Spreading depolarization triggers pro- and anti-inflammatory signalling: a potential link to headache.

Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation.

Breast Cancer Specificities of Patients With Anti-Ri Paraneoplastic Neurologic Syndromes.

Background And Objectives: Breast cancers (BCs) of patients with paraneoplastic neurologic syndromes and anti-Yo antibodies (Yo-PNS) overexpress human epidermal growth factor receptor 2 (HER2) and display genetic alterations and overexpression of the Yo-onconeural antigens. They are infiltrated by an unusual proportion of B cells. We investigated whether these features were also observed in patients with PNS and anti-Ri antibodies (Ri-PNS).

Insights into the origin, hybridisation and adaptation of Candida metapsilosis hybrid pathogens.

Hybridisation is a source of genetic diversity, can drive adaptation to new niches and has been found to be a frequent event in lineages harbouring pathogenic fungi. However, little is known about the genomic implications of hybridisation nor its impact on pathogenicity-related traits. A common limitation for addressing these questions is the narrow representativity of sequenced genomes, mostly corresponding to strains isolated from infected patients.

Composition and functional diversity of soil and water microbial communities in the rice-crab symbiosis system.

Rice-crab co-culture is an environmentally friendly agricultural and aquaculture technology with high economic and ecological value. In order to clarify the structure and function of soil and water microbial communities in the rice-crab symbiosis system, the standard rice-crab field with a ring groove was used as the research object. High-throughput sequencing was performed with rice field water samples to analyze the species and abundance differences of soil bacteria and fungi.

RING finger protein 5 is a key anti-FMDV host factor through inhibition of virion assembly.

Foot-and-mouth disease virus (FMDV) are small, icosahedral viruses that cause serious clinical symptoms in livestock. The FMDV VP1 protein is a key structural component, facilitating virus entry. Here, we find that the E3 ligase RNF5 interacts with VP1 and targets it for degradation through ubiquitination at the lys200 of VP1, ultimately inhibiting virus replication.

Parents' Experiences and Views About Use of Wearable Technology for Research and Treatment Monitoring of Children with Neurodevelopmental Disorders.

Objective: Wearable technology has potential benefits for clinical measurement with children who have neurodevelopmental disorders (NDDs). However, this cohort may experience sensory processing disorder, behavioral dysregulation, and cognitive challenges. For effective and considerate implementation, the experiences and views of parents of children with NDDs on this topic need in-depth investigation.

LEDGF/p75 promotes transcriptional pausing through preventing SPT5 phosphorylation.

SPT5 exhibits versatile functions in RNA Pol II promoter proximal pausing, pause release, and elongation in metazoans. However, the mechanism underlying the functional switch of SPT5 during early elongation has not been fully understood. Here, we report that the phosphorylation site-rich domain (PRD)/CTR1 and the prion-like domain (PLD)/CTR2, which are situated adjacent to each other within the C-terminal repeat (CTR) in SPT5, play pivotal roles in Pol II pausing and elongation, respectively.

Pellino 3 E3 ligase promotes starvation-induced autophagy to prevent hepatic steatosis.

Nutrient deprivation is a major trigger of autophagy, a conserved quality control and recycling process essential for cellular and tissue homeostasis. In a high-content image-based screen of the human ubiquitome, we here identify the E3 ligase Pellino 3 (PELI3) as a crucial regulator of starvation-induced autophagy. Mechanistically, PELI3 localizes to autophagic membranes, where it interacts with the ATG8 proteins through an LC3-interacting region (LIR).

A metagenomic perspective on the microbial prokaryotic genome census.

Following 30 years of sequencing, we assessed the phylogenetic diversity (PD) of >1.5 million microbial genomes in public databases, including metagenome-assembled genomes (MAGs) of uncultivated microbes. As compared to the vast diversity uncovered by metagenomic sequences, cultivated taxa account for a modest portion of the overall diversity, 9.

Biologically relevant integration of transcriptomics profiles from cancer cell lines, patient-derived xenografts, and clinical tumors using deep learning.

Cell lines and patient-derived xenografts are essential to cancer research; however, the results derived from such models often lack clinical translatability, as they do not fully recapitulate the complex cancer biology. Identifying preclinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers is critically important. Here, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings while removing confounder information.

Activation of locus coeruleus noradrenergic neurons rapidly drives homeostatic sleep pressure.

Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).

An expanding universe of mutational signatures and its rapid evolution in single-stranded RNA viruses.

The study of mutational processes in somatic genomes has gained recent momentum, uncovering a wide array of endogenous and exogenous factors associated with somatic changes. However, the overall landscape of mutational processes in germline mutations across the tree of life and associated evolutionary driving forces are rather unclear. In this study, we analyzed mutational processes in single-stranded RNA (ssRNA) viruses which are known to jump between different hosts with divergent exogenous environments.

Nitrous oxide production via enzymatic nitroxyl from the nitrifying archaeon .

Ammonia oxidizing archaea (AOA) are among the most abundant microorganisms on earth and are known to be a major source of nitrous oxide (NO) emissions, although biochemical origins of this NO remain unknown. Enzymological details of AOA nitrogen metabolism are broadly unavailable. We report the recombinant expression, purification, and characterization of a multicopper oxidase, Nmar_1354, from the AOA .

An evolutionarily conserved cation channel tunes the sensitivity of gustatory neurons to ephaptic inhibition in .

In ephaptic coupling, physically adjacent neurons influence one another's activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic coupling's effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition between gustatory receptor neurons (GRNs).

Stimulating the regenerative capacity of the human retina with proneural transcription factors in 3D cultures.

Retinal diseases often lead to degeneration of specific retinal cell types with currently limited therapeutic options to replace the lost neurons. Previous studies have reported that overexpression of or combinations of proneural factors in Müller glia (MG) induce regeneration of functional neurons in the adult mouse retina. Recently, we applied the same strategy in dissociated cultures of fetal human MG and although we stimulated neurogenesis from MG, our effect in 2D cultures was modest and our analysis of newborn neurons was limited.

Action potential-independent spontaneous microdomain Ca transients-mediated continuous neurotransmission regulates hyperalgesia.

Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown.

Plant BCL-DOMAIN HOMOLOG proteins play a conserved role in SWI/SNF complex stability.

The SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are evolutionarily conserved, ATP-dependent chromatin remodelers crucial for multiple nuclear functions in eukaryotes. Recently, plant BCL-DOMAIN HOMOLOG (BDH) proteins were identified as shared subunits of all plant SWI/SNF complexes, significantly impacting chromatin accessibility and various developmental processes in Arabidopsis. In this study, we performed a comprehensive characterization of mutants, revealing the role of BDH in hypocotyl cell elongation.

Cellular Senescence Genes as Cutting-Edge Signatures for Abdominal Aortic Aneurysm Diagnosis: Potential for Innovative Therapeutic Interventions.

Abdominal aortic aneurysm (AAA) is the most prevalent dilated arterial aneurysm that poses a significant threat to older adults, but the molecular mechanisms linking senescence to AAA progression remain poorly understood. This study aims to identify cellular senescence-related genes (SRGs) implicated in AAA development and assess their potential as therapeutic targets. Four hundred and twenty-nine differentially expressed genes (DEGs) were identified from the GSE57691 training set, and 867 SRGs were obtained.

Aucubin Promotes BMSCs Proliferation and Differentiation of Postmenopausal Osteoporosis Patients by Regulating Ferroptosis and BMP2 Signalling.

Postmenopausal osteoporosis (PMOP) is a chronic systemic bone metabolism disorder. Promotion in the patterns of human bone marrow mesenchymal stem cells (hBMSCs) differentiation towards osteoblasts contributes to alleviating osteoporosis. Aucubin, a natural compound isolated from the well-known herbal medicine Eucommia, was previously shown to possess various pharmacological effects.

Anticancer Effects of MAPK6 siRNA-Loaded PLGA Nanoparticles in the Treatment of Breast Cancer.

siRNA-loaded nanoparticles open new perspectives for cancer treatment. MAPK6 is upregulated in breast cancer and is involved in cell growth, differentiation and cell cycle regulation. Herein, we aimed to investigate the anticancer effects of MAPK6 knockdown by using MAPK6 siRNA-loaded PLGA nanoparticles (siMAPK6-PLGA-NPs) in MCF-7 breast cancer cells.

Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis.

This study identifies microRNAs (miRNAs) with significant discriminatory power in distinguishing melanoma from nevus, notably hsa-miR-26a and hsa-miR-211, which have exhibited diagnostic potential with accuracy of 81% and 78% respectively. To enhance diagnostic accuracy, we integrated miRNAs into various machine-learning (ML) models. Incorporating miRNAs with AUC scores above 0.

Effective Reduction of Transgene-Specific Immune Response With rAAV Vectors Co-Expressing miRNA-UL112-5p or ERAP1 shRNA.

Recombinant adeno-associated virus (rAAV) has emerged as one of the best gene delivery vectors for human gene therapy in vivo. However, the clinical efficacy of rAAV gene therapy is often hindered by the host immune response against its transgene products. Endoplasmic reticulum aminopeptidase 1 (ERAP1) is specialised to process peptides presented by class I molecules of major histocompatibility complex.

Single cell approaches define neural stem cell niches and identify microglial ligands that can enhance precursor-mediated oligodendrogenesis.

Here, we used single cell RNA sequencing and single cell spatial transcriptomics to characterize the forebrain neural stem cell (NSC) niche under homeostatic and injury conditions. We defined the dorsal and lateral ventricular-subventricular zones (V-SVZs) as two distinct neighborhoods and showed that, after white matter injury, NSCs are activated to make oligodendrocytes dorsally for remyelination. This activation is coincident with an increase in transcriptionally distinct microglia in the dorsal V-SVZ niche.

Novel Allele HLA-B*52:130, Identified by Next-Generation Sequencing.

The new HLA-B*52:130 allele showed one nonsynonymous nucleotide difference compared to the HLA-B*52:01:01:01 allele in codon 170.