Culture

A study of 49 patients reveals that toxins from the bacterial pathogen Staphylococcus aureus can destroy the body's blood-clotting platelets, raising the risk of death during bacterial blood infections. Further experiments in mice also showed that the approved drugs ticagrelor and oseltamivir protected platelets and helped treat infections, suggesting these compounds could be repurposed into badly needed therapies for blood infections. Bacterial blood infections have mortality rates as high as 20% to 30% even with supportive care, and these rates have remained high for decades. Blood infections can also cause complications such as sepsis and endocarditis, and the rise of multidrug resistance has only compounded what was already a serious threat to public health. Infections with S. aureus are particularly difficult to treat, as the bacteria possess a range of tricks and defense mechanisms that allow them to evade or resist immune cells and antibiotics. While studying 49 patients with S. aureus blood infections, Josh Sun and colleagues discovered that many patients who succumbed showed abnormally low counts of platelets - small blood-clotting cells that can also combat infections. Follow-up experiments showed that S. aureus targeted platelets by secreting a toxin that destroyed platelet proteins, and by accelerating the clearance of platelets through the Ashwell-Morell receptor on liver cells. However, the approved blood thinner ticagrelor and the flu antiviral oseltamivir both protected platelets from the toxin-induced clearance in mice with S. aureus blood infections and improved survival. Sun et al. speculate that these drugs, if repurposed, could be combined with platelet infusions to further restore and protect platelet counts in ailing patients.

Immunotherapy, which recruits the body's own immune system to attack cancer, has given many cancer patients a new avenue to treat the disease.

But many cancer immunotherapy treatments can be expensive, have devastating side effects, and only work in a fraction of patients.

Researchers at the Pritzker School of Molecular Engineering at the University of Chicago have developed a new therapeutic vaccine that uses a patient's own tumor cells to train their immune system to find and kill cancer.

The vaccine, which is injected into the skin just like a traditional vaccine, stopped melanoma tumor growth in mouse models. It even worked long-term, destroying new tumors long after the therapy was given.

The results were published March 24 in the journal Science Advances.

"This is a new strategy for immunotherapy," said Prof. Melody Swartz, who led the research. "It has the potential to be more efficacious, less expensive and much safer than many other immunotherapies. It is truly personalized medicine that has the potential to overcome many issues that arise with other treatments."

Recruiting a broad immune response

In many ways, the vaccine works like a traditional flu vaccine: it uses a less-potent version of the pathogen (here, a patient's own cancer cells, which are lethally irradiated before injection) to train the immune system to fight the disease.

However, rather than a preventive measure, this is a therapeutic vaccine, meaning it activates the immune system to destroy cancer cells anywhere in the body. To create it, Swartz and her team used melanoma cells from mice and then engineered them to secrete vascular endothelial growth factor C (VEGF-C).

VEGF-C causes tumors to strongly associate with the body's lymphatic system, which is normally considered bad for the patient, since it can promote metastasis. But the team recently found that when tumors activate surrounding lymphatic vessels, they are much more responsive to immunotherapy and promote "bystander" T cell activation, leading to a more robust and long-lasting immune response.

The team then had to figure out how to harness the benefits of lymphatic activation in a therapeutic strategy while avoiding the potential risks of metastasis.

'Training' the immune system

Maria Stella Sasso, a postdoctoral fellow and first author of the paper, tested many different strategies before settling on the vaccine approach, which allowed immune "training" in a site distant from the actual tumor.

The strategy of using a patient's own irradiated tumor cells in a therapeutic vaccine had previously been established by Glenn Dranoff and colleagues at the Novartis Institutes for BioMedical Research. Dranoff and team developed GVAX, a cancer vaccine that has been shown safe in clinical trials. Sasso decided to try this approach with VEGF-C rather than the cytokine used in GVAX. She dubbed the strategy "VEGFC-vax."

After engineering the cells to express VEGF-C, the research team irradiated them, so they would die within a few weeks. When they injected the cells back into the skin of mice, they found that the dying tumor cells could attract and activate the immune cells, which then could recognize and kill the actual tumor cells growing on the opposite side of the mouse. Since each tumor has its own unique signature of hundreds of molecules that the immune system can recognize, the vaccine promoted a broad, robust immune response.

That led to the prevention of tumor growth in all of the mice. It also led to immunological memory, preventing new tumor growth when tumor cells were re-introduced 10 months later.

"This shows that the therapy may provide long-term efficacy against metastasis and relapse," said Swartz, William B. Ogden Professor of Molecular Engineering.

Potential therapy for many types of cancers

Conceptually, this is the first strategy to exploit the benefits of local lymphatic vessel activation for more robust and specific immune response against tumor cells.

Unlike immunotherapeutic strategies that stimulate the immune system in a general way, such as checkpoint blockade or the many cytokines currently in preclinical development, this new immunotherapy activates only tumor-specific immune cells. Theoretically, this would avoid common side effects of immune stimulants, including immunotoxicity and even death.

And while many other cancer immunotherapies, such as CAR-T cell therapy, are tumor-specific, these strategies only work against tumor cells that express specific pre-identified tumor markers called antigens. Cancer cells can eventually overcome such treatments by shedding these markers or mutating, for example.

VEGFC-vax, however, can train immune cells to recognize a large number and variety of tumor-specific antigens. More importantly, these antigens do not need to be identified ahead of time.

The researchers are working to test this strategy on breast and colon cancers and think it could theoretically work on any type of cancer. They hope to ultimately take this therapy to clinical trials.

"We think this has huge promise for the future of personalized cancer immunotherapy," Swartz said.

News coverage of expert scientific evidence on vaccine safety is effective at increasing public acceptance of vaccines, but the positive effect is diminished when the expert message is juxtaposed with a personal narrative about real side effects, new research has found.

The study, by researchers affiliated with the Annenberg Public Policy Center (APPC) of the University of Pennsylvania and the University of Illinois, tested the effects of messages about vaccination in televised news reports. These included video clips of Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, talking about evidence supporting the value and safety of the MMR (measles, mumps and rubella) vaccine, and a mother who's refusing to vaccinate her youngest child because her middle child, who is shown with a rash, had what she characterized as severe reactions after receiving the MMR vaccine.

The research, published in PLOS ONE, is based on an experiment with a nationally representative sample of 2,345 participants during the 2019 U.S. measles outbreak.

The study, "The Effects of Scientific Messages and Narratives About Vaccination," found that:

Fauci's "science-supporting" message had significant positive effects on views about vaccination when compared with a control message. Participants exposed to the expert message had lower perceptions of risk from vaccination; stronger pro-vaccine policy views; and stronger intentions to send a pro-vaccine letter to a state representative and to encourage other people to vaccinate their children.

The "hesitancy-inducing" narrative by the mother had no significant effect by itself on these outcomes.

But when the two messages were juxtaposed, with video of the mother preceding Fauci, the mother's hesitancy narrative diminished the effectiveness of the pro-vaccine message, according to some measures.

"In this paper," the authors write, "we treated parental reports of potentially real side effects as Hesitancy-Inducing Narratives because, even when accurate, their portrayal in media can lead to overgeneralization and fuel vaccine hesitancy by leading the public to draw inaccurate inferences about the prevalence and severity of side effects. In short, individual cases of vaccine side effects, even if true, may elicit false inferences, and the media's reliance on dramatic and vivid cases may lead to overestimation of risks that are relatively rare."

The research

The experiment was conducted from February 28-March 18, 2019, during the largest U.S. measles outbreak in over a quarter-century. "We often wondered about stories of vaccine side effects - like the concerns we've heard recently with the COVID-19 vaccines," said lead author Ozan Kuru, who worked on the study as a postdoctoral fellow at APPC and is now an assistant professor in the Department of Communications and New Media at the National University of Singapore. "Do those stories have negative effects on support for vaccines, and how do we ensure that people have an accurate understanding of the science?"

Prior research has failed to simulate the actual news environment by assessing the effects of exposure both to experts' messages about the value of vaccination and to personal accounts of the reasons for vaccination hesitance that discuss actual but relatively rare side effects.

According to the Centers for Disease Control and Prevention (CDC), "soreness, redness or rash where the shot is given and rash all over the body can happen after MMR vaccine," while "more serious reactions happen rarely," including seizures, temporary pain and stiffness in the joints, pneumonia, and swelling of the brain and/or spinal cord covering. "As with any medicine, there is a very remote chance of a vaccine causing a severe allergic reaction, other serious injury or death."

The researchers said, "This dual aspect of vaccine side effects - their rare existence and people's tendency to overgeneralize from individual stories - places their portrayal in the media in what we consider a gray zone between accurate and misleading information. We thus posit that media coverage of such stories without proper contextualization can be misleading and has the potential to influence public opinion."

Vaccine videos

In this experiment, the researchers used edited videos from televised news coverage with the network identification removed. The 2,345 participants were randomly assigned to view one of six short, edited video clips:

(1) the mother's "hesitancy-inducing" narrative;

(2) Fauci's expert, "science-supporting" statistics-heavy video;

(3) a "science-supporting" video of parents whose children would be endangered if exposed to measles but could not get the vaccine for other health reasons or who had caught measles and experienced complications;

a combination of the mother's narrative (1) and Fauci (2);

a combination of the mother's narrative (1) and the other parents (3);

a control video about the benefits of aspirin.

After watching the videos, the participants answered questions about vaccine risk, support for pro-vaccine policies, their intentions to encourage parents to vaccinate their children, and whether they would agree to send a pro-vaccine letter to a state representative.

On the findings

Contrary to the researchers' initial hypothesis, the mother's "hesitancy-inducing" narrative did not by itself affect outcomes - which, the authors say, is "generally consistent with research suggesting that exposure to single messages rarely produced an impact." However, the fact that it lessened the positive effects of the Fauci video raises concerns and invites further study.

"It might be that when we hear the mother's narrative in isolation, we don't make a big deal of it," said co-author Dolores Albarracín, a professor of psychology and business administration at the University of Illinois at Urbana-Champaign and a distinguished research fellow at APPC. "But when people subsequently hear about the science, it prompts them to think about vaccines, they recall the mom, and this leaves them haunted by doubts."

Kathleen Hall Jamieson, a co-author and director of the Annenberg Policy Center, noted that Fauci is delivering an unconditional "it's safe" message about the MMR vaccine. "Nothing the mother says is inaccurate," Jamieson said. "We assume that exposure to her story and visualized evidence of her rash-ridden older child calls into question Dr. Fauci's categorical assertions about the safety of the vaccine."

The "science-supporting" video from the parents was found to be relatively ineffective compared with Fauci's message.

Implications for COVID-19 messaging

The researchers said the findings have important implications for public health messaging and newsroom decisions about coverage of COVID-19 vaccines.

"We are not recommending that the media stop reporting about vaccine safety and side effects," Albarracín said. "But our recommendation is that statistical information about vaccine trials should be communicated to the public repeatedly and early, before vivid narratives of side effects take hold."

Jamieson added, "The scientific community needs to remind the public that the benefits of using approved vaccines outweigh the risks - and that the risks associated with contracting the disease are substantially higher than any associated with the vaccine."

Scientists make pivotal discovery of method for wireless modulation of neurons with X-rays that could improve the lives of patients with brain disorders. The X-ray source only requires a machine like that found in a dentist’s office.

Many people worldwide suffer from movement-related brain disorders. Epilepsy accounts for more than 50 million; essential tremor, 40 million; and Parkinson’s disease, 10 million.

Relief for some brain disorder sufferers may one day be on the way in the form of a new treatment invented by researchers from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and four universities. The treatment is based on breakthroughs in both optics and genetics. It would be applicable to not only movement-related brain disorders, but also chronic depression and pain.

“Our high precision noninvasive approach could become routine with the use of a small X-ray machine, the kind commonly found in every dental office.” — Elena Rozhkova, a nanoscientist in Argonne’s Center for Nanoscale Materials

This new treatment involves stimulation of neurons deep within the brain by means of injected nanoparticles that light up when exposed to X-rays (nanoscintillators) and would eliminate an invasive brain surgery currently in use. 

“Our high-precision noninvasive approach could become routine with the use of a small X-ray machine, the kind commonly found in every dental office,” said Elena Rozhkova, a lead author and a nanoscientist in Argonne’s Center for Nanoscale Materials (CNM), a DOE Office of Science User Facility.

Traditional deep brain stimulation requires an invasive neurosurgical procedure for disorders when conventional drug therapy is not an option. In the traditional procedure, approved by the U.S. Food and Drug Administration, surgeons implant a calibrated pulse generator under the skin (similar to a pacemaker). They then connect it with an insulated extension cord to electrodes inserted into a specific area of the brain to stimulate the surrounding neurons and regulate abnormal impulses.

“The Spanish-American scientist José Manuel Rodríguez Delgado famously demonstrated deep brain stimulation in a bullring in the 1960s,” said Vassiliy Tsytsarev, a neurobiologist from the University of Maryland and a co-author of the study. “He brought a raging bull charging at him to a standstill by sending a radio signal to an implanted electrode.”

About 15 years ago, scientists introduced a revolutionary neuromodulation technology, “optogenetics,” which relies on genetic modification of specific neurons in the brain. These neurons create a light-sensitive ion channel in the brain and, thereby, fire in response to external laser light. This approach, however, requires very thin fiberoptic wires implanted in the brain and suffers from the limited penetration depth of the laser light through biological tissues.

The team’s alternative optogenetics approach uses nanoscintillators injected in the brain, bypassing implantable electrodes or fiberoptic wires. Instead of lasers, they substitute X-rays because of their greater ability to pass through biological tissue barriers.

“The injected nanoparticles absorb the X-ray energy and convert it into red light, which has significantly greater penetration depth than blue light,” said Zhaowei Chen, former CNM postdoctoral fellow.

“Thus, the nanoparticles serve as an internal light source that makes our method work without a wire or electrode,” added Rozhkova. Since the team’s approach can both stimulate and quell targeted small areas, Rozhkova noted, it has other applications than brain disorders. For example, it could be applicable to heart problems and other damaged muscles.    

One of the team’s keys to success was the collaboration between two of the world-class facilities at Argonne: CNM and Argonne’s Advanced Photon Source (APS), a DOE Office of Science User Facility. The work at these facilities began with the synthesis and multi-tool characterization of the nanoscintillators. In particular, the X-ray excited optical luminescence of the nanoparticle samples was determined at an APS beamline (20-BM). The results showed that the particles were extremely stable over months and upon repeated exposure to the high-intensity X-rays.

According to Zou Finfrock, a staff scientist at the APS 20-BM beamline and Canadian Light Source, “They kept glowing a beautiful orange-red light.”

Next, Argonne sent CNM-prepared nanoscintillators to the University of Maryland for tests in mice. The team at University of Maryland performed these tests over two months with a small portable X-ray machine. The results proved that the procedure worked as planned. Mice whose brains had been genetically modified to react to red light responded to the X-ray pulses with brain waves recorded on an electroencephalogram.

Finally, the University of Maryland team sent the animal brains for characterization using X-ray fluorescence microscopy performed by Argonne scientists. This analysis was performed by Olga Antipova on the Microprobe beamline (2-ID-E) at APS and by Zhonghou Cai on the Hard X-ray Nanoprobe (26-ID) jointly operated by CNM and APS.

This multi-instrument arrangement made it possible to see tiny particles residing in the complex environment of the brain tissue with a super-resolution of dozens of nanometers. It also allowed visualizing neurons near and far from the injection site on a microscale. The results proved that the nanoscintillators are chemically and biologically stable. They do not wander from the injection site or degrade.

“Sample preparation is extremely important in these types of biological analysis,” said Antipova, a physicist in the X-ray Science Division (XSD) at the APS. Antipova was assisted by Qiaoling Jin and Xueli Liu, who prepared brain sections only a few micrometers thick with jeweler-like accuracy.

“There is an intense level of commercial interest in optogenetics for medical applications,” said Rozhkova. “Although still at the proof-of-concept stage, we predict our patent-pending wireless approach with small X-ray machines should have a bright future.”

The related article “Wireless optogenetic modulation of cortical neurons enabled by radioluminescent nanoparticles” appeared in ACS Nano. In addition to Rozhkova, Chen, Finfrock, Antipova and Cai, another Argonne author is Rosemarie Wilton. University contributors include Vassiliy Tsytsarev, Dongyi Wang, Yi Liu, Brandon Gaitan, Yang Tao and Yu Chen from the University of Maryland, Department of Bioengineering; Hiroyuki Arakawa and Reha Erzurumlu from the University of Maryland School of Medicine; Fritz Lischka from the Uniformed Services University of the Health Sciences; Bryan Hooks from the University of Pittsburgh, Department of Neurobiology; and Huanghao Yang from Fuzhou University.

Researchers Mario Guarracino the HSE Laboratory of Algorithms and Technologies for Networks Analysis in Nizhny Novgorod and Julius ?ilinskas and Algirdas Lančinskas from Vilnius University, have proposed a new method of testing for COVID-19. This group method allows results to be obtained 13 times faster as compared to individual testing of each sample. The research paper was published in the journal Scientific Reports.

The COVID-19 pandemic has already affected millions of people from over 200 countries. The rapid virus expansion demonstrated how fast such infections can spread in today's globalized world. At the beginning of the pandemic, when little was known about the virus and vaccines had not yet been developed, it was possible to slow its spread only by means of limiting the population's mobility. Almost everyone around the world went through various lockdowns and periods of isolation. If large groups of people can be tested quickly, the restrictions can be less strict and more effective at the same time, believe the authors of the paper 'Pooled testing with replication as a mass testing strategy for the COVID-19 pandemics.'

Present COVID-19 testing solutions are based on the extraction of RNA from patients using oropharyngeal and nasopharyngeal swabs, and then testing with real?time PCR for the presence of specific RNA filaments identifying the virus. The speed of this approach is limited by the availability of reactants, trained technicians and laboratories.

One way to speed up the testing procedures is group testing, where the swabs of multiple patients are grouped together and tested. The swabs from groups that return a positive result are then tested individually in order to detect specific COVID-19 positive patients. This approach helps decrease the number of tests twofold or more (depending on the spread of the disease) as compared to individual testing of each swab.

For example, suppose 96 samples should be tested and pools of up to 12 samples are possible. In individual testing, 96 tests are necessary. In pool testing, 8 pools of 12 samples are taken and testing is performed. If the result of one pool is positive, then additional 12 individual tests are needed. If two or three groups return a positive result, 24 or 36 additional tests are required, which, together with the first eight tests, will mean a decrease in the number of tests from two to five times as compared to individual testing.

The researchers believe that the number of tests can be decreased by optimizing the size of groups that takes into account the total number of swabs and the forecasted number of infected individuals. As the number of infected individuals increases, the possibility of saving swabs decreases but is still about 40% in the event of an incidence of 100 positive samples per 1,000, and 18% for an incidence of 200 per 1,000.

There are ways to optimize group testing, such as choosing the optimal group size based on the total number of swabs and the projected level of disease spreading. Another is the binary splitting method, in which a positive group is split into halves and is tested again, until individual positive swabs are detected. The second method, however, is very time-consuming, which decreases its attractiveness during a pandemic.

In addition, to optimize group testing, transposition-based replication is used: after grouping the swabs, researchers form additional control groups from the same swabs and test them together with the main groups. This helps further cut the number of tests, and if the disease levels are low, it also helps to detect positive swabs in one step, which speeds up the testing considerably.

However, this method does not allow for experimenting with group sizes to detect the optimal group size under specific conditions. Researchers from HSE University and Vilnius University suggested OptReplica technology, which uses a more complicated algorithm of swab grouping in key and control groups and helps decrease the number of control groups. In addition, the algorithm helps calculate the optimal group size for the present number of swabs and the forecasted level of disease spreading.

The authors conducted experimental research on samples of 96 and 384 swabs, carrying out 100 randomized tests for each sample size, and compared the effectiveness of transposition-based replication and OptReplica method for different levels of disease incidence. The studies have shown that if the optimal size of groups is chosen, OptReplica is more effective than transposition-based replication. In cases with low incidence, the use of OptReplica, a 13x average reduction of tests can be achieved compared to individual testing without time delay.

'Our simulations are actually proving that using this optimization replication strategy is always advantageous and, even in case of high spread of the disease (10% or 20% of positives in the population), we are still competitive with individual testing strategy', explained Mario Guarracino, Chief Research Fellow of the Laboratory of Algorithms and Technologies for Networks Analysis.

The authors of the new technology suggest using it for asymptomatic populations with seemingly low incidence of coronavirus cases, where it will help detect the infected individuals at a maximum speed with a minimum number of tests, and timely apply the quarantine measures in order to prevent spreading of the disease. In regions with disease incidents over 50 cases per 1,000 tests, the authors suggest using other methods of group replication, or testing without replication.

An old technique flexes its muscles

Sarcomeres are small repeating subunits of myofibrils, the long cylinders that bundle together to make the muscle fibres. Inside the sarcomeres, filaments of the proteins myosin and actin interact to generate muscle contraction and relaxation. So far, traditional experimental approaches to investigate the structure and function of muscle tissue were performed on reconstructed protein complexes or suffered from low resolution. "Electron cryo-tomography, instead, allows us to obtain detailed and artefact-free 3D images of the frozen muscle", says Raunser.

Cryo-ET was for a long time an established yet niche methodology. But recent technical advances in electron cryo-microscopy (cryo-EM) as well as the new development of cryo focused ion beam (FIB) milling are pushing cryo-ET resolution. Similar to cryo-EM, researchers flash-freeze the biological sample at a very low temperature (- 175 °C). Through this process, the sample preserves its hydration and fine structure and remains close to its native state. FIB milling is then applied to shave away extra material and obtain an ideal thickness of around 100 nanometers for the transmission electron microscope, which acquires multiple images as the sample is tilted along an axis. Finally, computational methods reconstruct a three-dimensional picture at high resolution.

Raunser's team performed cryo-ET on mouse myofibrils isolated at the King's College, and obtained a resolution of one nanometer (a millionth of a millimetre, enough to see fine structures within a protein): "We can now look at a myofibril with details thought unimaginable only four years ago. It's fascinating!", says Raunser.

Fibres in their natural context

The calculated reconstruction of the myofibrils revealed the three-dimensional organisation of the sarcomere, including the sub regions M-, A-, and I- bands, and the Z-disc, which unexpectedly forms a more irregular mesh and adopts different conformations. The scientists used a sample with myosin strongly bound to actin, representing a stage of the contracting muscle that is called the rigor state. And indeed, they could visualise for the first time in the native cell how two heads of the same myosin bind to an actin filament. They also discovered that the double head not only interacts with the same actin filament but is also found split between two actin filaments. This has never been seen before and shows that proximity to the next actin filament is stronger than the cooperative effect between the neighbouring heads.

"This is just the beginning. Cryo-ET is moving from niche to widespread technology in structural biology", says Raunser. "Soon we will be able to investigate muscle diseases at molecular and even atomic level". Mouse muscles are very similar to those of humans, yet scientists plan to investigate muscle tissue from biopsies or derived from pluripotent stem cells.

In the heart of black cherry's native range, including a part of the Allegheny Hardwoods that bills itself as the "Black Cherry Capital of the World," the tree's regeneration, growth and survival have all been declining for more than a decade. In a new analysis, a team of USDA Forest Service and University of Missouri scientists identify likely factors behind the tree's decline and, more significantly, conclude that black cherry may be the tip of the iceberg in terms of change in eastern deciduous forests.

Scientists used a combination of synthesis of existing research and new analyses to examine the leading hypotheses for black cherry's regeneration failure. They conclude that the two factors that are most likely contributing to declining abundance of black cherry are an increase in pathogens and less nitrogen deposition in soil.

"We began this project wanting to narrow down the potential drivers behind the change in black cherry; what we found is that this may be a story of change on a much bigger scale, with mixed species forests in the coming century likely to reflect the response of many individual tree species to changing environmental conditions, biotic stressors, and their interactions," said Alejandro Royo, a research ecologist with the Northern Research Station and the study's lead author.

URBANA, Ill. - Pumpkin growers dread the tiny tan scabs that form on their fruit, each lesion a telltale sign of bacterial spot disease. The specks don't just mar the fruit's flesh, they provide entry points for rot-inducing fungus and other pathogens that can destroy pumpkins and other cucurbits from the inside out. Either way, farmers pay the price, with marketable yields reduced by as much as 90%.

Despite the disease's severity, scientists don't know much about the genetics of the pathogen that causes it; nearly all the molecular information required for accurate diagnostic testing and targeted treatments is lacking for the disease.

In a new study, University of Illinois scientists, with the help of two undergraduate students, have assembled the first complete genome for the bacteria that causes the disease, Xanthomonas cucurbitae, and identified genes that are activated during infection.

"Assembling a complete circular genome means we now have the resources to better understand what's happening in the field. We can use this information to look at how the pathogen is spreading, whether there are differences in host specificity among sub-populations or strains, or how likely it is to develop resistance to chemical controls," says Sarah Hind, assistant professor in the Department of Crop Sciences at Illinois and senior author on the Phytopathology study.

After sequencing the genome, Hind's group compared it to genomes from 12 other Xanthomonas species that cause diseases in a variety of crop plants like tomato, rice, citrus, and wheat. Surprisingly, given its penchant for creating havoc in the field, Xanthomonas cucurbitae had the smallest genome and had fewer genes known to be important for other Xanthomonas species to cause disease.

"As this pathogen lacks many of the known virulence (i.e., disease-causing) genes, we don't know exactly which genes are needed by the pathogen to infect cucurbit plants," Hind says. "It could be something we've never seen before, such as a new gene or a mechanism that evolved in this species that isn't seen in the rest of the family. That could be very exciting."

To get closer to an answer, the research team grew the bacteria in liquid media that mimicked its host environment and identified more than 400 genes whose expression was altered when the pathogen interacted with its "host." In particular, they observed increased expression of genes for enzymes related to the breakdown of plant tissues, which are key for further development of the disease.

If Hind's team can learn more about these factors and how cucurbits respond to them, there may be a way to prevent the bacteria from penetrating pumpkin fruits in the first place. "That would really save the farmers," she says. "They don't care as much when it gets on the leaves, but if it infects the fruit, they're in trouble."

Hind adds, "This project wouldn't have been possible without the contributions of some really talented undergraduate students. We love having students participate in our research. They bring a sense of enthusiasm and eagerness - as well as really creative ideas - to the lab that would be hard to generate otherwise."

Although both students graduated, see new Crop Sciences students contributing to Hind's other pumpkin projects in this video. High school and transfer students can learn more about Crop Sciences coursework online.

Cambridge, MA - Astronomers have now obtained a new view of the supermassive black hole at the center of galaxy M87. Images released today by the Event Horizon Telescope (EHT) collaboration reveal how the black hole, some 55 million light-years away, appears in polarized light.

The image marks the first time astronomers have captured and mapped polarization, a sign of magnetic fields, so close to the edge of a black hole.

Scientists still don't understand how magnetic fields -- areas where magnetism affects how matter moves -- influence black hole activity. Do they help direct matter into the hungry mouths of black holes? Can they explain the mysterious jets of energy that extend out of the galaxy's core?

In two studies published today in the Astrophysical Journal Letters, EHT astronomers reveal their latest findings and how magnetic fields may be influencing the black hole at the center of M87.

"One of the main science drivers of the EHT is distinguishing different magnetic field configurations around the black hole," says Angelo Ricarte, a co-author and researcher at the Center for Astrophysics | Harvard & Smithsonian. "Polarization is one of the most direct probes into the magnetic field that nature provides."

The EHT collaboration has been studying the supermassive object at the heart of M87 for well over a decade. In April 2019, the team's hard work paid off when they revealed the very first image of a black hole. Since then, the scientists have delved deeper into the data, discovering that a significant fraction of the light around the M87 black hole is polarized.

Light becomes polarized when it goes through certain filters, like the lenses of polarized sunglasses, or when it is emitted in hot regions of space that are magnetized. In the same way polarized sunglasses help us see better by reducing reflections and glare from bright surfaces, astronomers can sharpen their view of the black hole by looking at how light originating from there is polarized. Specifically, polarization allows astronomers to map the magnetic field lines present around the inner edge of the black hole.

"In order to gain confidence in our analysis, we used as many as five distinct methods to calibrate the data and reconstruct polarimetric images," says Maciek Wielgus, a researcher at Harvard's Black Hole Initiative and the Center for Astrophysics (CfA) who participated in the study. "This huge team effort paid off as we found very good consistency between results obtained with all the different techniques."

These new polarized observations of the M87 black hole are key to explaining how the galaxy is able to launch energetic jets from its core, the EHT team says.

One of M87's most mysterious features is the bright jet of matter and energy that emerges from its core and extends at least 100,000 light years away. Most matter lying close to the edge of a black hole falls in. However, some of the surrounding particles escape moments before capture and are blown far out into space in the form of these jets.

Astronomers don't know how jets larger than the galaxy itself are launched from its core, nor how only certain matter falls into the black hole.

Now, with the new image of the black hole in polarized light, the team has looked directly into the region just outside the black hole where this interplay between inflowing and ejected matter occurs.

The observations provide new information about the structure of the magnetic fields just outside the black hole, revealing that only theoretical models featuring strongly magnetized gas can explain what astronomers are seeing at the event horizon.

"Magnetic fields are theorized to connect black holes to the hot plasma surrounding them," says Daniel Palumbo, a co-author and researcher at the Center for Astrophysics. "Understanding the structure of these fields is the first step in understanding how energy can be extracted from spinning black holes to produce powerful jets."

To observe the heart of the M87 galaxy, the EHT collaboration linked eight telescopes around the world, including the Smithsonian Astrophysical Observatory's Submillimeter Array, to create a virtual Earth-sized telescope. The impressive resolution obtained with the EHT is equivalent to that needed to image a credit card on the surface of the Moon.

This unprecedented resolving power allowed the team to directly observe the black hole with polarized light, revealing the presence of a structured magnetic field near the event horizon.

"This first polarized image of the black hole in M87 is just the beginning," says Dominic Pesce, CfA researcher and study co-author. "As the EHT continues to grow, future observations will refine the picture and allow us to study how the magnetic field structure changes with time."

Sheperd Doeleman, founding director of the EHT, added, "Even now we are designing a next-generation EHT that will allow us to make the first black hole movies. Stay tuned for true black hole cinema."

The EHT collaboration involves more than 300 researchers from across the globe and includes 30 scientists and engineers at the Center for Astrophysics | Harvard & Smithsonian.

Curtin University research has uncovered the first solid clues about the very beginning of the supercontinent cycle of Earth, finding it was kick-started two billion years ago.

Detailed in a paper published in Geology, a team of researchers from Curtin's Earth Dynamics Research Group found that plate tectonics operated differently before two billion years ago, and the 600 million years supercontinent cycle likely only started during the second half of Earth's life.

Lead researcher Dr Yebo Liu from Curtin's School of Earth and Planetary Sciences said that the shift in plate tectonics marked a regime change in the Earth System.

"This regime change impacted on the eventual emergence of complex life and even how Earth resources are formed and preserved," Dr Liu said.

"Pangea was the first supercontinent scientists discovered early last century that existed some 300 million years ago and lasted until the age of the dinosaurs. Geologists realised more recently that at least two older supercontinents existed before Pangea in the past two billion years (Ga) in a 600 million year cycle. But what happened in the first 2.5 billion years of Earth's history is anybody's guess."

"Our research was essentially testing two hypotheses - one is that the supercontinent cycle started prior to two billion years ago. Alternatively, the ancient continents (called cratons) only managed to get together in multiple clusters called supercratons, instead of forming a singular supercontinent."

To conduct their tests, the Curtin researchers ventured into the hills east of Perth, Western Australia, an area known as the Yilgarn craton.

Dr Liu said Yilgarn was a critical piece of the puzzle not only because it is old, but also because there are a series of dark rocks or dolerite dykes that recorded Earth's ancient magnetic field at the time that the rocks formed.

"By precisely dating the rocks and measuring the samples' magnetic record, using a technique called palaeomagnetism, we are able to reconstruct where those rocks were (relative to the magnetic North pole) when they formed," Dr Liu said.

Co-author John Curtin Distinguished Professor Zheng-Xiang Li, from Curtin's School of Earth and Planetary Sciences, said by analysing their new data from Yilgarn, and comparing it with data available globally for other cratons, one thing became clear.

"It was clear that we can almost rule out the existence of a long-lived single supercontinent before two billion years ago (2 Ga), although transient supercontinents may have existed" Professor Li said.

"More likely, there could have been two long-lived clusters of cratons, or supercratons, before 2 Ga that were geographically isolated from each other, never forming a singular supercontinent."

Professor Ross Mitchell of the Chinese Academy of Sciences, who was previously a member of Curtin's Earth Dynamics Research Group, said the research goes some way to solving a long-standing mystery.

"The idea of an even older supercontinent has been speculated about for years. But while it has been difficult to prove, it has also been difficult to disprove," Professor Mitchell said.

Dr Liu said more studies now need to be done.

"This study surely isn't the final word on the debate, but it's certainly a step in the right direction and we need to collect data from a lot more similar rocks to further test the hypotheses," Dr Liu said.

Obsessive compulsive disorder (OCD) among those who have recently given birth is more common than previously thought, and much of this can be attributed to thoughts of harm related to the baby, new UBC research has found.

The researchers also learned that OCD can go undetected when new parents aren't asked specifically about infant-related harm.

OCD is an anxiety-related condition characterized by the recurrence of unwanted, intrusive and distressing thoughts. If left untreated, it can interfere with parenting, relationships and daily living.

The study estimates that eight per cent of postpartum women report symptoms that meet criteria for a diagnosis of OCD at some point during pregnancy, and 17 per cent do so in the 38 weeks after delivery. Prior research had estimated the prevalence of OCD at about 2.2 per cent over the pregnancy and postpartum period.

"What really matters now is that we screen for and assess OCD among perinatal women with perinatal-specific questions and assessment methods. It is especially important that we include questions about intrusive thoughts of infant-related harm. This ensures that perinatal women suffering from OCD are not missed and can be directed toward appropriate treatment," said Dr. Nichole Fairbrother, a clinical associate professor in the UBC department of psychiatry who was lead author of the study. "Perinatal OCD is common and we have a responsibility to identify those who experience it and ensure they receive timely, evidence-based treatment."

The study is one of the first to use newly updated criteria for diagnosing OCD which somewhat lowers the threshold for a diagnosis.

However, the researchers also believe they uncovered more OCD by asking the right questions. New mothers appear not to recognize their infant-related thoughts in the standard questions asked during OCD assessments. By including specific questions about harm to the baby, the researchers were better able to uncover symptoms.

"The traditional questions are framed in a way that doesn't really help women connect to the intrusive thoughts they've had about their baby." said Fairbrother. "If they don't recognize their experience in the questions that are asked, they may be underreporting."

Fairbrother and her team from UBC, the University of Victoria, the Women's Health Research Institute and King's College London surveyed 580 women in British Columbia during their third trimester of pregnancy and for six months afterward. Participants completed online questionnaires and interviews designed to assess the presence and severity of OCD symptoms.

The prevalence of OCD among new mothers peaked approximately eight weeks after delivery at nearly nine per cent. The study data suggests that it resolves naturally among some women as they become used to parenting, but for others it persists and may require treatment.

It's important for care providers to know when women are most at risk, because they may be reluctant to report their symptoms.

"When mothers have these kinds of thoughts they might think, 'There's something wrong with me and I can't tell anyone because there could be terrible consequences for me and my baby,' Fairbrother said.

Education for both women and their care providers is needed, she said. If care providers are able to distinguish between thoughts that are perfectly normal, those that might indicate a need for treatment, and those that might signal a threat to the baby, they are less likely to err on the side of caution in a way that would have consequences for women and their babies.

Cold Spring Harbor Laboratory (CSHL) President and CEO Bruce Stillman has been dissecting DNA replication, a critical step in cell division, since the 1980s. His lab studies how Origin Recognition Complexes--ORCs--coordinate DNA duplication. They discovered how our cells assemble and disassemble ORCs during the cell division cycle. One ORC protein is sequestered into small liquid droplets, keeping it apart until the right time to recruit other proteins and initiate DNA replication.

The ORC recognizes where to initiate replication at numerous locations along the long, linear stretches of DNA in our cells' chromosomes. Fully assembled ORCs recruit other proteins to make precise copies of the chromosomes. This mechanism is necessary to inherit DNA accurately without errors that can lead to disorders such as cancer.

Scientists have studied the structure of ORCs in several species. Stillman explains:

"We've previously studied this in baker's yeast, but it turns out that human cells have a different way of doing things."

Unlike single-celled yeast, humans have a variety of cells that divide at different times. To choreograph this, the researchers found that one human ORC protein, ORC1, has certain regions that yeast ORC1 lacks. When ORC binds to DNA, ORC1 recruits CDC6, a protein that assembles other DNA replication proteins. Some of the human-specific regions of ORC1 and CDC6 bind other proteins that regulate DNA replication. Manzar Hossain, a research investigator in Stillman's lab, says:

"We found that ORC1 and CDC6 interact in a very tangential manner. We found a very short time period which allows them to interact."

DNA-bound ORC1 is sequestered into liquid droplets that briefly change shape, then brings in CDC6. Kuhulika Bhalla, a postdoc in Stillman's lab, explains:

"So if you can imagine a lava lamp, like you've got liquid, but you've got other colored liquid within it. And they still managed to stay separated."

Throughout most of the cell division cycle, ORC1 and CDC6 amounts oscillate in the cell. Stillman explains that "both high and low amounts of ORC1 lead to severe consequences for cell viability. So, you have to have just the right amount" of each protein throughout the cell cycle. Stillman and his colleagues have shown that CDC6 recruits other regulatory proteins that control the activity and levels of ORC1 in both space and time. They published their findings in Molecular Cell.

Philadelphia, March 23, 2021 - During the COVID-19 pandemic, Joseph S. Alpert, MD, Editor-in-Chief of The American Journal of Medicine, published by Elsevier, has observed that although non-COVID inpatients suffered from the usual mix of conditions such as heart failure and chronic obstructive pulmonary disease exacerbations, the Internal Medicine inpatient population was distinctly different from what he had seen over the past decades. They were considerably sicker and closer to dying than in the past.

Dr. Alpert has been working on the Internal Medicine, Cardiac Care Unit, and Cardiology consult services. "At times, one third of our Internal Medicine patients were receiving consultations from the Palliative Care service and were being considered for inpatient or home hospice," notes Dr. Alpert, University of Arizona School of Medicine, Tucson, AZ, USA. "In the past, the usual situation was no patients or just one patient being considered for hospice at any particular time."

Why had patient demographics changed? The answer is simple, he says. "Patients were avoiding the hospital for as long as possible because they feared acquiring a lethal COVID infection on top of their chronic illness. For the same reason, many hospitalized patients refused post-discharge physical therapy or inpatient hospice transfer following acute care."

Recent studies in the United States and Europe have found that fewer patients with acute myocardial infarction or stroke were being seen in emergency departments. Moreover, hospital mortality was higher than usual, probably the result of delay in implementing evidence-based therapy. Patients often stated that they knew it was safer to stay home rather than come to the hospital, while others expressed fear that hospital staff would be so busy with COVID patients that they would not receive adequate care.

"I repeatedly told patients that they were safer with us on both our inpatient and outpatient services than they would be shopping for groceries, where they would not know the COVID status of the person standing next to them," Dr. Alpert explains. He would list all the things they were doing to avoid transmitting the COVID virus in hospitals and clinics, from social distancing and no-visitor policies to constant cleaning and, more recently, near-universal vaccination for everyone working in the hospital and clinics. "Unfortunately, much of this information fell on deaf ears. It seemed that fear had overcome rational thinking."

Dr. Alpert points to the airline industry, which has been dealing with irrational fears of flying for decades with special programs designed to help potential passengers overcome their flight anxiety. He suggests that the answer is likely to be the same for fear of medical attention.

"Medicine needs to use as many avenues of communication as possible to educate the public concerning safe conditions within hospitals and outpatient clinics." He urges his colleagues to spread the word. "If you are sick do not hesitate to call 911 or get someone to bring you to the closest emergency department where you can receive potentially life-saving therapy," he urges.

Domestication has a consistent effect on the gut microbiota of animals and is similar to the effects of industrialisation in human populations, with ecological differences such as diet having a strong influence.

These findings, published today in eLife, highlight how the flexibility of the gut microbiota can help animals respond to ecological change and could help identify ways of manipulating gut microbial communities in the service of health.

Animals typically have complex communities of microbes living in their gut that can strongly influence functions such as immunity and metabolism. These communities can be extremely diverse and differ greatly between species and even individuals. We know, for instance, that domesticated animals, such as lab mice, have different gut microbial communities than their wild relatives. We have even seen large changes in the gut microbiota of industrialised human populations, some of which have been linked to the rise of certain diseases.

During domestication, animals experienced profound ecological changes that likely shaped their gut microbiota. "Domesticated animals and industrialised human populations potentially experienced similar ecological changes such as less diverse, more easily digestible diets, higher population densities, and more medical interventions," explains first author Aspen Reese, who was a postdoctoral Junior Fellow in the Society of Fellows, Harvard University, US, at the time the study was carried out, and is now Assistant Professor at the University of California, San Diego, US. "We wanted to find out if domestication had consistent effects on the gut microbiota of animals and if the effects were indeed similar to those of industrialisation in humans."

To assess the effects of domestication, the team sequenced and compared microbial DNA extracted from fecal samples of 18 species of wild and domesticated mammals. They found that domestication did have a clear global effect on gut microbiota, although the specific differences depended on the species.

Domestication involves strong selection pressure on animals, leading to important genetic and physiological changes that may also affect gut microbial communities. To unpack the relative roles of ecology and genetics, the team then swapped the diets of wild and domesticated animals. They found that the gut microbial communities of related animals, such as wolves and dogs, became much more similar to one another, supporting the idea that altered diets explain at least some of the changes in the gut microbiota seen with domestication.

To understand whether such differences also occur in humans, they then compared the gut microbial communities of humans to those of chimpanzees, one of our closest living relatives, and between humans living in industrialised versus non-industrialised populations. They found that differences between the gut microbiota of humans and chimpanzees were similar to those seen between domesticated and wild animals, with the largest changes evident in industrialised populations. Because all humans are equally related to chimpanzees, these results showed that ecological factors rather than genetics drive aspects of the gut microbiota shared between domesticated animals and humans living in industrialised populations.

"Our research highlights that the flexibility of the gut microbiota likely helps animals and humans respond to rapid ecological change," concludes senior author Rachel Carmody, Assistant Professor in the Department of Human Evolutionary Biology at Harvard University. "But, at the same time, this flexibility can create opportunities for mismatch between the gut microbiota we have and the one our bodies have evolved to expect. As we increasingly appreciate the central role of the gut microbiota in biology, understanding the factors that shape it in animals and humans may help us identify new ways to improve experimental animal models, the wellbeing of animals we depend on, and ultimately, human health."

"Several countries, including the United Kingdom and Canada have stated that they will delay second doses of COVID-19 vaccines in response to supply shortages, but also in an attempt to rapidly increase the number of people immunized," explains Chadi Saad-Roy, a graduate student in the Departments of Ecology and Evolutionary Biology (EEB) and Quantitative and Computational Biology in the Lewis-Sigler Institute at Princeton and the lead author of the study.

"The original clinical trials of the vaccines, plus subsequent epidemiology, are quite optimistic regarding the efficacy of the first dose. However, we are still uncertain how the strength and duration of immunity from a single dose (or the full two-dose course or natural infection, for that matter) will persist in the longer term", adds Saad-Roy.

The researchers used a simple model to project forward the incidence of COVID-19 cases, as well as the degree of immunity of the population, under a range of vaccine dosing regimes and assumptions related to immune responses. "Given the immunological and epidemiological uncertainties driving these outcomes, simple models are an essential tool to explore future possibilities" says Caroline Wagner, an Assistant Professor in the Department of Bioengineering at McGill, and the senior author on this paper.

One dose may not always be enough

The study found that one-dose strategies may, as expected, reduce case numbers in the short term by more rapidly immunizing a greater number of individuals. However, if immune responses after one dose are less robust, subsequent epidemic peaks may be larger.

"More optimistically, we find that as vaccine capacity increases, increasing vaccination rates or changing the dosing regime to closer to the recommended two-dose schedule can mitigate these longer term epidemiological effects, which is important for public health planning," adds Wagner.

Another important outcome associated with imperfect immune responses is the potential for viral immune escape. To start addressing this complex issue, the authors adapted a previous simple 'phylodynamic' model for viral immune escape, developed by co-authors Bryan Grenfell, Oliver G. Pybus, and Edward C. Holmes, along with other colleagues not involved with the current work. This theory predicts that in individuals with partial immunity, moderate selection pressure combined with sufficient viral transmission could drive evolution. Here, the authors explore this possibility along with a range of other scenarios, including the more optimistic case of minimal potential for adaptation in hosts with waned immunity following one or two vaccine doses.

"At least one variant has already emerged that may be adapted for partial immune escape," notes Holmes. "Simple theory underlines that the evolution and transmission of variants by infected hosts with intermediate levels of immunity may be important. Therefore, the strength and duration of immunity, and particularly the effect of these on retransmission, are key parameters to determine" adds Grenfell.

One intuitive finding that the paper emphasizes is that very low rates of vaccine administration may be associated with larger case numbers and, possibly, more elevated potential for viral adaptation. "This strongly underlines the importance of equitable global vaccine distribution, as immune escape in one location will rapidly spread," explains C. Jessica E. Metcalf, a co-author on the paper, and an Associate Professor in EEB and the School of Public and International Affairs at Princeton and an associated faculty member at the High Meadows Environmental Institute.

"The models are relatively simple conceptually, but they illustrate the complexities of the problem and highlight the challenges that we still face," notes Michael Boots, a Professor of Integrative Biology at UC Berkeley who was not affiliated with the present study. "This important piece of work provides a framework that we can use to inform our approach going forward and moreover identifies the key knowledge gaps that we need to address," adds Boots.