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Lifelong behavioral screen reveals an architecture of vertebrate aging

By tracking nearly every movement of a tiny fish’s life from adolescence to death, a new Science study reveals a hidden behavioral blueprint of aging—one that can predict a fish’s age or how long an individual will live.

Mapping behavior of individual vertebrate animals across lifespan could provide an unprecedented view into the lifelong process of aging. We created a platform for high-resolution continuous behavioral tracking of the African killifish across natural lifespan from adolescence to death. We found that animals follow distinct individual aging trajectories. The behaviors of long-lived animals differed markedly from those of short-lived animals, even relatively early in life, and were linked to organ-specific transcriptomic shifts. Machine-learning models accurately inferred age and even forecasted an individual’s future lifespan, given only behavior at a young age. Finally, we found that animals progressed through adulthood in a sequence of stable and stereotyped behavioral stages with abrupt transitions, revealing precise structure for an architecture of aging.

Immune cells regulate eye pressure linked to glaucoma

In the study, researchers tracked fluorescently tagged resident macrophages in mouse eyes. Long-lived resident tissue macrophages were concentrated in the trabecular meshwork and Schlemm’s canal, whereas steady-state monocyte-derived macrophages were abundant around distal vessels.

When they selectively removed these cells, the eye’s drain became clogged, fluid built up, and eye pressure increased and was linked to aberrant extracellular matrix turnover in the resistance-generating tissues of the trabecular meshwork.

“Our findings show that resident macrophages are essential for maintaining healthy eye pressure,” said the author. “Disruption of this system may contribute directly to the development of glaucoma.”

This discovery could lead to the development of future glaucoma treatments. The next step is to do research that identifies these resident macrophages in human eye tissue. ScienceMission sciencenewshighlights.

When the eye’s drainage system clogs, pressure builds up and causes damage. The pressure can lead to glaucoma and vision loss.

New research published in the journal Immunity, reveals that a specialized set of immune cells act as the cleanup crew, pointing to a promising new target for therapies to prevent a major cause of blindness.

Continue reading “Immune cells regulate eye pressure linked to glaucoma” | >

Scientists Create Novel Organism with Primitive Nervous System

In a prospective cohort study involving more than 130 000 US adults followed for up to 43 years, higher intake of caffeinated coffee and tea was associated with lower risk of developing dementia and modestly better cognitive performance, as measured by both subjective and objective tests.

The inverse association was most pronounced at moderate intake, approximately 2 to 3 cups per day of caffeinated coffee or 1 to 2 cups per day of tea, while decaffeinated coffee intake showed no significant relationship to dementia risk or cognitive outcomes.

Question Is long-term intake of caffeinated and decaffeinated coffee associated with risk of dementia and cognitive outcomes?

Findings In this prospective cohort study of 131 821 individuals from 2 cohorts with up to 43 years of follow-up, 11 033 dementia cases were documented. Higher caffeinated coffee intake was significantly associated with lower risk of dementia. Decaffeinated coffee intake was not significantly associated with dementia risk.

Meaning Higher caffeinated coffee intake was associated with more favorable cognitive outcomes.

Abstract: Follow your nose!

https://doi.org/10.1172/JCI195784 Sylvie Alonso & team develop a nasal vaccine booster that induces robust and sustained, cross-clade systemic and mucosal protective immunity in COVID19 mRNA vaccinated populations.

1Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and.

2Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.

3Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.

Brain surgeries are opening windows for neuroscientists, but ethical questions abound

Surgeries are increasingly opening patients’ brains to research. But the opportunities that come with this intimate access also raise complex ethical issues.

Learn more during BrainAwarenessWeek.

Invasive treatments give scientists an intimate view of neural activity, but ethicists worry about mixing research and medical care.

Deep-learning-based de novo discovery and design of therapeutics that reverse disease-associated transcriptional phenotypes

Bulk and single-cell transcriptomics are widely used to characterize diseases and cellular states but remain underexplored for de novo drug discovery. Here, we present a strategy to screen and optimize compounds by matching disease transcriptomic profiles with compound-induced transcriptomic features predicted from chemical structures using a deep-learning model.

Gene expression program linked to neurotransmission in the living human brain identified

Researchers have identified a distinct and reproducible gene expression program associated with neurotransmission in the living human brain, offering unprecedented insight into the molecular mechanisms that support human cognition, emotion, and behavior. The findings were published in Molecular Psychiatry.

Neurotransmission—the electrical and chemical signaling between neurons—is fundamental to all brain function. Until now, most gene expression studies of the human brain have relied on postmortem tissue, limiting scientists’ ability to understand which genes are actively involved in real-time neuronal communication.

In this study, investigators integrated gene expression profiling from the prefrontal cortex with direct intracranial measures of neurotransmission collected from the brains of more than 100 individuals as they underwent neurosurgical procedures. By combining molecular data with real-time physiological recordings, the team identified a coordinated set of genes whose activity tracks with neuronal signaling—a transcriptional program associated with neurotransmission.

Sleep-like Slow Waves During Wakefulness Mediate Attention and Vigilance Difficulties in Adult Attention-Deficit/Hyperactivity Disorder

New in JNeurosci from Pinggal et al: Medication-withdrawn adults with ADHD exhibit more sleep-like brain activity while awake than neurotypical adults that is linked to poorer performance in a task that requires sustained attention.

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Attention-Deficit/Hyperactivity Disorder (ADHD) is characterised by behavioural variability and heightened inattention associated with increased mind wandering (MW) and mind blanking (MB). Individuals with ADHD frequently experience sleep disorders and excessive daytime sleepiness, suggesting interactions between attention and arousal systems. Research examining brain activity using electroencephalography (EEG) has demonstrated that sleep-like slow waves (SW) during wakefulness are linked to inattention in neurotypical individuals following sleep deprivation, yet their role in ADHD remains unclear. This study investigated whether individuals with ADHD present with altered waking SW distribution compared to neurotypical controls and whether SW explain attentional difficulties in ADHD.

Adults with (n = 32) and without ADHD (n = 31) completed a sustained attention task while EEG recorded brain activity. Mental state probes (on-task, MW, MB) were embedded within the task. Sleep-like SW reflect cortical slowing and were detected from EEG activity. Omission/commission errors, reaction time (RT), RT variability, mental state reports and subjective sleepiness were analysed. Mediation analysis examined whether SW density explained ADHD-related performance differences.

Individuals with ADHD exhibited more commission errors, MW and MB, more theta oscillations over fronto-temporal electrodes and higher SW density (SW/min) over parieto-temporal electrodes. Increased SW density correlated with higher omission errors, slower RTs, greater RT variability, and elevated sleepiness ratings. On-task reports were negatively correlated with SW density. Mediation analysis revealed that SW density significantly accounted for ADHD-related attentional difficulties.

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