Category Archives: DNA

Momentum has been widely commended by 888 as a crucial component to recent successes, with a significant ramp up in its US operations set to continue with further deployments throughout the year as the operator strives to execute against its strategic plan.

The comments come from Yaniv Sherman, SVP and head of the US at 888, who also confirmed quotes made by CEO Itai Pazner to Bloomberg last month, which suggested that the group is exploring a potential public listing as it looks at ways to further tap into the US market.

This isnt media speculation our CEO stated openly that is definitely part of our strategic direction, but how and when we do is still to be determined, and part of our overall company and US strategy, Sherman commented.

Last month, the online betting and gaming firm heaped praise on a landmark year, as it scored record levels of revenue and adjusted EBITDA amid significant strategic progress.

The digital gambling group reported revenue of $849.7m, a 51.6 per cent increase from the prior years $560.3m, with adjusted EBITDA up 69 per cent to $155.6m (2019: $92.1m), and profit before tax down 41.1 per cent from $45.3m to $26.7m.

The groups B2C business, made up of casino, sports, poker, and bingo, rose 53.5 per cent to $814.3m (2019: $530.5m), with the former of those taking the lions share, rising 63.3 per cent to $586.8m (2019: $359.3m). 888 puts this down to the result of added investment, which brought an enhanced suite of content.

Sherman said of the major contributing factors: We entered 2020 with strong momentum, having just concluded our best acquisition year in 2019 with over one million new members and growth around our casino and sport verticals.

Growing any vertical in the UK nowadays should be considered an achievement

Obviously the global pandemic has accelerated what looks like a structural shift from retail to online, so the heightened activity levels through the second and third quarters translated into a tailwind which translated to even higher growth trend.

On delivering growth across the aforementioned four core B2C divisions, he added: It was extremely satisfying, especially considering the challenges this year brought, with all of our global sites working from home for the majority of the year. The 888 DNA really shined through.

In delivering its latest trading update, 888 said that, despite B2C bingo delivering growth, of 9.9 per cent to $42.3m (2019: $38.5m), the increasingly strict regulatory atmosphere combined with limited growth opportunity in its main market, the UK, led to an increased focus on other product and geographic opportunities.

Bingo and our overall UK business was no exception as far as outperforming our peers, Sherman commented on the division, as well as the UK region in general.

Growing any vertical in the UK nowadays should be considered an achievement, and we did so because we embrace regulation and responsible gaming as opposed to treating it as a threat. Your ability to operate under such conditions becomes a differentiator and a competitive edge.

The US possibilities, particularly regarding 888, have been widely documented on CasinoBeats thus far in 2021, however, it perhaps comes as little surprise that attention turns to the jurisdiction once more when looking at the period that lies ahead.

After the US was again pinpointed for particular praise regarding its significant potential, Sherman closes the discussion by touching upon what the immediate future holds in the country for the company: 2020 and 2021 mark a significant ramp up in our US focus and investments, with additional market access deals, a major platform overhaul and extending our strategic relationship with Caesars and WSOP.

This investment is expected to deliver a return this year and into the next few years, as we further expand our product and commercial footprint into more and more states.

We aim to deploy Poker8 and our Spectate proprietary sportsbook later this year, which should further enable us to execute against our strategic plan in the US.

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Yaniv Sherman The 888 DNA shined through in a landmark year - Casino Beats

When you're short of ideas for somebody's birthday,this tale of a DNA test gone wrong may just convince you to stick to picking up chocolates and flowers at a gas station because honestly, anything is better than this.

A 22-year-old Canadian namedMatilda has explained the story of when her then-boyfriend bought her a genetic test to help her figure out some of her family history.

"For my birthday last year, my exgot me one of those DNA test kits," she said in a video that has received over 100,000 likes. "My mom is adopted and I never really knew my biological father.So I was mostly interested in the health information, you know, see if there was anything that I needed tolook out for."

He got one for himself because they were on sale (some more great boyfriending there), and they sent them off to be analyzed.

"So we got the results back about a month later and I was looking through the genetic relatives because the only person that I know that I'm technically related to is my mom," Matildacontinued in her video. "And I was scrolling down and I turned to my boyfriend at the time and I say, 'hey this is pretty nifty,This person hasthe same name as you'."

"And that's how I found out I was dating my cousin."

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The comment section of the TikTok turned into a round of Everybody Confesses To Incest, a game show I just invented that all the networks are too cowardly to commission.

"I'm from NL and me and my husband did 23 and me," one user wrote."We are distantly related."

For others, things progressbeyond marriage to the point where things get genetically quite complicated, as this study on the incest of royal families in Europe will attest.

"My parents found out they were cousins too and well," one person wrote. "They didn't stop dating cause obviously I'm here. Uhhh."

Others made weird discoveries that they were their own sixth cousin. Strange as this sounds, it's possible, given that the various stages of cousins mean you share an ancestor. For instance, the person above would be their own secondcousin, as asecond cousin is your parents cousins child, and their parents were first cousins.

Here's a cousin calculator if you're interested, or have just taken a DNA test with results that do not spark joy. Or if you'd like a general explainer of how complicated family trees can get, even without getting very incesty, check out this song and diagram about a man who becomes his own grandpa.

Back toMatilda. They broke up, partly because of other issues and partly because they discovered they were related.

She later discovered that the site thought that they were likely third cousins, as they shared great-great-grandparents.

"I was able to do a bit of research into my biological father's side of the family and I actually found someone that had done a genealogical report back to the 1500s," she added.

"Based on the stuff from that person's research, as well as the percentage of DNA my ex and I shared which was a little bit too high to be third cousins I'mpretty sure we are actually second cousins, related through my paternal great grandmother Katerina."

"My ex is a great guy and I still care for him deeply," she added in her final video on the topic. "But yeah..."

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Man Buys Girlfriend A DNA Testing Kit For Her Birthday, They Find Out They're Closely Related - IFLScience

Enhancing liquid biopsies

Liquid biopsies, analyses of cell-free DNA that circulates in the blood, can be used in prenatal testing, oncology, and to monitor organ transplant recipients. Lo et al. review the nongenetic information that can be gleaned from analyses of cell-free DNA, which offers additional promise for the applications of this procedure. These analyses include DNA methylation patterns, fragmentation profiles, and topology, which can be informative about the health and origin of the tissue from which they are derived.

Science, this issue p. eaaw3616

Liquid biopsies that are based on analysis of cell-free DNA from plasma offer diagnostic information that is otherwise accessible conventionally through invasive biopsies. Noninvasive prenatal testing has been used globally for the screening of fetal chromosomal aneuploidies and has led to a considerable reduction in invasive prenatal testing, such as use of amniocentesis. Cancer liquid biopsies have been used for the selection of targeted therapies and monitoring of disease progression. Liquid biopsies for organ transplant patients have been used to monitor graft dysfunction. The first applications of liquid biopsies are based on the detection of genetic markers in cell-free DNA, such as sex differences, genetic polymorphisms, or mutations. By studying nongenetic features of cell-free DNA moleculesincluding DNA methylation, fragmentation, and topologyunderstanding of cell-free DNA biology has expanded the spectrum and utilities of liquid biopsies.

Cell-free DNA in plasma consists of a mixture of fragmented DNA molecules released from various tissues within the body. Each cell-free DNA fragment bears molecular signatures of its cell of origin, such as DNA methylation status. The methylation profile of circulating fetal DNA in the mothers plasma correlates with that of the placenta and has been exploited as a means to develop noninvasive fetus-specific biomarkers that are not dependent on fetal sex or genotype. Circulating tumor-derived DNA bear methylation states that resemble the tumor tissue and have enabled the development of tests for the screening and localization of cancer. The fragmentation of plasma DNA is related to the nucleosomal organization, chromatin structure, gene expression, and nuclease content of the tissue of origin, resulting in characteristic signatures in the form of fragment size, nucleotide motifs at the fragment ends, single-stranded jagged ends, and the genomic locations of the fragmentation endpoints. For mitochondrial DNA that is originally in a circular form, fragmentation will also change its topology into a linear form. By noting these features of cell-free DNA fragments, the anatomical site of pathology could potentially be deduced, providing additional information than just quantifying mitochondrial DNA without regard to its form. The study of such characteristics has also enhanced our understanding of the biology and generation of cell-free DNA. The roles of nucleases in plasma DNA biology, such as deoxyribonuclease 1like-3, have been explored by using gene-deletion mouse models and confirmed in humans bearing nuclease gene mutations, with potential implications for the pathogenesis of autoimmune diseases.

The use of DNA methylation, fragmentomic, and topologic analyses of circulating DNA, either in a targeted fashion or in a genomewide manner, will be expected to impact clinical practice. Clinical specimens covering more disease entities will need to be investigated to identify tissue-specific and disease-relevant signatures. During the discovery phase, to better delineate these signatures, mining is performed on high volumes of DNA data pooled within and across samples by using customized bioinformatics algorithms. Once these putative sets of signatures have been identified, signature- and target-specific assays could be developed, and large-scale clinical trials will be needed to validate these approaches. One application is in the development of plasma DNAbased cancer screening. One advantage of these approaches is the potentially large number of markers that can be developed to differentiate cancer and noncancer cells and in the ability to locate the tissue of origin of the detected cancer, possibly including cancers of unknown primary. In the area of noninvasive prenatal testing, the correlation of DNA methylation, fragmentomic, and topologic aberrations in circulating DNA to clinical outcomes would expand the spectrum of diagnostic applications beyond current ones. Fragmentomic approaches have the potential for enriching the cell-free DNA species of interest, such as through the use of automated platforms that allow the size separation of circulating DNA. In the area of organ transplant monitoring, the development of DNA methylation, fragmentomic, and topologic markers would provide an alternative to genetic markers for detecting rejection. These nongenetic markers may enable further differentiation of the donors contribution to the circulating DNA pool into its constituent tissue components. The understanding between circulating DNA and nucleases is in its infancy. Circulating DNA signatures attributable to changes in nuclease expression in health and disease need to be elucidated and may have emerging diagnostic applications.

Different tissues, including cancer cells and trophoblasts in pregnancy, contribute cell-free DNA to the circulation. The cell-free DNA molecules may bear methylation states reflective of the cell of origin. The DNA molecule size, fragment end locations, and end motifs are influenced by the nucleosome organization, chromatin structure, nuclease content, and gene expression of the tissue of origin. Parameters that can be measured to quantify these characteristics are shown on the right.

Liquid biopsies that analyze cell-free DNA in blood plasma are used for noninvasive prenatal testing, oncology, and monitoring of organ transplant recipients. DNA molecules are released into the plasma from various bodily tissues. Physical and molecular features of cell-free DNA fragments and their distribution over the genome bear information about their tissues of origin. Moreover, patterns of DNA methylation of these molecules reflect those of their tissue sources. The nucleosomal organization and nuclease content of the tissue of origin affect the fragmentation profile of plasma DNA molecules, such as fragment size and end motifs. Besides double-stranded linear fragments, other topological forms of cell-free DNA also existnamely circular and single-stranded molecules. Enhanced by these features, liquid biopsies hold promise for the noninvasive detection of tissue-specific pathologies with a range of clinical applications.

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Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies - Science

What if a fugitive could be detected just by testing the air from the crime scene?

Humans leave DNA everywhere. So do animals, even plants and fungi. Some species tend to be so elusive that it becomes nearly impossible to find them. Researchers wanted to see whether endangered or invasive species could be tracked just by the invisible trail left behind when skin cells and other micro-evidence they cast off ends up floating around, and vacuuming the air showed that it is sometimes possible to use airDNA to detect where an animal has been. They also hypothesize that their methods could be used to someday track criminals who have all but vanished.

When an organism sheds DNA into its environment, from land to water to anything it might touch, that genetic material is known as eDNA(environmental DNA), which becomes airDNA when airborne.

Any biological material can be a source of eDNA, ecologist Elizabeth Clare, who led a study recently published in PeerJ, told SYFY WIRE.

Future forensics aside, airDNA could be critical to saving endangered species before their time is up. It could even help discover species we never even knew existedand undiscovered animals are thought to be mostly small creatures that have easily been able to hide from us for so long. Clare and her team saw airDNA in action with naked mole rats that had their own enclosure at an animal facility. They vacuumed the air with filters similar to a HEPA filter you may already have, which your DNA is probably trapped in. They might not be Godzilla, but they are still the first proof of airDNA coming from relatively large animals.

It wasnt as easy as sucking up air. It was already a plus that the naked mole rats werent hanging out with other animals, because, as the researchers noted in their study, there were already enough issues with contamination from the DNA of humans who went inside to vacuum.

The researchers also ran into the problem of genetic material from the mole rats coming up as that of other species, such as another type of mole rat, which is difficult to differentiate even through samples of hair or any other source of DNA. Even distantly related species including dogs, cows and sheep, showed up in the results. Human DNA was all over.

Then there was the issue of DNA scattering all over the air. There was a better chance of detecting naked mole rats in a closed space than out in the open, where airDNA molecules would not only disperse further apart from each other but possibly get confused with DNA from other organisms in the area. There is also a possibility that wind can carry airDNA over from places that are not in the immediate vicinity of an area where scientists might be searching for an animal infamous for hiding. If naked mole rats were being searched for in the wild, it would probably be easier to find their DNA from sucking up air in an abandoned burrow. Clare and her team are currently working on finding out how to best detect airDNA with these obstacles.

This is an area of active research, she said. One challenge outside will be the dilution. In largerspaces this may not be possible without really changing the technology involved. The other challenges will include how complex the sources are and how many species are contributing.

Though Clare and her team have only theorized about what airDNA can do for forensics, and are not pursuing it any further themselves, forensic scientists are undoubtedly going to see this as a breakthrough. Current methods of detecting criminals through DNA are mostly limited to hair and bodily fluids left behind at the crime scene or on a trail otherwise gone cold. Combined with other detection techniques such as fingerprinting, airDNA could potentially help catch fugitives who would otherwise literally get away with murder. We might find out when further scientific investigations on this start turning into criminal investigations.

It is even possible that eDNA and airDNA could someday be used to detect life on other planets. Unknown species on Earth have a much better chance of being found with an air vacuum because there is are already extensive references that could connect something like a new type of lizard with species it is already related to. While it is much too early to tell, since we are still working on figuring out how to characterize the atmospheres of exoplanets without starlight getting in the way, it could happen.

Its fun to think about such ideas, but in a very science fiction way, Clare admitted. It would depend on whether some alien life even uses DNA the way we do and in the format we do. Assuming it exists, and that it does, the problem would be that these methods rely on having a well established reference database we can compare our unknown to. Without the references we cant learn very muchbut it is still an interesting idea to consider.

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Smell that? DNA in the air might not let criminals get away so fast in the future - SYFY WIRE

Researchers in the UK have successfully isolated airborne mammalian DNA, showing that in air, just as in water, animals leave behind invisible but useful traces of themselves that scientists can monitor. The results, published March 31 in PeerJ, represent a new direction for environmental DNA (eDNA) research that could one day lead to advances in forensic science and public health, in addition to ecological surveillance.

This is really the first time airborne samples have been used to look at mammals, and its very exciting, says Mark Johnson, an ecologist at Texas Tech University who has used airborne DNA to study plants and was not involved in the current work. Through his own research, Johnson adds, weve learned that airborne DNA is a lot broader than what we originally gave it credit for, and I think this paper opens the door for expanding into new areas.

Environmental DNA is one of the fastest growing ecological tools for biomonitoring in aquatic systems, according to study coauthor Elizabeth Clare, a molecular ecologist at Queen Mary University of London. Its use is premised on the fact that all organisms leave genetic fingerprints wherever they go in the environment. That DNA can yield valuable information about what species frequent an area.

In the last few years, eDNA has helped scientists monitor endangered species, such as the highly protected great crested newt, as well as species such as the white shark that are difficult to track using conventional methods. As the tool has been further refined, researchers have also started pushing eDNA into new territories, including the detection of pathogens in the aquaculture industry and even the monitoring of terrestrial organisms, including mammals. But in all of these instances, the samples have come from water sources such as lakes or rivers, or in rare cases, moist soil.

To see whether eDNA could be detected in air, Clare started by designing a simple experiment looking for airborne mammalian eDNA in a small, three-meter by four-meter room housing a colony of 225 naked mole rats. They had been established for a very long time in that room . . . so if DNA does accumulate [in air], it would be there, Clare tells The Scientist.

Drawing on existing aquatic eDNA procedures, Clare rigged a pump to draw air, rather than a water sample, through either a 45- or 22-micrometer filter. Because eDNA can come in a variety of formspieces of hair, skin, or free-floating, naked DNAit was likely that she would capture particles of many different sizes. The team also tested different filtering times to see if the quantity of DNA differed after 5, 10, or 20 minutes. In total, the experiment generated a total of 12 samples (six from the air trapped within the mole rats system of burrows and six from the open room) plus two positive and two negative controls.

Elizabeth Clare, a molecular ecologist at Queen Mary University of London, discusses how she pulled from techniques developed to sample environmental DNA, or eDNA, in water to search for genetic traces of mammals in the air.

PEERJ

All but two samples yielded mole rat sequences. Neither the filter size nor the time (and thus the volume of air being filtered) led to significant differences in DNA yield, although the burrows generated a stronger signal than the larger room did.

It surprised us that it worked as well as it did right away, Clare says. We had actually anticipated a bunch of things we were going to modify . . . that we never had to use. It worked the first time with the first thing we tried.

The current study is a solid foundation for future work, says University of Amsterdam evolutionary ecologist Kathryn Stewart, who works with eDNA and was not involved in the current research. Clare sees a role for airborne DNA in spaces that can be difficult to access, such as burrows, caves, and hollows. Johnson had previously applied for a grant to use airborne eDNA to noninvasively monitor for white nose syndrome in bats, but at the time, the project was deemed too experimental.

After the successes of eDNA in aquatic science, its exhilarating to see somebody take it one step further and ask what other kinds of media we can extract DNA from, Stewart tells The Scientist. The only claim that they make is that you can accurately collect DNA from the air, but we need that forward thinking momentum for the field. I think the challenges that lie ahead are also exciting opportunities.

One such challenge will be the issue of contamination. Despite carrying out their extractions in a clean hood, the team was surprised to find human DNA, but not mole rat DNA, in the studys negative controls, suggesting that the contamination is coming from the scientists themselves. In some samples, the human component was as strong as that of the mole rats, even within their burrows. For researchers targeting nonmammals, this is less of a concern, as the sequencing tools they use pick out only their species of interest. But for sampling aimed at detecting mammalian DNA, contamination is going to be one of the biggest challenges, Stewart says.

Clare has already started to brainstorm possible means for addressing contamination, either by having researchers collect samples while wearing suits that include respirators, deploying dust traps in the field for days or weeks to passively collect airborne materialas Johnson does for his studies on plant airborne DNAor by using so-called blocking probes during sequencing that keep human DNA from amplifying. She is also designing studies to better understand how genetic material behaves and persists in the airs changing environment. All of this is a push to validate airborne eDNA using the same rigorous standards applied to aquatic research.

The silver lining of human contamination, Clare says, is that it made her realize that airborne DNA could have forensic or public health applications. DNA from crime scenes is often degraded or sparse, but she was able to pull minute traces of the nucleic acid from the air and produce usable results.

Any such uses remain speculative, and Clare is quick to point out how much remains unknown. In terms of what we could do with it, were very much at the speculatory stage of this, she tells The Scientist. Is extracting airborne DNA possible? Yes. Can we say anything beyond that? No.

E.L. Clare et al., eDNAir: proof of concept that animal DNA can be collected from air sampling,PeerJ, doi:10.7717/peerj.11030, 2021.

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Environmental DNA Can Be Pulled from the Air - The Scientist

STONY BROOK, N.Y.--(BUSINESS WIRE)--Applied DNA Sciences, Inc. (NASDAQ: APDN) (Applied DNA or the Company), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing, announced an interview with President and CEO Dr. James A. Hayward conducted by the BBCs Business Daily as part of an episode titled Tracing cottons DNA. The episode is available at https://www.bbc.co.uk/sounds/play/w3ct1jn9.

CertainT for Cotton Traceability

CertainT, Applied DNAs traceability platform, provides an approach to authenticate goods within large and complex supply chains for materials such as cotton, and leather, home textiles and apparel, pharmaceuticals and nutraceuticals, personal care, cannabis, and other products. To date, CertainT has ensured the authenticity of approximately 300 million pounds of North American Pima and Upland cotton and has been deployed to secure Egyptian and Australian cotton.

CertainT begins by authenticating the fiber content in cotton to confirm its origin. The platform then employs a unique molecular identifier produced by the Companys LinearDNA platform to mark cotton fibers in bulk. The cotton fiber is then tested for the presence of the identifier via the Companys proprietary, portable readers as the cotton fiber travels throughout a global supply chain and is converted into yarn, fabric, and finished goods. The detection of the identifier confirms origin and authenticity; its absence can signal for blending with illicit cotton, including cotton potentially produced by means of forced labor. The CertainT logo signifies to consumers of cotton products that they can trust the products they are buying with said trust grounded in forensic, science-based authentication. Consumers can therefore be confident in the knowledge that Brands and their supply chains have taken the necessary steps to assure that the cotton product itself is authentic and sustainably and responsibly sourced from a known origin.

About Applied DNA Sciences

Applied DNA is commercializing LinearDNA, its proprietary, large-scale polymerase chain reaction (PCR)-based manufacturing platform that allows for the large-scale production of specific DNA sequences.

The LinearDNA platform has utility in the nucleic acid-based in vitro diagnostics and preclinical nucleic acid-based drug development and manufacturing market. The platform is used to manufacture DNA for customers as components of in vitro diagnostic tests and for preclinical nucleic acid-based drug development in the fields of adoptive cell therapies (CAR T and TCR therapies), DNA vaccines (anti-viral and cancer), RNA therapies, clustered regularly interspaced short palindromic repeats (CRISPR) based therapies, and gene therapies. Applied DNA has also established a COVID-19 diagnostic and testing offering that is in the early stages of commercialization and is grounded in the Companys deep expertise in DNA.

The LinearDNA platform also has non-biologic applications, such as supply chain security, anti-counterfeiting and anti-theft technology. Key end-markets include textiles, pharmaceuticals and nutraceuticals, and cannabis, among others.

Visit adnas.com for more information. Follow us on Twitter and LinkedIn. Join our mailing list.

The Companys common stock is listed on NASDAQ under ticker symbol APDN, and its publicly traded warrants are listed on OTC under ticker symbol APPDW.

Applied DNA is a member of the Russell Microcap Index.

Forward-Looking Statements

The statements made by Applied DNA in this press release may be forward-looking in nature within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Forward-looking statements describe Applied DNAs future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to, its history of net losses, limited financial resources, limited market acceptance, the uncertainties inherent in research and development, our ability to successfully enter into commercial contracts for the implementation of our CertainT platform, disruptions in the supply of raw materials and supplies, and various other factors detailed from time to time in Applied DNAs SEC reports and filings, including our Annual Report on Form 10-K filed on December 17, 2020 and our subsequent quarterly reports on Form 10-Q filed on February 11, 2021, and other reports we file with the SEC, which are available at http://www.sec.gov. Applied DNA undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, unless otherwise required by law.

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Applied DNA CEO Discusses Relevance of DNA-based Cotton Traceability as Enabler of Ethical and Responsible Textile Manufacturing on BBC Business Daily...

SAN DIEGO--(BUSINESS WIRE)--Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in aggressive cancers, today will present data at the 2021 American Association for Cancer Research (AACR) Annual Meeting. The poster, Extrachromosomal DNA (ecDNA)-driven switching of oncogene dependency facilitates resistance to targeted therapy, is available to registered attendees today, from 8:30 a.m. 11:59 p.m. ET. AACR is being held virtually this year due to COVID-19.

The oncology field has long known that tumors with oncogene amplification are aggressive, lead to a poor prognosis, and are very difficult to treat, said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. This study provides rationale for why patients with oncogene amplified tumors have not benefited from targeted therapies. We have demonstrated that ecDNA facilitate a powerful evasive mechanism of switching driver oncogenes when under targeted therapeutic pressure, thereby rendering targeted therapies futile against ecDNA-enabled, gene amplified cancers. Our findings underscore an urgent need and Boundless Bios focus in developing precision medicines targeting the underlying vulnerabilities of ecDNA.

Study Summary

Oncogenes are frequently amplified on ecDNA, circular units of DNA that are separate from chromosomes and that are highly transcribed. Because ecDNA lack centromeres, during mitosis they are passed to daughter cells asymmetrically and can thereby lead to exponential increase in copy number of genes encoded on ecDNA, which in turn facilitates tremendous genomic heterogeneity in tumor cells. The tumor heterogeneity and plasticity enabled by ecDNA can provide a mechanism of resistance for cancer cells against cancer treatment. The study set out to understand the role of ecDNA in facilitating poor responses to targeted therapies in gene amplified cancer.

The study employed the SNU16 gastric cancer model, which contains MYC and FGFR2 amplification at baseline, to characterize ecDNA content, genomic heterogeneity, and ecDNA kinetics in forming resistance to targeted therapy. Boundless Bio scientists performed a longitudinal assessment of cellular resistance and ecDNA dynamics, initially in response to the FGFR2 inhibitor, infigratinib. Upon identifying EGFR amplification on ecDNA as the dominant mechanism of resistance to infigratinib, the study subsequently also evaluated response and resistance to the EGFR inhibitor, erlotinib, delivered either sequentially or in parallel with infigratinib.

The results from the study show differential and dose-dependent resistance of SNU16 cells to infigratinib driven by the heterogeneity of oncogenes residing on ecDNA. First, low doses of infigratinib led to additional amplification of FGFR2 on ecDNA that resulted in levels of FGFR2 that were able to outcompete the drug exposure. High doses of infigratinib resulted in amplification of a new oncogene, EGFR, on ecDNA, representing an ecDNA-mediated switching of oncogene dependency from FGFR2 to EGFR. Next, upon exposing the infigratinib resistant cells (now with EGFR amplification on ecDNA) to single agent EGFR inhibitor, erlotinib, the cells again became resistant, as the emergent ecDNA-enabled EGFR dependency switched back to the original FGFR2 dependency, again via amplification on ecDNA. Lastly, the study tested dual upfront inhibition of both FGFR2 and EGFR with infigratinib and erlotinib, respectively, in previously untreated SNU16 cells. Although initial cytotoxicity was more robust than with either agent alone, the cell population inevitably became resistant. Remarkably, resistance to the up-front dual blockade was also driven by ecDNA, with amplification of various oncogenes, including MET and KRAS, on ecDNA.

This study and its results build upon and confirm previous studies that observe similar dynamics of ecDNA-driven amplification under therapeutic pressure. Such findings help explain the lack of responses and short durations associated with treatment of gene amplified cancers with targeted therapies in the clinic. The inability to a priori predict which new oncogenes would amplify on ecDNA as a mechanism of resistance to single-agent or multi-target inhibition suggest that both sequential and combination approaches of oncogene targeted therapies are suboptimal, if not largely ineffective clinical strategies for patients with ecDNA-driven cancers. These findings highlight the urgent need to take a new therapeutic approach, one that disables the underlying ecDNA machinery used by the tumor cell to drive tumor growth and resistance.

About ecDNA

Extrachromosomal DNA, or ecDNA, are distinct circular units of DNA lacking centromeres but containing functional genes, including oncogenes, that are separated from tumor cell chromosomes. ecDNA replicate within cancer cells and can be passed to daughter cells asymmetrically during cell division, thereby constituting a primary driver of focal gene amplification and copy number heterogeneity in cancer. By leveraging the plasticity afforded by ecDNA, cancer has the ability to increase or decrease copy number of select oncogenes located on ecDNA to enable survival under selective pressures, including chemotherapy, targeted therapy, immunotherapy, or radiation, making ecDNA one of cancer cells primary mechanisms of recurrence and treatment resistance. ecDNA are not found in healthy cells but are present in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

About Boundless Bio

Boundless Bio is a next-generation precision oncology company interrogating a novel area of cancer biology, extrachromosomal DNA (ecDNA), to deliver transformative therapies to patients with previously intractable cancers.

For more information, visit http://www.boundlessbio.com.

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Boundless Bio Presents Data on the Role of Extrachromosomal DNA (ecDNA) in Mediating Resistance to Targeted Therapies at the American Association for...

Enlarge / X-ray image of the mysterious fetus found in the coffin of the 17th-century Swedish Bishop Peder Winstrup.

Gunnar Menander

When Swedish archaeologists in 2015 X-rayed the remains of a 17th-century bishop, they were shocked when the images revealed that the bishop shared his coffin with the remains of a stillborn premature baby.Now, ancient DNA analysis has revealed that the fetus was likely the bishop's grandson, according toa new paper published in the Journal of Archaeological Science: Reports.

Born in Copenhagen in 1605, Bishop Peder Winstrupwas a prominent church figure in Denmark and Sweden during his lifetime, who helped found Lund University in 1666 while deftly navigating the constantly shifting political environment. (He was ennobled by the Swedish king, Charles X Gustav, when his diocese passed from Danish hands in 1658.) Winstrup died in late December 1679 and was buried in Lund Cathedral in January 1680. When his coffin was opened in the early 19th and 20th centuries, the body was remarkably well-preserved.

So when the curators of the Lund University Historical Museum heard, in 2012, that the bishop's coffin would be moved to a new burial site outside the cathedral, they joined with scientists in a multidisciplinary collaboration to study the bishop's remains before they were reinterred. The body was X-rayed and CT-scanned, along with the bishop's clothing, various artifacts, and plant and insect remains.

The scientists found that the bishop's body had not been embalmed. Rather, the body was placed on a mattress stuffed with herbs (like juniper and wormwood), with the head resting on a pillow of hops, which helped preserve itincluding the bishop's clothing, although the colors had faded. Theyalso found that Winstrup likely died of pneumonia and that he suffered from gout, arthritis, arterial plaque, and gallstones (a sign of a diet high in fatty foods), among other illnesses. He had also lost many teeth, and those that remained showed signs of decay, indicating the bishop was fond of sweets. (The coffin contained a small pouch holding several teeth.)

The bishop's lungs also proved to be remarkably well-preserved, and anthropologists found small calcifications in those lungsevidence of a prior infection, most likely tuberculosis. The anthropologists surmised that Winthrop likely contracted the disease during the so-called "White Plague" epidemic that swept through Europe in the 17th century. In fact, last year, researchers at Lund University, the Max Planck Institute for the Science of Human History, and the Swedish Natural Historical Museum were able to reconstruct the genome for a TB sample (Mycobacterium tuberculosis) taken from one of those calcified nodules. Because the bishop's precise date of death is known, the team was able to determine that the TB pathogen is much younger than scientists previously believed.

But by far the most significant discovery was that the bishop was not alone in his coffin. The CT scans showed a linen-wrapped bundle containing the remains of a stillborn fetus (roughly five to six months along, in terms of development), nestled within the layers of herbs just under the bishop's right tibia. It was initially assumed that someone (unrelated to the bishop) had taken advantage of the bishop's burial to ensure their illegitimate offspring was buried on sanctified ground.

Bishop Peder Winstrup on a contemporary engraving printed in one of his own theological works in 1666.

Peder Winstrup in the coffin, where researchers also discovered a fetus wrapped in a bundle between his calves.

Gunnar Menander

The bundle found at the feet of the remains of Bishop Peder Winstrup.

Gunnar Menander

In fact, "It was not uncommon for small children to be placed in coffins with adults," said Torbjrn Ahlstrm, a professor of historical osteology at Lund University who co-authored the new study. "The fetus may have been placed in the coffin after the funeral, when it was in a vaulted tomb in Lund Cathedral and therefore accessible." That jibes with evidence that the wrapped fetus had been hastily placed in the coffin. And other coffins in the same vault also held remains of several children. But it would take ancient DNA analysis to definitively rule out the possibility that the fetus was related to Winstrupso that's whatAhlstrm and his colleagues set out to do.

The Lund researchers took DNA samples from Winstrup's right femur and the left femur of the fetus. They determined that the stillborn fetus was male and that there was a second-degree kinship with Winstrup, meaning that they shared about 25 percent of the same genes. There was a Y-chromosome match but the mitochondrial DNA was different, indicating the connection was on the paternal side of the family tree. The second-degree relationship could have been grandparent-grandchild, uncle-nephew, or even half siblings or double cousins.

To narrow the possibilities, Ahlstrm et al. turned to a close examination of the Winstrup family's genealogy. According to the genealogical records maintained at the House of Nobility in Stockholm, Sweden, the bishop was one of six children (four daughters and two sons). Since the Lund researchers were only concerned with paternal lineage, they could ignore the four sisters in their analysis. Winstrup's brother, Elias, died in 1633 at the age of 27, unmarried and childless. This enabled the Lund team to rule out certain possibilities: uncle/nephew, half siblings, and double cousins, specifically.

Bishop Peder Winstrup in turn fathered five children with his first wife, Anne Marie Ernstatter Baden, three of whom (two daughters and a son) survived to adulthood. He had no children with his second wife, Dorothea von Andersen.

So the most likely possible relationship, the authors concluded, was that Winstrup was the stillborn child's grandfatheri.e., the issue of his son, Peder Pedersen Winstrup, who bucked the family theological tradition to focus on military matters (particularly fortification), lost the family estate in the Great Reduction, and died destitute. However, there is a small likelihood that the fetus may have been that of the bishop's sister Anna Maria (who may have died in childbirth) and her husband Casper vonBhnen, assuming Casper belonged to a similar Y haplogroup.

As for how the fetus came to rest with the bishop, "It seems probable that the relatives would have had access to the crypt where the coffins of the Winstrups were stored, and, thus, a possibility to deposit the fetus in one of the coffins, in this case that of Peter Winstrup," the authors concluded.

DOI: Journal of Archaeological Science: Reports, 2021. 10.1016/j.jasrep.2021.102939 (About DOIs).

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DNA analysis solves curious case of the stillborn fetus in the bishops coffin - Ars Technica

A woman who traveled with Kylr Yust on the day after Jessica Runions went missing in September of 2016 said she was scared for her life as Yust was behaving nervously and erratically.Crystal Taylor, Jessep Carters ex-wife, said they traveled to Kansas City so she and Carter could meet up with Yust at his grandfathers house on September 9, 2016. It was after one day after Runions went missing from a party in Kansas City, after leaving with Yust.Carter was Kylr Yusts half-brother. He died by suicide in the Jackson County jail in 2018.Yust is accused of killing Kara Kopetsky in 2007. She was last seen leaving Belton High School in May of that year. He's also accused of killing Runions. They were last seen leaving a party together in 2016. A mushroom hunter found their remains in a Cass County farm field in 2017.After leaving Yusts grandfathers house on Sept. 9, 2016, Carter, Taylor and Yust went to visit Jesseps uncles house, Taylor testified. At the house, Taylor said Yust told her he had broken up with Runions the week before.But, Taylor testified minutes later that Yust received a phone call at the house and overheard him say he had seen Runions that day.As they left Carters uncles house, she saw Yust hide something in the bushes.They returned to Yusts grandfathers house where Yust showed her downstairs to watch TV. Thats when Carter and Yust left for a time, then returned. Carter looked shocked and scared when he returned, Taylor said.Kind of like mind blown, Taylor said.Cass County prosecutor Ben Butler asked Taylor if Carters behavior stood out to her.Yeah, it did. For him to be scared was not like him, she said.[ OPENING STATEMENT UPDATES ] [ SECOND DAY UPDATES ] [ THIRD DAY UPDATES ] [ FOURTH DAY UPDATES ] [ FIRST WEEK RECAP ] [ SIXTH DAY RECAP ] Taylor testified the three traveled around Raytown, Kansas City, Lone Jack, then eventually back to Edwards, Missouri.Along the way, she said Yust asked Carter and Taylor to take the batteries out of their cell phones. She testified they stopped off at a cousins house in Lone Jack where Carter went in to get a gun and give it to her. Police pulled them over around 3:25 a.m., on Sept. 10, where police confiscated the gun on Taylor, and gave Carter a ticket for driving on a suspended license.They returned to Edwards, Missouri, dropped Yust off at a trailer, and gave him some food. Police caflled later that evening, to get statements from Carter and Taylor.Taylor testified in the year after September of 2016, Carters behavior became abusive. She eventually left him to go to a shelter.She later learned Carter was arrested for setting his uncle Pauls house on fire.Carter died by suicide in the Jackson County jail in 2018.The prosecution also called Jarrah Kennedy from the Kansas City Police Department Crime Lab to discuss DNA collected from a red and gray hoodie recovered found near Yust's grandfather's house.Kennedy said there was brownish and blackish staining with four areas of interest on the shirt. She testified genetic information from Yust and Runions was collected from several areas of the shirt.There was also a potential third profile in the genetic mix on the shirt, Kennedy said, but she said she cannot provide an assumption of who it is due to the minimal nature of DNA.Cass County prosecutor Julie Tolle also questioned Matthew Forrest, a former KCPD crime scene technician. In pictures taken by Forrest that were obtained through a search warrant on Sept. 11, 2016, a blister on inside of finger, scratch on side of face and redness on hand could be observed. The pictures were taken days after Runions went missing, and her SUV was found burned. Melanie Fields, KCPD Crime Scene Unit Supervisor, also testified on Sept. 13, 2016 a second search warrant was executed on Yust and more pictures were taken. In the pictures, Fields noticed burnt facial hair, singed hair and injuries to his hand.

A woman who traveled with Kylr Yust on the day after Jessica Runions went missing in September of 2016 said she was scared for her life as Yust was behaving nervously and erratically.

Crystal Taylor, Jessep Carters ex-wife, said they traveled to Kansas City so she and Carter could meet up with Yust at his grandfathers house on September 9, 2016. It was after one day after Runions went missing from a party in Kansas City, after leaving with Yust.

Carter was Kylr Yusts half-brother. He died by suicide in the Jackson County jail in 2018.

Yust is accused of killing Kara Kopetsky in 2007. She was last seen leaving Belton High School in May of that year. He's also accused of killing Runions. They were last seen leaving a party together in 2016. A mushroom hunter found their remains in a Cass County farm field in 2017.

After leaving Yusts grandfathers house on Sept. 9, 2016, Carter, Taylor and Yust went to visit Jesseps uncles house, Taylor testified. At the house, Taylor said Yust told her he had broken up with Runions the week before.

This content is imported from Twitter.You may be able to find the same content in another format, or you may be able to find more information, at their web site.

But, Taylor testified minutes later that Yust received a phone call at the house and overheard him say he had seen Runions that day.

This content is imported from Twitter.You may be able to find the same content in another format, or you may be able to find more information, at their web site.

As they left Carters uncles house, she saw Yust hide something in the bushes.

They returned to Yusts grandfathers house where Yust showed her downstairs to watch TV. Thats when Carter and Yust left for a time, then returned.

Carter looked shocked and scared when he returned, Taylor said.

Kind of like mind blown, Taylor said.

Cass County prosecutor Ben Butler asked Taylor if Carters behavior stood out to her.

Yeah, it did. For him to be scared was not like him, she said.

[ OPENING STATEMENT UPDATES ] [ SECOND DAY UPDATES ] [ THIRD DAY UPDATES ] [ FOURTH DAY UPDATES ] [FIFTH DAY UPDATES ] [ FIRST WEEK RECAP ] [ SIXTH DAY RECAP ]

Taylor testified the three traveled around Raytown, Kansas City, Lone Jack, then eventually back to Edwards, Missouri.

Along the way, she said Yust asked Carter and Taylor to take the batteries out of their cell phones. She testified they stopped off at a cousins house in Lone Jack where Carter went in to get a gun and give it to her. Police pulled them over around 3:25 a.m., on Sept. 10, where police confiscated the gun on Taylor, and gave Carter a ticket for driving on a suspended license.

They returned to Edwards, Missouri, dropped Yust off at a trailer, and gave him some food. Police caflled later that evening, to get statements from Carter and Taylor.

Taylor testified in the year after September of 2016, Carters behavior became abusive. She eventually left him to go to a shelter.

She later learned Carter was arrested for setting his uncle Pauls house on fire.

Carter died by suicide in the Jackson County jail in 2018.

The prosecution also called Jarrah Kennedy from the Kansas City Police Department Crime Lab to discuss DNA collected from a red and gray hoodie recovered found near Yust's grandfather's house.

Kennedy said there was brownish and blackish staining with four areas of interest on the shirt. She testified genetic information from Yust and Runions was collected from several areas of the shirt.

There was also a potential third profile in the genetic mix on the shirt, Kennedy said, but she said she cannot provide an assumption of who it is due to the minimal nature of DNA.

This content is imported from Twitter.You may be able to find the same content in another format, or you may be able to find more information, at their web site.

Cass County prosecutor Julie Tolle also questioned Matthew Forrest, a former KCPD crime scene technician.

In pictures taken by Forrest that were obtained through a search warrant on Sept. 11, 2016, a blister on inside of finger, scratch on side of face and redness on hand could be observed. The pictures were taken days after Runions went missing, and her SUV was found burned.

This content is imported from Twitter.You may be able to find the same content in another format, or you may be able to find more information, at their web site.

Melanie Fields, KCPD Crime Scene Unit Supervisor, also testified on Sept. 13, 2016 a second search warrant was executed on Yust and more pictures were taken. In the pictures, Fields noticed burnt facial hair, singed hair and injuries to his hand.

This content is imported from Twitter.You may be able to find the same content in another format, or you may be able to find more information, at their web site.

Read the rest here:
THE TRIAL OF KYLR YUST: DNA experts testify on evidence linking Yust to Runions death - KMBC Kansas City

Theres a new crime-fighting tool being used by the Santa Barbara County Sheriffs Office and for the first time, its being used in a cold case.

The ANDE rapid DNA instrument is being used in the cold case homicide of Paul Ornelas.

The 16-year-old Goleta resident was found dead more than four decades ago and his killer was never found. Ornelas's body was discovered near the train tracks below the Turnpike Road overpass on June 21, 1975.

Detective Matt Maxwell, assigned to the Major Crimes Bureau, is working on the reopened case.

Santa Barbara County Sheriff's Office

Ive been in contact with his family and the thing that they've expressed to me, more than anything, is just that the grieving process has never ended for them. They never got the closure, Detective Maxwell said.

The rapid DNA instrument, created by a Colorado-based company, is designed to identify decedents and solve crimes.

If you touch a handgun or a steering wheel of a car, we can collect DNA from that, said Sgt. Jarrett Morris of the Santa Barbara County Sheriffs Office Coroners Bureau.

Tissue samples, blood samples, or touch samples along with buccal swabs will work.

If we have a sample from like a suspect, we obtain a cheek swab from them and that generates a profile and I can compare it with any profiles we generated from any evidence that was collected, said Detective Brice Bruening of the Coroners Bureau.

ANDE

The Santa Barbara County Sheriffs Office was first introduced to the rapid technology back in 2019 following the deadly Conception boat fire.

That helped us identify all 34 decedents of that boat fire within a matter of days, Sgt. Morris said.

In January of 2020, they drove it down to Calabasas to help identify those killed in the Kobe Bryant helicopter crash.

Its since been used in a variety of local homicide cases, felony cases, some misdemeanor cases, and several decedent ID cases.

They even helped the San Luis Obispo County Sheriffs Office identify a human foot found in Templeton that was linked to a car crash last summer.

We can run five different cases through this instrument, Sgt. Morris said.

The biggest benefit is that it cuts down on time, bringing detectives the name of the suspect, for example, much quicker.

We get results in a matter of hours so at the most, two hours, Sgt. Morris said.

Normally, they would have to send the samples to labs, taking weeks or months to get the results back.

We're able to get these answers and able to move forward whether it's a criminal investigation or again, just bringing closure to a family, Sgt. Morris added.

As for the Ornelas case, the goal is to do just that - get the case solved with preserved evidence and this new technology, bringing the family closure.

The company that makes the technology says roughly a dozen law enforcement agencies have the instrument in California at this time. Its also in over 20 countries.

The Santa Barbara County Sheriffs Office says they currently have 31 cold cases. The San Luis Obispo County Sheriffs Office says it has 41 cases, mostly dating back to the 1970s and 80s. It adds that its in the process of getting the rapid DNA technology as well.

Continued here:
Detectives turn to rapid DNA technology for clues in 45-year-old cold case - KSBY San Luis Obispo News