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Mashup Score: 0
Melanin-Concentrating Hormone (MCH) is a cyclic peptide initially isolated from salmon and later found to be conserved in mammals. It plays a role in regulating melanin changes and rhythmic behaviors such as sleep and feeding, though its relationship with these processes is not fully understood. Our preliminary research revealed significant differences in melanin degradation in zebrafish under varying light conditions, suggesting a link to MCH. This study aims to explore MCH’s role in lighting-induced changes in rhythmic behavior patterns and melanin of zebrafish.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 1CMP-sialic acid synthetase in Drosophila requires N-glycosylation of a non-canonical site - 5 day(s) ago
Sialylation plays important roles in animals, affecting numerous molecular and cell interactions. In Drosophila, sialylation regulates neural transmission and mediates communication between neurons and glia. Drosophila CMP-sialic acid synthetase (CSAS), a key enzyme of the sialylation pathway, is localized to the Golgi and modified by N-glycosylation, suggesting that this modification can affect CSAS function. Here we tested this hypothesis using in vitro and in vivo approaches. We found that CSAS proteins from divergent Drosophila species have two conserved N-glycosylation sites, including the rarely glycosylated non-canonical N-X-C sequon.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 1The glycolytic enzyme PKM2 regulates inflammatory osteoclastogenesis by modulating STAT3 phosphorylation - 20 day(s) ago
Periodontitis is a prevalent chronic inflammatory disease characterized by alveolar bone resorption mediated by osteoclasts. Pyruvate kinase M2 (PKM2), a key enzyme in glycolysis and pyruvate metabolism, has recently been recognized for its regulatory roles beyond metabolism, including gene expression and protein kinase activity. However, its exact role in osteoclastogenesis remains unclear. This study investigates the function of PKM2 in inflammatory osteoclastogenesis and explores its potential as a therapeutic target for periodontitis.
Source: www.jbc.orgCategories: General Medicine NewsTweet
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Mashup Score: 0Signal termination of the chemokine receptor CCR9 is governed by an arrestin-independent phosphorylation mechanism - 20 day(s) ago
The chemokine receptor CCR9 coordinates immune cell migration from the thymus to the small intestine along gradients of the chemokine CCL25. Receptor dysregulation is associated with a variety of inflammatory bowel diseases such as Crohn’s and ulcerative colitis, while aberrant CCR9 overexpression correlates with tumor metastasis. Despite being an attractive therapeutic target, attempts to clinically antagonize CCR9 have been unsuccessful. This highlights the need for a deeper understanding of its specific regulatory mechanisms and signaling pathways.
Source: www.jbc.orgCategories: General Medicine NewsTweet
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Mashup Score: 0Rational Design, Synthesis, and Evaluation of Novel Polypharmacological Compounds Targeting NaV1.5, KV1.5, and K2P Channels for Atrial Fibrillation - 1 month(s) ago
Atrial fibrillation (AF) involves electrical remodeling of the atria, with ion channels such as NaV1.5, KV1.5, and TASK-1 playing crucial roles. This study investigates acetamide-based compounds designed as multi-target inhibitors of these ion channels to address AF. Compound 6f emerged as the most potent in the series, demonstrating a strong inhibition of TASK-1 (IC50 ∼0.3 μM), a moderate inhibition of NaV1.5 (IC50 ∼21.2 μM) and a subtle inhibition of KV1.5 (IC50 ∼81.5 μM), alongside unexpected activation of TASK-4 (∼40% at 100 μM).
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 1Distinct neuronal vulnerability and metabolic dysfunctions are characteristic features of fast-progressing Alzheimer's patients with Lewy bodies - 1 month(s) ago
Tau protein accumulation is linked to dementia progression in Alzheimer’s disease (AD), with potential co-pathologies contributing to it. The progression of dementia in patients with AD varies between individuals, and the association between co-pathology and heterogeneity in dementia progression rate remains unclear. We used longitudinal cohort data, postmortem brain tissues, and biochemical methods such as immunoassays and proteomic profiling to investigate the molecular components associated with progression rate.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 0RNA G-quadruplexes regulate mammalian mirtron biogenesis - 2 month(s) ago
Mirtrons are a predominant class of noncanonical microRNAs derived from introns through a Drosha-independent, splicing-dependent pathway. Unregulated splicing of introns containing hairpins may adversely impact Dicer/Ago-mediated canonical microRNA biogenesis. However, the mechanism regulating mirtron biogenesis remains poorly understood. We found that the 5′ arm of plant mirtrons and invertebrate mirtrons are enriched for uracils; in contrast, the 5′ arm of vertebrate mirtrons are enriched for guanines.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 0Tau destabilization in a familial deletion mutant K280 accelerates its fibrillization and enhances the seeding effect - 3 month(s) ago
Tauopathies cover a range of neurodegenerative diseases in which natively unfolded tau protein aggregates and spreads in the brain during disease progression. To gain insights into the mechanism of tau structure and spreading, here, we examined the biochemical and cellular properties of human full-length wild-type and familial mutant tau, ΔK280, with a deletion at lysine 280. Our results showed that both wild-type and mutant tau are predominantly monomeric by analytical ultracentrifugation. The mutant tau may lose intramolecular contacts and is significantly destabilized assessed by cross-linking mass spectrometry and urea denaturation.
Source: www.jbc.orgCategories: General Medicine News, Allergy-ImmunologyTweet
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Mashup Score: 0N-terminal fragment shedding contributes to signaling of the full-length adhesion receptor ADGRL3 - 3 month(s) ago
Most adhesion G protein–coupled receptors (GPCRs) undergo autoproteolytic cleavage during receptor biosynthesis, resulting in noncovalently bound N-terminal fragments (NTFs) and C-terminal fragments (CTFs) that remain associated during receptor trafficking to the plasma membrane. While substantial evidence supports increased G protein signaling when just the CTF is expressed, there is an ongoing debate about whether NTF removal is required to initiate signaling in the context of the WT receptor.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
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Mashup Score: 1Human α10 nicotinic acetylcholine receptor subunits assemble to form functional receptors - 3 month(s) ago
Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. In mammals, there are 16 individual nAChR subunits allowing for numerous possible heteromeric compositions. nAChRs assembled from α7 or α9 subunits will form homopentamers. In contrast, the structurally related α10 nAChR subunit has historically been thought to require α9 subunits for function. Recently, however, strychnine was shown to enable the expression of human α10 nAChRs in Xenopus laevis oocytes or mammalian cells, prompting a re-examination of whether the human α10 subunit can self-assemble in the absence of strychnine.
Source: www.jbc.orgCategories: General Medicine News, NeurologyTweet
Guo et al.'s findings reveal a mutually regulatory loop in zebrafish between melanin-concentrating hormone (MCH) and sleep pressure. https://t.co/qLWRwmgoQd