Microglial P2Y calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis.

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRAB, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions.

Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology.

Accumulation of amyloid-beta (Aβ) can lead to the formation of aggregates that contribute to neurodegeneration in Alzheimer's disease (AD). Despite globally reduced neural activity during AD onset, recent studies have suggested that Aβ induces hyperexcitability and seizure-like activity during the early stages of the disease that ultimately exacerbate cognitive decline. However, the underlying mechanism is unknown.

Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension.

Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length are thought to precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity.

Microglial P2Y calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis.

Microglial calcium signaling is rare in a baseline state but shows strong engagement during early epilepsy development. The mechanism and purpose behind microglial calcium signaling is not known. By developing an UDP fluorescent sensor, GRAB, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions.

Oligodendrocyte calcium signaling sculpts myelin sheath morphology.

Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity.

Exploring the causal role of the immune response to varicella-zoster virus on multiple traits: a phenome-wide Mendelian randomization study.

Background: The immune response to infections could be largely driven by the individual's genes, especially in the major histocompatibility complex (MHC) region. Varicella-zoster virus (VZV) is a highly communicable pathogen. In addition to infection, the reactivations of VZV can be a potential causal factor for multiple traits.

Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice.

Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) to satisfy regional energy demand. Ca elevation in astrocytes can drive arteriole dilation to increase CBF, yet affirmative evidence for the necessity of astrocytes in functional hyperemia in vivo is lacking. In awake mice, we discovered that functional hyperemia is bimodal with a distinct early and late component whereby arteriole dilation progresses as sensory stimulation is sustained.

Molecular basis of astrocyte diversity and morphology across the CNS in health and disease.

Astrocytes, a type of glia, are abundant and morphologically complex cells. Here, we report astrocyte molecular profiles, diversity, and morphology across the mouse central nervous system (CNS). We identified shared and region-specific astrocytic genes and functions and explored the cellular origins of their regional diversity.

Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents.

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2.

A suggested shared aetiology of dementia - a colocalization study.

Identification of shared causal genes between dementia and its related clinical outcomes can help understand shared aetiology and multimorbidity surrounding dementia. We performed the HyPrColoc colocalization analysis to detect possible shared causal genes between dementia or Alzheimer's disease (AD) and 5 selected traits: stroke, diabetes, atherosclerosis, cholesterol level, and alcohol consumption within 601 dementia or AD associated genetic regions using summary results of the UK Biobank genome-wide association studies. Functional analysis was performed on the candidate causal genes to explore potential biological pathways.

Hippocampal astrocytes represent navigation space.

Hippocampal place cells, which display location-specific activity, are known to encode spatial information. A recent study in PLOS Biology by Curreli and colleagues shows that hippocampal astrocytes are implicated in encoding complementary spatial information, suggesting the existence of glial place cells.

TCMNER and PubMed: A Novel Chinese Character-Level-Based Model and a Dataset for TCM Named Entity Recognition.

Intelligent traditional Chinese medicine (TCM) has become a popular research field by means of prospering of deep learning technology. Important achievements have been made in such representative tasks as automatic diagnosis of TCM syndromes and diseases and generation of TCM herbal prescriptions. However, one unavoidable issue that still hinders its progress is the lack of labeled samples, i.

Specific and behaviorally consequential astrocyte G GPCR signaling attenuation in vivo with iβARK.

Astrocytes respond to neurotransmitters and neuromodulators using G-protein-coupled receptors (GPCRs) to mediate physiological responses. Despite their importance, there has been no method to genetically, specifically, and effectively attenuate astrocyte G GPCR pathways to explore consequences of this prevalent signaling mechanism in vivo. We report a 122-residue inhibitory peptide from β-adrenergic receptor kinase 1 (iβARK; and inactive D110A control) to attenuate astrocyte G GPCR signaling.

Local and CNS-Wide Astrocyte Intracellular Calcium Signaling Attenuation with CalEx Mice.

Astrocytes exist throughout the CNS and affect neural circuits and behavior through intracellular Ca signaling. Studying the function(s) of astrocyte Ca signaling has proven difficult because of the paucity of tools to achieve selective attenuation. Based on recent studies, we generated and used male and female knock-in mice for Cre-dependent expression of mCherry-tagged hPMCA2w/b to attenuate astrocyte Ca signaling in genetically defined cells (CalEx mice for lcium trusion).

Long-term results of uncemented allograft prosthesis composite reconstruction for the tumor in proximal femur: a minimum follow-up of sixty-five months.

Background: Uncemented allograft prosthesis composite (APC) has been applied for tumorous bone defect reconstruction in the proximal femur. However, the long-term results are rarely reported. This study aimed to evaluate long-term outcomes of uncemented APC.

Behaviorally consequential astrocytic regulation of neural circuits.

Astrocytes are a large and diverse population of morphologically complex cells that exist throughout nervous systems of multiple species. Progress over the last two decades has shown that astrocytes mediate developmental, physiological, and pathological processes. However, a long-standing open question is how astrocytes regulate neural circuits in ways that are behaviorally consequential.

Design Comorbidity Portfolios to Improve Treatment Cost Prediction of Asthma Using Machine Learning.

Comorbidity is an important factor to consider when trying to predict the cost of treating asthma patients. When an asthmatic patient suffered from comorbidity, the cost of treating such a patient becomes dependent on the nature of the comorbidity. Therefore, lack of recognition of comorbidity on asthmatic patient poses a challenge in predicting the cost of treatment.

Context-Specific Striatal Astrocyte Molecular Responses Are Phenotypically Exploitable.

Astrocytes tile the central nervous system and are widely implicated in brain diseases, but the molecular mechanisms by which astrocytes contribute to brain disorders remain incompletely explored. By performing astrocyte gene expression analyses following 14 experimental perturbations of relevance to the striatum, we discovered that striatal astrocytes mount context-specific molecular responses at the level of genes, pathways, and upstream regulators. Through data mining, we also identified astrocyte pathways in Huntington's disease (HD) that were reciprocally altered with respect to the activation of striatal astrocyte G protein-coupled receptor (GPCR) signaling.

Applying Queuing Theory and Mixed Integer Programming to Blood Center Nursing Schedules of a Large Hospital in China.

Blood centers in large hospitals in China are facing serious problems, including complex patient queues and inflexible nursing schedules. This study is aimed at developing a flexible scheduling method for blood center nurses. By systematically analyzing the constraints that affect scheduling, a flexible scheduling model is established based on queuing theory and mixed integer programming.

The Efficacy and Safety of Apatinib in Advanced Synovial Sarcoma: A Case Series of Twenty-One Patients in One Single Institution.

Background: Synovial sarcoma (SS) is a highly aggressive soft-tissue sarcoma (STS) with poor prognosis. Tyrosine kinase inhibitor (TKI) has shown a promising impact on advanced STS patients. This study aimed to evaluate the efficacy and safety of apatinib, an oral multi-TKI, which especially inhibited vascular endothelial growth factor receptor, as second-line therapy for patients with advanced SS.

Improved tools to study astrocytes.

Astrocytes are a type of glial cell that tile the CNS. They interact with multiple cell types, including neurons, glial cells and blood vessels, and are involved or implicated in brain disorders. Progress has been made in understanding astrocytes, but the field lacks detailed information concerning how they perform their multifarious functions, and how and when they influence the operations of the neural circuits with which they interact.

The functional outcomes and complications of different reconstruction methods for Giant cell tumor of the distal radius: comparison of Osteoarticular allograft and three-dimensional-printed prosthesis.

Background: En bloc excision has been increasingly used for the management of giant cell tumors (GCTs) in the distal radius. An osteoarticular allograft has been used extensively for decades, and custom-made prosthesis reconstruction has been more recently applied. We aimed to compare the clinical outcomes of the two procedures.

Astrocyte molecular signatures in Huntington's disease.

Astrocytes are implicated in neurodegenerative disorders and may contribute to striatal neuron loss or dysfunction in Huntington's disease (HD). Here, we assessed striatal astrocyte gene and protein signatures in two HD mouse models at three stages and compared our results to human HD data at four clinical grades and to mice exhibiting polyglutamine length-dependent pathology. We found disease-model and stage-specific alterations and discovered a core disease-associated astrocyte molecular signature comprising 62 genes that were conserved between mice and humans.