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Category: neuroscience – Page 80

Histone proteins provide essential structural support for DNA in chromosomes, acting as spools around which DNA strands wrap. These proteins have been well studied, but most current tools to study gene expression rely on RNA sequencing. Histone RNA is unique in that its structure prevents the RNA molecules from being detected by current methods.

Thus, the expression of histone genes may be significantly underestimated in tumor samples. The researchers hypothesized that the increased proliferation of cancer cells leads to a very elevated expression, or hypertranscription, of histones to meet the added demands of cell replication and division.

To test their hypothesis, the researchers used CUTAC profiling to examine and map RNAPII, which transcribes DNA into precursors of messenger RNA. They studied 36 FFPE samples from patients with meningioma – a common and benign brain tumor – and used a novel computational approach to integrate this data with nearly 1,300 publicly available clinical data samples and corresponding clinical outcomes.

In tumor samples, the RNAPII enzyme signals found on histone genes were reliably able to distinguish between cancer and normal samples.

RNAPII signals on histone genes also correlated with clinical grades in meningiomas, accurately predicting rapid recurrence as well as the tendency of whole-arm chromosome losses. Using this technology on breast tumor FFPE samples from 13 patients with invasive breast cancer also predicted cancer aggressiveness.

Using a new technology and computational method, researchers have uncovered a biomarker capable of accurately predicting outcomes in meningioma brain tumors and breast cancers.

Continue reading “RNA polymerase II at histone genes predicts outcome in human cancer” | >

Getting mRNA into the brain could allow scientists to instruct brain cells to produce therapeutic proteins that can help treat or prevent disease by replacing missing proteins, reducing harmful ones, or activating the body’s defenses.

The research team designed and tested a library of lipids to optimize their ability to cross the blood-brain barrier. Through a series of structural and functional analyses, they identified a lead formulation, termed MK16 BLNP, that exhibited significantly higher mRNA delivery efficiency than existing lipid nanoparticles approved by the Food and Drug Administration (FDA). This system takes advantage of natural transport mechanisms within the blood-brain barrier, including caveolae-and γ-secretase-mediated transcytosis, to move nanoparticles across the barrier, say the investigators.

In studies using mouse models of disease, the BLNP platform successfully delivered therapeutic mRNAs to the brain, demonstrating its potential for clinical application.

Scientists have developed a lipid nanoparticle system capable of delivering messenger RNA (mRNA) to the brain via intravenous injection, a challenge that has long been limited by the protective nature of the blood-brain barrier.

The findings, in mouse models and isolated human brain tissue, were published in Nature Materials. They demonstrate the potential of this technology to pave the way for future treatments for a wide range of conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis, brain cancer, and drug addiction.

The blood-brain barrier serves as a protective shield, preventing many substances—including potentially beneficial therapies—from reaching the brain. While previous research introduced a platform for transporting large biomolecules such as proteins and oligonucleotides into the central nervous system, this new study focuses on a different approach: using specially designed lipid nanoparticles to transport mRNA across the barrier.

Continue reading “New lipid nanoparticle platform delivers mRNA to the brain through the blood-brain barrier” | >

How does the human brain learn to see? Research from Max Planck Florida Institute for Neuroscience, Frankfurt Institute for Advanced Studies, and Goethe University Frankfurt explores how early visual experiences restructure circuits in the visual cortex. This research sheds light on the fundamental mechanisms of brain development and visual perception.

Explore the research.

How early visual experience builds reliable brain circuits Because it does it so well, we often take for granted how our brain creates reliable visual representations of our surroundings that are critical for guiding our behavior. While scientists understand a lot about how mature neural circuits support reliable vision, the sequence of developmental events before and after birth that build these circuits is not clear. Collaborating scientists at Max Planck Florida Institute for Neuroscience, the Frankfurt Institute for Advanced Studies, and Goethe University Frankfurt have discovered how early visual experience dramatically changes the brain networks that process vision – changes that are essential for establishing reliable visual perception.

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For the first time, it has been confirmed that individual neurons represent the concepts we learn, regardless of the context in which they are encountered, challenging previous beliefs.

A study led by Dr. Rodrigo Quian Quiroga, head of the Neural Mechanisms of Perception and Memory Research Group at the Hospital del Mar Research Institute, has provided the first direct evidence of how neurons in the human brain store memories independently of the context in which they are acquired.

Published in Cell Reports.

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A research team has identified different subtypes of white matter (WM) astrocytes, including a unique type with the ability to multiply and potentially aid in brain repair. Using single-cell RNA sequencing and spatial transcriptomics, the scientists mapped astrocyte diversity across different brain regions and species, providing the first detailed molecular profile of WM astrocytes.

The team was led by Dr. Judith Fischer-Sternjak from Helmholtz Munich and Ludwig-Maximilians-Universität (LMU) München, alongside Prof. Magdalena Götz from Helmholtz Munich, LMU and the Munich Cluster for Systems Neurology (SyNergy). The research is published in the journal Nature Neuroscience.

Unveiling white matter astrocyte diversity Astrocytes, known for their crucial role in supporting neurons and maintaining brain health, have been predominantly studied in gray matter (GM), which is involved in information processing. However, white matter astrocytes, which support long-range neural connections, remain poorly understood. This study fills a major knowledge gap by showing that WM astrocytes are not a uniform population but consist of distinct subtypes with specialized roles.

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Despite its success, FNP has some limitations: it can’t create stable particles larger than 400 nm, the maximum drug content is about 70 percent, the output is low, and it can only work with very hydrophobic (water-repelling) molecules. These issues arise because the particle core formation and particle stabilization happen simultaneously in FNP. The new SNaP process overcomes these limitations by separating the core formation and stabilization steps.

In the SNaP process, there are two mixing steps. First, the core components are mixed with water to start forming the particle core. Then, a stabilizing agent is added to stop the core growth and stabilize the particles. This second step must happen quickly, less than a few milliseconds after the first step, to control the particle size and prevent aggregation. Current SNaP setups connect two specialized mixers in series, controlling the delay time between steps. However, these setups face challenges, including high costs and difficulties in achieving short delay times needed for small particle formation.

A new approach using 3D printing has solved many of these challenges. Advances in 3D printing technology now allow the creation of precise, narrow channels needed for these mixers. The new design eliminates the need for external tubing between steps, allowing for shorter delay times and preventing leaks. The innovative stacked mixer design combines two mixers into a single setup, making the process more efficient and user-friendly.

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Can you pass me the whatchamacallit? It’s right over there next to the thingamajig.

Many of us will experience “lethologica”, or difficulty finding words, in everyday life. And it usually becomes more prominent with age.

Frequent difficulty finding the right word can signal changes in the brain consistent with the early (“preclinical”) stages of Alzheimer’s disease – before more obvious symptoms emerge.

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Scientists at the Okinawa Institute of Science and Technology (OIST), the National Institute of Information and Communications Technology, and the University of Tokyo have found a mathematical connection between spatial navigation and language processing, creating a model called “Disentangled Successor Information” (DSI).

This model generates patterns that closely resemble the activity of actual brain cells involved in both spatial awareness (place cells and grid cells) and concept recognition (concept cells).

The DSI model shows that the hippocampus and entorhinal cortex— previously known primarily for —likely use comparable computational processes to handle both physical spaces and meaningful ideas or words. Using this shared framework, both types of information can be processed through similar mathematical computations, which could be achieved in the brain by partial activation of specific groups of neurons.

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Mind Control: Past and Future https://www.hks.harvard.edu/sites/default/files/2025-01/24_Meier_02.pdf

On Jan. 28, 2024, Noland Arbaugh became the first person to receive a brain chip implant from Neuralink, the neurotechnology company owned by Elon Musk. The implant seemed to work: Arbaugh, who is paralyzed, learned to control a computer mouse with his mind and even to play online chess.

The device is part of a class of therapeutics, (BCIs), that show promise for helping people with disabilities control prosthetic limbs, operate a computer, or translate their thoughts directly into speech. Current use of the technology is limited, but with millions of global cases of spinal cord injuries, strokes, and other conditions, some estimates put the market for BCIs at around $400 billion in the U.S. alone.

A new discussion paper from the Carr Center for Human Rights welcomes the potential benefits but offers a note of caution drawn from the past, detailing unsettling parallels between an era of new therapies and one of America’s darkest chapters: experiments into psychological manipulation and mind control.

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