Genetic Tools Help Identify a Cellular Culprit for Type 1 Diabetes (Medicine)

By mapping its genetic underpinnings, researchers at University of California San Diego School of Medicine have identified a predictive causal role for specific cell types in type 1 diabetes, a condition that affects more than 1.6 million Americans.

The findings are published in the May 19, 2021 online issue of Nature.

Type 1 diabetes is a complex autoimmune disease characterized by the impairment and loss of insulin-producing pancreatic beta cells and subsequent hyperglycemia (high blood sugar), which is damaging to the body and can cause other serious health problems, such as heart disease and vision loss. Type 1 is less common than type 2 diabetes, but its prevalence is growing. The U.S. Centers for Disease Control and Prevention projects 5 million Americans will have type 1 diabetes by 2050. Currently, there is no cure, only disease management.

The mechanisms of type 1 diabetes, including how autoimmunity is triggered, are poorly understood. Because it has a strong genetic component, numerous genome-wide association studies (GWAS) have been conducted in recent years in which researchers compare whole genomes of persons with the same disease or condition, searching for differences in the genetic code that may be associated with that disease or condition.

In the case of type 1 diabetes, identified at-risk variants have largely been found in the non-coding regions of the genome. In the Nature study, senior author Kyle Gaulton, PhD, an assistant professor in the Department of Pediatrics at UC San Diego School of Medicine, and colleagues integrated GWAS data with epigenomic maps of cell types in peripheral blood and the pancreas. Epigenomic mapping details how and when genes are turned on and off in cells, thus determining the production of proteins vital to specific cellular functions.

Specifically, researchers performed the largest-to-date GWAS of type 1 diabetes, analyzing 520,580 genome samples to identify 69 novel association signals. They then mapped 448,142 cis-regulatory elements (non-coding DNA sequences in or near a gene) in pancreas and peripheral blood cell types.

“By combining these two methodologies, we were able to identify cell type-specific functions of disease variants and discover a predictive causal role for pancreatic exocrine cells in type 1 diabetes, which we were able to validate experimentally,” said Gaulton.

Pancreatic exocrine cells produce enzymes secreted into the small intestine, where they help digest food.

Co-author Maike Sander, MD, professor in the departments of Pediatrics and Cellular and Molecular Medicine at UC San Diego School of Medicine and director of the Pediatric Diabetes Research Center, said the findings represent a major leap in understanding the causes of type 1 diabetes. She described the work as “a landmark study.”

“The implication is that exocrine cell dysfunction might be a major contributor to disease. This study provides a genetic roadmap from which we can determine which exocrine genes may have a role in disease pathogenesis.”

First author Joshua Chiou, PhD, a recent graduate of the Biomedical Sciences graduate program at UC San Diego added: “Understanding how type 1 diabetes originates at the cellular level is a critical step in finding treatments for reversing its course and, ultimately, preventing the disease altogether.”

Co-authors include: Ryan J. Geusz, Mei-Lin Okino, Jee Yun Han, Michael Miller, Rebecca Melton, Elisha Beebe, Paola Benaglio, Serina Huang, Katha Korgaonkar, and Sebastian Preissl all at UC San Diego; David U. Gorkin, Emory University; and Sandra Heller and Alexander Kleger, Ulm University, Germany.

Funding for this research came, in part, from the National Institutes of Health (grants DK112155, DK120429, DK122607 AND T32 GM008666).


Reference: Chiou, J., Geusz, R.J., Okino, ML. et al. Interpreting type 1 diabetes risk with genetics and single-cell epigenomics. Nature (2021). https://doi.org/10.1038/s41586-021-03552-w


Provided by UC San Diego

Unexpected ‘Black Swan’ Defect Discovered In Soft Matter For First Time (Physics)

Using an advanced microscopy technique, Texas A&M researchers have uncovered a twin boundary defect in a soft polymer that has never been observed before.

Texas A&M University scientists have for the first time revealed a single microscopic defect called a “twin” in a soft-block copolymer using an advanced electron microscopy technique. This defect may be exploited in the future to create materials with novel acoustic and photonic properties.

“This defect is like a black swan — something special going on that isn’t typical,” said Edwin Thomas, professor in the Department of Materials Science and Engineering. “Although we chose a certain polymer for our study, I think the twin defect will be fairly universal across a bunch of similar soft matter systems, like oils, surfactants, biological materials and natural polymers. Therefore, our findings will be valuable to diverse research across the soft matter field.”

The results of the study are detailed in the Proceedings of the National Academy of Sciences (PNAS).

Materials can be broadly classified as hard or soft matter. Hard materials, like metal alloys and ceramics, generally have a very regular and symmetric arrangement of atoms. Further, in hard matter, ordered groups of atoms arrange themselves into nanoscopic building blocks called unit cells. Typically, these unit cells are comprised of only a few atoms and stack together to form the periodic crystal. Soft matter can also form crystals consisting of unit cells, but now the periodic pattern is not at the atomic level; it occurs at a much larger scale from assemblies of large molecules.

In particular, for an A-B diblock copolymer, a type of soft matter, the periodic molecular motif comprises of two linked chains: one chain of A units and one chain of B units. Each chain, called a block, has thousands of units linked together and a soft crystal forms by selective aggregation of the A units into domains and B units into domains that form huge unit cells compared to hard matter.

Another notable difference between soft and hard crystals is that structural defects have been much more extensively studied in hard matter. These imperfections can occur at a single atomic location within material, called a point defect. For example, point defects in the periodic arrangement of carbon atoms in a diamond due to nitrogen impurities create the exquisite “canary” yellow diamond. In addition, imperfections in crystals can be elongated as a line defect or spread across an area as a surface defect.

By and large, defects within hard materials have been extensively investigated using advanced electron imaging techniques. But in order to be able to locate and identify defects in their block copolymer soft crystals, Thomas and his colleagues used a new technique called slice-and-view scanning electron microscopy. This method allowed the researchers to use a fine ion beam to trim off a very thin slice of the soft material, then they used an electron beam to image the surface below the slice, then slice again, image again, over and over. These slices were then digitally stacked together to get a 3D view.

For their analysis, they investigated a diblock copolymer made of a polystyrene block and a polydimethylsiloxane block. At the microscopic level, a unit cell of this material exhibits a spatial pattern of the so-called “double gyroid” shape, a complex, periodic structure consisting of two intertwined molecular networks of which one has a left-handed rotation and the other, a right-handed rotation.

While the researchers were not actively looking for any particular defect in the material, the advanced imaging technique uncovered a surface defect, called a twin boundary. At either side of the twin juncture, the molecular networks abruptly transformed their handedness.

“I like to call this defect a topological mirror, and it’s a really neat effect,” Thomas said. “When you have a twin boundary, it’s like looking at a reflection into a mirror, as each network crosses the boundary, the networks switch handedness, right becomes left and vice versa.”

The researcher added that the consequences of having a twin boundary in a periodic structure that does not by itself have any inherent mirror symmetry could induce novel optical and acoustic properties that open new doors in materials engineering and technology.

“In biology, we know that even a single defect in DNA, a mutation, can cause a disease or some other observable change in an organism. In our study, we show a single twin defect in a double gyroid material,” Thomas said. “Future research will explore to see whether there’s something special about the presence of an isolated mirror plane in a structure, which otherwise has no mirror symmetry.”

Other contributors to this research include Xueyan Feng from the materials sciences and engineering department and Mujin Zhuo and Hua Guo from Rice University.

This research was support by a grant from the National Science Foundation.

Journal link: https://www.pnas.org/content/118/12/e2018977118

Featured image: Edwin Thomas and his team have found a twin boundary defect in a soft polymer material having a double gyroid shape for the first time. © Dharmesh Patel/Texas A&M Engineering


Provided by Texas A&M University

Astronomers Discover Circumbinary Planet TIC 172900988b (Planetary Science)

A team of international astronomers reported on the discovery of the first TESS circumbinary planet (CBP), “TIC 172900988 b”, using the multiple-transits-in-one-conjunction technique. Their study recently appeared in Arxiv.

A circumbinary planet is a planet that orbits two stars instead of one. Finding transiting planets around binary stars is much more difficult than around single stars. The transits are shallower (due to the constant ‘third-light’ dilution from the binary companion), noisier (due to starspots and stellar activity from two stars), and can be blended with the stellar eclipses.

In the current study, astronomers detected planet, “TIC 172900988 b” from a single sector of TESS data. They found that, during Sector 21, the planet TIC 172900988b transited the primary star and then 5 days later it transited the secondary star i.e. it produced just two transits.

They also revealed, a prominent apsidal motion of the binary orbit, caused by the dynamical interactions between the binary and the planet, from an extensive archival data from multiple surveys like ASAS-SN, Evryscope, KELT, and SuperWASP.

In addition, they found, binary star is itself eclipsing, with an orbital period of 19.7 days and an eccentricity of 0.45. Moreover, stellar masses of 1.24 and 1.2 M respectively, and stellar radii of 1.38 and 1.31 R have been found for the primary and secondary stars respectively.

Upper panels, from left to right: the TESS data for the primary eclipse, the secondary eclipse, the planet transit of the primary, and the planet transit of the secondary. Lower panels: Configuration of the system at the times of the two transits. © Veselin Kostov

For a circumbinary planet, the radius is found to be 11.07 R (1.009 RJup). However, they couldn’t able to determine the planet’s mass and orbital properties uniquely—there are six solutions with nearly equal likelihood. Specifically, they found that the planet’s mass is in the range of 820-980 M, its orbital period could be in between 190-205 days, and the eccentricity is in between 0.02 and 0.09.

“Follow-up observations from other instruments are key for strongly constraining the orbit and mass of the CBP. In particular, observing the predicted 2022 February-March conjunction of the CBP is critical for solving the currently-ambiguous orbit of the planet.”

Finally, they concluded that, as a relative bright target (V=10.141 mag), the system is accessible for high resolution spectroscopy, e.g. Rossiter-McLaughlin effect, transit spectroscopy.

Featured image: The inset image is of the primary target to within 300 of the target, with an arrow marking the position of the detected companion. © Veselin Kostov


Reference: Veselin B. Kostov, Brian P. Powell, Jerome A. Orosz, William F. Welsh, William Cochran, Karen A. Collins, Michael Endl, Coel Hellier, David W. Latham, Phillip MacQueen, Joshua Pepper, Billy Quarles, Lalitha Sairam, Guillermo Torres, Robert F. Wilson, Serge Bergeron, Pat Boyce, Robert Buchheim, Caleb Ben Christiansen, David R. Ciardi, Kevin I. Collins, Dennis M. Conti, Scott Dixon, Pere Guerra, Nader Haghighipour, Jeffrey Herman, Eric G. Hintz, Ward S. Howard, Eric L. N. Jensen, Ethan Kruse, Nicholas M. Law, David Martin, Pierre F. L. Maxted, Benjamin T. Montet, Felipe Murgas, Matt Nelson, Greg Olmschenk, Sebastian Otero, Robert Quimby, Michael Richmond, Richard P. Schwarz, Avi Shporer, Keivan G. Stassun, Denise C. Stephens, Amaury H. M. J. Triaud, Joe Ulowetz, Bradley S. Walter, Edward Wiley, David Wood, Mitchell Yenawine, Eric Agol, Thomas Barclay, Thomas G. Beatty, Isabelle Boisse, Douglas A. Caldwell, Jessie Christiansen, Knicole D. Colon, Magali Deleuil, Laurance Doyle, Daniel Fabrycky, Michael Fausnaugh, Gabor Furesz, Emily A. Gilbert, Guillaume Hebrard, David J. James, Jon Jenkins, Stephen R. Kane, Richard C. Kidwell Jr., Ravi Kopparapu, Gongjie Li, Jack J. Lissauer, Michael B. Lund, Steve Majewski, Tsevi Mazeh, Samuel N. Quinn, George Ricker, Joseph E. Rodriguez, Jason Rowe, Alexander Santerne, Joshua Schlieder, Sara Seager, Matthew R. Standing, Daniel J. Stevens, Eric B. Ting, Roland Vanderspek, Joshua N. Winn, “TIC 172900988: A Transiting Circumbinary Planet Detected in One Sector of TESS Data”, Arxiv, pp. 1-64, 2021. https://arxiv.org/abs/2105.08614


Note for editors of other websites: To reuse this article fully or partially kindly give credit either to our author/editor S. Aman or provide a link of our article

Triple-drug Therapy Safely Cuts Serious Asthma Flares (Medicine)

Including third drug to commonly used dual-drug inhalers can reduce asthma exacerbations

Researchers have found that the inclusion of a third drug to commonly used dual-drug inhalers can reduce asthma exacerbations and improve control over the disease in children, adolescents, and adults with moderate-to-severe asthma.

A team from McMaster University and The Research Institute of St. Joe’s Hamilton announced their findings from a systematic review and meta-analysis. Data from 20 randomized controlled trials, which included a total of almost 12,000 patients, were analyzed in the study.

Dual-drug inhalers used to treat asthma typically contain an inhaled corticosteroid (ICS) to reduce inflammation, as well as a long-acting beta-adrenoceptor agonist (LABA) that acts as a bronchodilator. High-certainty evidence showed that the inclusion of a third drug to ICS-LABA combination therapy, known as a long-acting muscarinic antagonist (LAMA), reduced severe asthma exacerbations and slightly improved asthma control without an increase in adverse events. Previously, the benefits and harms of adding a LAMA to ICS-LABA therapy for asthma treatment were unclear and based off of only 1300 patients – mainly adults – leading to weak recommendations in treatment guidelines.

“Our findings provide clear, high-quality evidence on the benefits and harms of triple therapy that will inform asthma care and should prompt revision of current asthma guidelines,” said Dr. Derek Chu, lead author of the study.

Dr. Chu is a clinical scholar in the Departments of Medicine and Health Research Methods, Evidence, and Impact (HEI) at McMaster University and an affiliate of The Research Institute of St. Joe’s Hamilton.

“If we can reach optimal control of patients’ asthma and reduce asthma exacerbation rates through the LAMA add-on therapy, patients may be able to avoid other treatments that carry a higher risk of adverse events, such as oral corticosteroids, or therapies that are substantially more expensive, such as biologics,” said Lisa Kim, a clinical scholar in the Department of Medicine at McMaster and co-author of the study.

Inhaled LAMAs are currently available in separate inhalers or as three-in-one inhalers that also contain an ICS and LABA. According to the study, both approaches to administering the third drug work similarly.

More than 8 percent of Canadians over the age of 12 have been diagnosed with asthma, making it the most common chronic condition among children. The disease is characterized by constriction of the bronchial tubes, which impedes air flow to and from the lungs. Symptoms can include coughing or wheezing attacks, shortness of breath, chest tightness, and more. The exact causes of asthma may vary, adding to treatment complexity.

The study was published in the Journal of the American Medical Association (JAMA) in coordination with a presentation by the authors at the Advances in Asthma Therapies symposium. The symposium is part of the American Thoracic Society’s annual conference – ATS 2021 – which is being held virtually this year.

Featured image: Dr. Derek Chu © McMaster University


Reference: Lisa H. Y. Kim, Carol Saleh, Anna Whalen-Browne, et al., “Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma”, JAMA. Published online May 19, 2021. doi:10.1001/jama.2021.7872. The paper is available here: https://jamanetwork.com/journals/jama/fullarticle/2780374


Provided by McMaster University

Oncotarget: Inhibition of Resistant Triple-negative Breast Cancer Cells (Medicine)

The cover for issue 7 of Oncotarget features Figure 5, “SUM149-MA cells surviving a 6-MP treatment are sensitive to chemotherapeutic drugs,” published in “Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine” by Singh, et al. which reported that the authors have reported that a lengthy treatment with low-dose 6-mercaptopurine, a clinically useful anti-inflammatory drug, inhibits such resistant cells.

They found that a lengthy treatment with 1 μM 5-azacitidine, without a significant effect on cell proliferation, sensitized cancer cells to the inhibitory effects of low-dose 6-mercaptopurine.

Importantly, treatment for several weeks with low doses of 6-mercaptopurine and/or 5-azacitidine did not render cancer cells resistant to chemotherapeutic drugs doxorubicin or paclitaxel.

In fact, the cells became more sensitive to chemotherapeutic drugs upon treatment with 6-mercaptopurine and/or 5-azacitidine.

The Oncotarget author’s analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in their model. Their results showed that safe drugs such as low-dose 6-mercaptopurine singly or combined with 5-azacitidine, which are suitable for use prior to disease relapse, have a potential of inhibiting highly resistant triple-negative breast cancer cells.

The Oncotarget author’s analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in their model.

Dr. Anthony Lucci and Dr. Balraj Singh both from The University of Texas MD Anderson Cancer Center said, “Breast cancer patients who have minimal residual disease (MRD) after surgery or systemic therapies are at a higher risk of relapse.

The model involves choosing cancer cell lines established from therapy-resistant breast cancers, such as inflammatory breast cancer, and subjecting them to prolonged glutamine deficiency to select progenitor-like cancer cells that are highly resistant and can metastasize to multiple organs in nude mice.

To explain this experimental strategy for therapeutic evaluation against resistant cancer cells, although their selection protocol for resistant cells is very robust, a majority of the progeny cells would gradually revert back to non-resistant cells in non-selective in vitro conditions.

Since a majority of relatively sensitive cells are preferentially eliminated first by most therapies, lengthy therapeutic evaluations in cell culture provide more useful information about the resistant subpopulation of cancer cells than rapid cell proliferation assays.

6-MP treatment affects cells via mis-incorporation of 6-thioguanine triphosphate into RNA and deoxy-6-thioguanine triphosphate into DNA along with other effects on nucleoside pools and cell signaling. The authors chose low-dose 6-MP for evaluation in our model of adaptable cancer cells because of 6-MP’s ability to induce and maintain remission in inflammatory bowel disease and childhood acute lymphoblastic leukemia.

It has also been shown to stabilize quiescence in cancer cells and to sensitize resistant cancer cells to cell death with an apoptosis-inducing agent in a preclinical model of multiple myeloma.

The Lucci/Balraj Research Team concluded in their Oncotarget Research Output that finally, because immune checkpoint blockade therapy is likely to become common in both neoadjuvant and adjuvant settings in a heterogeneous cancer such as TNBC, the industry must consider any new therapy in this new context.

A common hurdle with the immune checkpoint therapy is severe autoimmune reaction toxicities.

When such therapies are given in the setting of metastasis, they may be combined with other therapies such as cytotoxic agents, which may also adversely affect immunity.

Although therapies like TNF antibodies are useful in managing the acute phase of IBD, 6-MP has been a mainstay for several decades for keeping the disease in remission.

Applying the lessons from IBD treatment to the setting cancer treatment, low-dose 6-MP followed by immune checkpoint blockade could be a good way of limiting severe autoimmune toxicities, thereby increasing the chances of success with these promising therapies.

DOI – https://doi.org/10.18632/oncotarget.27922

Full text – https://www.oncotarget.com/article/27922/text/

Featured image: SUM149-MA cells surviving a 6-MP treatment are sensitive to chemotherapeutic drugs. After a 32 days treatment with 2 μM 6-MP, surviving cells were allowed to recover in a drug-free medium for 33 days. Following this, cells were treated in parallel with 5 nM paclitaxel or 50 nM doxorubicin for 6 days and then allowed to recover and grow into colonies for 17 days before staining with crystal violet. Cells treated with DMSO solvent in parallel served as controls. DMSO treated control plates were stained after 6 days. The number of colonies, counted manually on full-size images, are shown on the top right of photographs of dishes. Representative cell cultures are shown. © Correspondence to – Anthony Lucci – alucci@mdanderson.org and Balraj Singh – bsingh@mdanderson.org


Reference: Singh B., Sarli V. N., Lucci A. Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine. Oncotarget. 2021; 12: 626-637. Retrieved from https://www.oncotarget.com/article/27922/text/


Provided by Impact Journals LLC

Vegan And Omnivorous Diets Promote Equivalent Muscle Mass Gain, Study Shows (Food)

Protein intake is more important than protein source if the goal is to gain muscle strength and mass. This is the key finding of a study that compared the effects of strength training in volunteers with a vegan or omnivorous diet, both with protein content considered adequate. 

In the study, which was conducted by researchers at the University of São Paulo (USP) in Brazil, 38 healthy young adults, half of whom were vegans and half omnivores, were monitored for 12 weeks. In addition to performing exercises to increase muscle strength and mass, the volunteers followed either a mixed diet with both animal and plant protein, or an entirely plant-based diet, both with the recommended protein content (1.6 gram of protein per kilogram of body weight per day). At the end of three months, there was no difference between vegans and omnivores in terms of muscle strength and mass increase. 

“Like any other protein in our organism, such as the proteins in our skin and hair cells, which die and are renewed, our muscles undergo synthesis and breakdown every day. Diet [protein intake] and exercise are the main protein balance regulators, favoring synthesis over breakdown,” said Hamilton Roschel, last author of the published study. Roschel is a University of São Paulo professor affiliated with both USP’s Sports and Physical Education School (EEEE) and Medical School (FM). He also heads the Applied Physiology and Nutrition Research Group jointly run by EEEE-USP and FM-USP.

Protein sources are characterized primarily on the basis of essential amino acids, especially leukin, which plays a key role in anabolic stimulation of skeletal muscles. “Animal protein has more leukin than plant protein. Leukin is an essential amino acid in the anabolic stimulus signaling process. A plant-based diet is often thought to contain less leukin and hence trigger less anabolic stimulation, potentially affecting vegans’ capacity for muscle mass gain,” Roschel said.

The study is published in Sports Medicine and resulted from the master’s research of Victoria Hevia-Larraín, with support from FAPESP.  

The study innovated by including a clinical analysis of the effects of protein source quality on muscle adaptation in vegans as compared with omnivores, since most research on the topic to date has focused on the acute anabolic response of muscles to protein intake under laboratory conditions and not on muscle mass as such. “Our findings show that there is no impairment of muscle mass gain for young adult vegans if they ingest the right amount of protein. In fact, the outcome of both diets was the same in this respect,” Roschel said. 

However, the researchers stress that, for the purposes of experimental control, protein intake was made the same in both diets by means of protein supplements. Omnivores and vegans were given milk serum protein isolate or soy protein respectively in accordance with individual dietary needs in order to attain the targeted protein intake. 

“In clinical practice, we know foods of animal origin generally have a higher protein content,” Roschel said. “Meat, milk and eggs contain more protein per gram than rice and beans, for example. In a clinical application with plant-based foods as the sole protein source, vegans would need to ingest a large amount of food to obtain the same amount of protein. In some specific cases, this could be a major challenge.”

The protein source (mixed or plant-based diet) made no difference, provided each subject received an adequate amount of protein.  “This result corroborates other data in the literature showing that a vegan diet can absolutely be complete if it is properly planned and executed,” Roschel said. “Previous studies suggest it can even be healthier than an omnivorous diet. For this to be the case, however, it requires appropriate nutritional counseling and education regarding people’s choices in restricting their intake to plant-based sources.” 

Another point noted by Roschel is that the subjects were healthy young adults, and the results might be different for older people or subjects with health problems. “Aging entails a phenomenon known as anabolic resistance, meaning a suboptimal anabolic response to the stimuli provided by diet and exercise compared with young people. Optimal response is possible in older people only if their protein intake is higher than that of the average healthy youngster. So we should be cautious about generalizing our findings for the entire population.”

The article “High-protein plant-based diet versus a protein-matched omnivorous diet to support resistance training adaptations: a comparison between habitual vegans and omnivores” (doi: 10.1007/s40279-021-01434-9) by Victoria Hevia-Larraín, Bruno Gualano, Igor Longobardi, Saulo Gil, Alan L. Fernandes, Luiz A. R. Costa, Rosa M. R. Pereira, Guilherme G. Artioli, Stuart M. Phillips and Hamilton Roschel can be retrieved from: link.springer.com/article/10.1007/s40279-021-01434-9.

Featured image: Trials performed by researchers at the University of São Paulo with healthy young adults show that the right level of protein intake is the key to muscle health, regardless of protein source (image: Chelsea Shapouri/Unsplash)


Provided by FAPESP

Nodal and Deltoid Radiotracer Uptake on Post-COVID-19 Vaccination PET (Medicine)

According to an open-access article in ARRS’ American Journal of Roentgenology (AJR), increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after Pfizer-BioNTech or Moderna COVID-19 vaccination.

“Recognition of occasional abnormal axillary lymph node or deltoid uptake on PET examinations performed after COVID-19 vaccination will aid interpreting physicians and reduce unnecessary biopsies,” wrote corresponding author Jason R. Young from the department of radiology at Mayo Clinic in Rochester, MN.

Young and colleagues’ retrospective study included 67 patients (43 men, 24 women; mean age, 75.6 years) who underwent PET examination (PET/CT in 66, PET/MRI in 1; FDG in 54, 11C-choline in 13) between December 14, 2020 and March 10, 2021 following COVID-19 vaccination (Pfizer-BioNTech vaccine in 52, Moderna vaccine in 15) and who had undergone pre-vaccination PET without visible axillary node uptake. PET was performed a median of 13 and 10 days after vaccination in patients who had received one (n = 44) and two (n = 23) doses, respectively.

“We observed positive axillary lymph nodes in 7.4% of FDG and 23.1% of 11C-choline PET examinations performed after COVID-19 vaccination (10.4% of PET examinations) in patients without visible axillary nodal uptake on PET performed before vaccination,” Young et al. concluded. Ipsilateral deltoid uptake with a characteristic appearance was observed in 14.5% of examinations, and one patient exhibited extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). 

“All examinations showing positive axillary lymph nodes were performed within 24 days of vaccination,” the authors of this AJR article added

Featured image: (A) 57-year-old woman with right upper arm melanoma who received the first dose of the COVID-19 vaccine (Pfizer-BioNTech) in the left deltoid 15 days prior to FDG PET/CT. FDG uptake is observed within left axillary lymph nodes (arrow, SUVmax = 9.3). (B) 62-year-old man with metastatic prostate carcinoma who received the second dose of COVID-19 vaccine (Pfizer-BioNTech) in the right deltoid 7 days prior to 11C-choline PET/CT. 11C-choline uptake is observed within right axillary lymph nodes (arrows, SUVmax = 3.1) as well as the right deltoid muscle (circle, SUVmax = 1.7). © American Roentgen Ray Society (ARRS), American Journal of Roentgenology (AJR)


Provided by ARRS

A Revolutionary Method To Drastically Reduce Stray Light on Space Telescopes (Astronomy)

A team of researchers at the Centre Spatial de Liège (CSL) of the University of Liège has just developed a method to identify the contributors and origins of stray light on space telescopes. This is a major advance in the field of space engineering that will help in the acquisition of even finer space images and the development of increasingly efficient space instruments. This study has just been published in the journal Scientific Reports.

Space telescopes are becoming more and more powerful. Technological developments in recent years have made it possible, for example, to observe objects further and further into the universe or to measure the composition of the Earth’s atmosphere with ever greater precision. However, there is still one factor limiting the performance of these telescopes: stray light. A phenomenon that has been known fora long time, stray light results in light reflections (ghost reflections between lenses, scattering, etc.) that damage the quality of images and often lead to blurred images. Until now, the methods for checking and characterizing this stray light during the development phase of the telescopes have been very limited, making it possible to “just” know whether or not the instrument was sensitive to the phenomenon, forcing engineers to revise all their calculations in positive cases, leading to considerable delays in the commissioning of these advanced tools.

Researchers at the Centre Spatial de Liège (CSL), in collaboration with the University of Strasbourg, have just developed a revolutionary method for solving this problem by using a femto-second pulsed laser to send light beams to illuminate the telescope. “Stray light rays take (in the telescope) different optical paths from the rays that form the image,” explains Lionel Clermont, an expert in space optical systems and stray light at CSL. Thanks to this, and using an ultra-fast detector (of the order of 10-9 seconds of resolution, i.e. a thousandth of a millionth of a second), we are measuring the image and the different stray light effects at different times. In addition to this decomposition, we can identify each of the contributors using their arrival times, which are directly related to the optical path, and thus know the origin of the problem.”

At time passes, different stray light contributors (ghost) appear and disapear on the detector. The time of arrival is related to the optical path length, we can identify each contributor and compare them with the theoretical model ©×Lionel Clermont / Centre Spatial de Liège / Université de Liège

The CSL engineers have now demonstrated the effectiveness of this method in a paper, just published in the journal Scientific Reports, in which they present the first film showing ghost reflections in a refractive telescope arriving at different times. “We have also been able to use these measurements to reverse engineer theoretical models,” says Lionel Clermont, “which will make it possible, for example, to build better image processing models in the future.” By correlating these measurements with numerical models, the scientists will now be able to determine precisely the origin of the stray light and thus act accordingly to improve the system, both by improving the hardware and with the development of correction algorithms.

More than just a scientific curiosity, this method developed at the CSL could well lead to a small revolution in the field of high-performance space instruments. “We have already received a great deal of interest from the ESA (European Space Agency) and from industrialists in the space sector,” says Marc Georges, an expert in metrology and lasers at CSL and co-author of the study. This method responds to an urgent problem that has been unresolved until now.” In the near future, CSL researchers intend to continue the development of this method, to increase its TRL (Technology Readiness Level) and bring it to an industrial level. An industrial application is already planned for the FLEX (Fluorescence Explorer) project, an earth observation telescope that is part of ESA’s Living Planet Program. The researchers hope to be able to apply it to scientific instruments as well.

Featured image: Stray light decomposition by ultrafast time-of-flight imaging. © Lionel Clermont / Centre Spatial de Liège / Université de Liège


Reference: Clermont, L., Uhring, W. & Georges, M. Stray light characterization with ultrafast time-of-flight imaging. Sci Rep 11, 10081 (2021). https://doi.org/10.1038/s41598-021-89324-y


Provided by University of Liege

Study Solves Mystery of How Amyloid Beta Forms in Brain Nerve Cells (Neuroscience)

In a major breakthrough, researchers at Massachusetts General Hospital (MGH) have discovered how amyloid beta–the neurotoxin believed to be at the root of Alzheimer’s disease (AD)–forms in axons and related structures that connect neurons in the brain, where it causes the most damage. Their findings, published in Cell Reports, could serve as a guidepost for developing new therapies to prevent the onset of this devastating neurological disease.

Among his many contributions to research on AD, Rudolph Tanzi, PhD, vice chair of Neurology and co-director of the McCance Center for Brain Health at MGH, led a team in 1986 that discovered the first Alzheimer’s disease gene, known as APP, which provides instructions for making amyloid protein precursor (APP). When this protein is cut (or cleaved) by enzymes–first, beta secretase, followed by gamma secretase–the byproduct is amyloid beta (sometimes shortened to Abeta). Large deposits of amyloid beta are believed to cause neurological destruction that results in AD. Amyloid beta formed in the brain’s axons and nerve endings causes the worst damage in AD by impairing communication between nerve cells (or neurons) in the brain. Researchers around the world have worked intensely to find ways to block the formation of amyloid beta by preventing cleavage by beta secretase and gamma secretase. However, these approaches have been hampered by safety issues.

Despite years of research, a major mystery has remained. “We knew that Abeta is made in the axons of the brain’s nerve cells, but we didn’t know how,” says Tanzi. He and his colleagues probed the question by studying the brains of mice, as well as with a research tool known as Alzheimer’s in a dish, a three-dimensional cell culture model of the disease created in 2014 by Tanzi and a colleague, Doo Yeon Kim, PhD. Earlier, in 2013, several other MGH researchers, including neurobiologist Dora Kovacs, PhD (who is married to Tanzi), and Raja Bhattacharyya, PhD, a member of Tanzi’s lab, showed that a form of APP that has undergone a process called palmitoylation (palAPP) gives rise to amyloid beta. That study indicated that, within the neuron, palAPP is transported in a fatty vesicle (or sac) known as a lipid raft. But there are many forms of lipid rafts. “So the question was, Which lipid rafts? And which ones are most relevant to the neuronal processes making up the neural networks of the brain?” says Tanzi.

The new investigation revealed that palAPP is stabilized and prepared for cleavage by beta secretase in special lipid rafts within the neuron known as mitochondria-associated endoplasmic reticulum membranes (MAMs). “We showed for the first time not only that the MAM is where palAPP is processed by beta secretase to make Abeta, but that this happens exclusively in axons and neuronal processes where Abeta does most of its damage,” says Bhattacharyya, lead author of the Cell Reports paper. This role for MAMs was previously unknown, though earlier research indicated that they are increased in number and activity in the brains of people with Alzheimer’s disease.

Next, the MGH team wanted to learn what happens when MAM levels and activity were intentionally altered. They showed for the first time that preventing assembly of MAMs, either with gene therapy or a drug that blocked a key protein called the sigma-1 receptor (S1R), dramatically decreased beta secretase cleavage of palAPP in axons and lowered Abeta production. Conversely, a drug that activated S1R triggered an increase in beta secretase cleavage of palAPP and increased production of amyloid beta in axons.

“Our results suggest that the sigma-1 receptor might be a viable therapeutic target for reducing Abeta production, specifically in axons,” says Tanzi. The study also lends support for a strategy already under investigation by Tanzi and his team, which is developing an experimental treatment that inhibits the palmitoylation of APP, the process that produces palAPP. It’s also known that another class of drugs that Kovacs is studying for preventing formation of amyloid beta, called ACAT inhibitors, works directly in MAMs. In the future, these and other interventions that thwart production of this most dangerous pool of axonal amyloid beta could be used in concert with early detection (through blood or imaging tests) to stop or slow the progression of AD.

Tanzi directs the Genetics and Aging Research Unit and co-directs the Henry and Allison McCance Center for Brain Health at MGH and is the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School (HMS). Bhattacharyya is also an instructor in Neurology at HMS.

This study was funded by grants from the National Institutes of Health and the Cure Alzheimer’s Fund.

Featured image: Graphical abstract © Bhattacharyya et al.


Reference: Raja Bhattacharyya, Sophia E. Black et al., “Axonal generation of amyloid-β from palmitoylated APP in mitochondria-associated endoplasmic reticulum membranes”, Cell reports, 35(7), 2021. DOI: https://doi.org/10.1016/j.celrep.2021.109134


Provided by Massachusetts General Hospital