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Updates found with 'process cells'

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Updates found with 'process cells'

Newswise — As a basic unit of life, the cell is one of the most carefully studied components of all living organisms. Yet details on basic processes such as how cells are shaped have remained a mystery. Working at the intersection of biology and physics, scientists at the University of California San Diego have made an unexpected discovery at the root of cell formation.As reported in the journal Cell on Feb. 8, 2018, biologists Javier Lopez-Garrido, Kit Pogliano and their colleagues at UC San Diego and Imperial College in London found that DNA executes an unexpected architectural role in shaping the cells of bacteria.Studying the bacterium Bacillus subtilis, the researchers used an array of experiments and technologies to reveal that DNA, beyond serving to encode genetic information, also “pumps up” bacterial cells.“Our study illustrates that DNA acts like air in a balloon, inflating the cell, ” said Lopez-Garrido, an assistant research scientist in UC San Diego’s Division of Biological Sciences and the study’s first author. “DNA is best known for being the molecule with genetic information but it’s becoming more and more obvious that it does other things that are not related to that.”The researchers say the results could have relevance in human cells in terms of how they are generated and shaped, as well as aid explanations of basic mechanical processes and the structure of the nucleus and mitochondria. The results could also allow scientists to have a glimpse into the origins of cellular life itself. Modern bacterial cells have evolved a variety of mechanisms to control their internal pressure, said Lopez-Garrido. However, those mechanisms were absent in primitive cells at the dawn of life on earth. The finding that DNA can inflate a cell might allow scientists to achieve a better understanding of the physiology of the first cells on the planet.“Biologists tend to think of cell growth as following normal, biosynthetic pathways, but we found a pathway that is not normal, as it does not depend on processes normally required for growth, ” said Pogliano, a professor in the Section of Molecular Biology and the paper’s senior author. “All you need for this cell to grow is to inflate it with DNA and its associated positively charged ions, and the ability to make more membrane so the cell can get bigger. Nothing else seems to be required.”The researchers employed time-lapse fluorescent microscopy to methodically track cell formation in Bacillus subtilis through a process known as sporulation. During this process cells split into a mother cell and a smaller cell, or forespore. Also using cryo-electron tomography to capture extreme close-ups of the process unfolding, the researchers witnessed the mother cells inflating the forespore with DNA in a stretching and swelling process, ultimately leading to a new, egg-shaped cell.“It’s amazing how we are just beginning to scratch the surface of how physics impacts living organisms, ” said Pogliano. “This is a unique example of a very simple biophysical property impacting cell shape and it illustrates the value of physicists working closely with biologists. Understanding how physics and biology intersect is a huge area for future growth.”Coauthors of the study include Nikola Ojkic and Robert Endres of Imperial College; and Kanika Khanna, Felix Wagner and Elizabeth Villa of UC San Diego.Funding was provided by the European Research Council (starting grant 280492-PPHPI), National Institutes of Health (grant R01-GM57045), NIH Director’s New Innovator Award (1DP2GM123494-01) and a European Molecular Biology Organization (EMBO) Long Term Fellowship (ALTF 1274-2011). The researchers used the UC San Diego Cryo-EM Facility (supported by NIH grant R01-GM33050) and the San Diego Nanotechnology Infrastructure of UC San Diego (supported by National Science Foundation grant ECCS-1542148).
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HUMAN DEVELOPMENTHow to build a human brainSome steps for growing mini versions of human organs are easier than othersBY INGFEI CHEN 3:30PM, FEBRUARY 20, 2018SHARE ARTICLEorganoid brainBRAIN-MAKING 101 As blobs of two types of brainlike tissue fuse, interneurons (green) migrate from the left clump to the right, linking with neurons (not stained) in the right blob. On both sides, neural support cells called glia appear in purple.PAŞCA LAB/STANFORD UNIV.Magazine issue: Vol. 193, No. 4, March 3, 2018, p. 22SPONSOR MESSAGEIn a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half.When growing human brains, sometimes you need to do some pruning.The blobs are 8-week-old bits of brainlike tissue. While they wouldn’t be mistaken for Lilliputian-sized brains, some of their fine-grained features bear a remarkable resemblance to the human cerebral cortex, home to our memories, decision making and other high-level cognitive powers.Vishlaghi created these “minibrains” at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, where she’s a research assistant. First she immersed batches of human pluripotent stem cells — which can morph into any cell type in the body — in a special mix of chemicals.The free-floating cells multiplied and coalesced into itty-bitty balls of neural tissue. Nurtured with meticulously timed doses of growth-supporting ingredients, the cell clumps were eventually transferred to petri dishes of broth laced with Matrigel, a gelatin-like matrix of proteins.On day 56, the blobs display shadowy clusters of neural “rosettes.” Under a laser scanning microscope, razor-thin slices of those rosettes reveal loose-knit layers of a variety of dividing neural stem cells and the nerve cells, or neurons, they give rise to. The layered structures look similar to the architecture of a human fetal brain at 14 weeks of gestation.By eight weeks, brainlike clumps (top) show neural clusters called rosettes. Within one cluster (red box, expanded at bottom), stem cells (blue and teal) churn out layers of neural precursor cells (pink) and neurons (not stained).BOTH: M. WATANABE ET AL/CELL REPORTS 2017Across the globe, labs such as this one, led by UCLA developmental biologist and neuroscientist Bennett Novitch, are cultivating thousands of these brainy clumps for research. Less than five years ago, a team of biologists in Austria and the United Kingdom and one in Japan wowed the world when they announced they had made rudimentary bits of 3-D human cerebral cortex in a dish. Since then, researchers have been eagerly tinkering with techniques for producing these miniature brain models, like chefs obsessively refining their favorite recipes.“It’s like making a cake: You have many different ways in which you can do it, ” says Novitch, who prefers using the Japanese method with a few tweaks. “There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”For instance, because the brain blobs lack a built-in blood supply, they must absorb enough oxygen and nutrients from the tissue-culture broth to remain healthy. To help, some labs circulate the broth around the tissue clumps. The UCLA researchers choose instead to grow theirs at higher oxygen levels and chop the blobs at the 35-day mark, when they are as wide as three millimeters, and then about every two weeks after. Sounds radical, but the slicing gives cells on the inside — some of which start dying — exposure to much-needed oxygen and nutrients. Those divided bits then continue growing separately. But cutting can be done only so many times before the expanding rosette structures inside are damaged.With all the experimenting, researchers have cooked up a lot of innovations, including some nifty progress reported in just the last year. Scientists have concocted tiny versions of several brain regions ranging from the hypothalamus, which regulates body temperature, thirst and hunger, to the movement-controlling basal ganglia. Electrical chatter among neurons, reflecting active brain circuits, has been detected. And research groups have recently begun linking bits of specific regions like Legos. Scientists have even observed some early developmental processes as they happen within the human brain blobs.Stem cell payoffThe work is part of a broader scientific bonanza that comes from coaxing human stem cells to self-assemble into balls of organlike tissue, known as organoids, that are usually no bigger than a lentil. Although the organoids don’t grow enough to replicate entire human organs, these mini-versions can mimic the 3-D cellular infrastructure of everything from our guts to our lungs. That’s something you can’t get from studies of rodents, which have different biology than humans do.Mini-organ models promise enormous advantages for understanding basic human biology, teasing apart human disease processes, and offering an accurate testing ground for finding or vetting drug therapies. And by creating personalized organoids from the reprogrammed cells of patients, scientists could study disease in a very individualized way — or maybe even use organoid structures to replace certain damaged tissues, such as in the liver or spinal cord.“Organoids offer an unprecedented level of access into the inner workings of the human brain, ” Novitch says, noting that our brains are largely off-limits to poking and cutting into for research. If scientists can study accurate models of working neural circuits in these brain bits, he and others say, researchers might finally get a handle on uniquely human neurological conditions. Such disorders, which include epilepsy and, experts theorize, schizophrenia and autism (SN Online: 7/17/15), can arise when the brain’s communication networks develop off-kilter.
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In the future we won’t edit genomes—we’ll just print out new onesWhy redesigning the humble yeast could kick off the next industrial revolution.by Bryan Walsh February 16, 2018At least since thirsty Sumerians began brewing beer thousands of years ago, Homo sapiens has had a tight relationship with Saccharomyces cerevisiae, the unicellular fungus better known as brewer’s yeast. Through fermentation, humans were able to harness a microscopic species for our own ends. These days yeast cells produce ethanol and insulin and are the workhorse of science labs.That doesn’t mean S. cerevisiae can’t be further improved—at least not if Jef Boeke has his way. The director of the Institute for Systems Genetics at New York University’s Langone Health, Boeke is leading an international team of hundreds dedicated to synthesizing the 12.5 million genetic letters that make up a yeast’s cells genome.In practice, that means gradually replacing each yeast chromosome—there are 16 of them—with DNA fabricated on stove-size chemical synthesizers. As they go, Boeke and collaborators at nearly a dozen institutions are streamlining the yeast genome and putting in back doors to let researchers shuffle its genes at will. In the end, the synthetic yeast—called Sc2.0—will be fully customizable.“Over the next 10 years synthetic biology is going to be producing all kinds of compounds and materials with microorganisms, ” says Boeke. “We hope that our yeast is going to play a big role in that.”Think of the project as something like Henry Ford’s first automobile—hand built and, for now, one of a kind. One day, though, we may routinely design genomes on computer screens. Instead of engineering or even editing the DNA of an organism, it could become easier to just print out a fresh copy. Imagine designer algae that make fuel; disease-proof organs; even extinct species resurrected.Jef Boeke leads an effort to create yeast with a man-made genome.“I think this could be bigger than the space revolution or the computer revolution, ” says George Church, a genome scientist at Harvard Medical School.Researchers have previously synthesized the genetic instructions that operate viruses and bacteria. But yeast cells are eukaryotic—meaning they confine their genomes in a nucleus and bundle them in chromosomes, just as humans do. Their genomes are also much bigger.That’s a problem because synthesizing DNA is still nowhere near as cheap as reading it. A human genome can now be sequenced for $1, 000, with the cost still falling. By comparison, to replace every DNA letter in yeast, Boeke will have to buy $1.25 million worth of it. Add labor and computer power, and the total cost of the project, already under way for a decade, is considerably more.Along with Church, among others, Boeke is a leader of GP-write, an organization advocating for international research to reduce the cost of designing, engineering, and testing genomes by a factor of a thousand over the next decade. “We have all kinds of challenges facing ourselves as a species on this planet, and biology could have a huge impact on them, ” he says. “But only if we can drive down costs.”Bottom upA scientist named Ronald Davis at Stanford first suggested the possibility of synthesizing the yeast genome at a conference in 2004—though initially, Boeke didn’t see the point. “Why would anyone want to do this?” he recalls thinking.But Boeke came around to the idea that manufacturing a yeast genome might be the best way to comprehend the organism. By replacing each part, you might learn which genes are necessary and which the organism can live without. Some team members call the idea “build to understand.”“It’s a different take on trying to understand how living things work, ” says Leslie Mitchell, a postdoctoral fellow in the NYU lab and one of the main designers of the synthetic yeast. “We learn what gaps in our knowledge exist in a bottom-up genetic approach.”Joel Bader, a computer scientist at Johns Hopkins, signed on to develop software that let scientists see the yeast chromosomes on a screen and keep track of versions as they changed, like a Google Docs for biology. And in 2008, to make the DNA, Boeke launched an undergraduate course at Hopkins called “Build a Genome.” Students would learn basic molecular biology as each one assembled a continuous stretch of 10, 000 DNA letters that would go toward the synthetic-yeast project. Later, several institutions in China joined to share the workload, along with collaborators in Britain, Australia, and Japan.“We assign chromosomes to individual teams, like assigning a chapter of a book, and they have the freedom to decide how to do it, as long as it’s based 100 percent on what we design, ” says Patrick Cai, a synthetic biologist at the University of Manchester and the yeast project’s international coordinator.Next stepsIt took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs, ” says Boeke.
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Harvard Medical SchoolControlling your weight is key to lowering stroke riskThere is a lot you can do to lower your chances of having a stroke. Even if you've already had a stroke or TIA ("mini-stroke"), you can take steps to prevent another.Controlling your weight is an important way to lower stroke risk. Excess pounds strain the entire circulatory system and can lead to other health conditions, including high blood pressure, diabetes, high cholesterol, and obstructive sleep apnea. But losing as little as 5% to 10% of your starting weight can lower your blood pressure and other stroke risk factors.Protect your brain: That’s the strategy that Harvard doctors recommend in this report on preventing and treating stroke. Whether you’ve already had a mini-stroke or a major stroke, or have been warned that your high blood pressure might cause a future stroke, Stroke: Diagnosing, treating, and recovering from a "brain attack" provides help and advice.Of course, you'll need to keep the weight off for good, not just while you're on a diet. The tips below can help you shed pounds and keep them off:Move more. Exercise is one obvious way to burn off calories. But another approach is to increase your everyday activity wherever you can — walking, fidgeting, pacing while on the phone, taking stairs instead of the elevator.Skip the sipped calories. Sodas, lattes, sports drinks, energy drinks, and even fruit juices are packed with unnecessary calories. Worse, your body doesn't account for them the way it registers solid calories, so you can keep chugging them before your internal "fullness" mechanism tells you to stop. Instead, try unsweetened coffee or tea, or flavor your own sparkling water with a slice of lemon or lime, a sprig of fresh mint, or a few raspberries.Eat more whole foods. If you eat more unprocessed foods — such as fruits, vegetables, and whole grains — you'll fill yourself up on meals that take a long time to digest. Plus, whole foods are full of vitamins, minerals, and fiber and tend to be lower in salt — which is better for your blood pressure, too.Find healthier snacks. Snack time is many people's downfall — but you don't have to skip it as long as you snack wisely. Try carrot sticks as a sweet, crunchy alternative to crackers or potato chips, or air-popped popcorn (provided you skip the butter and salt and season it with your favorite spices instead). For a satisfying blend of carbs and protein, try a dollop of sunflower seed butter on apple slices.For more information on lifestyle changes you can make to help prevent a stroke, buy Stroke: Diagnosing, treating, and recovering from a "brain attack, " a Special Health Report from Harvard Medical School.Stroke: Know when to act, and act quicklyIdentifying and treating a stroke as quickly as possible can save brain cells, function, and lives. Everyone should know the warning signs of a stroke and when to get help fast.The warning signs of a stroke can begin anywhere from a few minutes to days before a stroke actually occurs. The National Stroke Association has devised the FAST checklist to help determine whether a person is having a stroke.Act FASTIf the answer to any of the questions below is yes, there's a high probability that the person is having a stroke.Face: Ask the person to smile. Does one side of the face droop?Arms: Ask the person to raise both arms. Does one arm drift downward?Speech: Ask the person to repeat a simple sentence. Are the words slurred? Does he or she fail to repeat the sentence correctly?Time: If the answer to any of these questions is yes, time is important! Call the doctor or get to the hospital fast. Brain cells are dying.When stroke symptoms occur, quick action is vital. If you think you or someone with you is having a stroke, call the doctor. Ideally, the person affected should be taken to a hospital emergency room that has expertise and experience in treating stroke as it occurs (called acute stroke). If you or someone you love is at high risk for having a stroke, you should know the name and location of the nearest hospital that specializes in treating acute stroke.The goal of stroke treatment is to restore blood circulation before brain tissue dies. To prevent brain cell death that is significant enough to cause disability, treatment is most effective if it starts within 60 minutes of the onset of symptoms. But it can still be very effective if given within 3 hours of symptom onset.An important goal of ongoing stroke research is to find treatments that can buy time by protecting the person's brain until blood circulation is restored, which can increase the chances of survival and decrease the chances of disability.
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Clog Resistance of non-Pressure Based Flow CytometersBy Greg Kaduchak, PhD10.25.2017Flow cell clogs have been a long standing issue in flow cytometry. The small dimensions of the flow cell and fluidic path are susceptible to clogs especially when using larger or ‘sticky’ cells. In addition, historically, flow cytometer systems have been pressure-based which compounds this issue even more.In pressure-based systems, the particles are transported through the system by applying pressure to the fluid. It is a straightforward method to move the fluids through the small channels. To ensure a smooth delivery of fluids and particles through the flow cell without fluctuations, the systems employ pressure regulators. For those that have used these systems, it is a proven design to deliver particles in a flow cytometer and has been successful over the years. But, in the event of a clog, there is not much these systems can do.Figure 1(a) and (b) show what happens when a clog is encountered in a pressure-based fluidic system. When the system is in normal operation (a), the fluid is pushed through the system a specified pressure. For this example, we have used 7 psi. But, as seen in (b), when a clog is encountered the regulator keeps the system at 7 psi. No additional pressure is exerted to move the clog through the flow cell and the flow stops.Figure 1In contrast, in systems that employ positive displacement to drive the fluidic system (e.g. syringe pumps), the pressure is not held constant. These systems operate by a principle of constant volumetric flow. They are designed for fluid to flow with a specified volume delivery rate regardless of the pressure. An example of such a system facing a potential clog is shown in Figs. 1(c) and (d). As seen, the system operates at the same pressure as the pressure-based system when all is fine. But, once a clog is encountered, the system will build pressure to maintain the volumetric delivery rate. Pressure will build until the clog is displaced.The fluidic system in the Attune NxT Acoustic Focusing Flow Cytometers is based on positive displacement fluid delivery. For the purpose of robust clog removal, the system is outfit with a sensor that monitors the system pressure. When a potential clog is encountered, the pressure is allowed to build all the way up to 60 psi before safely shutting down the system. An additional benefit is used by the Attune NxT Flow Cytometer to keep the flow cell clean: a rinse cycle automatically runs between samples, this clears the sample in the flow cell with excess sheath fluid to prevent any cellular buildup.This feature has made the Attune flow cytometer platforms extremely clog resistant. Its install base has grown considerably since its initial launch more than two years ago, but still only a few clogs have been encountered by users of properly maintained instruments. Due to this resistance to clog, positive displacement systems are great from applications where cells are large and sticky, especially for tissue-based samples.
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New DNA nanorobots successfully target and kill off cancerous tumorsBY SARAH BUHRFeb 12, 2018Science fiction no more — in an article out today in Nature Biotechnology, scientists were able to show tiny autonomous bots have the potential to function as intelligent delivery vehicles to cure cancer in mice.These DNA nanorobots do so by seeking out and injecting cancerous tumors with drugs that can cut off their blood supply, shriveling them up and killing them.“Using tumor-bearing mouse models, we demonstrate that intravenously injected DNA nanorobots deliver thrombin specifically to tumor-associated blood vessels and induce intravascular thrombosis, resulting in tumor necrosis and inhibition of tumor growth, ” the paper explains.DNA nanorobots are a somewhat new concept for drug delivery. They work by getting programmed DNA to fold into itself like origami and then deploying it like a tiny machine, ready for action.DNA nanorobots, Nature Biotechnology 2018The scientists behind this study tested the delivery bots by injecting them into mice with human breast cancer tumors. Within 48 hours, the bots had successfully grabbed onto vascular cells at the tumor sites, causing blood clots in the tumor’s vessels and cutting off their blood supply, leading to their death.Remarkably, the bots did not cause clotting in other parts of the body, just the cancerous cells they’d been programmed to target, according to the paper.The scientists were also able to demonstrate the bots did not cause clotting in the healthy tissues of Bama miniature pigs, calming fears over what might happen in larger animals.The goal, say the scientists behind the paper, is to eventually prove these bots can do the same thing in humans. Of course, more work will need to be done before human trials begin.Regardless, this is a huge breakthrough in cancer research. The current methods of either using chemotherapy to destroy every cell just to get at the cancer cell are barbaric in comparison. Using targeted drugs is also not as exact as simply cutting off blood supply and killing the cancer on the spot. Should this new technique gain approval for use on humans in the near future it could have impressive affects on those afflicted with the disease
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