New Model for Antibacterial Mechanism

Brookhaven Lab biologist Paul Freimuth and co-author Feiyue Teng, a scientist in Brookhaven Lab's Center for Functional Nanomaterials (CFN), at the light microscope used to image bacteria in this study.
Credit: Brookhaven National Laboratory

Biologists at the U.S. Department of Energy’s Brookhaven National Laboratory and their collaborators have discovered an aberrant protein that’s deadly to bacteria. In a paper just published in the journal PLOS ONE, the scientists describe how this erroneously built protein mimics the action of aminoglycosides, a class of antibiotics. The newly discovered protein could serve as a model to help scientists unravel details of those drugs’ lethal effects on bacteria—and potentially point the way to future antibiotics.

“Identifying new targets in bacteria and alternative strategies to control bacterial growth is going to become increasingly important,” said Brookhaven biologist Paul Freimuth, who led the research. Bacteria have been developing resistance to many commonly used drugs, and many scientists and doctors have been concerned about the potential for large-scale outbreaks triggered by these antibiotic-resistant bacteria, he explained.

“What we’ve discovered is a long way from becoming a drug, but the first step is to understand the mechanism,” Freimuth said. “We’ve identified a single protein that mimics the effect of a complex mixture of aberrant proteins made when bacteria are treated with aminoglycosides. That gives us a way to study the mechanism that kills the bacterial cells. Then maybe a new family of inhibitors could be developed to do the same thing.”

Engineers at UBC get under the skin of ionic skin

Dr. John Madden and Yuta Dobashi with one of the hydrogel sensors.
Photo by Kai Jacobson/UBC Faculty of Applied Science

In the quest to build smart skin that mimics the sensing capabilities of natural skin, ionic skins have shown significant advantages. They’re made of flexible, biocompatible hydrogels that use ions to carry an electrical charge. In contrast to smart skins made of plastics and metals, the hydrogels have the softness of natural skin. This offers a more natural feel to the prosthetic arm or robot hand they are mounted on, and makes them comfortable to wear.

These hydrogels can generate voltages when touched, but scientists did not clearly understand how — until a team of researchers at UBC devised a unique experiment, published in Science.

“How hydrogel sensors work is they produce voltages and currents in reaction to stimuli, such as pressure or touch – what we are calling a piezoionic effect. But we didn’t know exactly how these voltages are produced,” said the study’s lead author Yuta Dobashi, who started the work as part of his master’s in biomedical engineering at UBC.

Working under the supervision of UBC researcher Dr. John Madden, Dobashi devised hydrogel sensors containing salts with positive and negative ions of different sizes. He and collaborators in UBC’s physics and chemistry departments applied magnetic fields to track precisely how the ions moved when pressure was applied to the sensor.

UBC team discovers ‘silver bullet’ to keep medical devices free of bacteria

Photo of a coated versus an uncoated catheter.
Credit: Kizhakkedathu Lab

University of British Columbia researchers have found a ‘silver bullet’ to kill bacteria and keep them from infecting patients who have medical devices implanted.

The team from UBC and the Vancouver Coastal Health Research Institute has developed a silver-based coating that can easily be applied to devices such as catheters and stents. Their novel formulation, discovered by screening dozens of chemical components, overcomes the complications of silver that have challenged scientists for years.

Dr. Jayachandran Kizhakkedathu

“This is a highly effective coating that won’t harm human tissues and could potentially eliminate implant-associated infections. It could be very cost-effective and could also be applicable to many different products,” said Dr. Jayachandran Kizhakkedathu, professor in UBC’s department of pathology and laboratory medicine, Centre for Blood Research and Life Sciences Institute and co-senior author of the study published today in ACS Central Science.

Implanted medical devices can save lives, but they carry a great risk of infection which usually arises from contamination as the device is being implanted. Urinary tract infections from catheters, for example, are among the most common hospital-acquired infections.

Changes in vegetation shaped global temperatures over last 10,000 years

Alexander Thompson, a postdoctoral research associate in earth and planetary sciences in Arts & Sciences, updated simulations from an important climate model to reflect the role of changing vegetation as a key driver of global temperatures over the last 10,000 years.
Source: Washington University in St. Louis

Follow the pollen. Records from past plant life tell the real story of global temperatures, according to research from a climate scientist at Washington University in St. Louis.

Warmer temperatures brought plants — and then came even warmer temperatures, according to new model simulations published in Science Advances.

Thompson had long been troubled by a problem with models of Earth’s atmospheric temperatures since the last ice age. Too many of these simulations showed temperatures warming consistently over time.

But climate proxy records tell a different story. Many of those sources indicate a marked peak in global temperatures that occurred between 6,000 and 9,000 years ago.

Thompson had a hunch that the models could be overlooking the role of changes in vegetation in favor of impacts from atmospheric carbon dioxide concentrations or ice cover.

Protease inhibitors safer than thought for pregnant women with HIV

University of Oxford researchers assessed evidence from 34 studies, involving over 57,000 pregnant women with HIV, and found that protease inhibitor-based antiretroviral therapies significantly increased the risk of babies being small or very small for their gestational age, but there were no other adverse pregnancy outcomes, compared to therapies without protease inhibitors.

Globally, more than 37 million people were living with HIV in 2020, including 19 million women of childbearing age (UNAIDS). Each year, around 1.3 million of these women become pregnant, most of whom live in sub-Saharan Africa where rates of maternal and child mortality remain high.

Antiretroviral therapy is recommended for all pregnant women living with HIV, since this plays a crucial role in improving maternal health and reducing transmission of HIV from mother to child. However, to date there has been a critical lack of evidence on whether antiretroviral therapies increase the risk of adverse pregnancy outcomes such as preterm birth, low birth weight, stillbirth, and babies being small for their gestational age.*

In particular, there has been concern about a type of antiretroviral drug called protease inhibitors (including atazanavir, lopinavir, and darunavir). Current guidelines recommend that protease inhibitor-based therapies should be used in pregnancy only if ‘first-line’ treatments (such as integrase and reverse-transcriptase based treatments) are either unsuitable or unavailable. These guidelines also often advise against the use of a specific protease inhibitor, lopinavir/ritonavir (LPV/r), citing an increased risk of preterm birth. However, these recommendations are based on limited evidence, and can restrict treatment options for pregnant women with HIV.

Meat industry not threatened by plant-based alternatives, study suggests

Vegan patties like these made with pea protein may mimic the sensory experience of eating a real burger, but aren’t putting much of a dent in fresh meat sales.
Credit: Unsplash

At least for now, there is no reason for the traditional meat industry to have much of a beef with producers of plant-based burgers and other meat alternatives, new research suggests.

The study showed that while sales and market share of new-generation plant-based meat alternatives have grown in recent years, those gains haven’t translated into reduced consumer spending on animal meat products.

Overall, the analysis of national meat purchases suggested that plant-based meats sold in patty, link and ground form are mostly an add-on to beef and pork and tend to serve as a substitute for chicken, turkey and fish.

Wuyang Hu Source: OSU

“We thought plant-based meat alternatives would be a potential replacement for red meat, but they’re not. It’s more of a complement,” said study co-author Wuyang Hu, professor of agricultural, environmental and development economics at The Ohio State University. “People buy pork and beef, and at the same time they also buy plant-based meats.”

Researchers noted the study is not intended to take any industry’s side or give consideration to the comparative healthfulness of products.

“This new generation of plant-based meat, by mimicking the taste and sensory experience of eating real meat, appeals to consumers who are not only vegetarian but also people who are curious about plant-based meat and even meat eaters,” said lead author Shuoli Zhao, assistant professor of agricultural economics at the University of Kentucky.

“We wanted to look at the most up-to-date market response to a new product and see how the demand for such a product is interacting with the rest of the meat categories, especially within the fresh meat sector.”

World-leading simulation model to improve future pandemic quarantine response

A world-leading epidemiological simulation model to help improve future border quarantine practices for Australia and overseas has been developed by researchers at the University of Melbourne, the Peter Doherty Institute for Infection and Immunity and collaborating institutions.  

The team of researchers – who advised the Federal Government on its National Plan to Transition Australia's National COVID Response last August – have published their model findings in the journal Sciences Advances.

The simulation model combines a detailed representation of person-to-person contact and virus transmission among both travelers and the quarantine workforce, with an accurate simulation of how infectiousness and virus testing accuracy varies over the course of a person’s period of infection.

Researchers were able to include these factors into the simulation model by drawing on growing data from the operation of Australian hotel quarantine during the COVID-19 pandemic, and their inclusion can aid the design of quarantine systems to reduce the risk of virus transmission from infected arrivals in quarantine to the wider community.

Lead researchers Associate Professor Nic Geard and Dr Cameron Zachreson, from the University’s School of Computing and Information Systems (CIS), said the simulation model was developed to be adaptable and better calculate risks associated with various quarantine pathways including hotel quarantine, home quarantine and dedicated quarantine facilities such as the Victorian Quarantine Hub at Mickleham.

Gel delivery enhances cancer treatment

As shown in this demonstration, the hydrogel can be easily injected through a needle and then rapidly self-heals after injection to form a solid-like gel. The needle in this image is a 21-gauge needle, a relevant size for human injection.
Image credit: Abigail K. Grosskopf

One cutting-edge cancer treatment exciting researchers today involves collecting and reprogramming a patient’s T cells – a special set of immune cells – then putting them back into the body ready to detect and destroy cancerous cells. Although effective for widespread blood cancers like leukemia, this method rarely succeeds at treating solid tumors.

Now, Stanford University engineers have developed a delivery method that enhances the “attack power” of the modified immune cells, called chimeric antigen receptor (CAR) T cells. Researchers add CAR-T cells and specialized signaling proteins to a hydrogel – a water-filled gel that has characteristics in common with biological tissues – and inject the substance next to a tumor. This gel provides a temporary environment inside the body where the immune cells multiply and activate in preparation to fight cancerous cells, according to a new study published April 8 in Science Advances. The gel acts like a leaky holding pen that pumps out activated CAR-T cells to continuously attack the tumor over time.

“A lot of the CAR-T cell field is focusing on how to make better cells themselves, but there is much less focus on how to make the cells more effective once in the body,” said Eric Appel, assistant professor of materials science and engineering at Stanford and senior author of the paper. “So, what we’re doing is totally complementary to all of the efforts to engineer better cells.”

The art of smell: Research suggests the brain processes smell both like a painting and a symphony

What happens when we smell a rose? How does our brain process the essence of its fragrance? Is it like a painting – a snapshot of the flickering activity of cells – captured in a moment in time? Or like a symphony, an evolving ensemble of different cells working together to capture the scent? New research suggests that our brain does both.

“These findings reveal a core principle of the nervous system, flexibility in the kinds of calculations the brain makes to represent aspects of the sensory world,” said Krishnan Padmanabhan, Ph.D., an associate professor of Neuroscience and senior author of the study recently published in Cell Reports. “Our work provides scientists with new tools to quantify and interpret the patterns of activity of the brain.”

Researchers developed a model to simulate the workings of the early olfactory system – the network the brain relies on for smelling. Employing computer simulations, they found a specific set of connections, called centrifugal fibers, which carry impulses from other parts of the central nervous system to the early sensory regions of the brain, played a critical role. These centrifugal fibers act as a switch, toggling between different strategies to efficiently represent smells. When the centrifugal fibers were in one state, the cells in the piriform cortex – where the perception of an odor forms – relied on the pattern of activity within a given instant in time. When the centrifugal fibers were in the other state, the cells in the piriform cortex improved both the accuracy and the speed with which cells detected and classified the smell by relying on the patterns of brain activity across time.

These processes suggest the brain has multiple responses to representing a smell. In one strategy, the brain uses a snapshot, like a painting or a photograph, at a given moment to capture the essential features of the odor. In the other strategy, the brain keeps track of the evolving patterns. It is attuned to which cells turn on and off and when – like a symphony.

When maggots uncover a murder

These maggots belong to the latrine fly. They are quasi criminal officers.
Credit: Roberto Schirdewahn

Investigators still have to go in search of traces. But if they find crawling animals at the scene, they can be of great help to them.

First come the blowflies. A few hours after death, they control the eyes, nose, mouth and wounds of a lifeless body. Here they lay their eggs - and just a few days later it is teeming with life: numerous maggots hatch and feed on the dead tissue until they finally become new flies. Not only gliding, other types of flies join in over time, and finally various beetles are crawled on. The hustle and bustle that takes place on corpses can be quite revealing - for example, if you want to find out when and under what circumstances a person died.

With these questions, Dr. Ersin Karapazarlioglu is only too good. He conducts research in the RUB Faculty of Biology and Biotechnology in the Prof. Dr. Wolfgang Kirchner. Before coming to Germany in 2020, he worked for 17 years in Turkey as a criminal officer and as a lecturer at the police college and a university. He always looked for insects at crime scenes. With their help, he was able to determine the time of death of a body more precisely than with other methods. The method is called forensic entomology. The method was initially established in the USA and is still in its infancy in Europe.

A tool for predicting the future

MIT researchers created a tool that enables people to make highly accurate predictions using multiple time-series data with just a few keystrokes. The powerful algorithm at the heart of their tool can transform multiple time series into a tensor, which is a multi-dimensional array of numbers (pictured). Credits: Figure courtesy of the researchers Source: MIT

Whether someone is trying to predict tomorrow’s weather, forecast future stock prices, identify missed opportunities for sales in retail, or estimate a patient’s risk of developing a disease, they will likely need to interpret time-series data, which are a collection of observations recorded over time.

Making predictions using time-series data typically requires several data-processing steps and the use of complex machine-learning algorithms, which have such a steep learning curve they aren’t readily accessible to nonexperts.

To make these powerful tools more user-friendly, MIT researchers developed a system that directly integrates prediction functionality on top of an existing time-series database. Their simplified interface, which they call tspDB (time series predict database), does all the complex modeling behind the scenes so a nonexpert can easily generate a prediction in only a few seconds.

The new system is more accurate and more efficient than state-of-the-art deep learning methods when performing two tasks: predicting future values and filling in missing data points.

NUS-Monash University collaboration produces universal flu vaccine candidate

Current influenza vaccines have shortcomings
Credit: NUS Yong Loo Lin School of Medicine

Influenza, commonly referred to as “flu”, is a major global public health concern and a huge economic burden to societies. Seasonal influenza epidemics afflict between 13 to 100 million individuals annually, including three to five million cases of severe illness and 300,000 to 600,000 deaths worldwide. This represents a top global public health concern and an extraordinary economic burden to all societies. Pandemics are less frequent, but are generally more severe and pose a greater threat. Over the past century, there have been at least four devastating pandemics caused by Influenza A virus which took the lives of hundreds of millions of individuals.

Although vaccination arguably represents the most effective way to prevent influenza, current vaccination strategies suffer from certain limitations, chief of which require current influenza vaccines to be updated annually to match circulating strains. This results in low vaccination take-up rates and poor coverage due to inaccurate prediction of circulating strains. Broadly protective, “universal” flu vaccines that do not need to be updated annually have therefore been pursued.

Molecular key may unlock new treatments for neurodegenerative disorders

Structure of SARM1 in complex with inhibitor.
Credit: Thomas Ve

Researchers have worked out how to successfully switch off a key pathway of nerve fiber breakdown in debilitating neurodegenerative disorders such as Parkinson’s disease, traumatic brain injury and glaucoma.

The study, led by Griffith University’s Institute for Glycomics and Disarm® Therapeutics, a wholly owned subsidiary of pharmaceutical company Eli Lilly, reveals the structural processes behind activation and inhibition of SARM1, a key molecule in the destruction of nerve fibers.

“As a trigger for nerve fiber degeneration, understanding how the enzyme SARM1 works may help us treat several neurodegenerative conditions,” said Dr Thomas Ve from the Institute for Glycomics.

“In this study we show the molecular interactions that can switch SARM1 on and off. This gives us a clear avenue for the design of new drug therapeutics.”

In neurodegenerative conditions like peripheral neuropathy, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), traumatic brain injury and glaucoma, when the nerve fibers are damaged, SARM1 is activated.

“This sparks a cascade of molecular processes that leads to the self-destruction of the nerve cell’s axon, the cable that carries electric impulse away from the body of the nerve cell to the next,’’ Dr Ve said.

Blow flies can be used to detect use of chemical weapons and other pollutants

Blow flies are common across many environments.
Photo by Fir0002/Flagstaffotos

Researchers at the School of Science at IUPUI have found that blow flies can be used as chemical sensors, with a particular focus on the detection of chemical warfare agents.

Despite widespread bans, chemical weapons have been deployed in recent conflicts such as the Syrian civil war, and some experts fear they may be used in the war in Ukraine. An IUPUI study shows that blow flies could be used as a safer alternative for investigating the use of these weapons -- as well as other chemicals in the environment -- keeping humans out of potentially dangerous situations.

The work appears in the journal Environmental Science and Technology. The research was funded through a contract from the U.S. Defense Advanced Research Projects Agency.

Research Says Docile Gecko is a Savage Scorpion Predator

SDSU researchers document geckos violently shaking from side to side to immobilize their scorpion prey.

When western banded geckos are hungry, they pounce on crickets, beetles, or other small arthropods in their environment, and quickly gobble them up.

But when they catch scorpions, they begin to shake themselves violently from side to side at high speeds, smashing their prey back and forth against the ground for several seconds until it is immobilized. After the fracas, the gecko devours the much smaller scorpion.

“It's a really kind of physically stunning behavior, something totally unexpected from a lizard like that,” said San Diego State University biologist Rulon Clark.

“They seem to be kind of body slamming the scorpions into the ground. If you ever see seals, they'll pick fish up and they'll slap them against the water. I think geckos are doing essentially the same thing, just blunt force trauma.” said Malachi Whitford (‘20), who studied the geckos’ unusual feeding behavior as a graduate student in the joint SDSU and University of California, Davis Ph.D. program in ecology. The University of California, Riverside, also participated in the research.

A Laser-Powered Upgrade to Cancer Treatment

Kei Nakamura, Antoine Snijders and Lieselotte Obst-Huebl (from left) at the BELLA laser facility aligning cartridges containing human cells in the proton beam path. This setup enabled measurements of the biological effects of laser-driven protons.
Credit: Lawrence Berkeley National Laboratory

Biologists and physicists at Lawrence Berkeley National Laboratory (Berkeley Lab) have teamed up to create new opportunities for cancer treatment using laser-generated proton beams.

The ongoing project seeks to adapt the nascent technology of laser-driven ion accelerators – which are as cool as they sound – to make a more effective type of radiation therapy more readily available to patients.

“Proton therapy centers are large, expensive facilities, so they are limited around the world,” said co-lead author Antoine Snijders, a cancer researcher and senior scientist in the Biological Sciences and Engineering (BSE) Division. “There is currently limited geographic distribution and access to proton therapy worldwide.  The way to get broader access, and potentially lower costs, is to reduce the cost and footprint of these types of facilities. And that means we need more compact sources of ions for proton accelerators.”

Scientists are also investigating the potential benefit of using these accelerators to deliver proton beam radiation therapy at ultrahigh doses within extremely short exposure times – a technology called FLASH radiotherapy. Though the approach remains experimental for now, FLASH radiotherapy could change the landscape of radiation oncology. “If our work could also bring FLASH radiotherapy to patients, it could be the best of both worlds,” Snijders added.

A robot small enough to explore the lungs

The image shows a life-size model of part of a bronchial tree built from anatomical data. A section of the magnetic tentacle robot is seen on the right.
Credit: University of Leeds

Engineers and scientists have paved the way for a robot that can reach some of the smallest bronchial tubes in the lungs – to take tissue samples or deliver cancer therapy.

Known as a magnetic tentacle robot, it measures just 2 millimeters in diameter, about twice the size of the tip of a ballpoint pen.

Magnets on the outside of the patient will be used to guide the magnetic tentacle robot into place.

The device has been developed by a team of engineers, scientists and clinicians based at the STORM Lab at Leeds, which is pioneering the use of robotic systems to assist in endoscopy and catheter procedures, where a fine tube is inserted into the body.

The researchers have published their findings in the journal Soft Robotics.

The proof of concept they have developed was based on laboratory tests involving a 3D replica of a bronchial tree modelled from anatomical data. The next phase of the research will investigate the effectiveness of the device in navigating lungs taken from a cadaver.

Research suggests interrupting immune response improves multiple sclerosis outcomes

Multiple sclerosis is a chronic disease that damages neurons. A WVU doctoral student, Kelly Monaghan, is researching the role that a protein, STAT5, plays in the development of MS.
Credit: WVU Illustration/Aira Burkhart

A human immune system is a lot like the board game Mouse Trap: it’s a Rube Goldberg system of interacting parts. Only instead of a falling ball causing a tiny diver to leap into a tub—which, in turn, springs a trap on some plastic mice—proteins trigger other proteins to activate immune cells and direct them toward germs. But if those proteins mistakenly direct immune cells toward healthy tissue, autoimmune diseases like multiple sclerosis – which attacks neurons - can arise.

Kelly Monaghan
Footnote 1 Credit: WVU Photo/Tyler Mertins

A new study led by Kelly Monaghan—a researcher with the West Virginia University School of Medicine—suggests that part of the “Rube Goldberg” immune system shows promise as a potential target for MS therapies.

“Anytime you have any kind of central nervous system issues, you have to go through a series of steps to have cells get into the brain or spinal cord,” said Monaghan, a doctoral candidate in the Department of Microbiology, Immunology and Cell Biology. “Gaining a better understanding of those immune mechanisms associated with MS can help to inform novel therapies.”

Her findings appeared in the Proceedings of the National Academy of Science.

Her study—funded by the National Institutes of Health—focused on STAT5, one of the many proteins circulating in the body that can metaphorically turn genes on or off.

Nanoparticle-based COVID-19 vaccine could target future infectious diseases

SNAs are ball-like forms of DNA and RNA
arranged on the surface of a nanoparticle

Just one dose of a new nanoparticle-based COVID-19 vaccine was enough to produce an immune response in animals on track with vaccines currently in clinical use. And with minor changes, Northwestern University researchers hope the same vaccine platform could target other infectious diseases.

In a new study, 100% of mice who received the protein-based immunization survived when challenged with lethal doses of the SARS-CoV-2 virus, which causes COVID-19. None of the mice experienced lung damage due to SARS-CoV-2 exposure. All mice who did not receive this nanoparticle vaccine died in a 14-day trial.

The results, published this week in the Proceedings of the National Academy of Sciences, outline the structure-function relationships between the first spherical nucleic acid (SNA) vaccine developed to protect against viral infections.

“What makes this vaccine different than other vaccines is the approach we take to design them,” said Dr. Michelle Teplensky, co-first author of the paper. “Even as recently as a few years ago people focused on selecting the right target to train the immune system and the right stimulant to activate it, not on how those components were arranged structurally and presented to the body.”

Called SNAs, the nanoparticles that house the immune target are a form of globular DNA that can enter and stimulate immune cells with extreme efficiency. SNAs have been tested in more than 60 cell types. Researchers experimentally determined the ideal ratio between the SNA’s shell and core density that produces the most potent response.

SNA vaccines have been used to treat mice with triple negative breast cancer — and more vaccines for other cancers are in development.

New study defines spread of SARS-CoV-2 in white-tailed deer

White-Tailed Deer
Credit: Heidi-Ann Fourkiller / SFLORG

North American white-tailed deer – shown in 2021 surveys of five states to have SARS-CoV-2 infection rates of up to 40% – shed and transmit the virus for up to five days once infected, according to a new study.

“It’s a relatively short window of time in which the infected animals are shedding and are able to transmit the virus,” said Dr. Diego Diel, associate professor in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the College of Veterinary Medicine’s Animal Health Diagnostic Center. “However, the virus is very efficient at transmitting to white-tailed-deer entering contact with infected animals.”

The study, “From Deer-to-Deer: SARS-CoV-2 is Efficiently Transmitted and Presents Broad Tissue Tropism and Replication Sites in White-Tailed Deer,” which published online on March 21 in PLOS Pathogens, also identified that the virus develops and replicates in the deer’s respiratory tract, lymphoid tissues – including tonsils and several lymph nodes – and in central nervous system tissues.

“Virus replication in the upper respiratory tract – especially the nasal turbinates [nose structures] - is comparable with what is observed in humans and in other animals that are susceptible to the infection,” Diel said, “and I think that’s probably one of the reasons why the virus transmits so efficiently.” As with humans, the virus spreads between deer through nasal and oral secretions and aerosols.