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#437293 These Scientists Just Completed a 3D ...
Human brain maps are a dime a dozen these days. Maps that detail neurons in a certain region. Maps that draw out functional connections between those cells. Maps that dive deeper into gene expression. Or even meta-maps that combine all of the above.
But have you ever wondered: how well do those maps represent my brain? After all, no two brains are alike. And if we’re ever going to reverse-engineer the brain as a computer simulation—as Europe’s Human Brain Project is trying to do—shouldn’t we ask whose brain they’re hoping to simulate?
Enter a new kind of map: the Julich-Brain, a probabilistic map of human brains that accounts for individual differences using a computational framework. Rather than generating a static PDF of a brain map, the Julich-Brain atlas is also dynamic, in that it continuously changes to incorporate more recent brain mapping results. So far, the map has data from over 24,000 thinly sliced sections from 23 postmortem brains covering most years of adulthood at the cellular level. But the atlas can also continuously adapt to progress in mapping technologies to aid brain modeling and simulation, and link to other atlases and alternatives.
In other words, rather than “just another” human brain map, the Julich-Brain atlas is its own neuromapping API—one that could unite previous brain-mapping efforts with more modern methods.
“It is exciting to see how far the combination of brain research and digital technologies has progressed,” said Dr. Katrin Amunts of the Institute of Neuroscience and Medicine at Research Centre Jülich in Germany, who spearheaded the study.
The Old Dogma
The Julich-Brain atlas embraces traditional brain-mapping while also yanking the field into the 21st century.
First, the new atlas includes the brain’s cytoarchitecture, or how brain cells are organized. As brain maps go, these kinds of maps are the oldest and most fundamental. Rather than exploring how neurons talk to each other functionally—which is all the rage these days with connectome maps—cytoarchitecture maps draw out the physical arrangement of neurons.
Like a census, these maps literally capture how neurons are distributed in the brain, what they look like, and how they layer within and between different brain regions.
Because neurons aren’t packed together the same way between different brain regions, this provides a way to parse the brain into areas that can be further studied. When we say the brain’s “memory center,” the hippocampus, or the emotion center, the “amygdala,” these distinctions are based on cytoarchitectural maps.
Some may call this type of mapping “boring.” But cytoarchitecture maps form the very basis of any sort of neuroscience understanding. Like hand-drawn maps from early explorers sailing to the western hemisphere, these maps provide the brain’s geographical patterns from which we try to decipher functional connections. If brain regions are cities, then cytoarchitecture maps attempt to show trading or other “functional” activities that occur in the interlinking highways.
You might’ve heard of the most common cytoarchitecture map used today: the Brodmann map from 1909 (yup, that old), which divided the brain into classical regions based on the cells’ morphology and location. The map, while impactful, wasn’t able to account for brain differences between people. More recent brain-mapping technologies have allowed us to dig deeper into neuronal differences and divide the brain into more regions—180 areas in the cortex alone, compared with 43 in the original Brodmann map.
The new study took inspiration from that age-old map and transformed it into a digital ecosystem.
A Living Atlas
Work began on the Julich-Brain atlas in the mid-1990s, with a little help from the crowd.
The preparation of human tissue and its microstructural mapping, analysis, and data processing is incredibly labor-intensive, the authors lamented, making it impossible to do for the whole brain at high resolution in just one lab. To build their “Google Earth” for the brain, the team hooked up with EBRAINS, a shared computing platform set up by the Human Brain Project to promote collaboration between neuroscience labs in the EU.
First, the team acquired MRI scans of 23 postmortem brains, sliced the brains into wafer-thin sections, and scanned and digitized them. They corrected distortions from the chopping using data from the MRI scans and then lined up neurons in consecutive sections—picture putting together a 3D puzzle—to reconstruct the whole brain. Overall, the team had to analyze 24,000 brain sections, which prompted them to build a computational management system for individual brain sections—a win, because they could now track individual donor brains too.
Their method was quite clever. They first mapped their results to a brain template from a single person, called the MNI-Colin27 template. Because the reference brain was extremely detailed, this allowed the team to better figure out the location of brain cells and regions in a particular anatomical space.
However, MNI-Colin27’s brain isn’t your or my brain—or any of the brains the team analyzed. To dilute any of Colin’s potential brain quirks, the team also mapped their dataset onto an “average brain,” dubbed the ICBM2009c (catchy, I know).
This step allowed the team to “standardize” their results with everything else from the Human Connectome Project and the UK Biobank, kind of like adding their Google Maps layer to the existing map. To highlight individual brain differences, the team overlaid their dataset on existing ones, and looked for differences in the cytoarchitecture.
The microscopic architecture of neurons change between two areas (dotted line), forming the basis of different identifiable brain regions. To account for individual differences, the team also calculated a probability map (right hemisphere). Image credit: Forschungszentrum Juelich / Katrin Amunts
Based on structure alone, the brains were both remarkably different and shockingly similar at the same time. For example, the cortexes—the outermost layer of the brain—were physically different across donor brains of different age and sex. The region especially divergent between people was Broca’s region, which is traditionally linked to speech production. In contrast, parts of the visual cortex were almost identical between the brains.
The Brain-Mapping Future
Rather than relying on the brain’s visible “landmarks,” which can still differ between people, the probabilistic map is far more precise, the authors said.
What’s more, the map could also pool yet unmapped regions in the cortex—about 30 percent or so—into “gap maps,” providing neuroscientists with a better idea of what still needs to be understood.
“New maps are continuously replacing gap maps with progress in mapping while the process is captured and documented … Consequently, the atlas is not static but rather represents a ‘living map,’” the authors said.
Thanks to its structurally-sound architecture down to individual cells, the atlas can contribute to brain modeling and simulation down the line—especially for personalized brain models for neurological disorders such as seizures. Researchers can also use the framework for other species, and they can even incorporate new data-crunching processors into the workflow, such as mapping brain regions using artificial intelligence.
Fundamentally, the goal is to build shared resources to better understand the brain. “[These atlases] help us—and more and more researchers worldwide—to better understand the complex organization of the brain and to jointly uncover how things are connected,” the authors said.
Image credit: Richard Watts, PhD, University of Vermont and Fair Neuroimaging Lab, Oregon Health and Science University Continue reading
Posted in Human Robots
#437236 Why We Need Mass Automation to ...
The scale of goods moving around the planet at any moment is staggering. Raw materials are dug up in one country, spun into parts and pieces in another, and assembled into products in a third. Crossing oceans and continents, they find their way to a local store or direct to your door.
Magically, a roll of toilet paper, power tool, or tube of toothpaste is there just when you need it.
Even more staggering is that this whole system, the global supply chain, works so well that it’s effectively invisible most of the time. Until now, that is. The pandemic has thrown a floodlight on the inner workings of this modern wonder—and it’s exposed massive vulnerabilities.
The e-commerce supply chain is an instructive example. As the world went into lockdown, and everything non-essential went online, demand for digital fulfillment skyrocketed.
Even under “normal” conditions, most e-commerce warehouses were struggling to meet demand. But Covid-19 has further strained the ability to cope with shifting supply, an unprecedented tidal wave of orders, and labor shortages. Local stores are running out of key products. Online grocers and e-commerce platforms are suspending some home deliveries, restricting online purchases of certain items, and limiting new customers. The whole system is being severely tested.
Why? Despite an abundance of 21st century technology, we’re stuck in the 20th century.
Today’s supply chain consists of fleets of ships, trucks, warehouses, and importantly, people scattered around the world. While there are some notable instances of advanced automation, the overwhelming majority of work is still manual, resembling a sort of human-powered bucket brigade, with people wandering around warehouses or standing alongside conveyor belts. Each package of diapers or bottle of detergent ordered by an online customer might be touched dozens of times by warehouse workers before finding its way into a box delivered to a home.
The pandemic has proven the critical need for innovation due to increased demand, concerns about the health and safety of workers, and traceability and safety of products and services.
At the 2020 World Economic Forum, there was much discussion about the ongoing societal transformation in which humans and machines work in tandem, automating and augmenting the way we get things done. At the time, pre-pandemic, debate trended toward skepticism and fear of job losses, with some even questioning the ethics and need for these technologies.
Now, we see things differently. To make the global supply chain more resilient to shocks like Covid-19, we must look to technology.
Perfecting the Global Supply Chain: The Massive ‘Matter Router’
Technology has faced and overcome similar challenges in the past.
World War II, for example, drove innovation in techniques for rapid production of many products on a large scale, including penicillin. We went from the availability of one dose of the drug in 1941, to four million sterile packages of the drug every month four years later.
Similarly, today’s companies, big and small, are looking to automation, robotics, and AI to meet the pandemic head on. These technologies are crucial to scaling the infrastructure that will fulfill most of the world’s e-commerce and food distribution needs.
You can think of this new infrastructure as a rapidly evolving “matter router” that will employ increasingly complex robotic systems to move products more freely and efficiently.
Robots powered by specialized AI software, for example, are already learning to adapt to changes in the environment, using the most recent advances in industrial robotics and machine learning. When customers suddenly need to order dramatically new items, these robots don’t need to stop or be reprogrammed. They can perform new tasks by learning from experience using low-cost camera systems and deep learning for visual and image recognition.
These more flexible robots can work around the clock, helping make facilities less sensitive to sudden changes in workforce and customer demand and strengthening the supply chain.
Today, e-commerce is roughly 12% of retail sales in the US and is expected to rise well beyond 25% within the decade, fueled by changes in buying habits. However, analysts have begun to consider whether the current crisis might cause permanent jumps in those numbers, as it has in the past (for instance with the SARS epidemic in China in 2003). Whatever happens, the larger supply chain will benefit from greater, more flexible automation, especially during global crises.
We must create what Hamza Mudassire of the University of Cambridge calls a “resilient ecosystem that links multiple buyers with multiple vendors, across a mesh of supply chains.” This ecosystem must be backed by robust, efficient, and scalable automation that uses robotics, autonomous vehicles, and the Internet of Things to help track the flow of goods through the supply chain.
The good news? We can accomplish this with technologies we have today.
Image credit: Guillaume Bolduc / Unsplash Continue reading
Posted in Human Robots
#437216 New Report: Tech Could Fuel an Age of ...
With rapid technological progress running headlong into dramatic climate change and widening inequality, most experts agree the coming decade will be tumultuous. But a new report predicts it could actually make or break civilization as we know it.
The idea that humanity is facing a major shake-up this century is not new. The Fourth Industrial Revolution being brought about by technologies like AI, gene editing, robotics, and 3D printing is predicted to cause dramatic social, political, and economic upheaval in the coming decades.
But according to think tank RethinkX, thinking about the coming transition as just another industrial revolution is too simplistic. In a report released last week called Rethinking Humanity, the authors argue that we are about to see a reordering of our relationship with the world as fundamental as when hunter-gatherers came together to build the first civilizations.
At the core of their argument is the fact that since the first large human settlements appeared 10,000 years ago, civilization has been built on the back of our ability to extract resources from nature, be they food, energy, or materials. This led to a competitive landscape where the governing logic is grow or die, which has driven all civilizations to date.
That could be about to change thanks to emerging technologies that will fundamentally disrupt the five foundational sectors underpinning society: information, energy, food, transportation, and materials. They predict that across all five, costs will fall by 10 times or more, while production processes will become 10 times more efficient and will use 90 percent fewer natural resources with 10 to 100 times less waste.
They say that this transformation has already happened in information, where the internet has dramatically reduced barriers to communication and knowledge. They predict the combination of cheap solar and grid storage will soon see energy costs drop as low as one cent per kilowatt hour, and they envisage widespread adoption of autonomous electric vehicles and the replacement of car ownership with ride-sharing.
The authors laid out their vision for the future of food in another report last year, where they predicted that traditional agriculture would soon be replaced by industrial-scale brewing of single-celled organisms genetically modified to produce all the nutrients we need. In a similar vein, they believe the same processes combined with additive manufacturing and “nanotechnologies” will allow us to build all the materials required for the modern world from the molecule up rather than extracting scarce natural resources.
They believe this could allow us to shift from a system of production based on extraction to one built on creation, as limitless renewable energy makes it possible to build everything we need from scratch and barriers to movement and information disappear. As a result, a lifestyle worthy of the “American Dream” could be available to anyone for as little as $250/month by 2030.
This will require a fundamental reimagining of our societies, though. All great civilizations have eventually hit fundamental limits on their growth and we are no different, as demonstrated by our growing impact on the environment and the increasing concentration of wealth. Historically this stage of development has lead to a doubling down on old tactics in search of short-term gains, but this invariably leads to the collapse of the civilization.
The authors argue that we’re in a unique position. Because of the technological disruption detailed above, we have the ability to break through the limits on our growth. But only if we change what the authors call our “Organizing System.” They describe this as “the prevailing models of thought, belief systems, myths, values, abstractions, and conceptual frameworks that help explain how the world works and our relationship to it.”
They say that the current hierarchical, centralized system based on nation-states is unfit for the new system of production that is emerging. The cracks are already starting to appear, with problems like disinformation campaigns, fake news, and growing polarization demonstrating how ill-suited our institutions are for dealing with the distributed nature of today’s information systems. And as this same disruption comes to the other foundational sectors the shockwaves could lead to the collapse of civilization as we know it.
Their solution is a conscious shift towards a new way of organizing the world. As emerging technology allows communities to become self-sufficient, flows of physical resources will be replaced by flows of information, and we will require a decentralized but highly networked Organizing System.
The report includes detailed recommendations on how to usher this in. Examples include giving individuals control and ownership of data rights; developing new models for community ownership of energy, information, and transportation networks; and allowing states and cities far greater autonomy on policies like immigration, taxation, education, and public expenditure.
How easy it will be to get people on board with such a shift is another matter. The authors say it may require us to re-examine the foundations of our society, like representative democracy, capitalism, and nation-states. While they acknowledge that these ideas are deeply entrenched, they appear to believe we can reason our way around them.
That seems optimistic. Cultural and societal change can be glacial, and efforts to impose it top-down through reason and logic are rarely successful. The report seems to brush over many of the messy realities of humanity, such as the huge sway that tradition and religion hold over the vast majority of people.
It also doesn’t deal with the uneven distribution of the technology that is supposed to catapult us into this new age. And while the predicted revolutions in transportation, energy, and information do seem inevitable, the idea that in the next decade or two we’ll be able to produce any material we desire using cheap and abundant stock materials seems like a stretch.
Despite the techno-utopianism though, many of the ideas in the report hold promise for building societies that are better adapted for the disruptive new age we are about to enter.
Image Credit: Futuristic Society/flickr Continue reading
Posted in Human Robots
#437209 A Renaissance of Genomics and Drugs Is ...
The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and Editing
Your genome is the software that runs your body. A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity for disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean. Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare. When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later article).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works. The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome. A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for moral and ethical dilemmas. In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera. Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals, and Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely. These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse. Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification to localized inflammatory conditions such as osteoarthritis to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology, and pulmonary disease.
Oisin Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
(1) Rapamycin
Originally extracted from bacteria found on Easter Island, rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division. Currently, rapamycin derivatives are widely used for immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which went public in 2018) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include decreased incidence of infection, improved influenza vaccination response, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
(2) Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients. Researchers have found that metformin also reduces oxidative stress and inflammation, which otherwise increase as we age. There is strong evidence that metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of metformin’s protective effect against cancer.
(3) Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next article in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer toward a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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This article originally appeared on diamandis.com. Read the original article here.
Image Credit: Arek Socha from Pixabay Continue reading
Posted in Human Robots