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‘ALS on a chip’ model reveals altered motor neuron signaling

Using stem cells from patients with ALS (amyotrophic lateral sclerosis), Cedars-Sinai has created a lifelike model of the mysterious and fatal disease that could help identify a cause of the illness as well as effective treatments.

In a study published in the journal Cell Stem Cell, investigators detail how they created “ALS on a chip” and the clues the specialized laboratory chip has already produced about nongenetic causes of the disease, also known as Lou Gehrig’s disease.

The work builds on previous studies where adult cells from ALS patients were reverted into . The cells were then pushed forward to produce motor neurons, which die in the disease, causing progressive loss of the ability to move, speak, eat and breathe.

A Novel Platform for Root Protection Applies New Root-Coating Technologies to Mitigate Soil-Borne Tomato Brown Rugose Fruit Virus Disease

Tomato brown rugose fruit virus (ToBRFV) is a soil-borne virus showing a low percentage of ca. 3% soil-mediated infection when the soil contains root debris from a previous 30–50 day growth cycle of ToBRFV-infected tomato plants. We designed stringent conditions of soil-mediated ToBRFV infection by increasing the length of the pre-growth cycle to 90–120 days, adding a ToBRFV inoculum as well as truncating seedling roots, which increased seedling susceptibility to ToBRFV infection. These rigorous conditions were employed to challenge the efficiency of four innovative root-coating technologies in mitigating soil-mediated ToBRFV infection while avoiding any phytotoxic effect. We tested four different formulations, which were prepared with or without the addition of various virus disinfectants. We found that under conditions of 100% soil-mediated ToBRFV infection of uncoated positive control plants, root-coating with formulations based on methylcellulose (MC), polyvinyl alcohol (PVA), silica Pickering emulsion and super-absorbent polymer (SAP) that were prepared with the disinfectant chlorinated-trisodium phosphate (Cl-TSP) showed low percentages of soil-mediated ToBRFV infection of 0%, 4.3%, 5.5% and 0%, respectively. These formulations had no adverse effect on plant growth parameters when compared to negative control plants grown under non ToBRFV inoculation conditions.

New MRI approach maps brain metabolism, revealing disease signatures

A new technology that uses clinical MRI machines to image metabolic activity in the brain could give researchers and clinicians unique insight into brain function and disease, researchers at the University of Illinois Urbana-Champaign report. The non-invasive, high-resolution metabolic imaging of the whole brain revealed differences in metabolic activity and neurotransmitter levels among brain regions; found metabolic alterations in brain tumors; and mapped and characterized multiple sclerosis lesions—with patients only spending minutes in an MRI scanner.

Led by Zhi-Pei Liang, a professor of electrical and computer engineering and a member of the Beckman Institute for Advanced Science and Technology at the U. of I., the team reported its findings in the journal Nature Biomedical Engineering.

“Understanding the brain, how it works and what goes wrong when it is injured or diseased is considered one of the most exciting and challenging scientific endeavors of our time,” Liang said. “MRI has played major roles in unlocking the mysteries of the brain over the past four decades. Our new technology adds another dimension to MRI’s capability for brain imaging: visualization of brain metabolism and detection of metabolic alterations associated with brain diseases.”

Cerebellum may set the stage for development of mental empathy in early childhood

We can’t see what other people are thinking, so we have to infer it and that’s very crucial for our communication as humans. That’s how we create shared meaning and that’s how we choose our words to be understood, a kind of mental empathy.

A pivotal milestone in the development of Theory of Mind reasoning occurs between the ages of 3 and 5 years, a breakthrough period in which children typically start succeeding in false-belief tasks, widely regarded as a critical test of Theory of Mind abilities. These tasks require children to recognize false beliefs held by a story character, typically in the context of the character’s mental misrepresentations regarding an object’s location, content, or nature. Successfully passing false-belief tasks is argued to reflect the emergence of representations of others’ mental states.

To find out more about this critical period where evolves, scientists from the Max Planck Institute for Human Cognitive and Brain Sciences used collected data from 41 children between 3 and 12 years old.

Gene editing treats smooth muscle disease in preclinical model

Using gene editing in a preclinical model, researchers at UT Southwestern Medical Center blocked the symptoms of a rare smooth muscle disease before they developed. Their findings, published in Circulation, could eventually lead to gene therapies for this and other genetic diseases affecting smooth muscle cells.

“Gene editing has been used in other disease contexts, but its application to inherited vascular diseases, particularly targeting in vivo, is still emerging. Our approach advances the field by demonstrating functional correction in a cell type that’s notoriously difficult to target,” said Eric Olson, Ph.D., Chair and Professor of Molecular Biology and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Dr. Olson co-led the study with Ning Liu, Ph.D., Professor of Molecular Biology, and first author Qianqian Ding, Ph.D., postdoctoral researcher, both members of the Olson Lab.

Rare Gene Mutation Delays Alzheimer’s by Damping Immune Cell Inflammatory Signaling

Researchers at Weill Cornell Medicine report that a rare gene mutation that delays Alzheimer’s disease does so by damping inflammatory signaling in brain-resident immune cells in a preclinical study. The finding adds to growing evidence that brain inflammation is a major driver of neurodegenerative disorders such as Alzheimer’s—and that it may be a key therapeutic target for these disorders.

In their study “The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway,” in Immunity, the investigators examined the effects of the mutation APOE3-R136S—known as the “Christchurch mutation”—which was recently found to delay hereditary early-onset Alzheimer’s. The scientists showed that the mutation inhibits the cGAS-STING pathway, an innate immune signaling cascade that is abnormally activated in Alzheimer’s and other neurodegenerative diseases. The researchers found that pharmacologically blocking the cGAS-STING pathway with a drug-like inhibitor replicated key protective effects of the mutation in a preclinical model.

“This is an exciting study because it suggests that inhibiting this cGAS-STING pathway could make the brain more resistant to the Alzheimer’s process, even in the face of significant tau accumulation,” said study senior author Li Gan, PhD, the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases and director of the Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell Medicine.

Two-step system makes plastic from carbon dioxide, water and electricity

What if a machine could suck up carbon dioxide from the atmosphere, run it through a series of chemical reactions, and essentially spit out industrially useful plastic?

“I think that is something that we, as a society, would be interested in. After all, in addition to being a , carbon dioxide is an abundant and inexpensive feedstock,” says Theo Agapie, Ph.D., the John Stauffer Professor of Chemistry and the executive officer for chemistry at Caltech. “With our new work, we have taken a significant step in that direction.”

Reporting in the journal Angewandte Chemie International Edition, Agapie and a team of Caltech chemists have developed a system that uses electricity from sustainable sources to carry out the chemical conversion of carbon dioxide (CO2) into molecules, such as ethylene and , that are useful for making more complex compounds.

Turning captured carbon into natural gas could provide cost-competitive energy storage

Solar and wind energy are highly variable, dependent on the day, weather and location of the facilities. At times, they can generate more electricity than is needed, but they can also fall short when demand is at its peak. Unfortunately, any extra energy created by these sources is often wasted, as there are few methods that adequately store it long-term. To improve energy security in the United States, the nation requires both sources of energy and novel ways to store and distribute it.

In a new study, published in Cell Reports Sustainability, researchers from Lawrence Livermore National Laboratory (LLNL) have explored how a reactive capture and conversion (RCC) process could be used to produce synthetic renewable natural gas—a chemical form of long-duration energy storage.

“Rather than sourcing carbon from below-ground, RCC enables the use of above-ground carbon as a resource,” said LLNL scientist and lead author Alvina Aui. “Synthetic renewable natural gas, when used as an energy-storage option, can reduce grid instability caused by the intermittency of energy sources like wind and solar.”

“Delete-To-Recruit” — Scientists Discover Simpler Approach to Gene Therapy

Repositioning genes awakens fetal hemoglobin to treat disease. CRISPR editing may change future gene therapy.

Researchers have discovered a promising new approach to gene therapy by reactivating genes that are normally inactive. They achieved this by moving the genes closer to regulatory elements on the DNA known as enhancers. To do so, they used CRISPR-Cas9 technology to cut out the piece of DNA separating the gene from its enhancer. This method could open up new ways to treat genetic diseases. The team demonstrated its potential in treating sickle cell disease and beta-thalassemia, two inherited blood disorders.

In these cases, a malfunctioning gene might be bypassed by reactivating an alternative gene that is usually turned off. This technique, called “delete-to-recruit,” works by altering the distance between genetic elements without introducing new genes or foreign material. The study was conducted by researchers from the Hubrecht Institute (De Laat group), Erasmus MC, and Sanquin, and published in the journal Blood.