. However, until recently, it was not known whether the base editor was working only in the area of the faulty gene or if it was unnecessarily substituting Cs in off-target areas.

Just one month after reporting the first successful base editing in animals in Nature Biotechnology to modify a single nucleotide in dystrophin and tyrosinase genes, the same team demonstrated the accuracy of this method at the genome scale.

In order to identify the soundness of the method, IBS researchers modified the error-checking technique known as Digenome-seq, in order to adapt it to the base editor method. Digenome-seq was used and validated last year, when the team analyzed the accuracy of CRISPR-Cpf1 and Cas9. IBS researchers also improved the computer program Digenome 2.0 to identify off-targets more comprehensively and compared different guide RNAs to find the one that reduces malfunctions and increases specificity.

Using this technique, the team found the base editing technique to be even more accurate than the current third-generation CRISPR-Cas9. The base editing technique induced C-to-T conversions in multiple sites in the human genome, while CRISPR-Cas9 caused cleavages in multiple sites, meaning that the new base editor technique makes fewer off-target changes. "Therefore, it is expected that these base editors will be used as widely as the popular CRISPR technology," says KIM.

Explore further: First CRISPR single-nucleotide edited transgenic mice

More information: Genome-wide target specificities of CRISPR RNA-guided programmable deaminases, Nature Biotechnology (2017). nature.com/articles/doi:10.1038/nbt.3852

Cystic fibrosis, sickle cell anemia, Huntington's disease and phenylketonuria are all examples of disorders caused by the mutation of a single nucleotide, a building block of DNA. The human DNA consists of approximately 3 ...

A team from the Center for Genome Engineering, within the Institute for Basic Research (IBS), succeeded in editing two genes that contribute to the fat contents of soybean oil using the new CRISPR-Cpf1 technology: an alternative ...

(Phys.org)A team of researchers affiliated with Harvard University and the Howard Hughes Medical Institute has announced the development of a gene-editing system that improves on the performance of CRISPR/Cas9 by allowing ...

(Phys.org)A team of researchers with members from several institutions in Japan has developed a new way to edit genes that involves cutting just one strand of DNA rather than both of them, as is normal for CRISPR-Cas9. ...

CRISPR-Cas9's popularity continues to grow ever since its first use in genome editing in January, 2013. What makes CRISPR-Cas9 so remarkable is its astonishing efficiency and availability; relatively speaking, it is easy ...

Researchers from Memorial Sloan Kettering Cancer Center (MSK) have harnessed the power of CRISPR/Cas9 to create more-potent chimeric antigen receptor (CAR) T cells that enhance tumor rejection in mice. The unexpected findings, ...

A University of Wyoming weed scientistfrustrated with the noise surrounding genetically modified organisms and glyphosate useanalyzed data to see for himself if biotech adoption has had a negative or positive effect ...

How can you tell if an individual is expressing sexual interest? With males, it's usually quite obvious and can be anything from lavish theatrical displays of song and dance to downright relentless insistence. Females, on ...

Researchers at the University of Alberta have demystified the way that polar bears search for their typical prey of ringed seals. The answer, it turns out, is simple: they follow their nose using the power of wind.

Asian elephants are able to recognise their bodies as obstacles to success in problem-solving, further strengthening evidence of their intelligence and self-awareness, according to a new study from the University of Cambridge.

Millions of years before humans discovered agriculture, vast farming systems were thriving beneath the surface of the Earth. The subterranean farms, which produced various types of fungi, were cultivated and maintained by ...

One of the largest colonies of gentoo penguins in Antarctica was decimated by volcanic eruptions several times during the last 7,000 years according to a new study. An international team of researchers, led by British Antarctic ...

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Accurate DNA misspelling correction method - Phys.Org