Tony Wyss-Coray studies the impact of aging on the human body and brain. In this eye-opening talk, he shares new research from his Stanford lab and other teams which shows that a solution for some of the less great aspects of old age might actually lie within us all.
Cancer researchers dream of the day they can force tumor cells to morph back to the normal cells they once were. Now, researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
The finding, published in Nature Cell Biology, represents “an unexpected new biology that provides the code, the software for turning off cancer,” says the study’s senior investigator, Panos Anastasiadis, Ph.D., chair of the Department of Cancer Biology on Mayo Clinic’s Florida campus.
That code was unraveled by the discovery that adhesion proteins — the glue that keeps cells together — interact with the microprocessor, a key player in the production of molecules called microRNAs (miRNAs). The miRNAs orchestrate whole cellular programs by simultaneously regulating expression of a group of genes. The investigators found that when normal cells come in contact with each other, a specific subset of miRNAs suppresses genes that promote cell growth. However, when adhesion is disrupted in cancer cells, these miRNAs are misregulated and cells grow out of control. The investigators showed, in laboratory experiments, that restoring the normal miRNA levels in cancer cells can reverse that aberrant cell growth.
“The study brings together two so-far unrelated research fields — cell-to-cell adhesion and miRNA biology — to resolve a long-standing problem about the role of adhesion proteins in cell behavior that was baffling scientists,” says the study’s lead author Antonis Kourtidis, Ph.D., a research associate in Dr. Anastasiadis’ lab. “Most significantly, it uncovers a new strategy for cancer therapy,” he adds.
That problem arose from conflicting reports about E-cadherin and p120 catenin — adhesion proteins that are essential for normal epithelial tissues to form, and which have long been considered to be tumor suppressors. “However, we and other researchers had found that this hypothesis didn’t seem to be true, since both E-cadherin and p120 are still present in tumor cells and required for their progression,” Dr. Anastasiadis says. “That led us to be believe that these molecules have two faces — a good one, maintaining the normal behavior of the cells, and a bad one that drives tumorigenesis.”
Their theory turned out to be true, but what was regulating this behavior was still unknown. To answer this, the researchers studied a new protein called PLEKHA7, which associates with E-cadherin and p120 only at the top, or the “apical” part of normal polarized epithelial cells. The investigators discovered that PLEKHA7 maintains the normal state of the cells, via a set of miRNAs, by tethering the microprocessor to E-cadherin and p120. In this state, E-cadherin and p120 exert their good tumor suppressor sides.
However, “when this apical adhesion complex was disrupted after loss of PLEKHA7, this set of miRNAs was misregulated, and the E-cadherin and p120 switched sides to become oncogenic,” Dr. Anastasiadis says.
“We believe that loss of the apical PLEKHA7-microprocessor complex is an early and somewhat universal event in cancer,” he adds. “In the vast majority of human tumor samples we examined, this apical structure is absent, although E-cadherin and p120 are still present. This produces the equivalent of a speeding car that has a lot of gas (the bad p120) and no brakes (the PLEKHA7-microprocessor complex).
“By administering the affected miRNAs in cancer cells to restore their normal levels, we should be able to re-establish the brakes and restore normal cell function,” Dr. Anastasiadis says. “Initial experiments in some aggressive types of cancer are indeed very promising.”
The study was supported by the National Institutes of Health grants R01 CA100467, R01 NS069753, P50 CA116201, R01 GM086435, R01CA104505, R01CA136665; the Florida Department of Health, Bankhead-Coley grants 10BG11; the Breast Cancer Research Foundation; the Swiss Cancer League; and the Jay and Deanie Stein Career Development Award for Cancer Research at Mayo Clinic.
The above post is reprinted from materials provided by Mayo Clinic. Note: Materials may be edited for content and length.
Siu Ngok, Ryan Feathers; Lomeli Carpio; Tiffany Baker; Jennifer Carr; Irene Yan; Sahra Borges, Edith Perez, Peter Storz, John Copland, Tushar Patel, E. Aubrey Thompson, Pamela Pulimeno, Sandra Citi. Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120-catenin activity. Nature Cell Biology, 2015 DOI: 10.1038/ncb3227
By tweaking a single gene, scientists have turned average mice into supersmart daredevils. The findings are preliminary but hint at therapies that may one day ease the symptoms of such disorders as Alzheimer’s disease and schizophrenia, scientists report August 14 in Neuropsychopharmacology.
The altered gene provides instructions for a protein called phosphodiesterase-4B, or PDE4B, which has been implicated in schizophrenia. It’s too early to say whether PDE4B will turn out to be a useful target for drugs that treat these disorders, cautions pharmacologist Ernesto Fedele of the University of Genoa in Italy. Nonetheless, the protein certainly deserves further investigation, he says.
The genetic change interfered with PDE4B’s ability to do its job breaking down a molecular messenger called cAMP. Mice designed to have this disabled form of PDE4B showed a suite of curious behaviors, including signs of smarts, says study coauthor Alexander McGirr of the University of British Columbia. Compared with normal mice, these mice more quickly learned which objects in a cage had been moved to a new location, for instance, and could better recognize a familiar mouse after 24 hours. “The system is primed and ready to learn, and it doesn’t require the same kind of input as a normal mouse,” McGirr says.
These mice also spent more time than usual exploring brightly lit spaces, spots that normal mice avoid. But this devil-may-care attitude sometimes made the “smart” mice blind to risky situations. The mice were happy to spend time poking around an area that had been sprinkled with bobcat urine. “Not being afraid of cat urine is not a good thing for a mouse,” McGirr says.
PDE4B may play other roles in the brain, McGirr says. And because the protein has jobs in the heart, lungs and immune system as well, it might be difficult to find drugs that have the desired effect on PDE4B in the brain but few side effects elsewhere. “It’s a very reasonable target but we are quite a ways from having good medicines,” McGirr says.
A little known Seattle startup could do for metal what 3D printing is doing for other materials like plastic.
A Seattle startup has found a way to grow high performance metals in a cheap and energy efficient way, marking an important breakthrough for industries like construction, automotive, and oil and gas.
You can already find some of the metals from seven-year-old company Modumetal on oil rigs off of the Australian and African coasts, as well as the U.S., off of Texas. Those metals can withstand the ocean’s corrosive power for up to eight times longer than conventional materials, according to the company.
On Tuesday, Modumetal took a big step towards its goal of gaining a bigger market for its innovative recipe. The company said that it had raised $33.5 million in funding that will go to increasing production and sales along with developing new uses for its metals.
The funding was led by the Founders Fund, the firm co-created by Silicon Valley investor Peter Thiel that has previously invested in space cargo company SpaceX, room rental service Airbnb and data giant Palantir. Other investors include the venture arms of three oil big companies, Chevron Technology Ventures, BP Ventures and ConocoPhillips.
Modumetal’s CEO and co-founder Christina Lomasney, a physicist who’s spent years working on electrochemistry and advanced materials, told Fortune that the company’s metal growing process is “the ideal way of making materials.” It is similar to the way that “Mother Nature has evolved [growing things] over eons,” she said.
Some of the more conventional ways to extract and use various types of metals often include large amounts of heat. Many metals are mined and then extracted from the ores through smelting at a high temperature. Companies can also reuse metal scraps, but they must be melted and cast into usable shapes.
In contrast, Modumetal’s process only uses electricity, and therefore uses far less energy. The company’s metal process is similar to the more conventional method of electroplating, which is when electricity is used to create a metal coating on a surface.
However, Modumetal uses nanotechnology — manipulation of matter at the molecular level — to micromanage at a very small scale to better control the conditions and substances through which electroplating occurs. Basically, the company grows metal on a surface in a way that makes it easier to shape and tinker with the material’s characteristics. Lomasney says it’s similar to how nature controls the environment related to a tree’s growth— sunlight, soil, location, temperature—and then creates a tree that is a product those conditions.
The process creates a metal that is grown layer-by-layer. The different ways to grow the layers creates variety in the metal’s properties and shape. Lomasney says to think about the resulting material like plywood, but the plies, or pieces, are created at the nanotech level.
The industry calls these layered metals “metal laminates,” and they’ve been around in the industry for a while. Lomasney’s breakthrough is using a chemical and electrical production process combined with nanotechnology to create the metal plywoods at a low cost, with low energy and with the ability to make the metal pieces in large volumes and with large pieces (think oil rig big).
The company is making a laminated zinc alloy for its customers that want a metal that won’t corrode as fast as standard zinc. But laminated steel could be the big market for Modumental. The company considers its strong and long-lasting steel product as the next-generation of the steel industry.
Modumetal’s original technology was created by Lomasney and her co-founder, chemical engineer John Whitaker. The partners previously worked on using electricity and chemistry to clean up toxic environments. After noticing their work, the Defense Department approached them to work on making advanced materials that could produce armor for soldiers that would be both very strong (stop bullets) but also last a long time (stop bullets over many years).
Lomasney and Whitaker spun out the core armor-making tech to start Modumetal. The company now has a research and development lab in Seattle, a factory in Maltby, Wash., and a field services office in Houston, Tex. The funds will help the company grow production at its factory in Maltby.
Despite the company’s ambition and promise, the startup world can be extraordinarily difficult. Expanding factory production can be particularly hard for a small company. Large scale manufacturing requires production to be precisely repeated over and over again, with little variation, which can be challenging with new technologies.
In addition the company is selling into long established and sometimes slow moving industries. While the company seems to have won over oil companies early on, big metal makers, car companies, aviation firms and construction companies can be notoriously risk averse and tend to shy away from partnering with young venture-capital backed startups.
Some of the biggest materials and metals companies around the world, which have some of the deepest pockets, and also are likely working on competitive technologies. The company will need to aggressively protect its patents —the core of its business—through both acquisition and legal action.
Modumetal sees the corrosion-protected metals as its first big market. But there are many other possibilities that the company and its customers are interested in. For example, Modumetal has a joint venture with one of the largest U.S. sheet metal makers, Steel Dynamics, to come up with applications for an upgraded version of sheet metal in the future.
Metal production isn’t often talked about. It’s not a particularly sexy topic. But if Modumetal can get its metals into everything from skyscrapers to airplanes, the company could make a big mark. It’s like how 3D printing is introducing an entirely new and easier way to print plastics and other materials into shapes that either couldn’t previously be made or would otherwise take a lot of effort to create.
In the 1800’s, aluminum was so expensive to make that it was confined to trinkets like Napoleon’s buttons and flatwear, Lomasney says. But in the late 1800’s, inventor Charles Martin Hall created a way to inexpensively make aluminum. He created a massive new industry and co-founded aluminum giant Alcoa AA-0.37% . If Modumetal could gain a fraction of the traction that Alcoa has had it would be a major success.
For more about metal innovation, watch this Fortune video:
A piece of metal made using Seattle-based startup Modumetal’s novel metal-making process.Photo courtesy of Will Foster willfosterphoto.com
Everything you have ever done or will do could simply be the product of a highly-advanced computer code.
Every relationship, every sentiment, every memory could have been generated by banks of supercomputers.
This was the terrifying theory first proposed by British philosopher Nick Bostrom.
The shocking hypothesis was penned four years after Andrew and Lana Wachowski wrote and directed The Matrix, a film set in a dystopian future in which humans are subdued by a simulated reality.
In his paper, Dr Bostrom suggested a race of far-evolved descendants could be behind our digital imprisonment.
The futuristic beings – human or otherwise – could be using virtual reality to simulate a time in the past or recreate how their remote ancestors lived.
Sound crazy? Well, it turns out NASA thinks Dr Bostrom might be right.
The Standard Model of Physics does not yet hold an explanation for the force of gravity
Rich Terrile, director of the Centre for Evolutionary Computation and Automated Design at NASA’s Jet Propulsion Laboratory, has spoken out about the digital simulation.
“Right now the fastest NASA supercomputers are cranking away at about double the speed of the human brain,” the NASA scientist told Vice.
“If you make a simple calculation using Moore’s Law [which roughly claims computers double in power every two years], you’ll find that these supercomputers, inside of a decade, will have the ability to compute an entire human lifetime of 80 years – including every thought ever conceived during that lifetime – in the span of a month.
“In quantum mechanics, particles do not have a definite state unless they’re being observed.
“Many theorists have spent a lot of time trying to figure out how you explain this.
“One explanation is that we’re living within a simulation, seeing what we need to see when we need to see it.
“What I find inspiring is that, even if we are in a simulation or many orders of magnitude down in levels of simulation, somewhere along the line something escaped the primordial ooze to become us and to result in simulations that made us – and that’s cool.”
The idea that our Universe is a fiction generated by computer code solves a number of inconsistencies and mysteries about the cosmos.
Professor Fermi known for achieving the first controlled nuclear reaction, leads a lecture
Enrico Fermi outside an atomic energy plant in Newport in October 1957
The first is the Fermi Paradox – proposed by physicist Enrico Fermi during the 1960s – which highlights the contradiction between the apparent high probability of extraterrestrial civilisations within our ever-expanding universe and humanity’s lack of contact with, or lack of evidence for, these alien colonies.
“Where is everybody?” Mr Fermi asked.
It could simply be that Earth and mankind truly is the centre of the universe.
Another mystery explained by Dr Bostrom’s Matrix-like theory is the role of Dark Matter.
US theoretical cosmologist Michael Turner has called the hypothetical material “the most profound mystery in all of science”.
Dark Matter is one of many hypothetical materials used to explain a number of anomalies in the Standard Model – the all-encompassing theory science has used to explain the particles and forces of nature for the last 50 years.
The Standard Model of particle physics tells us that there are 17 fundamental particles which make up atomic matter.
A scientist works within the ATLAS control room, part of the Large Hadron Collider facility
Scientists hope to prove the existence of Dark Matter within the CERN accelerator
The Higgs boson, which was first theorised by scientists during the 1960s, is amongst these 17 fundamental particles.
In summer 2012, scientists at CERN observed what is now believed to be the elusive “God particle”.
But the Standard Model is as-yet unable to explain a number of baffling properties of the universe – including the fact that the universe is expanding at an ever-increasing speed.
Dark Matter is believed to be a web-like matter that binds visible matter together.
If it exists, it would explain why galaxies spin at the speed they do – something which remains unexplained based only on what we can currently observe.
The Standard Model does not yet hold an explanation for the force of gravity.
The as-yet unproven existence of Dark Matter could be explained by a virtual universe.
But not everybody is convinced about The Matrix explanation.
Professor Peter Millican, who teaches philosophy and computer science at Oxford University, thinks the virtual reality explanation is flawed.
“The theory seems to be based on the assumption that ‘superminds’ would do things in much the same way as we would do them,” he said.
“If they think this world is a simulation, then why do they think the superminds – who are outside the simulation – would be constrained by the same sorts of thoughts and methods that we are?
“They assume that the ultimate structure of a real world can’t be grid like, and also that the superminds would have to implement a virtual world using grids.
“We can’t conclude that a grid structure is evidence of a pretend reality just because our ways of implementing a pretend reality involve a grid.”
Professor Millican does believe there is worth in investigating the idea.
“It is an interesting idea, and it’s healthy to have some crazy ideas,” he told The Telegraph.
“You don’t want to censor ideas according to whether they seem sensible or not because sometimes important new advances will seem crazy to start with.
“You never know when good ideas may come from thinking outside the box.
“This Matrix thought-experiment is actually a bit like some ideas of Descartes and Berkeley, hundreds of years ago.
“Even if there turns out to be nothing in it, the fact that you have got into the habit of thinking crazy things could mean that at some point you are going to think of something that initially may seem rather way out, but turns out not to be crazy at all.”
Boston Dynamics, which Google bought in 2013, has begun testing one of its humanoid robots — those that are designed to function like humans — out in the wild.
Marc Raibert, the founder of Boston Dynamics, talked about the research and showed footage of the project during a talk on Aug. 3 at the 11th Fab Lab Conference and Symposium in Cambridge, Mass.
“Out in the world is just a totally different challenge than in the lab,” Raibert said at the conference, which was organized by the Fab Foundation, a division of the Massachusetts Institute of Technology’s Center for Bits and Atoms. “You can’t predict what it’s going to be like.”
The question of why we age is one of the most fascinating questions for humankind, but nothing close to a satisfactory answer has been found to date. Scientists at the Leibniz-Institut für Molekulare Pharmakologie in Berlin have now taken one step closer to providing an answer. They have conducted a study in which, for the first time, they have shown that a certain area of the cell, the so-called endoplasmic reticulum, loses its oxidative power in advanced age. If this elixir of life is lost, many proteins can no longer mature properly. At the same time, oxidative damage accumulates in another area of the cell, the cytosol. This interplay was previously unknown and now opens up a new understanding of aging, but also of neurodegenerative diseases such as Alzheimer’s or Parkinson’s.
Each cell consists of different compartments. One of them is the endoplasmic reticulum (ER). Here, proteins which are then secreted e.g. into the bloodstream, such as insulin or antibodies of the immune system, mature in an oxidative environment. A type of quality control, so-called redox homoeostasis, ensures that the oxidative milieu is maintained and disulphide bridges can form. Disulphide bridges form and stabilise the three-dimensional protein structure and are thus essential for a correct function of the secretory proteins, e.g. those migrating into the blood.
Equilibrium thrown off balance
Scientists at the Leibniz-Institut für Molekulare Pharmakologie in Berlin have now shown, for the first time, that the ER loses its oxidative power in advanced age, which shifts the reducing/oxidising equilibrium — redox for short — in this compartment. This leads to a decline in the capacity to form the disulphide bridges that are so important for correct protein folding. As a consequence, many proteins can no longer mature properly and become unstable.
Although, it was already known that increased protein misfolding occurs with the progression of aging, it was not known whether the redox equilibrium is affected. Likewise, it was not known that the loss of oxidative power in the ER also affects the equilibrium in another compartment of the cell: in reverse, namely, the otherwise protein-reducing cytosol becomes more oxidising during aging, which leads to the known oxidative protein damage such those caused by the release of free radicals.
“Up to now, it has been completely unclear what happens in the endoplasmic reticulum during the aging process. We have now succeeded in answering this question,” says Dr. Janine Kirstein, first author of the study, which has been published in EMBO Journal*. At the same time, the scientists were able to show that there is a strong correlation between protein homoeostasis and redox equilibrium. “This is absolutely new and helps us to understand why secretory proteins become unstable and lose their function in advanced age and after stress. This may explain why the immune response declines as we get older,” the biologist explains further.
Stress has the same effects as aging
The researchers also demonstrated the decline of the oxidative milieu of the ER after stress. When they synthesised amyloid protein fibrils in the cell, which cause diseases such as Alzheimer’s, Parkinson’s or Huntington’s disease, they set the same cascade in motion. Apart from this, they were able to show that amyloids that are synthesised in a certain tissue also have negative effects on the redox equilibrium in another tissue within the same organism. “Protein stress leads to the same effects as aging,” explains Kirstein. “Our findings are thus not only interesting with regards to aging, but also concerning neurodegenerative diseases such as Alzheimer’s.”
For their experiments, the team of researchers used nematodes — an established model system for investigating aging processes on a molecular level. Since the nematode is transparent, the researchers were able to use fluorescence-based sensors in order to measure oxidation in the individual cell compartments. It was thus possible to track precisely in the living nematode how the redox condition changes with advancing age. In addition, the influence of protein aggregation on the redox homeostasis was investigated in cultivated cells of human origin. The data were fully consistent with those from the nematode.
Using the findings to identify new diagnostic biomarkers
“We gained a lot of insight, but have also learned that aging is much more complex than previously assumed,” stresses the biologist Kirstein. Thus, for example, the mechanism of the signal transduction of protein folding stress to the redox equilibrium — both within the cell from one compartment to another and also between two different tissues — remains completely unclear.
Nevertheless, research of aging has taken a major step forward as a result of the findings from Berlin, particularly since it promises a practical benefit. The redox equilibrium may serve as a basis for new biomarkers for diagnosing both aging and neurodegenerative processes in the future. Janine Kirstein: “The approach is less likely to be useful for therapeutic purposes at present, but the development of diagnostic tools is certainly conceivable.”
J. Kirstein, D. Morito, T. Kakihana, M. Sugihara, A. Minnen, M. S. Hipp, C. Nussbaum-Krammer, F. U. Hartl, K. Nagata, R. I. Morimoto. Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments. The EMBO Journal, 2015; DOI: 10.15252/embj.201591711
In 2025, in accordance with Moore’s Law, we’ll see an acceleration in the rate of change as we move closer to a world of true abundance. Here are eight areas where we’ll see extraordinary transformation in the next decade:
1. A $1,000 Human Brain
In 2025, $1,000 should buy you a computer able to calculate at 10^16 cycles per second (10,000 trillion cycles per second), the equivalent processing speed of the human brain.
2. A Trillion-Sensor Economy
The Internet of Everything describes the networked connections between devices, people, processes and data. By 2025, the IoE will exceed 100 billion connected devices, each with a dozen or more sensors collecting data. This will lead to a trillion-sensor economy driving a data revolution beyond our imagination. Cisco’s recent report estimates the IoE will generate $19 trillion of newly created value.
3. Perfect Knowledge
We’re heading towards a world of perfect knowledge. With a trillion sensors gathering data everywhere (autonomous cars, satellite systems, drones, wearables, cameras), you’ll be able to know anything you want, anytime, anywhere, and query that data for answers and insights.
4. 8 Billion Hyper-Connected People
Facebook (Internet.org), SpaceX, Google (Project Loon), Qualcomm and Virgin (OneWeb) are planning to provide global connectivity to every human on Earth at speeds exceeding one megabit per second.
We will grow from three to eight billion connected humans, adding five billion new consumers into the global economy. They represent tens of trillions of new dollars flowing into the global economy. And they are not coming online like we did 20 years ago with a 9600 modem on AOL. They’re coming online with a 1 Mbps connection and access to the world’s information on Google, cloud 3D printing, Amazon Web Services, artificial intelligence with Watson, crowdfunding, crowdsourcing, and more.
5. Disruption of Healthcare
Existing healthcare institutions will be crushed as new business models with better and more efficient care emerge. Thousands of startups, as well as today’s data giants (Google, Apple, Microsoft, SAP, IBM, etc.) will all enter this lucrative $3.8 trillion healthcare industry with new business models that dematerialize, demonetize and democratize today’s bureaucratic and inefficient system.
Biometric sensing (wearables) and AI will make each of us the CEOs of our own health. Large-scale genomic sequencing and machine learning will allow us to understand the root cause of cancer, heart disease and neurodegenerative disease and what to do about it. Robotic surgeons can carry out an autonomous surgical procedure perfectly (every time) for pennies on the dollar. Each of us will be able to regrow a heart, liver, lung or kidney when we need it, instead of waiting for the donor to die.
6. Augmented and Virtual Reality
Billions of dollars invested by Facebook (Oculus), Google (Magic Leap), Microsoft (Hololens), Sony, Qualcomm, HTC and others will lead to a new generation of displays and user interfaces.
The screen as we know it — on your phone, your computer and your TV — will disappear and be replaced by eyewear. Not the geeky Google Glass, but stylish equivalents to what the well-dressed fashionistas are wearing today. The result will be a massive disruption in a number of industries ranging from consumer retail, to real estate, education, travel, entertainment, and the fundamental ways we operate as humans.
7. Early Days of JARVIS
Artificial intelligence research will make strides in the next decade. If you think Siri is useful now, the next decade’s generation of Siri will be much more like JARVIS from Iron Man, with expanded capabilities to understand and answer. Companies like IBM Watson, DeepMind and Vicarious continue to hunker down and develop next-generation AI systems. In a decade, it will be normal for you to give your AI access to listen to all of your conversations, read your emails and scan your biometric data because the upside and convenience will be so immense.
If you haven’t heard of the blockchain, I highly recommend you read up on it. You might have heard of bitcoin, which is the decentralized (global), democratized, highly secure cryptocurrency based on the blockchain. But the real innovation is the blockchain itself, a protocol that allows for secure, direct (without a middleman), digital transfers of value and assets (think money, contracts, stocks, IP). Investors like Marc Andreesen have poured tens of millions into the development and believe this is as important of an opportunity as the creation of the Internet itself.
Bottom Line: We Live in the Most Exciting Time Ever
We are living toward incredible times where the only constant is change, and the rate of change is increasing.