Evolving insights on the role of microglia in neuroinflammation, plasticity, and regeneration of the injured spinal cord.

Microglia have emerged as central players in the pathophysiology of traumatic spinal cord injury (SCI). The purpose of this brief review is to highlight the evolution of knowledge on the role of microglia in SCI. We explore the initial discovery of macrophages and their role in SCI lesions, followed by how microglia were examined and distinguished from monocyte-derived macrophages.

Bidirectional Relationship between the BDNF Gene and miRNA: Implications for PD Pathogenesis.

Parkinson's disease (PD) is a neurological degenerative condition that primarily affects older people. Although reduced motor skills, stiffness, dyslexia, and other motor symptoms predominate in PD, the nonmotor symptoms, such as cognitive impairment, also play an important part in the PD-affected brain. Studies have reported that the brain-derived neurotrophic factor () has a pivotal role in monitoring the nonmotor symptoms of PD.

Real-world data and evidence in pain research: an IMMPACT comprehensive review and best practice recommendations.

Real-world data (RWD) can be defined as routinely collected clinical or administrative data that might be used for research purposes and to generate real-world evidence (RWE). Computerized search and data mining methods, large electronic databases, and the development of novel computational and statistical methods allow for improved access to and analysis of RWD. Although RWD afford the opportunity to generate RWE with potentially improved efficiency and generalizability over prospective clinical studies, it is important to understand and apply best practices when analysing RWD, particularly when the goal is to generate RWE of diagnostic, prognostic, or treatment effectiveness.

Shape and word parts combine linearly in the Bouba-Kiki effect.

Languages have evolved in part due to cross-modal associations between shape and sound. A famous example is the Bouba-Kiki effect, wherein humans associate words like bouba/kiki to round/angular shapes. How does the Bouba-Kiki effect work for natural words and shapes that contain a mixture of features? If the effect is holistic, the effect for a composite stimulus would not be explainable using the parts.

Anchored screening identifies transcription factor blueprints underlying dendritic cell diversity and subset-specific anti-tumor immunity.

Transcription factor cooperation is essential for specifying the heterogeneous dendritic cell (DC) lineages that orchestrate adaptive immunity, yet how it drives subset diversification remains poorly understood. Here, we employed a sequential anchored screen of 70 transcription factors using direct cellular reprogramming to identify regulators that specify type 2 conventional DCs (cDC2s) and plasmacytoid DCs (pDCs). We identified PU.

Acute restraint stress and pain modulation depend on the interaction between the periaqueductal gray and the lateral septum.

Acute restraint stress causes analgesia in humans and laboratory animals, but the underlying mechanisms are unknown. Recently, we have shown that a multi-nodal circuitry between the dorsal lateral septum (dLS), lateral hypothalamic area (LHA), and rostral ventromedial medulla (RVM) plays an instructive role in restraint stress-induced analgesia (SIA). We found that the LS neurons are activated when mice struggle to escape the restraint, and we wondered about the origin of the escape signals.

Beyond divisive normalization: Scalable feed-forward networks for multisensory integration across reference frames.

The integration of multiple sensory inputs is essential for human perception and action in uncertain environments. This process includes reference frame transformations as different sensory signals are encoded in different coordinate systems. Studies have shown multisensory integration in humans is consistent with Bayesian optimal inference.

The Multifaceted Role of Extracellular Vesicles in Alzheimer's Disease.

Extracellular vesicles (EVs) are lipid bilayer nano- to micro-sized particles that carry biomolecules, such as proteins, lipids, and genetic material. Their composition depends on the cellular microenvironment and the health status of tissues. EVs are released by different cell types under distinct circumstances, mediating intercellular communication in both physiological and pathological contexts.

Endothelial mitochondria in the blood-brain barrier.

The blood-brain barrier (BBB) is a highly selective interface between the peripheral circulation and the central nervous system (CNS), crucial for maintaining brain homeostasis. Disruptions to the BBB, such as increased permeability or structural damage, can lead to neurological damage. Mitochondria, the primary energy producers within endothelial cells, play a key role in the function of the BBB by maintaining its integrity and low permeability.

Urinary P75: a promising biomarker for amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.

Methods: This study measured urinary p75 using an enzyme-linked immunoassay and normalised the results against urinary creatinine.

An RFamide signaling system balances turning and forward locomotion to optimize global food search in .

Neuromodulators such as neuropeptides activate specific G-protein-coupled receptors to reconfigure activity patterns of neural circuits and alter animal behavior. However, we have an incomplete understanding of the context-dependent mechanisms through which neuromodulators alter behavioral states. Here, we report a novel off-food behavioral requirement of the RFamide receptor .

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells.

The efficacy of cancer immunotherapy relies on the recruitment and activation of cytotoxic T cell responses against solid tumors by type 1 conventional dendritic cells (cDC1s). However, the generation of cDC1s for cancer immunotherapy faces significant limitations, including poor cell yield, functional heterogeneity, and susceptibility to immunosuppression in the tumor microenvironment (TME). We recently developed an immunotherapy modality based on in vivo reprogramming of cancer cells into immunogenic cDC1-like cells, which enabled cancer cells to present tumor antigens as cDC1s and elicited polyclonal cytotoxic T cell responses and durable systemic anti-tumor immunity.

The influence of perceptual load on behavioral interference of simultaneous positive and negative emotional distractors.

Prioritized processing of emotional stimuli could be detrimental in contexts where the affective information is not goal relevant. To examine whether the behavioral interference of task-irrelevant emotional stimuli depends on the primary task demands, several past studies varied the perceptual load, thus manipulating the resources available for processing emotional distractors. In particular, some previous work reported valence asymmetry in the effects of high (vs.

Burst estimation through atomic decomposition (BEAD): A toolbox to find oscillatory bursts in brain signals.

Recent studies have shown that brain signals often show oscillatory bursts of short durations, which have been linked to various aspects of computation and behavior. Traditional methods often use direct spectral estimators to estimate the power of brain signals in spectral and temporal domains, from which bursts are identified. However, direct spectral estimators are known to be noisy, such that even stable oscillations may appear bursty.

Neural processing of rhythmic speech by children with developmental language disorder (DLD): An EEG study.

Sensitivity to rhythmic and prosodic cues in speech has been described as a precursor of language acquisition. Consequently, atypical rhythmic processing during infancy and early childhood has been considered a risk factor for developmental language disorders. Despite many behavioural studies, the neural processing of rhythmic speech has not yet been explored in children with developmental language disorder (DLD).

Agonist-antagonist muscular co-contraction improves rapid corrective responses.

Muscular co-contraction (simultaneous activation of both agonist and antagonist muscle groups) has been observed to emerge across a range of challenging tasks. But is it beneficial? In this study we address this untested assumption by quantifying the performance benefits of muscular co-contraction when making rapid corrective responses to mechanical perturbations. Even small levels of co-contraction resulted in significant performance improvements compared to the relaxed condition in a target recapture task following a mechanical perturbation.

"Exploring Lymphovenous Anastomosis for Alzheimer's Disease: Addressing Brain Lymphatic Dysfunction, Feasibility, and Outcome Metrics".

Alzheimer's Disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, tau tangles, and neuroinflammation, with emerging evidence highlighting a potential role for brain lymphatic dysfunction. Lymphovenous anastomosis (LVA), a microsurgical technique traditionally used in lymphedema management, offers a novel solution to enhance brain metabolite clearance by bypassing impaired lymphatic pathways and enhancing glymphatic outflow. By connecting lymphatic vessels to veins, LVA compensates for aging-related declines in lymphatic/glymphatic flow, with preliminary studies supporting this theory.

Role of contingency in the effects of appetitive and aversive motivation on emotional distraction.

The presence of task-irrelevant emotional stimuli impedes behavioural performance. Some past studies have reported that performance-based monetary rewards mitigate emotional interference by enhancing cognitive control. In such manipulations, the effects of the expected reward and the between a successful response and reward outcome were conflated.

PV and SOM cells play distinct causal roles in controlling network oscillations and stability.

The causal roles of parvalbumin (PV)- and somatostatin (SOM)-positive interneurons in regulating cortical oscillations and stability remain unclear. We developed a biologically grounded microcircuit model composed of excitatory (E), PV, and SOM neurons that explains key experimental findings, including the precise phase locking of PV cells, delayed firing of SOM cells, and the distinct effects of optogenetic perturbations. By perturbing the spike timing of cells while preserving their firing rates, we show that network oscillations depend on the precise timing of both PV and SOM cells: PV cells regulate oscillation frequency and network stability, while SOM cells control oscillation amplitude.

Integrating sensitive motor tasks with histopathology detects sex differences in recovery after spinal cord injury.

Biological sex governs a myriad of molecular, cellular, and physiological features of the intact and injured nervous system. In traumatic spinal cord injury (SCI), biological sex is thought to influence functional recovery and tissue pathology. However, the open-field Basso Mouse Scale (BMS) used to track experimental SCI recovery relies on observer-based non-parametric scoring, which may not be sensitive enough to detect sex differences in motor behavior.

EEG microstates, acute phase negative symptoms of schizophrenia and antipsychotic treatment response.

EEG microstates are transient scalp topographies reflecting whole-brain electric potential that remain quasi-stable for 60-120 ms. Microstates exhibitalterations across all phases of schizophrenia; especially an increased microstate C and a decreased microstate D were linked to aberrant salience. We aimed to investigate the relationship of microstates with illness severity in the positive, negative, disorganized, excited and depressed symptoms domains, and with response to antipsychotics.

Enhancing the validity of CAIDE dementia risk scores with resting heart rate and machine learning: An analysis from the National Alzheimer's Coordinating Center across all races/ethnicities.

Introduction: The clinical utility of dementia prognostic scores has limited validity across diverse populations. This study aimed to enhance the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) model by incorporating resting heart rate (RHR) using a machine learning method across a diverse population.

Methods: We developed CAIDE and CAIDE-RHR models using a random forest algorithm in the National Alzheimer's Coordinating Center (NACC) dataset.

Large-scale plasma proteomics uncovers preclinical molecular signatures of Parkinson's disease and overlap with other neurodegenerative disorders.

Parkinson's disease (PD) remains incurable, with a long preclinical phase currently undetectable by existing methods. In the largest proteomic study in neurodegenerative diseases to date, we analyzed blood samples from ~74,000 individuals across discovery and validation cohorts. In the EPIC4PD discovery case-cohort, large-scale profiling of 7,285 proteins (SomaScan-7K) in 4,538 initially unaffected participants (574 incident cases) identified 17 proteins that predict PD up to 28 years before diagnosis.

Sex, Attraction, and Social Norms: Distinguishing Romantic and Non-Romantic Relationships in Non-Sexual Contexts.

Close relationships are typically distinguished by whether they are "romantic" versus "platonic" and this distinction is often based on sexual attraction and/or behavior. However, several forms of close relationships do not follow this pattern. Thus, the purpose of this research was to explore how individuals distinguish between romantic relationships and close, non-romantic relationships in non-sexual contexts.