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  • richardmitnick 2:15 pm on May 17, 2019 Permalink | Reply
    Tags: , Bacteria-killing viruses – bacteriophages, Biology, Cholera outbreaks occur worldwide, In regions of the world lacking clean water and proper sanitation 2.5 billion people are at risk., , , Phages are very specific and infect only their particular host species of bacteria., Phages infect and kill multi-drug resistant strains of bacteria just as well as drug-sensitive ones., Phages provide immediate protection., Potential weapons to fight bacteria that are resistant to multiple antibiotics   

    From The Conversation: “Viruses to stop cholera infections – the viral enemy of deadly bacteria could be humanity’s friend” 

    Conversation
    From The Conversation

    May 17, 2019

    Andrew Camilli
    Professor of Molecular Biology & Microbiology, Tufts University

    Minmin Yen
    Research Associate of Molecular Microbiology, Tufts University

    1

    In the latest of a string of high-profile cases in the U.S., a cocktail of bacteria-killing viruses successfully treated a cystic fibrosis [Nature Biotechnology] patient suffering from a deadly infection caused by a pathogen that was resistant to multiple forms of antibiotics.

    Curing infections is great, of course. But what about using these bacteria-killing viruses – bacteriophages – to prevent infections in the first place? Could this work for some diseases? Although using viruses to prevent infections caused by bacterial infections might seem counterintuitive, in the case of bacteriophages: “The enemy of my enemy is my friend.”

    Discovered a little more than 100 years ago [BMC], bacteriophages, or phages, are generating renewed interest as potential weapons to fight bacteria that are resistant to multiple antibiotics – the so-called superbugs. Although the recent phage therapy has been focused on the treatment of sick patients, preventing infection stops a disease before it begins, keeping people healthy and preventing the spread of the germ to others.

    We are microbiologists [Nature Communications] who study cholera because this ancient disease continues to thrive and can have a devastating impact on communities and entire countries. The Camilli lab has been focused on the disease for over two decades. We are interested in developing vaccines and phage products to prevent cholera from sickening people and triggering outbreaks.

    3
    This cholera patient is drinking oral rehydration solution in order to counteract his cholera-induced dehydration. Centers for Disease Control and Prevention’s Public Health Image Library

    Cholera outbreaks occur worldwide

    In the case of cholera, which is caused by the bacterium Vibrio cholerae, prevention is preferred because it spreads like wildfire once it strikes a community. When this bacterial pathogen is ingested, it inhabits the small intestine, where it releases a potent toxin that triggers vomiting and watery diarrhea, which cause severe dehydration. The vomiting and diarrhea encourage the spread of the pathogen within households and contaminate local water sources. Left untreated, cholera kills 40% of its victims, sometimes within hours of the onset of symptoms. Fortunately, death can be largely prevented by prompt rehydration of cholera victims.

    In regions of the world lacking clean water and proper sanitation, 2.5 billion people are at risk, and the CDC estimates that there are up to 4 million cholera cases per year. New epidemics such as the recent massive epidemic in Yemen which has so far sickened over 1.2 million people and the outbreak in Mozambique are often the consequence of humanitarian crises. War and natural disasters often cause shortages of clean water and impact the poorest and most vulnerable communities.

    Cholera is highly transmissible in the community and within households. During outbreaks, an estimated 80% of cases are believed to result from rapid transmission within households, presumably occurring through contamination of household food, water or surfaces with diarrhea or vomit from the initial cholera victim.

    Family members typically experience cholera symptoms themselves two to three days after the initial household member became sick. Thus, the people in the most danger are usually siblings and loved ones taking care of the sick person. There is currently no approved medical intervention to immediately protect household members from contracting cholera when it strikes a household. Vaccines for cholera require at least 10 days to take effect, and thus miss the mark in this emergency situation.

    Prevention of cholera using phages

    To address this need, we developed a cocktail of phages to be taken orally each day by household members prior to, or soon after, exposure to Vibrio cholerae to protect them from contracting the disease. We believe the phages should remain in the intestinal tract long enough to serve as a shield against the incoming cholera bacteria. Although this has only been proven in animal models of cholera, we hope that the phage cocktail will work similarly in humans. There are three advantages to using phages in this manner.

    First, phages provide immediate protection. By acting fast, phages can eliminate the cholera bacteria from the gut in a targeted manner. That is important because cholera kills quickly.

    Second, phages infect and kill multi-drug resistant strains of bacteria just as well as drug-sensitive ones. This is crucial since the cholera bacteria have become multi-drug resistant [ALJM] in many parts of the world due to widespread antibiotic use [The Lancet].

    Third, in contrast to antibiotics, which kill bacteria indiscriminately, phages are very specific and infect only their particular host species of bacteria. Thus, when using phages against a pathogen, they will not disrupt the good bacteria residing in and on our patients’ bodies which are part of the microbiome. In research in our lab phages, called ICP1, ICP2 and ICP3, which we are using, kill only Vibrio cholerae and should not disrupt the good bacteria in the intestinal tract. This is important because our good bacteria are essential for defending the body against other pathogens and vital for our general nutrition and health.

    4
    People fill buckets with water from a well that is alleged to be contaminated water with the bacterium Vibrio cholera, on the outskirts of Yemen. Yemen’s raging two-year conflict has served as an incubator for lethal cholera. AP Photo/Hani Mohammed

    From test tube to product

    In collaboration with international researchers, we have been studying the cholera bacteria and its phages for over two decades at Tufts University, trying to uncover the details of how cholera spreads and how phages might affect its spread. The use of phages for prevention of cholera transmission was a natural outcome of this research, but by no means was it straightforward.

    Development of our phage product required finding phages that kill Vibrio cholerae in the intestinal tract, having intimate knowledge of how the phages infect the bacteria and discovering how the bacteria become resistant to the phages and how this affects their virulence.

    Our goal now is to test the phage cocktail in people during a cholera epidemic. Specifically, we need to determine if it is effective at preventing cholera transmission to family members in households where cholera strikes.

    In this day and age, we need to change the paradigm of relying entirely on antibiotics to treat infections and develop other types of antimicrobial solutions. It’s time to bring phages in from the cold, and utilize them both for treating multi-drug resistant bacterial infections and in the prevention of infections.

    See the full article here .

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    The Conversation launched as a pilot project in October 2014. It is an independent source of news and views from the academic and research community, delivered direct to the public.
    Our team of professional editors work with university and research institute experts to unlock their knowledge for use by the wider public.
    Access to independent, high quality, authenticated, explanatory journalism underpins a functioning democracy. Our aim is to promote better understanding of current affairs and complex issues. And hopefully allow for a better quality of public discourse and conversation.

     
  • richardmitnick 11:06 am on May 17, 2019 Permalink | Reply
    Tags: , Biology, , Cholesterol is an essential component of the membranes that enclose all of our cells., Squalene monooxygenase has a “destruction code” that acts to bind ubiquitin when unlocked initiating its own destruction., Squalene monooxygenase has also been linked to high cholesterol in human cancers including liver; breast; and prostate cancers., , Why biology has introduced such an unusual chemical modification is still not well-understood.   

    From University of New South Wales: “Scientists find ‘molecular destruction code’ for enzyme involved in cholesterol production” 

    U NSW bloc

    From University of New South Wales

    17 May 2019
    Isabelle Dubach

    A newly identified mechanism that regulates a particular enzyme could lead to the development of new, cholesterol-lowering drugs.

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    UNSW PhD Candidate Jake Chua is the lead author on a paper that shows how a key enzyme that contributes to cholesterol production can be regulated – and destroyed – using a particular molecule.

    A team of UNSW scientists at the School of Biotechnology and Biomolecular Sciences led by Professor Andrew Brown have shown how a key enzyme that contributes to cholesterol production can be regulated – and destroyed – using a particular molecule.

    The findings have implications for the development of cholesterol-lowering drugs: knowing how to regulate this enzyme – squalene monooxygenase – may offer a new way to control its abundance in a bid to lower cholesterol levels.

    In the paper – published today in the Journal of Biological Chemistry – the scientists demonstrated how squalene monooxygenase, when linked to a particular molecule called ubiquitin, gets destroyed and inhibits the synthesis of cholesterol.

    The scientists showed that squalene monooxygenase has a “destruction code” that acts to bind ubiquitin when unlocked, initiating its own destruction.

    “Knowing the molecular mechanisms of how this enzyme – which plays a key role in cholesterol production – is regulated will allow us to understand how drugs can help maintain healthy levels of cholesterol in the cells of our body,” says UNSW PhD candidate Ngee Kiat (Jake) Chua, the paper’s lead author.

    2
    Squalene monooxygenase is depicted in blue (top and bottom). Under certain conditions, a helix in squalene monooxygenase (coiled structure, top right) is unravelled to reveal the destruction code (bottom blue squalene monooxygenase). The ubiquitin molecules are shown as purple spheres, linked to squalene monooxygenase in grey rods. Cholesterol is shown as ringed structures (yellow).

    For nearly twenty years, squalene monooxygenase has been proposed to be an enzyme in the pathway which should be investigated as another drug target to lower cholesterol.

    More recently, squalene monooxygenase has also been linked to high cholesterol in human cancers, including liver, breast and prostate cancers.

    Cholesterol is an essential component of the membranes that enclose all of our cells. Cholesterol is also the starting material for bile acids that allow us to digest fat as well as for steroid hormones like estrogen and testosterone. But high levels of cholesterol are still a major health concern, given their connection to heart disease.

    “What a lot of people don’t realise is that our body produces the bulk of cholesterol to meet our metabolic requirements – dietary cholesterol contributes a smaller proportion,” Mr Chua says.

    The body produces cholesterol through a pipeline called the cholesterol synthesis pathway. That’s the pipeline that statins – the most common cholesterol-lowering drugs – target. Statins limit cholesterol production by blocking one of the enzymes that is responsible for one early chemical reaction in this pathway.

    “Statins are not without their shortcomings – for example, they have been linked to muscle pain in some people who take them and some patients experience statins intolerance.

    “That’s why researchers are investigating other enzymes in the pathway, with hopes of finding alternative druggable targets to help lower cholesterol.

    “Enzymes are proteins that are made up of combinations of about 20 different building blocks called amino acids. In this paper, we reported that joining ubiquitin to a serine amino acid in squalene monooxygenase triggers its destruction. New knowledge of this initial chemical linkage raises new prospects to control cholesterol production. For instance, enhancing the formation of this chemical linkage speeds up the destruction of squalene monooxygenase,” Mr Chua says.

    The formation of the chemical linkage between ubiquitin and the serine amino acid on squalene monooxygenase is still not well-represented in the scientific literature

    “Why biology has introduced such an unusual chemical modification is still not well-understood,” Mr Chua says.

    “In the entire cholesterol synthesis pathway, which has about 20 steps each carried out by separate enzymes, squalene monooxygenase is the first-known enzyme to possess this unusual chemical linkage with ubiquitin.”

    With the emergence of newer techniques in modulating enzymes, including gene-editing and chemical molecules to trigger enzyme destruction, researchers are trying new approaches, rather than conventional drugs that simply block enzyme activity.

    “While our study has identified the molecular destruction code, future research should focus on identifying ways to unlock it for initiating the destruction of squalene monooxygenase as a strategy to lower cholesterol levels,” Mr Chua says.

    See the full article here .


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    U NSW Campus

    Welcome to UNSW Australia (The University of New South Wales), one of Australia’s leading research and teaching universities. At UNSW, we take pride in the broad range and high quality of our teaching programs. Our teaching gains strength and currency from our research activities, strong industry links and our international nature; UNSW has a strong regional and global engagement.

    In developing new ideas and promoting lasting knowledge we are creating an academic environment where outstanding students and scholars from around the world can be inspired to excel in their programs of study and research. Partnerships with both local and global communities allow UNSW to share knowledge, debate and research outcomes. UNSW’s public events include concert performances, open days and public forums on issues such as the environment, healthcare and global politics. We encourage you to explore the UNSW website so you can find out more about what we do.

     
  • richardmitnick 3:13 pm on May 16, 2019 Permalink | Reply
    Tags: An open-source RNA analysis platform has been successfully used on plant cells for the first time, , Biology, DOE Joint Genome Institute (JGI), Drop-seq,   

    From Lawrence Berkeley National Lab: “Breakthrough Technique for Studying Gene Expression Takes Root in Plants” 

    Berkeley Logo

    From Lawrence Berkeley National Lab

    May 16, 2019
    Aliyah Kovner
    akovner@lbl.gov
    510-486-6376

    Berkeley Lab scientists adapt open-source genetic analysis method for use in plant cells for the first time.

    1
    Researcher Christine Shulse tends to Arabidopsis plants in a lab at the DOE Joint Genome Institute (JGI). (Photo credit: Marilyn Chung/Berkeley Lab)

    An open-source RNA analysis platform has been successfully used on plant cells for the first time – an advance that could herald a new era of fundamental research and bolster efforts to engineer more efficient food and biofuel crop plants.

    The technology, called Drop-seq, is a popular method for measuring the RNA present in individual cells, allowing scientists to see what genes are being expressed and how this relates to the specific functions of different cell types. Developed at Harvard Medical School in 2015, the freely shared protocol had previously only been used in animal cells.

    “This is really important in understanding plant biology,” said lead researcher Diane Dickel, a scientist at the Department of Energy’s Lawrence Berkeley National Lab (Berkeley Lab). “Like humans and mice, plants have multiple cell and tissue types within them. But learning about plants on a cellular level is a little bit harder because, unlike animals, plants have cell walls, which make it hard to open the cells up for genetic study.”

    For many of the genes in plants, we have little to no understanding of what they actually do, Dickel explained. “But by knowing exactly what cell type or developmental stage a specific gene is expressed in, we can start getting a toehold into its function. In our study, we showed that Drop-seq can help us do this.”

    “We also showed that you can use these technologies to understand how plants respond to different environmental conditions at a cellular level – something many plant biologists at Berkeley Lab are interested in because being able to grow crops under poor environmental conditions, such as drought, is essential for our continued production of food and biofuel resources,” she said.

    Dickel, who studies mammalian genomics in Berkeley Lab’s Environmental Genomics and Systems Biology Division, has been using Drop-seq on animal cells for several years. An immediate fan of the platform’s ease of use and efficacy, she soon began speaking to her colleagues working on plants about trying to use it on plant cells.

    However, some were skeptical that such a project would work as easily. First off, to run plant cells through a single-cell RNA-seq analysis, they must be protoplasted – meaning they must be stripped of their cell walls using a cocktail of enzymes. This process is not easy because cells from different species and even different parts of the same plant require unique enzyme cocktails.

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    Microscope images of flowering plant root cells in their natural state (left) and after protoplasting (right). (Image credit: Berkshire Community College Bioscience Image Library and Department of Biological Sciences, Louisiana State University)

    Secondly, some plant biologists have expressed concern that cells are altered too significantly by protoplasting to provide insight into normal functioning. And finally, some plant cells are simply too big to be put through existing single-cell RNA-seq platforms. These technologies, which emerged in the past five years, allow scientists to assess the RNA inside thousands of cells per run; previous approaches could only analyze dozens to hundreds of cells at a time.

    Undeterred by these challenges, Dickel and her colleagues at the DOE Joint Genome Institute (JGI) teamed up with researchers from UC Davis who had perfected a protoplasting technique for root tissue from Arabidopsis thaliana (mouse-ear cress), a species of small flowering weed that serves as a plant model organism.

    After preparing samples of more than 12,000 Arabidopsis root cells, the group was thrilled when the Drop-seq process went smoother than expected. Their full results were published this week in Cell Reports.

    “When we would pitch the idea to do this in plants, people would bring up a list of reasons why it wouldn’t work,” said Dickel. “And we would say, ‘ok, but let’s just try it and see if it works’. And then it really worked. We were honestly surprised how straightforward it actually ended up being.”

    The open-source nature of the Drop-seq technology was critical for this project’s success, according to co-author Benjamin Cole, a plant genomics scientist at JGI. Because Drop-seq is inexpensive and uses easy-to-assemble components, it gave the researchers a low-risk, low-cost means to experiment. Already, a wave of interest is building. In the time leading up to their paper’s publication, Dickel and her colleagues began receiving requests – from other scientists at Berkeley Lab, JGI, and beyond – for advice on how to adapt the platform for other projects.

    “When I first spoke to Diane about trying Drop-seq in plants I recognized the huge potential, but I thought it would be difficult to separate plant cells rapidly enough to get useful data,” said John Vogel, lead scientist of plant functional genomics at JGI. “I was shocked to see how well it worked and how much they were able to learn from their initial experiment. This technique is going to be a game changer for plant biologists because it allows us to explore gene expression without grinding up whole plant organs, and the results aren’t muddled by signals from the few most common cell types.”

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    A cartoon diagram of the 17 different root cell types profiled using the Drop-seq protocol. (Image credit: Diane Dickel/Berkeley Lab)

    The authors anticipate that the platform, and other similar RNA-seq technologies, will eventually become routine in plant investigations. The main hurdle, Dickel noted, will be developing protoplasting methods for each project’s plant of interest.

    “Part of Berkeley Lab’s mission is to better understand how plants respond to changing environmental conditions, and how we can apply this understanding to best utilize plants for bioenergy,” noted first author Christine Shulse, who is currently a JGI affiliate. “In this work, we generated a map of gene expression in individual cell types from one plant species under two environmental conditions, which is an important first step.”

    JGI is a DOE Office of Science user facility that was originally founded to advance the landmark Human Genome Project. After helping set the stage for a new era of medical and developmental science, JGI turned its focus to investigating how plants and microbes can provide solutions to pressing energy and environmental challenges.

    This research was funded by the Laboratory Directed Research and Development (LDRD) program. The other authors were Doina Ciobanu, Junyan Lin, Yuko Yoshinaga, Mona Gouran, Gina Turco, Yiwen Zhu, Ronan O’Malley, and Siobhan Brady.

    See the full article here .

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    Bringing Science Solutions to the World

    In the world of science, Lawrence Berkeley National Laboratory (Berkeley Lab) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the National Academy of Sciences (NAS), one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the National Academy of Engineering, and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

    Berkeley Lab is a member of the national laboratory system supported by the U.S. Department of Energy through its Office of Science. It is managed by the University of California (UC) and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above the UC Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

    Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a UC Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

    A U.S. Department of Energy National Laboratory Operated by the University of California.

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  • richardmitnick 11:55 am on May 13, 2019 Permalink | Reply
    Tags: , Biology, Buildings of the future may be lit by collections of glowing plants and designed around an infrastructure of sunlight harvesting water transport and soil collecting and composting systems., , Collaboration between MIT architect and chemical engineer could be at the center of new sustainable infrastructure for buildings., , Nanobionic plant technology,   

    From MIT News: “Ambient plant illumination could light the way for greener buildings” 

    MIT News
    MIT Widget

    From MIT News

    May 9, 2019
    Becky Ham

    Collaboration between MIT architect and chemical engineer could be at the center of new sustainable infrastructure for buildings.

    1
    Glowing nanobionic watercress plants illuminate the Plant Properties Reading Room. Image: KVA Matx and Strano Research Group

    2
    Glowing nanobionic watercress illuminates the book “Paradise Lost.” Image: Strano Research Group

    3
    Pollinator Port – A Plant Properties room featuring an access port for light and pollinators to reach interior plants. Image: KVA Matx and Strano Research Group

    Buildings of the future may be lit by collections of glowing plants and designed around an infrastructure of sunlight harvesting, water transport, and soil collecting and composting systems. That’s the vision behind an interdisciplinary collaboration between an MIT architecture professor and a professor of chemical engineering.

    The light-emitting plants, which debuted in 2017, are not genetically modified to produce light. Instead, they are infused with nanoparticles that turn the plant’s stored energy into light, similar to how fireflies glow. “The transformation makes virtually any plant a sustainable, potentially revolutionary technology,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT. “It promises lighting independent of an electrical grid, with ‘batteries’ you never need to charge, and power lines that you never need to lay.”

    But Strano and his colleagues soon realized that they needed partners who could expand the concept and understand its challenges and potential as part of a future of sustainable energy. He reached out to Sheila Kennedy, professor of architecture at MIT and principal at Kennedy and Violich Architecture, who is known for her work in clean energy infrastructure.

    “The science was so new and emergent that it seemed like an interesting design challenge,” says Kennedy. “The work of this design needed to move to a different register, which went beyond the problem of how the plant nanobionics could be demonstrated in architecture. As a design team, we considered some fundamental questions, such as how to understand and express the idea of plant lighting as a living, biological technology and how to invite the public to imagine this new future with plants.”

    “If we treat the development of the plant as we would just another light bulb, that’s the wrong way to go,” Strano adds.

    In 2017, Kennedy and Strano received a Professor Amar G. Bose Research Grant to build on their collaboration. The MIT faculty grants support unconventional, ahead-of-the-curve, and often interdisciplinary research endeavors that are unlikely to be funded through traditional avenues, yet have the potential to lead to big breakthroughs.

    Their first year of the Bose grant yielded several generations of the light-emitting watercress plants, which shine longer and brighter than the first experimental versions. The team is evaluating a new component to the nanobiotic plants that they call light capacitor particles. The capacitor, in the form of infused nanoparticles in the plant, stores spikes in light generation and “bleeds them out over time,” Strano explains. “Normally the light created in the biochemical reaction can be bright but fades quickly over time. Capacitive particles extend the duration of the generated plant light from hours to potentially days and weeks.”

    The researchers have added to their original patent on the light-emitting plant concept, filing a new patent on the capacitor and other components as well, Strano says.

    Designing for display

    As the nanobionic plant technology has advanced, the team is also envisioning how people might interact with the plants as part of everyday life. The architectural possibilities of their light-emitting plant will be on display within a new installation, “Plant Properties, a Future Urban Development,” at the Cooper Hewitt, Smithsonian Design Museum in New York opening May 10.

    Visitors to the installation, part of the 2019 “Nature—Cooper Hewitt Design Triennial” exhibition, can peek into a scaled architectural model of a New York City tenement building — which also serves as a plant incubator — to see the plants at work. The installation also demonstrates a roadmap for how an existing residential building could be adapted and transformed by design to support the natural growth of plants in a future when available energy could be very limited.

    “In Plant Properties, the nanobionic plant-based infrastructure is designed to use nature’s own resources,” says Kennedy. “The building harvests and transports sunlight, collects and recycles water, and enriches soil with compost.”

    The invitation to contribute to the Cooper Hewitt exhibition offered an unexpected way to demonstrate the plants’ possibilities, but designing an exhibit brought about a whole new set of challenges, Kennedy explains. “In the world of design museums, you’re usually asked to show something that’s already been exhibited, but this is new work and a new milestone in this project.”

    “We learned a lot about the care of plants,” Strano adds. “It’s one thing to make a laboratory demonstration, but it’s another entirely to make 33 continuous weeks of a public demonstration.”

    The researchers had to come up with a way to showcase the plants in a low-light museum environment where dirt and insects attracted by living plants are usually banished. “But rather than seeing this as a sort of insurmountable obstacle,” says Kennedy, “we realized that this kind of situation — how do you enable living plants to thrive in the enclosed setting of a museum — exactly paralleled the architectural problem of how to support significant quantities of plants growing inside buildings.”

    In the installation, multiple peepholes into the building model offer glimpses into the ways people in the building are living with the plants. Museum visitors are encouraged to join the experiment and crowdsource information on plant growth and brightness, by uploading their own photos of the plants to Instagram and tagging the MIT Plant Nanobiotics lab, using @plantproperties.

    The team is also collecting data on how the plants respond to the nanoparticles and other potential stresses. “The plants are actually under more stress from being in the museum environment than from the modifications that we introduce, but these effects need to be studied and mitigated if we are to use plants for indoor lighting,” Strano notes.

    Bright and nurturing futures

    Kennedy and Strano say the plants could be at the center of a new — but also “pre-eclectic” — idea in architecture.

    For most of human history, Kennedy explains, natural processes from sunlight to waste composting were part of the essential infrastructure of buildings. But these processes have been excluded in modern thinking or hidden away, preventing people from coming face to face with the environmental costs of energy infrastructure made from toxic materials and powered by fossil fuels.

    “People don’t question the impacts of our own mainstream electrical grid today. It’s very vulnerable, it’s very brittle, it’s so very wasteful and it’s also full of toxic material,” she says. “We don’t question this, but we need to.”

    “Lighting right now consumes a vast portion of our energy demand, approaching close to 20 percent of our global energy consumption, generating two gigatons of carbon dioxide per year,” Strano adds. “Consider that the plants replace more than just the lamp on your desk. There’s an enormous energy footprint that could potentially be replaced by the light-emitting plant.”

    The team is continuing to work on new ways to infuse the nanoparticles in the plants, so that they work over the lifetime of the plant, as well as experimenting on larger plants such as trees. But for the plants to thrive, architects will have to develop building infrastructure that integrates the plants into a new internal ecosystem of sunlight, water and waste disposal, Kennedy says.

    “If plants are to provide people with light, we need to keep plants healthy to benefit from everything they provide for us,” she says. “We think this is going to trigger a much more caring or nurturing relationship of people and their plants, or plants and the people that they illuminate.”

    See the full article here .


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  • richardmitnick 8:18 am on May 11, 2019 Permalink | Reply
    Tags: , Beta-lactam; gamma-lactam: and delta-lactam molecules, Biology, , , In the ongoing arms race with humans and their antibiotics on one side and bacteria with their ability to evolve defenses to antibiotics on the other humans have enlisted a new ally: other bacteria.   

    From Caltech: “Directed Evolution Opens Door to New Antibiotics” 

    Caltech Logo

    From Caltech

    May 09, 2019
    Emily Velasco
    626‑395‑6487
    evelasco@caltech.edu

    1
    Caltech

    In the ongoing arms race with humans and their antibiotics on one side, and bacteria with their ability to evolve defenses to antibiotics on the other, humans have enlisted a new ally—other bacteria.

    Many common antibiotics, including the most famous antibiotic, penicillin, are based around a molecular structure known as a beta-lactam ring. These drugs, aptly named beta-lactam antibiotics, interfere with a bacterium’s ability to build its cell wall.

    2
    Penicillin. Credit: Caltech

    As bacteria develop resistance to existing antibiotics, researchers and pharmaceutical companies work to create new ones. That means a lot of work is done creating new kinds of beta-lactams, and that is where Frances Arnold’s lab enters the picture.

    6
    Frances H. Arnold

    The paramount challenge is to control precisely where along the molecule the reaction takes place. With traditional synthetic chemistry, chemists have to tack extra pieces onto molecules that they want to turn into beta-lactams. Without those extra pieces, the knots will end up tied in inconsistent spots, resulting in some loops that are large and some that are small. That’s undesirable for someone trying to manufacture a consistent batch of antibiotics. But the addition of those extra pieces makes the synthesis more complicated because additional steps are required to add them and still more steps to remove them after the looping is complete.

    3
    Caltech
    Beta-lactams are made by taking a chainlike molecule and looping it, kind of like taking one end of a string and tying it in a knot to the middle of the string.

    Graduate student Inha Cho and postdoctoral scholar Zhi-Jun Jia, both from Arnold’s lab, have developed something simpler by using directed evolution, a technique developed by Arnold, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, and director of the Donna and Benjamin M. Rosen Bioengineering Center. In directed evolution, which Arnold developed in the 1990s and for which she received the 2018 Nobel Prize in Chemistry, enzymes are evolved in a lab until they behave in a desired way. The genetic code of a useful enzyme is transferred into bacteria like Escherichia coli. As the bacteria grow, divide, and go about their lives, they churn out the enzyme.

    In this case, Cho and Jia took an enzyme known as cytochrome P450, which has been a versatile workhorse in the Arnold lab, and evolved it to produce beta-lactams. Two other versions of enzymes were also created to construct other ring sizes of lactams. One version creates a gamma-lactam, a loop of four carbon atoms and one nitrogen atom. And the other version creates a delta-lactam, a loop of five carbon atoms and one nitrogen atom.

    6
    The enzyme developed in Arnold’s lab can create beta-lactam, gamma-lactam, and delta-lactam molecules. Credit: Caltech

    “We’re developing new enzymes with activity that cannot be found in nature,” says Cho. “Lactams can be found in many different drugs, but especially in antibiotics, and we’re always needing new ones.”

    Jia points out that the enzymes they have created are also incredibly efficient, with each molecule of enzyme capable of producing up to one million beta-lactam molecules. “They represent the most efficient enzymes created in our lab, and are ready for industrial applications,” Jia says.

    The paper, titled “Site-selective enzymatic C-H amidation for synthesis of diverse lactams” and co-authored by Arnold, appears in the May 10 issue of Science.

    Support for the research was provided by the National Science Foundation, the Joseph J. Jacobs Institute for Molecular Engineering for Medicine, and Deutsche Forschungsgemeinschaft.

    See the full article here .


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    Please help promote STEM in your local schools.


    Stem Education Coalition

    The California Institute of Technology (commonly referred to as Caltech) is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. “The mission of the California Institute of Technology is to expand human knowledge and benefit society through research integrated with education. We investigate the most challenging, fundamental problems in science and technology in a singularly collegial, interdisciplinary atmosphere, while educating outstanding students to become creative members of society.”

    Caltech campus

     
  • richardmitnick 12:22 pm on May 10, 2019 Permalink | Reply
    Tags: , Biology, , , , ,   

    From Brookhaven National Lab: “New Approach for Solving Protein Structures from Tiny Crystals” 

    From Brookhaven National Lab

    May 3, 2019
    Karen McNulty Walsh
    kmcnulty@bnl.gov
    (631) 344-8350

    Peter Genzer,
    genzer@bnl.gov
    (631) 344-3174

    Technique opens door for studies of countless hard-to-crystallize proteins involved in health and disease.

    1
    Wuxian Shi, Martin Fuchs, Sean McSweeney, Babak Andi, and Qun Liu at the FMX beamline at Brookhaven Lab’s National Synchrotron Light Source II [see below], which was used to determine a protein structure from thousands of tiny crystals.

    Using x-rays to reveal the atomic-scale 3-D structures of proteins has led to countless advances in understanding how these molecules work in bacteria, viruses, plants, and humans—and has guided the development of precision drugs to combat diseases such as cancer and AIDS. But many proteins can’t be grown into crystals large enough for their atomic arrangements to be deciphered. To tackle this challenge, scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory and colleagues at Columbia University have developed a new approach for solving protein structures from tiny crystals.

    The method relies on unique sample-handling, signal-extraction, and data-assembly approaches, and a beamline capable of focusing intense x-rays at Brookhaven’s National Synchrotron Light Source II (NSLS-II)—a DOE Office of Science user facility—to a millionth-of-a-meter spot, about one-fiftieth the width of a human hair.

    “Our technique really opens the door to dealing with microcrystals that have been previously inaccessible, including difficult-to-crystallize cell-surface receptors and other membrane proteins, flexible proteins, and many complex human proteins,” said Brookhaven Lab scientist Qun Liu, the corresponding author on the study, which was published on May 3 in IUCrJ, a journal of the International Union of Crystallography.

    Deciphering protein structures

    Protein crystallography has been a dominant method for solving protein structures since 1958, improving over time as x-ray sources have grown more powerful, allowing more precise structure determinations. To determine a protein structure, scientists measure how x-rays like those generated at NSLS-II diffract, or bounce off, the atoms in an ordered crystalline lattice consisting of many copies of the same protein molecule all arrayed the same way. The diffraction pattern conveys information about where the atoms are located. But it’s not sufficient.

    2
    A cartoon representing the structure of a well-studied plant protein that served as a test case for the newly developed microcrystallography technique. Magenta mesh patterns surrounding sulfur atoms intrinsic to the protein (yellow spheres) indicate the anomalous signals that were extracted using low-energy x-ray diffraction of thousands of crystals measuring less than 10 millionths of a meter, the size of a bacterium.

    “Only the amplitudes of diffracted x-ray ‘waves’ are recorded on the detector, but not their phases (the timing between waves),” said Liu. “Both are required to reconstruct a 3-D structure. This is the so-called crystallographic phase problem.”

    Crystallographers have solved this problem by collecting phase data from a different kind of scattering, known as anomalous scattering. Anomalous scattering occurs when atoms heavier than a protein’s main components of carbon, hydrogen, and nitrogen absorb and re-emit some of the x-rays. This happens when the x-ray energy is close to the energy those heavy atoms like to absorb. Scientists sometimes artificially insert heavy atoms such as selenium or platinum into the protein for this purpose. But sulfur atoms, which appear naturally throughout protein molecules, can also produce such signals, albeit weaker. Even though these anomalous signals are weak, a big crystal usually has enough copies of the protein with enough sulfur atoms to make them measurable. That gives scientists the phase information needed to pinpoint the location of the sulfur atoms and translate the diffraction patterns into a full 3-D structure.

    “Once you know the sulfur positions, you can calculate the phases for the other protein atoms because the relationship between the sulfur and the other atoms is fixed,” said Liu.

    But tiny crystals, by definition, don’t have that many copies of the protein of interest. So instead of looking for diffraction and phase information from repeat copies of a protein in a single large crystal, the Brookhaven/Columbia team developed a way to take measurements from many tiny crystals, and then assemble the collective data.

    Tiny crystals, big results

    To handle the tiny crystals, the team developed sample grids patterned with micro-sized wells. After pouring solvent containing the microcrystals over these well-mount grids, the scientists removed the solvent and froze the crystals that were trapped on the grids.

    3
    Micro-patterned sample grids for manipulation of microcrystals.

    “We still have a challenge, though, because we can’t see where the tiny crystals are on our grid,” said Liu. “To find out, we used microdiffraction at NSLS-II’s Frontier Microfocusing Macromolecular Crystallography (FMX) beamline to survey the whole grid. Scanning line by line, we can find where those crystals are hidden.”

    As Martin Fuchs, the lead beamline scientist at FMX, explained, “The FMX beamline can focus the full intensity of the x-ray beam down to a size of one micron, or millionth of a meter. We can finely control the beam size to match it to the size of the crystals—five microns in the case of the current experiment. These capabilities are crucial to obtain the best signal,” he said.

    Wuxian Shi, another FMX beamline scientist, noted that “the data collected in the grid survey contains information about the crystals’ location. In addition, we can also see how well each crystal diffracts, which allows us to pick only the best crystals for data collection.”

    The scientists were then able to maneuver the sample holder to place each mapped out microcrystal of interest back in the center of the precision x-ray beam for data collection.

    They used the lowest energy available at the beamline—tuned to approach as closely as possible sulfur atoms’ absorption energy—and collected anomalous scattering data.

    “Most crystallographic beamlines could not reach the sulfur absorption edge for optimized anomalous signals,” said co-author Wayne Hendrickson of Columbia University. “Fortunately, NSLS-II is a world-leading synchrotron light source providing bright x-rays covering a broad spectrum of x-ray energy. And even though our energy level was slightly above the ideal absorption energy for sulfur, it generated the anomalous signals we needed.”

    But the scientists still had some work to do to extract those important signals and assemble the data from many tiny crystals.

    “We are actually getting thousands of pieces of data,” said Liu. “We used about 1400 microcrystals, each with its own data set. We have to put all the data from those microcrystals together.”

    4
    Scientists used a five-micron x-ray beam at the FMX beamline at NSLS-II to scan the entire grid and locate the tiny invisible crystals. Then a heat map (green) was used to guide the selection of positions for diffraction data acquisition.

    They also had to weed out data from crystals that were damaged by the intense x-rays or had slight variations in atomic arrangements.

    “A single microcrystal does not diffract x-rays sufficiently for structure solution prior to being damaged by the x-rays,” said Sean McSweeney, deputy photon division director and program manager of the Structural Biology Program at NSLS-II. “This is particularly true with crystals of only a few microns, the size of about a bacterial cell. We needed a way to account for that damage and crystal structure variability so it wouldn’t skew our results.”

    They accomplished these goals with a sophisticated multi-step workflow process that sifted through the data, discarded outliers that might have been caused by radiation damage or incompatible crystals, and ultimately extracted the anomalous scattering signals.

    “This is a critical step,” said Liu. “We developed a computing procedure to assure that only compatible data were merged in a way to align the individual microcrystals from diffraction patterns. That gave us the required signal-to-noise ratios for structure determination.”

    Applying the technique

    This technique can be used to determine the structure of any protein that has proven hard to crystallize to a large size. These include cell-surface receptors that allow cells of advanced lifeforms such as animals and plants to sense and respond to the environment around them by releasing hormones, transmitting nerve signals, or secreting compounds associated with cell growth and immunity.

    “To adapt to the environment through evolution, these proteins are malleable and have lots of non-uniform modifications,” said Liu. “It’s hard to get a lot of repeat copies in a crystal because they don’t pack well.”

    In humans, receptors are common targets for drugs, so having knowledge of their varied structures could help guide the development of new, more targeted pharmaceuticals.

    But the technique is not restricted to just small crystals.

    “The method we developed can handle small protein crystals, but it can also be used for any size protein crystals, any time you need to combine data from more than one sample,” Liu said.

    This research was supported in part by Brookhaven National Laboratory’s “Laboratory Directed Research and Development” program and the National Institutes of Health (NIH) grant GM107462. The NSLS-II at Brookhaven Lab is a DOE Office of Science user facility (supported by DE-SC0012704), with beamline FMX supported primarily by the National Institute of Health, National Institute of General Medical Sciences (NIGMS) through a Biomedical Technology Research Resource P41 grant (P41GM111244), and by the DOE Office of Science.

    See the full article here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

    BNL Campus


    BNL Center for Functional Nanomaterials

    BNL NSLS-II


    BNL NSLS II

    BNL RHIC Campus

    BNL/RHIC Star Detector

    BNL RHIC PHENIX

    One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. The Laboratory’s almost 3,000 scientists, engineers, and support staff are joined each year by more than 5,000 visiting researchers from around the world. Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
    i1

     
  • richardmitnick 11:29 am on May 10, 2019 Permalink | Reply
    Tags: "Invasive species are Australia’s number-one extinction threat", , Australia has the highest rate of vertebrate mammal extinction in the world and invasive species are our number one threat., Biology, , , Invasive species are found in almost every part of Australia from our rainforests to our deserts; our farms; to our cities; our national parks and our rivers., It’s not all bad news. Australia actually has a long history of effectively managing invasive species., The effects of invasive species are getting worse, These affect our unique biodiversity as well as the clean water and oxygen we breath – not to mention our cultural values.   

    From CSIROscope: “Invasive species are Australia’s number-one extinction threat” 

    CSIRO bloc

    From CSIROscope

    10 May 2019
    Andy Sheppard
    Linda Broadhurst
    Asaesja Young

    1
    Feral foxes and cats are known predators of the eastern pygmy possum, which is threatened with extinction. Photo by Phil Spark.

    This week many people across the world stopped and stared as extreme headlines announced that one eighth of the world’s species – more than a million – are threatened with extinction.

    According to the UN report from the Intergovernmental Science-Policy Platform for Biodiversity and Ecosystem Services (IPBES) which brought this situation to public attention, this startling number is a consequence of five direct causes: changes in land and sea use; direct exploitation of organisms; climate change; pollution; and invasion of alien species.

    It’s the last, invasive species, that threatens Australian animals and plants more than any other single factor.

    Australia’s number one threat

    Australia has an estimated 600,000 species of flora and fauna. Of these, about 100 are known to have gone extinct in the last 200 years. Currently, more than 1,770 are listed as threatened or endangered.

    While the IPBES report ranks invasive alien species as the fifth most significant cause of global decline, in Australia it is a very different story.

    Australia has the highest rate of vertebrate mammal extinction in the world, and invasive species are our number one threat.

    Cats and foxes have driven 22 native mammals to extinction across central Australia and a new wave of decline – largely from cats – is taking place across northern Australia. Research has estimated 270 more threatened and endangered vertebrates are being affected by invasive species.

    Introduced vertebrates have also driven several bird species on Norfolk Island extinct.

    3
    The introduction of the European red fox (Vulpes vulpes) has been disastrous for our wildlife. Image: Harlz_

    The effects of invasive species are getting worse

    Although Australia’s stringent biosecurity measures have dramatically slowed the number of new invasive species arriving, those already here have continued to spread and their cumulative effect is growing.

    Recent research highlights that 1,257 of Australia’s threatened and endangered species are directly affected by 207 invasive plants, 57 animals and three pathogens.

    These affect our unique biodiversity, as well as the clean water and oxygen we breath – not to mention our cultural values.

    When it comes to biodiversity, Australia is globally quite distinct. More than 70% of our species (69% of mammals, 46% of birds and 93% of reptiles) are found nowhere else on earth. A loss to Australia is therefore a loss to the world.

    Some of these are ancient species like the Wollemi Pine, may have inhabited Australia for up to 200 million years, well before the dinosaurs.

    But invasive species are found in almost every part of Australia, from our rainforests, to our deserts, our farms, to our cities, our national parks and our rivers.

    4
    Feral cats are a major driver of biodiversity loss, contributing to 26% of bird, mammal and reptile extinctions. Image credit: Mark Marathon via Wikimedia Commons

    The cost to Australia

    The cost of invasive species in Australia continue to grow with every new assessment.

    The most recent estimates found the cost of controlling invasive species and economic losses to farmers in 2011-12 was A$13.6 billion. However this doesn’t include harm to biodiversity and the essential role native species play in our ecosystems, which – based on the conclusions of the IPBES report – is likely to cost at least as much, and probably far more.

    Rabbits, goats and camels prevent native desert plant community regeneration; rabbits alone impacting over 100 threatened species. Rye grass on its own costs cereal farmers A$93M a year.

    Aquaculture diseases have affected oysters and cost the prawn industry $43M.

    From island to savannah

    Globally, invasive species have a disproportionately higher effect on offshore islands – and in Australia we have more than 8,000 of these. One of the most notable cases is the case of the yellow crazy ants, which killed 15,000,000 red land crabs on Christmas Island.

    6
    The yellow crazy ant is one of the world’s top 100 most invasive pests. They can form huge colonies, totally displacing native animals and seriously disrupting ecological processes.

    Nor are our deserts immune. Most native vertebrate extinctions caused by cats have occurred in our dry inland deserts and savannas, while exotic buffel and gamba grass are creating permanent transformation through changing fire regimes.

    Australia’s forests, particularly rainforests, are also under siege on a number of fronts. The battle continues to contain Miconia weed in Australia – the same weed responsible for taking over 70% of Tahiti’s native forests. Chytrid fungus, thought to be present in Australia since 1970, has caused the extinction of at least four frog species and dramatic decline of at least ten others in our sensitive rainforest ecosystems.

    Myrtle rust is pushing already threatened native Australian Myrtaceae closer to extinction, notably Gossia gonoclada, and Rhodamnia angustifoliaand changing species composition of rainforest understories, and Richmond birdwing butterfly numbers are under threat from an invasive flower known as the Dutchman’s pipe.

    Australia’s rivers and lakes are also under increasing domination from invasive species. Some 90% of fish biomass in the Murray Darling Basin are European carp, and tilapia are invading many far north Queensland river systems pushing out native species .

    Invasive alien species are not only a serious threat to biodiversity and the economy, but also to human health. The Aedes aegypti mosquito found in parts of Queensland is capable of spreading infectious disease such as dengue, zika, chikungunya and yellow fever.

    And it’s not just Queensland that is under threat from diseases spread by invasive mosquitoes, with many researchers and authorities planning for when, not if, the disease carrying Aedes albopictus establishes itself in cooler and southern parts of Australia.

    7
    We have been testing in quarantine a new virus to control invasive carp. CSIRO

    What solutions do we have?

    Despite this grim inventory, it’s not all bad news. Australia actually has a long history of effectively managing invasive species.

    Targeting viruses as options for controlling rabbits, carp and tilapia; we have successfully suppressed rabbit populations by 70% in this way for 50 years.

    Weeds too are successful targets for weed biological control, with over a 65% success rate controlling more than 25 targets.

    The IPBES report calls for “transformative action”. Here too Australia is at the forefront, looking into the potential of gene-technologies to suppress pet hates such as cane toads.

    Past and current invasive species programs have been supported by governments and industry. This has provided the type of investment we need for long-term solutions and effective policies.

    Australia is better placed now, with effective biosecurity policies and strong biosecurity investment, than many countries. We will continue the battle against invasive species to stem biodiversity and ecosystem loss.

    See the full article here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

    SKA/ASKAP radio telescope at the Murchison Radio-astronomy Observatory (MRO) in Mid West region of Western Australia

    So what can we expect these new radio projects to discover? We have no idea, but history tells us that they are almost certain to deliver some major surprises.

    Making these new discoveries may not be so simple. Gone are the days when astronomers could just notice something odd as they browse their tables and graphs.

    Nowadays, astronomers are more likely to be distilling their answers from carefully-posed queries to databases containing petabytes of data. Human brains are just not up to the job of making unexpected discoveries in these circumstances, and instead we will need to develop “learning machines” to help us discover the unexpected.

    With the right tools and careful insight, who knows what we might find.

    CSIRO campus

    CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

     
  • richardmitnick 7:32 am on May 8, 2019 Permalink | Reply
    Tags: "Arsenic-breathing life discovered in the tropical Pacific Ocean", , Biology, , ,   

    From University of Washington: “Arsenic-breathing life discovered in the tropical Pacific Ocean” 

    U Washington

    From University of Washington

    May 1, 2019
    Hannah Hickey

    Arsenic is a deadly poison for most living things, but new research shows that microorganisms are breathing arsenic in a large area of the Pacific Ocean. A University of Washington team has discovered that an ancient survival strategy is still being used in low-oxygen parts of the marine environment.

    “Thinking of arsenic as not just a bad guy, but also as beneficial, has reshaped the way that I view the element,” said first author Jaclyn Saunders, who did the research for her doctoral thesis at the UW and is now a postdoctoral fellow at the Woods Hole Oceanographic Institution and the Massachusetts Institute of Technology.

    The study was published this week in the Proceedings of the National Academy of Sciences.

    1
    Jaclyn Saunders (far right) fixes the line on a McLane instrument that pumps large volumes of seawater in order to extract the DNA. The instrument on the left measures properties such as temperature, salinity and depth and collects smaller samples of seawater. Noelle Held/Woods Hole Oceanographic Institution

    “We’ve known for a long time that there are very low levels of arsenic in the ocean,” said co-author Gabrielle Rocap, a UW professor of oceanography. “But the idea that organisms could be using arsenic to make a living — it’s a whole new metabolism for the open ocean.”

    The researchers analyzed seawater samples from a region below the surface where oxygen is almost absent, forcing life to seek other strategies. These regions may expand under climate change.

    “In some parts of the ocean there’s a sandwich of water where there’s no measurable oxygen,” Rocap said. “The microbes in these regions have to use other elements that act as an ‘electron acceptor’ to extract energy from food.”

    The most common alternatives to oxygen are nitrogen or sulfur. But Saunders’ early investigations suggested arsenic could also work, spurring her to look for the evidence.

    The team analyzed samples collected during a 2012 research cruise to the tropical Pacific, off the coast of Mexico. Genetic analyses on DNA extracted from the seawater found two genetic pathways known to convert arsenic-based molecules as a way to gain energy. The genetic material was targeting two different forms of arsenic, and authors believe that the pathways occur in two organisms that cycle arsenic back and forth between different forms.

    2
    A purple arsenic atom surrounded by four oxygen atoms is arsenate (left). An arsenic atom surrounded by three oxygen atoms is arsenite (right). The study found evidence of marine organisms that can convert one to the other to get energy in oxygen-deficient environments.Wikimedia

    Results suggest that arsenic-breathing microbes make up less than 1% of the microbe population in these waters. The microbes discovered in the water are probably distantly related to the arsenic-breathing microbes found in hot springs or contaminated sites on land.

    “What I think is the coolest thing about these arsenic-respiring microbes existing today in the ocean is that they are expressing the genes for it in an environment that is fairly low in arsenic,” Saunders said. “It opens up the boundaries for where we could look for organisms that are respiring arsenic, in other arsenic-poor environments.”

    3
    California’s Mono Lake is naturally high in arsenic and is known to host microbes that survive by breathing arsenic. The organisms that live in the marine environment are likely related to the ones on land. Pixabay

    Biologists believe the strategy is a holdover from Earth’s early history. During the period when life arose on Earth, oxygen was scarce in both the air and in the ocean. Oxygen became abundant in Earth’s atmosphere only after photosynthesis became widespread and converted carbon dioxide gas into oxygen.

    Early lifeforms had to gain energy using other elements, such as arsenic, which was likely more common in the oceans at that time.

    “We found the genetic signatures of pathways that are still there, remnants of the past ocean that have been maintained until today,” Saunders said.

    Arsenic-breathing populations may grow again under climate change. Low-oxygen regions are projected to expand, and dissolved oxygen is predicted to drop throughout the marine environment.

    “For me, it just shows how much is still out there in the ocean that we don’t know,” Rocap said.

    Saunders recently collected more water samples from the same region and is now trying to grow the arsenic-breathing marine microbes in a lab in order to study them more closely.

    “Right now we’ve got bits and pieces of their genomes, just enough to say that yes, they’re doing this arsenic transformation,” Rocap said. “The next step would be to put together a whole genome and find out what else they can do, and how that organism fits into the environment.”

    Co-author Clara Fuchsman collected the samples and led the DNA sequencing effort as a UW postdoctoral research scientist and now holds a faculty position at the University of Maryland. The other co-author is Cedar McKay, a research scientist in the UW School of Oceanography. The study was funded by a graduate fellowship from NASA and a research grant from the National Science Foundation.

    See the full article here .


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    Please help promote STEM in your local schools.

    Stem Education Coalition

    u-washington-campus
    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 11:55 am on May 6, 2019 Permalink | Reply
    Tags: "Organ bioprinting gets a breath of fresh air", 3D printing replacement organs, , Biology, , ,   

    From Rice University and UW Medicine: “Organ bioprinting gets a breath of fresh air” 

    U Washington
    University of Washington

    UW Medicine Newsroom

    Rice U bloc

    From Rice University

    May 2, 2019
    David Ruth
    713-348-6327
    david@rice.edu

    Jade Boyd
    713-348-6778
    jadeboyd@rice.edu

    Bioengineers clear major hurdle on path to 3D printing replacement organs.

    Bioengineers have cleared a major hurdle on the path to 3D printing replacement organs with a breakthrough technique for bioprinting tissues.

    1
    The May 3 issue of Science features a breakthrough bioprinting technique developed by Rice University bioengineer Jordan Miller and colleagues. (Reprinted with permission from AAAS. Photo by Dan Sazer, Jeff Fitlow and Jordan Miller/Rice University)

    The new innovation allows scientists to create exquisitely entangled vascular networks that mimic the body’s natural passageways for blood, air, lymph and other vital fluids.

    The research is featured on the cover of this week’s issue of Science. It includes a visually stunning proof-of-principle — a hydrogel model of a lung-mimicking air sac in which airways deliver oxygen to surrounding blood vessels. Also reported are experiments to implant bioprinted constructs containing liver cells into mice.

    The work was led by bioengineers Jordan Miller of Rice University and Kelly Stevens of the University of Washington (UW) and included 15 collaborators from Rice, UW, Duke University, Rowan University and Nervous System, a design firm in Somerville, Massachusetts.

    “One of the biggest road blocks to generating functional tissue replacements has been our inability to print the complex vasculature that can supply nutrients to densely populated tissues,” said Miller, assistant professor of bioengineering at Rice’s Brown School of Engineering. “Further, our organs actually contain independent vascular networks — like the airways and blood vessels of the lung or the bile ducts and blood vessels in the liver. These interpenetrating networks are physically and biochemically entangled, and the architecture itself is intimately related to tissue function. Ours is the first bioprinting technology that addresses the challenge of multivascularization in a direct and comprehensive way.”

    Stevens, assistant professor of bioengineering in the UW College of Engineering, assistant professor of pathology in the UW School of Medicine, and an investigator at the UW Medicine Institute for Stem Cell and Regenerative Medicine, said multivascularization is important because form and function often go hand in hand.

    3
    Rice University bioengineering graduate student Bagrat Grigoryan led the development of a new technique for 3D printing tissue with entangled vascular networks similar to the body’s natural passageways for blood, air and other vital fluids. (Photo by Jeff Fitlow/Rice University)

    “Tissue engineering has struggled with this for a generation,” Stevens said. “With this work we can now better ask, ‘If we can print tissues that look and now even breathe more like the healthy tissues in our bodies, will they also then functionally behave more like those tissues?’ This is an important question, because how well a bioprinted tissue functions will affect how successful it will be as a therapy.”

    The goal of bioprinting healthy, functional organs is driven by the need for organ transplants. More than 100,000 people are on transplant waiting lists in the United States alone, and those who do eventually receive donor organs still face a lifetime of immune-suppressing drugs to prevent organ rejection. Bioprinting has attracted intense interest over the past decade because it could theoretically address both problems by allowing doctors to print replacement organs from a patient’s own cells. A ready supply of functional organs could one day be deployed to treat millions of patients worldwide.

    “We envision bioprinting becoming a major component of medicine within the next two decades,” Miller said.

    4
    Rice University bioengineers (from left) Bagrat Grigoryan, Jordan Miller and Daniel Sazer and collaborators created a breakthrough bioprinting technique that could speed development of technology for 3D printing replacement organs and tissues. (Photo by Jeff Fitlow/Rice University)

    “The liver is especially interesting because it performs a mind-boggling 500 functions, likely second only to the brain,” Stevens said. “The liver’s complexity means there is currently no machine or therapy that can replace all its functions when it fails. Bioprinted human organs might someday supply that therapy.”

    To address this challenge, the team created a new open-source bioprinting technology dubbed the “stereolithography apparatus for tissue engineering,” or SLATE. The system uses additive manufacturing to make soft hydrogels one layer at a time.

    Layers are printed from a liquid pre-hydrogel solution that becomes a solid when exposed to blue light. A digital light processing projector shines light from below, displaying sequential 2D slices of the structure at high resolution, with pixel sizes ranging from 10-50 microns. With each layer solidified in turn, an overhead arm raises the growing 3D gel just enough to expose liquid to the next image from the projector. The key insight by Miller and Bagrat Grigoryan, a Rice graduate student and lead co-author of the study, was the addition of food dyes that absorb blue light. These photoabsorbers confine the solidification to a very fine layer. In this way, the system can produce soft, water-based, biocompatible gels with intricate internal architecture in a matter of minutes.

    5
    Rice University bioengineer Daniel Sazer prepares a scale-model of a lung-mimicking air sac for testing. In experiments, air is pumped into the sac in a pattern that mimics breathing while blood is flowed through a surrounding network of blood vessels to oxygenate human red blood cells. (Photo by Jeff Fitlow/Rice University)

    Tests of the lung-mimicking structure showed that the tissues were sturdy enough to avoid bursting during blood flow and pulsatile “breathing,” a rhythmic intake and outflow of air that simulated the pressures and frequencies of human breathing. Tests found that red blood cells could take up oxygen as they flowed through a network of blood vessels surrounding the “breathing” air sac. This movement of oxygen is similar to the gas exchange that occurs in the lung’s alveolar air sacs.

    To design the study’s most complicated lung-mimicking structure, which is featured on the cover of Science, Miller collaborated with study co-authors Jessica Rosenkrantz and Jesse Louis-Rosenberg, co-founders of Nervous System.

    “When we founded Nervous System it was with the goal of adapting algorithms from nature into new ways to design products,” Rosenkrantz said. “We never imagined we’d have the opportunity to bring that back and design living tissues.”

    6
    Experiments performed by Rice University and University of Washington researchers explored whether liver cells called hepatocytes would function normally if they were incorporated into a bioprinted implant and surgically implanted in mice for 14 days. (Image courtesy of Jordan Miller/Rice University)

    In the tests of therapeutic implants for liver disease, the team 3D printed tissues, loaded them with primary liver cells and implanted them into mice. The tissues had separate compartments for blood vessels and liver cells and were implanted in mice with chronic liver injury. Tests showed that the liver cells survived the implantation.

    Miller said the new bioprinting system can also produce intravascular features, like bicuspid valves that allow fluid to flow in only one direction. In humans, intravascular valves are found in the heart, leg veins and complementary networks like the lymphatic system that have no pump to drive flow.

    “With the addition of multivascular and intravascular structure, we’re introducing an extensive set of design freedoms for engineering living tissue,” Miller said. “We now have the freedom to build many of the intricate structures found in the body.”

    Miller and Grigoryan are commercializing key aspects of the research through a Houston-based startup company called Volumetric. The company, which Grigoryan has joined full time, is designing and manufacturing bioprinters and bioinks.

    7
    Assistant professor Kelly Stevens (left) and graduate student Daniel Corbett (right) from the University of Washington Departments of Bioengineering and Pathology helped develop a new method to bioprint liver tissue. (Photo by Dennis R. Wise/University of Washington)

    Miller, a longstanding champion of open-source 3D printing, said all source data from the experiments in the published Science study are freely available [see the Science paper above]. In addition, all 3D printable files needed to build the stereolithography printing apparatus are available, as are the design files for printing each of the hydrogels used in the study.

    See the full Rice university article here .
    See the full U Washington Medicine article here .


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    Stem Education Coalition

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    In his 1912 inaugural address, Rice University president Edgar Odell Lovett set forth an ambitious vision for a great research university in Houston, Texas; one dedicated to excellence across the range of human endeavor. With this bold beginning in mind, and with Rice’s centennial approaching, it is time to ask again what we aspire to in a dynamic and shrinking world in which education and the production of knowledge will play an even greater role. What shall our vision be for Rice as we prepare for its second century, and how ought we to advance over the next decade?

    This was the fundamental question posed in the Call to Conversation, a document released to the Rice community in summer 2005. The Call to Conversation asked us to reexamine many aspects of our enterprise, from our fundamental mission and aspirations to the manner in which we define and achieve excellence. It identified the pressures of a constantly changing and increasingly competitive landscape; it asked us to assess honestly Rice’s comparative strengths and weaknesses; and it called on us to define strategic priorities for the future, an effort that will be a focus of the next phase of this process.

    About UW Medicine

    UW Medicine is one of the top-rated academic medical systems in the world. With a mission to improve the health of the public, UW Medicine educates the next generation of physicians and scientists, leads one of the world’s largest and most comprehensive biomedical research programs, and provides outstanding care to patients from across the globe.

    The UW School of Medicine, part of the UW Medicine system, leads the internationally recognized, community-based WWAMI Program, serving the states of Washington, Wyoming, Alaska, Montana and Idaho. The school has been ranked No. 1 in the nation in primary-care training for more than 20 years by U.S. News & World Report. It is also second in the nation in federal research grants and contracts with $749.9 million in total revenue (fiscal year 2016) according to the Association of American Medical Colleges.

    UW Medicine has more than 27,000 employees and an annual budget of nearly $5 billion. Also part of the UW Medicine system are Airlift Northwest and the UW Physicians practice group, the largest physician practice plan in the region. UW Medicine shares in the ownership and governance of the Seattle Cancer Care Alliance with Fred Hutchinson Cancer Research Center and Seattle Children’s, and also shares in ownership of Children’s University Medical Group with Seattle Children’s.

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 9:31 am on May 4, 2019 Permalink | Reply
    Tags: "Putting vision models to the test", , Biology, , , , Study shows that artificial neural networks can be used to drive brain activity.   

    From MIT News: “Putting vision models to the test” 

    MIT News
    MIT Widget

    From MIT News

    May 2, 2019
    Anne Trafton

    1
    A computer model of vision created by MIT neuroscientists designed these images that can stimulate very high activity in individual neurons. Image: Pouya Bashivan

    Study shows that artificial neural networks can be used to drive brain activity.

    MIT neuroscientists have performed the most rigorous testing yet of computational models that mimic the brain’s visual cortex.

    Using their current best model of the brain’s visual neural network, the researchers designed a new way to precisely control individual neurons and populations of neurons in the middle of that network. In an animal study, the team then showed that the information gained from the computational model enabled them to create images that strongly activated specific brain neurons of their choosing.

    The findings suggest that the current versions of these models are similar enough to the brain that they could be used to control brain states in animals. The study also helps to establish the usefulness of these vision models, which have generated vigorous debate over whether they accurately mimic how the visual cortex works, says James DiCarlo, the head of MIT’s Department of Brain and Cognitive Sciences, an investigator in the McGovern Institute for Brain Research and the Center for Brains, Minds, and Machines, and the senior author of the study.

    “People have questioned whether these models provide understanding of the visual system,” he says. “Rather than debate that in an academic sense, we showed that these models are already powerful enough to enable an important new application. Whether you understand how the model works or not, it’s already useful in that sense.”

    MIT postdocs Pouya Bashivan and Kohitij Kar are the lead authors of the paper, which appears in the May 2 online edition of Science.

    Neural control

    Over the past several years, DiCarlo and others have developed models of the visual system based on artificial neural networks. Each network starts out with an arbitrary architecture consisting of model neurons, or nodes, that can be connected to each other with different strengths, also called weights.

    The researchers then train the models on a library of more than 1 million images. As the researchers show the model each image, along with a label for the most prominent object in the image, such as an airplane or a chair, the model learns to recognize objects by changing the strengths of its connections.

    It’s difficult to determine exactly how the model achieves this kind of recognition, but DiCarlo and his colleagues have previously shown that the “neurons” within these models produce activity patterns very similar to those seen in the animal visual cortex in response to the same images.

    In the new study, the researchers wanted to test whether their models could perform some tasks that previously have not been demonstrated. In particular, they wanted to see if the models could be used to control neural activity in the visual cortex of animals.

    “So far, what has been done with these models is predicting what the neural responses would be to other stimuli that they have not seen before,” Bashivan says. “The main difference here is that we are going one step further and using the models to drive the neurons into desired states.”

    To achieve this, the researchers first created a one-to-one map of neurons in the brain’s visual area V4 to nodes in the computational model. They did this by showing images to animals and to the models, and comparing their responses to the same images. There are millions of neurons in area V4, but for this study, the researchers created maps for subpopulations of five to 40 neurons at a time.

    “Once each neuron has an assignment, the model allows you to make predictions about that neuron,” DiCarlo says.

    The researchers then set out to see if they could use those predictions to control the activity of individual neurons in the visual cortex. The first type of control, which they called “stretching,” involves showing an image that will drive the activity of a specific neuron far beyond the activity usually elicited by “natural” images similar to those used to train the neural networks.

    The researchers found that when they showed animals these “synthetic” images, which are created by the models and do not resemble natural objects, the target neurons did respond as expected. On average, the neurons showed about 40 percent more activity in response to these images than when they were shown natural images like those used to train the model. This kind of control has never been reported before.

    “That they succeeded in doing this is really amazing. It’s as if, for that neuron at least, its ideal image suddenly leaped into focus. The neuron was suddenly presented with the stimulus it had always been searching for,” says Aaron Batista, an associate professor of bioengineering at the University of Pittsburgh, who was not involved in the study. “This is a remarkable idea, and to pull it off is quite a feat. It is perhaps the strongest validation so far of the use of artificial neural networks to understand real neural networks.”

    In a similar set of experiments, the researchers attempted to generate images that would drive one neuron maximally while also keeping the activity in nearby neurons very low, a more difficult task. For most of the neurons they tested, the researchers were able to enhance the activity of the target neuron with little increase in the surrounding neurons.

    “A common trend in neuroscience is that experimental data collection and computational modeling are executed somewhat independently, resulting in very little model validation, and thus no measurable progress. Our efforts bring back to life this ‘closed loop’ approach, engaging model predictions and neural measurements that are critical to the success of building and testing models that will most resemble the brain,” Kar says.

    Measuring accuracy

    The researchers also showed that they could use the model to predict how neurons of area V4 would respond to synthetic images. Most previous tests of these models have used the same type of naturalistic images that were used to train the model. The MIT team found that the models were about 54 percent accurate at predicting how the brain would respond to the synthetic images, compared to nearly 90 percent accuracy when the natural images are used.

    “In a sense, we’re quantifying how accurate these models are at making predictions outside the domain where they were trained,” Bashivan says. “Ideally the model should be able to predict accurately no matter what the input is.”

    The researchers now hope to improve the models’ accuracy by allowing them to incorporate the new information they learn from seeing the synthetic images, which was not done in this study.

    This kind of control could be useful for neuroscientists who want to study how different neurons interact with each other, and how they might be connected, the researchers say. Farther in the future, this approach could potentially be useful for treating mood disorders such as depression. The researchers are now working on extending their model to the inferotemporal cortex, which feeds into the amygdala, which is involved in processing emotions.

    “If we had a good model of the neurons that are engaged in experiencing emotions or causing various kinds of disorders, then we could use that model to drive the neurons in a way that would help to ameliorate those disorders,” Bashivan says.

    The research was funded by the Intelligence Advanced Research Projects Agency, the MIT-IBM Watson AI Lab, the National Eye Institute, and the Office of Naval Research.

    See the full article here .


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