. Scientific Frontline

Thursday, August 11, 2022

MIT scientists discover new antiviral defense system in bacteria

A team led by researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT has discovered that organisms across all three domains of life — bacteria, archaea, and eukaryotes (which includes plants and animals) — use pattern recognition of conserved viral proteins to defend against pathogens.
Credits: Image courtesy of Feng Zhang

Bacteria use a variety of defense strategies to fight off viral infection, and some of these systems have led to groundbreaking technologies, such as CRISPR-based gene-editing. Scientists predict there are many more antiviral weapons yet to be found in the microbial world.

A team led by researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT has discovered and characterized one of these unexplored microbial defense systems. They found that certain proteins in bacteria and archaea (together known as prokaryotes) detect viruses in surprisingly direct ways, recognizing key parts of the viruses and causing the single-celled organisms to commit suicide to quell the infection within a microbial community. The study is the first time this mechanism has been seen in prokaryotes and shows that organisms across all three domains of life — bacteria, archaea, and eukaryotes (which includes plants and animals) — use pattern recognition of conserved viral proteins to defend against pathogens.

The study appears in Science.

Large number of stem cell lines carry significant DNA damage, say researchers

Our Sun Credit:
Alexas Fotos / Public Domain

DNA damage caused by factors such as ultraviolet radiation affect nearly three-quarters of all stem cell lines derived from human skin cells, say Cambridge researchers, who argue that whole genome sequencing is essential for confirming if cell lines are usable.

Stem cells are a special type of cell that can be programmed to become almost any type of cell within the body. They are currently used for studies on the development of organs and even the early stages of the embryo.

Increasingly, researchers are turning to stem cells as ways of developing new treatments, known as cell-based therapies. Other potential applications include programming stem cells to grow into nerve cells to replace those lost to neurodegeneration in diseases such as Parkinson’s.

Originally, stem cells were derived from embryos, but it is now possible to derive stem cells from adult skin cells. These so-called induced pluripotent stem cells (iPSCs) have now been generated from a range of tissues, including blood, which is increasing in popularity due to its ease of derivation.

However, researchers at the University of Cambridge and Wellcome Sanger Institute have discovered a problem with stem cell lines derived from both skin cells and blood. When they examined the genomes of the stem cell lines in detail, they found that nearly three quarters carried substantial damage to their DNA that could compromise their use both in research and, crucially, in cell-based therapies. Their findings represent the largest genetic study to date of iPSCs and are published today in Nature Genetics.

DNA is made up of three billion pairs of nucleotides, molecules represented by the letters A, C, G and T. Over time, damage to our DNA, for example from ultraviolet radiation, can lead to mutations – a letter C might change to a letter T, for example. ‘Fingerprints’ left on our DNA can reveal what is responsible for this damage. As these mutations accumulate, they can have a profound effect on the function of cells and in some cases lead to tumors.

Genome Editing Terminology Is Standardized in NIST-Led Effort

These words are included in the new Genome Editing Vocabulary. 
Credit: N. Hanacek/NIST

Genome editing can cure diseases, boost food production and open vast new fields of scientific discovery. But to realize its full potential, scientists need to precisely describe the details of their genome editing attempts to one another and the wider world.

For instance, if a company is developing a new gene therapy for use in the United States, it needs to tell the U.S. Food and Drug Administration (FDA) what the product does and demonstrate that it is safe and effective. Scientists could do that more precisely if they had a standard set of terms and definitions.

As of recently, they have one. In November 2021 the International Organization for Standardization (ISO) published the Genome Editing Vocabulary — an internationally agreed-upon list of 42 precisely defined terms that will help scientists from all over the world avoid errors of communication. (The word “genome” refers to all the inherited DNA in an organism.)

This effort was spearheaded by the National Institute of Standards and Technology (NIST) Genome Editing Consortium — an international group of industry, academic and government scientists who work in this field. NIST first convened the consortium in 2018 so that experts and organizations that often compete with one another would have a venue for collaborating on standards that advance the field for all. The FDA joined the consortium last year.

Do you keep secrets from your loved ones, family, or friends?

Ninety percent of people have kept an everyday consumer decision a secret from a spouse or other close relationship 
Photo Credit: Noelle Otto

It turns out that many people do. Whether ordering something online and hiding the package when it arrives, hiring a cleaning service and not telling your roommate, or eating a pizza instead of dieting, we often have secret purchases that we just prefer not to divulge.

UConn marketing professor Danielle Brick is investigating this behavior and discovering the little “errors of omissions” that go on in many households.

“I think what makes this research important, and fun, is how relatable it is,’ says Brick, a new member of the UConn School of Business faculty.

Her research, titled “Secret Consumer Behaviors in Close Relationships,” has just been published in the Journal of Consumer Psychology.

She and her colleagues found that this clandestine behavior not only impacts relationships in an unexpected and significant way, but also has considerable marketing implications.

Nearly a hundred genes have been lost during the woolly mammoth’s evolution

Tusk from woolly mammoth emerging from the permafrost on Wrangel Island.
Photo Credit: Love Dalén/Stockholm University.

A new study shows that 87 genes have been affected by deletions or short insertions during the course of the mammoth’s evolution. The researchers note that their findings have implications for international efforts to resurrect extinct species, including the woolly mammoth. The study was published in the journal iScience by researchers at the Centre for Palaeogenetics in Stockholm, a collaboration between Stockholm University and the Swedish Museum of Natural History.

One of the most widely discussed methods to resurrect extinct species is to use genome editing techniques such as Crispr-Cas9 to insert key gene variants from an extinct species into a genome from its living relative. However, the results in this new study indicate that one might also need to remove certain genes to preserve important biological traits while reconstructing extinct genomes.

“Editing the genome of a living species to mimic that from an extinct relative was never going to be easy, and these new findings certainly illustrate the complexity and difficulties that lie ahead”, says Love Dalén, a professor of evolutionary genomics at the Centre for Palaeogenetics.

New research "UNCOVERS" hidden objects in high resolution

Target objects and the images of them created with UNCOVER NLOS technology.
Credit: Caltech

Imagine driving home after a long day at work. Suddenly, a car careens out of an obscured side street and turns right in front of you. Luckily, your autonomous car saw this vehicle long before it came within your line of sight and slowed to avoid a crash. This might seem like magic, but a novel technique developed at Caltech could bring it closer to a reality.

With the advent of autonomous vehicles, advanced spacecraft, and other technologies that rely on sensors for navigation, there is an ever-increasing need for advanced technologies that can scan for obstacles, pedestrians, or other objects. But what if something is hidden behind another object?

In a paper recently published in the journal Nature Photonics, Caltech researchers and their colleagues describe a new method that essentially transforms nearby surfaces into lenses that can be used to indirectly image previously obscured objects.

The technology, developed in the laboratory of Changhuei Yang, Thomas G. Myers Professor of Electrical Engineering, Bioengineering, and Medical Engineering; and Heritage Medical Research Institute investigator, is a form of non-line-of-sight (NLOS) sensing—or sensing that detects an object of interest outside of the viewer's line of sight. The new method, dubbed UNCOVER, does this by using nearby flat surfaces, such as walls, like a lens to clearly view the hidden object.

Genetic mapping of tumors reveals how cancers grow


Understanding which cells give rise to which areas of cancer can improve our understanding of how a tumor has grown and developed, including how it has changed genetically, over time. This has been made possible using a new technique called spatial transcriptomics, which allows scientists to see what genetic changes take place without breaking up the tissue they’re looking at. This adds a new dimension which researchers have now used to reveal which cells have mutated and where within the ecosystem of an organ.

Current techniques for studying the genetics of cells within tumors involve taking a sample from the cancerous area and analyzing the DNA of those cells. The problem is that many cancers, such as prostate cancer, are three dimensional, which means that any one sample would only give a small snapshot of the tumor.

In a new study published in Nature, the researchers used spatial transcriptomics to create a cross-sectional map of a whole prostate, including areas of healthy and cancerous cells. By grouping cells according to similar genetic identity, they were surprised to see areas of supposedly healthy tissue that already had many of the genetic characteristics of cancer. This finding was surprising because of both the genetic variability within the tissue as well as the large number of cells that would be considered healthy, but which contained mutations usually identified with cancerous cells.

Alastair Lamb of Oxford’s Nuffield Department of Surgical Sciences, who jointly led the study, said: 'Prostate tissue is three-dimensional, and like most organs that can develop cancer we still have much to learn about what cellular changes cause cancer and where it starts. One thing we are fairly confident of is that it starts with genetic mutations.

World first chronic fatigue syndrome findings could fast track response to Long COVID

Professor Sonya Marshall-Gradisnik from the National Centre for Neuroimmunology and Emerging Diseases (NCNED) at Griffith University.
Credit: Griffith University

Griffith University researchers are hoping to find a treatment for Long COVID after proving the illness shares the same biological impairment as patients with Chronic Fatigue Syndrome (known internationally as Myalgic Encephalomyelitis (ME/CFS)).

In a world first, their study suggests COVID-19 could be a potential trigger for ME/CFS and their 10 years of research on ME/CFS could help fast track understanding and treatment of Long Covid.

Griffith University’s National Centre for Neuroimmunology and Emerging Diseases Director, Professor Sonya Marshall-Gradisnik, said the breakthrough findings will assist with investigations into therapeutic strategies to help both Long COVID and ME/CFS patients.

“Patients with Long COVID report neurocognitive, immunological, gastrointestinal, and cardiovascular manifestations, which are also symptoms of ME/CFS,” Professor Marshall-Gradisnik said.

“Our researchers have pioneered a specialized technique known as electrophysiology or ‘patch-clamp’ in immune cells.”

“This technique previously led the team to report on the pathology of ME/CFS and to examine specific ion channels in cells.

Wednesday, August 10, 2022

How dinos carried their enormous weight

 3D paleoreconstruction of a sauropod dinosaur
Credit: Dr. Andreas Jannel

Scientists have cracked an enduring mystery, discovering how sauropod dinosaurs – like Brontosaurus and Diplodocus – supported their gigantic bodies on land.

A University of Queensland and Monash University-led team used 3D modeling and engineering methods to digitally reconstruct and test the function of foot bones of different sauropods.

Dr. Andréas Jannel conducted the research during his PhD studies at UQ’s Dinosaur Lab and said the team found that the hind feet of sauropod had a soft tissue pad beneath the ‘heel’, cushioning the foot to absorb their immense weight.

“We’ve finally confirmed a long-suspected idea and we provide, for the first time, biomechanical evidence that a soft tissue pad – particularly in their back feet – would have played a crucial role in reducing locomotor pressures and bone stresses,” Dr. Jannel said.

“It is mind-blowing to imagine that these giant creatures could have been able to support their own weight on land.”

Sauropods were the largest terrestrial animals that roamed the Earth for more than 100 million years.

They were first thought to have been semi-aquatic with water buoyancy supporting their massive weight, a theory disproved by the discovery of sauropod tracks in terrestrial deposits in the mid-twentieth century.

Monash University’s Dr. Olga Panagiotopoulou said it had also been thought sauropods had feet similar to a modern-day elephant.

Ageing neutralizes sex differences in the brain

When male and female fruit flies age, their brains become desexualized.
Credit: Erik Karits on Unsplash

When male and female fruit flies age, their brains become desexualized. Age-related changes take place in both sexes, but the male brain becomes feminized to a larger extent than the female brain becomes masculinized. This is the conclusion of a study performed by a research group at Linköping University.

It is a well-known fact that weaker individuals cannot afford to “invest” in sexual behaviors to the same extent as their healthier conspecifics. However, it is not clear if ageing, which weakens individuals, also leads to a reduced investment in sexual activities. You might think that for individuals close to the end of their lives, going “all in” on reproduction, in order to pass on their genes before it is too late, would be best. Sexual behaviors are directed from the brain, and to find out what happens to sex differences in this tissue when fruit flies age the researchers have investigated how genes expressed to different degrees in young males and females change over time.

“Our results show that gene expression in male and female brains become more similar with age, and that both sexes contribute to this pattern”, says Dr Antonino Malacrinò, one of the study’s main authors who now works at the University of Reggio Calabria in Italy.

What the study shows is that if the expression of a certain gene is higher in the brains of young females than in young males, the gene’s expressions is reduced in older females and increased in old males – and vice versa for genes with higher expression in young males.

“The results also show that the changes are larger in males than in females”, says Antonino Malacrinò.

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