Monthly Archives: March 2021
A new cancer-causing gene and protein which creates highly aggressive hard to treat breast cancers has been discovered by cancer researchers at the Harry Perkins Institute in Australia.
A team of researchers lead by Associate Professor Pilar Blancafort, Perkins’ Cancer Program Head and Group Leader for Cancer Epigenetics, made the discovery after analysing a major collection of data from Stanford USA of thousands of breast cancers. Pilar said her team looked at the hormone receptor positive cancers with the worst outcomes and analysed how they were different from cancers with better survival rates.
“Hormone sensitive cancers make up 70% of all breast cancers. They usually have better outcomes for patients than the hormone receptor negative ones, such as triple negative breast cancer. “However, we found a small percentage of patients experience a very aggressive cancer that results in the worst outcomes of all breast cancers, with half of all women dying from the disease.” This group was previously not recognised as a sub-group of hormone sensitive breast cancers.
“When we looked at these cancers, we found that approximately 1 out of 4 women diagnosed with this aggressive disease carry an amplification, or high level of this gene, and that the presence of the gene is associated with larger tumours, with cancer spread into lymph nodes and with treatment resistance. “What we needed was to find a way to identify them and then find other targeted strategies to treat them,” says Pilar.
Pilar and her team discovered these aggressive cancers with extra copies of the particular cancer-causing gene use this gene to make a cancer driving protein at higher than normal levels. “This protein is not like any other protein yet discovered, it is unique. It has a different structure or shape to all other proteins so far discovered in the human body. “It promotes growth of the cancer, but it is unusual in that it does so independently of the estrogen and progesterone, the hormones in breast tissue which are typically the major controllers of cell growth in the breast tissue. “As a result, this cancer protein makes the breast cancer unresponsive to anti-cancer hormone treatments typically used to treat hormone sensitive breast cancers,” she says.
The newly discovered protein can reprogram the metabolism of breast cancer cells, making them more adaptable when cancer treatments starve them of nutrients and energy supplies.
The discovery has been published in Nature Communications journal.
Five years ago, scientists created a single-celled synthetic organism that, with only 473 genes, was the simplest living cell ever known. However, this bacteria-like organism behaved strangely when growing and dividing, producing cells with wildly different shapes and sizes. Now, scientists have identified seven genes that can be added to tame the cells’ unruly nature, causing them to neatly divide into uniform orbs.
Identifying these genes is an important step toward engineering synthetic cells that do useful things. Such cells could act as small factories that produce drugs, foods and fuels; detect disease and produce drugs to treat it while living inside the body; and function as tiny computers. But to design and build a cell that does exactly what you want it to do, it helps to have a list of essential parts and know how they fit together.
“We want to understand the fundamental design rules of life,” said Elizabeth Strychalski, a co-author on the study and leader of NIST’s Cellular Engineering Group. “If this cell can help us to discover and understand those rules, then we’re off to the races.”
Scientists at JCVI constructed the first cell with a synthetic genome in 2010. They didn’t build that cell completely from scratch. Instead, they started with cells from a very simple type of bacteria called a mycoplasma. They destroyed the DNA in those cells and replaced it with DNA that was designed on a computer and synthesized in a lab. This was the first organism in the history of life on Earth to have an entirely synthetic genome. They called it JCVI-syn1.0.
Since then, scientists have been working to strip that organism down to its minimum genetic components. The super-simple cell they created five years ago, dubbed JCVI-syn3.0, was perhaps too minimalist. The researchers have now added 19 genes back to this cell, including the seven needed for normal cell division, to create the new variant, JCVI-syn3A. This variant has fewer than 500 genes. To put that number in perspective, the E. coli bacteria that live in your gut have about 4,000 genes. A human cell has around 30,000.
This achievement, a collaboration between the J. Craig Venter Institute (JCVI), the National Institute of Standards and Technology (NIST) and the Massachusetts Institute of Technology (MIT) Center for Bits and Atoms, is described in the journal Cell.
Some people have developed dangerous blood clots in the brain after receiving the corona vaccination with the AstraZeneca preparation The University Medical Center Greifswald in Germany has now broken down the likely cause of the blood clots. According to Andreas Greinacher, he and his team found special antibodies in the blood of those affected, which are directed against the body’s own blood platelets. These cells play an important role in blood clotting. The antibodies activate the platelets: they clump together, as they normally do to close a wound, and thus form blood clots. The basic problem is therefore an autoimmune reaction.
In Germany, 13 cases of sinus vein thrombosis were reported shortly after an AstraZeneca vaccination, all of which were associated with a lack of blood platelets, i.e. a so-called thrombocytopenia. Around 1.6 million people in Germany were vaccinated. According to Greinacher, the problems that arose shortly after the vaccination are similar to a long-known complication with the administration of another agent, heparin-induced thrombocytopenia, or HIT for short. There, too, antibodies activate platelets so that clots form. In both cases the symptoms appear within 5 to 14 days after administration of the preparation. Greinacher therefore emphasized that the flu-like symptoms that often occur on the day after the vaccination are not a warning signal that a blood clot is developing. But anyone who has a painful leg about five days after the vaccination – as a sign of a deep vein thrombosis – or a severe headache should see a doctor immediately.
The Society for Thrombosis and Hemostasis Research has already published recommendations for doctors based on the Greifswald findings. She assumes that the formation of clots in people with sinus vein thrombosis and thrombocytopenia can be stopped by giving high doses of intravenous immunoglobulins. Greinacher could not answer how reliably this therapy helps those affected. That is not his area of expertise, he said.
Climate change has wrought major changes to ocean stability faster than previously thought, according to a study published recently, raising alarms over its role as a global thermostat and the marine life it supports. The research published in the journal Nature looked at 50 years of data and followed the way in which surface water “decouples” from the deeper ocean. Climate change has disrupted ocean mixing, a process that helps store away most of the world’s excess heat and a significant proportion of CO2.
Water on the surface is warmer – and therefore less dense – than the water below, a contrast that is intensified by climate change. Global warming is also causing massive amounts of fresh water to flush into the seas from melting ice sheets and glaciers, lowering the salinity of the upper layer and further reducing its density. This increasing contrast between the density of the ocean layers makes mixing harder, so oxygen, heat and carbon are all less able to penetrate to the deep seas.
“Similar to a layer of water on top of oil, the surface waters in contact with the atmosphere mix less efficiently with the underlying ocean,” said lead author Jean-Baptiste Sallee of Sorbonne University and France’s CNRS national scientific research center. He said while scientists were aware that this process was under way, “we here show that this change has occurred at a rate much quicker than previously thought: more than six times quicker.”
A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.
The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia (DCG) and the study’s corresponding author. There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia (MCG) investigators write in the Journal of Alzheimer’s Disease.
“Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease,” says Morgan, a study coauthor.
The DCG and MCG investigators decided to look at CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.
They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer’s, that includes turning down inflammation and trying to restore balance to the immune system, he says.
CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.
Overseen by the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) and Swinburne University of Technology in Australia, the reviews looked back at 138 previous studies and reanalyzed over 100 experiments to look for possible dangers in the millimeter wave frequencies (low-level radio waves above 6 GHz).
While the research and scientific analysis will likely continue, this in-depth look at what we know so far about 5G and its associated technologies points to it being perfectly safe at the kinds of levels that people would be exposed to it.
“In conclusion, a review of all the studies provided no substantiated evidence that low-level radio waves, like those used by the 5G network, are hazardous to human health,” says Ken Karipidis, Assistant Director of Assessment and Advice at ARPANSA.
While frequencies above 6 GHz have regularly been used in radar, medical instruments, and security equipment – like the airport screening scanners you have probably walked through – they’re about to be used much more widely as 5G networks get rolled out worldwide.
Combing through the data and the reported results on genotoxicity (mutations), cell proliferation, gene expression, cell signalling, membrane function, and other biological effects, the researchers could find “no confirmed evidence that low-level RF fields above 6 GHz such as those used by the 5G network are hazardous to human health“.
If you want to build a fully functional nanosized robot, you need to incorporate a host of capabilities, from complicated electronic circuits and photovoltaics to sensors and antennas. But just as importantly, if you want your robot to move, you need it to be able to bend.
Cornell researchers have created micron-sized shape memory actuators that enable atomically thin two-dimensional materials to fold themselves into 3D configurations. All they require is a quick jolt of voltage. And once the material is bent, it holds its shape – even after the voltage is removed. As a demonstration, the team created what is potentially the world’s smallest self-folding origami bird. And it’s not a lark.
The group’s paper, “Micrometer-Sized Electrically Programmable Shape Memory Actuators for Low-Power Microrobotics,” published in Science Robotics and was featured on the cover. The paper’s lead author is postdoctoral researcher Qingkun Liu. The project is led by Itai Cohen, professor of physics, and Paul McEuen, the John A. Newman Professor of Physical Science, both in the College of Arts and Sciences.
“We humans, our defining characteristic is we’ve learned how to build complex systems and machines at human scales, and at enormous scales as well,” said McEuen. “But what we haven’t learned how to do is build machines at tiny scales. And this is a step in that basic, fundamental evolution in what humans can do, of learning how to construct machines that are as small as cells.”
McEuen and Cohen’s ongoing collaboration has so far generated a throng of nanoscale machines and components, each seemingly faster, smarter and more elegant than the last.
“We want to have robots that are microscopic but have brains on board. So that means you need to have appendages that are driven by complementary metal-oxide-semiconductor (CMOS) transistors, basically a computer chip on a robot that’s 100 microns on a side,” Cohen said.
Imagine a million fabricated microscopic robots releasing from a wafer that fold themselves into shape, crawl free and go about their tasks, even assembling into more complicated structures. That’s the vision.
“We found this absolutely fascinating mechanism of our own bodies that stops the production of rogue antibodies that can cause either autoimmunity or allergies,” senior author, ANU Professor Carola Vinuesa, said. “It’s been known for years that neuritin has a role in the brain and in the nervous system but we found an abundance of neuritin in the immune system and its mechanism – which has never been described in biology. “We have shown it is one of our immune system’s own mechanisms to prevent autoimmunity and allergy and now we have the evidence, we can go on to harness that for treatment.”
The researchers say they set out over five years ago to bridge a knowledge gap on how the immune system works following an educated guess that neuritin might have a regulatory function in stopping allergies and autoimmune disease.
The study, published today in Cell, found neuritin can prevent the production of pathogenic antibodies.
“It is an incredible discovery. We saw that in the absence of neuritin there is increased susceptibility to death from anaphylaxis, highlighting its role in the prevention of life-threatening allergies,” first author, ANU researcher Dr Paula Gonzalez Figueroa, said.
For people with allergies, when the immune system overreacts to allergens – like pollen, dust or peanut butter – it produces antibodies called Immunoglobulin E, (IgE). Allergies happen when the body produces excessive IgE in response to otherwise harmless substances, leading to the release of histamine that causes allergic reactions. “We have discovered neuritin prevents excessive formation of IgE that is typically associated with some common forms of allergy and food intolerances,” Professor Vinuesa said.
Many autoimmune diseases are caused or exacerbated by antibodies that go on to destroy our own tissues and cause autoimmune diseases like lupus and rheumatoid arthritis. “There are over 80 autoimmune diseases, in many of them we find antibodies that bind to our own tissues and attack us instead of targeting pathogens – viruses and bacteria,” Dr Paula Gonzalez-Figueroa said. “We found neuritin supresses formation of rogue plasma cells which are the cells that produce harmful antibodies.”
The researchers hope the discovery will now form the basis of new treatments.