Category Archives: DNA

COLUMBUS, Ohio--(BUSINESS WIRE)--Clarametyx Biosciences Inc., (Clarametyx) a preclinical stage biotechnology company developing targeted, immune-enabling biologic therapies to counter serious infections associated with biofilms, today announced the publication of a new study in the prestigious journal CELL providing critical new insights about the components within bacterial biofilms that drive resistance to current medicines.

Bacterial biofilms are communities of bacteria embedded within a protective matrix that are associated with nearly 80 percent of bacterial infections. Because biofilms contribute to persistent infections, inflammation, and resistance to therapeutic interventions, there is a pressing need for novel strategies to combat this bacterial defense mechanism. Prior research has demonstrated that an extracellular DNA (eDNA) network stabilized by DNABII proteins are required for the structural integrity of biofilms across many bacterial pathogens. While enzymes that digest DNA can prevent biofilm formation, these enzymes are ineffective against biofilms that have fully formed.

This research initiative aimed to understand the development and maturation of the biofilm to elucidate its resistance to the innate immune system. A series of studies indicated that the biofilm structure is not built on the typical B-form of DNA, but instead relies on the rare Z-form of eDNA, which accumulates as biofilms mature and provides structural integrity to the biofilms matrix. Importantly, the assessments found Z-DNA to be the primary structural form of eDNA within mature biofilms across a range of bacterial pathogens, including Escherichia coli, Klebsiella pneumoniae, and nontypeable Haemophilus influenzae, each of which contribute significant patient burden today. These findings suggest that the development of therapeutic agents designed to drive biofilm eDNA back into its native B-form could enhance the prevention or clinical resolution of biofilm-mediated diseases.

This seminal publication answers a critical piece of the biofilm puzzle by articulating the central role of Z-DNA in the pathogenesis of the biofilm and its resistance to immune intervention, said Steven Goodman, Ph.D., study author, Director of the Oral GI Microbiology Research Affinity Group in the Center for Microbial Pathogenesis at the Abigail Wexner Research Institute (AWRI) at Nationwide Childrens Hospital and co-chair of the Clarametyx scientific advisory board. This improved understanding of the key contributors to biofilm development and defense will transform research efforts to overcome the mature biofilm and prevent its development.

The publication of our research in the globally renowned CELL journal validates the significance of this finding to the research community trying to solve the challenge of persistent bacterial infections and antimicrobial resistance, said Lauren Bakaletz, Ph.D., study author, Director of the Center for Microbial Pathogenesis and Vice President of Basic Sciences for AWRI and co-chair of the Clarametyx scientific advisory board. That the Z-form is the primarily form of eDNA found in mature biofilms provides a vital insight into how we approach the biofilm. If we know what to target, we can efficiently dismantle the eDNA structure, rendering the bacteria much more vulnerable to immune or antibiotic intervention and resolving infections more efficiently to improve patient outcomes while also reducing the risk of antibiotic resistance.

A more sophisticated understanding of the role of the molecular components that strengthen the biofilm and protect the bacteria is critical in our design of novel therapeutics and vaccines that could benefit many people who contract a wide range of severe bacterial infections, said Charles McOsker, Ph.D., co-founder and Chief Scientific Officer of Clarametyx. This invaluable research not only reinforces the central scientific strategy we are pursuing at Clarametyx but also informs the ongoing development of our CMTX-101 novel anti-biofilm antibody therapy that could transform the treatment of bacterial infections by disrupting both newly-formed and mature biofilms.

About Clarametyx Biosciences

Clarametyx Biosciences is combating the formidable challenge of persistent and recalcitrant infections through an innovative technology platform targeting the biofilmbacteria embedded in a protective matrixto enable a more effective immune response or antibiotic intervention. The Columbus, Ohio-based company is building a dynamic pipeline of immune-enabling therapies and vaccines for life-threatening bacterial infections associated with biofilms. Its lead candidate, CMTX-101, is a humanized monoclonal antibody in preclinical development for hospital-acquired pneumonia. For more information, visit us on the web or on LinkedIn.

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New Publication in CELL Implicates a Rare Form of DNA Driving Antimicrobial Resistance in Bacterial Biofilms - Business Wire

Famed 19th century Native American leader Sitting Bull, who died in 1890, is seen in this picture from circa 1885. National Portrait Gallery, Smithsonian Institution/Handout via REUTERS

WASHINGTON, Oct 27 (Reuters) - A sample of Sitting Bull's hair has helped scientists confirm that a South Dakota man is the famed 19th century Native American leader's great-grandson using a new method to analyze family lineages with DNA fragments from long-dead people.

Researchers said on Wednesday that DNA extracted from the hair, which had been stored at the Smithsonian Institution in Washington, confirmed the familial relationship between Sitting Bull, who died in 1890, and Ernie LaPointe, 73, of Lead, South Dakota.

"I feel this DNA research is another way of identifying my lineal relationship to my great-grandfather," said LaPointe, who has three sisters. "People have been questioning our relationship to our ancestor as long as I can remember. These people are just a pain in the place you sit - and will probably doubt these findings, also."

The study represented the first time that DNA from a long-dead person was used to demonstrate a familial relationship between a living individual and a historical figure - and offers the potential for doing so with others whose DNA can be extracted from remains such as hair, teeth or bones.

The new method was developed by scientists led by Eske Willerslev, director of the Lundbeck Foundation GeoGenetics Centre at the University of Cambridge.

The researchers took 14 years to discover a way of extracting useable DNA from the hair, which was degraded after being stored at room temperature before being handed over by the Smithsonian to LaPointe and his sisters in 2007.

Willerslev said he read in a magazine about the Smithsonian turning over the lock of hair from Sitting Bull's scalp and reached out to LaPointe.

"LaPointe asked me to extract DNA from it and compare it to his DNA to establish relationship," said Willerslev, senior author of the research published in the Science Advances. "I got very little hair and there was very limited DNA in it. It took us a long time developing a method that, based on limited ancient DNA, can by compared to that of living people across multiple generations."

The novel technique centered on what is known as autosomal DNA in the genetic fragments extracted from the hair. Traditional analysis involves specific DNA in the Y chromosome passed down the male line or specific DNA in the mitochondria - powerhouses of a cell - passed down from mothers to children. Autosomal DNA instead is not gender specific.

"There existed methods, but they demanded for substantial amounts of DNA or did only allow to go to the level of grandchildren," Willerslev said. "With our new method, it is possible to establish deeper-time family relationships using tiny amounts of DNA."

Sitting Bull, whose Lakota name was Tatanka-Iyotanka, helped bring together the Sioux tribes of the Great Plains against white settlers taking tribal land and U.S. military forces trying to expel Native Americans from their territory. He led Native American warriors who wiped out federal troops led by George Custer at the 1876 Battle of the Little Bighorn in what is now the U.S. state of Montana.

Two official burial sites exist for Sitting Bull, one at Fort Yates, North Dakota and the other at Mobridge, South Dakota. LaPointe said he does not believe the Fort Yates site contains any of his great-grandfather's remains.

"I feel the DNA results can identify the remains buried at the Mobridge, South Dakota site as my ancestor," LaPointe said, raising the possibility of moving the Mobridge remains to another location in the future.

Reporting by Will Dunham, Editing by Rosalba O'Brien

Our Standards: The Thomson Reuters Trust Principles.

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DNA from Sitting Bull's hair confirms living great-grandson's ancestry - Reuters

PLYMOUTH MEETING, Pa., Nov. 3, 2021 /PRNewswire/ --INOVIO (NASDAQ:INO), a biotechnology company focused on bringing to market precisely designed DNA medicines to help protect people from infectious diseases, and help treat cancer, and HPV-associated diseases, today announced that it has received authorization from India's Central Drugs Standard Control Organization (CDSCO)'s Drug Controller General of India (DCGI) to proceed with the Phase 3 segment of INOVIO's global Phase 2/3 trial, INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy), in India for INO-4800, its DNA vaccine candidate for COVID-19. INOVIO is partnering with Advaccine Biopharmaceuticals Suzhou Co., Ltd. (Advaccine) to conduct the INNOVATE Phase 3 segment in multiple countries in Latin America, Asia, and Africa. Regulatory authorization in India follows authorizations from health authorities in Brazil, Philippines, Mexicoand Colombia.

The global Phase 3 segment of INNOVATE will evaluate the efficacy of INO-4800 in a two-dose regimen (2.0 mg per dose), administered one month apart, in a 2-to-1 randomization in men and non-pregnant women 18 years of age and older. The primary endpoint of this case-driven Phase 3 trial is virologically confirmed symptomatic COVID-19.

"As COVID-19 continues to threaten the health and safety of the global population, and many areas of the world are still awaiting sufficient access to safe and effective vaccines, INOVIO is pleased to receive regulatory authorization to proceed with our efficacy Phase 3 trial in India," said Dr. J. Joseph Kim, President and CEO of INOVIO. "INOVIO remains steadfast in its mission to fight COVID-19 through the development of INO-4800, which is designed to serve the needs of those in India and beyond, as both a primary series and a booster vaccine."

INNOVATE's Phase 3 segment builds upon the Phase 2 segment, which was conducted in the U.S. and funded by the U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, in coordination with the Office of the Assistant Secretary of Defense for Health Affairs and the Defense Health Agency. Interim Phase 2 data from the ongoing study was disclosedin a pre-print in MedRxiv in May 2021 and showed INO-4800 to be well-tolerated and immunogenic in adults 18 and older. In another previously disclosed study using clinical samples, INO-4800 was also foundto provide broad cross-reactive immune responses, including neutralizing antibodies and notable T cell responses, against variants of concern (alpha, beta, gamma and, in subsequent research, delta) factors which could be critical in containing COVID-19 as it shifts from pandemic to endemic spread.

This news builds on INOVIO's previously announcedauthorization to proceed in China with two Advaccine-sponsored clinical trials investigating the safety, tolerability, and immunogenicity of heterologous boost combinations with INO-4800, as well as recent positive homologous boostingdata for INO-4800, which was found to produce robust immune responses and was well-tolerated as both a two-dose series and as a homologous booster dose in all adults, including participants 65 years of age and older. Of note, a durable antibody response was observed six months following the second dose, and a homologous booster dose administered 6 to 10.5 months following the second dose also significantly increased antibody and T cell responses. INO-4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity and did not increase in frequency with age and subsequent dosing.

About INO-4800

INO-4800, INOVIO's DNA vaccine candidate against SARS-CoV-2, is composed of a precisely designed DNA plasmid that is injected intradermally followed by electroporation using a proprietary smart device, which delivers the DNA plasmid directly into cells in the body and is intended to produce a well-tolerated immune response. As one of the only nucleic-acid based vaccines that is stable at room temperature for more than a year, at 37C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage, INO-4800 is anticipated to be well-positioned for a primary series immunization as well as a booster.

About INOVIO

INOVIO is a biotechnology company focused on rapidly bringing to market precisely designed DNA medicines to treat and protect people from infectious diseases, cancer, and diseases associated with HPV. INOVIO is the first company to have clinically demonstrated that a DNA medicine can be delivered directly into cells in the body via a proprietary smart device to produce a robust and tolerable immune response. Specifically, INOVIO's lead therapeutic candidate VGX-3100 met primary and secondary endpoints for all evaluable subjects in REVEAL 1, the first of two, Phase 3 trials for precancerous cervical dysplasia, demonstrating ability to destroy and clear both high-grade cervical lesions and the underlying high-risk HPV-16/18. INOVIO is also evaluating INO-4800, a DNA vaccine candidate against COVID-19, in a Phase 2/3 clinical trial; the Phase 3 segment of which has received regulatory approvals to begin in Colombia, Mexico, Brazil, Philippines, and India. INOVIO's partners, Advaccine Biopharmaceuticals and International Vaccine Institute, are also evaluating INO-4800 in ongoing clinical trials in China and South Korea, respectively.

Partners and collaborators include Advaccine, ApolloBio Corporation, AstraZeneca, The Bill & Melinda Gates Foundation, Coalition for Epidemic Preparedness Innovations, Defense Advanced Research Projects Agency/Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense/Department of Defense, HIV Vaccines Trial Network, International Vaccine Institute, Kaneka Eurogentec, Medical CBRN Defense Consortium, National Cancer Institute, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Ology Bioservices, the Parker Institute for Cancer Immunotherapy, Plumbline Life Sciences, Regeneron, Richter-Helm BioLogics, Thermo Fisher Scientific, University of Pennsylvania, Walter Reed Army Institute of Research, and The Wistar Institute. For more information, visit http://www.inovio.com.

CONTACTS:

Media: Jeff Richardson, 267-440-4211, [emailprotected]Investors: Ben Matone, 484-362-0076, [emailprotected]

This press release contains certain forward-looking statements relating to our business, including our plans to develop and commercialize DNA medicines, our expectations regarding our research and development programs, including the planned initiation and conduct of pre-clinical studies and clinical trials and the availability and timing of data from those studies and trials, our ability to successfully manufacture and produce large quantities of our product candidates if they receive regulatory approval and planned collaborations with third parties. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, our ability to secure sufficient manufacturing capacity to mass produce our product candidates, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2020 , our Quarterly Report on Form 10-Q for the quarter ended September 30, 2021 and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.

SOURCE INOVIO Pharmaceuticals, Inc.

http://www.inovio.com

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INOVIO Further Expands INNOVATE Phase 3 Trial for COVID-19 DNA Vaccine Candidate INO-4800 With Regulatory Authorization from India - PRNewswire

Officials say a young hitchhiker who died in a car crash in Alabama in 1961 and was buried in a grave marked UNKNOWN has finally been identified through DNA testing. Killed when a vehicle from which hed accepted a ride crashed and plunged into a river in Bibb County, the hitchhiker didnt have any identification. Community members raised money for his burial, and a tombstone was engraved with the date of the wreck: March 27, 1961. Coroner CW West says a team of genealogists using DNA from the body confirmed the remains to be those of 15-year-old Daniel Paul Danny Armantrout. They've contacted a surviving brother who plans to come to Alabama.

Officials say a young hitchhiker who died in a car crash in Alabama in 1961 and was buried in a grave marked UNKNOWN has finally been identified through DNA testing.

Killed when a vehicle from which hed accepted a ride crashed and plunged into a river in Bibb County, the hitchhiker didnt have any identification.

Community members raised money for his burial, and a tombstone was engraved with the date of the wreck: March 27, 1961.

Coroner CW West says a team of genealogists using DNA from the body confirmed the remains to be those of 15-year-old Daniel Paul Danny Armantrout.

They've contacted a surviving brother who plans to come to Alabama.

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Victim of 1961 car wreck finally identified using DNA - WVTM13

by: Farrell SweeneyNov 2, 2021

Nicky Romero channels a new kind of energy with not so foreign origins in his latest release Acid Is My DNA. Departing from the progressive house sound that popularized him as a household name, Romero forays into sonic territory that harkens to his 2012 style, notably in Generation 303.

Although in recent times, Romeros music has historically leaned on a combination of vocals and upbeat progressive drops that give his tracks the adaptability of both radio play and live performances, Acid Is My DNA has an entirely different appealdriven by its ominous build, vintage synth usage, and hectic energy.

It remains to be seen whether Acid Is My DNA is indicative of a new direction for Romero, or simply a one-off release.

Acid Is My DNA is out now via Romeros own Protocol Recordings. Stream below.

Featured image: Kevin Anthony Canales

Tags: acid house, acid is my dna, Nicky Romero, protocol recordings

Categories: Music

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Nicky Romero renews origins with unexpected single, 'Acid Is My DNA' - Dancing Astronaut - Dancing Astronaut

Yi Li, professor of plant science in the College of Agriculture, Health, and Natural Resources is working on a new $500,000 Biotechnology Risk Assessment Research Grant (BRAG) from the USDA/NIFA to study a genetic editing technique in tomato plants.

Genetically engineered organisms are becoming increasingly popular given their potential applications to improve the food supply. Gene editing allows scientists to manipulate an organisms DNA, leading to produce that stays fresher longer, resists pests and viruses, or has higher nutritional content.

One common method of gene editing is manipulating DNA methylation. DNA methylation is the process by which methyl groups are added to a DNA molecule. This changes the activity of that DNA segment without changing the DNA itself. Methylation can suppress or promote the expression of certain genes and the proteins they code for.

This promising gene editing technique could improve crops on a large scale. However, the potential unintended side effects of this process are not well-studied, hindering its potential agricultural applications.

Tomatoes are one of the most popular forms of produce, making them an excellent candidate for potential gene editing enhancements. Furthermore, tomato quality and attributes are highly influenced by DNA methylation events.

Li will specifically look at CRISPR/dCas-mediated DNA methylation in tomatoes. Research on this technique has shown there are some off-target effects, or methylation changes to parts of the genome scientists were not intentionally changing. But no one has yet characterized what these effects are, creating a significant knowledge gap Li is now looking to fill.

Li will compare this methylation technique to genetic transformation, another gene editing technique. Genetic transformation differs from DNA methylation because it involves introducing foreign DNA into the plants genome, rather than working on changing the expression of its own. Li will compare these two gene editing techniques to more conventional growing techniques without gene editing.

Li will examine the DNA methylation, RNA sequences, fruit quality, and other observable characteristics for each method. This work will directly address the BRAG Programs priority to gain information about the types and frequencies of nucleic acid changes various genetic engineering techniques introduce into important crops, like tomatoes.

This work will also support the BRAG program goal of providing regulatory agencies with knowledge to make scientifically informed decisions regarding genetically engineered organisms to protect consumers and the environment. This aspect of the project will be largely carried out by co-principal investigator, Stacey Stearns. Stearns is a communications specialist in UConn Extension.

The knowledge generated from this study will aid plant breeders practicing DNA methylation editing in crops and facilitate the policy- and decision-making process at federal regulatory agencies, Li says.

Lis project includes a public education component. Li and his team will create and share articles, websites, videos, and presentations with the general public.

This outreach will help the public better understand gene editing technology and its applications for agriculture. Education about genetic engineering can help dispel misinformation and misunderstandings about gene editing.

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Plant Science Professor Studying Unintended Effects of Gene Editing in Tomatoes - UConn Today - UConn Today

Genetic detective work has uncovered an obscure ancestor of modern bread wheat, in a finding similar to uncovering a famous long-lost relative through DNA analysis in humans.

In a study which appears in Nature Biotechnology researchers sequenced the DNA from 242 unique accessions of Aegilops tauschii gathered over decades from across its native range from Turkey to Central Asia.

Population genome analysis led by Dr. Kumar Gaurav from the John Innes Centre revealed the existence of a distinct lineage of Aegilops tauschii restricted to present-day Georgia, in the Caucuses region some 500 kilometers from the Fertile Crescent where wheat was first cultivated an area stretching across modern-day Iraq, Syria, Lebanon, Palestine, Israel, Jordan, and Egypt.

First author of the study in Nature Biotechnology, Dr. Kumar Gaurav said, The discovery of this previously unknown contribution to the bread wheat genome is akin to discovering the introgression of Neanderthal DNA into the out of Africa human genome.

Researchers on a wild wheat relatives foraging trip in the central Zagros mountains in western Iran. Credit: Ali Mehrabi

It is most likely to have occurred through a hybridization outside the Fertile Crescent. This group of Georgian accessions form a distinct lineage that contributed to the wheat genome by leaving a footprint in the DNA.

The discovery comes via a major international collaboration to improve crops by exploring useful genetic diversity in Aegilops tauschii, a wild relative of bread wheat. The Open Wild Wheat Consortium brought together 38 research groups and researchers from 17 countries.

Further research by Dr. Jesse Polands group at Kansas State University was published in a companion paper in Communications Biology and shows that the ancestral Aegilops tauschii DNA found in modern bread wheat includes the gene that gives superior strength and elasticity to dough.

Dr. Poland said, We were amazed to discover that this lineage has provided the best-known gene for superior dough quality.

The researchers speculate that the newly discovered lineage may have been more geographically widespread in the past, and that it may have become separated as a refugium population during the last ice-age.

Reflecting on all that has come together to make this work possible, Dr Brande Wulff, corresponding author of the study, remarked, Fifty or sixty years ago at a time when we barely understood DNA, my scientific forebears were traversing the Zagros mountains in the middle east and Syria and Iraq. They were collecting seeds, perhaps having an inkling that one day these could be used for improving wheat. Now we are so close to unlocking that potential, and for me that is extraordinarily exciting.

Modern hexaploid wheat, is a complex genetic combination of different grasses with a huge genetic code, split into A, B and D sub-genomes. Hexaploid wheat accounts for 95 percent of all cultivated wheat. Hexaploid means that the DNA contains six sets of chromosomes three pairs of each.

Through a combination of natural hybridizations and human cultivation, Aegilops tauschii provided the D-genome to modern wheat. The D-genome added the properties for making dough, and enabled bread wheat to flourish in different climates and soils.

The origin of modern hexaploid bread wheat has long been the subject of intense scrutiny with archeological and genetic evidence suggesting that the first wheat was cultivated 10,000 years ago in the Fertile Crescent.

Domestication, while increasing yield and increasing agronomic performance, came at the cost of a pronounced genetic bottleneck eroding genetic diversity for protective traits to be found in Aegilops tauschii such as disease resistance and heat tolerance.

Analysis performed by Dr. Gaurav and the research team revealed that just 25% of the genetic diversity present in Aegilops tauschii made it into hexaploid wheat. To explore this diversity in the wild gene pool, they used a technique called association mapping to discover new candidate genes for disease and pest resistance, yield and environmental resilience.

Dr. Sanu Arora, who had earlier led a study to clone disease resistance genes from Aegilops tauschii said, Previously we were restricted to exploring a very small subset of the genome for disease resistance, but in the current study, we have generated data and techniques to undertake an unbiased exploration of the species diversity.

Further experiments demonstrated the transfer of candidate genes for a subset of these traits into wheat using genetic transformation and conventional crossing facilitated by a library of synthetic wheats specially bred material which incorporates Aegilops tauschii genomes.

This publicly available library of synthetic wheats captures 70 percent of the diversity present across all three known Aegilops tauschii lineages, enabling researchers to assess traits rapidly in a background of hexaploid wheats.

Our study provides an end-to-end pipeline for rapid and systematic exploration of the Aegilops tauschii gene pool for improving modern bread wheat, says Dr. Wulff.

High molecular weight glutenin gene diversity in Aegilops tauschii demonstrates unique origin of superior wheat quality, appears in Communications Biology.

Reference: Population genomic analysis of Aegilops tauschii identifies targets for bread wheat improvement by Kumar Gaurav, Sanu Arora, Paula Silva, Javier Snchez-Martn, Richard Horsnell, Liangliang Gao, Gurcharn S. Brar, Victoria Widrig, W. John Raupp, Narinder Singh, Shuangye Wu, Sandip M. Kale, Catherine Chinoy, Paul Nicholson, Jess Quiroz-Chvez, James Simmonds, Sadiye Hayta, Mark A. Smedley, Wendy Harwood, Suzannah Pearce, David Gilbert, Ngonidzashe Kangara, Catherine Gardener, Macarena Forner-Martnez, Jiaqian Liu, Guotai Yu, Scott A. Boden, Attilio Pascucci, Sreya Ghosh, Amber N. Hafeez, Tom OHara, Joshua Waites, Jitender Cheema, Burkhard Steuernagel, Mehran Patpour, Annemarie Fejer Justesen, Shuyu Liu, Jackie C. Rudd, Raz Avni, Amir Sharon, Barbara Steiner, Rizky Pasthika Kirana, Hermann Buerstmayr, Ali A. Mehrabi, Firuza Y. Nasyrova, Noam Chayut, Oadi Matny, Brian J. Steffenson, Nitika Sandhu, Parveen Chhuneja, Evans Lagudah, Ahmed F. Elkot, Simon Tyrrell, Xingdong Bian, Robert P. Davey, Martin Simonsen, Leif Schauser, Vijay K. Tiwari, H. Randy Kutcher, Pierre Hucl, Aili Li, Deng-Cai Liu, Long Mao, Steven Xu, Gina Brown-Guedira, Justin Faris, Jan Dvorak, Ming-Cheng Luo, Ksenia Krasileva, Thomas Lux, Susanne Artmeier, Klaus F. X. Mayer, Cristobal Uauy, Martin Mascher, Alison R. Bentley, Beat Keller, Jesse Poland and Brande B. H. Wulff, 1 November 2021, Nature Biotechnology.DOI: 10.1038/s41587-021-01058-4

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How Bread Wheat Got Its Gluten: DNA Detective Work Uncovered an Obscure Ancestor of Modern Bread Wheat - SciTechDaily

The rules of inheritance are supposedly easy. Dads DNA mixes with moms to generate a new combination. Over time, random mutations will give some individuals better adaptability to the environment. The mutations are selected through generations, and the species becomes stronger.

But what if that central dogma is only part of the picture?

A new study in Nature Immunology is ruffling feathers in that it re-contextualizes evolution. Mice infected with a non-lethal dose of bacteria, once recovered, can pass on a turbo-boosted immune system to their kids and grandkidsall without changing any DNA sequences. The trick seems to be epigenetic changesthat is, how genes are turned on or offin their sperm. In other words, compared to millennia of evolution, theres a faster route for a species to thrive. For any individual, its possible to gain survivability and adaptability in a single lifetime, and those changes can be passed on to offspring.

We wanted to test if we could observe the inheritance of some traits to subsequent generations, lets say independent of natural selection, said study author Dr. Jorge Dominguez-Andres at Radboud University Nijmegen Centre.

The existence of epigenetic heredity is of paramount biological relevance, but the extent to which it happens in mammals remains largely unknown, said Drs. Paola de Candia at the IRCCS MultiMedica, Milan, and Giuseppe Matarese at the Treg Cell Lab, Dipartimento di Medicina Molecolare e Biotecnologie Mediche at the Universit degli Studi di Napoli in Naples, who were not involved in the study. Their work is a big conceptual leap.

The paper is controversial because it builds upon Darwins original theory of evolution.

You know this example: giraffes dont have long necks because they had to stretch their necks to reach higher leaves. Rather, random mutations in the DNA that codes for long necks was eventually selected, mostly because those giraffes were the ones that survived and procreated.

Yet recent studies have thrown a wrench into the long-standing dogma around how species adapt. At their root is epigenetics, a mechanism above DNA to regulate how our genes are expressed. Its helpful to think of DNA as base, low-level codeASCII in computers. To execute the code, it needs to be translated into a higher language: proteins.

Similar to a programming language, its possible to silence DNA with additional bits of code. Its how our cells develop into vastly different organs and body partslike the heart, kidneys, and braineven though they have the same DNA. This level of control is dubbed epigenetics, or above genetics. One of the most common ways to silence DNA is to add a chemical group to a gene so that, like a wheel lock, the gene gets stuck as its trying make a protein. This silences the genetic code without damaging the gene itself.

These chemical markers are dotted along our genes, and represent a powerful way to control our basic biologyanything from stress to cancer to autoimmune diseases or psychiatric struggles. But unlike DNA, the chemical tags are thought to be completely wiped out in the embryo, resulting in a blank slate for the next generation to start anew.

Not so much. A now famous study showed that a famine during the winters of 1944 and 1945 altered the metabolism of kids who, at the time, were growing fetuses. The consequence was that those kids were more susceptible to obesity and diabetes, even though their genes remained unchanged. Similar studies in mice showed that fear and trauma in parents can be passed onto pupsand grandkidsmaking them more susceptible, whereas some types of drug abuse increased the pups resilience against addiction.

Long story short? DNA inheritance isnt the only game in town.

The new study plays on a similar idea: that an individuals experiences in life can change the epigenetic makeup of his or her offspring. Here, the authors focused on trained immunitythe part of the immune system that we have at birth, but is capable of learning and remembering previous infections to better fight off the next round.

The team first exposed adult mice to infectious elements like fungi or yeast particles to simulate an infection. Once recovered, the mice were mated with healthy mice, resulting in normal-looking baby pups.

But they all had a superpower. When challenged with potential pathogenssay, the bacteria E. Colithey showed a much stronger immune reaction compared to mice with non-infected parents. The pups bodies were able to better recruit immune cells to infection sites, and they also triggered a more ferocious immune response against bacterial attackerseven though it was their first encounter with these pathogens.

Even more impressive, this superimmunity continued for the next generation. The grandkids of mice originally infected also had lower bacteria levels in their system after rummaging around a bacteria-rich environment. However, the protection tapered in the third generationthe great-grandkidssuggesting that whatever was passed on had an expiry date.

How can trained immunity be passed on to offspring?

The first head-scratcher was that on the surface, white blood cells and other attackers didnt seem any different between disease-resistant mice and normal ones. But when the team looked to the source of immune cellsthe bone marrowtheir epigenetic landscape painted a vastly changed picture.

Mice born from previously infected parents or grandparents had a more open epigenetic landscape. That is, several of their genes that help immune cells develop and activate were more easily accessible, allowing them to rapidly turn on in times of need. One type of immune soldier was especially primed for action in these mice, with a boosted metabolism and responsiveness to threats.

But how can these changes be passed along to the next generation when the parents never directly experienced an infection?

One answer seems to be altered sperm. Looking at the epigenetic landscape, the team found a fingerprint that better primed white blood cells to protect the pups from any bacteria. Fortified sperm isnt the only answer; mice born from previously infected moms also had turbo-boosted immunity, but how that works remains a mystery. How changes in immune cell epigenetics are telegraphed to reproductive cells is also anyones guess, although drifting biomolecules called small interfering RNA may be the messenger.

Bottom line? Epigenetic soft inheritance is more widespread than we thought. While the work is in mice, a previous study showed that children of parents who were given the BCG vaccine had substantially higher early-life survival. Like mice, we may also inherit our parents immunity and pass it on to our kids.

But its not all unicorns and rainbows. Strong inflammatory responses, while efficient at fighting off bacterial invaders, can also trigger atherosclerosis, heart and blood vessel diseases, and even accelerated aging. The question the team next seeks to answer is, does inherited superimmunity come with unexpected downsides?

For now, the results build upon previous observations that DNA isnt the end-all when it comes to inheritance. Im really curious to see how the scientific community sees this paper. Im sure therell be some criticism, said Dominguez-Andres.

Image Credit: Gerd Altmann from Pixabay

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How Mice Transmitted Turbocharged Immune Systems to Their Offspring Through Sperm - Singularity Hub

Even as the world is busy providing the first and second doses of the COVID-19 vaccines to its citizens, countries like the United States and some other European countries have started giving a third dose of the vaccine called the booster shot to fight against the deadly coronavirus.

New data suggests that while the current plasmid DNA and mRNA vaccines have so far proven effective against COVID-19, the protection they offer may fade after a while.COVID-19 is a completely new virus that continues to evolve and mutate throwingthe biggest challenge for experts.

The decision is also taken due to the fact that the Delta variant of the COVID-19 which is more infectious and spreads easily is driving a new surge of cases, including a rising number of breakthrough cases for fully vaccinated people. This is also responsible for why the attention has turned to the need for another COVID-19 vaccine dose.

New research suggests that the protection the main two mRNA vaccines - Pfizer and Moderna give against COVID-19 might fade after several months.

The study was conducted on vaccinated people in Israel who mostly got the Pfizer shot. Israel beganvaccination in December 2020 ahead of most countries.

The study indicates that as the Delta variant spread there was a correlation between receiving the vaccine at an earlier date and contracting a breakthrough case.

The study pointed out that patients vaccinated in January 2021 were 2.26 times more likely to contract a breakthrough infection than those vaccinated in April 2021.

It shows that more people are being exposed to the Delta variant andmore vaccinated people are getting breakthrough infections than the initial data suggested.

The study conducted inIsrael shows that the protection starts to fade around six months for some people from the time they become fully vaccinated.

There is an initial surge in the number of immune cells churning out antibodies and other molecules after vaccination, which then slowly drops.

This leaves behind a small pool of long-lasting 'memory' B and T cells that patrol the body for future infections by that pathogen.

A booster dose causes antibody-making B cells to multiply, elevating the levels of antibodies against the pathogen once again like after vaccination.

In time, the number ofantibodies will decrease but the pool of memory B cells left behind will be larger than before, leading to a faster, stronger response.

Boosters also promote a process called affinity maturation, in which 'engaged' B cells,triggered by the vaccine travel to the lymph nodes.

Here, they gain mutations making the antibodies they produce bind to pathogens more strongly, potentially enhancing their potency.

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DNA Explainer: What is the science behind COVID-19 vaccine booster shot - DNA India

A new discovery was extracted right from the biological structure of vertebrate genomes. The material, known as the microchromosomes, was found to have a more significant role in the life of mammals than first thought. The tiny specks of chromosomes that are exclusively present in the genes of every bird and reptile also bear the same function in mammals.

(Photo: Jennifer et al.)

The latest research conducted a comprehensive effort to identify and categorize the DNA information contained in various groups of species. The results format the readings present the prevalence of DNA molecules in many avian and scaled animals throughout the million years in evolutionary history. In a surprising analysis, the experts identified several fragments of the genetic codes in the birds and reptiles as part of the larger chromosomes composed in many placental and marsupial mammalian species. The findings suggest that contrary to the belief, the genetics in humans are not entirely unique since they are considered mammals, too.

La Trobe University genetics expert and author of the study Jenny Graves said in a New Atlasreport that their team was able to compare the sequences extracted from a wide array of vertebrate species, including snakes, platypus, birds, lizards, and even humans. The expert said that the microchromosomes are relatively similar between the bird and reptiles species based on the investigation's result. Surprisingly, the microchromosome identified from both groups was also discovered in a tiny fish-like creature with an anatomical structure with an absent backbone.

Known as Amphioxus, the species was determined to have a shared lineage with the vertebrates that existed 684 million years ago. When the genetic data was traced back to the ancient Amphioxus, it was found that the genetic links are still present to its collective descendants. The speck of the genome was deemed an essential part of the vertebrates and not as useless as it was first discovered.

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The mammals have members that, through evolving in millions of years, were able to pass, mix, and even absorb several microchromosomes with each other. The spectacular cross-overs of the genes in the mammalian species developed the 'normal' sequence today. Moreover, similar microchromosomes in mammals are charted in the same parts of their cells.

University of New South Wales biology expert and co-author of the study Paul Waters said in a Science Alertreport that the microchromosomes, along with being the same in each species, are also found to form a cluster in the central region of the nucleus. The tiny specks are known to have a way of relaying signals with each other, meaning that they indeed have a protein characteristic known as functional coherence. Graves added that normal chromosomes in both the mammal and human species are indeed a product of development between the numerous junk DNA accumulated over time. The study was published in the journal PNAS, titled "Microchromosomes are building blocks of bird, reptile, and mammal chromosomes."

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Microchromosomes Identified as Building Blocks of Every Vertebrate Animal; Junk DNA Specks More Essential than First Thought - Science Times