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Researchers at Howard Hughes Medical Institute have discovered that many genes linked to human cancer block the body's natural defense against cancer. "The shock was that these genes are all about getting around the immune system, as opposed to simply saying 'grow, grow, grow!',” says lead researcher Stephen Elledge in a press release issued by Howard Hughes Medical Institute. "These results reveal a fascinating and unexpected relationship between tumor suppressor genes and the immune system," says a Johns Hopkins University cancer geneticist who was not involved in the research work. A research paper is published in Science. It reveals that more than 100 mutated tumor suppressor genes can prevent the immune system from spotting and destroying malignant cells in laboratory mice. The researchers wanted to check whether defective tumor suppressor genes were doing something more than helping cancer cells to grow. Starting with a list of 7,500 genes, the researchers used CRISPR to engineer thousands of tumor cells. Each engineered tumor cell lacked a functioning version of one of those genes. The researchers put the cells into two types of laboratory mice. The first type was those with a functioning immune system. The second was those without. Then, the researchers studied the tumors that grew. The researchers analyzed which mutated genes were abundant in the tumors. In mice with functioning immune systems, the defective tumor suppressor genes showed up frequently. This suggests that those genes, which amount to about 30 percent of all tumor suppressor genes tested, work by enabling tumors to evade the immune system. It appears that many different genes can mutate to help cancer escape the immune system. And this is likely to play a role in the formation and growth of cancer. To explore possible mechanisms triggered by the mutations, the researchers investigated a gene called GNA13 in more detail. They found that mutating the gene protects cancer cells from the immune system's T-cells. And that creates a safe space for the tumor to thrive. Elledge explains that there seems to be a quick and fierce evolutionary arms race between cancer cells and the immune system, with tumors having hundreds of potential ways to foil the body's attack. But Elledge suspects that many of these mutated genes act via similar strategies, a possibility his team can now examine in detail. If this proves to be the case, an intervention to block one evasion technique could potentially thwart others as well. "There are a lot of genes that people can now study," concludes Elledge. I hope further study will unveil the role played by different genes in protecting cancer from the immune system. And I hope that will help us find new genetic therapies to fight cancer.

“[Our] work about ‘Single Cortical Neurons as Deep Artificial Neural Networks’ was finally published in Neuron,” tweeted David Beniaguev earlier this month. Beniaguev is a PhD student in Computational Neuroscience at Hebrew University, Israel. The paper is published in Neuron. It's authored by Beniaguev, Idan Segev, and Michael London, all at Hebrew University. And it follows a preprint with the same title published in bioRxiv in 2019. So the research results had been released two years ago. But of course publication in a prestigious peer-reviewed scientific journal like Neuron gives more visibility and credibility to the research results. “Our approach is to use deep learning capabilities to create a computerized model that best replicates the I/O properties of individual neurons in the brain,” Beniaguev explains in a press release issued by Hebrew University, titled “ Neurons are much smarter than we thought.” A neuron “receives electrochemical signals through its dendrites, filters those signals, and then selectively passes along its own signals (or spikes),” explains SingularityHub. The researchers “built a model of a biological neuron (in this case, a pyramidal neuron from a rat’s cortex).” Then the researchers investigated neural network algorithms that could most accurately approximate the model. The researchers found that, to replicate the I/O of a simulated “smart neuron,” a neural network must be 5-7 layers deep. Even the authors did not anticipate such complexity. “I thought it would be simpler and smaller,” said Beniaguev as reported by Quanta. The researchers are persuaded that artificial neural networks based on smart neurons would permit reproducing more features of the human brain. “An illustration of this would be for the artificial network to recognize a cat with fewer examples and to perform functions like internalizing language meaning,” adds Segev. “The end goal would be to create a computerized replica that mimics the functionality, ability and diversity of the brain - to create, in every way, true artificial intelligence.” This research builds “a bridge from biological neurons to artificial neurons,” said a neuroscientist not directly involved in this study, Quanta reports. Other neuroscientists are similarly intrigued by the results. However, much work remains to be done. “The relationship between how many layers you have in a neural network and the complexity of the network is not obvious,” says London. “We tried many, many architectures with many depths and many things, and mostly failed.” “Our brain developed methods to build artificial networks that replicate its own learning capabilities and this in return allows us to better understand the brain and ourselves,” Beniaguev concludes. I find this intriguing. And I think his research is a step toward closing the loop, using our understanding of how the brain works to build artificial systems that work like the brain. This is the goal of neuromorphic engineering research. It could deliver not only human-like Artificial Intelligence (AI), but also better brain-computer interfaces. And it suggests future possibilities that look like science fiction becoming science fact.

Researchers have investigated cognitive and metabolic outcomes in middle-aged adults following wild blueberry consumption. Previous research demonstrated cognitive and metabolic health benefits following blueberry consumption in children and young adults. This study has extended previous research work to middle-aged persons. Thirty-five persons aged 40-65 years participated in a study, as described in a research paper published in European Journal of Nutrition. On two occasions, along with breakfast, the participants consumed either a cup of wild blueberry juice or a placebo beverage. The participants completed the cognitive tasks described below, and had blood drawn before and at regular intervals for eight hours after each meal. Researchers evaluated changes in the cognitive and metabolic parameters described below. The wild blueberry beverage included 25 g freeze-dried whole wild blueberry powder. The placebo beverage contained the same ingredients minus the wild blueberry powder. Participants were given auditory stimuli to evaluate executive control functions essential to working memory, new learning, and retention (long-term memory). The protocol included two tasks measuring executive abilities and one test of episodic memory. The participants were also administered an Auditory Verbal Learning Task (AVLT) to evaluate learning, recall, and recognition memory. The AVLT is a simple word list learning task that usually requires less executive ability than other types of learning and memory tasks that involve integration and organization of complex material. Similar to previous research with other age groups, cognitive performance was improved in the wild blueberry group, compared to the placebo group, on delayed recognition memory and aspects of executive function. Importantly, these benefits were found on more demanding elements of the tasks where some form of additional cognitive effort was required. Participants in the wild blueberry group also had significantly lower glucose and insulin levels after the meal, compared to the placebo group. The researchers state that this is the first study to examine wild blueberry effects relative to metabolic responses in a middle-age population with realistic rest and fatigue patterns. The conclusions of the study suggest that wild blueberries can improve the cognitive skills and brain function of middle-aged persons without cognitive impairments, particularly in the context of demanding tasks and cognitive fatigue. Further research is required to understand the underlying mechanism by which wild blueberry consumption improves cognitive functions. Moreover, wild blueberries improve the metabolic response to a meal in terms of glucose and insulin levels. Thrivous develops Vitality Geroprotector to enhance metabolic function for better aging. Each serving of Vitality provides a clinical dose of concentrated Blueberry Anthocyanin, along with complementary nutrients. As suggested by this study, Vitality may enhance cognition, as well as metabolic function. Get your Vitality in the Thrivous online store today!

Bioengineers at Stanford University have built a smaller CRISPR molecule for DNA editing. Its small size should make it easier to deliver into human cells, tissues, and the body for gene therapy. The new "CasMINI" molecule (protein) developed by the Stanford scientists has only 529 amino acids. That's much less than the 1000 to 1500 amino acids in the Cas9 and Cas12a CRISPR proteins commonly used in CRISPR gene editing. A paper is published in Molecular Cell. The scientists report that CasMINI could delete, activate, and edit genetic code. The smaller size of CasMINI means it should be easier to deliver into human cells and the human body. The bioengineers started with the small CRISPR protein Cas12f. It contains only about 400 to 700 amino acids. But it's not suitable for editing the DNA of mammalian and human cells. "We thought, 'Okay, millions of years of evolution have not been able to turn this CRISPR system into something that functions in the human body. Can we change that in just one or two years?'" says Stanley Qi in a press release issued by Stanford University. "To my knowledge, we have, for the first time, turned a nonworking CRISPR into a working one." The bioengineers selected about 40 modifications of the molecule that could make it suitable for editing human cells. And they implemented the modifications. They also engineered the RNA that guides Cas12f to its target DNA. Modifications to both components were crucial to making the CasMINI system work in human cells. "At first, this system did not work at all for a year," says researcher Xiaoshu Xu. "But after iterations of bioengineering, we saw some engineered proteins start to turn on, like magic. It made us really appreciate the power of synthetic biology and bioengineering." The scientists tested CasMINI's ability to delete and edit genes in lab-based human cells. They included genes related to HIV infection, anti-tumor immune response, and anemia. It worked on almost every gene they tested, with robust responses in several. The Stanford bioengineers “used protein engineering to transform a Cas12f protein that didn’t appear to work in mammalian cells into one that did,” summarizes SingularityHub. They also noted that two other recent research papers indicate that Cas12f molecules could be packaged inside viruses along with their guide RNA. And they could be delivered to human cells to make effective edits. "This engineering approach can be so broadly helpful," concludes Qi. "That's what excites me - opening the door on new possibilities." Qi is persuaded that we should start thinking about how this new CasMini molecule can be applied for practical benefits.

Researchers investigated changes in the subjective feelings of healthy volunteers after administering Alpha GPC. Alpha GPC is a natural choline compound found in the brain. And it's a precursor of neurotransmitter acetylcholine. In other words, it can increase acetylcholine concentration in the brain. Thirty-nine volunteers participated in the study, described in a paper published in Nutrients. The participants were administered capsules containing either 200 mg of Alpha GPC or a placebo (cellulose). The results of the study suggest that Alpha GPC treatment could increase motivation during the treatment period. The participants completed a KOKORO scale test to quantify self-reported emotional states before and during the treatment. The KOKORO scale (KOKORO means mind in Japanese) uses a four-quadrant diagram with measures of mood such as security, anxiety, excitement, or irritability. In this study, the x-axis and y-axis of the KOKORO scale were set to “Anxiety-Relief” and “Lethargy-Motivation.” The participants were instructed to input their feelings into the four-quadrant diagram using a smartphone app. They did this three times a day for two weeks preceding treatment. And then they continued doing this for another two weeks while self-administering treatment. Previous clinical studies indicate that the oral administration of Alpha GPC doesn’t lead to serious side effects or toxicities in human patients. This is confirmed by the results of this study. The findings suggest that the risk of toxicity in administering Alpha GPC for 2 weeks is extremely low. The administration of Alpha GPC did not lead to side effects or addictions during the 2 weeks of intervention and for at least 12 months after taking the supplement. The placebo had no effect on motivation, whereas the Alpha GPC group showed an increasing trend in motivation during the intervention period. In particular, the self-reported motivation levels significantly improved at night. In the anxiety-relief axis, the change in feelings in both groups showed similar patterns. But in the lethargy-motivation axis, the change in feelings in the Alpha GPC group increased significantly at night when compared with that in the placebo group. I looked for explanations of why the positive effects of Alpha GPC are most evident at night. This may be due to the time of administration, or to the interaction of Alpha GPC with the dopamine circuits in the brain. In fact, use of Alpha GPC increases dopamine levels, as well as dopamine active transporter expression in the brain. However, the researchers emphasize that the detailed mechanism of action of Alpha GPC remains unclear at present. Thrivous develops Alpha Neuroprotector to enhance brain and nerve function for better aging. Each serving of Alpha provides a clinical dose of Alpha GPC, along with complementary nutrients. As indicated by the results of this clinical study, Alpha Neuroprotector may also increase dopamine levels and enhance motivation. Get your Alpha from the Thrivous online store now.

Researchers at the University of Washington and Microsoft have created genetically encoded reporter proteins. They can be directly read by a commercially available nanopore sensing device. This may revolutionize access to nanoscale information from the body. "This is a fundamentally new interface between cells and computers," said senior researcher Jeff Nivala. The researchers have built a system called "NanoporeTERs" (Nanopore-addressable protein Tags Engineered as Reporters). It can detect multiple protein expression levels from bacterial and human cell cultures far beyond the capacity of existing techniques. The system acts as a "nanopore-tal." That's a portal based on nanopores. Nanopores are nano-scale holes that can be embedded in electronic devices to capture molecules and perform precise molecular analyses. NanoporeTERs are able to probe what happens inside complex biological systems. "NanoporeTERs offer a new and richer lexicon for engineered cells to express themselves and shed new light on the factors they are designed to track. They can tell us a lot more about what is happening in their environment all at once," said researcher Nicolas Cardozo. "We're essentially making it possible for these cells to 'talk' to computers about what's happening in their surroundings at a new level of detail, scale and efficiency that will enable deeper analysis than what we could do before." A paper is published in Nature Biotechnology. Researchers explain that NanoporeTERs were designed to carry distinct protein "barcodes" composed of strings of amino acids. The NanoporeTERs have been engineered with charged "tails" so that they can be pulled into a nanopore sensor by an electric field. And they can be collected and analyzed using a commercially available nanopore device. "This is the first paper to show how a commercial nanopore sensor device can be repurposed for applications other than the DNA and RNA sequencing for which they were originally designed," said researcher Kathryn Doroschak. "This is exciting as a precursor for nanopore technology becoming more accessible and ubiquitous in the future. You can already plug a nanopore device into your cell phone. I could envision someday having a choice of 'molecular apps' that will be relatively inexpensive and widely available outside of traditional genomics." "We are currently working to scale up the number of NanoporeTERs to hundreds, thousands, maybe even millions more," said researcher Karen Zhang. "The more we have, the more things we can track." "We're particularly excited about the potential in single-cell proteomics, but this could also be a game-changer in terms of our ability to do multiplexed biosensing to diagnose disease and even target therapeutics to specific areas inside the body. And debugging complicated genetic circuit designs would become a whole lot easier and much less time-consuming if we could measure the performance of all the components in parallel instead of by trial and error.” In simple words, my explanation of this development goes like this. Doctors will be able to rapidly and cheaply acquire a hell of a lot of information on whatever molecular processes are going on in your body. Perhaps you’ll be able to do it yourself with smartphone apps. And perhaps this technology will be combined with precise therapies.

Researchers at MIT and Howard Hughes Medical Institute have developed a new way to deliver molecular therapies to cells. The system, called SEND, can be programmed to encapsulate and deliver different RNA cargoes. SEND (Selective Endogenous eNcapsidation for cellular Delivery), "dazzles with its sheer ingenuity," notes Singuarity Hub. SEND "commandeers human proteins to make delivery vehicles that shuttle in new genetic elements. In a series of tests, the team embedded RNA cargo and CRISPR components inside cultured cells in a dish. The cells, acting as packing factories, used human proteins to encapsulate the genetic material, forming tiny balloon-like vessels that can be collected as a treatment." "The biomedical community has been developing powerful molecular therapeutics, but delivering them to cells in a precise and efficient way is challenging," says senior researcher Feng Zhang, a CRISPR pioneer, in a press release issued by MIT. "SEND has the potential to overcome these challenges." SEND takes advantage of molecules made by human cells. A paper published in Science describes how the researchers engineered a protein called PEG10, which exists naturally in humans, to selectively package and deliver RNA cargos. The researchers used SEND to deliver the CRISPR-Cas9 gene editing system to mouse and human cells to edit targeted genes. Using SEND, the researchers delivered a CRISPR system that removes a cancer-causing gene in cells in a dish originally derived from brain cancer. "The system efficiently cut out roughly 60 percent of the gene in recipient cells," notes Singularity Hub. "But it only did so when SEND shuttled the CRISPR components into the cell, showing that SEND only delivers genetic material that’s been custom-made for its transport." Since SEND is composed of proteins that are produced naturally in the body, it could open up opportunities to deliver gene therapies repeatedly without triggering adverse immune responses, and with minimal side effects. "This study shows that there are probably other RNA transfer systems in the human body that can also be harnessed for therapeutic purposes,” says researcher Michael Segel. “It also raises some really fascinating questions about what the natural roles of these proteins might be." The researchers plan to test SEND in animals and further engineer the system to deliver molecular therapies to a variety of living cell types. "We're excited to keep pushing this approach forward," concludes Zhang. "The realization that we can use PEG10, and most likely other proteins, to engineer a delivery pathway in the human body to package and deliver new RNA and other potential therapies is a really powerful concept."

Caffeine is considered a cognitive enhancer at low to moderate doses because it improves alertness, vigilance, attention, and reaction time. Now, researchers in Madrid have investigated and assessed the effect of acute caffeine intake on e-sports-specific performance. Electronic-sports (e-sports) represent a relatively new sport discipline consisting of gamers playing competitive video game tournaments. E-sports share a common structure where the player, seated in front of a screen, has to direct the movements and decisions of a virtual avatar through a controller. E-sports have similar characteristics to more traditional sport disciplines, mainly due to their competitive nature, but also because of the physical skills necessary to play at a high level. For example, in a first-person shooting video game, players have to rapidly react to fast-moving visual and auditory stimuli. The most important factors for gaming performance in first-person shooting video games are precision to hit a target that suddenly appears and moves on the screen, together with a low response time to perform the shooting. The researchers studied the effect of ingesting 3 mg of caffeine per kg of body mass on simple reaction time in a color test and on hit accuracy and reaction time during a first-person shooting game. Fifteen professional e-gamers participated in an experimental trial. The results of the trial are reported and discussed in a 2020 research paper published in Physiology & Behavior. In two trials three days apart, the participants either ingested a placebo (cellulose) or 3 mg/kg of caffeine in an opaque and unidentifiable capsule. 45 minutes after ingestion, the participants performed a simple reaction time test and completed a first-person shooting game. The game was intense and stressful, because the participants had to hit 60 targets that appeared anywhere on the screen in a 2 minute time period. The researchers measured the reaction times and accuracy of the participants. In comparison to the placebo, caffeine decreased the reaction time, the mean time taken to hit the targets, and enhanced hit accuracy. The researchers conclude that caffeine supplementation might be considered as an aid for e-sports gamers based on its effect to enhance hit accuracy and time. The researchers “recommend the use of caffeine only on those days with a high load of training or before e-sports competitions in order to avoid tolerance and to reduce the prevalence of the main caffeine-associated drawbacks.” I’m unable to comment because since I was ten or so I have had no experience of living without a regular dose of caffeine (taken in the form of cups of hot black espresso coffee). I can only say that, though I never liked action video games too much, I used to be quite good at them. Thrivous develops Surge Acute Nootropic to enhance energy and focus when you need it most. Each capsule provides a clinical dose of Caffeine, combined with L Theanine and Ginseng. Many clinical studies have observed superior effects, such as decreased jitters and distraction, from the combination. Get your Surge from the Thrivous store online today.

Researchers at Brown University, UC San Diego, Baylor University, and Qualcomm have developed a new neural interface system that coordinates the activity of hundreds of tiny brain sensors. This new Brain-Computer Interface (BCI) system could one day deepen our understanding of the brain and lead to new medical therapies. BCI systems depend on implantable sensors that record electrical signals in the brain. They use those brain signals to drive external devices like computers or prosthetic limbs such as robotic arms. An operational BCI system should be able to gather data from large groups of brain cells. "One of the big challenges in the field of brain-computer interfaces is engineering ways of probing as many points in the brain as possible," said senior researcher Arto Nurmikko in a press release issued by Brown University. "Up to now, most BCIs have been monolithic devices -- a bit like little beds of needles. Our team's idea was to break up that monolith into tiny sensors that could be distributed across the cerebral cortex. That's what we've been able to demonstrate here." The researchers designed wireless microscale neural sensors, each about the size of a grain of salt, to record and stimulate brain activity. The sensors, dubbed "neurograins," independently record the electrical pulses made by firing neurons and send the signals wirelessly to a central hub, which coordinates and processes the signals. The central hub is a thin thumbprint-sized patch that attaches to the scalp outside the skull. It works like a miniature cellular phone tower, employing a network protocol to coordinate the signals from the neurograins, each of which has its own network address. The patch also supplies power wirelessly to the neurograins, which are designed to operate using a minimal amount of electricity. In a study published in Nature Electronics, the researchers demonstrate the use of a coordinated network with nearly 50 neurograins to record neural activity in a laboratory rat. The neurograins, placed on the outer layer of the animal's brain, successfully recorded neural signals. The researchers also tested the ability of the BCI system to stimulate the brain as well as record from it. "This work was a true multidisciplinary challenge," said researcher Jihun Lee. "We had to bring together expertise in electromagnetics, radio frequency communication, circuit design, fabrication and neuroscience to design and operate the neurograin system." "It was a challenging endeavor, as the system demands simultaneous wireless power transfer and networking at the mega-bit-per-second rate, and this has to be accomplished under extremely tight silicon area and power constraints," added researcher Vincent Leung. "Our team pushed the envelope for distributed neural implants." The current configuration of the BCI system could support up to 770 neurograins. The researchers plan to scale the BCI system up to many thousands of neurograins, which would provide a currently unattainable picture of brain activity. "Our hope is that we can ultimately develop a system that provides new scientific insights into the brain and new therapies that can help people affected by devastating injuries," concluded Nurmikko. It’s worth noting that next-generation BCI systems could do much more than that. They could enable artificial intelligence (AI) implants, enable artificial telepathy (streaming thoughts to other users via wireless networks), and gradually approach the capabilities of wildly futuristic neural interfaces such as the “neural lace” envisioned by the late lamented science fiction writer Iain Banks.

University of Copenhagen scientists have suggested that the beneficial effects of physical exercise may in part result from changes to the structure of our DNA. These structural changes are referred to as "epigenetic." While it is widely known that regular physical exercise decreases the risk of virtually all chronic illnesses, the mechanisms at play are not fully known. This research shed light on the deep mechanisms through which exercise leads to better health. "Our findings provide a mechanism for the known beneficial effects of exercise," says Professor Romain Barrès in a press release issued by University of Copenhagen. "By connecting each enhancer with a gene, we further provide a list of direct targets that could mediate this effect." A study is published in Molecular Metabolism. The scientists report evidence that exercise rewires the enhancers in regions of our DNA that are known to be associated with the risk to develop disease. Enhancers are sections of our DNA that regulate which genes are switched on or off, when, and in which tissue. To show that exercise remodels the activity of gene enhancers in skeletal muscle, the scientists recruited healthy young men and put them through a six-week endurance exercise program. The scientists collected a biopsy of the thigh muscle of the participants before and after the exercise intervention and found changes in the structure of DNA in enhancers that have been already associated with human disease. According to the scientists, these research results show how exercise remodels DNA in skeletal muscle, so that new signals are established to keep the body healthy. The findings suggest that enhancers remodeled after exercise training may participate in disease prevention, especially of cardiovascular, renal, and cognitive disorders, by regulating transcription of enhancer connected genes. The disease categories, that these research results link, reprogrammed enhancers that have all previously been associated with exercise. For instance, exercise training is robustly correlated with decreased risk of cardiovascular disease, lower blood pressure, improved renal functions, better cognitive performance, and higher academic achievement. "Our data provides evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans," adds Assistant Professor Kristine Williams. “By providing insight into the mechanisms that may mediate the positive effects of exercise on cardiovascular function, platelet biology, cognitive performance, and renal function,” reads the conclusion of the study, “our study constitutes a powerful resource for the identification of key factors involved in the beneficial effects of endurance training on human health.”