Posts belonging to Category genetics

Inkjet Printers Grow Nerve Stem Cells

Inkjet printers and lasers are parts of a new way to produce cells important to research on nerve regeneration. Researchers at Iowa State University have developed a nanotechnology that uses inkjet printers to print multi-layer graphene circuits….It turns out mesenchymal stem cells adhere and grow well on the treated circuit’s raised, rough, and 3D nanostructures. Add small doses of electricity—100 millivolts for 10 minutes per day over 15 days—and the stem cells become Schwann-like cells, [which secrete substances that promote the health of nerve cells].

nerve cells

This technology could lead to a better way to differentiate stem cells,” says Metin Uz, a postdoctoral research associate in chemical and biological engineering. The researchers report the results could lead to changes in how nerve injuries are treated inside the body. “These results help pave the way for in vivo peripheral nerve regeneration where the flexible graphene electrodes could conform to the injury site and provide intimate electrical stimulation for nerve cell regrowth,” the researchers write in a summary of their findings.


Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”


How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”


Artificial Embryo From Stem Cells

Scientists at the University of Cambridge have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells – the body’s ‘master cells’ – and a 3D scaffold on which they can grow. Understanding the very early stages of embryo development is of interest because this knowledge may help explain why a significant number of human pregnancies fail at this time.

Once a mammalian egg has been fertilised by a sperm, it divides multiple times to generate a small, free-floating ball of stem cells. The particular stem cells that will eventually make the future body, the embryonic stem cells (ESCs) cluster together inside the embryo towards one end: this stage of development is known as the blastocyst. The other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta, and primitive endoderm stem cells that will form the so-called yolk sac, ensuring that the foetus’s organs develop properly and providing essential nutrients.

Using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D scaffold known as an extracellular matrix, Cambridge researchers were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural embryo.  There is a  remarkable degree of communication between the two types of stem cell: in a sense, the cells are telling each other where in the embryo to place themselves.

artificial embryo

We knew that interactions between the different types of stem cell are important for development, but the striking thing that our new work illustrates is that this is a real partnership – these cells truly guide each other,”  says Professor Zernicka-Goetz. “Without this partnership, the correct development of shape and form and the timely activity of key biological mechanisms doesn’t take place properly.”

Comparing their artificial ‘embryo’ to a normally-developing embryo, the team was able to show that its development followed the same pattern of development. The stem cells organise themselves, with ESCs at one end and TSCs at the other.

The study has been published in the journal Science.


A Brain-computer Interface To Combat The Rise of AI

Elon Musk is attempting to combat the rise of artificial intelligence (AI) with the launch of his latest venture, brain-computer interface company NeuralinkLittle is known about the startup, aside from what has been revealed in a Wall Street Journal report, but says sources have described it as “neural lace” technology that is being engineered by the company to allow humans to seamlessly communicate with technology without the need for an actual, physical interface. The company has also been registered in California as a medical research entity because Neuralink’s initial focus will be on using the described interface to help with the symptoms of chronic conditions, from epilepsy to depression. This is said to be similar to how deep brain stimulation controlled by an implant helps  Matt Eagles, who has Parkinson’s, manage his symptoms effectively. This is far from the first time Musk has shown an interest in merging man and machine. At a Tesla launch in Dubai earlier this year, the billionaire spoke about the need for humans to become cyborgs if we are to survive the rise of artificial intelligence.

cyborg woman

Over time I think we will probably see a closer merger of biological intelligence and digital intelligence,”CNBC reported him as saying at the time. “It’s mostly about the bandwidth, the speed of the connection between your brain and the digital version of yourself, particularly output.” Transhumanism, the enhancement of humanity’s capabilities through science and technology, is already a living reality for many people, to varying degrees. Documentary-maker Rob Spence replaced one of his own eyes with a video camera in 2008; amputees are using prosthetics connected to their own nerves and controlled using electrical signals from the brain; implants are helping tetraplegics regain independence through the BrainGate project.

Former director of the United States Defense Advanced Research Projects Agency (DARPA), Arati Prabhakar, comments: “From my perspective, which embraces a wide swathe of research disciplines, it seems clear that we humans are on a path to a more symbiotic union with our machines.


Shape-shifting Molecular Robots

A research group at Tohoku University and Japan Advanced Institute of Science and Technology has developed a molecular robot consisting of biomolecules, such as DNA and protein. The molecular robot was developed by integrating molecular machines into an artificial cell membrane. It can start and stop its shape-changing function in response to a specific DNA signal.

This is the first time that a molecular robotic system has been able to recognize signals and control its shape-changing function. What this means is that molecular robots could, in the near future, function in a way similar to living organisms.

Using sophisticated biomolecules such as DNA and proteins, living organisms perform important functions. For example, white blood cells can chase bacteria by sensing chemical signals and migrating toward the target. In the field of chemistry and synthetic biology, elemental technologies for making various molecular machines, such as sensors, processors and actuators, are created using biomolecules. A molecular robot is an artificial molecular system that is built by integrating molecular machines. The researchers believe that realization of such a system could lead to a significant breakthrough – a bio-inspired robot designed on a molecular basis.

molecular robot

The molecular robot developed by the research group is extremely small – about one millionth of a meter – similar in size to human cells. It consists of a molecular actuator, composed of protein, and a molecular clutch, composed of DNA. The shape of the robot’s body (artificial cell membrane) can be changed by the actuator, while the transmission of the force generated by the actuator can be controlled by the molecular clutch. The research group demonstrated through experiments that the molecular robot could start and stop the shape-changing behavior in response to a specific DNA signal.

The findings were published in Science Robotics.


Mental Viagra

As Valentines Day approaches, love may be in the air…. but it’s also in the mind. Scientists in London say a natural hormone – appropriately named kisspeptinenhances brain regions associated with sex and love. In placebo-controlled trials, 29 healthy young men were injected with kisspeptin and their brains scanned using MRI.


During the MRI they performed tasks designed to activate certain areas of the brain. So we used tasks to activate the sexual arousal centres of the brain and task to activate the romance sensors of the brain using images. And we observed that kisspeptin boosted the activity in sexual arousal and romantic circuits in the brain,” says Dr. Alexander Comninos, Endocrinologist at Imperial College  London.

Kisspeptin is found in all men and women, and is vital for stimulating puberty. “So there’s a link, not just with the hormones, but also the stimulation of reproductive hormones but also stimulating how we perceive sexual images in the brain, and that’s what the really exciting part of this study been; is how for the first time having a link between a hormone that’s stimulating reproductive hormones, but also how our brains perceive sexual images,” explains Waljit Dhillo, Professor in Endocrinology at Imperial College London .

Psychological sexual disorders can make it difficult for couples to conceive. Biological factors play a large part, but the role of the brain and emotion can’t be overlooked. A kisspeptin-based therapy could be an answer, say researchers. It differs from drugs like Viagra, which only trigger a physiological response. “Viagra is very different. So Viagra will cause vasodilation, it will make the vessels essentially dilate, blood will go down to the genital area. So it’s a completely different action, it’s mechanical if you like. Whereas this is much more psychological in terms of its altering how we perceive sexual images in our brains. So it’s a completely different mechanism of action“, adds Professor Dhillo.

More research is needed – including on women and then eventually in patients with psychological issues. Kisspeptin could one day help treat sexual disorders of the mind… in effect, mental Viagra.


How To Track Stem Cells In The Body

Rice University researchers have synthesized a new and greatly improved generation of contrast agents for tagging and real-time tracking of stem cells in the body. The agent combines ultrashort carbon nanotubes and bismuth clusters that show up on X-rays taken with computed tomography (CT) scanners. The stable compound performs more than eight times better than the first-generation material introduced in 2013, according to the researchers.

An improved compound of bismuth and carbon nanotubes called Bi4C@US-tubes, developed at Rice University could enhance the ability to track stem cells as they move through the body and target diseases

The primary application will be to track them in stem-cell therapies to see if the cells are attracted to the site of disease — for example, cancer — and in what concentration,” said Rice chemist Lon Wilson of the compound the researchers call Bi4C@US-tubes.

Magnetic resonance imaging is currently used for that purpose and it works quite well, but X-ray technology in the clinic is much more available,” he said. “It’s faster and cheaper, and it could facilitate preclinical studies to track stem cells in vivo.”

Bismuth is used in cosmetics, pigments and pharmaceuticals, notably as the active ingredient in pink bismuth (aka Pepto-Bismol), an antacid. For this application, bismuth nanoclusters developed by the lab of Rice chemist Kenton Whitmire, a co-author of the paper, are combined with carbon nanotubes chemically treated to shorten them to between 20 and 80 nanometers and add defects to their side walls. The nanoclusters, which make up about 20 percent of the compound, appear to strongly attach to the nanotubes via these defects.

When introduced into stem cells, the treated nanotubes become easy to spot, Wilson said. “It’s very interesting to see a cell culture that is opaque to X-rays. They’re not as dark as bone (which X-rays cannot penetrate), but they’re really dark when they’re loaded with these agents.”

The process developed by Wilson’s team and colleagues at CHI St. Luke’s Health-Baylor St. Luke’s Medical Center and Baylor College of Medicine is detailed this month in the American Chemical Society journal ACS Applied Materials and Interfaces.


Understanding The Risks Of Nanotechnology

When radioactive materials were first introduced into society, it took a while before scientists understood the risks. The same is true of nanotechnology today, according to Dr Vladimir Baulin, from University Rovira i Virgili, in Tarragona, Spain, who together with colleagues has shown for the first time how nanoparticles can cross biological – or lipidmembranes in a paper published in the journal Science Advances
Nanotechnology is all around us, in building materials, in toothpaste and in cleaning products. Across Europe, hundreds of institutions are working together to look at how to monitor exposure, manage the risks and advise on what regulations may be needed under the EU’s NanoSafety Cluster.

nanoparticles effects on lipids

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer (main part of a biological membrane). This process was quantified and the time of each step was estimated. The lipid membrane is the ultimate barrier protecting cells from the outside environment and if the nanoparticles can cross this barrier they may go into cells.’

‘Dr Jean-Baptiste Fleury (from Saarland University in Germany) designed a special set-up with two chambers separated by a lipid bilayer, which contained fluorescent lipids (fat molecules). Non-fluorescent nanoparticles were added to only one of the chambers. In this set-up, nanoparticles became visible only when they touched the fluorescent bilayer and exchanged lipids with it. If one sees the fluorescent nanoparticle in the second chamber, this means it was in contact with the bilayer and it crossed the bilayer from one chamber to another. This was the proof. In addition, the process of translocation was quantified and the time of the crossing was estimated as milliseconds.’

All biological objects, biomolecules, proteins that exist in living organisms evolved over billions of years to adapt to each other. Nanoparticles which are synthesised in the laboratory are thus considered by a living organism as something foreign. It is a big challenge to make them compatible and not toxic.’ ‘I would count the applications of nanoparticles as starting from the 1985 Nobel Prize for the discovery of fullerenes (molecules of hollow football-shaped carbon). This was the start of the nanoparticle boom.’

This is becoming urgent because nanoparticles and nanotechnology in general are entering our lives. Now it is possible to synthesise nanomaterials with precise control, fabricate nanostructures on surfaces and do precise tailoring of the properties of nanoparticles.

‘It is becoming quite urgent to understand the exact mechanisms of nanotoxicity and make a classification depending on the mechanism. Radioactivity or X-rays entered our lives the same way. It took time until researchers understood the mechanisms of action on living organisms and the regulations evolved with our understanding.’

gold nanoparticles cross the membrane

This is the first observation to show directly how tiny gold nanoparticles can cross a lipid bilayer.

An empirical test of toxicity is that you put nanoparticles into the cells and you see the cells are dead, but you don’t understand what has happened, this is empirical. This is a legitimate tool, but it is not enough to address toxicity. Instead, one could start from the properties of nanoparticles and think about classifying nano-objects based on their physical or chemical properties by trying to predict the effect of a given nanoparticle on a cell or tissue beforehand.

I understand, it may look too ambitious, since there are a lot of tiny details that are not considered at the moment in theoretical models or any classification. However, even if it may not be exact, it can give some guidance and it would be possible to make predictions on how nanoparticles and polymers interact with lipid membranes. For example, in this study we used theoretical modelling to suggest the size and surface properties of the nanoparticle that is able to cross the lipid membrane through a certain pathway and it was observed experimentally.’


Damaged teeth can be regrown naturally

A way to naturally regrow damaged teeth has been discovered by scientists in a breakthrough that could significantly reduce the need for fillings. Researchers at King’s College London (KCL) found that a drug designed to treat Alzheimer’s disease was able to stimulate the tooth to create new dentine capable of filling in large cavitiesTeeth can already cope with small areas of damage using the same process, but when the holes become too large a dentist must insert artificial cements or the tooth will be lost.


The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine,” said Professor Paul Sharpe, lead author of a paper in the journal Scientific Reports.  “In addition, using a drug that has already been tested in clinical trials for Alzheimer’s disease provides a real opportunity to get this dental treatment quickly into clinics.”

If a tooth is damaged or infected, the soft inner pulp can become exposed, risking further infection. When this happens, a band of dentine, the hard material that makes up most of the tooth, will attempt to bridge the gap and seal off the pulp. But the researchers found that the natural repair mechanism could be boosted if the drug  Tideglusib was used. Previously it has been trialled as a treatment for various neurological disorders, including Alzheimer’s. It works by stimulating stem cells, which can turn into any type of tissue in the body, already present in the pulp to create new dentine.

The drug and a substance called glycogen synthase kinase were applied to the tooth on a biodegradable sponge made from collagen. As the sponge degraded, it was replaced by dentineleading to complete, natural repair”, according to a statement about the research issued by KCL.


Why North Atlantic Tuna Is Less Toxic ?

In a piece of welcome news for seafood lovers, a Stony Brook-led research team has found declining levels of mercury in bluefin tuna caught in the North Atlantic over the past decadeMercury is a neurotoxin harmful to humans, and tuna provide more mercury to humans than any other source.

A study led by Stony Brook University’s School of Marine and Atmospheric Sciences (SoMAS) and published in Environmental Science & Technology provides a new data set, the largest of its kind, of mercury concentrations in Atlantic bluefin tuna. The data demonstrate that, while tissue concentrations were higher than in most other fish species, there has been a consistent decline in mercury concentrations in these tuna over time, regardless of age of the fish.



The researchers measured mercury concentrations from the tissue of 1,292 bluefin tuna caught between 2004 and 2012

  • Over the eight-year period, mercury levels in the fish fell 19 percent.
  • Mercury concentrations were generally high, and were highest in the largest, oldest fish; no differences were noted between males and females.
  • Mercury in the air over the North Atlantic fell 20 percent from 2001 to 2009.
  • Global levels of mercury emissions have fallen 2.8 percent a year from 1990 to 2007.

The rate of decline parallels the declines – over the same time period — of mercury emissions, mercury levels in North Atlantic air, and mercury concentrations in North Atlantic seawater. Authors of the study include Stony Brook’s Cheng-Shiuan Lee, a Ph.D student in chemical/biological oceanography, and Nicholas S. Fisher, Distinguished Professor & Director, Consortium for Inter-Disciplinary Environmental Research at SoMAS.

According Fisher, the finding appears to indicate that changes in mercury levels in fish tissue respond in real time to changes in mercury loadings into the ocean. The study suggests that mercury levels may be improving as a result of declining coal use, reducing emissions that drift over the Atlantic.


How To Prevent Alzheimer’s

Researchers from Imperial College London (ICL) have prevented the development of Alzheimer’s disease in mice by using a virus to deliver a specific gene into the brain. The early-stage findings by scientists open avenues for potential new treatments for the disease. In the study, published in the journal Proceedings of the National Academy of Sciences, the team used a type of modified virus to deliver a gene to brain cells.

Previous studies by the same team suggest this gene, called PGC1 – alpha, may prevent the formation of a protein called amyloid-beta peptide in cells in the lab. Amyloid-beta peptide is the main component of amyloid plaques, the sticky clumps of protein found in the brains of people with Alzheimer’s disease. These plaques are thought to trigger the death of brain cellsAlzheimer’s disease affects around 520,000 people in the UK. Symptoms include memory loss, confusion, and change in mood or personality. Worldwide 47.5 million people are affected by dementia – of which Alzheimer’s is the most common form. There is no cure, although current drugs can help treat the symptoms of the disease.

Dr Magdalena Sastre, senior author of the research from the Department of Medicine at Imperial, hopes the new findings may one day provide a method of preventing the disease, or halting it in the early stages.


She explained: “Although these findings are very early they suggest this gene therapy may have potential therapeutic use for patients. There are many hurdles to overcome, and at the moment the only way to deliver the gene is via an injection directly into the brain. However this proof of concept study shows this approach warrants further investigation.”

The modified virus used in the experiments was called a lentivirus vector, and is commonly used in gene therapy explained Professor Nicholas Mazarakis, co-author of the study from the Department of Medicine: “Scientists harness the way lentivirus infects cells to produce a modified version of the virus, that delivers genes into specific cells. It is being used in experiments to treat a range of conditions from arthritis to cancer. We have previously successfully used the lentivirus vector in clinical trials to deliver genes into the brains of Parkinson’s disease patients.