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From: Savant5/4/2017 8:59:05 AM
   of 1179
 

Salk Institute...Better living through chemistry.. increasing endurance & insulin effectiveness

https://www.sciencedaily.com/releases/2017/05/170502142024.htm








'Exercise-in-a-pill' boosts athletic endurance by 70 percent
www.sciencedaily.com
Sedentary mice given the drug ran longer without training.




Salk scientists move one step closer to developing 'exercise-in-a-pill.' Partial view of a mouse calf muscle stained for different types of muscle fibers: oxidative slow-twitch (blue), oxidative fast-twitch (green), glycolytic fast-twitch (red).
Credit: Salk Institute/Waitt Center








Salk scientists move one step closer to developing 'exercise-in-a-pill.' Partial view of a mouse calf muscle stained for different types of muscle fibers: oxidative slow-twitch (blue), oxidative fast-twitch (green), glycolytic fast-twitch (red).
Credit: Salk Institute/Waitt Center
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Every week, there seems to be another story about the health benefits of running. That's great -- but what if you can't run? For the elderly, obese or otherwise mobility-limited, the rewards of aerobic exercise have long been out of reach.





Salk Institute scientists, building on earlier work that identified a gene pathway triggered by running, have discovered how to fully activate that pathway in sedentary mice with a chemical compound, mimicking the beneficial effects of exercise, including increased fat burning and stamina. The study, which appears in Cell Metabolism on May 2, 2017, not only deepens our understanding of aerobic endurance, but also offers people with heart conditions, pulmonary disease, type 2 diabetes or other health limitations the hope of achieving those benefits pharmacologically.

"It's well known that people can improve their aerobic endurance through training," says senior author Ronald Evans, Howard Hughes Medical Institute investigator and holder of Salk's March of Dimes Chair in Molecular and Developmental Biology. "The question for us was: how does endurance work? And if we really understand the science, can we replace training with a drug?"

Developing endurance means being able to sustain an aerobic activity for longer periods of time. As people become more fit, their muscles shift from burning carbohydrates (glucose) to burning fat. So researchers assumed that endurance is a function of the body's increasing ability to burn fat, though details of the process have been murky. Previous work by the Evans lab into a gene called PPAR delta (PPARD) offered intriguing clues: mice genetically engineered to have permanently activated PPARD became long-distance runners who were resistant to weight gain and highly responsive to insulin -- all qualities associated with physical fitness. The team found that a chemical compound called GW1516 (GW) similarly activated PPARD, replicating the weight control and insulin responsiveness in normal mice that had been seen in the engineered ones. However, GW did not affect endurance (how long the mice could run) unless coupled with daily exercise, which defeated the purpose of using it to replace exercise.





In the current study, the Salk team gave normal mice a higher dose of GW, for a longer period of time (8 weeks instead of 4). Both the mice that received the compound and mice that did not were typically sedentary, but all were subjected to treadmill tests to see how long they could run until exhausted.

Mice in the control group could run about 160 minutes before exhaustion. Mice on the drug, however, could run about 270 minutes -- about 70 percent longer. For both groups, exhaustion set in when blood sugar (glucose) dropped to around 70 mg/dl, suggesting that low glucose levels (hypoglycemia) are responsible for fatigue.

To understand what was happening at the molecular level, the team compared gene expression in a major muscle of mice. They found 975 genes whose expression changed in response to the drug, either becoming suppressed or increased. Genes whose expression increased were ones that regulate breaking down and burning fat. Surprisingly, genes that were suppressed were related to breaking down carbohydrates for energy. This means that the PPARD pathway prevents sugar from being an energy source in muscle during exercise, possibly to preserve sugar for the brain. Activating fat-burning takes longer than burning sugar, which is why the body generally uses glucose unless it has a compelling reason not to -- like maintaining brain function during periods of high energy expenditure. Although muscles can burn either sugar or fat, the brain prefers sugar, which explains why runners who "hit the wall" experience both physical and mental fatigue when they use up their supply of glucose.





"This study suggests that burning fat is less a driver of endurance than a compensatory mechanism to conserve glucose," says Michael Downes, a Salk senior scientist and co-senior author of the paper. "PPARD is suppressing all the points that are involved in sugar metabolism in the muscle so glucose can be redirected to the brain, thereby preserving brain function."

Interestingly, the muscles of mice that took the exercise drug did not exhibit the kinds of physiological changes that typically accompany aerobic fitness: additional mitochondria, more blood vessels and a shift toward the type of muscle fibers that burn fat rather than sugar. This shows that these changes are not exclusively driving aerobic endurance; it can also be accomplished by chemically activating a genetic pathway. In addition to having increased endurance, mice who were given the drug were also resistant to weight gain and more responsive to insulin than the mice who were not on the drug.

"Exercise activates PPARD, but we're showing that you can do the same thing without mechanical training. It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort," says Weiwei Fan, a Salk research associate and the paper's first author.

Although the lab's studies have been in mice, pharmaceutical companies are interested in using the research to develop clinical trials for humans. The team can envision a number of therapeutic applications for a prescription drug based on GW, from increasing fat burning in people suffering from obesity or type 2 diabetes to improving patients' fitness before and after surgery.






Story Source:

Materials provided by Salk Institute. Note: Content may be edited for style and length.



Journal Reference:

  • Weiwei Fan, Wanda Waizenegger, Chun Shi Lin, Vincenzo Sorrentino, Ming-Xiao He, Christopher E. Wall, Hao Li, Christopher Liddle, Ruth T. Yu, Annette R. Atkins, Johan Auwerx, Michael Downes, Ronald M. Evans. PPARd Promotes Running Endurance by Preserving Glucose. Cell Metabolism, 2017; 25 (5): 1186 DOI: 10.1016/j.cmet.2017.04.006


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  • Salk Institute. "'Exercise-in-a-pill' boosts athletic endurance by 70 percent." ScienceDaily. ScienceDaily, 2 May 2017. <www.sciencedaily.com/releases/2017/05/170502142024.htm

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    From: Savant5/8/2017 6:51:54 PM
       of 1179
     
    http://www.msn.com/en-us/health/healthtrending/scientists-discover-why-hair-turns-gray-and-goes-bald/ar-BBASSWM?li=BBmkt5R&ocid=spartanntp










    Scientists Discover Why Hair Turns Gray and Goes Bald
    www.msn.com
    Scientists have pinpointed the cells that cause hair to turn gray and to go bald in mice, but more research is needed to understand how the process works in humans.



    Scientists have pinpointed the cells that cause hair to turn gray and to go bald in mice, according to a new study published in the journal Genes & Development.




    Researchers from the University of Texas Southwestern Medical Center accidentally stumbled upon this explanation for baldness and graying hairs-at least in mouse models-while studying a rare genetic disease that causes tumors to grow on nerves, according to a press release from the center.



    They found that a protein called KROX20 switches on skin cells that become a hair shaft, which then causes cells to produce another protein called stem cell factor. In mice, these two proteins turned out to be important for baldness and graying.




    When researchers deleted the cells that produce KROX20, mice stopped growing hair and eventually went bald; when they deleted the SCF gene, the animals' hair turned white.




    "Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair," said lead researcher Dr. Lu Le, associate professor of dermatology at the University of Texas Southwestern Medical Center, in a statement.

    More research is needed to understand if the process works similarly in humans, and Le and his colleagues plan to start studying it in people. "With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems," he said.

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    From: Savant5/19/2017 9:26:01 PM
       of 1179
     

    Google/Android O/Project Treble/VR/TV upcoming features
    cnet.com

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    From: Savant5/22/2017 5:03:55 PM
       of 1179
     

    Princeton physicist give answer as to Why We Are Here?
    msn.com

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    From: Savant5/22/2017 6:50:13 PM
       of 1179
     

    Communicate w/Dolphins using computer AI by 2021

    thesun.co.uk

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    From: Savant6/12/2017 1:34:34 AM
       of 1179
     
    Nanoized Super Water....grows 40% more melons hydroponically


    Up to 40% more melons thanks to nanotechnology

    * wonder what's causing the wilted and brown edged leaves? The melons sure look good

    BUSINESSMAY 18, 2017






    Nanolabs, a company specialised in nanotechnology, has been able to increase the production of melons by up to 40% on a farm in Almeria, thanks to the installation of ASAR systems in the irrigation system of the farm.

    In 2015, 30,000 kilos were harvested, while in the same period of 2016, this figure increased to 50,000 kilos; a 40% growth.

    To achieve this, Nanolabs applies nanotechnology through its ASAR solution, which acts physically on water, emitting a quantum of energy that stimulates hydrogen bonds. As a result, these become more active, which translates into a better transport of nutrients to the crops and a significant improvement in the use of the nutrients present in the substrate.

    The increase in production has not been the only benefit of the project; it has also made it possible to improve the quality of the fruit and has reduced both the consumption of water for irrigation and the use of fertilisers and phytosanitary products by 20%.

    For Javier Llanes, CEO of Nanolabs, "the dramatic increase in the melon production is just one example of the great benefits that nanotechnology can bring to the agricultural sector. At Nanolabs, we apply technology to promote sustainability and we work on innovative projects with impressive results in both production improvement and savings in water consumption."

    https://nano-magazine.com/news/2017/5/18/up-to-40-more-melons-thanks-to-nanotechnology

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    From: Savant6/16/2017 7:40:43 PM
       of 1179
     

    Work on Y2K prep finally cancelled after 17 yrs....Time to work on Y10K??

    bloomberg.com

    Those monitors @ link are so way-back-when....time flies

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    From: Savant7/20/2017 12:32:21 PM
       of 1179
     

    An international team of researchers led by a group at the Australian National University (ANU) is the first to demonstrate ultra-fast transmission of information through an optical nanoantenna that has been imprinted onto an optical waveguide. These results could have significant implications for telecommunication applications, enabling high-speed data transmission through these devices.


    spectrum.ieee.org

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    From: Savant7/27/2017 12:34:43 PM
       of 1179
     

    Internet/censorship/AI/surveillance/Facial Recognition/'social credits'//China now, USA next?

    BEIJING--China's already formidable internet censors have demonstrated a new strength--the ability to delete images in one-on-one chats as they are being transmitted, making them disappear before receivers see them. Displays of this new image-filtering capability kicked into high gear last week as Chinese dissident Liu Xiaobo lay dying from liver cancer and politically minded Chinese tried to pay tribute to him, according to activists and a new research report. Wu Yangwei, a friend of the long-jailed Nobel Peace Prize laureate, said he used popular messaging app WeChat to send friends a photo of a haggard Mr. Liu embracing his wife. Mr. Wu believed the transmissions were successful, but he said his friends never saw them. "Sometimes you can get around censors by rotating the photo," said Mr. Wu, a writer better known by his pen name, Ye Du. "But that doesn't always work." Chinese internet censorship first concentrated on the development of word-screening software to root out politically objectionable content. As a result, internet users over the past couple of years turned to sending photos to evade cyber police. In response, censors upped their game by demonstrating the ability to purge images from group chats and public posts. And in a new report, researchers from the University of Toronto's Citizen Lab said they observed that WeChat expanded its image censorship to one-to-one chats for the first time, in the wake of Mr. Liu's death on Thursday. Citizen Lab said it is investigating how WeChat is able to filter the images. Since the images are blocked mid-transit, the speed is too fast for human intervention. The rapid blocking suggests an algorithm is at work, Citizen Lab researcher Lotus Ruan said. Though activists said they noticed image censoring over the past year, Ms. Ruan said Citizen Lab didn't detect this kind of targeted, person-to-person image blocking when it was investigating Chinese censorship in the spring. Tencent Holdings Ltd., the Chinese internet company that operates WeChat, didn't respond to requests for comment. Companies are required by law to maintain strict censorship of their platforms, a front-line defense that is augmented by police forces dedicated to internet monitoring. The use of enhanced image filtering comes as Chinese authorities engage in a broader push to step up surveillance by using new data-driven technologies.

    Security cameras with facial recognition software are being deployed in Chinese cities to catch jaywalkers and track criminal suspects.

    Local governments are rolling out "social credit" systems that catalog the digital lives of its citizens, ranging from their internet history to bill payments.

    These new capabilities are closing a gap in censorship that Chinese activists and ordinary internet users have counted on--that the sheer mass of messages was too much for censors to handle. "If you hire a million network police, it still wouldn't be enough to filter 1.4 billion people's messages," said Bao Pu, a Hong Kong-based publisher of political books that are banned on the mainland. "But if you have a machine doing it, it can instantly block everything. It doesn't matter if it's a billion messages or 10 billion." Citizen Lab researchers said an increase in image censoring was noticeable as part of a broader clampdown on messages about Mr. Liu. Citizen Lab researchers said they documented 19 images blocked in one-to-one chats, including a cartoon of an empty chair, in addition to images blocked in group chats. Mr. Liu was famously represented by an empty chair at the 2010 ceremony where he was awarded his Nobel Peace Prize. In tests conducted by The Wall Street Journal, some images of Mr. Liu were blocked in private WeChat messages, including a widely circulated one of him and his wife and another one overlaid with information about a vigil in Hong Kong. Some other photos transmitted successfully. Activists said that they have noticed more frequent image blocks on WeChat over the past year and that there are signs the censorship is automated: one image will be blocked while a similar one in a different color scheme will go through. Citizen Lab researcher Jeffrey Knockel said slight changes to an image or its metadata allow it to slip through the filter, while other modified pictures get blocked. That suggests WeChat is filtering based on certain data, or "hash," of the image, Mr. Knockel said. Alyssa Abkowitz contributed to this article.

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    From: Savant7/29/2017 12:20:31 PM
       of 1179
     

    Nanotechnology...Nanomachines headed for your blood stream...

    "But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world's tiniest engine – just a few billionths of a metre in size. It's biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

    The forces exerted by these 'ANTs' (for 'actuating nano-transducers') are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

    The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

    Working with Cambridge Enterprise, the University's commercialisation arm, the team in Cambridge's Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council"





    How to train your drugs: from nanotherapeutics to nanobots

    June 26, 2017


    Artist's impression of a nanobot. Credit: Yu JiNanotechnology is creating new opportunities for fighting disease – from delivering drugs in smart packaging to nanobots powered by the world's tiniest engines.

    Chemotherapy benefits a great many patients but the side effects can be brutal.

    When a patient is injected with an anti-cancer drug, the idea is that the molecules will seek out and destroy rogue tumour cells. However, relatively large amounts need to be administered to reach the target in high enough concentrations to be effective. As a result of this high drug concentration, healthy cells may be killed as well as cancer cells, leaving many patients weak, nauseated and vulnerable to infection.

    One way that researchers are attempting to improve the safety and efficacy of drugs is to use a relatively new area of research known as nanothrapeutics to target drug delivery just to the cells that need it.

    Professor Sir Mark Welland is Head of the Electrical Engineering Division at Cambridge. In recent years, his research has focused on nanotherapeutics, working in collaboration with clinicians and industry to develop better, safer drugs. He and his colleagues don't design new drugs; instead, they design and build smart packaging for existing drugs.

    Nanotherapeutics come in many different configurations, but the easiest way to think about them is as small, benign particles filled with a drug. They can be injected in the same way as a normal drug, and are carried through the bloodstream to the target organ, tissue or cell. At this point, a change in the local environment, such as pH, or the use of light or ultrasound, causes the nanoparticles to release their cargo.

    Nano-sized tools are increasingly being looked at for diagnosis, drug delivery and therapy. "There are a huge number of possibilities right now, and probably more to come, which is why there's been so much interest," says Welland. Using clever chemistry and engineering at the nanoscale, drugs can be 'taught' to behave like a Trojan horse, or to hold their fire until just the right moment, or to recognise the target they're looking for.

    "We always try to use techniques that can be scaled up – we avoid using expensive chemistries or expensive equipment, and we've been reasonably successful in that," he adds. "By keeping costs down and using scalable techniques, we've got a far better chance of making a successful treatment for patients."

    In 2014, he and collaborators demonstrated that gold nanoparticles could be used to 'smuggle' chemotherapy drugs into cancer cells in glioblastoma multiforme, the most common and aggressive type of brain cancer in adults, which is notoriously difficult to treat. The team engineered nanostructures containing gold and cisplatin, a conventional chemotherapy drug. A coating on the particles made them attracted to tumour cells from glioblastoma patients, so that the nanostructures bound and were absorbed into the cancer cells.

    Once inside, these nanostructures were exposed to radiotherapy. This caused the gold to release electrons that damaged the cancer cell's DNA and its overall structure, enhancing the impact of the chemotherapy drug. The process was so effective that 20 days later, the cell culture showed no evidence of any revival, suggesting that the tumour cells had been destroyed.

    While the technique is still several years away from use in humans, tests have begun in mice. Welland's group is working with MedImmune, the biologics R&D arm of pharmaceutical company AstraZeneca, to study the stability of drugs and to design ways to deliver them more effectively using nanotechnology.

    "One of the great advantages of working with MedImmune is they understand precisely what the requirements are for a drug to be approved. We would shut down lines of research where we thought it was never going to get to the point of approval by the regulators," says Welland. "It's important to be pragmatic about it so that only the approaches with the best chance of working in patients are taken forward."

    Video:
    https://phys.org/news/2017-06-drugs-nanotherapeutics-nanobots.html
    Credit: University of CambridgeThe researchers are also targeting diseases like tuberculosis (TB). With funding from the Rosetrees Trust, Welland and postdoctoral researcher Dr Íris da luz Batalha are working with Professor Andres Floto in the Department of Medicine to improve the efficacy of TB drugs.

    Their solution has been to design and develop nontoxic, biodegradable polymers that can be 'fused' with TB drug molecules. As polymer molecules have a long, chain-like shape, drugs can be attached along the length of the polymer backbone, meaning that very large amounts of the drug can be loaded onto each polymer molecule. The polymers are stable in the bloodstream and release the drugs they carry when they reach the target cell. Inside the cell, the pH drops, which causes the polymer to release the drug.

    In fact, the polymers worked so well for TB drugs that another of Welland's postdoctoral researchers, Dr Myriam Ouberaï, has formed a start-up company, Spirea, which is raising funding to develop the polymers for use with oncology drugs. Ouberaï is hoping to establish a collaboration with a pharma company in the next two years.

    "Designing these particles, loading them with drugs and making them clever so that they release their cargo in a controlled and precise way: it's quite a technical challenge," adds Welland. "The main reason I'm interested in the challenge is I want to see something working in the clinic – I want to see something working in patients."

    Could nanotechnology move beyond therapeutics to a time when nanomachines keep us healthy by patrolling, monitoring and repairing the body?

    Nanomachines have long been a dream of scientists and public alike. But working out how to make them move has meant they've remained in the realm of science fiction.

    But last year, Professor Jeremy Baumberg and colleagues in Cambridge and the University of Bath developed the world's tiniest engine – just a few billionths of a metre in size. It's biocompatible, cost-effective to manufacture, fast to respond and energy efficient.

    The forces exerted by these 'ANTs' (for 'actuating nano-transducers') are nearly a hundred times larger than those for any known device, motor or muscle. To make them, tiny charged particles of gold, bound together with a temperature-responsive polymer gel, are heated with a laser. As the polymer coatings expel water from the gel and collapse, a large amount of elastic energy is stored in a fraction of a second. On cooling, the particles spring apart and release energy.

    The researchers hope to use this ability of ANTs to produce very large forces relative to their weight to develop three-dimensional machines that swim, have pumps that take on fluid to sense the environment and are small enough to move around our bloodstream.

    Working with Cambridge Enterprise, the University's commercialisation arm, the team in Cambridge's Nanophotonics Centre hopes to commercialise the technology for microfluidics bio-applications. The work is funded by the Engineering and Physical Sciences Research Council and the European Research Council.

    "There's a revolution happening in personalised healthcare, and for that we need sensors not just on the outside but on the inside," explains Baumberg, who leads an interdisciplinary Strategic Research Network and Doctoral Training Centre focused on nanoscience and nanotechnology.

    "Nanoscience is driving this. We are now building technology that allows us to even imagine these futures."

    Read more at: https://phys.org/news/2017-06-drugs-nanotherapeutics-nanobots.html#jCp

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