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Archive - Jun 2020

June 30th

Nα-Acetylation of Virulence Factor EsxA of Mycobacterium tuberculosis Causes It to Dissociate from Its Chaperone EsxB; This Dissociation Is Known to Enable EsxA Membrane Permeabilization and Mycobacterial Cytosolic Translocation and Virulence

Biology students and faculty members from The University of Texas at El Paso (UTEP) have discovered a new target for tuberculosis drug development. Their study was published in the April 24, 2020 issue of the Journal of Biological Chemistry, a publication of the American Society of Biochemistry and Molecular Biology (ASBMB). The article is titled “Nα-Acetylation of the Virulence Factor EsxA Is Required for Mycobacterial Cytosolic Translocation and Virulence.” Jianjun Sun, PhD, Associate Professor in UTEP's Department of Biological Sciences, led the research on Mycobacterium tuberculosis (Mtb), the bacterial pathogen that causes tuberculosis (TB). TB is one of the leading infectious diseases in the world. Development of novel therapeutics against TB is urgently needed. Dr. Sun's lab has been investigating the mechanisms of Mtb pathogenesis for more than 10 years at UTEP, with a specific focus on EsxA, which is a virulence factor essential for Mtb virulence and a preferred target for developing novel anti-TB drugs and vaccines. During infection, Mtb is "eaten up" by human immune cells. Normally, bacteria are killed within the immune cells, but Mtb releases virulence factors, such as EsxA, to disarm the host's immune defense. The study discovered that the Nα-acetylation of EsxA can drastically affect the course of the infection. "This research was technically challenging, but the students were able to overcome the challenges and accomplished the goals," Dr. Sun said.

International Society for Extracellular Vesicles (ISEV) Annual Meeting (#ISEV2020), Including Exosomes, Is Now VIRTUAL (July 20-22); >600 Discussions (Plenary Addresses, Panel Sessions, Oral Abstract Talks, Poster Chats, & Educational Sessions)

The International Society for Extracellular Vesicles (ISEV) annual meeting, including exosomes (https://www.isev.org/mpage/2020Program), has become the “go to” meeting for intra- and interdisciplinary cross-fertilization of extracellular vesicle (EV) and exosome science within the EV/exosome community. It also plays a pivotal role in the training of junior scientists and trainees. Please join over 800 people who have already registered for this 3-day, live-streamed, online event. You may register for this outstanding virtual meeting at https://www.isev.org/mpage/2020Registration. Instead of spending 24 hours traveling across the world, have all the latest in EV/exosome research come to you, wherever you are! You can expect a similar amount of content as you would have experienced at the face-to-face conference. #ISEVirtual offers 5 live-streamed plenary talks, 4 live “hot-topic” panel sessions, 6 educational sessions, and 146 oral talks selected from your submitted abstracts. That’s 161 talks plus more than 470 interactive 3-minute poster pitches. That’s a total of over 600 discussions on the latest developments in EV/exosome work, all completely available online. Also, as you will be used to at the face-to-face meeting, there will also be the chance to ask questions of the speakers and panelists, interact with company sponsors, and chat with other delegates via the #ISEVirtual app. And if you can’t make it on the day? Don’t worry! ALL content will be available to view at your leisure for 60 days after the event. This is the first time in ISEV history that you’ll be able to see EVERYTHING, all from the comfort of your own home, wherever you are in the world.

Brain Exosomes from Blood Samples May Allow Earlier Diagnosis of ALS; Unique Signature of Eight Different MicroRNAs Distinguishes ALS Brain Exosomes; Rapid Diagnosis of "Lou Gehrig's Disease" May Be Possible from Single Blood Draw

Exosomes, microscopic packets that can contain genetic material, are shed by different tissues into the blood. By sequencing microRNA within exosomes originating in the brain, it is now possible to definitively distinguish blood samples of amyotrophic lateral sclerosis (ALS) (Lou Gehrig’s disease) patients from healthy controls, a team of researchers at the Brain Chemistry Labs (Jackson Hole, Wyoming) reported on June 24, 2020 in an article published in Royal Society Open Biology. The open-access article is titled ““An miRNA Fingerprint Using Neural-Enriched Extracellular Vesicles from Blood Plasma: Towards a Biomarker for Amyotrophic Lateral Sclerosis/Motor Neuron Disease.” ALS is a progressive neurodegenerative disease that typically affects people in the prime of life. "We think this is a game-changer: the methods we have pioneered will lead to the ability to rapidly diagnose ALS from a single blood draw, compared to current scientific measures where patients may have to wait for over a year for a confirmed diagnosis," says Sandra Banack (photo below; baseball star Lou Gehrig who died of ALS, is shown at left) (https://brainchemistrylabs.org/new-page-1), PhD, Brain Chemistry Labs Senior Scientist and first author on the new paper. "People with ALS typically live an average of two to three years after diagnosis, so a rapid assessment is crucial." The new test is based on exosomes, which are microscopic packets that can contain genetic material and are shed by different tissues in the body. The researchers purified brain exosomes from blood plasma by targeting a unique protein on the exosome surface.

Researchers Develop Novel Vaccine That Removes Senescent T-Cells from the Body to Improve Obesity-Induced Metabolic Disorders; “Striking Results” Obtained in Mouse Study

Aging is a multifaceted process that affects our bodies in many ways. In a new study, researchers from Osaka University in Japan developed a novel vaccine that removes aged immune cells and then demonstrated an improvement of diabetes-associated metabolic derangements by vaccinating obese mice. Aged, or senescent, cells are known to harm their surrounding younger cells by creating an inflammatory environment. A specific type of immune cell, called a T-cell (image), can accumulate in fat tissues in obese individuals in senescence, causing chronic inflammation, metabolic disorders, and heart disease. To reduce the negative effects of senescent cells on the body, senotherapy was developed to target and eliminate these rogue cells. However, as this approach does not discriminate between different types of senescent cells, it has remained unknown whether specific depletion of senescent T-cells can improve their adverse effects on organ physiology. “The idea that eliminating senescent cells improves the organ dysfunction that we experience during aging is fairly new,” says corresponding author of the study Hironori Nakagami, PhD,of the Department of Health Development and Medicine, Osaka University Graduate School of Medicine. “Because senescent T-cells can facilitate metabolic derangements similar to diabetes, we wanted to come up with a new approach to reduce the number of senescent T-cells to then reverse the negative effects they have on glucose metabolism.” To achieve their goal, the researchers developed a novel vaccine targeting the surface protein CD153 that is present on senescent T-cells populating fat tissues, thereby ensuring that normal T-cells are not affected.

American Chemical Society Names Paul Alivisatos 2021 Priestley Medalist, Society’s Highest Honor; Award Recognizes Alivisatos’ Foundational Contributions to the Chemistry of Nanoscience, Including Development of Nanocrystals As Nanotech Building Blocks

On June 30, 2020, the American Chemical Society (ACS) announced that it has selected Paul Alivisatos (photo), PhD, of the University of California (UC), Berkeley as the recipient of the 2021 Priestley Medal, the Society’s highest honor. Dr. Alivisatos (https://en.wikipedia.org/wiki/Paul_Alivisatos), the Samsung Distinguished Professor in Nanoscience and Nanotechnology Research and Professor of Chemistry and Materials Science and Engineering at the University of California (UC) Berkeley, is being recognized for “foundational contributions to the chemistry of nanoscience, development of nanocrystals as nanotechnology building blocks and leadership in the chemistry and nanoscience communities.” “Dr. Alivisatos is a true innovator in the field of nanoscience and chemistry as a whole,” says ACS CEO Thomas Connelly Jr., PhD. “His groundbreaking contributions to the fundamental physical chemistry of nanocrystals, as well as laying the foundation for the development of colloidal quantum dots, have led to significant advances in technology, medicine and renewable energy. That tremendous scientific legacy is now cemented, and I offer my heartfelt congratulations.” Dr. Alivisatos has spent the majority of his career studying nanocrystals, including their behavior and synthesis. In one of his first major breakthroughs as a pioneer in a then-emerging field, he demonstrated a method for growing quantum dots--semiconductor nanocrystals smaller than 10 nanometers--into two-dimensional shapes. This ability to create nanomaterials with precision and complexity is used by scientists and companies worldwide to create new biomedical imaging technology, high-resolution electronic displays, and energy-efficient technologies, all of which utilize quantum dots.

Particular Bacterium in Gut Microbiome Confers Resistance to Cholera; Blautia obeum Degrades Bile Salts That Normally Act As Signals for Cholera to Turn On Dormant Virulence Genes; Individuals with B. obeum in Their Gut Microbiome Are Resistant to Cholera

Many parts of the world are in the midst of a deadly pandemic of cholera, an extreme form of watery diarrhea. University of California (UC) at Riverside (UCR) scientists have discovered specific gut bacteria make some people resistant to cholera, a finding that could save lives. Cholera can kill within hours if left untreated, and it sickens as many as 4 million people a year. In a new article, published in the June 25, 2020 issue of Cell, researchers describe how gut bacteria help people resist the disease (https://www.cell.com/cell/fulltext/S0092-8674(20)30631-0) (see graphic abstract of Cell article at left and in a larger view at the bottom of this story). The article is titled “Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection.” Bacteria live everywhere on the planet--including inside the human body. UCR microbiologist Ansel Hsiao, PhD, studies whether the bacteria living in our bodies, collectively known as the human microbiome, can protect people from diseases caused by external bacteria such as Vibrio cholerae, which lives in waterways and causes cholera. Dr. Hsiao’s team examined the gut microbiomes from people in Bangladesh, where many suffer from cholera as a result of contaminated food, water, and poor sanitation infrastructure. “When people get sick, the diarrhea gets flushed into water systems that people drink from, and it’s a negative cycle,” Dr. Hsiao explained. His team wanted to determine whether prior infections or other stresses, like malnutrition, make people more vulnerable, as compared to Americans who don’t face these same pressures. The findings surprised the group, which expected stressed Bangladeshi microbiomes would allow for higher rates of infection.

Possibly Revolutionary New Treatment Alternative to Corneal Transplantation Developed in Montreal; “LiQD Cornea” Is Liquid Hydrogel That Promotes Tissue Regeneration, Thus Treating Corneal Perforations Without Need for Transplantation

A research team co-led by May Griffith (photo), PhD, a scientist at Maisonneuve-Rosemont Hospital Research Centre, which is affiliated with Université de Montréal and is part of the CIUSSS de l'Est-de-l'Île-de-Montréal, has reported results suggesting that a novel liquid hydrogel may be used to effectively treat corneal perforations and offers an alternative to corneal transplant. The results of this multinational project were published on June 17, 2020 in Science Advances. The open-access article is titled “LiQD Cornea: Pro-Regeneration Collagen Mimetics As Patches and Alternatives to Corneal Transplantation.” "Our work has led to an effective and accessible solution called LiQD Cornea to treat corneal perforations without the need for transplantation," said Dr. Griffith, who is also a full professor in the Department of Ophthalmology at Université de Montréal. "This is good news for the many patients who are unable to undergo this operation due to a severe worldwide shortage of donor corneas," she said. "Until now, patients on the waiting list have had their perforated corneas sealed with a medical-grade super glue, but this is only a short-term solution because it is often poorly tolerated in the eye, making transplantation necessary." A synthetic, biocompatible, and adhesive liquid hydrogel, LiQD Cornea, is applied as a liquid, but quickly adheres and gels within the corneal tissue. The LiQD Cornea promotes tissue regeneration, thus treating corneal perforations without the need for transplantation. Dr. Griffith praised the work of her trainees, Christopher McTiernan and Fiona Simpson, and her collaborators from around the world who have helped create a potentially revolutionary treatment to help people with vision loss avoid going blind.

June 29th

Bobwhites Listen to Each Other When Picking Habitat; University of Illinois Researchers Used Taped Calls to Lure Birds to Suitable Habitats; Hope to Increase Currently Declining Bobwhite Populations

[This article was written by Ananya Sen, a graduate student in Microbiology at the University of Illinois at Urbana-Champaign. Ms. Sen is also a science writer and her articles can be found at http://ananyasen.web.illinois.edu/. This article was originally published as a Research News article by the University of Illinois News Bureau (https://news.illinois.edu/view/6367).] Northern bobwhites are attracted to a habitat based on whether other bobwhites are present there, researchers at the University of Illinois at Urbana-Champaign report. This phenomenon, called con-specific attraction, could aid conservation efforts. Bobwhites, Colinus virginianus, are resident birds--they decide where to live and stick to that decision for the rest of their lives, said Michael Ward (https://nres.illinois.edu/directory/mpward), PhD, a Professor of Natural Resources And Environmental Sciences (https://nres.illinois.edu/), who led the research. “It’s an important decision,” he said. “It’s like sampling food at different restaurants before you decide where to eat.” The researchers played recordings of bobwhite songs to see whether they could attract the birds to unoccupied sites in the Cold Springs area of Fort Polk, Louisiana. “We played their calls on an MP3 player that was attached to a battery,” Dr. Ward said. “We tried to mimic their natural singing behavior by playing the recordings more often in the morning and less in the afternoon.” The researchers studied the sites for three years. They did not play any recordings in the first year. The next year they divided the sites into those with and without recordings. The sites were flipped the third year.

FDA Approves Merck’s KEYTRUDA® (Pembrolizumab) for First-Line Treatment of Patients with Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer, First Single-Agent, Anti-PD-1 Therapy Approved for the First-Line Treatment of These Patients

On June 29, 2020, Merck (NYSE: MRK), known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA (https://en.wikipedia.org/wiki/Pembrolizumab), Merck’s anti-PD-1 therapy, as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. The approval is based on results from the Phase 3 KEYNOTE-177 trial, in which KEYTRUDA significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0004]) compared with chemotherapy, the current standard of care. In the study, treatment with KEYTRUDA also more than doubled median progression-free survival (PFS) compared with chemotherapy (16.5 months [95% CI, 5.4-32.4] versus 8.2 months [95% CI, 6.1-10.2]). “Today’s approval has the potential to change the treatment paradigm for the first-line treatment of patients with MSI-H colorectal cancer, based on the important findings from KEYNOTE-177 that showed KEYTRUDA monotherapy demonstrated superior progression-free survival compared to standard of care chemotherapy,” said Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, Merck Research Laboratories. “Our commitment to pursuing biomarker research continues to help us bring new treatments to patients, particularly for those who have few available options.” Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, and these include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT).

ReNeuron Signs Collaboration to Produce Human Neural Stem Cell (hNSC)-Derived Exosomes & to Load Them with Novel Gene-Silencing Therapeutics from Un-Named Collaborating US Biotech Company; ReNeuron Will Provide Loaded Exosomes to Collaborator

On June 25, 2020, ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, announced that it has signed a new research evaluation agreement with a major US biotechnology company in connection with the use of the ReNeuron’s proprietary exosomes for the delivery of novel gene-silencing therapeutics. This latest research collaboration will focus on the use of ReNeuron’s human neural stem cell (hNSC)-derived exosomes for the delivery of the US biotechnology company’s neuroscience therapeutic candidates. ReNeuron will be responsible for manufacturing exosomes and then loading them with the gene-silencing sequences after which the US biotechnology company will evaluate the loaded exosomes. Assuming positive results, the parties will jointly own the novel therapeutic candidate created for future development. The research evaluation agreement is in line with ReNeuron’s strategy of partnering its exosome technology as a novel delivery vehicle. This new agreement follows an exosome research collaboration with a major pharmaceutical company announced by ReNeuron on April 7, 2020 (http://www.reneuron.com/wp-content/uploads/RENE-Exosome-research-collabo...), reflecting the increasing level of industry interest in exosomes. ReNeuron has developed exosomes derived from hNSCs that have a natural ability to cross the blood-brain barrier and can thus be used to deliver therapeutics for diseases of the brain. The hNSC-derived exosomes can be produced through a fully-qualified, xeno-free, scalable process and the clinical-grade hNSC source cell-line ensures consistent exosome product.