Culture

Autoimmunity may explain why an important immune system is absent in many bacteria

image: Researcher Anne Chevallereau

Image: 
Ellinor O. Alseth

New findings from University of Exeter researchers reveal how bacterial immune systems can be harmful for their hosts and explain why they are not found in many bacteria.

CRISPR-Cas is an immune system that protects bacteria against infection by viruses (called phages).

The system works by stealing a small piece of viral DNA and using this to target and destroy matching sections of virus genome during a future infection.

Targeting by CRISPR-Cas breaks down the virus genome, meaning that new copies of the virus cannot be made.

Previously, the Westra and van Houte groups of the Environment and Sustainability Institute on the University's Penryn Campus in Cornwall showed that CRISPR-Cas can provide excellent protection against "lytic" phages, that is phages that multiply inside the host cell and cause the bacterial cell to burst releasing more viral particles (10.1016/j.cub.2015.01.065, 10.1038/nature17436).

However, it is common for viruses to follow a "lysogenic" lifestyle, meaning they can integrate into the host genome and become dormant until a trigger (often associated with host stress, or signals from other phages) causes them to re-enter the lytic pathway.

Lead authors of the current study, Clare Rollie and Anne Chevallereau, both working in the Westra group, explain that: "Our new results show that the immune system was not able to eliminate lysogenic phages and often led to damaging autoimmunity for the host during phage infection."

This type of autoimmunity was caused by the CRISPR-Cas system targeting viral DNA that had been incorporated into the host's own genome, leading to host cell death and virus release.

They found that bacterial cells that had lost the CRISPR-Cas system from their genome avoided the damage caused by autoimmune targeting, survived and proliferated.

"Here, the absence of this key immune system was an advantage," explain the authors.

They also highlight that "anti-CRISPR proteins, which are small inhibitors produced by the phage to counteract the host CRISPR-Cas immune response and had previously been thought to only benefit the phage that makes them, also provide protection for the host. In this scenario, disabling the host immune system blocks autoimmunity and prevents bacterial death."

Bacterial autoimmunity is brought about by imperfectly matching "spacers" - sequences that guide the CRISPR-Cas system to viral DNA.

The authors showed that these imperfect matches to phages occur frequently in nature and so this autoimmune effect was likely to be a common consequence of possessing a CRISPR-Cas system.

Importantly, this may help to explain why CRISPR-Cas is only present in about 40% of bacterial genomes and is frequently gained and lost from closely related strains.

The research was carried out in collaboration with theoreticians from the University of Montpellier (France) and bioinformaticians from University of Otago (New Zealand).

University of Exeter researchers were funded by the European Research Council, NERC Independent Research Fellowship and a Marie Sk?odowska-Curie fellowship under the European Union's Horizon 2020 research and innovation programme.

Credit: 
University of Exeter

Preventing, healing tooth decay with a bioactive peptide

Cavities, or dental caries, are the most widespread non-communicable disease globally, according to the World Health Organization. Having a cavity drilled and filled at the dentist's office can be painful, but untreated caries could lead to worse pain, tooth loss, infection, and even illness or death. Now, researchers in ACS Applied Materials & Interfaces report a bioactive peptide that coats tooth surfaces, helping prevent new cavities and heal existing ones in lab experiments.

Conventional treatment for dental cavities involves removing decayed tissue and filling the hole with materials, such as amalgam or composite resin. However, this procedure can damage healthy tissue and cause severe discomfort for patients. Hai Ming Wong, Quan Li Li and colleagues wanted to develop a two-pronged strategy to prevent and treat tooth decay: 1) prevent colonization of the tooth surface by the plaque-forming bacteria that cause cavities, and 2) reduce demineralization, or the dissolving of tooth enamel, while increasing remineralization, or repair.

The researchers based their anti-cavity coating on a natural antimicrobial peptide called H5. Produced by human salivary glands, H5 can adsorb onto tooth enamel and destroy a broad range of bacteria and fungi. To promote remineralization, the team added a phosphoserine group to one end of H5, which they thought could help attract more calcium ions to repair the enamel than natural H5. They tested the modified peptide on slices of human molars. Compared with natural H5, the new peptide adsorbed more strongly to the tooth surface, killed more bacteria and inhibited their adhesion, and protected teeth from demineralization. Surprisingly, however, both peptides promoted remineralization to a similar degree. After brushing, people could someday apply the modified peptide to their teeth as a varnish or gel to protect against tooth decay, the researchers say.

Credit: 
American Chemical Society

2019's new medicines

With 48 drugs approved by the U.S. Food and Drug Administration (FDA), 2019 was another highly productive year for the pharmaceutical industry. The new medicines include treatments for various cancers, sickle cell disease, migraines and postpartum depression. However, the steady flow of drugs could be masking troubling signs about the health of the industry, according to Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society. 

2019 showed several notable trends for new drugs, according to Senior Correspondent Lisa M. Jarvis. First, about 42% of the medicines had new mechanisms of action -- so-called "first-in-class drugs" -- to treat a disease. As in past years, most of FDA's approvals were for small-molecule drugs, but 2019 also saw an influx of new molecular entities, including antibody-drug conjugates, an antisense oligonucleotide and a small interfering RNA. Another trend was the introduction of new therapies for underserved diseases, such as sickle cell anemia, treatment-resistant tuberculosis and postpartum depression.

Despite these successes, some analysts say certain aspects of the list point to trouble ahead for the pharmaceutical industry. For example, the proportion of new drugs produced by big pharma is declining. One explanation is that the industry has shifted its focus from primary-care treatments, which require large, expensive clinical trials, to rare diseases and specialty care indications, like cancer. These classes of drugs can be approved on the basis of much smaller studies, making it easier for small companies to bring a drug to market. Another concerning trend is that the number of companies directly contributing to drug development is shrinking, as large companies acquire the most productive small and medium biotech firms. Analysts worry that this industry consolidation will threaten the ability to introduce new medicines.

Credit: 
American Chemical Society

What it's like to live without a sense of smell

image: A new study from the University of East Anglia reveals the huge range of emotional and practical impacts caused by a loss of smell.

Image: 
University of East Anglia

The smell of cut grass, freshly baked bread, childhood memories, lost loved ones, Christmas. What happens when it's all gone?

A new study from the University of East Anglia reveals the huge range of emotional and practical impacts caused by a loss of smell.

It finds that almost every aspect of life is disrupted - from everyday concerns about personal hygiene to a loss of sexual intimacy and the break-down of personal relationships.

The researchers hope that their findings will help motivate clinicians to take smell problems more seriously, with better help and support offered to patients.

Prof Carl Philpott, from UEA's Norwich Medical School, said: "Smell disorders affect around five per cent of the population and cause people to lose their sense of smell, or change the way they perceive odours. Some people perceive smells that aren't there at all.

"There are many causes - from infections and injury to neurological diseases such as Alzheimer's and as a side effect of some medications.

"Most patients suffer a loss of flavour perception which can affect appetite and can be made even worse if distortions in their sense of smell also co-exist.

"Previous research has shown that people who have lost their sense of smell also report high rates of depression, anxiety, isolation and relationship difficulties.

"We wanted to find out more about how a loss of smell affects people."

The researchers worked with the Smell and Taste clinic at the James Paget University Hospital, Gorleston-On-Sea. The clinic opened in 2010 and was the UK's first clinic dedicated to taste and smell.

The study involved 71 participants aged between 31-80 who had written to the clinic about their experiences. It was carried out in collaboration with Fifth Sense, the charity for people affected by smell and taste disorders.

The research shows that sufferers experience wide-ranging impairments to their quality of life. These included a negative emotional impact, feelings of isolation, impaired relationships and daily functioning, impacts on physical health and the difficulty and financial burden of seeking help.

Prof Philpot said: "One really big problem was around hazard perception - not being able to smell food that had gone off, or not being able to smell gas or smoke. This had resulted in serious near misses for some.

"But smell is not just a life-saving sense - it is also life-enhancing.

"A large number of the participants no longer enjoyed eating, and some had lost appetite and weight. Others were eating more food with low nutritional value that was high in fat, salt and sugar - and had consequently gained weight.

"Participants had lost interest in preparing food and some said they were too embarrassed to serve dishes to family and friends which had an impact on their social lives.

"The inability to link smells to happy memories was also a problem. Bonfire night, Christmas smells, perfumes and people - all gone. Smells link us to people, places and emotional experiences. And people who have lost their sense of smell miss out on all those memories that smell can evoke.

"We found that personal hygiene was a big cause for anxiety and embarrassment, because the participants couldn't smell themselves.

"Parents of young children couldn't tell when their nappies needed changing, and this led to feelings of failure. One mother found it difficult bonding with her new baby because she couldn't smell him.

"Many participants described a negative impact on relationships - ranging from not enjoying eating together to an impact on sexual relationships," he added.

All of these problems led to diverse range of negative emotions including anger, anxiety, frustration, depression, isolation, loss of confidence, regret and sadness. And the problems were compounded by a lack of understanding about the disorder among clinicians.

Prof Philpott said: "The participants described a lot of negative and unhelpful interactions with healthcare professionals before coming to the James Paget Smell and Taste clinic. Those that did manage to get help and support were very pleased - even if nothing could be done about their condition, they were very grateful for advice and understanding."

Duncan Boak, Founder and Chair of Fifth Sense, said: "Anosmia can have a huge impact on people's quality of life in many ways, as this research demonstrates. An important part of Fifth Sense's work is giving our beneficiaries a voice and the opportunity to change the way society understands smell and taste disorders, whether through volunteering or participating in research studies like this one. The results of this study will be a big help in our ongoing work to improve the lives of those affected by anosmia."

Credit: 
University of East Anglia

Scientists take the first step towards extending the Standard Model in physics

image: Scientists analyzed their results using the King plot.

Image: 
Peter the Great St.Petersburg Polytechnic University

Researchers of Peter the Great St.Petersburg Polytechnic University (SPbPU) in collaboration with colleagues from the Physikalisch Technische Bundesanstalt (PTB) and a number of German scientific organizations, calculated previously unexplored effects in atoms. The results were published in the PHYSICAL REVIEW A, highlighted as an Editor's Choice article.

For many years, researchers all over the world have been looking for new particles beyond the currently accepted Standard Model of fundamental interactions in physics. Such research is most famously carried out at the Large Hadron Collider. A group of scientists from Russia and Germany is engaged in another approach to this problem based on methods of atomic spectroscopy. Such studies are less resource-intensive, but very promising due to the fact that the accuracy of experiments is higher in atomic physics than in high-energy physics.

SPbPU scientists calculated frequencies of electronic transitions in different isotopes of one element, in this case, argon.

Researchers examined several states of argon ions with four, five, and six electrons. These are optimal electronic configurations.On one hand, they can be reliably calculated, and on the other hand, they are accessible for experiments. Scientists analyzed their results using the King plot, a widely used method for systematic studies of the isotope shifts of two atomic transitions in a chain of isotopes.

Modern theory claims that the King plot should be linear to a very high accuracy. Until recently, possible nonlinear effects were considered much to small to be of any practical interest. Butthe international scientific group calculated thenew effectsand found that the nonlinearities in the King plot are by four orders stronger than was previously expected (at the 10 kHz level). Previously, due to the limitations of the instruments, such effects couldn't be detected, but a new generation of spectroscopic experiments increases the achievable accuracy by several orders of magnitude, thus making these effects observable. This is an important contribution to science, confirming that generally accepted ideas should to be adjusted.

"If the King plot turns out to be slightly curved, this may be a manifestation of new particles beyond the Standard Model of physics. It is necessary to continue studying these effects in other atoms with a larger number of electrons in order to reduce the influence of calculation errors,"said Vladimir Yerokhin, chief researcher at the Center for Advanced Studies of SPbPU.

In the near future, the theoretical predictions obtained by scientists of St. Petersburg Polytechnic University will be verified experimentally at the Physikalisch Technische Bundesanstalt using the facilities which trap ions in the magnetic and electric fields and investigate them using the quantum logic methods.

"If the experiment is successful, we can obtain restrictions on parameters of the proposed new particle beyond the Standard Model. In addition, such experiments will help to determine whether the fundamental constants change over time, which is of great importance for our understanding of the development of the Universe, "commented Vladimir Yerokhin.

Credit: 
Peter the Great Saint-Petersburg Polytechnic University

Hopkins news: Climate change could unlock new microbes and increase heat-related deaths

The Journal of Clinical Investigation (JCI) recently published "Viewpoint" articles by Johns Hopkins University School of Medicine professors who warn that global climate change is likely to unlock dangerous new microbes, as well as threaten humans' ability to regulate body temperature.

Johns Hopkins Bloomberg Distinguished Professors Rexford Ahima, M.D., Ph.D., and Arturo Casadevall, M.D., Ph.D., M.S., along with William Dietz, M.D., Ph.D., director of the George Washington University's Sumner M. Redstone Global Center for Prevention and Wellness, and Susan Pacheco, M.D., associate professor in the Department of Pediatrics at the University of Texas Health Science Center at Houston, authored journal articles relevant to their fields that detail how rising temperatures around the world pose dangerous threats to humanity.

Ahima, director of Johns Hopkins' Division of Endocrinology, Diabetes and Metabolism, wrote in the journal that "global warming threatens human thermoregulation and survival."

Ahima explains that people generate body heat and have the capacity to regulate their temperature within a few degrees. But "as heat waves become more common, more severe, and longer, we expect to see more heat-related illnesses and deaths," he writes.

Ahima cites a recent study that examined global heat-related mortality, pointing out that tropical and subtropical countries and regions will experience the sharpest surge in illness and death stemming from higher temperatures, while the United States and Europe can also expect increases.

Casadevall's article explores "the specter of new infectious diseases" as a result of the changing climate.

"Given that microbes can adapt to higher temperatures," writes the professor of molecular microbiology and immunology, and infectious diseases, at Johns Hopkins' schools of medicine and public health, "there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious diseases."

Endothermy allows humans and other warm-blooded mammals to maintain high temperatures that can protect against infectious diseases by inhibiting many types of microbes.

Casadevall cites a particular climate threat from the fungal kingdom.

"We have proposed that global warming will lead many fungal species to adapt to higher temperatures," he writes, "and some with pathogenic potential for humans will break through the defensive barrier provided by endothermy."

As an example, Casadevall points to the rise of Candida auris, a species of fungus identified in 2009 and called a "catastrophic threat" by the U.S. Centers for Disease Control and Prevention in 2017.

"The nearly simultaneous emergence of Candida auris on three continents, an event proposed to result from global warming, has raised the specter that increased warmth by itself will trigger adaptations on certain microbes to make them pathogenic for humans."

Casadevall says that, while fungi present the most immediate threat, other microbes also adapt to evolving conditions such as temperature. He writes that "the conceptual threat originally identified with fungi, and exemplified by C. auris as the canary in the coal mine, applies across the microbial world."

Dietz's article addresses climate change and malnutrition, calling obesity, undernutrition and climate change a "syndemic," or multiple epidemics that interact and share common underlying social or economic determinants and policy drivers. In her article, Pacheco discusses climate change's adverse consequences regarding pregnancy and maternal, fetal and child health.

In all four JCI "Viewpoint" articles, long-term strategies are urged to reduce greenhouse gas emissions and slow the trend of rising temperatures.

Credit: 
Johns Hopkins Medicine

Genetic identification of human remains from the Spanish Civil War and the dictatorship

image: The BIOMICs team works to optimise DNA extraction systems

Image: 
Miriam Baeta / UPV/EHU

It is estimated that around 114,000 people disappeared throughout Spain during the Spanish Civil War and subsequent dictatorship. Unfortunately, eight decades on, only a small percentage of these people have been found or identified, with around 9,000 victims from 700 mass graves (of which it is thought there are approximately 2,000) being recovered in the last fifteen years. As time goes by and the samples themselves continue to deteriorate, conventional methods are no longer precise enough to identify the remains of all these unknown people. However, genetic analyses constitute an effective tool for this purpose.

The BIOMICs research team at the UPV/EHU has spent the last ten years working to identify these disappeared persons by genetically analysing bone and teeth samples taken from remains recovered from various mass graves dating from the Spanish Civil War and subsequent dictatorship and comparing the results with DNA taken from family members. 'Once DNA has been obtained from the remains, we analyse a series of specific genetic markers, depending on the type of kinship relationship we wish to study,' explains Doctor Miriam Baeta, a member of the BIOMICs research team working at the University of the Basque Country's Department of Zoology and Cellular Animal Biology.

The aim of the genetic analyses is to determine the profile of the remains or to gather enough information to enable the team to compare them with the profiles of presumed family members or the information contained in the database of the DNA bank of relatives of disappeared persons. Data is also sometimes stored in the database itself in the hope that it will match future family profiles yet to be included. Each case is different because 'for example, if you want to analyse paternal lineage, you study the Y chromosome; but it you want to analyse maternal lineage, then you have to focus on mitochondrial DNA,' explains Dr Baeta.

We are increasingly able to study smaller and smaller markers

The task of identifying human remains is a complex one 'because we are talking about post mortem DNA, which is often extremely degraded, making it hard to obtain a complete genetic profile,' continues Dr Baeta. 'Identification or coincidence is easier to prove when more markers are studied. Moreover, in many cases, the most suitable relatives are not available, meaning that the ones still alive are not close enough or the markers obtained cannot be compared with those from the DNA samples of living family members,' she adds. Dr Baeta highlights the importance of the DNA bank of relatives of victims, 'so that more comparisons can be done during future exhumations'.

She claims to be optimistic, since 'thanks to technological advances, we are increasingly able to study smaller and smaller markers, which have a greater chance of success in the analysis, because being smaller, they are better able to survive degradation.' Over the ten years that the team has been working in this field, many advances have been made that have enabled them to optimise the identification system. 'Among other things, we have optimised the DNA extraction systems, as well as various different steps throughout the process with the aim of obtaining more informative profiles. We are constantly striving to improve every part of the process,' she explains. The latest advance proposed by the team 'enables us to study smaller fragments of mitochondrial DNA. Thanks to this technique, we can do an initial screening to dismiss, in a cost-effective manner, possible relationships through the maternal lineage; in other words, it makes it easier to determine maternal kinship: only if there is a coincidence in this first phase is it worth applying the methodologies used to date to analyse mitochondrial DNA.'

Researchers in the team have published a paper in which they present all the knowledge acquired over the past ten years. In specific terms, they explain the techniques and procedures used to identify 525 human remains. To enable this identification, they obtained saliva samples from 879 presumed relatives, enabling them to identify 137 disappeared persons. No informative profile was obtained for 17% of the samples analysed, as a result of limited DNA or degraded samples; however, profiles were obtained for another 297 human remains that, despite everything, had previously remained unidentified. 'In general, we obtain profiles for the majority of skeletal remains, but we do not have suitable relatives with which to compare them,' clarifies Dr Baeta.

She then comments that 'when we manage to identify someone it is a very happy moment, because in addition to the joy of the outcome itself, we know there is a lot of complicated work behind the result. At the end of the day, it is a collective effort by our team and the Aranzadi Science Society, the Gogora Institute and the associations of victims and relatives of people who disappeared during the Spanish Civil War and subsequent dictatorship.'

Credit: 
University of the Basque Country

Scientists isolate biomarkers that can identify delirium risk and severity

image: Regenstrief Institute and Indiana University School of Medicine researchers have identified blood-based biomarkers associated with both delirium duration and severity in critically ill patients. An estimated 7 million hospitalized Americans suffer from the acute confusion and disorientation, characteristics of delirium, including a majority of patients in medical or surgical ICUs.

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Regenstrief Institute

INDIANAPOLIS -- Regenstrief Institute and Indiana University School of Medicine researchers have identified blood-based biomarkers associated with both delirium duration and severity in critically ill patients. This finding opens the door to easy, early identification of individuals at risk for longer delirium duration and higher delirium severity and could potentially lead to new treatments of this brain failure for which drugs have been shown to be largely ineffective.

An estimated 7 million hospitalized Americans suffer from the acute confusion and disorientation, characteristics of delirium, including a majority of patients in medical or surgical intensive care units (ICUs). Individuals who experience delirium in the ICU are more likely to have more hospital-associated complications, longer stays and higher risk of readmission. They are more likely to experience cognitive impairment and also have a greater likelihood of dying for up to a year after their hospital stay than ICU patients who did not experience delirium.

"If you can tell which patients will have higher delirium severity and longer duration and therefore greater probability of death, there are important treatment implications," said Regenstrief Institute research scientist and IU School of Medicine faculty member Babar Khan, M.D., who led the research and is the president of the American Delirium Society. "Analyzing biomarkers to stratify risk for delirium is a promising approach with the potential to be applied regularly in ICU patients in the near future."

In a new observational study, Dr. Khan and colleagues report that biomarkers for astrocyte and glial activation as well as for inflammation were associated with increased delirium duration and severity and greater in-hospital mortality.

Biomarkers of the 321 study participants, all of whom experienced delirium in an ICU, were identified from samples obtained via simple blood draws. Delirium severity was determined using a tool developed by a team including Regenstrief, IU School of Medicine and Purdue College of Pharmacy scientists. The CAM-ICU-7, short for Confusion Assessment Method for the Intensive Care Unit 7 -- is easy to administer, even to patients on mechanical ventilators. More than half of ICU patients in the U.S. receive mechanical ventilation.

Each day with delirium in the ICU is associated with a 10 percent increased likelihood of death, according to Dr. Khan, so diminishing its duration and ultimately preventing it is critical. Regenstrief, IU School of Medicine and research scientists from other institutions have conclusively shown in several large trials that antipsychotics, such as the widely used haloperidol, are not effective for the management of delirium duration or severity.

Regenstrief and IU School of Medicine researchers are actively exploring other approaches to delirium. Dr. Khan is co-principal investigator of an ongoing study that is the first to test whether listening to music, a non-pharmacological strategy that has been shown to decrease over-sedation, anxiety and stress in critically ill patients -- all factors that predispose to ICU delirium - and lowers the likelihood of developing delirium. In a completed study, Regenstrief researchers determined that waking ICU patients and having them breathe on their own decreased acute brain failure.

The new study, "Biomarkers of Delirium Duration and Delirium Severity in the ICU" has been published online ahead of print in the journal Critical Care Medicine.

Credit: 
Regenstrief Institute

Earthquake catalog shows complex rupturing during 2019 ridgecrest sequence

The 2019 Ridgecrest earthquake sequence, which startled nearby California residents over the 4 July holiday with magnitude 6.4 and magnitude 7.1 earthquakes, included 34,091 earthquakes overall, detailed in a high-resolution catalog created for the sequence.

The catalog, developed by David Shelly at the U.S. Geological Survey in Golden, Colorado, was published in the Data Mine column in Seismological Research Letters. The paper is part of a larger Data Mine series aimed at rapidly sharing data from the Ridgecrest sequence among researchers.

"Because of the complexity in this sequence, I think there are still a lot of unanswered questions about what the important aspects of the triggering and evolution of this sequence were, so having this catalog can help people make more progress on answering those questions," said Shelly.

Shelly used a technique called template matching, which scanned through seismic signals to find those matching the "fingerprint" of 13,525 known and cataloged earthquakes, as well as precise relative relocation techniques to detect 34,091 earthquakes associated with the event. Most of the earthquakes were magnitude 2.0 or smaller.

The catalog covers the time period spanning the the foreshock sequence leading up to the 4 July 2019 magnitude 6.4 earthquake through the first 10 days of aftershocks following the magnitude 7.1 earthquake on 5 July.

By precisely locating the earthquakes, Shelly was able to discern several crosscutting fault structures in the region, with mostly perpendicular southwest- and northwest strikes. The foreshocks of the magnitude 6.4 event aligned on a northwest-striking fault that appears to have ruptured further in the aftershocks of that earthquake, along with a southwest-striking fault where a surface rupture was observed by teams who went out to the site.

Shelly said the magnitude 7.1 earthquake appears to have started at the northwestern edge of the magnitude 6.4 rupture, extending to the northwest and southeast and possibly extending that rupture to the northwest and southeast. The magnitude 7.1 event was highly complex, with several southwest-striking alignments and multi-fault branching and high rates of aftershocks, especially at the northwestern end of the rupture.

The Ridgecrest earthquakes took place along "a series of immature faults, in the process of developing," Shelly said, noting that this could explain in part why the earthquake sequence was so complex. Compared to the mature San Andreas Fault Zone to the west, which accommodates about half of the relative plate motion as the Pacific and North American tectonic plates collide, the Ridgecrest faults are broadly part of the Eastern California Shear Zone, where multiple faults accommodate up to 25 percent of this tectonic strain.

Shelly noted that the catalog benefitted from the long-established, densely instrumented, real-time seismic network that covers the region. "When there's a big earthquake in an area that's not well-covered, people rush out to try to at least cover the aftershocks with great fidelity," he explained. "Here, having this permanent network makes it so you can evaluate the entire earthquake sequence, starting with the foreshock data, to learn more about the earthquake physics and processes."

Credit: 
Seismological Society of America

Montana State researcher harnesses microorganisms to make living building materials

image: Chelsea Heveran uses a scanning electron microscope to examine Synechococcus cyanobacteria in MSU's Imaging and Chemical Analysis Laboratory on Jan. 14, 2020. MSU Photo by Adrian Sanchez-Gonzalez

Image: 
MSU Photo by Adrian Sanchez-Gonzalez

BOZEMAN -- To make a building material that's alive, Montana State University researcher Chelsea Heveran has a recipe: get some gelatin from the grocery store, make a broth with bacteria called Synechococcus that photosynthesize like plants, add a bit of calcium, then mix with sand and cool until hardened into an concrete-like solid that can be used to replicate itself.

Like many recipes, this one is underlaid by some complex chemistry and is the hard-won result of experimentation, according to Heveran, the lead author of a new paper published in the journal Matter that summarizes the research. The article appeared online Jan. 15 and was featured the same day in a story in the New York Times.

Heveran, assistant professor in the Department of Mechanical and Industrial Engineering in MSU's Norm Asbjornson College of Engineering, said the study marks the first time that microbes have been used as the main catalyst of a building material in a way that preserves them for later use. The team demonstrated that the Synechococcus cyanobacteria remained alive in the sandy bricks for a month or more under favorable conditions of humidity and temperature.

"You can break off a piece and use it to make new bricks," said Heveran, who conducted the study with a team of colleagues at University of Colorado Boulder, where she was a postdoctoral researcher before continuing to contribute to the project as an MSU faculty member.

That's a fundamental improvement over normal concrete, where each batch requires significant amounts of a chemical binder -- cement -- that must be mined, processed and hauled to the mixing site, Heveran explained. By contrast, she imagines a scenario in which a single living brick could be brought to a remote location; simple additives and some basic equipment are all that would then be needed to transform native earth into infrastructure.

The recipe works because the photosynthesizing Synechococcus cause calcium carbonate, the main mineral in limestone, to form in the solution and solidify the sand mixture. The researchers found that they could reliably control the cyanobacteria's behavior by adjusting temperature and humidity. High humidity and cool temperatures let the microbes stay alive for extended time periods, while higher temperatures caused the bricks to re-dissolve and promoted microbial growth and mineralization. In this way, one brick could be divided to generate multiple new living bricks. Maximum strength was achieved by drying the material, which killed the microbes.

According to Heveran, the material is surprisingly tough -- about as strong as cement mortar but weaker than concrete. "We aren't ready to build a skyscraper out of this stuff," she said. Compared to normal concrete, however, the bacterial bricks are relatively easy to recycle by dissolving them and adding new Synechococcus to re-solidify the mixture.

Heveran conducted the research in the Living Materials Laboratory run by Wil Srubar, assistant professor in CU Boulder's Department of Civil, Environmental, and Architectural Engineering, as well as at MSU, where she joined the faculty in August 2018. She said MSU is known for its research in biomineralization -- the process by which living organisms produce minerals that can modify their surroundings. A team of MSU researchers that includes assistant professor of civil engineering Adrienne Phillips has used other biomineralizing bacteria to seal leaks in oil and gas wells. Along with Phillips and Cecily Ryan, assistant professor of mechanical and industrial engineering, Heveran is now researching ways to make an effective concrete filler from discarded plastic that has been shredded and biomineralized to improve its chemical bonding ability.

"We're very excited to have Chelsea here," said Dan Miller, head of the mechanical and industrial engineering department. "Her expertise is a great contribution to MSU's research in materials science and the crossover with biology, which is creating a cutting-edge and growing field in engineering right now."

Heveran said she draws inspiration from bone, a living material she studied while earning her doctorate at CU Boulder. "Bone is amazing because it's made by cells -- it self-repairs and maintains high strength and toughness for decades," she said. The new study published in Matter suggests potential for additional properties engineered into building materials using other microorganisms.

"We're happy with what we engineered -- it has some neat properties," Heveran said. "But we're thinking of this more as a platform to say, 'We really could start to engineer living building materials. We could do so much more.'"

Credit: 
Montana State University

Both simple and advanced imaging can predict best stroke patients for thrombectomy

image: Amrou Sarraj, MD, of McGovern Medical School at UTHealth, is leading research on endovascular thrombectomy for stroke patients

Image: 
Maricruz Kwon, UTHealth

Both simple and advanced computed tomography (CT) were effective in accurately predicting which stroke patients would benefit from endovascular thrombectomy to remove a large cerebral clot, but together they were even better, reported researchers at The University of Texas Health Science Center at Houston (UTHealth).

Results of the multicenter study, Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT), were published in yesterday's Early View edition of the Annals of Neurology.

Stroke is the leading cause of long-term disability and fourth-leading cause of death in the world. An ischemic stroke, caused by a blockage of an artery, is the most common form. Endovascular thrombectomy can be performed to remove a clot lodged in a blood vessel with a mechanical device threaded through an artery. It has been shown to be an effective treatment for improving clinical outcomes in stroke up to 24 hours from onset.

"Endovascular thrombectomy has revolutionized the treatment for acute stroke patients presenting with large vessel occlusion. Different imaging techniques are used to identify patients who may benefit from this treatment. However, how these imaging profiles correlate with each other and with the stroke outcomes is unknown," said Amrou Sarraj, MD, lead author and associate professor of neurology at McGovern Medical School at UTHealth.

Imaging must be done to determine the location of the clot and whether the patient is a good candidate for thrombectomy, meaning they have a smaller area of brain tissue death. Physicians use non-contrast simple CT and/or CT with an injected contrast dye (CT perfusion) to view the clot and surrounding area of cellular death. While simple CT is readily available at most hospitals, CT perfusion tends to be only available at more advanced stroke centers.

Of the 361 patients enrolled, a significant proportion of patients had favorable imaging results on both the CT and CT perfusion, meaning they were candidates for endovascular thrombectomy. Those patients also had significantly higher odds of receiving endovascular therapy and higher 90-day functional independence rates after recovery (58%).

Even when the two imaging modalities disagreed, the functional and safety outcomes were reasonable (38% achieved functional independence), which was better than the patients who did not receive thrombectomy. Patients with an unfavorable result on CT perfusion imaging, but favorable on simple CT, had higher rates of symptomatic hemorrhage in the brain tissue and death after stroke. Patients with unfavorable imaging profiles on both modalities had very poor outcomes.

"While best outcomes were observed in patients with a favorable profile on both imaging modalities, patients who had a favorable profile on at least one imaging modality also achieved reasonable outcomes," said Sarraj, who sees patients at UT Physicians, the clinical practice of McGovern Medical School, and is an attending neurologist at Memorial Hermann-Texas Medical Center.

The ongoing international Phase III randomized controlled trial, SELECT2, also led by Sarraj, will assess the efficacy and safety of thrombectomy procedure in patients with unfavorable profile on one or both imaging modalities. The SELECT trials are funded by grants from Stryker Neurovascular.

Credit: 
University of Texas Health Science Center at Houston

Scientists identify gene that puts brakes on tissue growth

image: Results from a Northwestern University study of the planarian flatworm could have ramifications for novel tissue engineering methods.

Image: 
Northwestern University

The planarian flatworm is a simple animal with a mighty and highly unusual ability: it can regenerate itself from nearly every imaginable injury, including decapitation. These tiny worms can regrow any missing cell or tissue -- muscle, neurons, epidermis, eyes, even a new brain.

Since the late 1800s, scientists have studied these worms to better understand fundamental principles of natural regeneration and repair, information that could provide insights into tissue healing and cancer. One mechanism that is yet unknown is how organisms like these control the proportional scaling of tissue during regeneration.

Now, two Northwestern University molecular biologists have identified the beginnings of a genetic signaling pathway that puts the brakes on the animal's growth. This important process ensures the appropriate amount of tissue growth in these highly regenerative animals.

"These worms have essentially discovered a natural form of regenerative medicine through their evolution," said Christian Petersen, who led the research. "Planarians can regenerate their whole lives, but how do they limit their growth? Our discovery will improve understanding of the molecular components and organizing principles that govern perfect tissue restoration."

The findings ultimately may have important ramifications for novel tissue engineering methods or strategies to promote natural repair mechanisms in humans.

Petersen is an associate professor of molecular biosciences in Northwestern's Weinberg College of Arts and Sciences. He and Erik G. Schad, a graduate student in Petersen's lab, conducted the study.

The results were published in the Jan. 20 issue of the journal Current Biology. Petersen is the corresponding author, and Schad is the paper's first author.

The researchers have identified a control system for limiting regeneration and also a new mechanism to explain how stem cells can influence growth. Specifically, Petersen and Schad discovered that a gene called mob4 suppresses tissue growth in the animals. When the researchers inhibited the gene in experiments, the animal grew to twice its normal size.

The gene, they found, works in a rather surprising way: by preventing the descendants of stem cells from producing a growth factor called Wnt, a protein released from cells to communicate across distances. The Wnt signaling pathway is known to play a role in cancer cell regeneration.

Planarians are 2 to 20 millimeters in size and have a complex anatomy with around a million cells. They live in freshwater ponds and streams around the world. The worm's genome has been sequenced, and its basic biology is well-characterized, making planarians popular with scientists.

Credit: 
Northwestern University

Fungal diversity and its relationship to the future of forests

image: Stanford researchers gathered soil samples from dozens of North American forests, including Pike National Forest in Colorado. They used these samples to better understand the influence of climate change on symbiotic soil microbes that control the health of forests.

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Kabir Peay

If you indulge in truffles, or porcini and chanterelle mushrooms, you have enjoyed a product of ectomycorrhizal fungi. Forming symbiotic relationships with plants - including pine, birch, oak and willow tree species - these fungi have existed for millions of years, their sprawling filaments supporting ecosystems throughout their reach.

According to research from Stanford University, published Jan. 21 in the Journal of Biogeography, by the year 2070, climate change could cause the local loss of over a quarter of ectomycorrhizal fungal species from 3.5 million square kilometers of North American pine forests - an area twice the size of Alaska.

"These are critical organisms for the functioning and the health of forests," said Kabir Peay, associate professor of biology in Stanford's School of Humanities and Sciences and senior author of the study. "We have evidence to suggest that these fungi are as susceptible to climate change as other kinds of organisms and their response may be even more important."

Previously, the Peay lab had mapped the global distributions of forests where trees associate with different types of symbiotic fungi, finding that over 60 percent of all trees on Earth currently associate with ectomycorrhizal fungi. Now, by learning more about the communities these fungi form in different climates, the researchers projected how climate change might affect them in the future.

Microbial maps

Over several years, the Peay lab has gathered about 1,500 soil samples from 68 pine forests, which represent a swath of North America from Florida to Alaska. In past work, they sequenced DNA in each sample to understand what fungal species live in that soil, and in what abundance. Their results, published previously, suggested that fungi were different in each region, contradicting a common assumption that those communities would look similar in most places in the world. They followed that up by mapping the associations between trees and symbiotic microbes around the world.

For their latest paper, Brian Steidinger, a postdoctoral scholar in the Peay lab, explored the relationship between these geographical fungi patterns and historical climate data.

"We took soil from the cores and climatic data unique to each site," said Steidinger, who was lead author of the study. "We found that climate was by far the most important predictor of contemporary fungal diversity patterns across North America."

Steidinger also found that different regions of North America had unique optimal temperatures for fungal diversity. For example, cold boreal forests had a diversity peak around 5 C mean annual temperature, while Eastern temperate forests peaked in diversity near 20 C.

The researchers then applied these data to predict future diversity, given projections of climate change produced by the Intergovernmental Panel on Climate Change. Because of the regional differences in optimal climate for fungal diversity, some forests, particularly those in the North and Northwest, could experience major decreases in fungal diversity.

"According to our models, climate change over the next 50 years could eliminate more than a quarter of ectomycorrhizal species inside 3.5 million square kilometers of North American pine forests," said Steidinger. "That's an area twice the size of Alaska."

Other regions, such as the Eastern temperate forests, could experience gains of 30 to 50 percent - assuming it is as easy to develop new species as to lose them.

"One of the things that's kind of shocking and a little bit scary is that we predict there will be some pretty significant decreases in diversity in western North America, well known culturally for fungal diversity and for people who are interested in collecting edible mushrooms," Peay said.

Buffering against climate change

Ectomycorrhizal fungi form a sheath around their hosts' roots, which can help prevent erosion and protect roots from damage and disease. The fungi seem to boost carbon storage in soil by slowing down decomposition and encouraging the buildup of soil. They also help their host trees grow more quickly - and therefore take in more carbon - by improving their ability to take in nitrogen, which they need in order to grow.

"In terms of ecosystem function, particularly buffering the atmosphere against climate change, ectomycorrhizal fungi are among the last microbes you want to lose," said Steidinger. "We're expecting to lose the species that seem to be the most functionally intense - the ones with the greatest enzyme activity, the ones that forage out the farthest."

Building on this work, the researchers are considering studying forests with low diversity of fungi and conducting experiments to better understand how these altered fungal communities might function in the future.

"For microbiome work, I feel like we're in a new era of discovery," said Peay. "Like Darwin and Wallace getting on ships and going to new places and seeing new things and changing the way they view the world, that is what is happening in this field."

Credit: 
Stanford University

Study provides insight into 'rapport-building' during victim interviews

A University of Liverpool research paper, published in Psychology, Public Policy, and Law, provides details of the approaches needed to help build rapport with victims of crime during interviews.

Interviewing victims is one of the most challenging aspects of sexual offence investigations. Victims can be unwilling to reveal information, specifically within a formal interviewing setting and it is crucial to obtain information since they are often the only source of information.

In the UK, US, Canada and Israel there are a number of models and protocols in place, such as the 'PEACE' model and the National Institute of Child Health and Human Development (NICHD) interview protocol, which helps to ensure a non-accusatory, information gathering approach to interviewing victims.

South Korea

In South Korea, sexual offences are a serious social problem. According to recent official statistics, the total number of sexual crimes occurring per year rose 12% from 2014 to 2018.

The Korean National Police Agency has attempted to improve competences in investigating sex offences, with an emphasis on interviewing due to the limited amount of physical evidence that is often a hallmark of such cases. Since 2004 KNPA have introduced the PEACE model to spread the recent knowledge on investigative interviewing principles and techniques. The KNPA also executed nationwide video-recorded interview system to improve the admissibility of police interviews and to protect the human rights of interviewees in 2007. Further, the KNPA disseminated the NICHD protocol to assist officers interviewing child victims in 2010.

To enhance and maintain the officers' expertise related to the guidelines introduced, the KPIA (Korean Police Investigation Academy), which is the professional training institution of the KNPA, provides relevant investigative interviewing courses composed of learning theories and simulation exercises

Rapport-based interviewing

Unfortunately, research has found that Korean officers often do not adopt the methods recommended by the NICHD in practice. Especially, the establishment and building of rapport when interviewing victims. Rapport-building offers a friendly atmosphere and consequently reduces the uneasiness that may exert a negative impact on information gathered

Rapport-based interviewing can mitigate the negative feelings of child victims during police interviews and increase the amount of information generated. Despite these findings, little is known about how to create an environment of rapport and, more specifically, there is very little known about the set of behaviours or approaches that underpin it.

To find out more researchers from the University's Centre for Critical and Major Incident Psychology, led by Centre Director Professor Laurence Alison, analysed over 100 hours of KNPA investigative interviews using a framework called ORBIT.

ORBIT

The observing rapport-based interpersonal techniques (ORBIT) framework analyses rapport-based interviewing skills along two dimensions: motivational interviewing (MI) skills and interpersonal competence (use of adaptive interviewing behaviours and absence of maladaptive interviewing behaviours).

MI is a counselling method that helps people resolve ambivalent feelings and insecurities to find the internal motivation they need to change their behaviour. For example finding the motivation to tell an interviewer what has happened or details of a perpetrator despite wanting to forget or not want to talk about it.

The researchers coded 103 hours of investigative interviews with sexual offence victims - a sample of 86 single victim cases conducted by 26 police interviewers in South Korea. In all cases, there was a subsequent conviction.

Results

Results showed that humanistic approaches positively influence adaptive interactions between interviewer and victim whilst simultaneously reducing maladaptive ones. This results in an increase in yield.

Researchers also found that interviewer adaptive behaviours directly increase victim adaptive behaviour (with the same effect for maladaptive behaviour). Victim adaptive behaviour is positively associated with interview yield, and victim maladaptive behaviour is negatively associated with it.

Professor Alison, said: "These results suggest that interviews conducted in a humanistic-consistent fashion strongly positively influence adaptive victim behaviour, which, in turn, increases interview yield."

Credit: 
University of Liverpool

Study results will inform immunization programs globally

video: Professor Helen Marshall (University of Adelaide) and study participant Harry Spurrier discuss the findings of the B Part of It meningococcal B study.

Image: 
University of Adelaide.

The results of the B Part of It study - the largest meningococcal B herd immunity study ever conducted - are published today in the New England Journal of Medicine.

The results have implications for all meningococcal B vaccine programs globally.

Led by Professor Helen Marshall from the University of Adelaide's Robinson Research Institute, the B Part of It study involved almost 35,000 senior school students in South Australia, aged 15 to 18 years, during 2017 and 2018.

"Our study has shown good protection was provided by the meningococcal B vaccine against meningococcal disease in those vaccinated but did not show an overall reduction in the proportion of adolescents carrying the bacteria, including the B strain," Professor Marshall says.

Adolescents can harmlessly carry the meningococcus bacteria in the back of the throat with only a very small proportion developing the disease. Meningococcal B is one of the most common strains that causes meningococcal disease, an acute bacterial infection that kills approximately 10% of those infected, and causes permanent disabilities in about 20% of cases. Those most at risk are babies and children up to the age of five years, and teenagers and young adults from ages 15 to 24 years.

"We are pleased to report not a single case of meningococcal disease among our study participants to date, over the three years since the study began, compared to 12 cases in the same age group in the two years prior to the study.

"Potentially this means a life or lives were saved, as, on average, one in every 10 children with meningococcal disease dies from it," Professor Marshall says.

"These results highlight the importance of individual vaccination for adequate protection, as the vaccine is unlikely to be able to stop spread of the bacteria between individuals," Professor Marshall says. "The study has identified the critical finding that individuals need to be vaccinated to protect themselves against meningococcal B disease, rather than expecting community protection through reduced transmission of the bacteria," she says.

The study also identified a number of high-risk behaviours associated with carriage of meningococcal strains in young people, including: smoking cigarettes, attending bars or clubs, and intimate kissing. Older school students, school boarders, and those who had recently had a cold or sore throat were also more likely to carry the meningococcus in their throat.

The outcomes of the B Part of It study are now being used in Australia and globally, to assess the cost-effectiveness of meningococcal B immunization programs for children and young people.

Gill and Oren Klemich, who lost their 18-year-old son, Jack, to meningococcal B in 2009, have supported the B Part of It program as ambassadors and followed the results closely.

"We are extremely proud of the impact this study has had in informing both local and global policy around meningococcal B, as well as the impact the study and South Australian Government funded program have had in vaccinating and protecting over 60,000 young people against this horrible disease," says Oren.

Credit: 
University of Adelaide