Culture

Screening DNA of Parkinson's patients in the Christine Van Broeckhoven laboratory (VIB-UAntwerpen Center for Molecular Neurology) identified a new risk gene for Parkinson's disease. Mutations in ATP10B resulted in loss of ATP10B protein. The function of the ATP10B gene was revealed by the Peter Vangheluwe lab (KU Leuven, Laboratory of Cellular Transport Systems). They identified ATP10B as a transporter for glucosylceramide, a lipid that plays a central role in Parkinson's disease. Disease mutations disturb this function. Also, a reduced expression of ATP10B leads to neuronal loss and sensitizes neurons to environmental risk factors of Parkinson's disease. Therefore, ATP10B is emerging as an interesting therapeutic target for Parkinson's disease.

Parkinson's disease affects over 10 million people worldwide and more than 2 million people in Europe. Clinically, patients display a variety of motor and non-motor symptoms, impeding their ability to perform basic everyday activities. With currently no effective therapy, the chronic and progressive nature of Parkinson's disease has a profound impact on the quality of life of patients and caregivers.

The identification of Parkinson's disease genes and mutations contributed substantially to our understanding of the underlying disease mechanisms. In 5 to 15% of Parkinson's patients, genetic studies identified mutations in different genes that explained the segregation of disease in Parkinson's families between generations. Familial mutations are considered high penetrant, meaning that the carrier of the mutation is highly likely to get Parkinson's disease during lifespan. In the larger part of non-familial Parkinson's patients, so-called sporadic patients, much less is known of the genetic contribution to Parkinson's disease, but several genes have been associated with increased genetic disease risk. In sporadic patients, different risk genes and mutations, in combination with environmental factors, might contribute to the overall genetic etiology of sporadic Parkinson's disease.

Identification of the ATP10B gene

Mutations in ATP10B were identified by Stefanie Smolders in the VIB-UAntwerpen laboratory in children with Parkinson's disease at early age while the parents were healthy. These children carried two mutations in ATP10B, one on each chromosome inherited from the parents, mimicking recessive inheritance. In a group of 617 unrelated Parkinson's patients she identified another six carriers of two ATP10B mutations. Among the carriers we observed a high variability in the onset age at disease. This can indicate that the combination of multiple mutations might have different effects on ATP10B expression leading to variable losses of ATP10B protein and function.

From risk gene to disease mechanism

Shaun Martin in the KU Leuven team studied the gene function of ATP10B and found that ATP10B works as a transporter that removes lipids out of the lysosome, the compartment in the cell that degrades and recycles obsolete cell material. In particular, ATP10B transports glucosylceramide, a lipid that plays an important role in Parkinson's disease. This process is disturbed by the disease mutations. ATP10B is important to preserve the health of the lysosomes and protects neuronal cells against environmental risk factors of Parkinson's disease.

A new potential target for therapeutic intervention

A better understanding of key targets and pathways in Parkinson's disease pathogenesis is necessary to overcome the major hurdle in the development of effective therapies for the disease. Glucosylceramide homeostasis seems to play a major role in the pathogenesis of Parkinson's disease. With the identification and characterization of ATP10B, we provide a new potential target involved in glucosylceramide homeostasis to tackle Parkinson's disease. Without any doubt, strategies to modulate ATP10B activity will be further explored for Parkinson's disease therapy, which is already under investigation by our teams and has raised interest of pharmaceutical companies.

Action real-time strategy video games such as World of Warcraft, Age of Empires, and Total War are played by millions. These games, which can be won through strategic planning, selective attention, sensorimotor skills, and teamwork place considerable demands on the brain.

Research has shown that experience of playing games can improve cognitive development such as greater sensitivity to contrasts, better eye-to-hand coordination, and superior memory. But the long-term effects of gaming on a key cognitive function called temporal visual selective attention - the capacity to distinguish between important and irrelevant information within a rapid stream of visual stimuli - has never been studied.

Here, researchers show for the first time that expert players of real-time strategy games have faster information processing, allocate more cognitive power to individual visual stimuli, and allocate limited cognitive resources between successive stimuli more effectively through time. These findings in Frontiers in Human Neuroscience suggest that playing such games can cause long-term changes in the brain and lead to an improvement in temporal visual selective attention.

"Our aim was to evaluate the long-term effect of experience with action real-time strategy games on temporal visual selective attention," says author Dr Diankun Gong, Associate Professor in the Ministry of Education Key Laboratory for Neuroinformation at the University of Electronic Science and Technology of China.

"In particular, we wanted to reveal the time course of cognitive processes during the attentional blink task, a typical task used by neuroscientists to study visual selective attention."

Attentional blink is the tendency of focused observers to "blink" - that is, to fail to properly register - a visual stimulus if it appears so quickly after a previous stimulus that cognitive processing of the first hasn't finished. In a typical blink task, human subjects are shown a stream of digits and letters in quick succession (with 100 ms intervals) and asked to press a button each time they see one of two target letters (for example D and M).

People often "blink" a second target if it appears within 200-500 ms of the first, and electroencephalograms (EEGs) suggest that this is due to competition for cognitive resources between the first stimulus - with the need to encode it in working and episodic memory, and to select the appropriate response - versus the second. In other words, people often fail to register M because brain resources are temporarily used up by the ongoing need to process any D shown more than 200 ms and less than 500 ms earlier.

To study the effect of gaming on temporal visual selective attention, Gong and colleagues selected 38 volunteers, health young male students from the University of Electronic Science and Technology. Half of the volunteers were expert players of the typical action real-time strategy game League of Legend, where teammates work together to destroy the towers of an opposing team. They had played the game for at least two years and were masters, based on their ranking among the top 7% of players. The others were beginners, with less than six months experience of the same game, and ranked among the bottom 30-45%. All volunteers were seated in front of a screen and tested in a blink task, with 480 trials over a period of approximately 2 h. The greater a volunteer's tendency to "blink" targets, the less frequently he would press the correct button when one of the two targets appeared on the screen, and the worse he did overall in the task.

The volunteers also wore EEG electrodes on the parietal (i.e. sides and top) region of their scalp, allowing the researchers to measure and localize the brain's activity throughout the experiment. These electrodes recorded Event-Related Potentials (ERPs), tiny electric potentials (from -6 to 10 μV) that last from 0 to 800 ms after each non-blinked stimulus, and which represent the neural processes for registering and consolidating its memory. The researchers focused on the so-called P3b phase of the ERP, a peak between 200 and 500 ms after the stimulus, because previous research has shown that its timing and amplitude accurately reflects performance in the blink task: the later P3b occurs and the less pronounced it is, the more likely it is that a stimulus will be "blinked".

"We found that expert League of Legend players outperformed beginners in the task. The experts were less prone to the blink effect, detecting targets more accurately and faster, and as shown by their stronger P3b, gave more attentional cognitive resources to each target," says coauthor Dr Weiyi Ma, Assistant Professor in Human Development and Family Sciences at the University of Arkansas, USA.

"Our results suggest that long-term experience of action real-time strategy games leads to improvements in temporal visual selective attention: the expert gamers had become more effective in distributing limited cognitive resources between successive visual targets," says author Dr Tiejun Liu. "We conclude that such games can be a powerful tool for cognitive training."

Dr. Hyoungchul Kim's research team, from the Center for Energy Materials Research at the Korea Institute of Science and Technology (KIST, Acting President Yoon, Seok-jin), have successfully developed a sulfide-based *superionic conductor that can be used to a high-performance solid electrolyte in all-solid-state batteries. This new material delivers the Li-ion conductivity of 10.2 mS/cm at room temperature and is comparable to that of liquid electrolytes used for typical Li-ion batteries. The research team has also reported a new synthesis technology that can reduce the processing time of existing synthesis technologies by more than one third. We expect that this technology will greatly accelerate the mass production of superionic solid electrolyte materials and contribute to the commercialization of all-solid-state batteries.

* Superionic conductor: A material with high ion transport property corresponding to ion conductivity of 10 to 100 mS/cm at room temperature. These materials have been receiving much attention recently as they are used as electrolytes in various electrochemical devices such as batteries, fuel cells, and sensors.

Currently, Li-ion batteries based on liquid electrolytes are mainly used for batteries for electric vehicles and energy storage devices. However, as battery safety issues have recently been raised several times, various concerns about the use of existing batteries using flammable liquid electrolytes have increased. To solve this safety issue, all-solid-state battery technology, in which all battery components are replaced with solid materials, has recently attracted great attention. However, unlike a liquid electrolyte in which Li-ions can freely move, a solid electrolyte has a low Li-ion conductivity of 1/10 to 1/100 of that of a liquid electrolyte because the movement of Li-ions is confined within a rigid solid lattice. This is one of the most important and difficult challenges in the development of all-solid-state battery technology, and its technical and economic value is very great.

Dr. Kim's research team at KIST has developed a solid electrolyte with superionic conductivity using a sulfide-based crystalline structure called **argyrodite. Meanwhile, this crystal structure had high expectations for utilization due to its high Li-ion concentration and structural stability, but its Li-ion conductivity remained below 4 mS/cm due to the structural uniqueness of Li-ions trapped in the octahedral cage in the argyrodite crystal. The research team has newly developed a novel Li-ion pathway that crosses the octahedral cage by applying a technique for selectively substituting chlorine, a halogen element, at specific atomic positions. The new solid electrolyte material, developed by KIST researchers, has an Li-ion conductivity of 10.2 mS/cm, which is equivalent to that of a conventional liquid electrolyte at room temperature, and still maintains electrochemical stability under various battery operating conditions.

**Argyrodite: A crystal structure that was discovered in the mineral of Ag8GeS6 by Clemens Winkler in 1886. Recently, much research has been conducted on replacing cation sites with alkali metals such as Li and applying them to electrochemical devices.

In addition, the new synthesis method reported by KIST research team has attracted more attention as it is possible to maximize the mass productivity of superionic solid electrolyte materials. While the conventional ***solid-state reaction process requires more than several days of processing time, this study proposed a simple synthesis method that combines the nanocrystalline nucleation process and an infrared rapid heat treatment technology to shorten the process time to within 10 hours.

***Solid-state reaction process: A dry-based material process in which one or more solid reaction products are formed with the diffusion of elementary particles. It generally requires high-temperature heat treatment in order to make reactions to occur at an appropriate rate.

According to Dr. Kim, "In the field of all-solid-state battery technology, foreign researchers including Japan are leading the research. In this study, there is great significance in developing a high-performance solid electrolyte material with excellent mass productivity." He further comments, "Synthesis of superionic sulfide materials through rapid process is very likely to be commercialized, and can be widely used in electric vehicles and energy storage system as a solid electrolyte in the future."

Bethesda, Maryland (April 10, 2020) -- Today, the American Gastroenterological Association (AGA) published new COVID-19 guidance for gastroenterologists treating patients with inflammatory bowel disease (IBD): AGA Clinical Practice Update on Management of Inflammatory Bowel Disease During the COVID-19 Pandemic: Expert Commentary.

While the COVID-19 pandemic is a global health emergency, patients with IBD have particular concerns for their risk for infection and management of their medical therapies. This clinical practice update incorporates the emerging understanding of COVID-19 and summarizes available guidance for patients with IBD and the providers who take care of them.

Recommendations for gastroenterologists & their patients who have IBD:

1. During this pandemic, patients with IBD should continue IBD therapies including scheduled infusions.

2. Having IBD does not appear to increase the risk of SARS-CoV-2 infection or the development of COVID-19.

3. Instructions for patients with IBD who develop COVID-19 (fever, respiratory symptoms, digestive symptoms, etc.):

a. Stop thiopurines, methotrexate, tofacitinib.

b. Stop biological therapies (including anti-TNF, ustekinumab, vedolizumab).

c. Can restart therapies after complete resolution of COVID-19 symptoms. Patients should

always speak with their health care team before stopping any medication.

4. Doctors should submit cases of IBD and confirmed COVID-19 to the SECURE-IBD registry at
COVIDIBD.org.

A new X-ray detector prototype is on the brink of revolutionizing medical imaging, with dramatic reduction in radiation exposure and the associated health risks, while also boosting resolution in security scanners and research applications, thanks to a collaboration between Los Alamos National Laboratory and Argonne National Laboratory researchers.

"The perovskite material at the heart of our detector prototype can be produced with low-cost fabrication techniques," said Hsinhan (Dave) Tsai, an Oppenheimer Postdoctoral fellow at Los Alamos National Laboratory. "The result is a cost-effective, highly sensitive, and self-powered detector that could radically improve existing X-ray detectors, and potentially lead to a host of unforeseen applications."

The detector replaces silicon-based technology with a structure built around a thin film of the mineral perovskite, resulting in a hundred times more sensitivity than conventional silicon-based detectors. In addition, the new perovskite detector does not require an outside power source to produce electrical signals in response to X-rays.

High sensitivity perovskite detectors could enable dental and medical images that require a tiny fraction of the exposure that accompanies conventional X-ray imaging. Reduced exposure decreases risks for patients and medical staff alike. The fact that perovskite detectors can be made very thin allows them to offer increased resolution for highly detailed images, which will lead to improved medical evaluations and diagnoses. Lower-energy and increased-resolution detectors could also revolutionize security scanners and imaging in X-ray research applications.

Because perovskite is rich in heavy elements, such as lead and iodine, X-rays that easily pass through silicon undetected are more readily absorbed, and detected, in perovskite. As a result, perovskite significantly outperforms silicon, particularly at detecting high-energy X-rays. This is a crucial advantage when it comes to monitoring X-rays at high-energy research facilities, such as synchrotron light sources.

Perovskite films can be deposited on surfaces by spraying solutions that cure and leave thin layers of the material behind As a result, the thin-layer detectors will be much easier and cheaper to produce than silicon-based detectors, which require high-temperature metal deposition under vacuum conditions.

"Potentially, we could use ink-jet types of systems to print large scale detectors," said Tsai. "This would allow us to replace half-million-dollar silicon detector arrays with inexpensive, higher-resolution perovskite alternatives."

In addition to the promise of thin-layer perovskites in X-ray detectors, thicker layers work well provided they include a small voltage source. This suggests that their useful energy range could be extended beyond X-rays to low-energy gamma-rays.

Researchers are interested in genetically modifying trees for a variety of applications, from biofuels to paper production. They also want to steer clear of modifications with unintended consequences. These consequences can arise when intended modifications to one gene results in unexpected changes to other genes. A new model aims to predict these changes, helping to avoid unintended consequences, and hopefully paving the way for more efficient research in the fields of genetic modification and forestry.

The research at issue focuses on lignin, a complex material found in trees that helps to give trees their structure. It is, in effect, what makes wood feel like wood.

"Whether you want to use wood as a biofuel source or to create pulp and paper products, there is a desire to modify the chemical structure of lignin by manipulating lignin-specific genes, resulting in lignin that is easier to break down," says Cranos Williams, corresponding author of a paper on the work and an associate professor of electrical and computer engineering at NC State. "However, you don't want to make changes to a tree's genome that compromise its ability to grow or thrive."

The researchers focused on a tree called Populus trichocarpa, which is a widely used model organism - meaning that scientists who study genetics and tree biology spend a lot of time studying P. trichocarpa.

"Previous research generated models that predict how independent changes to the expression of lignin genes impacted lignin characteristics," says Megan Matthews, first author of the paper, a former Ph.D. student at NC State and a current postdoc at the University of Illinois. "These models, however, do not account for cross-regulatory influences between the genes. So, when we modify a targeted gene, the existing models do not accurately predict the changes we see in how non-targeted genes are being expressed. Not capturing these changes in expression of non-targeted genes hinders our ability to develop accurate gene-modification strategies, increasing the possibility of unintended outcomes in lignin and wood traits.

"To address this challenge, we developed a model that was able to predict the direct and indirect changes across all of the lignin genes, capturing the effects of multiple types of regulation. This allows us to predict how the expression of the non-targeted genes is impacted, as well as the expression of the targeted genes," Matthews says.

"Another of the key merits of this work, versus other models of gene regulation, is that previous models only looked at how the RNA is impacted when genes are modified," Matthews says. "Those models assume the proteins will be impacted in the same way, but that's not always the case. Our model is able to capture some of the changes to proteins that aren't seen in the RNA, or vice versa.

"This model could be incorporated into larger, multi-scale models, providing a computational tool for exploring new approaches to genetically modifying tree species to improve lignin traits for use in a variety of industry sectors."

In other words, by changing one gene, researchers can accidentally mess things up with other genes, creating trees that aren't what they want. The new model can help researchers figure out how to avoid that.

VRAC/LRRC8 chloride channels do not only play a decisive role in the transport of cytostatics, amino acids and neurotransmitters. They can also transport the important messenger substance cGAMP from cell to cell and thus strengthen the immune response to infections with DNA viruses. This has now been demonstrated by Prof. Thomas Jentsch, who originally discovered LRRC8/VRAC channels and works at the Leibniz Research Institute for Molecular Pharmacology (FMP) and the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, together with colleagues from Shanghai led by Prof. Hui Xiao. Since cGAMP is always formed when cells detect DNA outside their nucleus, the discovery is potentially of great importance also for other pathologies such as cancer. The work has now been published in the scientific journal "Immunity".

If DNA viruses such as herpes simplex - the coronavirus, being an RNA virus, does not belong to this group! - infect human cells; this does not go unnoticed. In the cell interior, the so-called cytoplasm, DNA has no place. Thus, if DNA is detected there messenger substances are formed and begin to sound the alarm. The foreign DNA binds to the enzyme cGAS, which synthesizes the 'second messenger' cGAMP. By binding to a receptor called STING, cGAMP activates a cellular signaling cascade that triggers the production of interferons and other factors of the innate immune system. This mechanism has also been observed in tumor cells, in which DNA fragments are released from the nucleus into the cytoplasm, as well as in some bacterial infections.

cGAMP is a highly topical messenger substance

Research on cGAMP has exploded in recent years, partly because it not only acts in the cell where it is produced, but also passes on to other cells. However, it remains unclear how this may happen. In cells that directly contact each other, cGAMP can pass through cell-connecting channels known as "gap junctions". But what about cells that are not in the immediate vicinity?

Researchers led by Prof. Hui Xiao from the Institut Pasteur Shanghai had suspected that further transport pathways must play a role and came across the volume-regulated anion channel VRAC - the ion channel discovered in 2014 by Prof. Thomas Jentsch and his team, and in parallel by Prof. Zhaozhu Qiu (now Johns Hopkins University), who also contributed to the publication in "Immunity". Together, the German-Chinese research team was able to demonstrate with a whole variety of methods that VRAC transports cGAMP both out of the producing cell and into the recipient cell. This leads to the production of interferons in cells that are not infected, thereby strengthening the immune response.

"We now know that VRAC definitely transports cGAMP" says Thomas Jentsch about this significant discovery. "We didn't know this function yet, but it fits well with our previous findings on VRAC, namely that it not only transports chloride, but also other small organic molecules, for instance neurotransmitters, amino acids and cytostatics. The dependence of the cGAMP transport on the subunit LRRC8E - VRAC is always composed of several subunits - which we have now observed, agrees well with our earlier findings, which showed that this subunit supports the transport of glutamate, which is also negatively charged."

The uptake of the messenger substance by VRAC was verified by various cell culture experiments and by electrophysiological approaches. In one experiment, for example, cells were infected with a DNA virus and separated from healthy cells using a filter. The virus infection could not be transmitted - but an interferon response was also observed in the non-infected cells.

Finally, experiments with knock-out mice generated in Berlin which lacked the VRAC subunit LRRC8E provided compelling evidence: if the rodents were infected with herpes viruses, a much higher viral load and lower interferon release were observed than in unmodified control animals. "This was exactly what we expected, because the messenger substance could no longer be transferred from infected cells to neighboring cells due to the absence of the channel. Since this transfer normally strengthens the immune response." explains Professor Jentsch. " the lack of cGAMP-transporting VRAC greatly reduces the defense mechanisms against such viruses."

New strategies against DNA viruses and cancer

The discovery of this new role of VRAC in the body's defense system against DNA viruses, a new addition to the many important functions of VRAC, will attract even more attention to this ion channel. The researchers assume that VRAC might play a similar role in cancer. Indeed, others have recently shown in animal experiments that cGAMP transport from cancer cells to neighboring host cells enhanced the immune response against tumors - but how cGAMP is transported had remained unclear.

Besides VRAC and gap junctions, a folate transporter also transports cGAMP across the membrane, as was shown last year. However, VRAC is found in more cell types and therefore probably plays a greater role. In the future, it might be a viable approach to activate VRAC to enhance the immune response. Possible ways to do this have already been described in the new work.

"The field is incredibly hot," says Thomas Jentsch, "and our discovery offers completely new perspectives for both, infection research and cancer research."

Harvesting sunlight to make energy is a complex reaction that plants do naturally, but isn't well understood.

A research team led by a Washington State University professor has developed a new tool to study how lipids interact with proteins in plants to help understand how photosynthesis happens.

In the paper, published in the Journal of Biological Chemistry earlier this year, the scientists used this new tool to find the lipid that controls when a photosynthetic protein switches from a light harvester to an energy dissipater in plants.

"There's a lot of potential danger with photosynthesis," said Helmut Kirchhoff, professor in WSU's Institute of Biological Chemistry. "If plants take in light energy that isn't used properly for their metabolism, it can poison the plant and kill cells. The switch of light-harvesting proteins is essential to protect the system when there's too much light available."

Until now, nobody knew for sure how plants avoided that toxicity on sunny days. It's an important scientific breakthrough.

High impact paper

The paper's impact was recently chosen by Science magazine as an editor's choice paper for March 2020.

"I was really surprised to be chosen," Kirchhoff said. "We were really excited and honored to be picked in such a top tier journal."

Kirchhoff wrote the paper with co-authors Stefanie Tietz, Ricarda Höhner, and Alice Olson from WSU and Michelle Leuenberger and Graham R Fleming from the University of California, Berkley.

How it works

In the paper, the researchers developed a method for studying how lipids, which are molecules in cell membranes that perform a variety of functions, interact with proteins in chloroplasts, the part of green plant cells that photosynthesize light.

They found that one specific type of lipid, called a nonbilayer lipid, seems to control the switch that the light harvesting protein makes when the plant has enough light and needs to dissipate some of the energy being received.

"We were suspicious that this nonbilayer lipid had a role in controlling the structure and function of membrane proteins," Kirchhoff said. "We knew it had to have a function to be there because it's the most abundant lipid in photosynthetic membranes. We just didn't know exactly what that role would be."

Future uses of findings

In a changing climate with an increasing human population, growing more food with fewer resources will be essential. This new finding could one day lead to a method for optimizing photosynthesis in crops for specific environments, so excess energy doesn't have to be wasted, Kirchhoff said.

"We're still very early on, but we're excited by what we've found in this paper," he said. "And we'll continue to use our new process to study other lipid-protein interactions to see what else we can learn."

In a recent study published in the Proceedings of the National Academy of Sciences (PNAS), University of California San Diego researchers moved one step closer to the ability to make heparin in cultured cells. Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible.

In particular, the researchers found a critical gene in heparin biosynthesis: ZNF263 (zinc-finger protein 263). The researchers believe this gene regulator is a key discovery on the way to industrial heparin production. The idea would be to control this regulator in industrial cell lines using genetic engineering, paving the way for safe industrial production of heparin in well-controlled cell culture.

Heparin is currently produced by extracting the drug from pig intestines, which is a concern for safety, sustainability, and security reasons. Millions of pigs are needed each year to meet our needs, and most manufacturing is done outside the USA. Furthermore, ten years ago, contaminants from the pig preparations led to dozens of deaths. Thus, there is a need to develop sustainable recombinant production. The work in PNAS provides new insights on exactly how cells control synthesis of heparin.

Heparin regulation

Heparin is a special subtype of a more general class of carbohydrates, called heparan sulfates, that are produced by a wide range of cells, both in the human body, as well as in cell culture. Yet, heparin is exclusively produced in a special type of blood cells called mast cells. To this day, heparin cannot be successfully produced in cell culture.

Researchers at UC San Diego reasoned that heparin synthesis must be under the control of certain gene regulators (called transcription factors), whose tissue-specific occurrence might give mast cells the unique ability to produce heparin.

Since regulators for heparin were not known, a research team led by UC San Diego professors Jeffrey Esko and Nathan Lewis used bioinformatic software to scan the genes encoding enzymes involved in heparin production and specifically look for sequence elements that could represent binding sites for transcription factors. The existence of such a binding site could indicate that the respective gene is regulated by a corresponding gene regulator protein, i.e. a transcription factor.

"One DNA sequence that stood out the most is preferred by a transcription factor called ZNF263 (zinc-finger protein 263)," explains UC San Diego professor Nathan E. Lewis, who holds appointments in the UC San Diego School of Medicine's Department of Pediatrics and in the UC San Diego Jacobs School of Engineering's Department of Bioengineering.

"While some research has been done on this gene regulator, this is the first major regulator involved in heparin synthesis," said Lewis. He is also Co-Director of the CHO Systems Biology Center at the UC San Diego Jacobs School of Engineering.

Using the gene-editing technology, CRISPR/Cas9, the UC San Diego researchers mutated ZNF263 in a human cell line that normally does not produce heparin. They found that the heparan sulfate that this cell line would normally produce was now chemically altered and showed a reactivity that was closer to heparin.

Experiments further showed that ZNF263 represses key genes involved in heparin production. Interestingly, analysis of gene expression data from human white blood cells showed suppression of ZNF263 in mast cells (which produce heparin in vivo) and basophils, which are related to mast cells. The researchers report that ZNF263 appears to be an active repressor of heparin biosynthesis throughout most cell types, and mast cells are enabled to produce heparin because ZNF263 is suppressed in these cells.

This finding could have important relevance in biotechnology. Cell lines used in industry (such as CHO cells that normally are unable to produce heparin) could be genetically modified to inactivate ZNF263 which could enable them to produce heparin, like mast cells do.

Philipp Spahn, a project scientist in Nathan Lewis' lab in the Departments of Pediatrics and Bioengineering at UC San Diego, described further directions the team is pursuing: "Our bioinformatic analysis revealed several additional potential gene regulators which can also contribute to heparin production and are now exciting objects of further study."

April 9, 2020 -- The Lancet commentary "Centring sexual and reproductive health and justice in the global COVID-19 response" highlights the detrimental impact of the global COVID-19 pandemic response on sexual and reproductive health and rights (SRHR). The piece emphasizes the threat to SRH services, caused by policies designating these services as non-essential and diverting resources, and calls for vigilance from the SRH community to prevent access to these services from being lost. "Global responses to the coronavirus disease 2019 (COVID-19) pandemic are converging with pervasive, existing sexual and reproductive health and justice inequities to disproportionately impact the health, wellbeing, and economic stability of women, girls, and vulnerable populations," writes Terry McGovern, Chair of the Heilbrunn Department of Population and Family Health, and co-authors.

Highlighting the disproportionate social and economic burden on women, girls, and vulnerable populations exacerbated by the pandemic, the authors argue that "a sexual and reproductive health and justice framework--one that centers human rights, acknowledges intersecting injustices, recognizes power structures, and unites across identities--is essential for monitoring and addressing the inequitable gender, health, and social effects of COVID-19.

A multi-disciplinary group of academics and practitioners, including epidemiologists, health care workers, lawyers, and community-based organizers, the authors have expertise in sexual and reproductive health service provision and access, gender-based violence, global humanitarian response, human rights, disease surveillance, stigma, and the specific needs of women, girls, and vulnerable populations.

"Advocates must continue to fight the exploitation of the COVID-19 crisis to further an agenda that restricts access to essential sexual and reproductive health services, particularly abortion, and targets immigrants and adolescents," noted McGovern, who is also director of the Program on Global Health Justice and Governance at Columbia Mailman School.

Nano-catalysts usually have higher catalytic activity than traditional bulk catalysts. And it is widely acknowledged that the smaller the particle size of the active component is, the higher the activity would be. However, the active component with small size tends to agglomerate or further grow into large particles. Many reaction processes, such as hydrocarbon cracking and combustion, methane dry/wet reforming and automobile exhaust gas purification, have to be operated at very high temperatures, it will lead to the decreasing of activity and product selectivity due to sintering at high temperatures, ultimately limits the practical application of nano-catalysts. Many researchers believe that the sintering of nanoparticles involves two processes: one is the ripening process, single atom or molecular species move from one particle to another; the other is the migration process, whole particles grow into large particles after migration and aggregation. Because the ripening process can hardly be avoided at high temperature, the current strategy to improve the stability of nano-catalysts is to inhibit the migration of nanoparticles on the basis of "confinement effect" or to construct a "migration barrier".

Recently, Pt/CeO2/NiAl2O4/Al2O3@SiO2 model catalyst, based on the "composite energy trap" model, was developed by the State Key Laboratory of Rare Earth Resource Utilization of Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, which can effectively inhibit the migration and agglomeration of loaded nanoparticles. The model catalyst still remains high activity after aging at 1000 ?. The results of DFT indicate that the higher stability of the model catalyst should be attributed to the existence of two kinds of "confinement effect" in its structure, the "composite energy well" model is also suitable for the research and development of other supported catalysts. The first authors of this paper are Jingwei Li and Kai Li, and the correspondent authors are associate professor Yibo Zhang and professor Xiangguang Yang.

Imagine the advances to predictive modeling if you could infer something about how light amplifies colors in a bird's plumage from the way seismic waves propagate through mountain systems.

That's a bit of hyperbole that nevertheless suggests the "beautiful" utility of new mathematical formulas devised by Princeton Professor of Chemistry Salvatore Torquato and sixth-year graduate student Jaeuk Kim of the Department of Physics as they advance our understanding of how different types of waves behave inside materials.

Torquato, the Lewis Bernard Professor of Natural Sciences and director of the Complex Materials Theory Group, published research this week in the Proceedings of the National Academy of Sciences (PNAS) linking wave phenomena that has never previously been linked. For the first time, the research employs a unified approach that melds the behavior of elastodynamic (sound) waves with that of electromagnetic (light) waves as they propagate through heterogeneous, or composite, materials.

Torquato and Kim also demonstrate that the way these waves move through a heterogeneous material in turn elucidates characteristics of the material microstructure itself. The microstructure - the spatial arrangement of the different materials that comprise the heterogeneous material - impacts the way waves propagate.

This is the basic idea behind ultrasound scans, or sonography, that create images of structures within your body.

A homogeneous system consists of a single material. A heterogeneous, or composite, system is a mixture. But the mixture of these individual materials - called phases - do not combine evenly; they inhabit distinct domains within that system. Light and sound waves move through a given composite and, as they encounter different phases with different physical properties, they behave differently, scatter, and interfere. Due to the resulting interference, the wave speeds change and the waves can attenuate, or lose energy.

The formulas developed under this research will allow scientists to predict how waves act in these complex systems without having to solve for two sets of differential equations that govern light and sound waves, respectively. They can estimate the effective wave speeds and degree of attenuation, or the rate at which waves degrade within a material, for a wider range of wavelengths than that on which previous theories operate.

"What we're predicting is the effective behavior of this wave through a complicated system," said Torquato, a theoretical chemist. "And it turns out that the effective properties of both electromagnetic and elastodynamic waves will depend upon the wavelengths associated with those particular waves.

"Light waves, for instance, are governed by Maxwell's differential equations for electromagnetic waves. Sound waves are governed by another set of differential equations. So normally, when you're working on wave phenomena, you have these two communities that typically don't talk to each other," added Torquato. "What we have done, which is way out of the box, is to create a formulation that allows us to attack each problem in a unified manner.

"Then, we melded the formulas together to show that if you can tell me the response of a material to an electromagnetic wave, I can tell you something about the response of that same material to sound waves. So now, you have these predictive formulas that can be applied so that you don't have to constantly validate the theory via full-blown computer simulations every time you change the parameters. You're able to access and predict phenomena that people could not even contemplate before."

The research centers on heterogeneous systems because these systems are ideal to achieve multiple types of desired properties, called multifunctionality, which means that the best properties of composites can be combined to exhibit specific responses to the different types of waves. Materials can then be designed, for example, to absorb waves or allow them to be transmitted without attenuation.

"Previous multifunctional designs mainly have focused on static transport and elastic properties because conventional theories were not accurate in predicting wave phenomena," said Kim. "Thus, our theory will aid the rational design of multifunctional composites with desired wave characteristics."

Driving towards a future application, these formulas could allow for the design of new, multifunctional materials that exhibit specific responses to waves, paving the way to engineered hyperuniform materials with exotic effective properties. They could one day enable the design of multifunctional composites that might include structural components for spacecraft, which require high stiffness and electromagnetic absorption, or heat sinks for central processing units (CPUs) and other electrical devices that can simultaneously suppress mechanical vibrations.

"This work was successful thanks to Professor Torquato's insights in working across disciplines. It was exciting to bridge the knowledge of two different communities - optics and acoustics - to achieve this research," said Kim.

CHICAGO (April 9, 2020): Within a month of the University of California San Francisco (UCSF) Health treating its first patient with coronavirus disease 2019 (COVID-19) on Feb. 3, UCSF surgeons began formulating a plan to respond to the pandemic and help manage the health care system's available resources. The comprehensive rapid response plan--one of the earliest surgical strategies for handling the outbreak reported in the nation--appears online as an "article in press" on the Journal of the American College of Surgeons website in advance of print.

The multitier plan was a collaboration between the UCSF department of surgery and the hospital's other departments, according to the article's authors. Their actions included reducing operating room volume by 80 percent to ensure adequate capacity to care for an anticipated influx of COVID-19 patients, safeguarding personal protective equipment (PPE), preparing for a dwindling workforce due to illness and other reasons, and providing regular communication to departmental staff about the pandemic.

"In two weeks, we have dramatically changed the way we approach surgical care and come together as a community for the greater good of our city and patients. The speed with which this has occurred is unprecedented," the authors write. "Our response efforts were early and aggressive, and we made tough decisions," said study coauthor Elizabeth Wick, MD, FACS, professor of surgery at UCSF. "We canceled elective surgical cases before any other facility in the country that we know of. By starting early, we figured out a way to focus on urgent operations before the situation became worse."

Prioritizing operations

On March 13, the American College of Surgeons (ACS)1 recommended that hospitals consider postponing elective, nonurgent surgical procedures, thus freeing hospital beds and other resources for COVID-19 patients. This recommendation left it to individual institutions to determine how to triage, or assign degrees of urgency to, scheduled operations, and was followed with another guidance document on March 17 to aid in surgical decision making to triage operations.2 Even before then, in early March, the UCSF department of surgery had already developed triage guidelines for operations, according to Dr. Wick.

Initially the multidisciplinary team of surgeons defined essential surgical cases as those that would result in an adverse outcome (such as disease progression) if the patient did not undergo the procedure within seven days. The surgeons flagged the priority level in each patient's electronic health record, which Dr. Wick said is helping with organizing the case backlog.

As virus-related health care shortages in other countries became news, the surgical team quickly responded with changes. They reportedly began to prioritize cases based on not only the expected results of delaying the procedure but also the extent that the procedure would use hospital resources, such as ventilators and blood. Additionally, they considered whether nonsurgical treatment was an option.

From an initial 25 percent reduction in operating room volume starting on March 2, the surgeons succeeded in lowering the surgical volume by 80 percent in mid-March, Dr. Wick reported.

Because adjusting surgical care was a crucial step in managing available health care resources, she said surgeons had representation on all UCSF COVID-19 work committees.

Reassigning surgeons to optimize workforce

The department of surgery also developed a plan to optimize the workforce during the pandemic. For instance, the department reassigned some surgeons, based on their competencies, to work in inpatient units, the emergency department, or the system's Level I trauma center.

To minimize workers' exposure to the coronavirus, the department limited surgeons to work at a single hospital site in the health care system and reduced the number of surgeons on each surgical service daily. The same surgical team worked for several days straight so others would be available to work if a viral exposure occurred on that service, Dr. Wick said.

Anticipating shortages of masks, the surgical department created guidelines for which types of PPE to wear in the operating room and when to wear single-use masks versus reusing them.

Putting patients first

It is too soon, Dr. Wick noted, to know whether their rapid response improved outcomes for patients and staff. She said, "We hope we took the necessary measures that will allow UCSF Health to continue to safely and effectively care for surgical patients requiring urgent operations as well as for COVID-19 patients."

She credits their ability to implement a rapid COVID-19 response to San Francisco's early city ordinances requiring residents to stay home and mandating hospitals to restrict visitors. These directives helped patients understand the need to have their nonurgent operations postponed, Dr. Wick said. She also commended strong departmental leadership that emphasized that everyone should prioritize "what was right for the patients."

Dr. Wick said her team members decided to quickly publicize their response plan hoping their experience would help other surgical facilities navigate "this uncharted territory." She said their plan is scaleable to other health care systems and smaller hospitals that have strong leadership and good communication about the purpose of the changes.

Analyses of four fossilized molars newly excavated along the left bank of the Yuruá River in the Peruvian Amazon suggest another primate lineage distinct from the Platyrrhini - until now considered to be the only primate group ever to inhabit the New World - also occupied the New World for a brief period of time. The teeth strongly resemble those of Parapithecidae, a now-extinct family of higher-order primates that resided in Northern Africa around the Eocene (56 to 33.9 million years ago) and Oligocene period (33.9 million to 23 million years ago). Like ancestors of platyrrhine primates, these African-originated parapithecids potentially rafted across the Atlantic - a narrower, yet turbulent ocean at the time - around 35 to 32 million years ago, the researchers postulate. Their results offer another intriguing detail about the origins of New World mammals and may help inform how the ancestors shaped one of the most biodiverse regions on Earth. Erik Seiffert and colleagues analyzed primate teeth discovered at a 100-meter-long sedimentary deposit along Yuruá River and found these teeth were radically different - lumpier and more bulbous, among other features - than those of platyrrhines. Statistical probability analysis placed the species, which the authors named Ucayalipithecus perdita, deep within African primate groups Parapithecoidea and Parapithecidae. Ucayalipithecus' ancestors possibly rafted to the New World across the Atlantic Ocean around the time when sea levels had dropped, in an independent rafting event from the African platyrrhines, the analyses showed. Both parapithecids and Platyrrhini must have been remarkably adaptable to harsh conditions to have survived the crossing, the authors note. Upon arrival, the primates must also have had to immediately adjust their foraging behavior to the unfamiliar land and compete for food and territory, as they both appeared to have persisted around the same time - for at least 11.5 million years. Thus, these early primates were likely highly resilient and behaviorally versatile, the authors say. In a related Perspective, Marc Godinot further explores this concept and poses questions for future exploration.