Lifeboat Foundation

Women are more likely than men to have conditions such as lupus, rheumatoid arthritis, and autoimmune hepatitis (depicted above in a cellular micrograph), in which their immune response attacks healthy, functioning parts of their body. Yet the reason behind this sex-based imbalance has long eluded scientists. Now, a study published last week in proposes that a molecule associated with the X chromosome may be partly to blame. Researchers noticed that many of the proteins commonly targeted by the immune system in people with autoimmune diseases had something in common: They help a molecule called Xist carry out its function. Xist molecules act a bit like quality control inspectors for women’s extra X chromosomes, preventing them from producing a toxic amount of proteins. The scientists suspect that when immune cells encounter large bunches of these Xist-related proteins—for instance, when a dead cell spills them into the bloodstream—they may react by making antibodies to attack them throughout the body. To test the idea, the team studied genetically engineered mice in which both males and females produced Xist. Like their female counterparts, these males were also at an increased risk of developing severe cases of lupus. The researchers also found that people with autoimmune disorders had more antibodies for Xist-related proteins in their blood. Still, Xist molecules may not be the only factor at play: Experts note that some people produce these Xist-related antibodies without developing autoimmune disorders, reports.

A new study adds to the growing literature showing that motor neurons are not the only sites affected in amyotrophic lateral sclerosis, writes Dr. Leana Doherty.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor neurons. However, nonmotor manifestations, including sensory, cognitive, and autonomic impairments, increasingly have been reported. In the current study, investigators examined cutaneous innervation and its correlation with disease severity in patients with ALS using the Small Fiber Neuropathy Symptoms Inventory Questionnaire, nerve conduction studies, and distal leg, thigh, and fingertip (glabrous skin) punch biopsies. Patients with alternate diagnoses including endocrinopathies, autoimmune disorders, and vitamin deficiencies were excluded.

Among 149 participants with ALS (mean age, 63; median disease duration, 14.3 months), 35% experienced large-fiber or small-fiber sensory symptoms or both. The frequency of small-fiber symptoms was higher in patients with more severe disease based on King’s staging; scores increase on the scale from 1 to 5 with increasing regions involved. Nearly one quarter of patients had one or more sensory nerve action potential abnormalities. The density of Meissner corpuscles (MC) was reduced in most ALS patients (53÷100), and intraepidermal nerve fiber (IENF) density was reduced at all sites (5th percentile: at the leg, 58%; thigh, 78%) compared with healthy controls. While MC density decreased with increasing King’s stage, IENF density increased. Increasing IENF density on repeat thigh biopsies at 6 and 12 months was associated with shorter survival. The researchers postulated that this may reflect an upregulation of reparative pathways paralleling disease aggressiveness.

Continue reading “Peripheral Sensory Abnormalities in ALS” »

A team of researchers at the Carl Gustav Carus Faculty of Medicine, TUD Dresden University of Technology, led by Prof. Frank Buchholz, has achieved a major breakthrough in genome editing technology. They’ve developed a cutting-edge method that combines the power of designer-recombinases with programmable DNA-binding domains to create precise and adaptable genome editing tools.

Traditional genome editing faced limitations in achieving ultimate precision until now. Prof. Buchholz’s team has broken through this barrier by creating what many have sought after: a zinc-finger conditioned recombinase. This innovative approach involves integrating a zinc-finger DNA-binding domain into specially designed recombinases. These enzymes remain inactive until the DNA-binding domain engages with its target site, adjacent to the recombinase binding area.

The significance of this achievement lies in the fusion of two key strengths: the targeting ease of programmable nucleases and the precise DNA editing capabilities of recombinases. This breakthrough overcomes existing limitations in genome editing techniques and holds vast promise for therapeutic gene editing and various biomedical applications.

For years, there has been a long-held belief that acute viral infections like Zika or COVID-19 are directly responsible for neurological damage, but researchers from McMaster University have now discovered that it’s the immune system’s response that is behind it.

The research, published on Feb. 5, 2024, in Nature Communications, was led by Elizabeth Balint, a Ph.D. student at McMaster, and Ali Ashkar, a professor with the Department of Medicine and the Canada Research Chair in Natural Immunity and NK Cell Function.

“We were interested in trying to understand why so many viral infections are associated with neurological diseases,” says Balint. “Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage.”

Acetamiprid-induced oxidative stress can harm DNA and tRNA, leading to health problems. A study conducted by Huixia Zhang at Macau University of Science and Technology in 2023 introduced a comprehensive approach to assessing acetamiprid-induced oxidative damage to tRNA in human cells through oxidized nucleotide and tRNA profiling. Acetamiprid, a modern insecticide, is known for causing oxidative stress and related toxicity. Despite its impact on oxidative stress, the effects of acetamiprid-induced oxidative stress on RNA, especially tRNA, remained unexplored until this study.

Acetamiprid was found to elevate reactive oxygen species (ROS) production in HepG2 and LO2 cells, contributing to mitochondrial damage, free radical generation, and antioxidant status depletion. Oxidative damage to DNA and RNA can harm organisms, with prior research addressing RNA damage in aging, neurodegenerative diseases, and mental illnesses. However, its role in acetamiprid-induced toxicities has not been investigated.

The study employed TMSD labeling-based LC-MS/MS to measure oxidized nucleotide levels in HepG2 and LO2 cells treated with two mM acetamiprid. It also examined the impact of acetamiprid on the 8-oxo-G content of tRNAs and created volcano plots to compare RNase T1 digestion products of tRNAs from untreated and acetamiprid-treated cells.

Immune guardians called complement proteins are manufactured by gut cells and help to protect against pathogens.

A team of scientists at the University of Wisconsin-Madison claim to have 3D-printed functional human brain tissue for the first time.

They hope their research could open the doors for the development of treatments for existing neurological disorders, including Alzheimer’s and Parkinson’s disease.

As detailed in a new paper published in the journal Cell Stem Cell, the team flipped the usual method of 3D-printing on its side, fabricating horizontal layers of brain cells encased in soft “bio-ink” gel.

Two decades ago, engineering designer proteins was a dream.

Now, thanks to AI, custom proteins are a dime a dozen. Made-to-order proteins often have specific shapes or components that give them abilities new to nature. From longer-lasting drugs and protein-based vaccines, to greener biofuels and plastic-eating proteins, the field is rapidly becoming a transformative technology.

Custom protein design depends on deep learning techniques. With large language models—the AI behind OpenAI’s blockbuster ChatGPT—dreaming up millions of structures beyond human imagination, the library of bioactive designer proteins is set to rapidly expand.