Mast cell precursor cells do not just cause an increase in mature mast cells during inflammation, they also play an active role in diseases like asthma. This finding is in a new study by immunology researchers published in the Journal of Allergy and Clinical Immunology. The study also emphasises that precursor cells in general can play an active role in inflammation and challenges the current idea that only mature immune cells are involved in immune reactions.
“We have shown that mast cell precursor cells are activated immunologically when they are exposed to allergic stimulation. They can produce the cytokine IL-13, known to contribute to asthma development,” says Erika Mendez-Enriquez, an immunology researcher at Uppsala University.
Mast cells are rare immune cells found in tissues that come into contact with the external environment, such as the airways and the skin. Unlike other immune cells, mast cells develop from precursor cells that migrate to the tissues through the blood. Mast cells play a detrimental role in the development of asthma and allergies, mainly through their expression of the high-affinity receptor for IgE, the main antibody related to allergic reactions. Mast cells become activated when IgE bound to the IgE receptors binds to allergens and releases substances that trigger physiological reactions such as the contraction of the airways in allergic asthma.
Mast cell precursors are extremely rare in healthy individuals, but their frequency increases during inflammation, which later causes an increase in mature mast cells. It is well documented that mast cells increase with many types of inflammatory diseases.
“Our previous studies demonstrated that, during acute inflammation, mast cell precursor cells dominate over the mature mast cells in number. The mast cell precursor cells in both mice and humans also have IgE receptors. For this reason, we wondered if the mast cell precursors can also be activated through allergic stimulation, and in our new study we have been able to confirm this. In the future, we will study if and how different types of asthma treatments impact mast cell precursor cells,” says Jenny Hallgren Martinsson, Senior Lecturer in Immunology at Uppsala University and the leader of the study.
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Wei Chen, professor of physics at The University of Texas at Arlington, is the senior author of two papers detailing the effects of copper cysteamine, a next-generation cancer photodrug invented in Chen’s laboratory.
The first article, “A new type of cuprous-cysteamine sensitizers: Synthesis, optical properties and potential applications,” was published in Materials Today Physics. It reports that copper cysteamine photosensitizers, or light-activated molecules, exhibit a range of luminescent properties, allowing them to produce more reactive oxygen species that kill cancer cells.
The second, “Study of copper-cysteamine based X-ray induced photodynamic therapy and its effects on cancer cell proliferation and migration in a clinical mimic setting,” was published in the journal Bioactive Materials. The study reports that copper cysteamine inhibits the proliferation of deep-seated tumor cells and minimizes toxic side effects associated with cancer treatment that impact healthy cells.
Nil Kanatha Pandey, a Ph.D. student in Chen’s lab, is among the coauthors of both papers.
Treating hard-to-reach tumors
With the development of nanotechnology, photodynamic therapy (PDT) has become a promising alternative to traditional cancer treatments. PDT combines photosensitive molecules, or photosensitizers, with light at the site of a tumor to produce a powerful oxygen species that destroys cancer cells.

Almost every living thing on Earth — from bacteria to plants to people — have a circadian rhythm, the biological clock that controls both physiology and behavior of organisms over a 24-hour period.
This internal timekeeping has been the subject of intense study for decades (the discovery of the genes that drive it led to the Nobel Prize in 2017), yet just how circadian rhythms work within living cells has not been understood until recently.
Using the relatively simple clocks found in fruit flies (Drosophila melanogaster), University of Michigan researchers Yangbo Xiao, Ph.D., Ye Yuan, Ph.D., Swathi Yadlapalli, Ph.D. and their colleagues reveal that subcellular location of clock proteins and genes fluctuate with the daily passage of time, indicating that spatial information is translated into time-related signals.
“We can now visualize these proteins within Drosophila brains while the clocks are ticking,” said Yadlapalli, an assistant professor with the Department of Cell and Developmental Biology at Michigan Medicine.
The internal clock within a fruit fly and a person is generated by the rhythm of the expression of certain genes in response to environmental cues, like light. Some genes are more expressed during the day, while others are more expressed at night.
One of the most well-known processes controlled by the circadian rhythm is the sleep-wake cycle. This cycle is due in part to the production of the hormone melatonin, which fluctuates and is highest in the evening, causing drowsiness.

What makes pancreatic cancer so deadly is its covert and quick spread. Now, a “time machine” built by Purdue University engineers has shown a way to reverse the course of cancer before it spreads throughout the pancreas.
“These findings open up the possibility of designing a new gene therapy or drug because now we can convert cancerous cells back into their normal state,” said Bumsoo Han, a Purdue professor of mechanical engineering and program leader of the Purdue Center for Cancer Research. Han has a courtesy appointment in biomedical engineering.
The time machine that Han’s lab built is a lifelike reproduction of a pancreatic structure called the acinus, which produces and secretes digestive enzymes into the small intestine. Pancreatic cancer tends to develop from chronic inflammation that happens when a mutation has caused these digestive enzymes to digest the pancreas itself.
If there were a way to go back in time to reprogram the cancerous acinar cells that produce those enzymes, then it might be possible to completely reset the pancreas.
For the past decade, Stephen Konieczny, professor emeritus in Purdue’s Department of Biological Sciences, has studied a potential reset button: a gene called PTF1a.
“The PTF1a gene is absolutely critical for normal pancreas development. If you lack the PTF1a gene, you don’t develop a pancreas,” Konieczny said. “So, our whole idea was, if we turn the PTF1a gene back on in a pancreatic cancer cell, what happens? Will we revert the cancer phenotype? Indeed, that’s exactly what happens.”
Konieczny collaborated with Han’s lab to take these findings in molecular biology studies to the next level by testing them in a realistic model of the acinus — the time machine. The published study is featured on the cover of the Oct. 7 issue of Lab on a Chip, a journal by the Royal Society of Chemistry.

Researchers at the University of Illinois Urbana-Champaign can now rapidly isolate and chemically characterize individual organelles within cells. The new technique tests the limits of analytical chemistry and rapidly reveals the chemical composition of organelles that control biological growth, development and disease.
The findings of the new study, led by chemistry professor Jonathan Sweedler, are published in the journal Nature Methods.
The new approach locates and isolates individual organelles using light microscopy, then chemically analyzes them via MALDI MS, or matrix-assisted laser desorption/ionization mass spectrometry. The entire process takes an hour — a task that could take human analysts years to complete.
“Cells are not just little sacks full of chemicals,” Sweedler said. “They contain organelles that perform specific functions. The ability to characterize the chemical composition of individual organelles should lead to a better understanding of how cells develop and express diseases.”
The researchers said they are not the first to characterize organelles chemically. But using their automated targeting and chemical analysis approach is faster and more accurate, and assures that they analyze exactly what they intend. This way, they can determine the chemical makeup of a single organelle — not the average composition of a larger sample containing many organelles.
For this study, the team focused on the cell’s vesicles — both dense-core and lucent varieties — collected from sea slugs, which are a commonly used neuroscience study model. Vesicles were selected as the organelle of interest because they are involved in chemical cell-to-cell signaling. The researchers said they are also larger than many of the other organelles, making them excellent first candidates to demonstrate the capabilities of the new approach.
“We analyzed approximately 1,000 individual vesicles from sea slugs,” chemistry professor Stanislav Rubakhin said. “We found heterogeneity among the types of lipids and biologically active peptides, indicating that MALDI MS is sensitive enough to detect chemical differences between what were thought to be the same types of organelles.”
Because disease is often spotted when heterogenous cells appear within a single tissue type, Rubakhin said, the ability to discern these differences at the subcellular level could lead to earlier detection and treatment.
“Our new workflow can help the scientific community complete the ‘parts list’ of the organelles found within cells,” graduate student Daniel Castro said. “Having that parts list will help us determine if something is missing or extra within the organelles, helping us spot subtle changes and study how those changes correlate to diseases such cancer and those related to the brain and mental health.”
The National Institute on Drug Abuse and the National Human Genome Research Institute supported this study.
Sweedler is the director of the School of Chemical Sciences and is affiliated with the Beckman Institute for Advanced Science and Technology, the Carl R. Woese Institute for Genomic Biology and the Carle Illinois College of Medicine.
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Materials provided by University of Illinois at Urbana-Champaign, News Bureau. Original written by Lois Yoksoulian. Note: Content may be edited for style and length.

In geographic atrophy, a late form of age-related macular degeneration (AMD), reading ability is closely related to the altered retinal structure. This has been demonstrated by researchers from the Department of Ophthalmology at the University Hospital Bonn with colleagues at the National Eye Institute and the University of Utah. Reading speed makes everyday functional impairment measurable, which the most common functional test in ophthalmology — the best-corrected visual acuity assessment — cannot reflect. Retinal imaging can be used to assess loss of reading ability even when central visual acuity is still good. The study has now appeared in JAMA Ophthalmology.
As the proportion of older people grows, the number of patients with geographic atrophy (GA) also increases. This is a late form of age-related macular degeneration. The retinal disease leads to considerable limitations, among other things in reading or recognizing faces. So far it is not treatable. Everyday functional tests are important to assess the success of possible therapeutic approaches. “However, conventional functional tests such as visual acuity do not capture all the dismal functional consequences of the diesease,” explains Prof. Dr. Frank G. Holz, Director of the Department of Ophthalmology at the University of Bonn. “Therefore, it is crucial to explore further functional assessments, such as reading performance.”
This is where the study initiated by Prof. Monika Fleckenstein comes in, investigating the correlation of reading ability with retinal findings in 85 participants with geographic atrophy. “Especially patients in whom the site of sharpest vision is not yet affected still show good visual acuity in clinical examinations,” first author Sandrine Künzel reports from clinical practice at the University Eye Hospital in Bonn. “Nevertheless, they sometimes report severe limitations in their daily life, which also encompass reduced reading ability.”
This finding has now been confirmed by the study. Both reading ability and reading speed proved to be important functional tests for clinical therapy studies. In contrast, the suspected phenomenon of “binocular inhibition” — a negative influence of the worse-seeing eye during reading — did not show up. Thus, future therapeutic approaches should focus primarily on the better-seeing eye to achieve an overall improvement in visual ability. “We were able to contribute to the understanding of reading ability and its role as a study endpoint,” said Priv.-Doz. Dr. Maximilian Pfau of the University Eye Hospital in Bonn, who is currently a fellow of the German Research Foundation (DFG) at the National Eye Institute in Bethesda (USA).
The study was supported by the German Research Foundation (DFG), the German Ophthalmological Society, and the BONFOR program of the Medical Faculty of the University of Bonn.
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Americans with a disability were more likely to want coronavirus vaccines but were having a harder time getting them than other people, according to data released on Thursday by the Centers for Disease Control and Prevention, a stark signal of what the agency’s scientists said was a need for health officials to remove barriers to access.In a survey of nearly 57,000 people from May to June, unvaccinated people with a disability such as serious difficulty seeing, hearing or walking were nearly twice as likely as their unvaccinated counterparts without a disability to say that they would definitely get vaccinated. (The survey only included people outside of nursing homes and other institutions.)And yet, people with a disability were less likely to be vaccinated: Among 50- to 64-year-olds, 63 percent of people with a disability had received coronavirus shots, compared with 72 percent of other people. Among people older than 75, the gap was smaller but still evident: Eighty-eight percent of people with a disability were vaccinated, compared with 90 percent of people without one.“Covid-19 vaccination coverage was lower among U.S. adults with a disability than among those without a disability, even though adults with a disability reported less hesitancy to getting vaccinated,” the study’s authors wrote.The study noted that state-run vaccine registration websites were not all compliant with basic accessibility recommendations. It suggested that online scheduling systems offer call lines for people who needed help booking vaccinations.It also said that not all vaccination sites had American Sign Language interpreters or workers trained in helping people with developmental disabilities, and that getting to those sites in the first place was often difficult for people with a disability.“These efforts would be relevant to the reduction of health disparities related to disability beyond the Covid-19 pandemic,” the study said.

Cancer immunotherapy seeks to turn “cold” tumors into “hot” tumors — those that respond to immunotherapy — by awakening and enlisting the body’s own immune system.
Unfortunately, few people benefit from the most common form of immunotherapy, called immune checkpoint inhibitors, and scientists are actively seeking new and safe molecules called agonists to augment the body’s immune response. One promising drug in clinical trials is the STING agonist. STING is a protein essential to the immune response against infection as well as cancer.
In searching for molecules that would augment the STING pathway, a team of scientists at the University of Michigan School of Pharmacy and the Rogel Cancer Center looked to nutritional metal ions, which we absorb from food, and are important for immune regulation.
They found that adding the nutritional metal ion manganese to STING agonists boosted STING’s tumor-fighting capability up to 77-fold, compared to STING agonists used alone, said James Moon, the J.G. Searle Professor of Pharmaceutical Sciences and professor of biomedical engineering.
When researchers added the manganese ions to STING agonists, they formed nano-sized crystals, which significantly increased cellular uptake of STING agonists and STING activation by immune cells. To develop a STING agonist for intravenous administration, the researchers coated these nanocrystals with a lipid layer (similar to those found in mRNA COVID19 vaccines), resulting in a nanoparticle system called CMP.
Most STING agonists must be delivered directly into the tumor, but this isn’t suitable for metastatic cancers, a major cause of mortality. Even with intratumoral injections, conventional STING agonists are challenged by limited clinical response.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesFacebook has defended the impact of its products, saying Instagram has “affirmatively helped” young people.Its global head of safety, Antigone Davis, testified to the US Senate, about child protection.It comes after a leak exposed how Instagram’s own research had found the platform could harm children’s well-being.Previously, Instagram boss Adam Mosseri said the app’s effects on teenagers’ mental health were “quite small”.Instagram for kids paused after backlashFacebook under fire over secret teen researchThe committee opened by reiterating Facebook’s own research – first reported on by the Wall Street Journal (WSJ) – which found Instagram could have a negative impact on body image and self-esteem. Teenagers “blame Instagram for increases in the rate of anxiety and depression”, it said.But Ms Davis then told the committee: “We conduct this research, to make our platform better, to minimise the bad and maximise the good and to proactively identify where we can improve.”We want our platforms to be a place for meaningful interactions with friends and family and we cannot achieve that goal if people do not feel safe.”‘Indefensibly delinquent’But Richard Blumenthal, who chairs the Senate commerce, science, and transportation subcommittee on consumer protection, product safety, and data security, highlighted how Facebook had, in August, denied it was aware of any research that showed a negative correlation.”We know it chooses the growth of its products over the well-being of our children,” he said. “And we now know that it is indefensibly delinquent in acting to protect them. “It is failing to hold itself accountable and the question that haunts me is how can we or parents or anyone trust Facebook.”In the hearing, Ms Davis repeatedly failed to answer the committee’s questions and said she would have to check with the relevant Facebook teamsBody imageFacebook disputes the WSJ’s reporting.“It is simply not accurate that this research demonstrates Instagram is ‘toxic’ for teen girls,” head of research Pratiti Raychoudhury blogged.”The research actually demonstrated that many teens we heard from feel that using Instagram helps them when they are struggling with the kinds of hard moments and issues teenagers have always faced.”But Facebook, releasing slides to illustrate its research, admitted: “One exception was body image”.Image source, FacebookOne in three teenage girls who had already experienced body-image issues told Facebook using Instagram made them feel worse.In particular filtered images, posting selfies and viewing content with hashtags affect well-being, the slides suggest.Separate hearingIt comes just days after the company paused its scheduled rollout of Instagram Kids, which had been due to launch this year for users aged under 13.”As every parent knows when it comes to kids and tweens, they’re already online,” Ms Davis told the committee. “We believe it is better for parents to have the option to give tweens access to a version of Instagram that’s designed for them where parents can supervise and manage their experience – rather than to have them lie about their age to access the platform that wasn’t built for them.”Ms Davis said Instagram was also testing a feature called Take a Break which “would encourage somebody to take a break” from their screen. This would display “when we think [users] may be rabbit hole and down certain kinds of content or are on the app too long.”The whistleblower who leaked the documents to the Wall Street Journal will testify in a separate hearing next week and the committee said it would be seeking interviews from other social media companies in regards to children’s mental health harms.

After her son was found to be autistic, she started organizations to help children and adults. She also consulted on the making of the movie “Rain Man.”Ruth Sullivan, a public health nurse who became an influential advocate for autistic children and adults after one of her sons was diagnosed with the disorder in the early 1960s, died on Sept. 16 at a senior living center in Huntington, W.Va. She was 97.Her daughter Lydia Sullivan said the cause was atrial fibrillation, an abnormal heart rhythm.For more than 40 years, Dr. Sullivan was a tireless champion for educational and other opportunities for people on the autism spectrum. She was a founder of the Autism Society, a national grass-roots organization, and secured state funding to open the West Virginia Autism Training Center at Marshall University.She started and ran the Autism Services Center, which provides residential, therapeutic and community services, and for several years offered information and referrals by telephone from her home in Huntington, where she and her husband, William, raised seven children.“Our dinners were often interrupted by hysterical parents calling,” Lydia Sullivan said in a phone interview, “and my mother would spend the evenings talking to desperate parents from around the world.”Dr. Sullivan was once that parent desperate for information about autism. When her son Joseph received his diagnosis in 1963, at the age of 3, autism was a mysterious disorder that most pediatricians knew little about. She took Joseph to a doctor in Lake Charles, La., where the family was living at the time, and he quickly recognized that Joseph was autistic.“I said, ‘What is that?’” she recalled when she was interviewed on a podcast in 2016 by Marc Ellison, the executive director of the Autism Training Center and one of her protégés. “He said he will always be odd. But he couldn’t offer anything else.”Nearly as disturbing to Dr. Sullivan was a prevailing psychological theory that cold and distant parents — most notably what were referred to as “refrigerator mothers” — were responsible for causing their children’s autism.“I knew it wasn’t true,” she said on the podcast. “I didn’t love Joseph any less than the others. I treated him differently because he didn’t behave like the others.” She added: “I’m the oldest of seven. I have seven children. I was a nurse. I knew something about children.”Research led her to read the book “Infantile Autism: The Syndrome and Its Implications for a Neural Theory of Behavior” (1964), by Bernard Rimland, a psychologist with an autistic son. He rebutted the claim that neglectful parents caused autism in their children and argued that autism was a result of genetics and, possibly, environmental factors.Dr. Sullivan wrote to Dr. Rimland about starting a national network of parents that would receive the latest research about autism. In 1965, the two of them and a group of parents who had also written to Dr. Rimland met at a house in Teaneck, N.J., where they founded the National Society for Autistic Children (now the Autism Society), a support group that would eventually have numerous local chapters throughout the country. In 1969, she was elected its president.At about that time, Dr. Sullivan was also trying to overcome a local school board’s resistance to providing an education to autistic children like Joseph. She brought a prepared statement to a school board meeting, and local newspapers wrote about her campaign to educate Joseph.“For almost six weeks, I was on the phone every day trying to persuade them to set up a special class,” she told The Sunday Gazette-Mail of Charleston, W.Va., in 1972. “The next week,” Dr. Sullivan added, “there was a class for Joseph and 12 other children. With the help of some dedicated teachers, they’ve been attending school ever since.”She lobbied for the passage in 1975 of what came to be called the Individuals With Disabilities Education Act, which required public schools that received federal money to provide equal access to children with disabilities. She helped write the language to include autistic children when the law was amended 15 years later.She was a technical adviser to “Rain Man,” Barry Levinson’s 1988 film about an autistic man (Dustin Hoffman) and his brother (Tom Cruise). Mr. Hoffman studied two documentaries featuring Joseph to prepare for the role, including outtakes from “Portrait of an Autistic Young Man” (1986), which was shown on PBS stations.“That’s where I met Joe, in a sense,” Mr. Hoffman told The Associated Press in 1988 at a showing of “Rain Man” in Huntington that, at Dr. Sullivan’s request, was a fund-raiser for the Autism Services Center. “I buried myself there for the first two months.”Joseph’s favorite scene in the film was when Mr. Hoffman’s character, Raymond Babbit, quickly counted spilled toothpicks.Mr. Hoffman thanked Dr. Sullivan and Joseph when he accepted the Oscar for best actor. She believed that the film helped broaden the public’s understanding of autism.Dr. Sullivan in 2018. For more than 40 years, she fought for educational and other opportunities for people on the autism spectrum.Rick Lee/Huntington QuarterlyRuth Marie Christ was born on April 20, 1924, in Port Arthur, Texas, 90 miles east of Houston. Her father, Lawrence, worked in oil refineries, then turned to farming after he and his family moved to Mowata, La., when Ruth was very young. Her mother, Ada (Matt) Christ, worked in a department store.After graduating from the nursing program at Charity Hospital in New Orleans in 1943, Dr. Sullivan served in the Army Nurse Corps, treating soldiers during World War II at Fort Sam Houston in San Antonio (now Joint Base San Antonio).After the war ended, she moved to Lake Charles for four years, then attended Teachers College at Columbia University on the G.I. Bill. After receiving bachelor’s and master’s degrees in public health, she worked as a nurse in Manhattan. She married William Sullivan, an English professor, in 1952 and accompanied him to teaching posts in Columbia, Mo., Lake Charles and Albany, working part time as a nurse until her fourth child was born in 1958.Joseph, her fifth child, was born in 1960. He started speaking early but began to withdraw at 18 months. By his second birthday, Dr. Sullivan wrote in her journal — which was quoted by The Gazette-Mail in 1972 — “he could say only eight words. He would indicate what he wanted by grunts, guiding our hands to what he wanted.”In 1984, at 60, she earned a Ph.D. in special education, speech pathology and psychology from Ohio University, which gave her greater standing with the people she lobbied.Her relentless but gentle style of advocacy continued until her retirement in 2007.“Providing guidance to families nationally was obviously spectacular,” said Stephen Edelson, executive director of the Autism Research Institute. “But she was also one of the first people to talk about medical comorbidities associated with autism, like seizures, sleep problems and gastrointestinal problems. And she was one of the first to point to the importance of providing services to adults with autism.”Jimmie Beirne, chief executive of the Autism Services Center (the position Dr. Sullivan held from 1979 to 2007), was hired 33 years ago to work part time with Joseph on developing his social skills.“The philosophy that she worked so hard to instill in us was to have a parent’s perspective, to think as if this is our child receiving these services,” Dr. Beirne said by phone. “She’d say that the difference between good and excellent services is in the details, and, like a good coach, she had an eye for details.”Today, Joseph lives in a group home run by the Autism Services Center and works at the Autism Training Center.In addition to Joseph and her daughter Lydia, Dr. Sullivan is survived by her other sons, Larry, Richard and Christopher; her other daughters, Julie Sullivan, who is writing a book about her mother, and Eva Sullivan; her sisters, Geraldine Landry, Frances Buckingham and Julie Miller; her brother, Charles; 12 grandchildren; and four great-grandchildren.Dr. Sullivan’s influence was international. She received letters from parents around the world in search of solutions for their children, and she traveled widely to speak about autism.“She was invited to a conference on autism in Argentina in the 1990s,” her daughter Julie said by phone. “At the time, Argentina was in the grips of the ‘refrigerator mother’ thing, and she got together with parents and told them they needed to start their own group. So she’s the godmother of an autism parents’ group in Argentina.”