A lethal parasite’s secret weapon: infecting non-immune cells

Photomicrograph of spleen tissue showing the presence of numerous Leishmania donovani parasites in the amastigote form they take after infecting a host.
Image Credit: Centers for Disease Control and Prevention

The organisms that cause visceral leishmaniasis, a potentially deadly version of the parasitic disease that most often affects the skin to cause disfiguring disease, appear to have a secret weapon, new research suggests: They can infect non-immune cells and persist in those uncommon environments. 

Researchers found the Leishmania donovani parasites in blood-related stem cells in the bone marrow of chronically infected mice – precursor cells that can regenerate all types of cells in the blood-forming system. The finding may help explain why some people who develop visceral leishmaniasis, which is fatal if left untreated, often also have blood disorders such as anemia. 

Identifying these cells and other unexpected locations in which these parasites live improve scientists’ understanding of the disease and may lead to new treatment options, said senior study author Abhay Satoskar, professor of pathology in The Ohio State University College of Medicine. 

A new bioinfomatics pipeline solves a 50-year-old blood group puzzle

Photo Credit: Belova59

Currently, a lot is known about which genes are responsible for our individual blood groups, however not much is understood about how and why the levels of the blood group molecules differ between one person to another. This can be important for blood transfusion safety. Now a research group at Lund University in Sweden has developed a toolbox that finds the answer – and in doing so, has solved a 50-year-old mystery.

The study was published recently in Nature Communications.

For the past 30 years, the research group in Lund has studied the genetic basis of our many blood groups and their research has laid the foundation for six new blood group systems. On the surface of the red blood cell are found proteins and carbohydrates that are very similar between people.

However, small differences in these molecules have been shown to be due to genetic variants that encode what we know as blood group antigens. What has not been understood until now is why people with the same blood group can have different amounts of a certain blood group antigen on their red blood cells.

Study shows that Basophil Activation Test (BAT) is key for predicting allergic reactions

Photo Credit: Jakub Kapusnak

Researchers have found that BAT was the best biomarker to predict severity and threshold of allergic reactions to eggs

New research, published in the European Journal of Allergy and Clinical Immunology, has found that Basophil Activation Test (BAT) can be used to better detect allergies and predict the severity of allergic reactions than traditional predictions made via clinical criteria.

The MRC-funded Basophil Activation Test to Diagnose Food Allergy (BAT2) Study, led by Professor Alexandra Santos of King’s College London, aimed to identify if BAT testing could be used to predict the risk of severe allergic reactions and/or low threshold of reactivity.

For the study one hundred and fifty children, recruited from specialized tertiary Pediatric Allergy clinics in London, underwent double-blind placebo-controlled food challenge to determine possible allergies to baked egg. Patients who passed this underwent a similar process but this time with loosely cooked egg, with the severity of allergic reactions classified following Practall guidelines.

Researchers uncover critical clues about the origin of heart arrhythmias

Immunofluorescent staining demonstrating fibroblasts expressing the Channelrhodopsin protein in heart scar tissue. The ChR2-expressing fibroblast (green, arrow) is in close proximity to cardiomyocytes (red) within scar.
Image Credit: Courtesy of UCLA Health

In a research article published today in the journal Science, UCLA researchers have found that fibroblasts – scar-forming cells that reside in the scar tissue of an injured heart -- directly play a role in promoting a disturbance of the heart rhythm, otherwise known as an arrhythmia. This finding holds promise for novel approaches to life threatening rhythm problems of the heart. 

Every year in the U.S., sudden cardiac death kills upwards of 350,000 people who have had no previous symptoms of heart disease, and in the majority of cases, the underlying cause is an arrhythmia. While there is a strong association between the amount of scar tissue in the heart and the likelihood of an arrhythmia to occur, whether fibroblasts in scar tissue directly communicated with cardiac muscle cells to promote arrhythmias was not known.

In cardiac scar tissue, cardiac muscle cells are surrounded by cardiac fibroblasts and often come in close contact with cardiac fibroblasts. "For decades, scientists have wondered whether the cardiac fibroblasts are electrically passive and just form scar tissue or whether by coming in close contact with myocytes, they directly increased the excitability of cardiac muscle cells and promoted life threatening arrhythmias in vivo," said Dr. Arjun Deb, senior author, professor of medicine and director of the UCLA Cardiovascular Theme, at the David Geffen School of Medicine. 

Low-grade intestinal inflammation a long time after radiotherapy

Photo Credit: Jo McNamara

Patients who have undergone pelvic radiotherapy may live with low-grade chronic inflammation of the lower intestine 20 years after the treatment. This has been shown in a study by researchers at the University of Gothenburg.

Radiotherapy is often necessary to cure or slow down cancer. Even though today’s radiotherapies feature a high level of precision, healthy tissue in and around the radiation field is still affected. This study highlights a previously unknown side effect of radiotherapy to the lower abdomen.

The mucous membrane of the large intestine is normally protected against contact with bacteria in feces by a thin barrier of mucus. In the current study, researchers at the University of Gothenburg have shown that radiotherapy to the pelvic area affects this thin layer of mucus, allowing bacteria to come into contact with cells on the surface of the intestine. This could be a reason for the low-grade inflammation that the researchers also found in intestines that had been exposed to radiotherapy several years previously.  

Noninvasive, ultrasound-based brain biopsy is feasible

Graduate student Lu Xu wears a device designed by engineers, at Washington University in St. Louis, that targets ultrasound waves to precise spots in the brain. Such targeting is the first step in a sonobiopsy, a noninvasive technique invented by Washington University researchers that uses ultrasound and microbubbles to release biomolecules from brain tumors. The biomolecules then can be collected via a blood draw, analyzed and used to inform treatment decisions. Xu is part of a research team that demonstrated that sonobiopsy is safe and feasible for use in people.
Photo Credit: Courtesy of Hong Chen

The blood-brain barrier, the body’s way of shielding sensitive brain tissue from viruses, toxins and other harmful substances in the blood, can pose a problem for physicians caring for patients with suspected brain diseases such as cancer. Molecular and genetic information would be invaluable for confirming a diagnosis and guiding treatment decisions, but such molecules are normally confined to the brain by the barrier. Neurosurgeons routinely perform surgical brain biopsies to obtain this data on brain tumors, but such procedures carry risks and are not feasible for all tumors or for many other kinds of brain diseases.

Researchers at Washington University in St. Louis have developed an anatomically precise technique called sonobiopsy that uses ultrasound and microbubbles to disrupt the barrier temporarily and allow RNA, DNA and proteins from the brain to spill out into the blood, where they can be detected and analyzed. The researchers developed and previously tested the technique in animals. In a new study, available online in the journal NPJ Precision Oncology, they showed that the technique is feasible and safe for use in people, and could open the door to noninvasive biopsies for suspected brain tumors and other brain diseases.

How the Heart Starts Beating

Researchers were surprised to discover that heart cells in developing zebrafish abruptly start beating all at once, and quickly become regular. Here, heart cells are labeled with green fluorescent protein, which becomes brighter when calcium levels spike during each heartbeat.
Image Credit: Bill Jia

Becoming a full-fledged organism out of a handful of cells, complete with functioning tissues and organs, is a messy yet highly synchronized process that requires cells to organize themselves in a precise manner and begin working together.

This process is especially dramatic in the heart, where static cells must start beating in perfect unison.

Now, a cross-school collaboration led by researchers at Harvard Medical School and Harvard University has provided a glimpse into exactly how cells in the heart start beating.

In a study conducted in zebrafish, the team discovered that heart cells start beating suddenly and all at once as calcium levels and electrical signals increase. Moreover, each heart cell has the ability to beat on its own, without a pacemaker, and the heartbeat can start in different places, the researchers discovered. The findings are published Sep. 27 in Nature.

Tiny CRISPR tool could help shred viruses

Model of a minimal CRISPR-Cas13bt3 molecule generated with a cryo-electron microscope. The RNA to be recognized and cleaved is colored in light blue, while the scissor is formed by the magenta and cyan colored domains. The two loops for controlling the CRISPR-Cas13bt3 are shown in green and red.
 Illustration Credit: Courtesy of the Yang Gao lab/Rice University

Small and precise: These are the ideal characteristics for CRISPR systems, the Nobel-prize winning technology used to edit nucleic acids like RNA and DNA.

Rice University scientists have described in detail the three-dimensional structure of one of the smallest known CRISPR-Cas13 systems used to shred or modify RNA and employed their findings to further engineer the tool to improve its precision. According to a study published in Nature Communications, the molecule works differently than other proteins in the same family.

“There are different types of CRISPR systems, and the one our research was focused on for this study is called CRISPR-Cas13bt3,” said Yang Gao, an assistant professor of biosciences and Cancer Prevention and Research Institute of Texas Scholar who helped lead the study. “The unique thing about it is that it is very small. Usually, these types of molecules contain roughly 1200 amino acids, while this one only has about 700, so that’s already an advantage.”

Double Trouble: Infamous “Eagle Killer” Bacterium Produces Not One, But Two Toxins

Colony of A. hydrillicola
Photo Credit: Lenka Štenclová

The cyanobacterium Aetokthonos hydrillicola produces not just one, but two highly potent toxins. In the latest issue of the journal Proceedings of the National Academy of Sciences (PNAS), an international team led by Martin Luther University Halle-Wittenberg (MLU) and Freie Universität Berlin describes the second toxin, which had remained elusive until now. Even in low concentrations, it can destroy cells and is similar to substances currently used in cancer treatment. Two years ago, the same team established that the first toxin from the cyanobacterium is the cause of a mysterious disease among bald eagles in the USA.

Aetokthonos hydrillicola is particularly challenging for researchers. It is notoriously difficult to cultivate and produces one of its toxins only under specific conditions. The fact that it produces two toxins with very different chemical makeups is also unusual. Cyanobacteria normally produce only one toxin - and A. hydrillicola was established as the source of aetokthonotoxin in 2021. This discovery was made by Professor Susan Wilde from the University of Georgia (USA) and Professor Timo Niedermeyer, who worked at MLU until July 2023 and has now joined the researchers at Freie Universität Berlin. This toxin solved a riddle that had kept scientists busy for decades: it triggers the disease vacuolar myelinopathy (VM) among bald eagles in the United States. VM causes holes to form in the brain and, as a result, the birds lose control of their bodies. Science ran the breakthrough as a cover story at the time, and the international team picked up several awards for its work.

Increasing Steps by 3,000 Per Day Can Lower Blood Pressure in Older Adults

Photo Credit: Noelle Otto

An estimated 80% of older adults in the U.S. have high blood pressure. Maintaining healthy blood pressure can protect against serious conditions like heart failure, heart attacks, and strokes.

A new study including Linda Pescatello, distinguished professor of kinesiology in the College of Agriculture, Health and Natural Resources, found that adding a relatively minimal amount of movement, about 3,000 steps per day, can significantly reduce high blood pressure in older adults.

Pescatello worked with Elizabeth Lefferts, the lead author of the paper, Duck-chun Lee, and others in Lee’s lab at Iowa State University. They published their findings in a recent issue of the Journal of Cardiovascular Development and Disease.

“We’ll all get high blood pressure if we live long enough, at least in this country,” Pescatello says. “That’s how prevalent it is.”

Pescatello is an expert on hypertension (the clinical term for high blood pressure) and exercise. Her previous research has demonstrated that exercise can have a significant immediate and long-lasting impact on lowering blood pressure in hypertensive adults.

Researchers Develop AI Model to Improve Tumor Removal Accuracy During Breast Cancer Surgery

Radiology-specific
Image Credit: Courtesy of UNC School of Medicine

Kristalyn Gallagher, DO, Kevin Chen, MD, and Shawn Gomez, EngScD, in the UNC School of Medicine have developed an AI model that can predict whether or not cancerous tissue has been fully removed from the body during breast cancer surgery.

Artificial intelligence (AI) and machine learning tools have received a lot of attention recently, with the majority of discussions focusing on proper use. However, this technology has a wide range of practical applications, from predicting natural disasters to addressing racial inequalities and now, assisting in cancer surgery.

A new clinical and research partnership between the UNC Department of Surgery, the Joint UNC-NCSU Department of Biomedical Engineering, and the UNC Lineberger Comprehensive Cancer Center has created an AI model that can predict whether or not cancerous tissue has been fully removed from the body during breast cancer surgery. Their findings were published in Annals of Surgical Oncology.

Widely-used COVID-19 antiviral could be helping SARS-CoV-2 to evolve

Image Credit: visuals3Dde

The drug works by disrupting the virus’s genome, causing it to develop random mutations as it replicates, weakening the virus to prevent replication, thereby enabling clearance of infection.

But in research published today in Nature, scientists have shown that in some cases, mutated forms of the virus have been able to be transmitted from patients treated with molnupiravir and spread within the community.

Dr Christopher Ruis from the Department of Medicine at the University of Cambridge said: “Molnupiravir is one of a number of drugs being used to fight COVID-19. It belongs to a class of drugs that can cause the virus to mutate so much that it is fatally weakened. But what we’ve found is that in some patients, this process doesn’t kill all the viruses, and some mutated viruses can spread. This is important to take into account when assessing the overall benefits and risks of molnupiravir and similar drugs.”

Molnupiravir, marketed under the brand name Lagevrio, is licensed for the treatment of COVID-19 in several countries, including the UK, USA and Japan. It has been used to treat the disease since late 2021.

Could seaweed hold the key to the fountain of youth?

Photo Credit: Kindel Media

Scientists from Flinders University have discovered rich anti-aging properties in South Australian brown seaweed that significantly increase collagen levels in the skin and protect against the deterioration of both collagen and elastin.

“We found that extracts from South Australian brown seaweed have huge potential to be used to help slow the effects of aging on our skin,” says Professor Wei Zhang, College of Medicine and Public Health.

“Collagen acts as a building block for bones, teeth, muscles, skin, joints and connective tissue, while elastin gives skin its elasticity and strength – and both these proteins are popularly promoted by the beauty industry as essential for the appearance of healthy skin,” he says.

Professor Zhang explains the Flinders team has found that extracts from SA’s brown seaweed not only stimulated the growth of collagen, but also inhibited a process called glycation, which leads to the deterioration of collagen and elastin.

“So far anti-glycation agents haven’t been strong enough to have a major impact on anti-aging, so our discovery is really exciting as we can see the potential to develop stronger anti-glycation extracts from brown seaweed.”

Simple maintenance can reduce hospital Legionella risks

Photo Credit: PublicDomainPictures

Hospital water systems are a significant source of Legionella, resulting in the potentially fatal Legionnaires’ disease – but Flinders University researchers have proven simple maintenance that involves running hot water regularly and flushing the pipes has a huge effect in reducing the risk of the disease.

One of the biggest challenges for Legionella management within large hospital systems is that under unfavorable conditions, Legionella transforms itself into a state (called viable but non culturable – VBNC) that cannot be detected using standard methods.

To understand the extent of the problem, Flinders University researchers conducted the first comprehensive study that quantified all Legionella, including those in the VBNC state, and free-living amoebae from a hospital water system under dynamic flow and temperature conditions.

“We took a different approach because we didn’t know how often the standard method was returning false negative results for Legionella and it’s really hard to determine the optimal management approach if you can’t trust your testing method,” says Flinders University’s Associate Professor Harriet Whiley.

Diagnosis of rare, genetic muscle disease improved by new approach

Researchers at Washington University School of Medicine in St. Louis have developed an approach that could help doctors distinguish between the many subtypes of limb girdle muscular dystrophy, a rare, genetic muscle disease. With new therapies poised to enter the clinic, identifying the precise subtype is necessary to ensure that people get access to the treatment most likely to benefit them.
Image Credit: ANIRUDH

It’s not easy to distinguish between the dozens of subtypes of limb girdle muscular dystrophy — a rare, genetic muscle disease characterized by weakness in the hips and shoulders that causes difficulty walking and lifting the arms. Until now, determining the subtype has not been critical in caring for patients, because no specific treatments have been available. But gene therapies are on the horizon, and such therapies are targeted to specific genetic variants, so pinpointing the genetic roots of each patient’s disease has taken on a new importance.

In new research, a team at Washington University School of Medicine in St. Louis has developed an approach that could help doctors make more precise diagnoses. The study is published June 15 in The Journal of Clinical Investigation.

Hundreds of genes are associated with limb girdle muscular dystrophy. While genetic testing may identify a handful of rare genetic variants in each patient with the condition, there’s no way to know without painstaking, time-consuming additional experiments which, if any, of those variants is responsible for a patient’s symptoms. Unfortunately, no comprehensive catalog exists yet of all the variants of all the genes linked to limb girdle muscular dystrophy, and whether each of those variants can cause disease or is harmless.

Pharmacy researcher develops intervention for metabolic diseases like diabetes, stroke and heart disease

Photo Credit: Michal Jarmoluk

An investigator with the University of Kansas School of Pharmacy has filed an invention disclosure, part of a provisional patent application with the United States Patent and Trademark Office, for a treatment that could apply to heart disease, stroke and a host of other human diseases related to metabolism.

Liqin Zhao, KU associate professor of pharmacology & toxicology and investigator at the Life Span Institute2, has researched the human ApoE gene for years. A major focus of her work centers on how the ApoE2 variant — one of three major isoforms of ApoE gene — might protect people from Alzheimer’s disease3.

Now, based upon a discovery made during her Alzheimer’s-disease work, Zhao is patenting a way to leverage rhApoE2 to regulate blood lipids. Lipids, like fats and oils, are building materials of life at the cellular level that also are tied to heart disease and other metabolic diseases.

“In essence, we found that rhApoE2 significantly lowered blood levels of a number of ceramides,” Zhao said. “Moreover, rhApoE2 increased blood levels of a variety of ‘good triglycerides’ — triglycerides that contain health-promoting, long-chain polyunsaturated fatty acids such as alpha-linolenic acid, EPA and DHA, and lowered levels of ‘bad triglycerides,’ or triglycerides that contain saturated or monosaturated fatty acids that can impose a cardiovascular risk.”

Post-traumatic stress affects more than one in 10 cardiac device patients

Image Credit: Joshua Chehov

Nearly one-third of patients with an implanted device to prevent sudden death have anxiety in the first year, while depression affects one in five. That’s the finding of a study published this week in EP Europace, a journal of the European Society of Cardiology (ESC).

Lead author Professor Hannah Keage from the University of South Australia says implantable cardioverter defibrillators (ICDs) are effective at extending patients’ lives, “but we need to make sure that is a good quality life”.

“Rates of mood disorders in people with an ICD are much higher than in the general population, suggesting that psychological assessment and therapy should be integrated into the routine care of these patients,” Prof Keage says.

An ICD is recommended for people at high risk of a life-threatening heart rhythm and those who have had a cardiac arrest. Anxiety and depression are associated with a higher likelihood of premature death in patients with an ICD.

The study compiled the best available evidence to determine levels of depression, anxiety, and post-traumatic stress disorder (PTSD) in patients with an ICD.

Researchers created a new and improved way to view the mechanics of life

RESORT. A diagram to show the basic overview of the system. Firstly, the sample is labeled with the photoswitchable Raman probe. It’s then irradiated with two-color infrared laser pulses, ultraviolet light, and a special donut-shaped beam of visible light to constrain the area where Raman scattering can occur. As a result, the probe can be detected at a very precise point for high spatial resolution images.
Illustration Credit: ©2023 Ozeki et al.
(CC BY 2.0)

There are various ways to image biological samples on a microscopic level, and each has its own pros and cons. For the first time, a team of researchers, including those from the University of Tokyo, has combined aspects from two of the leading imaging techniques to craft a new method of imaging and analyzing biological samples. Its concept, known as RESORT, paves the way to observe living systems in unprecedented detail.

For as long as humanity has been able to manipulate glass, we have used optical devices to peer at the microscopic world in ever increasing detail. The more we can see, the more we can understand, hence the pressure to improve upon tools we use to explore the world around, and inside, us. Contemporary microscopic imaging techniques go far beyond what traditional microscopes can offer. Two leading technologies are super-resolution fluorescence imaging, which offers good spatial resolution, and vibrational imaging, which compromises spatial resolution but can use a broad range of colors to help label many kinds of constituents in cells.

Pregnancy hormone repairs myelin damage in MS mouse model

Photo Credit: Yassine Khalfalli

Treating a mouse model of multiple sclerosis with the pregnancy hormone estriol reversed the breakdown of myelin in the brain’s cortex, a key region affected in multiple sclerosis, according to a new UCLA Health study.

In multiple sclerosis, inflammation spurs the immune system to strip away the protective myelin coating around nerve fibers in the brain’s cortex, hampering electrical signals sent and received by the brain. Atrophy of the cortex in MS patients is associated with permanent worsening of disability, such as cognitive decline, visual impairment, weakness and sensory loss.

No currently available treatments for MS can repair damage to myelin. Instead, these treatments target inflammation to reduce symptom flare-ups and new nerve tissue scarring. Previous UCLA-led research found that estriol, a type of estrogen hormone produced in pregnancy, reduced brain atrophy and improved cognitive function in MS patients.

In the new study, researchers treated a mouse model of MS with estriol and found that it prevented brain atrophy and induced remyelination in the cortex, indicating that the treatment can repair damage caused by MS, rather than just slow the destruction of myelin.

Altered gut bacteria may be early sign of Alzheimer’s disease

 

Alzheimer’s disease causes changes to the brain that begin two decades or more before symptoms appear. A study by researchers at Washington University School of Medicine in St. Louis reveals that the bacteria that live in the gut also change before Alzheimer’s symptoms arise, a discovery that could lead to diagnostics or treatments for Alzheimer’s disease that target the gut microbiome.
Image Credit: Gerd Altmann

People in the earliest stage of Alzheimer’s disease — after brain changes have begun but before cognitive symptoms become apparent — harbor an assortment of bacteria in their intestines that differs from the gut bacteria of healthy people, according to a study by researchers at Washington University School of Medicine in St. Louis.

The findings, published June 14 in Science Translational Medicine, open up the possibility of analyzing the gut bacterial community to identify people at higher risk of developing dementia, and of designing microbiome-altering preventive treatments to stave off cognitive decline.

“We don’t yet know whether the gut is influencing the brain or the brain is influencing the gut, but this association is valuable to know in either case,” said co-corresponding author Gautam Dantas, PhD, the Conan Professor of Laboratory and Genomic Medicine. “It could be that the changes in the gut microbiome are just a readout of pathological changes in the brain. The other alternative is that the gut microbiome is contributing to Alzheimer’s disease, in which case altering the gut microbiome with probiotics or fecal transfers might help change the course of the disease.”