Culture

Protein therapies are often more potent and selective toward their biochemical targets than other types of drugs, particularly small molecules. However, proteins are also more likely to be quickly degraded by enzymes or cleared from blood by the kidneys, which has limited their clinical use. Now, researchers reporting in ACS Central Science have engineered red blood cell (RBC) carriers that release therapeutic proteins when stimulated by light, with the help of a honey bee peptide.

Because protein drugs are unstable in the body, they must be given at high levels, which can cause side effects. Scientists have tried to protect protein therapies from degradation by encapsulating them in carriers, such as liposomes, nanoparticles and RBCs. But it has been challenging to make the carriers release their cargo at the appropriate place and time. Brianna Vickerman, David Lawrence and colleagues wanted to engineer RBCs to release therapeutic proteins at specific regions of the body when triggered by certain wavelengths of light.

The researchers embedded a peptide, called melittin, into the cell membrane of RBCs. A component of European honey bee venom, melittin normally causes RBCs to rupture. But the team modified the peptide so that it would do so only when illuminated by a specific wavelength of light. As a proof of concept, the researchers loaded thrombin -- a blood-clotting enzyme that is used to prevent excessive bleeding -- into the engineered RBCs and injected them into mice. They then shone a light on a small region of each mouse's ear and examined sections of the tissue. The analysis showed thrombin-related blood clotting only at the illuminated sites. The strategy could prove useful for the light-triggered release of protein, peptide and nucleic acid therapeutics from a variety of lipid-based carriers, the researchers say.

In a study of older adults admitted to the hospital with influenza and other acute respiratory illnesses during the 2011-2012 flu season, functional decline was common--and for some, this decline was persistent and catastrophic. The findings are published in the Journal of the American Geriatrics Society
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Among the 925 patients included in the study, 8.4% died, and 18.2% experienced a clinically meaningful loss of function at 30 days post-discharge, of whom half experienced catastrophic disability. Higher frailty at the time of hospital admission was associated with a higher likelihood of experiencing functional decline, catastrophic disability, and death.

"We need to think about the longer-term implications of influenza for older adults--it is not just a short-term illness. This impact on function in the longer-term makes it all the more important to prevent influenza in the first place, including through vaccination," said lead author Melissa K. Andrew, MD, PhD, of Dalhousie University, in Canada.

Medicine misuse is a public health issue, but the term has different meanings to people in different settings. A recent analysis of published studies provides a comprehensive overview of the terms and definitions used to characterize medicine misuse. The findings are published in the British Journal of Clinical Pharmacology.

Among 51 relevant studies, there were 71 definitions and 74 examples of misuse. The authors of the analysis noted that a certain confusion has reigned between misuse, abuse, and medication errors, with a clear need for classifying and selecting terms and definitions to understand which situations truly involve medicine misuse.

"A novel, consensual and standardised definition of medicine misuse is required," the authors wrote. "Such a taxonomy could include the different key elements highlighted in the present review, namely initiator, intent, purpose and context of medicine misuse."

SAN ANTONIO - Early circulating tumor cell dynamics were associated with overall survival in patients with metastatic breast cancer, according to a meta-analysis presented at the 2020 San Antonio Breast Cancer Symposium, held Dec. 8-11.

"With the increasing number of treatment options available to patients with metastatic breast cancer, being able to predict and monitor treatment responses rapidly will be critical to aiding treatment decisions," said Wolfgang Janni, MD, PhD, a professor and director of the women's clinic at Ulm University Hospital in Ulm, Germany. Responses to breast cancer treatment are typically monitored by conventional imaging, but this method requires time--approximately three months, depending on the subtype--before changes can be detected, Janni explained. "We were interested in determining whether treatment response and prognosis could be predicted earlier using a simple blood test."

In this study, Janni and colleagues investigated the potential of circulating tumor cells (CTCs), which are shed from the primary tumor into the bloodstream, to predict overall survival. They analyzed global pooled datasets from peer-reviewed and published studies of 4,079 patients with metastatic breast cancer, all of whom had undergone baseline and follow-up CTC measurements using the CellSearch test. The median time from baseline to follow-up was 29 days. Changes in CTC levels between baseline and follow-up were analyzed to determine whether they were associated with overall survival.

Of the 2,961 patients who were CTC-positive at baseline, 1,855 remained CTC-positive after initiating treatment (positive/positive), and 1,106 patients had converted to CTC-negative (positive/negative). Of the 1,118 patients who were CTC-negative at baseline, 813 remained CTC-negative (negative/negative), while 305 had become CTC-positive (negative/positive).

Median overall survival was greatest for patients who were negative/negative (47 months), followed by positive/negative (32.2 months), negative/positive (29.67 months), and positive/positive (17.87 months). Compared to patients who were negative/negative, the risk of death was 215 percent greater for those who were positive/positive, 74 percent greater for negative/positive, and 52 percent greater for positive/negative. For patients who were CTC-positive at baseline, those who remained CTC-positive at follow-up had a 51 percent greater risk of death than those who converted to CTC-negative.

Similar trends were found when CTC dynamics were analyzed by breast cancer subtype, including for hormone receptor-positive, HER2-positive, and triple-negative breast cancers. CTC dynamics were associated with overall survival for all breast cancer subtypes.

"These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment," said Janni. "This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued. It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes."

A limitation of the study is that information about the type of treatment received was not available for many patients. "A strength of our study is that we have individual patient data from around the world, but this is also a limitation because different sources provided varying levels of details regarding treatment," Janni explained. The absence of these data precluded determining whether the predictive value of CTC dynamics varies by treatment.

SAN ANTONIO - A large meta-analysis of breast cancer survivors of childbearing age indicated that they are less likely than the general public to get pregnant, and they face higher risk of certain complications such as preterm labor. However, most survivors who do get pregnant deliver healthy babies and have no adverse effects on their long-term survival, according to data presented at the 2020 San Antonio Breast Cancer Symposium, held Dec. 8-11.

"With the availability of more effective anticancer treatments, survivorship has gained substantial attention. Today, returning to a normal life after cancer diagnosis and treatment should be considered as a crucial ambition in cancer care. In patients diagnosed during their reproductive years, this includes the possibility to complete their family planning," said the study's corresponding author, Matteo Lambertini MD, PhD, adjunct professor in medical oncology at the University of Genova - IRCCS Policlinico San Martino Hospital in Genova, Italy.

As the average age for pregnancy has risen over time, it has become more common for women to be diagnosed with breast cancer before having a child. Also, Lambertini explained that many of the anticancer therapeutics that have successfully reduced mortality from breast cancer have possible long-term toxic effects on the body, including potentially damaging fertility and future family planning. For example, the adjuvant endocrine therapy that is prescribed for women diagnosed with hormone receptor-positive breast cancer is given for five to 10 years after diagnosis; during this treatment, pregnancy is contraindicated.

In this study, researchers conducted a systematic literature review of 39 studies that identified women who had been pregnant after a breast cancer diagnosis. They evaluated the studies to assess the frequency of post-treatment pregnancies in these patients, fetal and obstetrical outcomes, disease-free survival, and overall survival. In all, they gathered data on 114,573 breast cancer patients.

Compared with women from the general population, patients who had gone through breast cancer had a 60 percent reduced chance of having a pregnancy. Lambertini explained that this study did not specifically capture the overall number of women who tried to conceive, so it is possible that some women did not try to have a pregnancy after treatment completion. Some studies included in the analysis did report such data, and Lambertini estimated that more than half of young women who tried to conceive did so. Also, some women who did not intend to conceive did get pregnant. Lambertini said this finding suggests that cancer patients of child-bearing age should also receive accurate information about contraception.

The study showed that compared with women in the general population, breast cancer survivors had 50 percent higher risk of having a baby with low birth weight; 16 percent higher risk of having a baby that was small for gestational age; 45 percent higher risk of preterm labor; and 14 percent higher risk of having a caesarean section.

However, importantly, there was no significant increased risk of congenital defects or other pregnancy or delivery complications. The increased risk of low birth weight and small gestational age appeared to be restricted mainly to women who had received prior chemotherapy.

Pregnancy after breast cancer was not associated with poor patient outcomes. Compared with breast cancer patients who did not have a subsequent pregnancy, those who did get pregnant had a 44 percent reduced risk of death and a 27 percent reduced risk of disease recurrence. When controlling for the "healthy mother effect," which suggests that women who feel well and have good prognoses are the most likely to try to conceive, women who got pregnant had a 48 percent reduced risk of death and a 26 percent reduced risk of disease recurrence.

The analysis further indicated that pregnancy appeared safe across BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval (the amount of time between breast cancer diagnosis and pregnancy), and pregnancy outcomes.

Overall, Lambertini said, the analysis showed that pregnancy after breast cancer was confirmed to be safe without negatively affecting patients' prognosis. "These findings are of paramount importance to raise awareness of the need for a deeper consideration of patients' pregnancy desire as a crucial component of their survivorship care plan. This starts with offering oncofertility counseling to all newly diagnosed young breast cancer patients," he said.

The study's first author, Eva Blondeaux, MD, a medical fellow in oncology at IRCCS Policlinico San Martino Hospital, said the higher risk of delivery and fetal complications indicates that physicians should more closely monitor pregnant breast cancer survivors compared with pregnant healthy women from the general population. However, the overall findings and the lack of negative effects on survival indicate that many women can successfully go through pregnancy after breast cancer.

The authors said the study's main limitation was that it did not allow for examination of individual patient data, and most of the included studies were retrospective analyses.

PORTLAND, Oregon | December 9, 2020 -- Across the North Pacific, salmon fisheries are struggling with climate variability, declining fish populations, and a lack of sustainable fishing opportunities. According to a study published today in BioScience from a team of Indigenous leaders and conservation scientists, help lies in revitalizing Indigenous fishing practices and learning from Indigenous systems of salmon management.

"Salmon and the communities that depend on them have been pushed to the brink by two centuries of extractive natural resource management," says lead author Dr. Will Atlas, Salmon Watershed Scientist with the Portland-based Wild Salmon Center. "But the tools, practices, and governance systems of Indigenous Peoples maintained healthy salmon runs for millennia before that. Their knowledge is still here."

The paper documents how, for thousands of years, Indigenous communities around the North Pacific maintained sustainable salmon harvests by using in-river and selective fishing tools like weirs, traps, wheels, reef nets and dip nets. Following European contact, these traditional fisheries and governance systems were suppressed, and often outlawed outright, as commercial fishing interests came to dominate fisheries.

"As they're currently built, mixed-stock salmon fisheries are undermining the biodiversity needed for Pacific salmon to thrive," says Dr. Atlas. "Luckily, we have hundreds of examples, going back thousands of years, of better ways to fish. These techniques can deliver better results for all communities."

A key example explored in the study is Indigenous people's focus on terminal fisheries. By targeting salmon runs in river systems--rather than in the ocean, where more vulnerable and healthy stocks intermingle--Indigenous people harvest individual, known salmon runs. Selective fishing tools, like the Heiltsuk Nation's traditional-style fish weir in the Koeye River in British Columbia, also enable in-season monitoring, where fishers can assess a run's health in real time, while releasing non-target species unharmed.

"In my Nation, we use fish wheels, an ancient technology that used to be made out of cedar and natural fibers," says co-author Andrea Reid, a citizen of the Nisga'a Nation and an assistant professor in Indigenous Fisheries at the University of British Columbia's Institute for Oceans and Fisheries. "Today, we use modernized fish wheels to monitor, mark, and study the fish, to understand how they are doing in a rapidly changing world."

Indigenous salmon management knowledge stems from more than respect for a primary food source. For many communities, salmon are at the center of creation stories, ceremonies, family structures, and cultural identity.

"The ancient relationship between Heiltsuk and salmon infiltrates every aspect of Heiltsuk life," says co-author William Housty, a member of the Heiltsuk Nation and Board Chair with the Heiltsuk Integrated Resource Management Department in Bella Bella, British Columbia. "Our modern-day management of salmon is based on the values of respect, reciprocity, and wellbeing."

As colonization severed access to traditional fisheries, Tribes and First Nations have experienced complex, ongoing harms. Restoring Indigenous co-governance to salmon management is a crucial part of the reconciliation process. According to the study's authors, restoring Indigenous governance can also help decentralize salmon management decisions at a time when diverse climate impacts are challenging watersheds like never before.

"In an era of rapid global change, we must explore different salmon management approaches," says co-author Dr. Jonathan Moore, a professor in Biological Sciences at British Columbia's Simon Fraser University. "By reinvigorating Indigenous practices, we can bring time-tested lessons to salmon fisheries and take a positive step toward recognizing the cultural fabric that has woven salmon and humans together for millennia."
There's still hope for these fisheries, the authors say, if managers embrace Indigenous communities' focus on terminal fisheries and selective fishing tools, strengthen Indigenous co-governance, and decentralize salmon management decisions with climate resiliency in mind.

The observation of a chemical reaction at the molecular level in real-time is a central theme in experimental chemical physics. An international research team has captured roaming molecular fragments for the first time. The work, under the supervision of Heide Ibrahim, research associate at the Institut national de la recherche scientifique (INRS), was published in the journal Science.

The research group of the Énergie Matériaux Télécommunications Research Centre of INRS, with support of Professor François Légaré, has used the Advanced Laser Light Source (ALLS). They have succeeded in shooting the first molecular film of "roamers" (hydrogen fragments, in this case, that orbit around HCO fragments) during a chemical reaction, by studying the photo-dissociation of formaldehyde, H2CO.

A molecular road trip

"What we see in this new discovery is that, just like in a "road trip", the final goal is not known at the beginning nor is the path always straightforward. In general, molecules, like humans, follow the easiest path to get from point A to point B, in order to minimize the energy expended", explains Heide Ibrahim. "However, sometimes travellers may decide to take a little detour". Apparently, the same is true for fragments of molecules. This process called "roaming" was first discovered in formaldehyde molecules in 2004. Since then, indirect traces of wandering fragments, called "roamers", have been detected in many molecular systems.

However, it is only recently that Dr. Ibrahim's team has been able to "catch them along the way", to pursue the analogy, and captured them in real-time. This is the first direct observation of the elusive phenomenon of "roaming" observed to date. "It is as if, following the discovery of dinosaur footprints, a film was discovered showing them wandering!", continues the researcher.

Mapping the fragments

In addition to this roaming journey, there is also conventional dissociation, where the molecule splits into fragments upon excitation by ultrashort UV laser pulses. The fragments can reach the same end-products by following direct (dissociation) or indirect (roaming) pathways. "To conduct this work, one cannot simply wait for the arrival of a fragment at the finish line, since this does not provide any information on the dynamics it has undergone. It was as if the road trip was done without GPS and we could not retrace the route taken by the travellers", underlines Heide Ibrahim. To remedy this, the team found a way to identify which fragment followed which path by placing checkpoints along the route, which act a bit like cell towers allowing a signal to be activated at a specific point along the route.

One of the numerous challenges in the experiments was related to the fact that the signal of these undecided molecules occurs statistically. Imagine wanting to take a picture of a traveller on the road, but you only have the name of the road and he may pass by at any time throughout the week. To add to the difficulty, the experimental signal, in this case, is ultrafast (on the scale of 100 femtoseconds, or ten billion times less than a millisecond) while extending over several orders of magnitude in time. Tomoyuki Endo, the first author of the study, a former post-doc of INRS now at the Kansai Photon Science Institute (Japan), was able to follow the "roamers" using a technique called time-resolved Coulomb Explosion Imaging (CEI).

The teams of Michael Schuurman (National Research Council, Ottawa), Paul Houston (Cornell University, Ithaca, USA) and Joel Bowman (Emory University, Atlanta, USA) provided high-level theoretical support at all critical experimental stages.

"The results show that time-resolved CEI can go beyond the imaging of coherent molecular dynamics - here, we follow statistical processes using conventional tabletop ultrafast lasers," says Professor Légaré, director of the ALLS lab where the experiments took place. "In the near future, thanks to advances in high repetition rate laser systems, it will be possible to study more complex molecules."

"Although roaming remains an elusive process that is difficult to grasp, this scientific breakthrough provides insight into how to measure it - as well as other statistical processes that require highly sensitive detection, in the face of disruptive background signals," concludes Heide Ibrahim. Ultimately, this may be just the beginning of another winding journey towards some of Mother Nature's secrets; roaming is a process whose role in environmental and atmospheric chemistry is only at the beginning of being understood."

Scientists have produced a tomato enriched in the Parkinson's disease drug L-DOPA in what could become a new, affordable source of one of the world's essential medicines.

The development of the genetically modified (GM) tomato has implications for developing nations where access to pharmaceutical drugs is restricted.

This novel use of tomato plants as a natural source of L-DOPA also offers benefits for people who suffer adverse effects - including nausea and behavioral complications - of chemically synthesised L-DOPA .

Tomato - was chosen as a widely cultivated crop that can be used for scaled up production and potentially offering a standardised and controlled natural source of L-DOPA .

The John Innes Centre led team modified the tomato fruit by introducing a gene responsible for the synthesis of L-DOPA in beetroot where it functions in the production of the pigments betalains.

L-DOPA is produced from tyrosine, an amino acid found in many foods. The research team inserted a gene encoding a tyrosinase, an enzyme that uses tyrosine to build molecules such as L-DOPA . This elevated the level of L-DOPA specifically in the fruit part of the plant and led to higher yields than those associated with L-DOPA production in the whole plant.

The levels achieved in the tomato fruit - 150mg of L-DOPA per kg of tomatoes - were comparable those observed in other L-DOPA accumulating plants - without some of the known drawbacks that have hampered plant metabolic production of the drug previously.

The aim now is to create a production pipeline where L-DOPA is extracted from the tomatoes and purified into the pharmaceutical product.

Professor Cathie Martin (FRS), corresponding author of the study explains: "The idea is that you can grow tomatoes with relatively little infrastructure. As GMOs (genetically modified organisms) you could grow them in screen houses, controlled environments with very narrow meshes, so you would not have pollen escape through insects.

"Then you could scale up at relatively low cost. A local industry could prepare L-DOPA from tomatoes because it's soluble and you can do extractions. Then you could make a purified product relatively low tech which could be dispensed locally."

Parkinson's disease is a growing problem in developing countries where many people cannot afford the daily $2 price of synthetic L-DOPA .

L-DOPA is an amino acid precursor of the neuro-chemical dopamine and is used to compensate for the depleted supply of dopamine in Parkinson's disease patients.

Also known as Levodopa, L-DOPA has been the gold standard therapy for Parkinson's disease since its establishment as a drug in 1967. It is one of the essential medicines declared by the World Health Organisation (WHO) and its market value is in the hundreds of billions of dollars.

The most common form of the drug is produced by chemical synthesis, but natural sources are also available. Only a few plants have been reported to contain measurable quantities of the molecule, mainly in seeds.

The most studied is the velvet bean, Mucuna pruriens, which contains up to 10% L-DOPA in its seeds. But this is problematic because the plant is covered in urticating hairs that contain mucunian that can cause irritation and allergic reactions in field workers who harvest the crop. The beans themselves cause elevated levels of tryptamines that can cause hallucinations in Parkinsons disease patients.

"We have demonstrated that the use of the tyrosinase-expressing tomatoes as a source of L-DOPA is possible. It's a further demonstration of tomato as a strong option for synthetic biology. Additionally, there were surprising beneficial effects including improvement in shelf-life and raised levels of amino-acids that we can investigate," says first author Dr Dario Breitel.

Bacteria is all around us--not just in bathrooms or kitchen counters, but also inside our bodies, including in tumors, where microbiota often flourish. These "small ecologies" can hold the key to cancer drug therapies and learning more about them can help development new life-saving treatments.

What happens when different strains of bacteria are present in the same system? Do they co-exist? Do the strongest survive? In a microbial game of rock-paper-scissors, researchers at the University of California San Diego's BioCircuits Institute uncovered a surprising answer. Their findings, titled "Survival of the weakest in non-transitive asymmetric interactions among strains of E. coli," appeared in a recent edition of Nature Communications.

The research team consisted of Professor of Bioengineering and Molecular Biology Jeff Hasty; Michael Liao and Arianna Miano, both bioengineering graduate students; and Chloe Nguyen, a bioengineering undergraduate. They engineered three strains of E. coli (Escherichia coli) so that each strain produced a toxin that could kill one other strain, just like a game of rock-paper-scissors.

When asked how the experiment came about, Hasty commented, "In synthetic biology, complex gene circuits are typically characterized in bacteria that are growing in well-mixed liquid cultures. However, many applications involve cells that are restricted to grow on a surface. We wanted to understand the behavior of small engineered ecologies when the interacting species are growing in an environment that is closer to how bacteria are likely to colonize the human body."

The researchers mixed the three populations together and let them grow on a dish for several weeks. When they checked back they noticed that, across multiple experiments, the same population would take over the entire surface--and it wasn't the strongest (the strain with the most potent toxin). Curious about the possible reasons for this outcome, they devised an experiment to unveil the hidden dynamics at play.

There were two hypotheses: either the medium population (called "the enemy of the strongest" as the strain that the strongest would attack) would win or the weakest population would win. Their experiment showed that, surprisingly, the second hypothesis was true: the weakest population consistently took over the plate.

Going back to the rock-paper-scissor analogy, if we assume the "rock" strain of E.coli has the strongest toxin, it will quickly kill the "scissor" strain. Since the scissor strain was the only one able to kill the "paper" strain, the paper strain now has no enemies. It's free to eat away at the rock strain slowly over a period of time, while the rock strain is unable to defend itself.

To make sense of the mechanism behind this phenomenon, the researchers also developed a mathematical model that could simulate fights between the three populations by starting from a wide variety of patterns and densities. The model was able to show how the bacteria behaved in multiple scenarios with common spatial patterns such as stripes, isolated clusters and concentric circles. Only when the strains were initially distributed in the pattern of concentric rings with the strongest in the middle, was it possible for the strongest strain to take over the plate.

It is estimated microbes outnumber human cells 10 to 1 in the human body and several diseases have been attributed to imbalances within various microbiomes. Imbalances within the gut microbiome have been linked to several metabolic and inflammatory disorders, cancer and even depression. The ability to engineer balanced ecosystems that can coexist for long periods of time may enable exciting new possibilities for synthetic biologists and new healthcare treatments. The research that Hasty's group is conducting may help lay the foundation to one day engineer healthy synthetic microbiomes that can be used to deliver active compounds to treat various metabolic disorders or diseases and tumors.

Vice Chancellor for Research Sandra Brown said, "Bringing together molecular biology and bionengineering has allowed discovery with the potential to improve the health of people around the world.  This is a discovery that may never have occurred if they weren't working collaboratively. This is another testament to the power of UC San Diego's multidisciplinary research."

Researchers have discovered a new superhighway network to travel through the Solar System much faster than was previously possible. Such routes can drive comets and asteroids near Jupiter to Neptune's distance in under a decade and to 100 astronomical units in less than a century. They could be used to send spacecraft to the far reaches of our planetary system relatively fast, and to monitor and understand near-Earth objects that might collide with our planet.

In their paper, published in the Nov. 25 issue of Science Advances, the researchers observed the dynamical structure of these routes, forming a connected series of arches inside what's known as space manifolds that extend from the asteroid belt to Uranus and beyond. This newly discovered "celestial autobahn" or "celestial highway" acts over several decades, as opposed to the hundreds of thousands or millions of years that usually characterize Solar System dynamics.

The most conspicuous arch structures are linked to Jupiter and the strong gravitational forces it exerts. The population of Jupiter-family comets (comets having orbital periods of 20 years)
as well as small-size solar system bodies known as Centaurs, are controlled by such manifolds on unprecedented time scales. Some of these bodies will end up colliding with Jupiter or being ejected from the Solar System.

The structures were resolved by gathering numerical data about millions of orbits in our Solar System and computing how these orbits fit within already-known space manifolds. The results need to be studied further, both to determine how they could be used by spacecraft, or how such manifolds behave in the vicinity of the Earth, controlling the asteroid and meteorite encounters, as well as the growing population of artificial man-made objects in the Earth-Moon system.

Membrane technology is widely used in various water treatment processes such as water desalination, sewage treatment, and advanced water treatment for producing clean tap water. The membrane filtration technology is a method that can significantly improve water quality and has been suggested as an alternative that can radically prevent larvae in the tap water that has become a widespread issue in Korea recently. However, the current membrane technology suffers from a rapid performance reduction due to the accumulation of bacterial adhesion on the membrane surface and the growth of microbial cells, leading to high maintenance costs.

The Korea Institute of Science and Technology (KIST) reported that the research team led by Dr. Jeehye Byun and Director Seok Won Hong from Water Cycle Research Center developed a membrane material that self-cleans biological contaminants through irradiation of sunlight. According to the team, the newly developed membrane material is expected to significantly reduce the cost of membrane management as the membrane can be reused after just 10 minutes of sunlight irradiation.

Water treatment membranes require periodic cleaning as the contaminants are accumulated on the membrane surface after water filtration. Currently, used membranes require to be cleaned with harsh chemicals for more than six hours at least once a week, which results in fairly high operating cost and damages the membranes due to the chemicals.

As a way to address these issues, the researchers at KIST firmly conjugated a visible-light-responsive photocatalyst to the water treatment membrane surface. This surface-modified photocatalytic membrane can fully decompose contaminants accumulated on the surface when irradiated with visible light, thereby easily cleaning the membrane. In particular, it displayed outstanding performance by removing 99.9% of bacteria, such as Escherichia coli and Staphylococcus aureus, and viruses, such as MS2 bacteriophage, accumulated on the membrane surface in less than an hour of light treatment. According to the team, the developed membrane can treat not only microbial cells but also organic contaminants such as dye solutions and heavy metals. Further, it showed the advantage of maintaining performance even after repeating the tests more than 10 times.

"Our research revealed that the efficiency of the water treatment processes can be improved by conjugating the photocatalytic technology and the water treatment membrane technology," Dr. Jeehye Byun from KIST said. "Based on these research results, we will endeavor to develop next-generation membranes that can lead the water treatment membrane market."

An interim analysis from the Swedish Drug-Elution Trial in Peripheral Arterial Disease (SWEDEPAD) has now been presented. It shows that, for patients with lower limb occlusive arterial disease, paclitaxel-coated balloons and stents do not bring about the rise in mortality previously reported. The study, led by the University of Gothenburg and published in The New England Journal of Medicine (NEJM), is expected to resonate internationally.

Peripheral arterial disease (PAD) is common, especially in older people, and causes poor blood circulation. The condition entails stenoses or occlusions of the arteries in the leg. This often causes severe pain, ulcers, and a high risk for lower limb amputation.

The most common treatment is endovascular balloon dilatation, sometimes combined with insertion of stents, small metal-mesh tubes that reinforce the vessel wall and prevent elastic recoil. The procedure, using a catheter inserted into the femoral artery in the groin, is minimally invasive -- that is, performed with the least possible surgical trauma to the body.

What the researchers did, as described in the current report, was to compare patients randomly assigned to undergo either dilation of the blood vessel with conventional devices, without any drug coating, or with the more expensive drug-coated devices, all of them using paclitaxel as coating agent. With data on approximately 2,300 patients included to date, the study is by far the largest of its kind in the world.

The finding, that mortality rates in the two different groups do not differ, is expected to be highly influential. The question of a possible increase in mortality among patients treated with paclitaxel coated balloons and stents has been a subject of lively debate in recent years.

In December 2018, a meta-analysis of all previous randomized studies was published by Dr Katsanos and co-workers. Surprisingly, the article reported increased mortality among patients who had received treatment with paclitaxel-eluting balloons and stents compared to control patients.

The use of these products then declined sharply all over the world and the U.S. Food and Drug Administration (FDA) was among the organizations that urged caution in using them. In the subsequent discussion, the 2018 results were called in question; but until now no randomized study sufficiently large to settle the matter has been carried out.

The first author of the NEJM article, and also chair of the steering group of this study, is Joakim Nordanstig, associate professor of vascular surgery at Sahlgrenska Academy, University of Gothenburg, and senior vascular surgeon at the Sahlgrenska University Hospital.

"We're proud and pleased that we in this way were able to provide a solution to the tricky clinical dilemma that arose when long-term patient safety relating to the treatment with paclitaxel-coated balloons and stents was called into question," Nordanstig says.

"Above all, our results are important for all the patients who are living with PAD and are facing a lower limb arterial procedure. Drug-eluting balloons and stents have been used widely around the world, and currently represent the most promising technique we have for preventing postoperative recurrence of stricture in the dilated artery. That kind of recurrent stricture is by far the most important limitation of invasive interventions in PAD, and it's something that affects a lot of patients," he continues.

"It's also hugely gratifying that Swedish vascular surgery and interventional radiology, working really well together, have truly been able to help solve an international treatment dilemma. Our study is definitely a team effort, and all the vascular surgeons, interventional radiologists and vascular and radiology nurses in Sweden who've taken part can stand a bit taller today."

The corresponding author, and also the principal investigator of SWEDEPAD, Mårten Falkenberg, professor of vascular interventions at Sahlgrenska Academy, adds that the study is funded mainly by the Swedish Research Council. It is carried out within the framework of Swedvasc (Sweden's National Quality Registry for Vascular Surgery), which is administered by the Uppsala Clinical Research Center (UCR) at Uppsala University. UCR is where the study platform was developed and the data processing has taken place. Scientists at UCR have previously conducted several studies of a similar design, and the collaboration between the University of Gothenburg and UCR has been a success factor.

"It's unusual for an interim analysis to be published in the world's top-ranking medical journal. The reason for it is that, in all probability, our finding -- although it's a negative one and thus doesn't demonstrate any differences between the treatment groups -- solves a medical dilemma with major clinical and financial implications world-wide," Falkenberg says.

"With this convincing and reassuring result, we've resumed our study, and a further 1,400 patients are now to be included. When it's all complete, we expect to be able to show whether the new technique, using drug-eluting balloons and stents, improves the outcomes that are most important for patients with peripheral arterial disease; decreased amputation rate and improved quality of life, as this still remains to be proven", Mårten Falkenberg concludes.

The mummified remains of ancient Egyptians hold many secrets, from the condition of the bodies to the artifacts placed within the burial garments. Now a team of researchers has found a way to unwrap those secrets, without unraveling the mummies themselves.

Three years ago, researchers from Northwestern University, in preparation for an exhibit on campus, carefully transported a 1,900-year-old mummy to the Advanced Photon Source (APS), a U.S. Department of Energy (DOE) Office of Science User Facility at DOE’s Argonne National Laboratory. There scientists used powerful X-ray beams to peer inside the layers of linen and resin to examine the 2,000-year-old bones and objects buried within.

“Such synergy between high technology and archaeology highlights what is possible when typical research boundaries are crossed.” — Marc Walton, Northwestern University’s Center for Scientific Studies in the Arts and McCormick School of Engineering

The results of this experiment, the first time an intact mummy was examined using X-ray diffraction techniques, were recently published in the Journal of the Royal Society Interface. The examinations confirmed several details about the mummy — the body belonged to a child of about five years old, most likely a girl, and was buried with what appears to be a scarab amulet of calcite, a sacred object meant to spiritually protect the body on its passage to the afterlife.

“We knew there were objects within the mummy, and we wanted to find out which materials were present,” said Stuart Stock, research professor of cell and molecular biology at Northwestern University’s Feinberg School of Medicine and the first author on the paper. “Short of opening the mummy, there’s no way other than X-ray diffraction to identify those materials.”

Ancient Egyptians believed it was important to preserve dead bodies in as lifelike a manner as possible. The extensive process they used is called mummification, and it involved removing all moisture from the body before wrapping the deceased in many layers of linens sealed with resin. Egyptians began mummifying the dead around 2,600 B.C, according to the Smithsonian Institution, and continued for more than 2,000 years.

Experts dated this particular mummy back to the Roman era (beginning in 30 B.C.). It was discovered in Hawara, Egypt and excavated in 1911, eventually making its way to the library of the Garrett-Evangelical Theological Seminary on Northwestern’s Evanston, Illinois campus. In 2018, the mummy became the centerpiece of an exhibition on campus, joining a series of Roman-Egyptian mummy portraits, representations of people embalmed within mummies that were excavated from areas near Hawara.

In preparation for the exhibit, Stock was asked to conduct research on the contents. He began by imaging it with a medical computed tomography (CT) scanner, which provided a roadmap of sorts for his work at the APS. The CT scan, Stock said, showed the team exactly where to aim the powerful X-ray beams generated by the APS, allowing them to complete their X-ray experiments in 24 hours.

“Without the CT scan to refer to, this literally would have taken two weeks,” Stock said.

The Northwestern team had the help of APS physicist and group leader Jonathan Almer of Argonne’s X-ray Science division, a co-author on the paper. Almer leads the scientific team at Beamline 1-ID, which makes use of high-energy X-rays that can penetrate larger samples. Even so, Almer said, this was one of the largest objects measured at the APS — more than three feet long, weighing roughly 50 pounds.

“This proves that we can find a needle in a haystack,” Almer said. “Often our research is looking for micron-level objects in a millimeter-sized sample. This was a scaling-up of work we do every day, and it shows that we can experiment with and see within a wide range of size scales.”

Also important, Almer noted, was that the X-ray beams could peer inside the mummy without damaging it. This non-invasive method, combined with the earlier CT scan, revealed several pieces of information that would not have been possible to determine otherwise.

The young girl’s skeleton, Stock said, is well preserved and shows no signs of trauma, meaning the child likely died of disease. While Stock and his colleagues were not able to conclusively determine the sex of the mummy, he said that evidence points to it being female, which would match the portrait discovered with the mummy. X-rays detected several small pins holding areas of the linen together, and Stock said he was able to determine they were made of modern metals, probably added 20 years ago as part of exhibiting the mummy.

Most surprising, Stock said, was the amulet (called Inclusion F in the paper), which turned out to be made of calcite, a carbonate mineral. While it is not unheard of for these amulets to be made of calcite, he said, it is rare, and knowing the composition will allow scientists to trace it to a time and place of origin.

Marc Walton, co-director of the Center for Scientific Studies in the Arts and research professor of materials science and engineering at Northwestern’s McCormick School of Engineering, worked with colleagues to place the mummy in a social and historical context for the 2018 exhibition, and was the scientist who brought Stock aboard the project. He said this study shows how an archaeological object can inspire new scientific directions.

“Not only does this work provide historians with data on the composition of the mummy, its burial conditions, and, therefore, its biography, but the complexity of the composite object pushed the authors to innovate new methods of synchrotron-based X-ray diffraction,” he said. “Such synergy between high technology and archaeology highlights what is possible when typical research boundaries are crossed.”

Stock said that while this method of examining the interiors of mummies may not be widely used in the future, given the logistical challenges, it may help scientists answer questions that otherwise would remain mysteries.

“It may be the only way to get out important information without disturbing the mummies,” he said.

Researchers from the Laboratory for Atmospheric and Space Physics (LASP) at the University of Colorado Boulder are diving into the dusty environment that surrounds the sun--a search that could help to reveal how planets like Earth come into being.

The pursuit comes by way of NASA's Parker Solar Probe, a pioneering mission that has taken scientists closer to Earth's home star than any spacecraft to date. Over two years, the probe has circled the sun six times, hitting maximum speeds of roughly 290,000 miles per hour.

In the process, the Parker team has learned a lot about the microscopic grains of dust that lie just beyond the sun's atmosphere, said David Malaspina, a space plasma physicist at LASP. In new research, for example, he and his colleagues discovered that the densities of these bits of rock and ice seem to vary wildly over the span of months--not something scientists were expecting.

"Every time we go into a new orbit, and we think we understand what we're seeing around the sun, nature goes and surprises us," said Malaspina, also an assistant professor in the Department of Astrophysical and Planetary Sciences.

He will present the group's results Tuesday, Dec. 8 at the 2020 virtual fall meeting of the American Geophysical Union (AGU).

Malaspina said that dust can give researchers an unexpected, and tiny, window into the processes that formed Earth and its neighboring planets more than 4.5 billion years ago.

"By learning how our star processes dust, we can extrapolate that to other solar systems to learn more about planet formation and how a cloud of dust becomes a solar system," he said.

Solar Dyson

The area just around the sun, a hot and radiation-rich environment, is often dustier than you might imagine, Malaspina said. It contains more grains of dust by volume than most other open expanses of space in the solar system. That's because the star, through gravity and other forces, pulls dust toward it from millions to billions of miles away, a bit like a vacuum cleaner.

But this vacuum cleaner is imperfect. As dust particles get closer to the sun, its radiation pushes on them more and more--some of those grains of dust will begin to blow in the other direction and can even fly out of the solar system entirely. The Wide-Field Imager for Parker Solar Probe (WISPR) instrument suite onboard the spacecraft found the first evidence for the existence of this dust-devoid region, known as the dust-free zone, more than 90 years after it was predicted.

"What you get is this really interesting environment where all of these particles are moving inward, but once they reach the near-sun environment, they can be blown away," Malaspina said.

Since launching in 2018, Parker Solar Probe--built and operated by the Johns Hopkins Applied Physics Laboratory, which also leads the mission for NASA--has flown to within about 11.6 million miles of the Sun's surface.

On each of Parker's orbits around the sun, the spacecraft collided with thousands of grains of dust. Many of these particles vaporize on the spot, creating a small burst of charged particles that the probe can detect using the five antennae that are part of its FIELDS Experiment. LASP plays an important role in this experiment, which is led by the University of California, Berkeley. Think of it like studying insect populations by counting the splatters on your car's windshield.

"You get a small puff of plasma," Malaspina said. "By looking at these spikes, we can understand how many dust impacts we're getting hit by."

New mysteries

Malaspina and his colleagues were originally hoping to use those puffs to pinpoint where exactly the solar system's inward-flying dust becomes outward-flying dust. But they stumbled on something puzzling in the process: The concentrations of dust that the team recorded seemed to vary by as much as 50% between Parker's six orbits around the Sun.

"That's really interesting because the timescale that it takes for dust to move in toward the Sun is thousands to millions of years," Malaspina said. "So how do we get variation in just three or four months?"

This dusty environment, in other words, may be a lot more complicated and fast-shifting than scientists previously thought. Malaspina said that the team will need to wait for Parker to complete more orbits to know exactly what's happening. He's just excited to be part of this once-in-a-lifetime chance to run a finger along the Sun's dusty shelves.

"This is the only in-situ measurement we are going to get for a long time in the inner solar system," Malaspina said. "We're trying to make the best of it and learn as much as we can."

Many proteins are required to maintain the structure, and to preserve the genetic integrity, of DNA. Sliding clamps are proteins that increase the efficiency of DNA replication. Without these proteins, cells would not be able to carry out continuous DNA synthesis, and organisms, from bacteria to humans, would not survive.

Sliding clamps are ring-shaped proteins that encircle DNA and bind to the DNA polymerase, the enzyme that performs the actual DNA replication. They effectively organize and orient the DNA and its ancillary proteins so as to enable replication. Sliding clamps are oligomeric proteins; they are made up of more than one identical copy of individual proteins called monomers.

The bacterial E. coli clamp, called beta, is made up of two identical monomers. Human cells contain clamps called PCNA, which are made up of three identical monomers. Strong intermolecular forces between these identical monomers ensure that the rings are stable in solution and do not fall off the DNA during replication.

The self-assembly of the monomers of sliding clamps into a stable doughnut-shape ring is controlled by ionic and other intermolecular forces. It is known that assembly of these structures can be influenced by the presence of salts, but other forms of molecular control over this self-assembly are not well understood. In an effort to understand the molecular basis for clamp self-assembly, associate Professor Marcia Levitus from School of Molecular Sciences and co-workers have now found that these protein doughnuts assemble in previously-unknown ways when exposed to molecules that bacteria typically use to tolerate high levels of salt in the environment.

Specifically, potassium glutamate (KGlu) and glycine betaine are found to promote self-assembly of beta and PCNA clamps into structures containing many doughnuts stacked face-to-face. These structures resemble tubes of doughnuts, and are only observed in the presence of compounds that cells produce when they need to tolerate high salt concentrations in the growing medium.

Their research, which has just been published in the Biophysical Journal, is a result of a long-standing collaboration with Professor Linda Bloom who works in the department of biochemistry and molecular biology, University of Florida.

"In this study we examine non-Coulombic effects on the self-assembly properties of sliding clamps," explained Levitus. "We determined relative diffusion coefficients of two sliding clamps using fluorescence correlation spectroscopy. Although so far we worked with two sliding clamps, our results suggest that our findings are not specific to these proteins and may be generalizable to a wide range of protein-protein interactions." Levitus is also part of the Biodesign Center for Single Molecule Biophysics.

Cells accumulate glutamate and related molecules under stress, and so formation of high-order protein assemblies under these conditions has important biological implications. Specifically, this would represent a mechanism by which the presence of stressor compounds in the cell could control DNA replication.