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Biology

Ancient DNA reveals the world’s oldest family tree

Analysis of ancient DNA from one of the best-preserved Neolithic tombs in Britain has revealed that most of the people buried there were from five continuous generations of a single extended family.

By analysing DNA extracted from the bones and teeth of 35 individuals entombed at Hazleton North long cairn in the Cotswolds-Severn region, the research team was able to detect that 27 of them were close biological relatives. The group lived approximately 5700 years ago — around 3700-3600 BC — around 100 years after farming had been introduced to Britain.

Published in Nature, it is the first study to reveal in such detail how prehistoric families were structured, and the international team of archaeologists and geneticists say that the results provide new insights into kinship and burial practices in Neolithic times.

The research team — which included archaeologists from Newcastle University, UK, and geneticists from the University of the Basque Country, University of Vienna and Harvard University — show that most of those buried in the tomb were descended from four women who had all had children with the same man.

The cairn at Hazleton North included two L-shaped chambered areas which were located north and south of the main ‘spine’ of the linear structure. After they had died, individuals were buried inside these two chambered areas and the research findings indicate that men were generally buried with their father and brothers, suggesting that descent was patrilineal with later generations buried at the tomb connected to the first generation entirely through male relatives.

While two of the daughters of the lineage who died in childhood were buried in the tomb, the complete absence of adult daughters suggests that their remains were placed either in the tombs of male partners with whom they had children, or elsewhere.

Although the right to use the tomb ran through patrilineal ties, the choice of whether individuals were buried in the north or south chambered area initially depended on the first-generation woman from whom they were descended, suggesting that these first-generation women were socially significant in the memories of this community.

There are also indications that ‘stepsons’ were adopted into the lineage, the researchers say — males whose mother was buried in the tomb but not their biological father, and whose mother had also had children with a male from the patriline. Additionally, the team found no evidence that another eight individuals were biological relatives of those in the family tree, which might further suggest that biological relatedness was not the only criterion for inclusion. However, three of these were women and it is possible that they could have had a partner in the tomb but either did not have any children or had daughters who reached adulthood and left the community so are absent from the tomb.

Dr Chris Fowler of Newcastle University, the first author and lead archaeologist of the study, said: “This study gives us an unprecedented insight into kinship in a Neolithic community. The tomb at Hazleton North has two separate chambered areas, one accessed via a northern entrance and the other from a southern entrance, and just one extraordinary finding is that initially each of the two halves of the tomb were used to place the remains of the dead from one of two branches of the same family. This is of wider importance because it suggests that the architectural layout of other Neolithic tombs might tell us about how kinship operated at those tombs.”

Iñigo Olalde of the University of the Basque Country and Ikerbasque, the lead geneticist for the study and co-first author, said: “The excellent DNA preservation at the tomb and the use of the latest technologies in ancient DNA recovery and analysis allowed us to uncover the oldest family tree ever reconstructed and analyse it to understand something profound about the social structure of these ancient groups.”

David Reich at Harvard University, whose laboratory led the ancient DNA generation, added: “This study reflects what I think is the future of ancient DNA: one in which archaeologists are able to apply ancient DNA analysis at sufficiently high resolution to address the questions that truly matter to archaeologists.”

Ron Pinhasi, of the University of Vienna, said: “It was difficult to imagine just a few years ago that we would ever know about Neolithic kinship structures. But this is just the beginning and no doubt there is a lot more to be discovered from other sites in Britain, Atlantic France, and other regions.”

The project was an international collaboration between archaeologists from the Universities of Newcastle, York, Exeter and Central Lancashire, and geneticists at the University of Vienna, University of the Basque Country and Harvard University. Corinium Museum, Cirencester, provided permission to sample the remains in their collection.

The work received primary funding from a Ramón y Cajal grant from the Ministerio de Ciencia e Innovación of the Spanish Government (RYC2019-027909-I), Ikerbasque — Basque Foundation of Science, the US National Institutes of Health (grant GM100233), the John Templeton Foundation (grant 61220), a private gift from Jean-François Clin, the Allen Discovery Center program, a Paul G. Allen Frontiers Group advised program of the Paul G. Allen Family Foundation, and the Howard Hughes Medical Institute

DNA sequencing illustration (stock image).
Categories
Biology human body

UCLA Researchers Discover How Immune Cells Can be Trained to Fight Viruses

“Like a soldier or an athlete, innate immune cells can be trained by past experiences to become better at fighting infections.”

UCLA researchers have discovered the fundamental rule that allows the human body’s immune cells to be trained to aggressively respond to viruses, bacteria and other invaders, the university announced Thursday.

UCLA researchers identified a molecular mechanism within macrophages, which are infection-fighting cells in the innate immune system, that determines whether and how well the cells can be trained to fight invaders.

“Like a soldier or an athlete, innate immune cells can be trained by past experiences to become better at fighting infections,” said the study’s lead author, Quen Cheng, an assistant clinical professor of infectious diseases at UCLA’s Geffen School of Medicine.

Cheng noted that some experiences appear to be better than others for immune training, and that “this surprising finding motivated us to better understand the rules that govern this process.”

The study was published in the journal “Science” Friday, according to UCLA, which added that the findings could lead to strategies that enhance the immune system’s function.

Researchers found that immune training can occur if a cell’s DNA becomes unwrapped and exposes new genes that enable the cell to respond more aggressively, according to the study’s senior author Alexander Hoffman, professor of microbiology and director of the Institute for Quantitative and Computational Biosciences. When DNA is wrapped, only selected regions are exposed and accessible to fight an infection.

The UCLA researchers found that the precise dynamics of a key immune signaling molecule in macrophages, which is called NFKB and helps immune cells identify threats, determine if the DNA unwraps and genes are exposed.

Researchers also reported that the dynamic activity of NFKB itself is determined by the precise type of extracellular stimulus introduced to the macrophages.

“Importantly, our study shows that innate immune cells can be trained to become more aggressive only by some stimuli and not others,” Cheng said. “This specificity is critical to human health because proper training is important for effectively fighting infection, but improper training may result in too much inflammation and autoimmunity, which can cause significant damage.”

The NFKB is activated when receptors on the immune cells detect threatening external stimuli. The dynamics of NFKB form a language that UCLA researchers compared to Morse code — it communicates to the DNA that there is an external threat and tells the genes to get ready for battle.

Researchers used the bone marrow of mice to follow the activity of NFKB in macrophages, according to UCLA. They tracked how the molecule’s dynamics changed in response to several stimuli. NFKB was successful only when the stimulus induced non-oscillating NFKB activity.

“For a long time, we’ve known intuitively that whether NFKB oscillates or not must be important, but have simply not been able to figure out how,” Cheng said. “These results are a real breakthrough for understanding the language of immune cells, and knowing the language will help us `hack’ the system to improve immune function.”

The training process was simulated with a mathematical model, as well, UCLA said. Mathematical modeling of immune regulatory systems is a key goal of Hoffman’s laboratory.

Hoffman and Cheng expect to inspire a wide range of other studies from their research, including investigations into diseases caused by immune cells, strategies to improve immune training to fight infections and how to complement existing vaccine approaches.

“This study shows how collaborations between researchers in the UCLA College and David Geffen School of Medicine can produce innovative and impactful science that benefits human health,” Hoffmann said. Cheng earned his Ph.D. under Hoffman’s guidance at UCLA’s Specialty Training and Advanced Research program.

The study’s co-lead author is Sho Ohta, an assistant professor at the University of Tokyo and a former postdoctoral scholar in Hoffmann’s UCLA laboratory. Co-authors also include UCLA M.D. and Ph.D. student Katherine Sheu; Roberto Spreafico, a former postdoctoral scholar in Hoffmann’s laboratory; Adewunmi Adelaja, UCLA M.D. student who earned his Ph.D. in Hoffmann’s laboratory; and Brooks Taylor, a former UCLA doctoral student in Hoffmann’s laboratory.

“For a long time, we’ve known intuitively that whether NFKB oscillates or not must be important, but have simply not been able to figure out how,” Cheng said. “These results are a real breakthrough for understanding the language of immune cells, and knowing the language will help us `hack’ the system to improve immune function.”

The training process was simulated with a mathematical model, as well, UCLA said. Mathematical modeling of immune regulatory systems is a key goal of Hoffman’s laboratory.

Hoffman and Cheng expect to inspire a wide range of other studies from their research, including investigations into diseases caused by immune cells, strategies to improve immune training to fight infections and how to complement existing vaccine approaches.

“This study shows how collaborations between researchers in the UCLA College and David Geffen School of Medicine can produce innovative and impactful science that benefits human health,” Hoffmann said. Cheng earned his Ph.D. under Hoffman’s guidance at UCLA’s Specialty Training and Advanced Research program.

The study’s co-lead author is Sho Ohta, an assistant professor at the University of Tokyo and a former postdoctoral scholar in Hoffmann’s UCLA laboratory. Co-authors also include UCLA M.D. and Ph.D. student Katherine Sheu; Roberto Spreafico, a former postdoctoral scholar in Hoffmann’s laboratory; Adewunmi Adelaja, UCLA M.D. student who earned his Ph.D. in Hoffmann’s laboratory; and Brooks Taylor, a former UCLA doctoral student in Hoffmann’s laboratory.

“For a long time, we’ve known intuitively that whether NFKB oscillates or not must be important, but have simply not been able to figure out how,” Cheng said. “These results are a real breakthrough for understanding the language of immune cells, and knowing the language will help us `hack’ the system to improve immune function.”

The training process was simulated with a mathematical model, as well, UCLA said. Mathematical modeling of immune regulatory systems is a key goal of Hoffman’s laboratory.

Hoffman and Cheng expect to inspire a wide range of other studies from their research, including investigations into diseases caused by immune cells, strategies to improve immune training to fight infections and how to complement existing vaccine approaches.

“This study shows how collaborations between researchers in the UCLA College and David Geffen School of Medicine can produce innovative and impactful science that benefits human health,” Hoffmann said. Cheng earned his Ph.D. under Hoffman’s guidance at UCLA’s Specialty Training and Advanced Research program.

The study’s co-lead author is Sho Ohta, an assistant professor at the University of Tokyo and a former postdoctoral scholar in Hoffmann’s UCLA laboratory. Co-authors also include UCLA M.D. and Ph.D. student Katherine Sheu; Roberto Spreafico, a former postdoctoral scholar in Hoffmann’s laboratory; Adewunmi Adelaja, UCLA M.D. student who earned his Ph.D. in Hoffmann’s laboratory; and Brooks Taylor, a former UCLA doctoral student in Hoffmann’s laboratory.

The study was funded by UCLA’s Department of Medicine’s STAR Program and the National Institutes of Health.Copyright CNS – City News Service

IMMUNE CELLS TO FIGHT AGAINST VIRUSES

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Biology human body Uncategorized

Scientists Devise Technique to Stop Cells from Aging, Reduce Chances of Cancer

Cells inside our body keep dividing regularly, as is the scheme of the nature. However, if the division fails to take place, the cells will eventually die, leading to the chance of developing age-related diseases as well as cancer.

There are stretches of Deoxy Ribonucleic Acid (DNA) called telomeres present at the ends of chromosomes like protective caps. During cell division, these telomeres become shorter which makes the productivity of the protective cap less effective. Hence, the telomeres need to be checked upon regularly and elongated because if these DNA components get too short, the cell will stop dividing and move towards cell aging.

Scientists have studied what helps the telomeres to function properly and have found that a RNA species called TElomeric Repeat-containing RNA (TERRA) helps to work like the maintenance mechanic for telomeres. These get recruited at sites where telomeres need regulation and send a signal indicating that the telomeres need to be elongated or repaired. Which form of a system sends TERRA to the chromosome end is not known.

TERRA are a type of molecules called the non-coding RNAs, which do not get translated into proteins but instead function as chromosomes’ structural components. To study how these were getting assigned to places and remaining there, scientists visualized TERRA molecules under a microscope and found that a short stretch of the ribonucleic acid (RNA) was instrumental to bring it to the telomeres.

Now once TERRA has reached its required location, several proteins regulate its association with telomeres. Here, a protein called RAD51 plays a crucial role. Scientists from Ecole Polytechnique Fédérale de Lausanne and Masaryk University found that RAD51 was helping TERRA stick to telomeric DNA to form a so-called RNA-DNA hybrid molecule.

This sort of hybrid molecule formation has been previously detected only in the case of DNA repair. To witness it taking place during telomere repair is revolutionary.

FREEZE THE AGEING PROCESS
Categories
Biology

“THE KILLER MUTATIONS”

Scientists have discovered a handful of ultrarare mutations present in our cells from birth that likely shave years off a person’s life. Each of these DNA variants, most likely inherited from our parents, can reduce life span by as much as 6 months, the researchers estimate. And different combinations can dictate how long people live before developing age-related diseases such as cancer, diabetes, and dementia.

A person’s genes don’t set a specific natural life span—diet and many other factors play large roles, too—but studies have shown that DNA variants can influence the aging process. Biologists chalk up less than one-third of that influence to the genes we inherit. The source of other age-influencing DNA variation is environmental: Sun damage, chemical exposure, and other insults that create thousands of random mutations. Each cell’s collection of these environmental mutations differs, and most don’t greatly impact a person’s life span.

Hunting for these rare mutations, which are found in less than one in every 10,000 people, required a group effort. Harvard University geneticist Vadim Gladyshev, a senior co-author in the new study, partnered with academic colleagues and a biotech company called Gero LLC to scour the UK Biobank, a public database containing the genotypes of about 500,000 volunteers.

Using more than 40,000 of these genotypes, the team looked for correlations between small changes in DNA and health conditions, a so-called genomewide association study. Specifically, the variants they were targeting knock out genes entirely, depriving all the cells in the body of certain proteins.

On average, each person is born with six ultrarare variants that can decrease life span and “health span,” the amount of time people live before developing serious diseases, the team reports this month in eLife. The more mutations, the more likely a person was to develop an age-related illness at a younger age or die. “The exact combination matters,” Gladyshev says, but in general, each mutation decreases life span by 6 months and health span by 2 months.

The results build on what is already known about aging: “Family genes” matter. But rather than studying the common mutations found in especially long-lived people, researchers can now target rarer variants present in everyone. Gladyshev hopes this information can be used in clinical trials to categorize participants by their mutations in addition to things like gender and actual age.

He admits the findings are potentially controversial, as they minimize the perceived contribution to

aging of environmental “somatic” mutations acquired throughout life. Somatic mutations “live in a larger universe of age-related changes” influenced by lifestyle, he says, adding that changes to hormone and gene expression also come with age. “They [all] contribute to the aging process, but on their own they do not cause it.”

Jan Vijg, a geneticist at the Albert Einstein College of Medicine who studies the role of somatic mutations in aging, agrees, though he adds that somatic mutations can still cause diseases such as skin cancer that decrease life span.

Alexis Battle, a biomedical engineer at the Johns Hopkins University School of Medicine, points to an important caveat, however: The new research only looked at the “exome,” the 1% of the genome that actively builds the proteins that direct our cells. The rest is largely a black box, although growing evidence shows it can affect gene expression. Both Battle and Vijg agree that this DNA could be even more important in aging than the regions targeted by Gladyshev and his colleagues.

Going forward, Gladyshev would like to repeat his analysis on DNA from centenarians: those that live to be older than 100. “Most of the previous research focused on what these people have that makes them long-lived,” he says. “But [we want to look at] the opposite—it’s what they don’t have.”

Illustration of a damaged ribonucleic acid or dna strand
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