Different Time Courses of Mono- and Bi-Liganded Bursts of Channel Openings of Adult nAChR Molecules Formed by the Reactions of Transmembrane Regions.

We recorded transmembrane currents through single nicotinic acetylcholine receptors (nAChRs) in cell-attached patches at high temporal resolutions from cultured and transiently transfected HEK 293 cells. Receptor activation was elicited by acetylcholine (ACh) or epibatidine (Ebd) at concentrations ranging from 0.01 to 100 µM, binding to one (R or R) or both extracellular ligand binding sites (R).

Peptide Lv and Angiogenesis: A Newly Discovered Angiogenic Peptide.

Peptide Lv is a small endogenous secretory peptide with ~40 amino acids and is highly conserved among certain several species. While it was first discovered that it augments L-type voltage-gated calcium channels (LTCCs) in neurons, thus it was named peptide "Lv", it can bind to vascular endothelial growth factor receptor 2 (VEGFR2) and has VEGF-like activities, including eliciting vasodilation and promoting angiogenesis. Not only does peptide Lv augment LTCCs in neurons and cardiomyocytes, but it also promotes the expression of intermediate-conductance K channels (K3.

Multiple mechanisms of action for an extremely painful venom.

Evolutionary arms races can lead to extremely specific and effective defense mechanisms, including venoms that deter predators by targeting nociceptive (pain-sensing) pathways. The venom of velvet ants (Hymenoptera: Mutillidae) is notoriously painful. It has been described as "Explosive and long lasting, you sound insane as you scream.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Enhancing safety monitoring in post-stroke rehabilitation through wearable technologies.

Objective: Current clinical practice guidelines support structured, progressive protocols for improving walking after stroke. Technology enables monitoring of exercise and therapy intensity, but safety concerns could also be addressed. This study explores functional mobility in post-stroke individuals using wearable technology to quantify movement smoothness-an indicator of safe mobility.

Aβ40 Fibril Assembly on Human Cerebral Smooth Muscle Cells Impairs Cell Viability.

Cerebral vascular deposition of the amyloid-β (Aβ) peptide, a condition known as cerebral amyloid angiopathy (CAA), is associated with intracerebral hemorrhaging and contributes to disease progression in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID). Familial mutations at positions 22 and 23 within the Aβ peptide lead to early onset and severe CAA pathology. Here, we evaluate the effects of fibrillar Aβ peptides on the viability of primary-cultured human cerebral smooth muscle (HCSM) cells, which are the major site of amyloid deposition in cerebral blood vessel walls.

Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy.

Peripheral Myelin Protein 22 (PMP22) and MPZ are abundant myelin membrane proteins in Schwann cells. The MPZ adhesion protein holds myelin wraps together across the intraperiod line. PMP22 is a tetraspan protein belonging to the Claudin superfamily.

Single-Molecule Tracking and Super-Resolution Microscopy Unveil Actin-Driven Membrane Nanotopography Shaping Stable Integrin Adhesions in Developing Tissue.

Single molecule tracking and super-resolution microscopy of integrin adhesion proteins and actin in developing Drosophila muscle attachment sites reveals that nanotopography triggered by Arp2/3-dependent actin protrusions promotes stable adhesion formation. The nanodomains formed during this process confine the diffusion of integrins and promote their immobilization. Spatial confinement is also applied to the motion of actin filaments, resulting in enhanced mechanical connection with the integrin adhesion complex.

Systematic review: REM sleep, dysphoric dreams and nightmares as transdiagnostic features of psychiatric disorders with emotion dysregulation - Clinical implications.

Background: Fragmented rapid eye movement (REM) sleep disrupts the overnight resolution of emotional distress, a process crucial for emotion regulation. Emotion dysregulation, which is common across psychiatric disorders, is often associated with sleep disturbances. This systematic review explores how REM sleep and nightmares affect emotion processing and regulation in individuals with psychiatric disorders where emotion dysregulation is a key concern, suggesting novel sleep-related treatment pathways.

Investigating a caregiver-assisted social skills group programme for primary and early high school-aged children with acquired brain injury or cerebral palsy: protocol for a pilot mixed-methods, two-group randomised trial of PEERS Plus.

Introduction: Reaching social milestones is an important goal of childhood. Children with acquired brain injury (ABI) and cerebral palsy (CP) frequently experience challenges with social functioning and participation. The Programme for the Education and Enrichment of Relational Skills (PEERS) is a group-based social skills programme for adolescents.

Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice.

The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β-estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration.

The American Clinical Neurophysiology Society Guideline on Indications for Continuous Electroencephalography Monitoring in Neonates.

Purpose: Continuous EEG (cEEG) monitoring is increasingly used in the management of neonates with seizures. There remains debate on what clinically relevant information can be gained from cEEG in neonates with suspected seizures, at high risk for seizures, or with definite seizures, as well as the use of cEEG for prognosis in a variety of conditions. In this guideline, we address these questions using American Clinical Neurophysiology Society structured methodology for clinical guideline development.

Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

Hyperactive delta isoform of PI3Kinase enables long distance regeneration of adult rat corticospinal tract.

Neurons in the central nervous system (CNS) lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonises PI3K signalling by hydrolysing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3.

NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity.

Multicolor Cell Lineage Tracing Using MAGIC Markers Strategies.

Multicolor MAGIC Markers strategies are useful lineage tracing tools to study brain development at a multicellular scale. In this chapter, we describe an in utero electroporation method to simultaneously label multiple neighboring progenitors and their respective progeny using these multicolor reporters. In utero electroporation enables the introduction of any gene of interest into embryonic neural progenitors lining the brain ventricles through a simple pipeline consisting of a micro-injection followed by the application of electrical pulses.

Resistance training protects the hippocampus and precuneus against atrophy and benefits white matter integrity in older adults with mild cognitive impairment.

Mild cognitive impairment (MCI) refers to cognitive alterations with preservation of functionality. Individuals with this diagnosis have a higher risk of developing dementia. Non-pharmacological interventions, such as physical exercise, are beneficial for the cognition of this population.

Sex-Based Differences in Endovascular Thrombectomy Outcomes for Large Ischemic Stroke: A SELECT2 Subanalysis.

Background: Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke.

Methods: The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022.

Dysregulation of mTOR signalling is a converging mechanism in lissencephaly.

Cerebral cortex development in humans is a highly complex and orchestrated process that is under tight genetic regulation. Rare mutations that alter gene expression or function can disrupt the structure of the cerebral cortex, resulting in a range of neurological conditions. Lissencephaly ('smooth brain') spectrum disorders comprise a group of rare, genetically heterogeneous congenital brain malformations commonly associated with epilepsy and intellectual disability.

Social odors drive hippocampal CA2 place cell responses to social stimuli.

Hippocampal region CA2 is essential for social memory processing. Interaction with social stimuli induces changes in CA2 place cell firing during active exploration and sharp wave-ripples during rest following a social interaction. However, it is unknown whether these changes in firing patterns are caused by integration of multimodal social stimuli or by a specific sensory modality associated with a social interaction.

Recent developments in translational imaging of in vivo gene therapy outcomes.

Gene therapy achieves therapeutic benefits by delivering genetic materials, packaged within a delivery vehicle, to target cells with defective genes. This approach has shown promise in treating various conditions, including cancer, metabolic disorders, and tissue degenerative diseases. Over the past five years, molecular imaging has increasingly supported gene therapy development in both preclinical and clinical studies.

The mechanisms of electrical neuromodulation.

The central and peripheral nervous systems are specialized to conduct electrical currents that underlie behaviour. When this multidimensional electrical system is disrupted by degeneration, damage, or disuse, externally applied electrical currents may act to modulate neural structures and provide therapeutic benefit. The administration of electrical stimulation can exert precise and multi-faceted effects at cellular, circuit and systems levels to restore or enhance the functionality of the central nervous system by providing an access route to target specific cells, fibres of passage, neurotransmitter systems, and/or afferent/efferent communication to enable positive changes in behaviour.

Early postoperative lumbar catheter severing in a lumboperitoneal shunt due to bite-off by the spinous processes following a fall on the buttocks: illustrative case.

Background: Rupture of the lumbar catheter in lumboperitoneal (LP) shunts is rare and typically occurs due to long-term mechanical stress. The authors describe an unusual case of early postoperative lumbar catheter severing after a fall on the buttocks.

Observations: A 78-year-old woman underwent LP shunt placement for communicating hydrocephalus after aneurysmal subarachnoid hemorrhage.

Biologically plausible gated recurrent neural networks for working memory and learning-to-learn.

The acquisition of knowledge and skills does not occur in isolation but learning experiences amalgamate within and across domains. The process through which learning can accelerate over time is referred to as learning-to-learn or meta-learning. While meta-learning can be implemented in recurrent neural networks, these networks tend to be trained with architectures that are not easily interpretable or mappable to the brain and with learning rules that are biologically implausible.