Synthetic biologists at Stanford University, Howard Hughes Medical Institute, and Caltech have developed a new technology for protein circuits between living cells. Gene circuits are synthetic networks of genes that can be integrated into cells to sense specific triggers and deliver a desired response. Gene circuit engineering permits adding new functions to cells, such as the ability to detect and respond to diseases. However, because genes must be translated into proteins to act, synthetic networks made directly of proteins would be more efficient. But natural protein circuits operate entirely within a particular cell. And the majority of biological processes require cells to be in communication with one another. The Stanford-led synthetic biologists have found a way for protein circuits to release proteins from the cell, or to display them on the cell surface. Other cells can then respond to these proteins. Researcher Alexander Vlahos describes the hoped-for end result of this research. In a press release issued by Stanford University, he says, “you can engineer a very small subset of cells that can then have an effect on other cells.” Synthetic protein circuits extend natural protein circuits found in living cells. A protein receives information and then passes the information along to the next protein. Efficient synthetic protein circuits would permit adding new functions to cells without changing with the cells' normal functions. Scientists have developed a new synthetic biology platform known as RELEASE (Retained Endoplasmic Cleavable Secretion). It is described in a research paper published in Nature Communications. It enables synthetic protein circuits to secrete and display proteins. The scientists “developed RELEASE with an end goal in mind: trying to have programmable cells that can talk to other things,” says Vlahos. “That’s fundamentally the big picture.” Vlahos and research leader Xiaojing Gao hope that engineered protein circuits will be able to attack cancers caused by mutant proteins that are difficult to target with traditional drugs. For these cancers, Vlahos and Gao envision a “circuit as medicine” approach. A subset of cells carrying the circuit would sense the mutant protein and respond in two ways. They would kill the mutant cell. And they would also secrete proteins that activate an immune response against the cancer. In the paper, the Stanford-led researchers argue that RELEASE could also have therapeutic applications in neurobiology, developmental biology, immunology, tissue engineering, and transplantation. RELEASE could be used to create sense-and-respond cells to control biological factors in order to facilitate the acceptance of engineered tissue implants. The proposed plug-and-play platform for sensing and secreting proteins would enable programming of such communications with unprecedented precision.

Bioengineers, led by UC San Diego, have shown that a new RNA editing technology can treat laboratory mice affected by Hurler syndrome. It's a rare genetic disease. The new technology can correct the disease-causing mutation in RNA. And it shows promise as a gene therapy for treating genetic diseases more generally. "We can simply deliver just a small piece of RNA inside the cell and repair mutations in vivo,” said bioengineering professor Prashant Mali in a press release issued by UC San Diego. RNA ( RiboNucleic Acid ) is a nucleic acid like DNA. A difference is that RNA is found in nature as a single strand folded onto itself, rather than a paired double strand like DNA. Nucleic acids are large molecules essential for all known forms of life. The findings are described in a research paper published in Nature Biotechnology. They could make it much simpler to repair disease-causing mutations in RNA, without compromising precision or efficiency. The innovative aspect of the new RNA editing technology is that it makes efficient use of RNA editing enzymes that naturally occur in the body's cells. These enzymes are called adenosine deaminases acting on RNA (ADARs). Until now, external ADARs had to be brought into a cell for targeted RNA editing. That made ADAR-based RNA editing complicated. But the bioengineers led by Mali have found ways to recruit a cell’s own ADARs to make edits at a precisely-targeted RNA region. As a proof of concept the bioengineers experimented with the new RNA editing technology on laboratory mice. Their aim was to correct a single mutation that causes Hurler syndrome. The mutation prevents the body from producing an enzyme that is necessary for breaking down complex sugars. Buildup of these sugars causes severe tissue damage, skeletal abnormalities, cognitive impairment, and other serious health problems. The bioengineers obtained encouraging results. After two weeks, the levels of mutant RNA and complex sugars in the diseased animals were significantly reduced. In conclusion, according to the bioengineers, the findings suggest that the new RNA editing technology could enable efficient programmable RNA editing in vivo. And it could be used for diverse protein modulation and gene therapeutic applications. "I'm hopeful that this work opens the door even more for RNA editing as another gene therapy tool," concluded Mali. At the same time, he cautioned that the research is still at an early stage, "and it remains to be seen how this RNA editing technology will work in primates." A new biotechnology company called Shape Therapeutics was co-founded by Mali. The company is working to bring RNA editing technologies to the clinic.

Scientists at University College London have developed a new cancer therapy. It uses an MRI scanner to guide a magnetic seed through the brain to heat and destroy tumors. Magnetic Resonance Imaging (MRI) is a medical imaging technique. It uses magnetic fields and radio waves to create detailed images of organs and tissues. A research paper is published in Advanced Science. It describes the new MRI guided cancer therapy, dubbed MINIMA (minimally invasive image-guided ablation). The paper also describes the first applications of MINIMA in experiments with laboratory mice, which demonstrate the viability of the new therapy. MINIMA works by first using magnetic propulsion gradients, generated by an MRI scanner, to guide a ferromagnetic thermoseed to a tumor. Then it remotely heats the seed to kill nearby cancer cells. With MINIMA, the MRI scanners that are routinely used in hospitals as diagnostic devices can be also used to deliver cancer therapy. “MINIMA is a new MRI-guided therapy that has the potential to avoid traditional side effects by precisely treating the tumor without harming healthy tissues,” says research leader Mark Lythgoe in a press release issued by University College London. “Because the heating seed is magnetic, the magnetic fields in the MRI scanner can be used to remotely steer the seed through tissue to the tumor. Once at the tumor, the seed can then be heated, destroying the cancer cells, while causing limited damage to surrounding healthy tissues." According to the scientists, the research results establish proof-of-concept for precise and effective treatment of glioblastoma. They also suggest the possibility of treating other cancers, such as prostate, that could benefit from less invasive therapies. Glioblastoma is the most common form of brain cancer. It is hard to reach with surgery. And the average survival time after surgery is only 12-18 months. Prostate cancer affects one in eight men. It can be treated more effectively, but with unwanted and debilitating side effects. The scientists say that MINIMA “has the potential to extend survival and limit damage to adjacent brain tissues” in glioblastoma patients. And it “may allow us to precisely target and destroy prostate tumor tissue, reducing harm to normal cells.” "We are now able to image and navigate a thermoseed in real-time through the brain using an MRI scanner,” explains Lythgoe. “As MRI is already used to detect the boundaries of cancers, the seed can be moved precisely to ensure it does not stray into surrounding healthy tissue. As the seed is guided through the tissue it can be heated to destroy the cancer. This combines therapy and diagnosis into a single device, creating a completely new class of imaging therapy." "In the longer term," concludes Lythgoe, "we will change the shape of the seed to act as a tiny cutting scalpel that could be guided through tissue, which would allow surgeons to perform remotely controlled operations, revolutionizing non-invasive surgery."

Hitting the half-century mark led me to seriously contemplate the type of life I want in retirement. If I really am going to backpack, long-distance bike, wilderness canoe, travel, and be the cool granny that enjoys the water park with her grandkids, I need to prioritize my health now. Too often, we put off healthy choices. We say things like, "tomorrow I will eat salad, but tonight I want a burger and fries." Or we say, "when things slow down, I will exercise every day." Vehicle Longevity My husband loves to see how many total miles he can put on a car. To get 300,000 or more miles, you have to start with a reliable and durable car. Then give it proper timely maintenance, and drive it gently. Our bodies are the ultimate machine, lasting almost 100 years depending on genetics and how we treat them. American Heart Association Recommendations “A healthy diet and lifestyle are the keys to preventing and managing cardiovascular disease. Remember, it is the overall pattern of your choices that counts.” - American Heart Association (AHA) It's just like maintaining a car for longevity, starting from day one. The cumulative effects of daily choices, starting now, determine the health factors you may face with age. Studies indicate that regular consumption of Omega-3 fatty acids (found abundantly in cold-water fish) suppresses the build-up of inflammation. Over time, inflammation plays devastating roles in cardiovascular diseases, cancer, arthritis, Alzheimer’s, and other geriatric concerns. To combat inflammation, AHA recommends consuming three ounces of fatty fish twice a week. Examples include Salmon, herring, mackerel, sardines, and anchovies. Do you like, let alone eat, two servings of cold-water fish a week? You Do You Face it. If you don’t like fish, or don't have the time, you won’t eat fish -- no matter how good it is for you. The best way to age with grace and promote long-term health is to know yourself. I have never liked running. When I decided (at age 39) my only option to lose weight was to run, I crashed and burned. A month of running put me in a worse place physically and mentally than if I had played to my strengths and went back to lifting weights and hiking and biking for pleasure. Starting a new lifestyle regime is not sustainable if you don't like it. Thankfully, when it comes to nutrition, dietary supplements can fill nutrition gaps to provide regular maintenance. Supplements Offer Support “A dietary supplement is a product taken by mouth that contains a ‘dietary ingredient’ intended to supplement the diet.” - US Food and Drug Administration Chemical reactions make everything in our bodies possible, from cognitive processing to digestion to removing dangerous free radicals. Sufficient nutrients keep things operating smoothly. Supplements harness the power of vitamins, minerals, herbs, and botanicals. They distill a recommended nutrient serving into a pill, capsule, powder, gummy, tablet, or liquid. Supplements can be powerful medicine based on the ingredients, dosage, and purity. Finding a Supplement Brand You Can Trust The Food and Drug Administration (FDA) regulates supplements more like food than drugs. They aren't intended to diagnose, treat, cure, or prevent any disease. And supplements are marketed without FDA approval. The FDA only removes marketed supplements after establishing that a supplement is unsafe or labeled with false or misleading claims. Your well-being and budget are on the line. How can you know if a supplement is safe and effective? These five queries can help you determine supplements that are honestly produced with the highest quality ingredients to meet desired outcomes. 1. Complete Disclosure of Ingredients with Exact Dosages The most elementary indicator of quality is the nutrition label. A high-quality supplement lists all ingredients and exact dosages by name. Listing a blend of ingredients (contained in so many milligrams) gives a fuzzy indication of dosage amounts. The FDA requi ...

Scientists led by ​​Centre for Genomic Regulation (CRG) have launched GENIGMA. The game enlists players to support cancer research and actively participate in the fight against cancer. A dedicated website describes GENIGMA as "a game for smartphones to explore genomic alterations in cancer cells." The game recruits "citizen scientists" in the construction of "genomic reference maps that will allow us to understand which parts of the human genome play a key role in the establishment and development of cancer." The GENIGMA app can be downloaded from Apple’s App store for iPhones and iPads. It can also be downloaded from Google Play for Android devices. "Anyone with a smartphone from anywhere in the world can download GENIGMA for free and make a direct contribution to research, lending their logic and dexterity to the service of science," says Elisabetta Broglio in a press release issued by CRG. Broglio is a CRG communications and PR specialist with the interesting job title of “citizen science facilitator.” To play GENIGMA, players have to solve a puzzle involving a string of blocks of different colors and shapes. Each string represents a genetic sequence in the cancer cell line. And how players organize the blocks is a potential solution to the location of genes. Players have to reorganize the blocks so that they attain the highest-score possible. The game has been designed to ensure that high scores indicate probable locations of genes. "Cell lines are responsible for the discovery of vaccines, chemotherapies for cancer or IVF for infertility. This makes them a pillar of modern biology," explains lead researcher Marc A. Marti-Renom. "However, the lack of genome reference maps limits current scientific progress. It's like asking people to navigate modern cities using maps from the past. With the help of other people, we can update these maps, which will allow us to make fast progress in breast cancer research." The game launched with a three-month GENIGMA Challenge focused on the T-47D breast cancer cell line. This cell line is one of the most commonly used resources in cancer research. The scientists estimate that 30,000 players solving an average of 50 games each would generate enough data to reveal the reference map of the 20,000 genes in this breast cancer cell line. "Science can often feel inaccessible for most people, which is why being able to pick up your phone to play GENIGMA is so exciting,” says game designer Oriol Ripoll. “Not only can you combine the universal appeal and popularity of videogames to contribute towards advancing medical research, you will also learn more about science." Physics World notes that solving scientific problems by turning them into games is a popular strategy of citizen science projects. The algorithms upon which GENIGMA is based require significant computational resources and sophisticated Artificial Intelligence (AI) systems. But GENIGMA could crowdsource the job to enthusiastic citizen scientists. The "herd intelligence" of the players could provide creative solutions in ways that AI might not be able to, the scientists hope. "GENIGMA will analyze the solutions provided by the players as a collective and not as individuals, and will take advantage of creative solutions impossible to find with deterministic algorithms," says Broglio.

Researchers at University of Waterloo and University of Granada have studied caffeine's effects on dynamic visual skills. They concluded that caffeine increases alertness and detection accuracy for moving targets. Caffeine also improves reaction times. Dynamic visual acuity is defined as clarity and sharpness of vision in dynamic (moving) conditions. Dynamic visual acuity is especially important in the many daily activities during which we, or objects around us, are moving. "A lot of what happens in our environment is moving - like trying to cross a busy intersection as a pedestrian or finding something on a shelf as you're walking through the aisles of a grocery store," said researcher Kristine Dalton in a press release issued by University of Waterloo. "Testing visual acuity under dynamic conditions can provide more information about our functional performance in these scenarios than traditional static visual acuity measurements alone." A paper is published in Psychopharmacology. In it, the researchers report their findings on the effects of caffeine intake on dynamic visual acuity. 21 low caffeine consumers, most in their early twenties, took part in this study. On two different days, and following a random order, participants ingested either caffeine (4 mg/kg) or placebo. And dynamic visual acuity was measured after one hour. The researchers found that the participants who had ingested the caffeine capsules showed significantly greater accuracy and faster speed when identifying smaller moving stimuli. Eye movement velocity and contrast sensitivity are implicated in dynamic visual acuity performance. They were also sensitive to caffeine intake. And caffeine intake was associated with a faster reaction time for horizontally moving targets. "While we already know that caffeine increases the velocity of rapid-eye movements, we wanted to further investigate how exactly caffeine enhances visual processing and facilitates the detection of moving visual stimuli by testing dynamic visual acuity," said researcher Beatríz Redondo. The study results suggest that caffeine intake has a positive effect on dynamic visual acuity. This may be of special relevance in real-word contexts that require accurately and rapidly detecting moving targets. Notable examples include sports, driving, and piloting. "Our findings show that caffeine consumption can actually be helpful for a person's visual function by enhancing alertness and feelings of wakefulness," concluded Dalton. "This is especially true for those critical, everyday tasks, like driving, riding a bike or playing sports, that require us to attend to detailed information in moving objects when making decisions." The caffeine intake used in the study is equivalent to approximately two cups of espresso coffee. I’m an avid coffee drinker and very much prefer the real thing. But it seems clear that those who prefer not to drink coffee can benefit from caffeine supplementation. Thrivous develops Surge Acute Nootropic to enhance energy and focus. Each serving provides a clinical dose of Caffeine. Each dose also includes complementary nutrients, such as L Theanine, to enhance the effects and mitigate the side effects of Caffeine. Surge is available in the online Thrivous store.

Researchers at University of Alabama have announced the publication of a paper related to pig kidney transplants. They say it's the first peer-reviewed research paper outlining the successful transplant of genetically modified, clinical-grade pig kidneys. The kidneys were placed in a brain-dead human individual, replacing the recipient's native kidneys. The paper is published in American Journal of Transplantation. It reports that the study recipient had two genetically modified pig kidneys transplanted in his abdomen after his native kidneys were removed. The kidneys were taken from a pig that had been genetically modified with 10 key gene edits that may make the kidneys suitable for transplant into humans. The transplanted kidneys filtered blood and produced urine. And, importantly, they were not immediately rejected. The kidneys remained viable until the study was ended, 77 hours after transplant. According to the researchers, these positive results demonstrate the long-term viability of xenotransplantation. That's transplantation of organs from non-human animals to human patients. The results also show how such a transplant might work in the real world. And they show how it could address the worldwide organ shortage crisis. "This game-changing moment in the history of medicine represents a paradigm shift and a major milestone in the field of xenotransplantation, which is arguably the best solution to the organ shortage crisis," said lead surgeon Jayme Locke in a press release issued by University of Alabama. "We have bridged critical knowledge gaps and obtained the safety and feasibility data necessary to begin a clinical trial in living humans with end-stage kidney failure disease." More than 800,000 patients in the United States are living with kidney failure. And far too few human organs are available for transplantation. Most patients with kidney failure never make it to the waiting list for transplantation. The wait for a deceased donor kidney can be as long as five years. And, in many states, it is closer to ten years. Almost 5,000 people per year die waiting on a kidney transplant. Alabama has one of the highest rates of chronic kidney disease in the nation. It's 2,348 cases per million residents, New York Times reports. "Our study demonstrates that major barriers to human xenotransplantation have been surmounted,” added Locke. This study was supported by the biotechnology company United Therapeutics (UT). The company was founded by long term xenotransplantation advocate Martine Rothblatt. “It is enormously gratifying to see these xenotransplantation breakthroughs achieved after working on this for over twenty years,” said Rothblatt in a press release issued by UT. “At UT, we are relentlessly pursuing our goal of producing an unlimited supply of transplantable organs from xenotransplantation, regenerative medicine, and 3D bioprinting technology, and we expect to make additional breakthrough announcements in each of these fields in the coming years. Indeed, we have commenced work on a large clinical-quality organ facility.” The researchers are designing a small clinical trial with live patients. And they hope that the trial could begin by the end of the year, said Locke as reported by New York Times.

Researchers led by RIKEN Center for Brain Science have shown that the free-energy principle can explain how neural networks are optimized for efficiency. The free-energy principle is a mathematical optimization principle that many systems, including living systems, are thought to follow. These systems are thought to always minimize a mathematical function called free energy. While at this moment the free-energy principle is not rigorously derivable from known science, it seems to work in many important cases. The free-energy principle is based on Bayesian inference. It's a mathematical technique that facilitates probability estimates. And it can help with planning optimization and decision making, as new information becomes available. Living systems are continuously updated by new incoming sensory data. And they remember their own past decisions. This, the researchers have shown, is also the case with neural networks. Biological optimization makes our bodies and behavior as efficient as possible. In the brain, neural networks are optimized to allow efficient control of behavior and transmission of information. This is done while still maintaining the ability to adapt and reconfigure to changing environments. The researchers compared the free-energy principle with well-established rules that control how the strength of neural connections within a network can be altered by changes in sensory input. In his recent and widely praised book, “ Being You: A New Science of Consciousness ” (2021), neuroscientist Anil Seth describes the free-energy principle. He writes that it's “a piece of mathematical philosophy” according to which “organisms maintain themselves in the low-entropy states that ensure their continued existence by actively minimising this measurable quantity called free energy.” And it's “basically the same thing as sensory prediction error.” There's also a forthcoming book, “ Active Inference: The Free Energy Principle in Mind, Brain, and Behavior ” (2022), co-authored by Karl Friston. He introduced the free-energy principle. And his book is likely to provide an end-to-end explanation. The researchers have demonstrated that standard neural networks “perform planning and adaptive behavioral control by taking their previous 'decisions' into account," says researcher Takuya Isomura in a press release issued by RIKEN. "Importantly, they do so the same way that they would when following the free-energy principle." An open access study is published in Communications Biology. It shows how the free-energy principle is the basis for any neural network that minimizes energy cost. Then, as proof-of-concept, it shows how a free-energy minimizing neural network can solve mazes. This research points the way to a better understanding of general neural networks. It suggests a better understanding of brain networks and their impairments and malfunctions in disorders such as schizophrenia. And it may contribute to the development of thinking machines based on neural networks. “Our findings guarantee that an arbitrary neural network can be cast as an agent that obeys the free-energy principle, providing a universal characterization for the brain,” adds Isomura. “Our theory can dramatically reduce the complexity of designing self-learning neuromorphic hardware to perform various types of tasks, which will be important for a next-generation artificial intelligence.”

Scientists at UC San Francisco have found that, when elderly people stay active, their brains have more of a class of proteins that enhances the connections between neurons to maintain healthy cognition. In other words, the benefits of exercise for older adults include brain health, learning, and memory. "It may be that physical activity exerts a global sustaining effect, supporting and stimulating healthy function of proteins that facilitate synaptic transmission throughout the brain," says research leader William Honer in a press release issued by UC San Francisco. Protection from toxic proteins, that cause synapses and neurons to fall apart, promotes synaptic integrity and reduces the risk of neurodegeneration. A research paper is published in Alzheimer's & Dementia. It analyzes data from the Memory and Aging Project at Rush University. That project tracked the late-life physical activity of elderly participants, who also agreed to donate their brains when they died. The UC San Francisco scientists found that active elderly people had higher levels of proteins that facilitate the exchange of information between neurons. Surprisingly, these effects ranged beyond the hippocampus, the brain's seat of memory. They encompassed other brain regions associated with cognitive function. Earlier findings indicated that people who had more of these proteins in their brains when they died were better able to maintain their cognition late in life. "Our work is the first that uses human data to show that synaptic protein regulation is related to physical activity and may drive the beneficial cognitive outcomes we see," says researcher Kaitlin Casaletto. In the paper, the researchers suggest “that [physical activity] may help build synaptic health, even at late ages … but that this is a potentially plastic process that may need to be sustained over time.” According to the researchers, this approach to cognitive functioning and resilience is “of high relevance in our aging population.” "Maintaining the integrity of these connections between neurons may be vital to fending off dementia, since the synapse is really the site where cognition happens," adds Casaletto. "Physical activity - a readily available tool - may help boost this synaptic functioning." I may have mentioned one or two times that I don’t enjoy physical activity too much. I very much prefer brainy activity. But I am not getting any younger. And I guess my brain is not as sharp as it used to be. I can see that physical activity helps my brain stay sharp enough. So yes, I force myself to do regular exercise. And so should you. "In older adults with higher levels of the proteins associated with synaptic integrity, this cascade of neurotoxicity that leads to Alzheimer's disease appears to be attenuated," concludes Casaletto. "Taken together, these two studies show the potential importance of maintaining synaptic health to support the brain against Alzheimer's disease."

Scientists at McGill University have developed a biomaterial tough enough to repair the heart, muscles, and vocal cords. This development combines advances in chemistry, physics, biology, and engineering. According to the scientists, it represents a major advance in regenerative medicine. "Our work highlights the synergy of materials science, mechanical engineering and bioengineering in creating novel biomaterials with unprecedented performance,” says research co-leader Jianyu Li in a press release issued by McGill University. “We are looking forward to translating them into the clinic." A paper is published in Advanced Science. It describes the new biomaterial, which is an injectable hydrogel for wound repair. The hydrogel is a type of biomaterial that provides room for cells to live and grow. Once injected into the body, the biomaterial forms a stable, porous structure allowing live cells to grow or pass through to repair the injured organs. "People recovering from heart damage often face a long and tricky journey. Healing is challenging because of the constant movement tissues must withstand as the heart beats. The same is true for vocal cords. Until now there was no injectable material strong enough for the job," says researcher Guangyu Bao. “The results are promising, and we hope that one day the new hydrogel will be used as an implant to restore the voice of people with damaged vocal cords, for example laryngeal cancer survivors." Physics World explains that “injectable hydrogels are desirable in many areas of regenerative medicine, from drug delivery to lab-on-a-chip disease models.” But many hydrogels break down under stress due to their porous structure. Porosity allows oxygen and nutrients to perfuse through implantable biomaterials. But it often comes at the expense of mechanical strength. Biological tissues such as the heart and the vocal cords are constantly vibrating. And designing synthetic tissue that can survive vibrations remains a challenge in regenerative medicine. The McGill researchers developed a porous “double-network” hydrogel that is able to withstand millions of cycles of mechanical loading better than the “single-network” hydrogels that have been used so far. “Most synthetic materials developed so far for vocal cord repair are based on single-network hydrogels,” Bao told Physics World. “Currently, patients may need periodic injections because those hydrogels do not last long. Our hydrogel offers a 5- to 40-fold increase in toughness, which could potentially improve the retention of the hydrogel after injection.” According to the scientists, this innovation could enable applications like drug delivery, tissue engineering, and the creation of model tissues for drug screening. The scientists are looking to use the hydrogel technology to create lungs to test COVID-19 drugs.