Tech

Simple, solar-powered water desalination

image: Tests on an MIT building rooftop showed that a simple proof-of-concept desalination device could produce clean, drinkable water at a rate equivalent to more than 1.5 gallons per hour for each square meter of solar collecting area.

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Image courtesy of Lenan Zhang, Lin Zhao, Zhenyuan Xu, Evelyn Wang, et. al

A completely passive solar-powered desalination system developed by researchers at MIT and in China could provide more than 1.5 gallons of fresh drinking water per hour for every square meter of solar collecting area. Such systems could potentially serve off-grid arid coastal areas to provide an efficient, low-cost water source.

The system uses multiple layers of flat solar evaporators and condensers, lined up in a vertical array and topped with transparent aerogel insulation. It is described in a paper appearing today in the journal Energy and Environmental Science, authored by MIT doctoral students Lenan Zhang and Lin Zhao, postdoc Zhenyuan Xu, professor of mechanical engineering and department head Evelyn Wang, and eight others at MIT and at Shanghai Jiao Tong University in China.

The key to the system's efficiency lies in the way it uses each of the multiple stages to desalinate the water. At each stage, heat released by the previous stage is harnessed instead of wasted. In this way, the team's demonstration device can achieve an overall efficiency of 385 percent in converting the energy of sunlight into the energy of water evaporation.

The device is essentially a multilayer solar still, with a set of evaporating and condensing components like those used to distill liquor. It uses flat panels to absorb heat and then transfer that heat to a layer of water so that it begins to evaporate. The vapor then condenses on the next panel. That water gets collected, while the heat from the vapor condensation gets passed to the next layer.

Whenever vapor condenses on a surface, it releases heat; in typical condenser systems, that heat is simply lost to the environment. But in this multilayer evaporator the released heat flows to the next evaporating layer, recycling the solar heat and boosting the overall efficiency.

"When you condense water, you release energy as heat," Wang says. "If you have more than one stage, you can take advantage of that heat."

Adding more layers increases the conversion efficiency for producing potable water, but each layer also adds cost and bulk to the system. The team settled on a 10-stage system for their proof-of-concept device, which was tested on an MIT building rooftop. The system delivered pure water that exceeded city drinking water standards, at a rate of 5.78 liters per square meter (about 1.52 gallons per 11 square feet) of solar collecting area. This is more than two times as much as the record amount previously produced by any such passive solar-powered desalination system, Wang says.

Theoretically, with more desalination stages and further optimization, such systems could reach overall efficiency levels as high as 700 or 800 percent, Zhang says.

Unlike some desalination systems, there is no accumulation of salt or concentrated brines to be disposed of. In a free-floating configuration, any salt that accumulates during the day would simply be carried back out at night through the wicking material and back into the seawater, according to the researchers.

Their demonstration unit was built mostly from inexpensive, readily available materials such as a commercial black solar absorber and paper towels for a capillary wick to carry the water into contact with the solar absorber. In most other attempts to make passive solar desalination systems, the solar absorber material and the wicking material have been a single component, which requires specialized and expensive materials, Wang says. "We've been able to decouple these two."

The most expensive component of the prototype is a layer of transparent aerogel used as an insulator at the top of the stack, but the team suggests other less expensive insulators could be used as an alternative. (The aerogel itself is made from dirt-cheap silica but requires specialized drying equipment for its manufacture.)

Wang emphasizes that the team's key contribution is a framework for understanding how to optimize such multistage passive systems, which they call thermally localized multistage desalination. The formulas they developed could likely be applied to a variety of materials and device architectures, allowing for further optimization of systems based on different scales of operation or local conditions and materials.

One possible configuration would be floating panels on a body of saltwater such as an impoundment pond. These could constantly and passively deliver fresh water through pipes to the shore, as long as the sun shines each day. Other systems could be designed to serve a single household, perhaps using a flat panel on a large shallow tank of seawater that is pumped or carried in. The team estimates that a system with a roughly 1-square-meter solar collecting area could meet the daily drinking water needs of one person. In production, they think a system built to serve the needs of a family might be built for around $100.

The researchers plan further experiments to continue to optimize the choice of materials and configurations, and to test the durability of the system under realistic conditions. They also will work on translating the design of their lab-scale device into a something that would be suitable for use by consumers. The hope is that it could ultimately play a role in alleviating water scarcity in parts of the developing world where reliable electricity is scarce but seawater and sunlight are abundant.

Credit: 
Massachusetts Institute of Technology

Bacterial influencers -- rhizosphere microbiome mediates root metabolite exudation

image: Bacterial communities trigger systemic signals that lead to regulatory and metabolic changes in distant roots, as well as in green parts of the plant. One function of such signaling is root system-wide management of the rhizosphere microbiota via exudation of specific molecules to the soil.

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J. Szymanski / IPK

Gatersleben, 07.02.2020 Roots are plant organs, that typically absorb water and minerals from soil. It is lesser known that roots also secrete metabolites, so-called root exudates, which impact the properties of soil directly around the root. This thin layer of soil is called the rhizosphere and is home to a rich microbial diversity, the root microbiota. By producing certain exudates, plants communicate with and govern the microbial life within their rhizosphere for their own benefit. Now, researchers have discovered that this is not a one-way process. Whilst investigating tomato plants, they found that the microbiota can also systemically shape and control root exudation.

When thinking of ecological hotspots, roots and the earth surrounding them might not immediately spring to mind. However, precisely this region, the rhizosphere, is considered as one of the most complex ecosystems found on earth. It harbours a divers microbiotic community, including numerous bacteria, fungi and archaea, thriving in an environment rich in biochemical compounds, that are exuded by plant roots at the core of the rhizosphere.

Plants govern the rhizosphere microbiota and shape the soil physical and chemical properties through their root exudates. At the same time, it is well known that roots sense changes in the rhizosphere and trigger systemic responses to defend against pathogens or to adjust to changes in nutrient availability. Nonetheless, there are still many open questions regarding the dynamics and impact of the microbiota on the root itself, and it was not clear how, or whether at all, the rhizosphere microbiota affects the root exudation. An international research team led by Dr. Elisa Korenblum, a scientist from the Weizmann Institute of Science in Israel in collaboration with Dr. Jedrzej Szymanski from the Leibniz Institute IPK in Gatersleben, recently took on this question whilst investigating roots of tomato plants.

Dr Korenblum and her team conducted and analysed a row of split-root experiments, where half of roots of each plant was exposed to a microbiome-rich soil, and the other half was grown in sterile and biochemically ambient conditions. This enabled them to investigate the effect of different microbial communities on the local root system, as well as the systemic changes in the distant roots in anticipation of the presence of new microorganisms. Dr. Szymanski, head of the Network Analysis and Modelling group, traced the complex network of biochemical and gene expression signals controlling this microbiome-root communication and their propagation from the place of origin to distant roots. They thereby discovered that the tomato rhizosphere microbiome can directly affect the chemical composition of roots and root exudates via a systemic root-to-root signalling mechanism. For example, bacteria of the genus Bacillus use this process, which the scientists termed Systemically Induced Root Exudation of Metabolites (SIREM), to trigger the secretion of acylsugars in the whole root system.

The discovery of SIREM is a first step towards untangling the regulatory network spanning the complex plant root-microbial relationship. It is likely that the SIREM process is a key feature of root-microbiota interactions within the rhizosphere, and that the microbiome-reprogrammed systemic root exudation promotes soil conditioning. The precise extent of the regulatory role and incidence of SIREM is yet to be determined.

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Leibniz Institute of Plant Genetics and Crop Plant Research

Designer proteins

image: David Baker,PhD, Director of the Institute for Protein Design with Dr. Neil King.

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Ian C Haydon / UW Institute for Protein Design

Proteins are the molecular machines that make all living things hum -- they stop deadly infections, heal cells and capture energy from the sun. Yet because our basic understanding of how proteins work has until now remained a mystery, humans have only been able to harness the power of proteins by modifying ones we happen to find in nature. This is beginning to change. Enabled by decades of basic research, the rise of inexpensive computing, and the genomics revolution in reading and writing DNA, scientists can now design new proteins from scratch with specific functions.

David Baker, Professor of Biochemistry and Director of the Institute for Protein Design at the University of Washington will speak about how algorithmic processes such as de novo design predict protein structures, protein folding mechanisms, and new protein functions. Computational protein design is now being used to create proteins with novel structures using iterative structure prediction and experimental structure characterization. These results suggest that new proteins -- encoded by synthetic genes --can be designed on computers with atomic-level accuracy.

In April 2019, the Institute for Protein Design (IPD) was selected as part of The Audacious Project, a successor to the TED Prize. As a result, the IPD is expanding its research on vaccine design, targeted drug delivery, 'smart' therapeutics, next-generation nanomaterials and more.

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ETH Zurich

Synthetic biology: Risk reduction, uncertainty and ethics

image: Joyce Tait, Director of the Innogen Institute at the University of Edinburgh.

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Innogen Institute

Joyce Tait, Innogen Founder and co-Director, has an interdisciplinary background in natural and social sciences including risk assessment and regulation, policy analysis, technology management, strategic and operational decision making in companies and public bodies. Tait speaks about re-engineering biological components through computational modelling and bio-systems design technologies and how they will require new frameworks for adaptive and responsible regulation that takes account of the relevant benefits and risks and also of the needs and wants of the full spectrum of stakeholders. It will be vital to achieve an equitable balance between promoting innovation and ensuring safety.

This talk will describe a systemic approach to risk management, uncertainty and stakeholder engagement to enable these design technologies to deliver their full potential to address today's global challenges for human health and the future environment.

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ETH Zurich

Generalist diet helps invasive crayfish thrive where it's introduced

image: The rusty crayfish is native to the Ohio River Valley but has been found in streams as far away as Minnesota, Wisconsin, Maine and Ontario, Canada.

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Andrew Higley/UC Creative Services

An invasive species of crayfish that is taking over streams from Minnesota to Maine might be successful because it's not a fussy eater, according to biologists with the University of Cincinnati.

In lab "taste tests," this crayfish native to the Ohio River valley displayed no preference for protein or plants, even after weeks on an exclusive diet of one or the other, according to a new UC study. The crayfish has more cellulose-digesting bacteria when its diet is restricted to plants.

"They tend to be more aggressive than native crayfish," said Mark Tran, a UC biologist who led the project. "They have relatively large claws compared to their body size. They will either force the other crayfish out or outcompete them for food."

Tran and his colleagues presented findings from two studies at the Society for Integrative and Comparative Biology conference in January.

The rusty crayfish looks like a little bronze lobster with its thick body and formidable pincers. It is native to creeks and ponds in Ohio, northern Kentucky and Indiana.

Wildlife managers suspect fishermen who catch rusty crayfish for bait introduced them into streams as far away as Oregon and Canada, where they are outcompeting native crayfish and destroying fish nurseries with their ravenous appetites. According to the Minnesota Sea Grant, the hungry crayfish feed on aquatic vegetation along with invertebrates that baby fish eat.

"The irony is that bass fishermen are responsible for releasing them into waters where they end up reducing the native sportfish population," said Tran, an assistant professor of biology for UC Blue Ash.

In Canada, Ontario took the extraordinary step of outlawing the transport of any crayfish anywhere in the province to try to stop the rusty crayfish from spreading. Fishermen there have to catch crayfish for bait in the same waters they fish.

"They tend to be opportunistic," Tran said. "They will actively kill things and eat them. But in the streams we studied, they tend to be more omnivorous. They eat a lot of plant material and supplement it with dead fish or eggs they find."

For the project, UC obtained a collection permit from the Great Parks of Hamilton County. Students collected 40 female crayfish from a suburban Cincinnati creek. Half were fed a plant-based diet; the others a meat-based diet.

After a month, the crayfish with the vegetarian diet had more cellulose-digesting bacteria compared to the meat-eating crayfish.

"Plants can be hard to digest because of their cell walls," Tran said. "To get nutrients from the plants, they need bacteria in their gut that can digest that cell wall. Rusty crayfish have a digestive system that is good at breaking down the plant's cell walls."

After a month on the strict diet, the crayfish were presented a choice of protein- or plant-based food through plastic tubes in an experimental arena. During a second trial, students offered each crayfish the two food choices in its individual habitat container.

Surprisingly, researchers found variety is not the spice of life for crayfish. The crayfish expressed no statistically significant preference for one food over another in either experiment despite their monthlong restricted diet.

The findings support what is known about rusty crayfish - they are generalists that will eat almost anything, which helps to explain why they are so successful colonizing new habitats where they are introduced as invasive species.

"Unfortunately, rusty crayfish are well established in Ontario and cannot be eradicated," said Jolanta Kowalski, a spokeswoman for the Ontario Ministry of Natural Resources and Forestry. "The introduction of the species occurred in the 1960s and they have become well established."

This was the third year of UC's crayfish project, which was conceived to give undergraduate students lab experience, associate professor Keen Wilson said.

"The point is to give students an introduction to a variety of biology specialties," Wilson said.

"For example, I don't go outside. I know that about myself, so I stick to lab work," he said. "But you might not know that about yourself as a freshman. So you go out in the field and collect crayfish and say, 'I'll never do that again as long as I live.' But you might love working in the lab or looking at the microbiology plates."

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University of Cincinnati

No clear path for golden rice to reach consumers

image: Rice fields in the Cordillera mountains of northern Luzon, the Philippines. A new study based on surveys and interviews of more than 115 rice farmers in the Nueva Ecija region, part of the 'rice bowl' of the Philippines, finds that that most families at risk for Vitamin A deficiency can't grow Golden Rice themselves, and most commercial farmers won't grow it either.

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Courtesy Glenn Davis Stone, Washington University in St. Louis

Heralded as a genetically modified crop with the potential to save millions of lives, Golden Rice has just been approved as safe for human and animal consumption by regulators in the Philippines. The rice is a beta carotene-enriched crop that is intended to reduce Vitamin A deficiency (VAD), a health problem in very poor areas.

But a new study finds that most families at risk for VAD can't grow Golden Rice themselves, and most commercial farmers won't grow it either.

"Many families with Vitamin A deficient kids don't even have rice land to plant it," said Glenn Davis Stone, professor of sociocultural anthropology and environmental studies in Arts & Sciences at Washington University in St. Louis and co-author of a new paper in the journal Technology in Society. "And those in the mountains won't plant it because it has been bred into the lowland varieties of rice known as IR-64 and RSC-82."

The regulatory approval in the Philippines is a landmark for the scientists who developed Golden Rice for nutritional purposes. It is the first such approval in the developing world. But even after nearly three decades of development, Golden Rice is still beset by problems, according to Stone.

Golden Rice still has to be approved for commercial sale, and it still needs a company to grow marketable quantities of seed. And even then, Stone argues, there is no clear path for the rice to get to poor children.

Stone, an internationally recognized expert on the human side of global agricultural trends, was an early advocate for keeping an open mind about 'humanitarian' GMO crops, such as Golden Rice. Since 2013, he has directed a major Templeton Foundation-funded research project on rice in the Philippines.

Stone's new study is based on surveys and interviews of more than 115 rice farmers in the Nueva Ecija region, considered part of the 'rice bowl' of the Philippines.

Writing in the Feb. 7 issue of The Conversation, Stone and his study co-author Dominic Glover, a rice researcher at the Institute for Development Studies at the University of Sussex, suggest that backers of Golden Rice -- and even some economists who have tried to project its health impacts -- have made certain flawed assumptions about farmers' willingness to plant the crop.

"The old claim, repeated again in a recent book, that Golden Rice was 'basically ready for use in 2002' is silly," Stone and Glover wrote. "As recently as 2017, IRRI made it clear that Golden Rice still had to be 'successfully developed into rice varieties suitable for Asia, approved by national regulators, and shown to improve vitamin A status in community conditions.'

"The Philippines has managed to cut its childhood VAD rate in half with conventional nutrition programs. If Golden Rice appears on the market in the Philippines by 2022, it will have taken over 30 years of development to create a product that may not affect vitamin levels in its target population, and that farmers may need to be paid to plant."

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Washington University in St. Louis

New CAR-T target yields promising results for multiple myeloma

image: Left to right: Drs. Atanackovic, Luetkens, and Radhakrishnan

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Huntsman Cancer Institute at the University of Utah

Too many patients with cancers like multiple myeloma relapse after treatment. This grim reality motivated researchers at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) to try to improve the depth and durability of treatment response in multiple myeloma through a new cancer cell targeting mechanism. Multiple myeloma is the second most common blood cancer and develops in the bone marrow. Approximately 30,000 new cases are diagnosed each year, and almost all patients eventually succumb to their disease.

In research published today in the journal Nature Communications, the Utah-based scientists describe a novel way to treat cancers using chimeric antigen receptor (CAR) T cell therapy. Laboratory tests using mouse models and tumor cells from patients displayed promising results for this novel cellular immunotherapy for multiple myeloma and other types of blood cancer.

The Utah-based scientists developed CAR T cells that target a molecule, CD229, that is present on the cancer cells of patients with myeloma throughout the course of their disease. Importantly, CD229 is also present on myeloma stem cells, which are the source of treatment-resistant tumor cells in patients who relapse.

Immunotherapies that activate a patient's own immune system to fight their cancer have proven to be highly effective for many types of blood cancers. In CAR T cell therapy, doctors take T cells from a patient's blood and engineer them to recognize and attack cancer cells via an added "hook," called a CAR, that recognizes a surface molecule on cancer cells. Engineered CAR T cells are returned to patients via intravenous infusion. The CAR T cells then find, attack, and destroy cancer cells in the patient's body. While these approaches have demonstrated remarkable progress and long-term results for some, many patients experience only brief improvement, followed by recurrence of their disease.

The study was led by Djordje Atanackovic, MD, a physician-scientist at HCI and an associate professor of internal medicine, division of hematology and hematologic malignancies at the U of U, who cares for patients with multiple myeloma. The study builds on earlier work by Atanackovic and his colleagues in which they identified CD229 as present on multiple myeloma and other B cell cancer cells. Once the CD229 target had been identified, it took several years to complete the complicated engineering and laboratory work to test whether CD229 was a viable new agent for a CAR T approach.

"We were dismayed that although some of our patients respond quite well to currently available immunotherapies, they relapsed as early as one year after treatment," says Atanackovic. "We thought if we could target every last cancer cell in a patient's body, including the cancer stem cell, this could make the critical difference and yield more durable, deeper responses to treatment."

HCI researchers Tim Luetkens, MD, an expert in cell and protein engineering, and Sabarinath Radhakrishnan, MD, assistant professor of internal medicine at the U of U, led the development of the therapy in Atanackovic's lab. They engineered the first fully human antibody against CD229 and, with this newly engineered "hook," produced CAR T cells targeting CD229. They confirmed their hypothesis CD229 CAR T kills mature multiple myeloma cells, as well as myeloma stem cells, using a mouse model, as well as stem cells derived from myeloma patients. They also showed that in this laboratory setting, the tumors treated with CD229 CAR T appeared to result in long-lasting responses.

The team plans to complete further analyses to understand whether this approach can be safely used in humans. They hope to open clinical trials to further understand the potential of CD229 as a novel therapy for multiple myeloma.

"An impressive set of resources and collaborators in Utah really enabled this study to progress," said Atanackovic. "Having access to tissues from patients willing to share their blood and bone marrow for research, working in partnership with other scientists providing their expertise, and receiving small grants to support early phases of this research have all been critical to our study. We have made remarkable progress on addressing a problem I see in my patients each day I am in the clinic."

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Huntsman Cancer Institute

Discovery paves path forward in the fight against the deadliest form of malaria

image: Plasmodium falciparum, a parasite that causes cerebral malaria.

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the global panorama

Scientists have identified a key molecule involved in the development of cerebral malaria, a deadly form of the tropical disease. The study identifies a potential drug target and way forward toward alleviating this condition for which few targeted treatments are available.

In studies with mice, investigators discovered that the EphA2 protein is important for onset of leaky brain, a hallmark symptom of cerebral malaria. The team also demonstrated that blocking EphA2 with different drugs prevented this dangerous symptom from occurring. According to the researchers, the findings indicate that a similar therapeutic strategy could potentially prevent the disease in humans.

"The advance is really significant," says Tracey Lamb, Ph.D., senior author of the study and associate professor in Pathology at University of Utah Health. "New targets to block a leaky brain in malaria are urgently needed to prevent mortality from cerebral malaria".

The research, led by scientists at U of U Health in collaboration with Centre Pasteur du Cameroun in Cameroon, appears online in the journal PLOS Pathogens.

Cerebral malaria strikes more than 575,000 each year, disproportionately affecting young children in sub-Saharan Africa. The tropical disease causes fluids to leak from the brain, and coma, eventually killing 20% of those who are infected. Among survivors, 80% develop long-term neurodevelopmental symptoms including seizures and mental health disorders.

Disruption of the blood brain barrier is a critical step in the pathogenesis of cerebral malaria that makes the disease so deadly. True to its name, the blood brain barrier is made up of cells that line blood vessels and fit together tightly, assembling into a barricade. The semi-permeable cell wall keeps fluids from the nervous system from mixing with the bloodstream while allowing essential metabolites to pass through.

Researchers took note of EphA2 when they saw that the molecule became activated at the site of the blood brain barrier just prior to its breakdown. Further investigation showed that EphA2 disrupts the blood brain barrier by loosening the tight junctions between cells, removing the glue that keeps these cells bound to each other.

With a key player identified, the scientists wondered whether blocking EphA2 would protect the blood brain barrier during infection. Treating infected mice with two different agents showed this seems to be the case. One agent was a repurposed cancer drug, Nilotinib, that inhibits several molecules including EphA2. The second was an engineered protein that specifically blocked molecules called ephrin ligands that will interact with EphA2 and prevent its activation.

According to the study's first author Thayer Darling, Ph.D., it is notable that both therapeutics were effective when given four days after infection. They did not need to be administered as a preventive prior to infection which can be difficult to do in a real-world situation.

"Usually children are not brought in to the clinic until they're already experiencing symptoms of malaria," says Darling, who carried out the research as a graduate student with Lamb. "We're hopeful that therapeutics that target EphA2 may be able to prevent cerebral malaria in children after the onset of those initial symptoms."

The work was primarily conducted in laboratory mice but additional results show clinical relevance. Blood from children with symptoms of cerebral malaria have elevated levels of an Ephrin protein that binds EphA2. Finding the marker in these children suggests the same pathway mediates the disease in both mice and humans.

"Understanding how infection with malaria parasites can lead to deleterious neurological conditions is key to discovering new therapeutic means to curb malaria-associated deaths globally," says co-author Lawrence Ayong, Ph.D., a professor at Centre Pasteur du Cameroun. "This research is very exciting and leads the way for future studies focused on modulating the activity of this protein in humans as a way to prevent malaria-associated deaths in children."

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University of Utah Health

CRISPR-edited immune cells can survive and thrive after infusion into cancer patients

image: Graphic showing genetic alternations of cells tested in trial

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Joseph Fraietta, PhD, University of Pennsylvania

PHILADELPHIA - Genetically-edited immune cells can persist, thrive, and function months after a cancer patient receives them, according to new data published by researchers from the Abramson Cancer Center of the University of Pennsylvania. The team showed cells removed from patients and brought back into the lab setting were able to kill cancer months after their original manufacturing and infusion. Further analysis of these cells confirmed they were successfully edited in three specific ways, marking the first-ever sanctioned investigational use of multiple edits to the human genome. This is the first U.S. clinical trial to test the gene editing approach in humans, and the publication of this new data today in Science follows on the initial report last year that researchers were able to use CRISPR/Cas9 technology to successfully edit three cancer patients' immune cells. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics.

"Our data from the first three patients enrolled in this clinical trial demonstrate two important things that, to our knowledge, no one has ever shown before. First, we can successfully perform multiple edits with precision during manufacturing, with the resulting cells surviving longer in the human body than any previously published data have shown. Second, thus far, these cells have shown a sustained ability to attack and kill tumors," said Carl June, MD, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine at the University of Pennsylvania and the study's senior author.

The findings are the latest milestone in Penn's history as cellular and gene therapy pioneers, including development of the first FDA-approved CAR T cell therapy, Kymriah, for pediatric and adult blood cancer patients.

Patients on this trial were treated by Edward A. Stadtmauer, MD, section chief of Hematologic Malignancies at Penn, who is the co-lead author on the study along with Joseph A. Fraietta, PhD, an assistant professor of Microbiology at Penn. The co-senior author is Simon F. Lacey, PhD, director of the Translational and Correlative Studies Laboratory in the Center for Cellular Immunotherapies.

The approach in this study is closely related to CAR T cell therapy, in which patient immune cells are engineered to fight cancer, but it has some key differences. Just like CAR T, researchers in this study began by collecting a patient's T cells from blood. However, instead of arming these cells with a receptor against a protein such as CD19, the team first used CRISPR/Cas9 editing to remove three genes. The first two edits removed a T cell's natural receptors so they can be reprogrammed to express a synthetic T cell receptor, allowing these cells to seek out and destroy tumors. The third edit removed PD-1, a natural checkpoint that sometimes blocks T cells from doing their job.

"This new analysis of the three patients has confirmed that the manufactured cells contained all three edits, providing proof of concept for this approach. This is the first confirmation of the ability of CRISPR/Cas9 technology to target multiple genes at the same time in humans and illustrates the potential of this technology to treat many diseases that were previously not able to be treated or cured," June said.

Once the three genes are knocked out, a fourth genetic modification was accomplished using a lentivirus to insert the cancer-specific synthetic T cell receptor, which tells the edited T cells to target an antigen called NY-ESO-1. Previously published data show these cells typically survive for less than a week, but this new analysis shows the edited cells used in this study persisted, with the longest follow up at nine months.

Several months after the infusion, researchers drew more blood and isolated the CRISPR-edited cells for study. When brought back into the lab setting, the cells were still able to kill tumors.

"Previous studies have shown these cells lose function within days, so the fact that the CRISPR-edited cells in this study retained anti-tumor function for a significantly longer period of time after a single infusion is very encouraging," June said.

The CRISPR-edited T cells used in this study are not active on their own like CAR T cells. Instead, they require the cooperation of a molecule known as HLA-A*02:01, which is only expressed in a subset of patients. This means that patients had to be screened ahead of time to make sure they were a match for the approach. Participants who met the requirements received other clinically-indicated therapy as needed while they waited for their cells to be manufactured. Once that process was completed, all three patients received the gene-edited cells in a single infusion after a short course of chemotherapy. Analysis of blood samples revealed that all three participants had the CRISPR-edited T cells take root and thrive in the patients. While none responded to the therapy, there were no treatment-related serious adverse events.

CRISPR technology has not previously been tested in humans in the U.S. Investigators at Penn have pioneered a number of other "first uses" of engineered T cells over the past decade. Even with that experience, moving this work into the clinic while ensuring appropriate patient safeguards meant the research team had to move through a comprehensive and rigorous series of institutional and federal regulatory approval steps, including approval by the National Institutes of Health's Recombinant DNA Research Advisory Committee and review by the U.S. Food and Drug Administration, as well as Penn's institutional review board and institutional biosafety committee. The entire process required more than two years.
Researchers say these new data will open the door to later stage studies to investigate and extend this approach to a broader field beyond cancer, several of which are already planned at Penn.

Credit: 
University of Pennsylvania School of Medicine

Sequencing sewage for antimicrobial resistance surveillance

In this Policy Forum, Frank Aarestrup and Mark Woolhouse advocate for the immediate establishment of a global antimicrobial resistance surveillance system based on the metagenomic sequencing of human sewage. Most current antimicrobial resistance (AMR) surveillance approaches focus on hospitalized patients in clinical environments. According to the authors, these approaches likely lead to biased understandings and underestimations of AMR spread in healthy humans or for the great majority of commonly used antimicrobial treatments. Raw sewage could provide a potentially powerful tool to accompany clinical AMR surveillance, these authors say. It anonymously combines material from a large and diverse population, which would be unfeasible to monitor otherwise. It has already been used to evaluate the usage of illegal drugs, pharmaceuticals, alcohol, nicotine and caffeine as well as to monitor polio. What's more, recent metagenomic studies have demonstrated the ability to describe the full profile of AMR-genes within human populations by measuring sewage. According to Aarestrup and Woolhouse, sewage-based AMR surveillance would be a valuable addition to the current efforts to combat AMR worldwide. They suggest that such a system could also be useful in identifying and tracking other significant public health concerns, including new and emergent intestinal and food-borne pathogens. The authors estimate that an effective continuous surveillance system could be established globally for less than $1 million USD annually - far cheaper than the annual cost of conventional approaches.

Credit: 
American Association for the Advancement of Science (AAAS)

Study: Two enzymes control liver damage in NASH

image: Suppression of the enzyme AMPK and activation of caspase-6, an enzyme involved in apoptosis or programmed cell death (in red), allows nonalcoholic steatohepatitis (NASH) to progress to liver cell death.

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UC San Diego Health Sciences

As much as 12 percent of adults in the United States are living with nonalcoholic steatohepatitis (NASH), an aggressive condition that can lead to cirrhosis or liver cancer. After identifying a molecular pathway that allows NASH to progress into liver cell death, University of California San Diego School of Medicine researchers were able to halt further liver damage in mouse models with NASH.

"We know that fatty liver causes inflammation and scarring in the organ and that it progresses to cirrhosis, liver cancer and liver failure," said senior author Alan Saltiel, PhD, director of the UC San Diego Institute for Diabetes and Metabolic Health. "What has never been clear is the trigger that allows the transition from chronic inflammation to cell death. We now see that there is a linear progression to liver failure and we found a way to stop it in mice."

The switch, report researchers in the February 7, 2020 online edition of Science, comes from the suppression of the enzyme AMPK, one of the master regulators of energy expenditure, and the increase in activity of caspase-6, an enzyme involved in apoptosis or programmed cell death.

When AMPK activity is low, a cell's ability to burn calories decreases, resulting in fat storage. The team fed mice a high-fat diet and turned AMPK off, expecting that their fatty liver condition would worsen, but it did not. However, progression to NASH and liver failure did.

"We were surprised to see that manipulating AMPK did not dramatically regulate metabolism as we presumed it would, but rather it seemed to be regulating something in transition from fatty liver to NASH and from NASH to hepatocellular cell death," said Saltiel. "In this case, AMPK acted as a sensor, keeping cell death in check. When AMPK activity was lost, cell death proceeded unchecked. It turns out that AMPK blocks activity of caspase-6, so when AMPK activity drops, caspase-6 is unleashed, acting as a death signal for liver cells."

Armed with this new understanding of the roles of AMPK and caspase-6, the team applied an AMPK activator, decreasing caspase-6 activity. While this action did not halt fatty liver, it did stop progression from fatty liver to NASH and subsequent liver cell death. The same result occurred when the team used a caspase-6 inhibitor.

"Caspase-6 was elevated in both mouse models and in samples from human patients who have NASH," said Saltiel. "Our study identifies two possible targets for putting the brakes on further liver damage. Both AMPK activators and caspase-6 inhibitors prevented the molecular pathway leading to sustained liver cell death."

The team is now developing caspase-6 inhibitors for further testing.

Credit: 
University of California - San Diego

Water-conducting membrane allows carbon dioxide to transform into fuel more efficiently

TROY, N.Y. -- Methanol is a versatile and efficient chemical used as fuel in the production of countless products. Carbon dioxide (CO2), on the other hand, is a greenhouse gas that is the unwanted byproduct of many industrial processes.

Converting CO2 to methanol is one way to put CO2 to good use. In research published today in Science, chemical engineers from Rensselaer Polytechnic Institute demonstrated how to make that conversion process from CO2 to methanol more efficient by using a highly effective separation membrane they produced. This breakthrough, the researchers said, could improve a number of industry processes that depend on chemical reactions where water is a byproduct.

For example, the chemical reaction responsible for the transformation of CO2 into methanol also produces water, which severely restricts the continued reaction. The Rensselaer team set out to find a way to filter out the water as the reaction is happening, without losing other essential gas molecules.

The researchers assembled a membrane made up of sodium ions and zeolite crystals that was able to carefully and quickly permeate water through small pores -- known as water-conduction nanochannels -- without losing gas molecules.

"The sodium can actually regulate, or tune, gas permeation," said Miao Yu, an endowed chair professor of chemical and biological engineering and a member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer, who led this research. "It's like the sodium ions are standing at the gate and only allow water to go through. When the inert gas comes in, the ions will block the gas."

In the past, Yu said, this type of membrane was susceptible to defects that would allow other gas molecules to leak out. His team developed a new strategy to optimize the assembly of the crystals, which eliminated those defects.

When water was effectively removed from the process, Yu said, the team found that the chemical reaction was able to happen very quickly.

"When we can remove the water, the equilibrium shifts, which means more CO2 will be converted and more methanol will be produced," said Huazheng Li, a postdoctoral researcher at Rensselaer and first author on the paper.

"This research is a prime example of the significant contributions Professor Yu and his team are making to address interdisciplinary challenges in the area of water, energy, and the environment," said Deepak Vashishth, director of CBIS. "Development and deployment of such tailored membranes by Professor Yu's group promise to be highly effective and practical."

The team is now working to develop a scalable process and a startup company that would allow this membrane to be used commercially to produce high purity methanol.

Yu said this membrane could also be used to improve a number of other reactions.

"In industry there are so many reactions limited by water," Yu said. "This is the only membrane that can work highly efficiently under the harsh reaction conditions."

Credit: 
Rensselaer Polytechnic Institute

What is your risk from smoking? Your network knows!

How many people will die from tobacco use in developed countries in 2030?

A new study from researchers at the Annenberg School for Communication found that most people, smokers and non-smokers alike, were nowhere near accurate in their answers to this and other questions about smoking's health effects. But critically, the study, conducted by doctoral candidate Douglas Guilbeault and Professor Damon Centola, found a way to help people be more accurate in their assessment of smoking's risks: discussing their ideas with other people.

"We talk a lot today about misinformation, but another problem is misunderstanding," says Centola. "Even if the information being disseminated is factual, people can nevertheless misunderstand or misinterpret that information."

The information shared in public health campaigns and on tobacco warning labels is accurate. It has been studied and tested over and over again to ensure it conveys factual information about the deadly effects of smoking. And yet, people continue to smoke. Centola and Guilbeault wondered whether that could be a problem of misunderstanding.

The researchers created an online network in which 1,600 participants, including both smokers and non-smokers, were asked to answer questions about the health risks associated with smoking. In the first round of the study, all participants answered the questions alone. For the second and third rounds, participants in the control group were allowed to change their answers but were still working alone. Their answers did not become any more accurate.

Meanwhile, two networked groups of participants were allowed to view the answers of others and use that information to revise their guesses for the second and third rounds. One group simply saw the answers of anonymous participants, while the other group was able to see whether the guesses were coming from smokers or non-smokers.

The answer to the question of how many people will die in developed countries is a daunting figure: 30 million, according to the World Health Organization. In both networked groups where participants shared answers, everyone's responses to the question improved dramatically. Just by talking in a social network, participants came away with a much better understanding of their own smoking risks, which is a key indicator of a smoker's intention to quit.

"At the individual level, people often aren't incentivized to change their beliefs," Guilbeault says, "but if you show them that other people think differently, it can encourage belief change under the right conditions."

After completing the three rounds of questions about smoking risks, participants were then asked to complete a survey about their experience. The survey showed that when people were in networks where they could see that others were smokers and non-smokers, they were the most likely to report having improved their opinion about the other group. If they were a smoker, they now thought more favorably of non-smokers, and vice versa.

"Most people think that when someone encounters an outgroup member, they are more likely to become entrenched in their position," Centola says, "but in this study with smokers and non-smokers, we found that they actually become more receptive to one another's points of view and developed mutual respect for each other."

Credit: 
University of Pennsylvania

NASA satellite finds wind shear adversely affecting tropical storm Francisco

image: NASA-NOAA's Suomi NPP satellite passed over Tropical Storm Francisco on Feb. 6, 2020 and revealed wind shear was pushing the bulk of its clouds to the southeast of its center.

Image: 
NASA Worldview, Earth Observing System Data and Information System (EOSDIS)

Forecasters use a variety of satellite imagery to understand what is happening in a storm, and sometimes just a visible picture can tell a lot. NASA-NOAA's Suomi NPP satellite provided forecasters with a visible image of the Tropical Storm Francisco in the Southern Indian Ocean that showed wind shear was pushing clouds away from the storm's center.

Visible imagery from satellites helps forecasters understand if a storm is organizing or weakening, or if it is being affected by vertical wind shear. The shape of a tropical cyclone provides forecasters with an idea of its organization and strength. When outside winds, that is, vertical wind shear, batter a storm it can change the shape of it and push much of the associated clouds and rains to one side of it.

In general, wind shear is a measure of how the speed and direction of winds change with altitude. Tropical cyclones are like rotating cylinders of winds. Each level needs to be stacked on top each other vertically in order for the storm to maintain strength or intensify. Wind shear occurs when winds at different levels of the atmosphere push against the rotating cylinder of winds, weakening the rotation by pushing it apart at different levels.

The Visible Infrared Imaging Radiometer Suite (VIIRS) instrument aboard Suomi NPP provided a visible image of Francisco on Feb. 6. The image showed vertical wind shear is displacing the deep convection about 125 nautical miles to the southeast. In addition, multispectral satellite imagery revealed that the low-level circulation center appeared elongated. When the circulation is not circular and appears elongated, it cannot spin as quickly, just like a tire. Thus, the storm weakens. Wind shear is causing the elongation and weakening the storm.

At 4 a.m. EDT (0900 UTC), the Joint Typhoon Warning Center (JTWC) issued their final advisory on Tropical Cyclone Francisco. At that time, Francisco was located near latitude 19.1 degrees south and longitude 71.7 degrees east, about 816 nautical miles east of Port Louis, Mauritius and moving southeast. Maximum sustained winds were near 35 knots (40 mph/65 kph) and weakening.

The JTWC expects Francisco will continue moving to the southeast until it dissipates.

Tropical cyclones/hurricanes are the most powerful weather events on Earth. NASA's expertise in space and scientific exploration contributes to essential services provided to the American people by other federal agencies, such as hurricane weather forecasting.

Credit: 
NASA/Goddard Space Flight Center

Trees in the Amazon are time capsules of human history, from culture to colonialism

image: This image shows a Brazil nut tree in Jaú National Park.

Image: 
Victor Caetano-Andrade

As society has progressed, the annals of human history have been recorded through text, art, and oral tradition. However, for hundreds of years tropical forests have also kept detailed records of the human activities that unfolded around them. In a Review published February 6 in the journal Trends in Plant Science, researchers describe how the rings, physical chemistry, and DNA of living tropical trees reveal the impacts of native culture as well as the scars of colonial occupation.

"As trees grow, they absorb details about their surroundings into their wood, creating snapshots of the environment through time," says first author Victor Caetano-Andrade (@VictorLCaetano1), a PhD candidate at the Max Planck Institute for the Science of Human History. "By combining techniques such as dendrochronology (the study of tree rings), carbon and oxygen isotope analysis, and genetics, we can obtain information about climate and the past human-mediated events in the rainforest."

As trees are some of the most long-lived organisms on the planet--some tropical species live for up to 600 years--many of those standing in the rainforest today bore witness to significant changes in human history. When the biological information gathered from living trees is combined with archaeological and historical records of native rainforest societies, we can evaluate, for example, how indigenous communities or foreign invaders managed their local environment or how their actions influenced the recruitment and growth patterns of trees.

In this way, researchers can construct inferences about how ancient native peoples interacted with the rainforest and responded to colonial pressure: "When ancient humans constructed dwellings within the forest they selectively created gaps in the canopy, allowing for additional light to cultivate preferred species; this is one way native societies influence the establishment of trees within their territories," says Caetano-Andrade. "One example is during the pre-colonial period in the central Amazon, where populations of Brazil nut experienced heavy recruitment and growth. However, when European colonists invaded the tropics, indigenous people abandoned the landscape, leading to Brazil nut trees to stop recruiting for nearly 70 years. This demonstrates how the forest actively responds to human occupation over time."

Similarly, by analyzing the responses of trees to human activity during specific periods of time, tropical forests act as repositories of cultural heritage. Indigenous groups promoted the growth of trees they found useful, such as those for food or construction. The marks of this care remain implanted in the biology of standing trees. "Part of the culture of these societies is how they managed the forest within their local ecosystem," says Caetano-Andrade. "As trees can live for hundreds of years, they register all of the impacts humans are making in the surrounding forest community."

Caetano-Andrade hopes that reframing tropical trees as living sites of cultural history will help motivate additional efforts in rainforest preservation. And their findings show that native communities could build sustained, successful economic systems without depleting the rainforest of its resources.

"It's possible to think of economic models that can keep the forest standing," he says. "The proof is that it's been happening for thousands of years before colonial expansions, as native people developed economic systems that maintained and even enriched the forest. Traditional populations who live on the riverbanks of tropical forests are the great heroes of preservation as they know the importance of keeping the forest standing to guarantee their well-being."

Credit: 
Cell Press