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Category: neuroscience

IPSC-induced multilineage liver organoids, small intestinal organoids and brain organoids sustain pangenotype hepatitis E virus propagation

Liu et al. present via https://bit.ly/4bV6X0s (Original research, Hepatology section).

A major step forward for translational research, this study shows that human organoid systems can support replication of multiple hepatitis E virus genotypes—offering a powerful new platform for studying infection and testing therapies.

Background Hepatitis E virus (HEV), the leading global cause of acute viral hepatitis, lacks robust in vitro models for virology and pathogenesis research.

Objective We evaluated induced pluripotent stem cell (iPSC)-induced human liver, intestinal and brain organoids (hLOs, hIOs and hBOs) as platforms for HEV infection and replication.

Methods Multilineage organoids were infected with clinical HEV genotypes 1, 3 and 4. Viral tropism, host responses and antiviral efficacy were assessed.

Results All organoids supported the complete life cycle of HEV. hLOs exhibited infection in hepatocytes, cholangiocytes, macrophages and stellate cells, accompanied by elevated interleukin-6 levels, impaired hepatic function (reduced secretion of albumin and Factor IX) and increased levels of alanine aminotransferase and aspartate aminotransferase, indicating hepatocellular injury.

Continue reading “IPSC-induced multilineage liver organoids, small intestinal organoids and brain organoids sustain pangenotype hepatitis E virus propagation” | >

Fluid restriction in patients with heart failure: a systematic review

Background Fluid restriction is a commonly prescribed non-pharmacological intervention in the management of heart failure (HF). However, data on its efficacy and safety are scarce. Recent randomised clinical trial (RCT) data prompt reassessment of the available evidence.

Methods CINAHL, EMBASE, PubMed and the Cochrane Library were searched up to 1 May 2025. RCTs were included if adults with HF were randomised to fluid restriction in comparison to a liberal or unrestricted intake, less strict restriction or usual care. Outcomes of interest were mortality, HF hospitalisation, quality of life (QoL), thirst distress, New York Heart Association (NYHA) class and N-terminal pro-Brain Natriuretic Peptide (CRD42022292319). No meta-analysis was performed due to high heterogeneity of the included trials.

Results In total, four RCTs were included, comprising 682 randomised inpatient, recently discharged and stable outpatient patients (ranging from 46 to 504 patients per trial). Only one study had a low risk of bias. None of the four trials found a significant difference in mortality or HF hospitalisations. For QoL, the results are contradictory, but overall, there is no clear benefit for fluid restriction, but it resulted in more thirst distress. No significant differences in NYHA class or (NT-pro)BNP were observed.

What changes happen in the aging brain?

A new study from the Salk Institute maps how the aging brain changes at the epigenetic level — cell type by cell type.

The researchers created one of the most detailed single-cell atlases yet of the aging mouse brain, spanning 8 brain regions, 36 cell types, and hundreds of thousands of cells. They found major age-related changes in DNA methylation, chromatin structure, and gene activity, with some of the strongest changes appearing in non-neuronal cells.

This kind of work matters because it moves brain aging closer to mechanism — not just describing decline, but identifying the molecular regulatory shifts that may drive vulnerability to neurodegenerative disease.

Highlights Salk researchers create epigenetic atlas of cell type-specific changes in the aging mouse brain The atlas represents eight different brain regions and 36 different cell types, and shows clear epigenetic differences associated with different ages The new resource—available publicly on Amazon Web services—can be used to unravel age-related contributions to neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS LA JOLLA—Neurodegenerative diseases affect more than 57 million people globally. The incidence of these diseases, from Alzheimer’s to Parkinson’s to ALS and beyond, is expected to double every 20 years. Though scientists know aging is a major risk factor for neurodegenerative diseases, the full mechanisms behind aging’s impact remain unclear.

Small RNAs offer new clues to schizophrenia and bipolar disorder

For decades, scientists studying brain disorders have focused almost exclusively on proteins and the genes encoding them. Now, research from Thomas Jefferson University’s Computational Medicine Center suggests that several classes of small regulatory molecules, fittingly known as small RNAs, may play a much larger role in schizophrenia and bipolar disorder, and in a healthy brain, than previously thought.

In a study recently published in Translational Psychiatry, a team led by Isidore Rigoutsos, Ph.D. took a comprehensive look at small RNAs in brain samples from people with schizophrenia, bipolar disorder and individuals without psychiatric illness. Their goal was to find out what kind of small RNAs are active in the brain, and whether their levels change in disease.

“Little attention had been paid to small RNAs in these disorders,” says Dr. Rigoutsos, “even though small RNAs help control numerous processes by modulating the abundance of genes.”

Brain computer interface enables rapid communication for two people with paralysis

Researchers from Brown University and Mass General Brigham have developed an implantable brain-computer interface that allowed two people with paralysis — one with ALS and one with a spinal cord injury — to communicate through rapid, accurate typing. The system uses microelectrode sensors in the motor cortex, maps letters to attempted finger movements on a QWERTY keyboard, and decodes those neural signals into text.

In the study, one participant reached a top speed of 110 characters per minute (about 22 words per minute) with a 1.6% word error rate, and both participants were able to use the system from home after calibration with as few as 30 sentences. The results were published in Nature Neuroscience.

This is the kind of neurotechnology that starts to close the gap between thought and communication.

Implantable device research from the BrainGate clinical trial enables communication through rapid typing for a patient with ALS and a patient with a spinal cord injury.

A foundation model of vision, audition, and language for in-silico neuroscience

‘The present results strengthen the possibility of a paradigm shift in neuroscience… moving from the fragmented mapping of isolated cognitive tasks toward the use of unified, predictive foundation models of brain and cognitive functions By aligning the representations of Al systems to those of the human brain, we demonstrate that a single architecture can integrate a vast range of fMRI responses across hundreds of individuals, extending the framework that led the 2025 Algonauts competition. The observed log-linear scaling of encoding accuracy mirroring power laws in both artificial intelligence and neuroscience suggests that the ceiling for predicting human brain activity is yet to be reached.’

Cognitive neuroscience is fragmented into specialized models, each tailored to specific experimental paradigms, hence preventing a unified model of cognition in the human brain. Here, we introduce TRIBE v2, a tri-modal (video, audio and language) foundation model capable of predicting human brain activity in a variety of naturalistic and experimental conditions. Leveraging a unified dataset of over 1,000 hours of fMRI across 720 subjects, we demonstrate that our model accurately predicts high-resolution brain responses for novel stimuli, tasks and subjects, superseding traditional linear encoding models, delivering several-fold improvements in accuracy. Critically, TRIBE v2 enables in silico experimentation: tested on seminal visual and neuro-linguistic paradigms, it recovers a variety of results established by decades of empirical research.

Characterization of a Splice Variant in FLNA Associated With Periventricular Nodular Heterotopia

This study broadens the phenotypic and genetic spectrum of PNH, demonstrating a dual PNH phenotype associated with a bi‑transcript mechanism and mosaic inheritance, including tissue‑specific mosaicism.

PNH is a neurodevelopmental brain malformation characterized by failure of the gray matter to properly migrate to the cerebral cortex during embryonic development. This results in ectopic localization around the ventricular ependyma.1 MRI serves as the primary diagnostic tool, showing bilateral periventricular gray matter nodules with a signal intensity similar to that of normal cortical gray matter.2,3 Its primary clinical manifestation is epilepsy, which is often accompanied by intellectual disabilities and learning difficulties.2,3 PNH is genetically heterogeneous and is linked to variants in multiple genes, including ARFGEF2, ERMARD, NEDD4L, ARF1, and MAP1B, as well as abnormalities in chromosome 5. Among these, pathogenic variants in FLNA are the most common genetic causes.4

FLNA is located at Xq28 and comprises 47 exons,5 encoding a 280 kDa actin binding protein, called filamin A. The N-terminal region contains an actin binding domain (ABD) and a rod-like structure composed of 24 immunoglobulin-like repeats. ABD interacts with actin to stabilize the cytoskeletal architecture and plays crucial roles in maintaining cell shape, migration, and transmitting mechanical force. FLNA regulates cellular migration and extension processes via interactions with several signaling proteins, including small GTPases Rac/Rho, TRAF2, integrins, and BRCA2.6–8 This gene possesses at least 2 transcription initiation sites (ENST00000369850.8 and ENST00000610817.4) that use distinct promoters and demonstrate tissue-specific expression.6–8 Rat FLNA-knockdown models exhibit impaired neuronal migration and elevated epileptic susceptibility.

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