‘Super-resolution’ imaging technology

Led by Stefan Wilhelm, Ph.D., assistant professor in the Stephenson School of Biomedical Engineering at the University of Oklahoma, a team of researchers from the Gallogly College of Engineering at OU, OU Health Sciences Center and Yale University recently published an article in ACS Nano that describes their development of a super-resolution imaging platform technology to improve understanding of how nanoparticles interact within cells.

As technology-driven capabilities in engineering and healthcare are ever-increasing, scientists and engineers are developing new technologies to advance the future of health. One such area, nanomedicine, explores the use of nanoparticles for drug delivery in the body to fight against infectious diseases or cancer. The assessment of these nanomedicines in cells, tissues and organs is often performed by optical imaging, which can have a limited quality of imaging resolution. New imaging technologies are needed to see nanoparticles in their 3-D ultrastructural context within biological tissues.

“To see nanomedicines in biological samples, researchers either use electron microscopy, which provides excellent spatial resolution but lacks 3-D imaging capabilities, or optical microscopy, which achieves excellent 3-D imaging, but exhibits relatively low spatial resolution,” Wilhelm said. “We demonstrate that we can perform 3-D imaging of biological samples with electron microscopy-like resolution. This technique, called super-resolution imaging, allows us to see nanomedicines inside individual cells. Using this new super-resolution imaging method, we can now start to track and monitor nanoparticles inside cells, which is a prerequisite for designing nanomedicines that are safer and more efficient in reaching certain areas within cells.”

The researchers applied a 3-D super-resolution imaging technique known as expansion microscopy which involves embedding cells within swellable hydrogels. Like water-absorbing materials used in diapers, the hydrogel materials physically expand up to 20-fold their original size upon contact with water.

“This expansion enables the imaging of cells with a lateral resolution of approximately 10 nanometers using a conventional optical microscope,” Wilhelm said. “We combined this method with an approach to image metallic nanoparticles within cells. Our approach exploits the inherent ability of metallic nanoparticles to scatter light. We used the scattered light to image and quantify nanoparticles inside cells without the need for any additional nanoparticle labels.”

The authors suggest their super-resolution imaging platform technology could be used to improve the engineering of safer and more effective nanomedicines to advance the translation of these technologies into the clinic.

Share Button

Emerade adrenaline pen users urged to swap brands

Users of Emerade pens, which treat anaphylaxis, are being warned to change to another brand.

Share Button

Antibiotics prescribed at pharmacies to free up GP time

Pharmacies will be able to prescribe drugs for seven common ailments, including sore throats and earaches.

Share Button

Lip fillers: Call for tighter regulation after botched treatments

Experts warn the lip filler industry is ‘like the wild west’, with procedures having to be corrected.

Share Button

Viruses could reshuffle the carbon cycle in a warming world

Microbes play important roles in ecosystems, and these roles are changing with global warming. Scientists also now know that most types of microbes are infected by viruses, but they know relatively little about how these viral infections could change how microbes react to warming. In this study, scientists describe many different ways that increasing temperatures could affect viruses and their microbial hosts. These changes could ultimately affect the responses of whole ecosystems to warming. The work exposes several important gaps in researchers’ current knowledge about the connections between viruses, warming, and ecosystem functioning. Filling these gaps is crucial for understanding and predicting the effects of climate change on ecosystems.

This study creates a roadmap for understanding the many different ways that viruses could modify the effects of warming on communities of microbes. Viruses likely have strong effects on processes with microbes and the ways ecosystems function. Incorporating these previously ignored effects into ecosystem models will help scientists improve their predictions of how ecosystems could respond to climate change.

Microorganisms play integral roles in ecosystems by controlling the flow of energy and matter through processes like photosynthesis (carbon uptake), respiration (carbon release), and decomposition (carbon recycling). Climate change is currently altering how ecosystems function by changing how organisms operate within microbial food webs. Scientists know that viruses can have strong impacts on microbial processes, but they have less knowledge of how these impacts will change with future warming.

In this study, scientists from Duke University, the University of Tennessee Knoxville, the Netherlands Institute of Ecology, and Oak Ridge National Laboratory reviewed the potential impacts of warming on viruses and how these might alter scientific understanding of ecosystem responses to climate change. Warming likely affects several different stages of the viral infection cycle, as well as virus-host dynamics. However, there are still many gaps in our understanding about these effects. Because viruses are ubiquitous across all habitats and have strong effects on microbial functioning, filling these gaps is critical to understanding how warming will affect the flow of energy and matter within ecosystems. The researchers’ preliminary models show that viruses could potentially tip the scales on natural carbon balances, causing some ecosystems to switch from being net carbon sources (releasing more carbon than they store) to being net carbon sinks (absorbing carbon). This study shows how incorporating viruses into predictive models can lead to new and unexpected effects on ecosystems in response to climate change.

This work was supported by the Department of Energy Office of Science, Biological and Environmental Research program.

Share Button

Scientists develop gene silencing DNA enzyme that can target a single molecule

Researchers from the University of California, Irvine have developed a DNA enzyme — or DNAzyme — that can distinguish between two RNA strands inside a cell and cut the disease-associated strand while leaving the healthy strand intact. This breakthrough “gene silencing” technology could revolutionize the development of DNAzymes for treating cancer, infectious diseases and neurological disorders.

DNAzymes are nucleic acid enzymes that cut other molecules. Through chemistry, UCI’s team developed the Dz 46 enzyme, which specifically targets the allele-specific RNA mutation in the KRAS gene, the master regulator of cell growth and division, found in 25 percent of all human cancers. A description of how the team achieved this enzyme evolution was recently published in the online journal Nature Communications.

“Generating DNAzymes that can effectively function in the natural conditions of cell systems has been more challenging than expected,” said corresponding author John Chaput, UCI professor of pharmaceutical sciences. “Our results suggest that chemical evolution could pave the way for development of novel therapies for a wide range of diseases.”

Gene silencing has been available for more than 20 years and some FDA-approved drugs incorporate various versions of the technology, but none can distinguish a single point mutation in an RNA strand. The benefit of the Dz 46 enzyme is that it can identify and cut a specific gene mutation, offering patients an innovative, precision medicine treatment.

The DNAzyme resembles the Greek letter omega and acts as a catalyst by accelerating chemical reactions. The “arms” on the left and right bind to the target region of the RNA. The loop binds to magnesium, and folds and cuts the RNA at a very specific site. But generating DNAzymes with robust multiple turnover activity under physiological conditions required some ingenuity, because DNAzymes are normally very dependent on concentrations of magnesium not found inside a human cell.

“We solved that problem by re-engineering the DNAzyme using chemistry to reduce its dependency on magnesium and did so in such a way that we could maintain high catalytic turnover activity,” Chaput said. “Ours is one of the very first, if not the first, example of achieving that. The next steps are to advance Dz 46 to a point that it’s ready for pre-clinical trials.”

Team members Kim Thien Nguyen, project scientist, and Turnee N. Malik, postdoctoral scholar, both from the Department of Pharmaceutical Sciences, also participated in this study.

The researchers and UCI have filed provisional patent applications on the chemical composition and cleavage preference of Dz 46. Chaput is a consultant for drug development company 1E Therapeutics, which supported this work.

Share Button

Cleanup of inactive Gulf of Mexico wells estimated at $30 billion

Wetlands, coastal areas and offshore waters near Alabama, Louisiana and Texas have more inactive oil and gas wells than producing ones, and the cost to permanently plug and abandon them could be $30 billion, University of California, Davis, researchers suggest.

A paper published today in the journal Nature Energy examines the cost to plug 14,000 wells that are inactive, have not produced for five years and are unlikely to be reactivated in the Gulf of Mexico region, which is the epicenter of U.S. offshore oil and gas operations.

The wells could pose future environmental and financial risks to the public, and the cost differential for plugging onshore wells versus those in offshore waters is large, said Mark Agerton, an assistant professor at UC Davis and lead author of the paper.

Leaks from wells closer to shore are more likely to damage coastal ecosystems and release greenhouse gases like methane into the atmosphere, compared to wells in deep waters. The study found that more than 90% of inactive wells are in shallow areas, and the cost to plug those would be $7.6 billion, or 25% of a total $30 billion.

Informing policy decisions

“The wells aren’t supposed to be leaking into the environment, but sometimes they do,” said Agerton, of the Department of Agricultural and Resource Economics. “How do you get the most environmental benefit for the least amount of money?”

The findings could help states decide cleanup priorities, especially as they access $4.7 billion in federal money authorized by the Infrastructure Investment and Jobs Act. That money is set aside for methane reduction programs, including cleanup of old oil and gas wells, said Gregory Upton, an associate research professor at the Louisiana State University Center for Energy Studies and co-author of the paper.

“States have a pretty good idea of what it costs to plug these wells on land, but there is really a lot of uncertainty as to what the costs were for these offshore wells,” Upton said during a media briefing about the paper.

Liability for cleaning up wells abandoned in federal waters falls to prior owners if the current owner becomes insolvent and is unable to cover costs. Large American oil companies currently own or have owned 88% of the wells in federal Gulf of Mexico waters and would legally shoulder cleanup liabilities before taxpayers, Agerton said.

But in state waters, each jurisdiction handles liability differently, and prior ownership doesn’t come into play. States oversee plugging programs for orphaned wells whose owners have gone bankrupt, though the cost to plug an abandoned offshore well increases with the length of the well and the depth of the water.

“The bulk of the costs comes from plugging wells in deeper water where the environmental consequences are less than for a shallow well closer to shore,” Agerton said. “That money is probably better spent on state waters where they can’t go after prior owners for cleanup costs and it’s going to be a cheaper cleanup job with more environmental benefit.”

Siddhartha Narra, Brian Snyder and Gregory B. Upton Jr. of Louisiana State University, are co-authors on the research.

Share Button

‘The NHS Trumps Woke’: Keir Starmer Slams Tories Over Culture Wars

Keir Starmer has declared that “the NHS trumps woke” as he slammed the Tories for focusing on culture wars rather than public services.

The Labour leader will on Tuesday address his shadow cabinet for the first time since last week’s local elections, in which they gained more than 500 councillors and take control of 22 more local authorities.

At the same time, the Tories lost more than 1,000 seats and 48 councils on a disastrous night for Rishi Sunak.

However, polling experts said that if the results were replicated across the country at a general election, Labour would fall short of winning an overall majority.

Starmer will tell his frontbench colleagues that while the party has “started to earn back voters’ trust” after Jeremy Corbyn’s leadership, it still has more to do to convince the public that it deserves to be in government.

He will say: “The local elections showed that the country was desperate for change.

“The fact that Labour won in all parts of the country was a sign of the strides we have made. People who turned away from us during the Corbyn years and the Brexit years are coming back.

“But there is understandably a lot of scepticism about politics out there and now we need to go from reassurance to hope. We need to show that we will be a big reforming government bringing hope of a better life for working people.”

Starmer believes the Tories made a strategic blunder in believing that so-called “woke” issues like the trans debate were more important to voters than the cost of living crisis and the state of the NHS.

He will say: “Labour’s plan to rebuild the NHS will be at the heart of our offer to the British people. The Tories are doing too little, too late to repair the damage they have done to the NHS.

“The NHS trumps ‘woke’ every day of the week.”

His comments echo the views of many Tories, who have criticised the “non-existent” campaign by the party’s HQ.

One told HuffPost UK: “Nobody cares about all of the culture war stuff – what they really want is the potholes to be fixed.”

One local Conservative association chair also wrote to colleagues saying the local election results were “not a reflection on us, it was part of the national picture”.

Share Button

Met Police Admits ‘Regret’ Over Arresting Six Anti-Monarchy Protesters

The Metropolitan Police has expressed “regret” over the arrests of six anti-monarchy protesters ahead of the King’s coronation after deciding no charges will be brought against them.

Scotland Yard issued a lengthy defence of its decision to arrest Graham Smith, chief executive of the campaign group Republic, and five others on Saturday.

The force said it had arrested the group under new powers after it was believed items found alongside a large number of placards could be used to “lock on” to an object or building, which the new Public Order Act made a jailable offence.

“The investigation team have now fully examined the items seized and reviewed the full circumstances of the arrest,” a statement released on Monday added.

“Those arrested stated the items would be used to secure their placards, and the investigation has been unable to prove intent to use them to lock on and disrupt the event.

“This evening all six have had their bail cancelled and no further action will be taken. We regret that those six people arrested were unable to join the wider group of protesters in Trafalgar Square and elsewhere on the procession route.”

Smith on Monday demanded a “full inquiry” into who authorised the arrests that prevented the group expressing their dissent during the “disgraceful episode”.

The force made 64 arrests on coronation day, with 46 people bailed after being detained on suspicion of causing a public nuisance or breaching the peace.

Smith, who said the group was are considering legal action against the Met, earlier accused Scotland Yard of having “every intention” of arresting demonstrators and of having “lied” in discussions ahead of the planned protests.

The campaigner said he was arrested on suspicion of conspiracy to cause a public nuisance unloading placards in St Martin’s Lane, Westminster.

Prime minister Rishi Sunak has backed the Met over the dozens of arrests of protesters amid concerns they were cracking down on dissent on Saturday at the behest of politicians.

Share Button

After 31 Years, I Read My Mother’s Suicide Note For The First Time. Five Words Changed Everything.

I read my mother’s suicide note for the first time at 36 years old while making chocolate chip protein pancakes for my daughter.

It was difficult to read — literally. It had been written on a hotel notepad 31 years ago and photographed as evidence after it was found. The photos sat in a filing cabinet until the case was closed, when the note was converted to microfiche. But I recently submitted a Freedom of Information Act request to the police department for my mother’s death investigation case file. Then, the note was printed on white copy paper and handed over to me.

At the kitchen counter, I turned to flip the pancakes and then flip through the file, reading about the housekeeper who found my mother’s body, the interviews that police conducted with my family, the medical examiner’s report. My daughter played with Lego bricks at the kitchen table. I had planned to wait until she went to school to read the report, but the compulsion to learn about my mother’s death after all those years proved an overwhelming draw.

My mother died when I was 5 years old and my sister 2. I was told at the time that my mother had a “brain disease.” I suppose that was the way a professional had advised my dad to explain mental illness to a child as young as I was. I remember being in kindergarten with the school social worker and drawing a pink, blobby brain shape with a graphite gray spot on it.

My dad was not, is not, shy about his love for my mother. Every anniversary, he writes a column — poems, song lyrics, words — about how much he misses her and how proud of us she would be. When I was younger, these columns were published in the local newspaper. In recent years, they have transformed into moving Facebook posts with pictures of the grandchildren she will never get to meet.

As children, my dad took us to the cemetery often to “visit” my mom. My sister and I took turns choosing the flowers that we put in the upturned urn on her headstone and snuggling with a small, tan teddy bear he told us had belonged to her. My mother’s side of the closet stayed full of her clothes for decades, and mementos of her still remain in my dad’s home. We talked about the loss, but we never really talked about the woman, her life and her death beyond the superficial.

At some point in my childhood, I must have worked up the nerve to ask more questions about her, although I do not remember a specific conversation. That is when I learned that my mother had taken her own life at a hotel near our home. No additional details were forthcoming, and perhaps that is why, over the decades in between, I never asked any more questions. What more did I need to know, and what good would it do?

As a young child, I was often angry that I didn’t have my mother as a “room mom” or to celebrate Mother’s Day with. I was resentful when teachers assumed that it was a mother who packed my lunches and signed my permission slips. But as I grew, I got good grades and received scholarships to college, and I met and married an incredible partner. It did not seem to matter that I did not have a mother — until I became one myself.

My daughter was born healthy, beautiful and colicky. She cried nearly constantly for the better part of six months. Nothing I did seemed to help — breastfeeding, baby-wearing, multiple trips to the pediatrician. I spent the days and nights listening to her incessant, incriminating howls. The cries accumulated in my psyche as evidence that I didn’t deserve to be a mother, that I would never be good enough. I began to have fleeting thoughts of leaving like my mother had. I also wished she was there to help and reassure me.

I survived those early months, when I wasn’t fantasizing about starting a new life, by writing to my daughter. I wrote messages of love in the covers of books I ordered for each holiday and piled in her room. I wrote cards and letters, crying onto them while she cried in the background. I wrote over and over again to my daughter about how special she was, the joy she brought to our family, my hopes and dreams for her future.

I sealed the notes to my daughter in envelopes and stacked them into a pink safe I ordered for this purpose. If it turned out that I couldn’t stay, at least my daughter would have tangible evidence that her mother loved her.

Eventually, the crying subsided — and along with it, my thoughts of departure.

As my daughter has grown, I have been awed by her empathy, compassion and creativity while simultaneously feeling unworthy of the privilege of being her mother. I have tried to fix this through frenzy; I enrolled her in private school, fed her fruits and vegetables, minimized screen time. We moved to a bigger house, bought her a scooter with light-up wheels, adopted a guinea pig. Checking all of the boxes kept the feelings of inadequacy at bay for a while.

Then the Covid-19 pandemic hit, and we went through the same shock and upheaval as many families across the world. For my daughter, the stresses were perhaps compounded by my working as a nurse in the emergency department and my husband in law enforcement. Again, nothing I did or tried could fix how she felt.

Out of desperation, I resumed writing. I signed up for a writing workshop and penned a 78,717-word novel about a woman with a dead mother trying to parent her daughter through hard times. After months of revising the draft, trying to write the happy ending that I wanted for my characters — and for me and my daughter — I gave up. There were too many holes in the story, and the biggest was the protagonist’s relationship with her dead mother, i.e., my relationship with mine. I finally confronted the fact that to write the ending, I needed to look back to my beginnings, to my relationship with my mother. Perhaps there would be wisdom in unraveling our history.

I began my journey by obtaining my mother’s death investigation file and court records. In hindsight, it seems revealing that I would rather look through a police file than have an honest conversation with my family about who my mother was.

When I finally read my mother’s suicide note for the first time, five words jumped out at me.

“I was a horrible mother.”

I surprised myself by feeling not shocked or sad, but relieved by her words. “I am a horrible mother” had been the refrain in my mind for my daughter’s entire nine years of life. Thirty-one years after my mother’s death, here was physical evidence of the thread that connected us across the decades.

It wasn’t until months later that I noticed additional text at the bottom, nearly impossible to make out. I had to reference the typed rendering in the police report. It was transcribed as my initials, then my sister’s, and then “I love you and I did the best things for you.”

Her last words were to tell us that she loved us and was trying to do right by us. I find this somewhat comforting. But having now known my daughter twice as long as my mother knew me, those words on that scrap of paper, and the intention, don’t make up for my loss.

Although my heart hurts for my mother and how sick she must have been, her actions sent out shock waves of trauma with intergenerational consequences. Their impact on me may be part of the reason that my daughter feels the hurts of the world so deeply.

But the moral of my mother’s story seems to be simple: My presence means more than perfection to my child. I hope that the more I am brave enough to ask the hard questions, and to speak and write honestly, the more my daughter and I can undo the “horrible mother” legacy, break the cycle and create a better future.

Help and support:

  • Mind, open Monday to Friday, 9am-6pm on 0300 123 3393.
  • Samaritans offers a listening service which is open 24 hours a day, on 116 123 (UK and ROI – this number is FREE to call and will not appear on your phone bill).
  • CALM (the Campaign Against Living Miserably) offer a helpline open 5pm-midnight, 365 days a year, on 0800 58 58 58, and a webchat service.
  • The Mix is a free support service for people under 25. Call 0808 808 4994 or email help@themix.org.uk
  • Rethink Mental Illness offers practical help through its advice line which can be reached on 0808 801 0525 (Monday to Friday 10am-4pm). More info can be found on rethink.org.
Share Button