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New York University scientists have discovered how working memory is formatted. And they have advanced toward better understanding of how visual memories are stored. Working memory is the ability to store and retrieve information for short periods of time. And impairments of working memory are associated with many psychiatric and neurologic conditions, including schizophrenia. "For decades researchers have wondered about the nature of the neural representations that support our working memory," explains research leader Clayton Curtis in a press release issued by New York University. "In this study, we used both experimental and analytical techniques to reveal the format of working memory representations in the brain." "Although we can predict the contents of your working memory from the patterns of brain activity, what exactly these patterns are coding for has remained impenetrable," adds Curtis. A paper is published in Neuron. Scientists measured the brain activity of participants in the study. They used functional magnetic resonance imaging (fMRI), while the participants performed visual working memory tasks. With the help of models of the brain, scientists created a representation of the neural activity of participants. Participants viewed a monitor. And their viewing patterns were translated into coordinates within the space of the monitor. This enabled the scientists to "see" how working memory is encoded. Participants were presented with two different visual stimuli. In some trials, the visual stimulus was a tilted grating. And in others it was a cloud of moving dots. After a delay, participants had to indicate the exact angle of the grating's tilt or the exact angle of the dot cloud's motion. The results of the study indicate that working memory uses the same format to encode the direction of the motion of the dots and the orientation of the titled grating. "We reasoned that only the task-relevant features of the tested stimuli were extracted and re-coded into a shared memory format, perhaps taking the form of an abstract line-like shape angled to match either the orientation of the grating or the direction of dot motion," explains Curtis. “We could see lines of activity across the topographic maps at angles corresponding to the motion direction and grating." Generalizing, it seems that the brain discards task-irrelevant features. And it also encodes task-relevant features into efficient memory formats. This confirms and extends a previously known feature of working memory. Visual working memory about letters and numbers is encoded using the same format as verbal working memory. That the brain uses an efficient format to represent many different things makes a lot of sense to me. It's an optimized strategy developed over the course of evolution. And it seems likely to me that this research program will not only shed more light on how our own brains work, but also permit advances toward human-like artificial intelligence.

Nutritional scientists report the result of their double-blind, placebo-controlled investigation on the effects of herbal supplements on cognitive health. A study was published in Nutritional Neuroscience. The scientists studied a multi-ingredient herbal supplement containing Bacopa monnieri (BM), Panax quinquefolius ginseng (PQ), and whole coffee fruit extract (WCFE). Their aim was to determine whether it could enhance cognitive performance and cerebral-cortical activation during tasks of working memory and attention. Motivated by growing evidence that herbal extracts, such as BM and PQ could acutely enhance cognitive performance, the scientists designed a rigorous study. Forty healthy adults between 18 and 60 years, 21 females and 19 males, participated. They completed tasks designed to test working memory and attention, without supplements, and 45 minutes after consuming either an active supplement or a placebo. The active supplement was made up of commercially available extracts of BM (150 mg/ tablet), PQ (50 mg/tablet), and WCFE (50 mg/tablet). The participants in the active supplement group consumed a two-tablet dose to provide a total dose of 300 mg BM, 100 mg PG, and 100 mg of WCFE, with a combined active ingredient intake of 500 mg. During the cognitive testing, changes in hemodynamic response in the prefrontal cortex (PFC) were continuously measured using functional near-infrared spectroscopy (fNIRS). The term hemodynamics refers to the dynamics of the blood flow. The results of the study indicate that working memory was significantly improved following active supplement consumption compared to placebo in terms of both accuracy and response time. The improved performance was associated with a reduction of PFC activation related to effortful mental demand. This reflected increased neural efficiency concomitant with improved cognitive performance. Taken together, the results show improved accuracy and response time across cognitively demanding working memory tasks following active treatment. According to the scientists, this was the first study to examine the combined dose effects of Bacopa, Ginseng, and whole coffee fruit extracts on cognitive performance and brain activation of the PFC using fNIRS. The results show that the combination can modulate brain activation and cognitive task performance. This is the first report of acute, significant changes in cognitive function following intake of a combined, multi-ingredient herbal supplement with concomitant observed changes in haemodynamic response in healthy adults. This study demonstrated that a single, combined dose of herbal extracts known to influence cognitive function improved working memory performance. An equivalent improvement in attention was not found, despite an overall increase in efficiency for response time. The scientists conclude that future studies are needed to replicate the current findings. They also recommend additional examination of the potential positive effects of these herbal supplements across different cognitive functions, with a focus on working memory tasks. Thrivous develops Clarity Daily Nootropic and Surge Acute Nootropic to enhance cognitive performance. Each serving of Clarity provides a clinical dose of Bacopa. And each serving of Surge provides a clinical dose of Ginseng and Caffeine. As indicated by this study, a single serving combination of Clarity and Surge may enhance performance on working memory tasks.

Scientists at the Telomere to Telomere (T2T) consortium led by National Institutes of Health (NIH), UC Santa Cruz, and University of Washington, have published the first complete, gapless sequence of a human genome. It has been two decades since the Human Genome Project produced the first draft human genome sequence. “Generating a truly complete human genome sequence represents an incredible scientific achievement, providing the first comprehensive view of our DNA blueprint,” says Eric Green. He is the director of the National Human Genome Research Institute, which is part of NIH. The statement comes from a press release issued by NIH. “This foundational information will strengthen the many ongoing efforts to understand all the functional nuances of the human genome, which in turn will empower genetic studies of human disease.” Six papers encompassing the completed sequence have been published in Science. And related papers have been published in other journals. “Ever since we had the first draft human genome sequence, determining the exact sequence of complex genomic regions has been challenging,” said Evan Eichler, researcher at University of Washington School of Medicine. “I am thrilled that we got the job done. The complete blueprint is going to revolutionize the way we think about human genomic variation, disease and evolution.” CNN notes that the Human Genome Project made history when it sequenced 92 percent of the human genome in 2003. But, after that, scientists have struggled to decipher the remaining eight percent. This is what the T2T scientists have accomplished. The new research adds 400 million letters to the previously sequenced DNA. The full genome will allow scientists to analyze how DNA differs between people and whether these genetic variations play a role in disease. “This complete human genome sequence has already provided new insight into genome biology, and I look forward to the next decade of discoveries about these newly revealed regions,” says Karen Miga, research leader at UC Santa Cruz. Geneticist Colin Johnson called the work “truly ground-breaking,” as reported by BBC News. He compared the previously missing eight percent of the human genome to “the dark matter of the genome that we knew was there but couldn't get to.” And he added that now we have “the full description of the book of life, with all of the paragraphs and pages assembled." Sequencing a person's entire genome should get less expensive and more straightforward in the coming years. “In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their healthcare,” says Adam Phillippy, research leader at NHGRI. "Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means."

Scientists, led by University of Washington, have developed a new method for designing and building protein based drugs. Using computers, the scientists designed molecules that can target important proteins in the body. They include the insulin receptor, as well as vulnerable proteins on the surface of viruses. "The ability to generate new proteins that bind tightly and specifically to any molecular target that you want is a paradigm shift in drug development and molecular biology more broadly," said David Baker in a press release issued by University of Washington. Baker was a recipient of the 2021 Breakthrough Prize in Life Sciences for “developing technology that allowed the design of proteins never seen before in nature, including novel proteins that have the potential for therapeutic intervention in human diseases.” Protein-based drugs bind to a specific molecular target, which then becomes either activated or deactivated. Antibodies are protein-based drugs that can treat a wide range of health disorders, including COVID-19 and cancer. However, protein-based drug development is challenging and expensive. A research paper is published in Nature. It describes how the scientists combined recent advances in computational protein design to develop a strategy for creating new proteins that bind molecular targets in a manner similar to antibodies. The scientists developed software that can scan a target molecule. It can identify potential binding sites and generate proteins targeting those sites. It can then screen from millions of candidate binding proteins to identify those most likely to function. "When it comes to creating new drugs, there are easy targets and there are hard targets," said research co-leader Longxing Cao. "In this paper, we show that even very hard targets are amenable to this approach. We were able to make binding proteins to some targets that had no known binding partners or antibodies." The scientists produced over half a million candidate binding proteins for twelve selected molecular targets. They included insulin receptors and proteins on the surface of the influenza virus and SARS-CoV-2 (the virus that causes COVID-19). "We look forward to seeing how these molecules might be used in a clinical context, and more importantly how this new method of designing protein drugs might lead to even more promising compounds in the future," said research co-leader Brian Coventry. SingularityHub summarizes the findings. They note that the candidate binding proteins “were highly efficient at blocking their targets.” Some cut off growth signals that can lead to cancer. Others point the way to a universal flu vaccine that could neutralize multiple strains. Previously published results indicate that the method provided protection against COVID-19 in mice. This may lead to new treatments for cancer, diabetes, infection, inflammation, and beyond. SingularityHub notes that the research results “could fundamentally change medicine.” They are based on powerful artificial intelligence methods for protein folding research. And they may allow scientists to design and build protein-like drugs from the ground up.

Researchers at Karolinska Institute have found a way of stabilizing the p53 protein, and making it more potent. P53 protects our cells from cancer. By adding a spider silk protein to p53, the researchers have shown that it is possible to create a protein that is more stable and more capable of killing cancer cells. P53 plays a key role in the body's defense against cancer. If a cell is lacking functional p53, it quickly becomes a cancer cell. And it starts to divide uncontrollably. "The problem is that cells only make small amounts of p53 and then quickly break it down as it is a very large and disordered protein," says researcher Michael Landreh in a press release issued by Karolinska Institute. "We've been inspired by how nature creates stable proteins and have used spider silk protein to stabilize p53. Spider silk consists of long chains of highly stable proteins, and is one of nature's strongest polymers." Discovered in the late 1970s, p53 has been called the guardian of the genome. It can stop cells with DNA damage from turning into cancer cells. Essentially, p53 shuts down a cell if it detects any damage that could cause the cell to grow into cancer. Mutations of the p53 gene are found in roughly half of all tumors. That makes it the most common genetic change in cancer. A paper is published in Structure. The researchers report that they attached a small section of a synthetic spider silk protein onto the human p53 protein. When they then introduced it into cells, they found that the cells started to produce p53 in large quantities. The new protein also proved to be more stable than ordinary p53 and more capable of killing cancer cells. Using electron microscopy, computer simulations, and mass spectrometry, the researchers were able to show that the likely reason for this was the way the spider silk part managed to give structure to p53's disordered sections. "Creating a more stable variant of p53 in cells is a promising approach to cancer therapy, and now we have a tool for this that's worth exploring," says senior researcher Sir David Lane, who was one of the discoverers of p53. "We eventually hope to develop an mRNA-based cancer vaccine, but before we do so we need to know how the protein is handled in the cells and if large amounts of it can be toxic." Writing in The Conversation, Landreh explains that spidroins are a bit like p53. They are proteins that spiders spin into silk. They are also large, floppy, and easily clumped together. But unlike p53, spidroins are capped by a small part that is very stable. And it can easily be made by the cellular protein production machinery. “To test if the spider silk-p53 protein is active, we put it into cancer cells that contain so-called ‘reporter genes’, which cause the cell to light up if p53 turns on genes that make the cell stop growing,” says Landreh. “To our surprise, the fusion protein gave a stronger response than normal p53, which means that we could in principle use the spider silk domain to increase the ability of p53 to shut down cancer cells.” Landreh comments that, while this research result is not a new cancer therapy, it opens up new possibilities for cancer therapy. The researchers now plan to test how well healthy human cells tolerate the spider silk proteins. They also plan to test whether the addition of spidroins extends the lifetime of the p53 protein inside the cells.

Longevity and healthy aging may seem like navigating a minefield. Do you feel like you are living life on the edge? Are you waiting for a miniature mine located in some system in your body to implode? Preventative measures support healthy aging on a molecular level. Supplements are not intended to diagnose, treat, cure, or prevent any disease. However, nature does provide powerful tools to support optimal metabolic functioning for better aging. Metabolic Functioning Metabolism is the constant chemical dance taking place on a molecular level to transform, store, and burn energy and remove generated byproducts. “Energy can neither be created nor destroyed; it can only be transformed from one form to another.” - Natural Law of the Conservation of Energy We consume (or eat) three forms of energy: Carbohydrates (broken down into glucose), Proteins (broken down into amino acids), and Fats (broken down into glycerol and fatty acids). The body, however, mostly only burns energy as adenosine triphosphate (ATP). Metabolism involves catabolic processes, to break down and convert food to storable and usable energy. And it involves anabolic processes, to generate new cells for growth and maintenance. The body readily shifts from catabolic and anabolic processing based on available fuel sources and current energy output. Role of Mitochondria Mitochondria are tiny organs contained inside a cell. It is in the mitochondria where the body breaks down glucose and fats (with the help of oxygen) into ATP. Mitochondria are like the boiler in a steam engine. They are the energy producers of the cell and are found in almost every cell in the human body. Some cells (mainly in the brain, heart, and eyes) live and function as long as the body does. But most human cells, especially those in the blood and digestive systems, die and need to be replaced every 3 to 120 days. Roughly 1% of all cells in the human body have to be replaced daily. For healthy cell turnover, precise DNA replication keeps our bodies on a smooth path for healthy aging, with active mitochondria providing plenty of energy. Role of Blood Glucose Red blood cells are one of the few cells in the body lacking mitochondria. However, they are the truckers delivering glucose and fatty acids to the mitochondria to formulate ATP. Carbohydrates are converted by the body into glucose. Insulin, secreted by the pancreas, facilitates moving glucose across cell walls and into the mitochondria for breakdown. If blood sugar levels drop too low, it interferes with cognitive functioning since carbohydrates are the fuel used by the nervous system. On the other hand, years of frequent heavy carbohydrate loading may result in high blood sugar levels. When this happens, the body either does not produce enough insulin or becomes insensitive to insulin. If insulin cannot move glucose into cells, the body turns to fat for fuel. That may sound tempting to only burn fat to increase weight loss, but it is deadly. The body cannot dispose of large amounts of the waste byproduct (ketones) from converting fat to ATP. When ketones build up in the blood, it can lead to a coma and death. The Intricate Biochemical Dance Your body works hard to give you what you want when you want it. Unfortunately, the metabolic system is surprisingly delicate. Free radicals (unstable highly-reactive unbonded molecules) are a natural byproduct of generating ATP. A free radical’s need to stabilize its ion charge creates destructive reactions that can damage DNA. This plays a role in speeding up the aging process. To improve the life of an engine, you change the oil on time as recommended by the manufacturer. If you do not, the microscopic flecks of metal from the natural wear inside the engine reduce its performance and life. Attention to diet and exercise changes your oil, so to speak, to reduce inflammation and fight free radicals. For example, blueberries are a functional food proven to offset DNA damage caused by free radicals. Die ...

Scientists at Salk Institute and Genentech have shown that they can safely and effectively reverse the aging process in middle-aged and elderly mice. They did this by partially resetting their cells to more youthful states. "We are elated that we can use this approach across the life span to slow down aging in normal animals. The technique is both safe and effective in mice," says researcher Juan Carlos Izpisua Belmonte in a press release issued by Salk Institute. "In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases." A research paper is published in Nature Aging. It describes how the scientists tested cellular rejuvenation approaches in healthy animals as they aged. Cells carry molecular clocks that record the passage of time. Reprogramming molecules known as "Yamanaka factors” permit resetting the molecular clocks. The results of previous studies indicate that Yamanaka factors can be successfully used to counter the signs of aging and increase life span in mice with a premature aging disease. In young mice, the Yamanaka factors can accelerate muscle regeneration and improve the function of other tissues like the heart, brain, and optic nerve. In the new study, one group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans. And a third group was treated for just one month at age 25 months, similar to age 80 in humans. "What we really wanted to establish was that using this approach for a longer time span is safe," says researcher Pradeep Reddy. "Indeed, we did not see any negative effects on the health, behavior or body weight of these animals." The results of the study indicate that after treatment the mice resembled younger animals in many ways. Both kidneys and skin resembled those of younger animals. And metabolic molecules in the blood of treated animals did not show normal age-related changes. Apparent restoration of youth was observed in the animals treated for seven or ten months with the Yamanaka factors, but not in the animals treated for just one month. When the treated animals were analyzed midway through their treatment, the effects were not yet as evident. This suggests that perhaps the treatment is not simply pausing aging, but actively turning it backwards. "At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury and disease," concludes Reddy. "This study shows that, at least in mice, there's a path forward to achieving that." The scientists are planning more research on how specific molecules and genes are changed by long-term treatment with the Yamanaka factors. They are also developing new ways of delivering the factors. Of course the road from mice in the laboratory to humans in the clinic will be long. But this seems like a promising beginning.

Scientists examined the impact of omega-3 supplements on cellular aging-related biomarkers. And they found reasons to recommend omega-3 supplements. It has been suggested that omega-3 supplements may lessen accelerated aging and early mortality. Previous studies indicate that men and women in the top 20 percent of omega-3 fatty acid intake had 15% and 18% lower cardiovascular disease mortality 16 years later, respectively. That's compared to those in the lowest 20 percent. There is also evidence that omega-3 promotes longevity at a cellular level. In fact, higher blood levels of omega-3 are associated with longer telomeres. Telomeres are DNA segments at the end of chromosomes. They help to maintain genomic integrity during cell division. And, thereby, they promote healthy cellular aging. There are indications that short telomeres accelerate age-related disease, especially cardiovascular disease. Another benefit of omega-3 supplements that has been suggested by previous studies is that they may regulate the response to stress. And, therefore, they may reduce the severity of stress and support healthy mood. A research paper is published in Nature Molecular Psychiatry. It summarizes previous results of the trial. They showed that 4 months of omega-3 supplementation lowered basal inflammation and oxidative stress. The study also provided new data related to the stress response of biomarkers relevant to telomere length and cellular aging. Biomarkers included cortisol, inflammatory cytokines, and telomerase. More than 100 sedentary, overweight, middle-aged participants of both genders received either omega-3 or a placebo for four months. Before and after the trial, participants underwent the Trier Social Stress Test. It's a standard acute stress test that reliably provokes strong stress-related physiological responses. The scientists measured salivary cortisol, telomerase in peripheral blood lymphocytes, and inflammation-related cytokines (various types of interleukin). It appears that omega-3 supplements altered telomerase, stress reactivity, overall cortisol, and inflammation levels. By lowering overall inflammation and cortisol levels during stress, and by boosting repair mechanisms during recovery, omega-3 may slow accelerated aging and enhance mood. The new results of the trial indicate that four months of omega-3 supplements led to a profile of stress resilience. This was manifest in lower overall levels of cortisol and inflammation during stress, and higher levels of telomerase and anti-inflammatory activity during recovery. The results have direct relevance to aging biology and psychiatry. The scientists emphasize that, in the US, dietary intake of omega-3 is well below the values recommended by, for example, the Academy of Nutrition and Dietetics. While cautioning that these findings are preliminary and need to be replicated for validation, the scientists suggest that omega-3 supplements may limit the impact of repeated stress on cellular aging and depression risk. Each serving of Thrivous Omega Cardioprotector provides a clinical dose of Omega 3 Lysine Complex. This form of Omega 3 is five times more bioavailable than traditional fish oil, and has a longer shelf life. Thrivous designed Omega Cardioprotector to enhance heart function and circulation for better aging. As indicated above, the Omega 3 in Thrivous Omega may also combat cellular aging and stress.

MIT researchers have devised a way to monitor individual populations of neurons. It can reveal how the neurons interact with each other. The engineers used a new functional magnetic resonance imaging (fMRI) probe, based on an engineered enzyme delivered by a virus. Functional MRI measures brain activity by detecting changes associated with blood flow. "If we want to figure out how brain-wide networks of cells and brain-wide mechanisms function, we need something that can be detected deep in tissue and preferably across the entire brain at once," says senior Alan Jasanoff in a press release issued by MIT. "The way that we chose to do that in this study was to essentially hijack the molecular basis of fMRI itself." A paper is published in Nature Neuroscience. In it, researchers describe a non-invasive imaging method that works across the brain. The method is based on a probe (or “genetic reporter”) delivered by viruses. It codes for a protein that sends out a signal whenever the neuron is active. Researchers called the protein NOSTIC (nitric oxide synthase for targeting image contrast). It's an engineered form of an enzyme, which is called nitric oxide synthase. The NOSTIC protein can detect elevated calcium levels that arise during neural activity. It then generates nitric oxide, leading to an artificial fMRI signal that arises only from cells that contain NOSTIC. The probe is delivered by a virus that is injected into a particular site. It then travels along axons of neurons that connect to that site. That way, the researchers can label every neural population that feeds into a particular location. "When we use this virus to deliver our probe in this way, it causes the probe to be expressed in the cells that provide input to the location where we put the virus," explains Jasanoff. "Then, by performing functional imaging of those cells, we can start to measure what makes input to that region take place, or what types of input arrive at that region." Experiments with laboratory rats allowed the researchers to determine which neural populations send input to the striatum. This is a brain region that is involved in planning movement and responding to reward. Input was monitored during or immediately following a rewarding stimulus. The researchers hope to use the same approach to study other networks in the brain. And they aim to develop a broader perspective on how the brain works as an integrated whole. "One of the things that's exciting about the approach that we're introducing is that you can imagine applying the same tool at many sites in the brain and piecing together a network of interlocking gears, which consist of these input and output relationships," concludes Jasanoff. “With regular fMRI, we see the action of all the gears at once. But with our new technique, we can pick up individual gears that are defined by their relationship to the other gears, and that's critical for building up a picture of the mechanism of the brain."

Researchers led by Linköping University have built an artificial organic neuron (a nerve cell). It can be integrated with a living plant, and an artificial organic synapse. Both the neuron and the synapse are made from printed organic electrochemical transistors. "We've developed ion-based neurons, similar to our own, that can be connected to biological systems," explains researcher Chi-Yuan Yang in a press release issued by Linköping University. “Organic semiconductors have numerous advantages - they're biocompatible, biodegradable, soft and formable. They only require low voltage to operate, which is completely harmless to both plants and vertebrates.” A paper is published in Nature Communications. In it, the researchers describe the artificial neuron. They report that they have integrated the neuron with a Venus flytrap, a carnivorous plant that catches its prey in a trap formed by the plant’s leaves. The electrical pulses from the artificial neuron can cause the plant's leaves to close, although no fly has entered the trap. "We chose the Venus flytrap so we could clearly show how we can steer the biological system with the artificial organic system and get them to communicate in the same language," says lead researcher Simone Fabiano. The researchers have used printable organic electronics - electrochemical circuits - optimized for manufacturing in printing presses on thin plastic foil. Thousands of transistors can be printed on a single plastic substrate. The printed transistors can emulate the neurons and synapses found in biological systems. "For the first time, we're using the transistor's ability to switch based on ion concentration to modulate the spiking frequency," says researcher Padinhare Cholakkal Harikesh. The spiking frequency gives the signal that causes the biological system to react. "We've also shown that the connection between the neuron and the synapse has a learning behavior, called Hebbian learning,” adds Fabiano. “Information is stored in the synapse, which makes the signaling more and more effective." Hebbian learning is “the process by which the strength of the connection between two neurons increases or decreases based on activity,” explains SingularityHub. This is similar to how information is encoded into the brain, with the strengths of connections between biological neurons controlling the function of different brain circuits. The researchers note their organic electrochemical technology could find applications in future brain-machine interfaces, prosthetics, and intelligent soft robotics. The technology could facilitate anything that requires integrating artificial devices with biological systems. And the possibility to fuse multiple sensing elements in artificial neurons could enable the development of event-based wearable electronics and medical implants, able to continuously monitor health in the human body. SingularityHub notes that the demonstration of an artificial neuron that can interface directly with biological systems is a significant breakthrough. “With further work, this could make the merging of man and machine a far more realistic prospect.”