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May 7th, 2021

CHOP Researchers Discover and Treat Rare Disease That Prevents Formation of Antibodies

When Luke Terrio was about seven months old, his mother began to realize something was off. He had constant ear infections, developed red spots on his face, and was tired all the time. His development stagnated, and the antibiotics given to treat his frequent infections stopped working. His primary care doctor at Children's Hospital of Philadelphia (CHOP) ordered a series of blood tests and quickly realized something was wrong: Luke had no antibodies. At first, the CHOP specialists treating Luke thought he might have X-linked agammaglobulinemia (XLA), a rare immunodeficiency syndrome seen in children. However, as the CHOP research team continued investigating Luke's case, they realized Luke's condition was unlike any disease described before. Using whole exome sequencing to scan Luke's DNA, CHOP researchers discovered the genetic mutation responsible for his condition, which prevents Luke and patients like him from making B cells and antibodies to fight infections. The study describing Luke's condition, which CHOP researchers, together with colleagues, named PU.1 mutated agammaglobulinemia (PU.MA), was published online on May 5, 2021 in the Journal of Experimental Medicine. The article is titled “Constrained Chromatin Accessibility in PU.1-Mutated Agammaglobulinemia Patients” ( "It can be pretty scary for a family whose child has a mysterious illness" said Neil D. Romberg, MD, an attending physician with the Division of Allergy and Immunology at CHOP and senior author of the paper.

Epithelial Cells Asymmetrically Release Two Distinct Types of Exosomes with Distinct Protein Compositions; Apical Release Controlled by ALIX, Basolateral Release by Ceramide; Results May Offer Clues to Metastasis

Cells talk to each other to coordinate nutrition, waste removal, energy use, and, in some cases, disease progression. The cells that line the surfaces of organs or specific tissues, called epithelial cells, appear to speak two different languages - one for either side of the cell, according to a new study by researchers based in Japan. The discovery, published online March 16, 2021 in EMBO Reports, could have implications for understanding how cancer spreads and, potentially, for advanced treatments, the team says. The article is titled “ALIX and Ceramide Differentially Control Polarized Small Extracellular Vesicle Release from Epithelial Cells” ( The team, led by Mitsunori Fukuda, PhD, Professor in the Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences at Tohoku University in Japan, examined epithelial cells from a kidney model. The cells release particles called exosomes that carry bits of the cells themselves or information about the cells. The proteins and other genetic information in the exosomes can then influence how other cells behave or function. In health, such an information exchange could help the immune system mount a more tailored approach to an invading pathogen. Some diseased cells, such as cancer, can release exosomes that make healthy cells less resistant to invasion. "Single cells are known to release various kinds of exosomes, but very little is known about the mechanisms by which they are produced and released," Dr. Fukuda said. "In this paper, we found that epithelial cells asymmetrically release two distinct types of exosomes with distinct protein compositions." The researchers developed a purification method to separate out exosomes based on their protein makeup.

May 5th

Surprising Discovery: Bats Know Speed of Sound from Birth, Map World in Units of Time Not Distance

A new Tel Aviv University study has revealed, for the first time, that bats know the speed of sound from birth. In order to prove this, the researchers raised bats from the time of their birth in a helium-enriched environment in which the speed of sound is higher than normal. They found that unlike humans, who map the world in units of distance, bats map the world in units of time. What this means is that the bat perceives an insect as being at a distance of nine milliseconds, and not one and a half meters, as was thought until now. The study published in the May 11, 2021 issue of PNAS. The article is titled “Echolocating Bats Rely on an Innate Speed-of-Sound Reference” ( In order to determine where things are in a space, bats use sonar--they produce sound waves that hit objects and are reflected back to the bat. Bats can estimate the position of the object based on the time that elapses between the moment the sound wave is produced and the moment it is returned to the bat. This calculation depends on the speed of sound, which can vary in different environmental conditions, such as air composition or temperature. For example, there could be a difference of almost 10% between the speed of sound at the height of the summer, when the air is hot and the sound waves spread faster, and the winter season. Since the discovery of sonar in bats 80 years ago, researchers have been trying to figure out whether bats acquire the ability to measure the speed of sound over the course of their lifetime or are born with this innate, constant sense.

A Trait of The Rare Few Whose Bodies Naturally Control HIV: "Trained" Immune Cells; Scientists Discover That "Elite Controllers" Have Myeloid Dendritic Cells That Display Characteristics of Trained Innate Immune Cells

Immunity often calls to mind the adaptive immune response, made up of antibodies and T cells that learn to fight specific pathogens after infection or vaccination. But the immune system also has an innate immune response, which uses a set number of techniques to provide a swift, non-specialized response against pathogens or support the adaptive immune response. In the past few years, however, scientists have found that certain parts of the innate immune response can, in some instances, also be trained in response to infectious pathogens, such as HIV. Xu Yu, MD, a Core Member of the Ragon Institute of Massachusettes General Hospital, MIT and Harvard, and colleagues recently published a study in the Journal of Clinical Investigation which showed that elite controllers, a rare subset of people whose immune system can control HIV without the use of drugs, have myeloid dendritic cells, part of the innate immune response, that display traits of a trained innate immune cell. The open-access article was published online on May 3, 2021 and is titled “Long Noncoding RNA MIR4435-2HG Enhances Metabolic Function of Myeloid Dendritic Cells from HIV-1 Elite Controllers” ( "Using RNA-sequencing technology, we were able to identify one long-noncoding RNA called MIR4435-2HG that was present at a higher level in elite controllers' myeloid dendritic cells, which have enhanced immune and metabolic states," says Dr. Yu. "Our research shows that MIR4435-2HG might be an important driver of this enhanced state, indicating a trained response." Myeloid dendritic cells' primary job is to support T cells, which are key to the elite controllers' ability to control HIV infection. Because MIR4435-2HG was found in higher levels only in cells from elite controllers, Dr.

May 4th

Cardea Bio Develops Exosome & EV Detection Technology Called EV-Chip, Showcasing Cancer & Aging Diagnostic Applications: Technology Paves Way for New Generation of Portable, Point-of-Care Devices for Real-Time Analysis of Liquid Biopsies

On May 4, 2021, Cardea Bio, a Tech+Bio company integrating molecular biology with semiconductor electronics via graphene-based biology-gated “Cardean Transistors,” has announced that its Chief Scientific Officer, Dr. Kiana Aran, and collaborators have published a paper titled “Rapid and Electronic Identification and Quantification of Age-Specific Circulating Exosomes via Biologically Activated Graphene Transistors” in the peer-reviewed journal Advanced Biology on April 30, 2021 ( The paper reports a novel biosensor called the EV-Chip, a prototype portable, low-cost reader for the detection and quantification of exosome biomarkers of cancer and other aging-related diseases. The paper demonstrates the EV-Chip’s clinical potential to evaluate human liquid biopsy samples through rapid, label-free identification of known biomarkers, CD63 and CD151. The publication was the result of a collaboration among Cardea Bio, Inc., the Keck Graduate Institute and the Keck Science Department in Claremont, California, and the University of California, Berkeley. “Modern clinical advances have extended the bounds of the human lifespan, revealing a new class of health issues related to the aging process, such as cancer as well as inflammatory and degenerative diseases,” said Dr. Aran. “Scientists will be able to use the EV-Chip for biomarker discovery and unlock a new source of diagnostic biomarkers and therapies to combat these diseases more effectively.” The EV-Chip has high-specificity antibodies that bind to one or more exosome biomarkers of interest embedded into a Cardean Transistor chip. It can be functionalized to detect virtually any exosome biomarker.

May 3rd

Bornean Rajah Scops Owl Rediscovered After 125 Years

The Bornean subspecies of Rajah scops owl (Otus brookii brookii) (photo) documented in the wild for the first time since 1892, may be its own unique species and deserving of a conservation designation. In an article published online on April 28, 2021 in The Wilson Journal of Ornithology, Smithsonian Migratory Bird Center ecologist Andy Boyce, PhD, reported the rediscovery and photographed this elusive subspecies in the mountainous forests of Mount Kinabalu in Sabah, Malaysia. "It was a pretty rapid progression of emotions when I first saw the owl--absolute shock and excitement that we'd found this mythical bird, then pure anxiety that I had to document it as fast as I could," Dr. Boyce said. "Based on size, eye color, and habitat, I knew it was the Bornean Rajah scops owl. What's more, taking into account this bird's specific plumage characters, known speciation patterns within the Otus genus, and phylogeographic patterns of montane birds in Borneo and Sumatra, O. b. brookii is likely its own unique species and further study is needed." Scops owls weigh approximately 100 grams (about 4 ounces), equivalent to four AA batteries. Both subspecies of Rajah scops owl are native to southeast Asia--Otus brookii brookii on the island of Borneo and Otus brookii solokensis on Sumatra. Small owls in the genus Otus often show rapid divergence following isolation in this region. In fact, the Indonesian archipelago is composed of islands that facilitate species divergence, and Borneo and Sumatra have been particularly prone to speciation events.

May 2nd

Move Over CRISPR, the Retrons Are Coming; With New Gene Editing Technique from George Church’s Lab, Millions of Genetic Experiments Can Be Performed Simultaneously; Retron Library Recombineering (RLR) May Overcome Many Limitations of CRISPR-Cas9

While the CRISPR-Cas9 gene editing system has become the poster child for innovation in synthetic biology, it has some major limitations. CRISPR-Cas9 can be programmed to find and cut specific pieces of DNA, but editing the DNA to create desired mutations requires tricking the cell into using a new piece of DNA to repair the break. This bait-and-switch can be complicated to orchestrate, and can even be toxic to cells because Cas9 often cuts unintended, off-target sites as well. Alternative gene editing techniques called recombineering instead perform this bait-and-switch by introducing an alternate piece of DNA while a cell is replicating its genome, efficiently creating genetic mutations without breaking DNA. These methods are simple enough that they can be used in many cells at once to create complex pools of mutations for researchers to study. Figuring out what the effects of those mutations are, however, requires that each mutant be isolated, sequenced, and characterized: a time-consuming and impractical task. Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) have created a new gene editing tool called Retron Library Recombineering (RLR) that makes this task easier. RLR generates up to millions of mutations simultaneously, and “barcodes” mutant cells so that the entire pool can be screened at once, enabling massive amounts of data to be easily generated and analyzed. The achievement, which has been accomplished in bacterial cells, is described in a paper published in the May 4, 2021 issue of PNAS.

April 30th

Periodic Fasting Lowers Blood Pressure by Reshaping Gut Microbiota in Animal Model

Nearly half of adults in the United States have hypertension, a condition that raises the risk for heart disease and stroke, which are leading causes of death in the U. S. At Baylor College of Medicine, Dr. David J. Durgan and his colleagues are dedicated to better understand hypertension, in particular the emerging evidence suggesting that disruption of the gut microbiota, known as gut dysbiosis, can have adverse effects on blood pressure. "Previous studies from our lab have shown that the composition of the gut microbiota in animal models of hypertension, such as the SHRSP (spontaneously hypertensive stroke-prone rat) model, is different from that in animals with normal blood pressure," said Dr. Durgan, Assistant Professor of Anesthesiology at Baylor. The researchers have also shown that transplanting dysbiotic gut microbiota from a hypertensive animal into a normotensive (having a healthy blood pressure) one results in the recipient developing high blood pressure. "This result told us that gut dysbiosis is not just a consequence of hypertension, but is actually involved in causing it," Dr. Durgan said. "This ground work led to the current study in which we proposed to answer two questions. First, can we manipulate the dysbiotic microbiota to either prevent or relieve hypertension? Second, how are the gut microbes influencing the animal's blood pressure?" To answer the first question, Dr. Durgan and his colleagues drew on previous research showing that fasting was both one of the major drivers of the composition of the gut microbiota and a promoter of beneficial cardiovascular effects. These studies, however, had not provided evidence connecting the microbiota and blood pressure.

Once-a-Week Insulin Treatment Could Be Game-Changing for Patients with Diabetes

Treating people with Type 2 diabetes with a new once-a-week injectable insulin therapy proved to be safe and as effective as daily insulin injections, according to the results of two international clinical trials published online on April 19, 2021 in Diabetes Care. The studies suggest that the once-weekly treatment could provide a convenient alternative to the burden of daily insulin shots for diabetes patients.Starting and maintaining insulin treatment remain a challenge for millions of patients worldwide with Type 2 diabetes. Fear of injections and the inconvenience and burden of injectable therapy contribute to the barriers against insulin therapy initiation and adherence. The effectiveness and safety of ongoing insulin treatment are also highly dependent on other factors, such as the accuracy of dosages, timing, and glycemic targets. Health care providers believe that reducing the frequency of treatment administration with advances, such as the once-weekly insulin used in these phase 2 trials, may decrease the reluctance to initiate insulin therapy while improving long-term adherence, glucose control, and ultimately, patient well-being. “Insulin, which has been the foundation of diabetes treatment for 100 years, is an effective glucose-lowering agent and is safe when used at the correct dose,” says Ildiko Lingvay (photo), MD, MPH, a Professor of Internal Medicine and Population and Data Sciences at the University of Texas Southwestern (UTSW). “Insulin treatment is burdensome, requires frequent injections, and continues to carry a certain stigma. The development of an effective and safe insulin that can be administered once a week is a huge advance in the field.”

The Genome of a Certain Plankton (Dinoflagellate Symbiodinium microadriaticum) Looks Nothing Like That of Other Eukaryotic Genomes

The genome of certain single-celled plankton, known as dinoflagellates, is organized in an incredibly strange and unusual way, according to new research. The findings lay the groundwork for further investigation into these important marine organisms and dramatically expand our picture of what a eukaryotic genome can look like. Researchers from Saudia Arabia’s KAUST (King Abdullah University of Science and Technology), the U.S., and Germany have investigated the genomic organization of the coral-symbiont dinoflagellate Symbiodinium microadriaticum (image). The genome of S. microadriaticum genome had already been sequenced and assembled into segments known as scaffolds but lacked a chromosome-level assembly. The team used a technique known as Hi-C to detect interactions in the dinoflagellate’s chromatin, the combination of DNA and protein that makes up a chromosome. By analyzing these interactions, they could figure out how the scaffolds were connected together into chromosomes, giving them a view into the spatial and structural organization of the genome. A striking finding was that the genes in the genome tended to be organized in alternating unidirectional blocks. “That’s really, really different from what you see in other organisms,” says Octavio Salazar, a PhD student in Manuel Aranda's (PhD) group at KAUST and one of the lead authors of the study. The orientation of genes on a chromosome is usually random. In this case, however, genes were consistently oriented one way and then the other, with the boundaries between blocks showing up clearly in the chromatin interaction data. “Nature can work in a completely different way than we thought,” Salazar said.