Monthly Archives: September 2021

Huge swaths of our DNA library are made up of non-coding genes that were long regarded as "junk DNA".Recent findings, however, have shown these bits of DNA actually have many purposes in mammals.

Some help form the structure in our DNA molecules so they can be packaged neatly within our cell nucleiwhile others are involved in gene regulation. Now, researchers from the University of New South Wales in Australia have discovered another potential purpose for these non-coding instructions, within the genomes of marsupials.

Some of the gene sequences once considered "junk" are actually fragments of viruses left buried in our DNA from an infection in a long-forgotten ancestor.

Whenever a virus infects you, there's a chance it will leave behind a piece of itself within your DNA, and if this happens in an egg or sperm cell, it will then be passed on through the generations. These are known as endogenous viral elements (EVEs).

In humans, fragments of viral DNA make up around 8 percent of our genome. They can provide a record of viral infections through our evolutionary history, like genetic memory.

"These viral fragments have been retained for a reason," said paleovirologist Emma Harding. "Over millions of years of evolution, we would expect all DNA to change, however, these fossils are preserved and kept intact."

To try to work out why, Harding and colleagues searched for EVEs in the genomes of 13 species of marsupials, including the tammar wallaby (Macropus eugeni), Tasmanian devil (Sarcophilus harrisii), and fat-tailed dunnarts (Sminthopsis crassicaudata).

They found EVEs from three viral groups Bornaviridae, Filoviridae, and Parvoviridae in all of the animals sampled.

"One of the EVEs I found was from the Bornaviridae family of viruses, which first entered the animals' DNA during the time of the dinosaurs when the South American and Australian land masses were still joined together," Harding said.Bornaviridae is present in the opossums of America as well as Australia's marsupials.

The Bornaviridae EVEs were particularly prevalent and more closely related to similar viral fossils found in birds and reptiles rather than those seen in placental mammals like us.

"Bornaviridae viruses were previously thought to have evolved 100 million years ago," Harding explained. "But the one I found in almost every marsupial DNA we looked at puts it at 160 million years old."

Surprisingly, some of these ancient viral fragments were still being transcribed into RNA. Often in cells, RNA transcriptions act as protein templates. But in this case they weren't being translated, effectively making them non-coding RNA.

That doesn't make them useless. Non-coding RNA is used in a number of cell functions, including the regulation of RNA transcription among other genes.

A tammar wallaby, one of the study species. (Hossein Anv/Unsplash)

Significantly, it is also known that this type of RNA is used for many cell functions, including regulating the creation of RNA, and it is also known to contribute to immune defense against viruses in plants and invertebrates. Bats have a particularly large cache of these fossil viral fragments too, and they're well known for their unfortunate ability to survive while carrying deadly viruses that do most other mammals in.

Looking at koalas in more detail, the researchers discovered some of the EVEs were indeed being transcribed into small RNA molecules known to be antiviral in invertebrates.

"This suggests the tantalizing possibility of this RNA defense system, previously thought to be abandoned in mammals in favor of the interferon system, still being active and protecting marsupial cells," Harding and colleagues wrote in Microbiology Australia.

As marsupials undergo most of their developmental time within their mother's pouch, some are born before they've even developed bones let alone fully functioning immune systems. So, this kind of antiviral defense could be critical to pouch young, the team suspects.

"This could be a mechanism similar to vaccination but is inherited through generations. By keeping a viral fossil, the cell is immunized against future infection," said Harding.

"If we can show it occurring in marsupials, it may also be occurring in other animals, including humans."

This researcher was published in Virus Evolution.

Continued here:
Mammals Carry a Graveyard of Viruses in Our DNA, And It Could Have a Crucial Purpose - ScienceAlert

It is less known that how DNA helix is neatly packed and stored inside cells. DNA is wound around protein structures known as histones. It forms an elegant, tightly packed structure known as chromatin.

For molecular processes to use that information, the chromatin needs to open and make the DNA available for binding by transcription factors. Transcription factors are proteins involved in the process of converting or transcribing DNA into RNA.

The proteins translate the DNA sequence made of base pairs into messenger RNA. This mRNA is then finally read by a ribosome to produce proteins based on the original blueprint.

Scientists from Tokyo Metropolitan University have uncovered a unique mechanism where two transcription factors stabilize each others binding to DNA in fission yeast. They found that Atf1 and Rst2 helped each other stably bind when they were close enough together.

Both proteins transcribe a gene that deals with poor glucose environments but belongs to entirely independent activation pathways.

Scientists studied how transcription factors (TF) bind to the chromatin by looking at a simpler organism, the fission yeast. They wanted changes in their environment.

Now, scientists have successfully caught a glimpse into the unique mechanism behind how transcription works in yeast cells responding to a lack of glucose in their surroundings.

Starved yeast cells cause two TFs, Atf1, and Rst2 to activate transcription of the fbp1 gene. When scientists studied the process, they found that not only that the activation of both was crucial to the function of fbp1, but that they helped stabilize each other.

Scientists also showed that this was due to how close these sites were, usually 45 base pairs apart.

Introduction of extra lengths of DNA between these sites, the TFs suddenly could not help each other. This also closed chromatin, hence leaving both factors unbound. Their relative orientation along the twisting grooves of the helix also proved vital.

Importantly, this effect was shown to be strong enough to counteract the effects of Tup11 and Tup12, co-repressors that help destabilize the random binding of independent TFs to the chromatin. All this suggests that this reciprocal relationship helps the TFs bind successfully and prevents either from attaching by themselves.

A fascinating fact is Completely independent chemical pathways activate TFS.

The process discovered by the team thus integrates these routes into a signal hub. Though a single piece in a complex biochemical puzzle, this finding helps highlight an unappreciated mechanism by which different TFs interact and effectively integrate pathways. The team hopes this new insight can help in the fight against cancer and other related illnesses.

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Proteins help each other stably bind to DNA - Tech Explorist

Hyejung Won, PhD, is principal investigator of five-year project, part of the NIHs $185-million Impact of Genomic Variation on Function consortium. UNCs Karen Mohlke, PhD, and Michael Love, are co-investigators.

Thousands of DNA variants may contribute to common diseases by affecting how well a gene is expressed, but the identity of these variants is unknown. To address this problem, The National Institutes of Health is providing approximately $185 million over five years to the Impact of Genomic Variation on Function (IGVF) consortium composed of 25 awards across 30 U.S. research sites. IGVF consortium investigators will work to understand how genomic variation alters human genome function, and how such variation influences human health and disease.

The proposed UNC-led $9.25 million study over five years, spearheaded by Hyejung Won, PhD, assistant professor in the UNC Department of Genetics, will identify specific DNA variants that alter gene expression level to influence risk of disease. The study will determine whether variants act differently in males and females; in the brain, liver, muscle, lung, and heart; and in or out of an inflamed environment.

As members of the IGVF Consortium, we will also generate a regulatory variant catalog for the community, and enable future studies through data collection and predictive models, said Won, who is a member of the UNC Neuroscience Center. The ultimate goal of the IGVF is to identify new targets to treat common diseases.

Co-investigators at UNC-Chapel Hill are Karen Mohlke, PhD, professor of genetics at the UNC School of Medicine, and Michael Love, PhD, assistant professor of genetics and biostatistics at the UNC Gillings School of Global Public Health.

Thousands of genetic loci specific locations on chromosomes are associated with human traits or disease risk, and these loci each typically contain tens to hundreds of variants, most of which are non-coding and lack direct evidence of effects on genes. Experimental tests of genomic variants are needed to identify functional effects, which can be specific to one sex, tissue, and/or perturbed environmental contexts, such as inflammation, a hallmark disease state.

The expertise of the study investigators in genome-wide association studies, statistical and computational genetics, human genomics, AAV delivery (gene therapy), and mouse physiology make achievement of these aims feasible and likely highly informative to understand how genomic variation impacts human health and disease, Won said.

Read the announcement of these IGVF grants from the National Human Genome Research Institute.

Read more here:
UNC Researchers Awarded $9.25 Million to Study DNA Variance Related to Disease | Newsroom - UNC Health and UNC School of Medicine

For the first time, bighead carp DNA has been found in the Milwaukee River, according to the U.S. Fish and Wildlife Service.

Thegenetic material, called environmental or eDNA, was detected in a water sample taken in June during routine sampling on the river.

Thetest resultwasconfirmed Friday by the Service and the Wisconsin Department of Natural Resources.

Bighead and its close relative thesilver carp are highly destructive, invasive species of carp spreading throughout North American waters.

To date, no live specimens of the fish have been found in the Wisconsin waters of Lake Michigan or its tributaries.

More: Fish barrier vs. carp DNA: What to believe?

More: Electric currents, underwater speakers scare up invasive Asian carp in Mississippi River near La Crosse

More: Asian Carp 'eDNA' found in Chicago creek near Lake Michigan. But what does it mean?

But fisheries biologists have been on the lookout due to the threat the carp pose to the multibillion-dollar fishery.

The Service uses the highly sensitive eDNA methodologyas part of its annual monitoring for invasive species in the Great Lakes.

The testingis designed to detect traces of skin cells, feces, reproductive secretions and other genetic material shed into the environment.

While DNA from the invasive fish canenter lakes and rivers in wastewater or other indirect means and doesn't necessarily signal the presence of a live fish, a positive testsends off an alarm, said Nick Frohnauer, USFWS eDNA and early detection and monitoring coordinator.

"We can't be sure of the source," Frohnauer said. "But people should have a heightened sense of concern for Lake Michigan and the Great Lakes overall because of how close the carp are in the river systems and the damage they can cause."

The positive bighead carp result came from one out of 100 samples taken from the Milwaukee River, according to the Service.

Silver and bighead carp are found in theChicago Sanitary and Ship Canal, about 35 miles from Lake Michigan. They are also found in Wisconsin waters of the Mississippi and St. Croix rivers.

And in 2020 the DNR brought charges against a Wisconsin man for illegally transporting the carp into the state and selling them in Madison.

The finding of invasive carp DNA in theMilwaukee River marks the third such detection in Wisconsin waters of Lake Michigan.

Silver carp DNA was found near Sturgeon Bay in 2013 and bighead carp DNA was found in the Fox River in 2014, according to state and federal biologists.

Subsequent netting and electroshocking in both areas failed to turn up a silver or bighead carp, dead or alive.

The Milwaukee River detection will trigger a similar response, saidTodd Kalish, DNR deputy fisheries director.

Additional water samples were collected this week, Kalish said, and beginning next week crews will use nets andshocking gear to search for invasive carp on the Milwaukee.

The eDNA results on the additional water samples are expected to be known later this month, according to Kalish.

Bighead, black, grass, and silver carp were imported from Asia to the United States in the 1970s as a method to control nuisance algal blooms in wastewater treatment plants and aquaculture ponds as well as for human food, according to the U.S. Geological Survey.

Within 10 years, the carp escaped confinement and spread to the waters of the Mississippi River basin and other large rivers like the Missouri and Illinois.

The invasivecarp are filter feeders that remove large quantities of plankton from the water and competewith native aquatic species for food and habitat.

Their rapid population increase is disrupting the ecology and food web of the large rivers of the Midwest, according to the USGS.

In areas where bighead and silvercarp are abundant, they have harmed native fish communities and interfered with commercial and recreational fishing.

Bighead carp can get very large. A 125-pounder was taken this summer by a bowfisherman in Missouri.

Kalish said it was criticalto keep bighead and silver carp out of the Great Lakes to help protect the region's estimated $7 billion-a-year fishing industry.

"I can't overemphasize how important it is to be vigilant and work to prevent the spread of these invasive carp," Kalish said. "We hope this DNA finding doesn't lead to finding a fish. But no matter what, it helps underscore this critical issue and the need to work together to keep these invasivesout."

Invasive carp info: It is a violation of federal law to transport live Asian carp in interstate commerce. In addition, Wisconsin law makes it illegal to possess, transport, transfer or introduce any species of live Asian carp.

If you catch or find a bighead, black, grass or silver carp in Wisconsin, the DNRadvises you to not return the fish to the water. Instead, take a photo of the fish andreport it to the DNR. If possible, put the fish on ice and take it the local DNR office.

For more information, visit dnr.wi.gov andinvasivecarp.us.

Our subscribers make this reporting possible. Please consider supporting local journalism by subscribing to the Journal Sentinel at jsonline.com/deal.

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Bighead carp DNA found in Milwaukee River for the first time - Milwaukee Journal Sentinel

According to two new studies, we need to reconsider the images depicting DNA is organized in the cells nucleus. Explaining it is essential since DNAs spatial arrangement in the nucleus can influence the expression of genes contained inside the DNA atom, and subsequently, the proteins found in the cell.

Scientists at the Weizmann Institute of Science studied the influence of mechanical forces in the cell nucleus within the muscle. They found that muscle contraction had an immediate effect on gene expression patterns.

Prof. Talila Volk of the Molecular Genetics Department said,We couldnt explore this further because existing methods relied on imaging of chemically preserved cells, so they failed to capture what happens in the cell nuclei of an actual working muscle.

This issue was addressed using a device that allowed scientists to study muscle nuclei in live fruit fly larvae. The device holds the tiny, translucent larva within a groove that permits it to contract and relax its muscles. This also keeps its movement constrained so a fluorescence microscope can scan it.

By doing so, scientists were able to obtain images of the internal, linearly-organized complexes of DNA and its proteins (known as chromatin), surrounded by the membrane of the muscle nuclei.

They found that- instead of filling up the entire volume of the nucleus, the noodles, or long chromatin molecules, were organized as a relatively thin layer attached to its inner walls. Like phase separation, the chromatin separated itself from the bulk of the liquid inside of the nucleus. It found its place at its outskirts.

These findings also addressed a fundamental biological question- how is chromatin, and hence DNA, organized in the nucleus in a living organism.

Scientists also developed a theoretical model that included the physical factors governing chromatin organization in the nucleus, such as the relative forces of attraction between chromatin and its liquid environment and between chromatin and the nuclear membrane.

The model anticipated that the chromatin should go through partition from the liquid phase, contingent upon the relative amount of liquid (hydration) in the nucleus. Besides, the phase-separated chromatin could then arrange itself along within the atomic film.

Prof. Sam Safran of the Chemical and Biological Physics Department at the Weizmann Institute of Science said,The groups also explained why in previous studies by other scientists, the chromatin appeared to fill the cell nuclei. When scientists plate cells on a glass slide to study them under a microscope, they change their volume and physically flatten them. This may perturb some of the forces governing chromatin arrangement and reduce the distance between the upper part of the nucleus to its base.

Scientists also examined live human white blood cells. This was done to ensure that the findings were not limited to fruit fly muscle cells.

Amiad-Pavlov said,This showed that what wed found was likely to be a general phenomenon and that this chromatin organization had probably been conserved throughout evolution.

The study opens up new avenues of research into DNAs organization in the cell and the physical forces that act upon the nucleus and chromatin that can affect gene expression. One potential direction is exploring whether theres a difference between DNA organization in health and disease. If so, this difference may be exploited in diagnosis, for example, as a new parameter for detecting cancer cells.

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A surprising arrangement of DNA in the cells nucleus revealed - Tech Explorist

Left: A 3D illustration of the nucleus representing the classical theory of DNA organization at its center. Right: Turning the ramen bowl on its head Microscopic image of the nucleus of a fruit fly larvas muscle cell. The long chains of DNA (red) are attached to the nuclear lamina (green) the inner layer of the nuclear membrane. Credit: Weizmann Institute of Science

If you open a biology textbook and run through the images depicting how DNA is organized in the cells nucleus, chances are youll start feeling hungry; the chains of DNA would seem like a bowl of ramen: long strings floating in liquid. However, according to two new studies one experimental[1] and the other theoretical[2] that are the outcome of the collaboration between the groups of Prof. Talila Volk of the Molecular Genetics Department and Prof. Sam Safran of the Chemical and Biological Physics Department at the Weizmann Institute of Science, this image should be reconsidered. Clarifying it is essential since DNAs spatial arrangement in the nucleus can affect the expression of genes contained within the DNA molecule, and hence the proteins found in the cell.

This story began when Volk was studying how mechanical forces influence cell nuclei in the muscle and found evidence that muscle contractions had an immediate effect on gene expression patterns. We couldnt explore this further because existing methods relied on imaging of chemically preserved cells, so they failed to capture what happens in the cell nuclei of an actual working muscle, she says.

(Left to right) Prof. Talila Volk, Prof. Sam Safran, Dr. Dana Lorber, Dr. Daria Amiad-Pavlov and Dr. Adriana Reuveny. Moving away from the center. Credit: Weizmann Institute of Science

To address this issue, Dr. Dana Lorber, a research associate in Volks group, led the design of a device that makes it possible to study muscle nuclei in live fruit fly larvae. The device holds the tiny, translucent larva within a groove that allows it to contract and relax its muscles but keeps its movement constrained so that it can be scanned by a fluorescence microscope. Using the device, the researchers obtained images of the internal, linearly-organized complexes of DNA and its proteins (known as chromatin), surrounded by the membrane of the muscle nuclei.

Expecting a bowl full of ramen, Lorber and Dr. Daria Amiad-Pavlov, a postdoctoral fellow in Volks group, were in for a surprise. Rather than filling up the entire volume of the nucleus, the noodles, or long chromatin molecules, were organized as a relatively thin layer, attached to its inner walls. Similar to the outcome of the interaction between oil and water, what is known as phase separation, the chromatin separated itself from the bulk of the liquid inside of the nucleus and found its place at its outskirts, while most of the fluid medium remained at the center. The researchers realized that they were on their way to addressing a fundamental biological question, that is how is chromatin, and hence DNA, organized in the nucleus in a living organism. But the findings were so unexpected, we had to make sure no error had crept in and that this organization was universal, Lorber says.

The surprising findings address a fundamental biological question how is DNA organized in the nucleus in a living organism.

After teaming up with Safrans group, they came to the conclusion thered been no mistake. Safran and postdoctoral fellow Dr. Gaurav Bajpai built a theoretical model that included the physical factors governing chromatin organization in the nucleus, such as the relative forces of attraction between chromatin and its liquid environment and between chromatin and the nuclear membrane. The model predicted that the chromatin should undergo separation from the liquid phase, depending on the relative amount of liquid (hydration) in the nucleus. Furthermore, the phase separated chromatin could then arrange itself along the inside of the nuclear membrane just as Volks team had found in their experiments.

Dr. Gaurav Bajpai. Credit: Weizmann Institute of Science

The groups also explained why in previous studies by other scientists, the chromatin appeared to fill the cell nuclei. When scientists plate cells on a glass slide in order to study them under a microscope, they change their volume and physically flatten them. This may perturb some of the forces governing chromatin arrangement and reduce the distance between the upper part of the nucleus to its base, Safran explains.

To make sure these findings were not limited to fruit fly muscle cells, Lorber and Amiad-Pavlov joined forces with Dr. Francesco Roncato from Prof. Ronen Alons group of the Immunology Department and examined live human white blood cells. In this case too, the chromatin was similarly organized as a layer lining the inner nuclear wall. This showed that what wed found was likely to be a general phenomenon, and that this chromatin organization had probably been conserved throughout evolution, says Amiad-Pavlov.

3D chromatin simulations reveal that chromatin organization in the nucleus is dependent on the physical interaction between chromatin and the nuclear lamina. When these interactions weaken (left to right) as is the case in several diseases ranging from muscle dystrophies to neurological disorders the chromatin shifts from the periphery of the nucleus to its center. Credit: Weizmann Institute of Science

The study opens up new avenues of research into DNAs organization in the cell and, by extension, into the physical forces that act upon the nucleus and chromatin that can affect gene expression. One potential direction is exploring whether theres a difference between DNA organization in health and disease. If so, this difference may be exploited in diagnosis, for example, as a new parameter for detecting cancer cells. In the study of embryonic development, exploring DNA organization may help clarify whether mechanical forces affect the differentiation of cells into new fates. Finally, its known that stiffness of the surface on which cells are placed can alter the expression of their genes. The new study suggests this may have to do with the surfaces push and pull on the nuclear membrane and the resultant impact on DNA organization within the nucleus. A better understanding of this interplay may help control gene expression in cells employed for engineering tissues with desired properties.

DNA and its chromatin packaging was thought to fill up to 60% of the nuclear volume. In their study, Weizmann Institute scientists found it to be 31%.

References:

Live imaging of chromatin distribution reveals novel principles of nuclear architecture and chromatin compartmentalization by Daria Amiad-Pavlov, Dana Lorber, Gaurav Bajpai, Adriana Reuveny, Francesco Roncato, Ronen Alon, Samuel Safran and Talila Volk, 2 June 2021, Science Advances.DOI: 10.1126/sciadv.abf6251

Mesoscale phase separation of chromatin in the nucleus by Gaurav Bajpai, Daria Amiad Pavlov, Dana Lorber, Talila Volk and Samuel Safran, 4 May 2021, eLife.DOI: 10.7554/eLife.63976

Also taking part in the experimental study was Dr. Adriana Reuveny from Prof. Talila Volks group in the Molecular Genetics Department.

Prof. Talila Volk is the incumbent of the Sir Ernst B. Chain Professorial Chair.

Prof. Volks research is supported by the Aharon Katzir-Katchalsky Center; the Benoziyo Endowment Fund for the Advancement of Science; and the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics.

Prof. Samuel Safran is the incumbent of the Fern & Manfred Steinfeld Professorial Chair.

Prof. Safrans research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; and the Harold Perlman Family

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Surprising Arrangement of DNA in the Cells Nucleus Revealed by Novel Imaging Method - SciTechDaily

It has been 20 years since the 9/11 terrorist attacks at the World Trade Center. In that time, not only has global politics changed but so has technology.

We look at some of the ways technology has changed since the tragedy.

The vast majority of people around the world first heard about the attacks through word of mouth, by phone call or by way of the traditional media. Social media platforms, such as Twitter and Facebook, didnt exist back then.

Nowadays, news spreads much quicker through social media platforms, instant messages, news notifications and websites. It is impossible to conceive a situation where something as big as a terrorist attack can happen and not know moments later details of what took place.

These platforms can help people protect themselves so they know which areas to avoid, and in the case of Facebook, alert loved ones as to their safety.

But social media is not without its downfalls, namely misinformation. It has pitted social groups against each other and arguably become a space to fuel extremism and polarisation.

This week, two more victims of the 9/11 attacks in New York have been identified, thanks to advancements in DNA testing. Dorothy Morgan is the 1,646th victim identified thanks to ongoing DNA analysis of remains.

The second person identified was a man, whose name his family wishes to remain anonymous. There are still more than 1,100 victims, at least 40 per cent of those who died on 9/11, that are still unidentified.

The process of identifying the victims has slowed over the years and the last identification was made in 2019.

According to The New York Times, forensic scientists are testing and retesting more than 22,000 body parts that were recovered from the World Trade Center. Much of the testing is done using bone fragments the size of a Tic Tac.

Newsday reported several weeks ago that the New York City medical examiners office has been approved to use the forensic method called Next Generation Sequencing. It is being used already to identify remains from World War II.

Post-September 11, its almost impossible not to have to show your photo ID when entering a large building in a big city.

Yes, surveillance has become a big part of daily life. Cameras have grown in quantity and so have their quality. Two decades ago, surveillance cameras would record just a few hours of low definition content.

But today, cameras now make up an entire network that can upload hours of clear images onto cloud devices. AI-powered tools can then identify people with facial recognition software. This is of course a blessing and a curse, as people worry over their security.

As well as cameras and facial recognition software, there are also licence plate readers and even surveillance drones that are being used to hover above mass protests.

We now have more robust communication networks, improved by private companies and governments to better cope in the event of a disaster. Much wired and wireless technology can now withstand antennae going offline or if wires are damaged.

This development does not just help in major incidents, such as terror attacks, but also for natural disasters, such as hurricanes. Communication is vital during emergencies, as not only can we stay in touch with our friends and family, but also as navigational tools that can tell us where to find safety.

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From social media to DNA testing: How has tech changed in the 20 years since 9/11? - Euronews