Category Archives: Transhuman News

To do their lab work, Laura Ross and her team must conduct an itty-bitty surgery. First, they dissect out the reproductive tissues of the black-winged fungus gnat, a diminutive black fly about one-sixteenth to one-eighth of an inch long. Then they home in on particular cells in that tissue: the germ cells, which produce eggs and sperm and so hold the keys to the genome of the next generation.

Ross, an evolutionary biologist at the University of Edinburgh in Scotland, roots around in fungus-gnat parts because theres something odd about the cells in these flies: They dont follow the textbook rules. In sexually reproducing creatures, one full copy of the mothers genetic material generally fuses with one full copy of the fathers to create the complete, doubled-up set of DNA found in cells throughout the body.

But the fungus gnat does something bizarre. Early in the embryos development, most of the cells jettison two specific chromosomes enormous ones, compared with the others so the pair never ends up in the lions share of the gnats body. Only the cells that become germ cells retain the bonus DNA and pass it on to the next generation.

How and why this feature evolved remains largely mysterious, though biologists first spotted it a century ago. And black-winged fungus gnats arent the only genetic screwballs. A surprisingly wide array of creatures, all the way up to some vertebrates, dump significant stretches of DNA during early development, so the stretches dont end up in most of their body cells.

To date, scientists have observed the phenomenon in various insects, in lampreys and hagfish, in hairy one-celled life forms called ciliates, in parasitic roundworms and tiny crustaceans called copepods. Theyve seen it in rat-like marsupials called bandicoots and in songbirds probably all songbirds, according to recent work. And they expect to find many more cases.

A lot of these weird genomic features tend to be fairly rare, but they do evolve repeatedly, Ross says. Its not just one freak event. Presumably, then, there must be some selective advantage to the creatures that go down that evolutionary route. But what is it?

J. WANG & R.E. DAVIS / CURRENT OPINION IN GENETICS & DEVELOPMENT 2014

From copepods and worms to lampreys and bandicoots, programmed DNA elimination crops up all over the multicellular treeof life, with more cases likely waiting to be found. The standout stars of this odd show are songbirds, which all appearto display the phenomenon. Animal groups in which cases have been documented are noted in red, as are dates when thediscoveries in a given group were first reported. (Ciliates are noted in blue to indicate the trees root:the most recent common ancestor of all the creatures shown.)

Beyond their fascinating oddness, these quirks may hold broader lessons on how genomes work the way they do, scientists think, and how and why the DNA in germ cells is treated differently from the DNA in the rest of the developing critters body.

Its a fundamental difference between the DNA thats going on to the next generation and the DNA thats in all the other cell types, says Jeramiah Smith, a geneticist at the University of Kentucky who studies the phenomenon in lampreys and described it in the 2020 Annual Review of Animal Biosciences.

Starting in the late 1800s, well before scientists nailed down the link between DNA and heredity, biologists peering down microscopes used dyes to study tiny, twig-like bodies inside dividing cells, watching as the twigs grouped together and then separated. German anatomist Wilhelm von Waldeyer-Hartz named these structures chromosomes in 1888, for the ease with which they took up dye.

Around the same time, cell biologists observed chunks of chromosomes being discarded in a parasitic roundworm called Parascaris univalens that infects horses a much-studied worm because its pair of huge chromosomes were easy to view under a microscope. In later decades, researchers described other worm species that dropped segments from several chromosomes during early rounds of cell division in embryos. But they didnt have the technology to really explore it, says Richard Davis, an emeritus molecular biologist at the University of Colorado School of Medicine in Aurora.

Davis, who dedicated the last decade of his career to studying how this casting-off happens in a handful of roundworms, initially thought that the DNA being eliminated carried no blueprint for any genes. Most biologists (those whove heard of the phenomenon, anyway) have assumed the same thing, he says.

WIKIMEDIA COMMONS / PUBLIC DOMAIN

The earliest noted case of programmed DNA loss was reported in the late 19th century in a species of nematode worm. The observation was made by German scientist Theodor Boveri (right), who was renowned for his careful examination of chromosomes as cells divided and for linking this chromosomal behavior to the inheritance of traits, among other work. The drawing on the left is one of many by Boveri, who also drew and painted in his youth. It documents chromosome loss in early embryonic divisions of the worm.

It turned out, though, that this ditched DNA contains genes lots of them. Roundworms from the genus Ascaris, which infect pigs and people, dump about 5 percent of their genes, while those of the genus Parascaris cast off about 10 percent. Only the cells that are destined to form the worms body do the DNA ditching: Just like the black-winged fungus gnat, the full set of genes remain in the cells destined to form eggs and sperm. The worms offspring, and its offsprings offspring, repeat the exact same process.

Davis also noticed something else: Most of the genes that are retained in the germ cells are active in those cells, implying theyre needed there. And so Davis thinks that tossing the genes away in all the other body cells may be the worms ironclad method of making sure the genes dont become active where they arent meant to.

Guaranteeing that genes are active at certain times but not others, or in some tissues but not others, is a critical function for any living thing. Think of the many different cell types in our bodies: All contain the same DNA sequence, but our heart cells produce different proteins than our skin cells do, so that each can do its specialized job. And even within a particular type of cell, the proteins that are produced vary during a creatures lifespan.

Perhaps what these dropped genes do would be so damaging to adult cells that eliminating them is a better-safe-than-sorry device, Davis says. Its total speculation, though because theres no proof of anything.

But that also presents a puzzler thats yet to be solved. Most living things already have ways to silence specific genes by adding chemical tags. So why do they choose to do this? Davis says.

Smith thinks the same type of extreme gene silencing may be at play in lampreys. His lab stumbled upon DNA elimination in these ancient jawless fish while working with colleagues on decoding the lamprey genome. Smith had seen research from the 1980s reporting chromosome loss in the closely related hagfish. He decided to see if lampreys were doing the same thing.

Lamprey physiology makes it easy to extract eggs and sperm from the animals Smith likens it to milking a cow or squeezing toothpaste out of a tube. He then fertilized the eggs and watched the embryos develop and found that they were dropping chromosomes 1.5 to 3 days after fertilization.

Lampreys lose 12 entire chromosomes out of their initial set of 96, and perhaps some bits and pieces from the chromosomes that remain. The losses are pre-programmed to occur in almost all the cells of the embryo except for a small handful of cells destined to soon become germ cells. Ultimately, those bits end up in sperm and egg cells, but not in any other lamprey cells.

Using advanced sequencing methods that were just coming online at the time, Smith and his colleagues identified many genes in the eliminated DNA. Intriguingly, about 60 percent to 70 percent of the genes are similar to ones that, in our species, are thought to boost cancer when their activity gets out of control. Whatever their normal function is, those genes might be especially dangerous ones to keep around in body cells. We think lamprey are getting rid of these genes as a means of permanently silencing them, Smith says.

Early in development, the sea lamprey loses genetic material as shown in this diagram. Most of the chromosomes segregate neatly to the poles during cell division but 12 do not, and as a consequence dont end up in the two new nuclei that result from a division. They form their own micronuclei, and the genes they contain are silenced and ultimately degraded. The result: The lamprey haploid chromosome count of 96 ends up as 84 in body cells.

Rosss fungus gnats, Bradysia ( Sciara) coprophila, have their own special mystery. They have been bred and maintained for decades, passing from lab to lab. Researchers in the 1920s studying how chromosomes behave in the cell noticed that these flies lose two chromosomes in some cells. (Some insects, its now known, have more than 80 chromosomes to dispose of.) But these chromosomes called germline restricted chromosomes because they are only retained in the germline are almost as large as the rest of the gnats genome.

In fact, they are basically an entire genome, as they contain an entire extra set of the genes a gnat has. But fungus gnats are weirder still. When Ross and her team sequenced the chromosomes, she found that the genes they bear arent especially similar to ones of the species they reside in. It looks like the genome of a completely different species, Ross says of an entirely different group of flies.

Rosss best guess is that during a rare mating event between two different species eons ago, the genome of one got integrated into the genome of the other and somehow got shunted to the germline alone. For her, this still-hypothetical freak event along with other weirdnesses over how flies pass on their genetic material points to a fundamental mystery. The definition of life is being able to copy and paste your genetic material into future generations, she says. Why is this process so variable, and what drives that variation?

That same question drives Alexander Suh, an evolutionary biologist at the University of East Anglia in the UK and Uppsala University in Sweden, who studies a germline-restricted chromosome in the zebra finch, a songbird. Researchers first reported its existence in 1998. As a zebra finch embryo develops, this chromosome somehow magically, says Suh, and I say that with quotes just because I have no explanation yet, gets dropped from all cells except the germ cells.

This bizarre chromosome, too, is chock-full of genes, many of them present in multiple sometimes hundreds of copies. And many are active in the germline. Suh and colleagues and another group independently reported in 2019 that the chromosome dates back to the common ancestor of songbirds, and that all songbirds about half of all birds carry it.

Whatever it is, its been around for 50 million years, Suh says. Its somehow made sure that the host cannot exist without it.

Now Suhs team and others are puzzling out the possible role of this chromosome by looking at the function of the genes it contains. In the zebra finch at least, many of them seem related to development of the female gonad. Others appear to be involved in other aspects of early development.

But its a head scratcher, Suh says, why these genes get passed down in a roundabout way that differs from the standard system of heredity. Smith, Ross and Davis are similarly pondering the reasons for the systems that they study in lampreys, flies and worms.

Perhaps the chromosomes (or bits of chromosomes) are selfish just in it for themselves and have engineered ways to be retained. Or maybe these germline-restricted chromosomes have a benefit for example, by serving as incubators where newly evolved genes are safely housed until it can be determined if theyre beneficial or damaging to the organism.

Alternatively, the processes could be holdovers from earlier evolutionary events. Maybe, says Smith, this silencing technique evolved before or in parallel with some of the silencing methods that vertebrates use today. Is this something that at one period of time defined our ancestors biology?

But whatever the answer or answers turns out to be, its striking, Suh says, how few people, even among biologists, are aware that genes and heredity so often work in peculiar ways.

Maybe, he says, this is something we need to start teaching earlier on: how even more fascinating the genome is than we already thought.

This article originally appeared in Knowable Magazine, an independent journalistic endeavor from Annual Reviews.

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The curious case of the shrinking genome - American Society for Biochemistry and Molecular Biology

Natural selection shapes all life on Earth. As the world aroundthemchanges, organismsthatcanadapt have a better chance at reproducing. Humans are no exception and whilea fewexamples of recent evolution are known, welack a deeper understanding of how the human genome is being shaped by natural selection.

New findings published in the journalNature Human Behaviorare a smallstep in better understanding human evolution. Theresearchers behind the study aimedto understand how the natural selection of complex traits unfolded. The team looked at 870 human traits that are created by multiple genes,finding that 755 of them were altered due to natural selection in the last 2,000 to 3,000 years.

The team was led by Weichen Song from the Shanghai Jiao Tong University.The researchersused modern human genetic data from the UK Biobank and Psychiatric Genomics Consortium. They comparedthis data to ancient genomic DNA from across Europe and the Near-East, providing insights into changes in the human genome across the last 45,000 years.

The team's most intriguing finding showed that skin pigmentation, body measurement, and dietary traits were "continuously under intense selection pressure" across the time scales investigated. Pressuresforskin color are due to a balancing act of reducing ultraviolet damage, important vitamin D requirements, and heat regulation. In fact, one of the earliest Britons, the Cheddar Man, had dark skin.

Body measurement and dietary traits have also been changed by genetic factors, together with external pressures such as ecology, climate, and migration.

The team also found that certain diseases have not been phased out quite as efficiently as one would expect. The genetic factors associated with conditions such as anorexia nervosa and inflammatory bowel disease were being suppressed, but cases persisted.

While the findings are intriguing, the team considers them just a preliminary foundational step needed for more detailed work. The study is limited by the use of genomes from the UK, which predominantly included people of European ancestry. It was also limited by the ancient genomes employed.

The work also is limited by the methodology of genome-wide association studies which do not distinguish between association and causality.

The Human Genome Project was finished in 2003, so a complete analysis of the human genome is not even 20 years old many mysteries remain to be uncovered in it, and how it has been shaped by evolutionary forces.

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Natural Selection Has Changed The European Genome In The Last 3000 Years - IFLScience

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MENLO PARK, Calif., Nov. 16, 2021 (GLOBE NEWSWIRE) -- PacBio (Nasdaq: PACB), a leading provider of high-quality, highly accurate sequencing platforms, today announced the launch of the HiFiViral SARS-CoV-2 Kit a fully kitted end-to-end solution for COVID-19 surveillance, which public health laboratories can use to identify new SARS-CoV-2 variants and detect all variants circulating within a population.

The HiFiViral SARS-CoV-2 Kit is PacBios first kitted solution for genomic surveillance of COVID-19 variants. The assay leverages PacBios trusted HiFi sequencing to give researchers a more complete view of novel mutations of all types, ensuring that emerging variants are captured.

Accurate and timely detection of new variants of concern is critical to protecting public health. Our new HiFiViral SARS-CoV-2 Kit is a powerful solution that enables robust detection of new variants as they emerge without requiring periodic updates and revalidation to keep pace with the evolving SARS-CoV-2 virus, said Christian Henry, Chief Executive Officer and President of PacBio. As we look to the future and continue to invest in applications to improve human health, this solution offers a differentiated technology based on proven HiFi sequencing and helps address workflow and supply chain bottlenecks that have affected SARS-CoV-2 surveillance efforts to date, enabling laboratories to scale their testing with ease.

The HiFiViral SARS-CoV-2 workflow is a cost-effective and accurate method for viral sequencing, utilizing molecular inversion probes (MIPs) that provide significant workflow improvements over traditional polymerase chain reaction (PCR) amplicon-based methods. HiFi sequencing also enables laboratories to identify multiple virus types present within a single sample. The companion SMRT Link v10.2 software provides a simplified solution to perform quality checks on experiments and capture all types of genetic variation, which is critical information for public health surveillance efforts. Combined with the flexibility to run up to 384 samples at a time, this kit allows more labs to take advantage of powerful HiFi sequencing in the convenience of a ready-to-use kit.

With the HiFiViral SARS-CoV-2 workflow, we were able to capture mutations of all types and saw significant performance improvements over our PCR amplicon approach. The workflow itself was phenomenal. We were able to reduce the hands-on time by almost 80 percent which was a game changer for us, said Melissa Smith, Ph.D., Assistant Professor, Department of Biochemistry & Molecular Genetics, University of Louisville.

Concurrently with the HiFiViral SARS-CoV-2 kit, PacBio is releasing an enhanced end-to-end HiFi microbial whole genome assembly application and companion SMRT Link software on the Sequel IIe System. The upgrade doubles the recommended multiplexing capacity, provides 96 kitted barcodes, and migrates the application to HiFi sequencing while continuing to deliver the industrys leading standard for reference quality microbial genomes. This updated application gives public health labs a new and improved tool for investigating outbreaks in the food supply, tracking antimicrobial resistance, and fully characterizing emerging pathogen threats. Paired with the new HiFiViral SARS-CoV-2 kit, these innovations provide public health and microbial research labs a powerful menu of applications to service a broad range of use cases on their Sequel IIe systems.

We are committed to supporting labs on the front line of this pandemic by providing easier, scalable, and more cost-effective solutions for pathogen surveillance. The launch of the HiFiViral SARS-CoV-2 kit, the upgrade to our microbial whole genome sequencing application, and the suite of SMRT Link companion software solutions are evidence of PacBios commitment to helping labs respond to infectious diseases today and in the future, said Henry.

The HiFiViral SARS-CoV-2 kit is currently shipping. The components for the HiFi microbial whole genome assembly application will ship this quarter.

To learn more, please visit the PacBio website: HiFiViral SARS-CoV-2 Kit and HiFi Microbial WGS application.

About Pacific Biosciences

Pacific Biosciences of California, Inc. (NASDAQ: PACB),is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments arebased onSingle Molecule, Real-Time (SMRT) Sequencing technology, whichdeliversacomprehensiveview of genomes, transcriptomes, and epigenomes,enablingaccess to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBiosequencingsystems arein use by scientists aroundthe world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visitwww.pacb.comand follow@PacBio.

PacBio products are provided for research use only. Not for use in diagnostic procedures.

Forward-Looking Statements

This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to future availability, release dates, uses, accuracy, advantages, quality or performance of, or benefits of using, PacBio products or technologies, the suitability or utility of such products or technologies for particular applications or projects, and the expected benefits of such products or technologies, in each case in connection with use of the HiFiViral SARS-CoV-2 kit and HiFi sequencing technology for viral surveillance, variant detection and other public health efforts, such as investigating outbreaks in the food supply, tracking antimicrobial resistance and characterizing emerging pathogen threats; ability and ease for laboratories to scale testing; potential to address supply bottlenecks; and other future events. Readers are cautioned not to place undue reliance on these forward-looking statements because they are subject to known and unknown risks and uncertainties that could cause actual results to differ materially from the information expressed or implied by forward-looking statements made in this press release. Reported results should not be considered as an indication of future performance. Factors that could materially affect actual results can be found, and readers are strongly encouraged to read the full cautionary statements contained, in PacBios most recent filings with the Securities and Exchange Commission, including its most recent reports on Forms 8-K, 10-K, and 10-Q. These forward-looking statements speak only as of the date hereof, and PacBio disclaims any obligation to update these forward-looking statements, even if new information becomes available.

Contacts

Investors:Todd Friedman+1 (650) 521-8450ir@pacificbiosciences.com

Media:Kathy Lynchpr@pacificbiosciences.com

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PacBio Launches HiFiViral SARS-CoV-2 Kit and Microbial Whole Genome Sequencing Enhancements to Combat Infectious Disease and Strengthen Public Health...

SAN DIEGO, Nov. 15, 2021 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (BNGO), pioneer of optical genome mapping (OGM) and provider of industry-leading data interpretation solutions for next-generation sequencing (NGS) and microarrays, today announced the lineup of content scheduled to be presented at the annual meeting of the Association for Molecular Pathology (AMP). The content is expected to include an oral platform presentation by Dr. Ravi Kolhe at Augusta Universty, six poster presentations, a corporate workshop and an innovation spotlight. The presentations this year span a wide range of applications, including prenatal analysis, genetic disease, hematological malignancies, solid tumor and advances in the OGM technique for detecting more clinically relevant variants, including absence of heterozygosity (AOH) and allelic imbalance. The AMP conference is being held virtually starting today, Monday, November 15 and goes until Friday, November 19, 2021.

Bionanos corporate workshop on Thursday, November 18 from 9:00am - 9:50am EST is planned to feature presentations from Dan Saul (BioDiscovery), Dr. Alex Hastie (Bionano), and Dr. Gordana Raca (Childrens Hospital LA), where theyll highlight the potential advantages of combining data from OGM and next-generation sequencing (NGS) to obtain the most comprehensive view of genome variation available.

The innovation spotlight will feature presentations from Dr. Soheil Shams (CIO), Dr. Alka Chaubey (CMO) and Dr. Adrian Dubuc from Brigham & Womens Hospital and Harvard Medical School. The content for the spotlight will cover Bionanos efforts in building a cancer knowledgebase for interpreting variants faster, the power of combining OGM and NGS data to reveal significantly more clinically relevant variants than with NGS alone and an illustration of an application of OGM as an alternative to karyotyping and FISH for revealing complex, clinically relevant structural variants in an aggressive leukemia/lymphoma subject.

Story continues

The table below outlines each presentation together with the program number for ease of location during the event.

OGM Application Area

Presentation / Poster Title

Affiliation

Genetics

G22. Comprehensive Evaluation and Validation of Amniocytes Using Optical Genome Mapping: From Sample Preparation to Reporting

Augusta University

Hematopathology

H02. Clinical Validation of Optical Genome Mapping to Replace Eosinophilic Leukemia FISH Panel

University Health Network, Toronto, Canada

H13. Comprehensive Detection of Structural Somatic Mutation in Hematological Cancers by Optical Genome Mapping

Bionano Genomics

H15. Clinical Utility of Optical Genome Mapping in Cytogenetic Analysis of Hematologic Malignancies

Augusta University

Informatics

I12. Detecting Absence of Heterozygosity Using High-Resolution Optical Genome Mapping

Bionano Genomics

Solid Tumors

ST74. Optical Genome Mapping for the Chromosomal Characterization of Solid Tumors

Augusta University

Technical Topics

TT24. Optical Genome Mapping: Optimizing Sample Types for Prenatal Testing, Constitutional Disorders, Hematological Malignancies, and Solid Tumor Profiling

Augusta University

Workshop

Topic

Date and Time

Corporate Workshop

Combining Optical Genome Mapping (OGM) with Next-Generation Sequencing (NGS) Data to Provide the Most Comprehensive Genome Analysis for Oncology Applications

Thursday, November 18th from 9:00am - 9:50am EST

We are thrilled to see the broad range of presentations featuring OGM at AMP this year, including coverage of the combination of OGM with NGS data to provide the most comprehensive picture of the genome, stated Erik Holmlin, PhD, CEO of Bionano Genomics. Our customers continue to push forward cutting-edge applications in molecular pathology and we look forward to the authors sharing their research with the AMP community.

For more details and to register for this online event please go to: https://amp21.amp.org/

About Bionano Genomics

Bionano is a provider of genome analysis solutions that can enable researchers and clinicians to reveal answers to challenging questions in biology and medicine. The Companys mission is to transform the way the world sees the genome through optical genome mapping (OGM) solutions, diagnostic services and software. The Company offers OGM solutions for applications across basic, translational and clinical research. Through its Lineagen business, the Company also provides diagnostic testing for patients with clinical presentations consistent with autism spectrum disorder and other neurodevelopmental disabilities. Through its BioDiscovery business, the Company also offers an industry-leading, platform-agnostic software solution, which integrates next-generation sequencing and microarray data designed to provide analysis, visualization, interpretation and reporting of copy number variants, single-nucleotide variants and absence of heterozygosity across the genome in one consolidated view. For more information, visit http://www.bionanogenomics.com, http://www.lineagen.com or http://www.biodiscovery.com

Forward-Looking Statements of Bionano Genomics

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and content of the posters and presentations regarding OGM to be presented at the AMP conference; and the effectiveness and utility of OGM, including in combination with NGS and in comparison to traditional standard of care methods. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: the accuracy of customer posters and presentations to be presented; observations from studies covered by the posters and presentations may not be replicated; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2020 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on managements assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations:Amy ConradJuniper Point+1 (858) 366-3243amy@juniper-point.com

Media Relations:Michael SullivanSeismic+1 (503) 799-7520michael@teamseismic.com

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Bionano Genomics Announces Extensive Lineup of Content to be Presented at the Annual Meeting of the Association for Molecular Pathology Featuring...

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