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Category: neuroscience

Organ cross-talk: molecular mechanisms, biological functions, and therapeutic interventions for diseases

3. Pathology as Network Dysregulation.

In recent years, a transformative view of physiology has emerged: the body operates not as isolated organs, but as an integrated communication network in which signals flow bidirectionally between the brain, the immune system, the gut, and peripheral organs. This comprehensive review synthesizes current mechanistic insights into this “organ cross-talk” and frames them within systems biology and neuroscience.

At its core, organ cross-talk encompasses neural, endocrine, metabolic, and immune signaling between organs that coordinate homeostasis and orchestrate responses to stress and disease. From a neuroscience vantage point, three themes stand out:

1. The Brain as a Communication Hub.

2. Peripheral Feedback to the CNS.

Continue reading “Organ cross-talk: molecular mechanisms, biological functions, and therapeutic interventions for diseases” | >

Motor protein discovery in fruit flies may unlock neurodegenerative secrets

Scientists have long known that inherited neurodegenerative disorders, including Alzheimer’s, Parkinson’s or motor neuron disease, can be traced back to genetic mutations. However, how they cause the diseases remains unanswered.

In today’s issue of the journal Current Biology Professor Andreas Prokop revealed that so-called “motor proteins” can provide key answers in this quest.

The research by the Prokop group focuses on nerve fibers, also called axons. Axons are the delicate biological cables that send messages between the brain and body to control our movements and behavior. Intriguingly, axons need to survive and stay functional for our entire lifetime.

Scientists Discover Brain Cancer Begins in “Normal” Cells Long Before Tumors Appear

New research reveals that certain brain tumors may originate silently within normal brain cells long before a tumor forms. IDH-mutant glioma is a malignant brain cancer linked to changes in a single gene (IDH), and it is the most common malignant brain tumor in adults younger than 50. Doctors oft

NVIDIA Releases PersonaPlex-7B-v1: A Real-Time Speech-to-Speech Model Designed for Natural and Full-Duplex Conversations

PersonaPlex runs in a dual stream configuration. One stream tracks user audio, the other stream tracks agent speech and text. Both streams share the same model state, so the agent can keep listening while speaking and can adjust its response when the user interrupts. This design is directly inspired by Kyutai’s Moshi full duplex framework.

NVIDIA Researchers released PersonaPlex-7B-v1, a full duplex speech to speech conversational model that targets natural voice interactions with precise persona control.

Conventional voice assistants usually run a cascade. Automatic Speech Recognition (ASR) converts speech to text, a language model generates a text answer, and Text to Speech (TTS) converts back to audio. Each stage adds latency, and the pipeline cannot handle overlapping speech, natural interruptions, or dense backchannels.

PersonaPlex replaces this stack with a single Transformer model that performs streaming speech understanding and speech generation in one network. The model operates on continuous audio encoded with a neural codec and predicts both text tokens and audio tokens autoregressively. Incoming user audio is incrementally encoded, while PersonaPlex simultaneously generates its own speech, which enables barge in, overlaps, rapid turn taking, and contextual backchannels.

UNM Researchers Discover New Master Regulator of Tau, a Protein Implicated in Many Neurodegenerative Diseases

In a surprising discovery, University of New Mexico researchers have found that OTULIN – an enzyme that helps regulate the immune system – also drives the formation of tau, a protein implicated in many neurodegenerative diseases, as well as brain inflammation and aging.

In a study published in the journal Genomic Psychiatry, the researchers reported that when they deactivated OTULIN, either by administering a custom-designed small molecule or knocking out the gene that codes for it, it halted the production of tau and removed it from neurons. The study was conducted on two different types of cells, some derived from a patient who had died from late-onset sporadic Alzheimer’s disease, and the rest from a line of human neuroblastoma cells that are frequently used in neuroscience research.

The discovery opens the door to potential treatments for Alzheimer’s and other neurodegenerative diseases, said Karthikeyan Tangavelou, PhD, a senior scientist in the lab of Kiran Bhaskar, PhD, professor in the Department of Molecular Genetics & Microbiology in the UNM School of Medicine.

Machine learning can predict patients’ responses to antidepressants—while disentangling drug and placebo effects

Depression is one of the most widespread mental health disorders worldwide, affecting approximately 4% of the global population. It is characterized by a persistent low mood, disruptions in typical sleeping and/or eating habits, a lack of motivation, a loss of interest in daily activities and unhelpful thought patterns.

There are now various treatments for depression, including psychotherapy-based interventions and different types of antidepressant medications. Identifying the best treatment strategy, however, is not always easy, and many patients try different medications before they find one that works for them.

Researchers at Stanford University, Lehigh University, the University of Texas at Austin and other institutes explored the potential of machine learning techniques, computational models that can identify patterns in data, for predicting the responses of individual patients to two different antidepressants and to a placebo (i.e., a pill that contains no active chemicals).

Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation

Significance.

Cellular rejuvenation through transcriptional reprogramming has emerged as exciting approach to counter aging. However, to date, only a few of rejuvenating transcription factor (TF) perturbations have been identified. In this work, we developed a discovery platform to systematically identify single TF perturbations that drive cellular and tissue rejuvenation. Using a classical model of human fibroblast aging, we identified more than a dozen candidate TF perturbations and validated four of them (E2F3, EZH2, STAT3, ZFX) through cellular/molecular phenotyping. At the tissue level, we demonstrate that overexpression of EZH2 alone is sufficient to rejuvenate the liver in aged mice, significantly reducing fibrosis and steatosis, and improving glucose tolerance. Our work expanded the list of candidate rejuvenating TFs for future translation. Abstract.

Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging. Using a fibroblast-based model of human cell aging and Perturb-seq screening, we developed a systematic approach to identify single transcription factor (TF) perturbations that promote rejuvenation without dedifferentiation. Overexpressing E2F3 or EZH2, and repressing STAT3 or ZFX, reversed cellular hallmarks of aging—increasing proliferation, proteostasis, and mitochondrial activity, while decreasing senescence. EZH2 overexpression in vivo rejuvenated livers in aged mice, reversing aging-associated gene expression profiles, decreasing steatosis and fibrosis, and improving glucose tolerance. Mechanistically, single TF perturbations led to convergent downstream transcriptional programs conserved in different aging and rejuvenation models. These results suggest a shared set of molecular requirements for cellular and tissue rejuvenation across species. Sign up for PNAS alerts.

Get alerts for new articles, or get an alert when an article is cited. Cellular rejuvenation through transcriptional reprogramming is an exciting approach to counter aging and bring cells back to a healthy state. In both cell and animal aging models, there has been significant recent progress in rejuvenation research. Systemic factors identified in young blood through models such as heterochronic parabiosis (in which the circulatory systems of a young and aged animal are joined) rejuvenate various peripheral tissues and cognitive function in the brain (1–4). Partial reprogramming at the cellular level with the Yamanaka factors (four stem cell transcription factors) reverses cellular and tissue-level aging markers and can extend lifespan in old mice (5–8). These discoveries support the notion that transcriptional reprogramming is a powerful approach to improving the health of cells and tissues, and one day could be used as an approach for human therapeutics. However, to date, only a couple of rejuvenating transcription factor (TF) perturbations have been identified (9, 10) and most of them require the overexpression of TFs. We hypothesized that there are multiple other TF perturbations which could reset cells and tissues back to a healthier or younger state—rejuvenating them. Identifying complementary rejuvenating strategies is important as it will increase the chance of successful future translation. We developed a high-throughput platform, the Transcriptional Rejuvenation Discovery Platform (TRDP), which combines computational analysis of TF binding motifs and target predictions (Materials and Methods), global gene expression data of old and young cell states, and experimental genetic perturbations to identify which TF can restore overall gene expression and cell phenotypes to a younger, healthier state. We developed TRDP to be applicable to any cell type, and in both aging and disease settings, with the only requirements being baseline comparison of gene expression data comparing the older/diseased state to the younger/healthier state and the ability to perform genetic perturbations. To model aging in vitro as a validation of our approach, we used the canonical aging model of passaged fibroblasts (11, 12). We tested 400 TF perturbations via our screen and validated reversal of key cellular aging hallmarks in late passage human fibroblasts for four top TFs: E2F3, EZH2, STAT3, and ZFX. Moreover, EZH2 overexpression in vivo rejuvenated livers in aged mice—reversing aging-associated global gene expression profiles, significantly reducing steatosis and fibrosis, and improving glucose tolerance. These findings point to a conserved set of molecular requirements for cellular and tissue rejuvenation.

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