Heat Shock Proteins Function as Signaling Molecules to Mediate Neuron-Glia Communication During Aging.

The nervous system is primarily composed of neurons and glia, and the communication between them plays profound roles in regulating the development and function of the brain. Neuron-glia signal transduction is known to be mediated by secreted or juxtacrine signals through ligand-receptor interactions on the cell membrane. Here, we report a novel mechanism for neuron-glia signal transduction, wherein neurons transmit proteins to glia through extracellular vesicles, activating glial signaling pathways.

MRI-based Deep Learning Assessment of Amyloid, Tau, and Neurodegeneration Biomarker Status across the Alzheimer Disease Spectrum.

Background PET can be used for amyloid-tau-neurodegeneration (ATN) classification in Alzheimer disease, but incurs considerable cost and exposure to ionizing radiation. MRI currently has limited use in characterizing ATN status. Deep learning techniques can detect complex patterns in MRI data and have potential for noninvasive characterization of ATN status.

Enhancing social connectedness with companion robots using AI.

Companion robots with AI may usher a new science of social connectedness that requires the development of ethical frameworks.

Differences in Risk of Alzheimer's Disease Following Later-Life Traumatic Brain Injury in Veteran and Civilian Populations.

Objective: To directly compare the effect of incident age 68+ traumatic brain injury (TBI) on the risk of diagnosis of clinical Alzheimer's disease (AD) in the general population of older adults, and between male veterans and nonveterans; to assess how this effect changes with time since TBI.

Setting And Participants: Community-dwelling traditional Medicare beneficiaries 68 years or older from the Health and Retirement Study (HRS).

Design: Fine-Gray models combined with inverse-probability weighting were used to identify associations between incident TBI, post-TBI duration, and TBI treatment intensity, with a diagnosis of clinical AD dementia.

GABA signaling triggered by TMC-1/Tmc delays neuronal aging by inhibiting the PKC pathway in .

Aging causes functional decline and degeneration of neurons and is a major risk factor of neurodegenerative diseases. To investigate the molecular mechanisms underlying neuronal aging, we developed a new pipeline for neuronal proteomic profiling in young and aged animals. While the overall translational machinery is down-regulated, certain proteins increase expressions upon aging.

Large-Scale G Protein-Coupled Olfactory Receptor-Ligand Pairing.

G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diverse. This work investigated how the amino-acid sequences of olfactory receptors (ORs)-the largest GPCR family-encode diversified responses to various ligands. We established a proteochemometric (PCM) model based on OR sequence similarities and ligand physicochemical features to predict OR responses to odorants using supervised machine learning.

Human brain evolution: Emerging roles for regulatory DNA and RNA.

Humans diverge from other primates in numerous ways, including their neuroanatomy and cognitive capacities. Human-specific features are particularly prominent in the cerebral cortex, which has undergone an expansion in size and acquired unique cellular composition and circuitry. Human-specific gene expression is postulated to explain neocortical anatomical differences across evolution.

C. elegans as a model to study glial development.

Glia make up roughly half of all cells in the mammalian nervous system and play a major part in nervous system development, function, and disease. Although research in the past few decades has shed light on their morphological and functional diversity, there is still much to be known about key aspects of their development such as the generation of glial diversity and the factors governing proper morphogenesis. Glia of the nematode C.

Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth.

NLR-1/CASPR Anchors F-Actin to Promote Gap Junction Formation.

Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the regulation of gap junction formation in multiple tissues across different developmental stages in C.

Robo functions as an attractive cue for glial migration through SYG-1/Neph.

As one of the most-studied receptors, Robo plays functions in many biological processes, and its functions highly depend on Slit, the ligand of Robo. Here we uncover a Slit-independent role of Robo in glial migration and show that neurons can release an extracellular fragment of Robo upon cleavage to attract glia during migration in . Furthermore, we identified the conserved cell adhesion molecule SYG-1/Neph as a receptor for the cleaved extracellular Robo fragment to mediate glial migration and SYG-1/Neph functions through regulation of the WAVE complex.

Health system utilization before age 1 among children later diagnosed with autism or ADHD.

Children with autism spectrum disorder (ASD) or attention deficit hyperactivity disorder (ADHD) have 2-3 times increased healthcare utilization and annual costs once diagnosed, but little is known about their utilization patterns early in life. Quantifying their early health system utilization could uncover condition-specific health trajectories to facilitate earlier detection and intervention. Patients born 10/1/2006-10/1/2016 with ≥ 2 well-child visits within the Duke University Health System before age 1 were grouped as ASD, ADHD, ASD + ADHD, or No Diagnosis using retrospective billing codes.

Regulation of Gliogenesis by /Atoh1 in .

The regulation of gliogenesis is a fundamental process for nervous system development, as the appropriate glial number and identity is required for a functional nervous system. To investigate the molecular mechanisms involved in gliogenesis, we used as a model and identified the function of the proneural gene Atoh1 in gliogenesis. We found that functions during embryonic development to negatively regulate the number of AMsh glia.

Publisher Correction: ASPI: a public-private partnership to develop treatments for autism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Vitamin B12 Regulates Glial Migration and Synapse Formation through Isoform-Specific Control of PTP-3/LAR PRTP Expression.

Vitamin B12 is known to play critical roles during the development and aging of the brain, and vitamin B12 deficiency has been linked to neurodevelopmental and degenerative disorders. However, the underlying molecular mechanisms of how vitamin B12 affects the development and maintenance of the nervous system are still unclear. Here, we report that vitamin B12 can regulate glial migration and synapse formation through control of isoform-specific expression of PTP-3/LAR PRTP (leukocyte-common antigen-related receptor-type tyrosine-protein phosphatase).

Relative Average Look Duration and its Association with Neurophysiological Activity in Young Children with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is characterized by early attentional differences that often precede the hallmark symptoms of social communication impairments. Development of novel measures of attentional behaviors may lead to earlier identification of children at risk for ASD. In this work, we first introduce a behavioral measure, Relative Average Look Duration (RALD), indicating attentional preference to different stimuli, such as social versus nonsocial stimuli; and then study its association with neurophysiological activity.

Critical Update on the Third Edition of the Guidelines for Managing Severe Traumatic Brain Injury in Children.

Background: Severe traumatic brain injury (TBI) is associated with high rates of death and disability. As a result, the revised guidelines for the management of pediatric severe TBI address some of the previous gaps in pediatric TBI evidence and management strategies targeted to promote overall health outcomes.

Objectives: To provide highlights of the most important updates featured in the third edition of the guidelines for the management of pediatric severe TBI.

State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018.

Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence.

Genetic variation across the human olfactory receptor repertoire alters odor perception.

Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict olfactory perception from receptor activity patterns. Genetic variation in human ORs is abundant and alters receptor function, allowing us to examine the relationship between receptor function and perception. We sequenced the OR repertoire in 332 individuals and examined how genetic variation affected 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity.