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The study of signal transduction is becoming a de facto part of the analysis of gene expression and protein profiling techniques. Many online tools are used to cluster genes in various ways or to assign gene products to signal transduction pathways. Among these, pathFinder is a unique tool that can find signal transduction pathways between first, second, or nth messengers and their targets within the cell. pathFinder can identify qualitatively all possible signal transduction pathways connecting any starting component and target within a database of two-component pathways (directional dyads). One or more intermediate pathway components can be excluded to simulate the use of pharmacological inhibitors or genetic deletion (knockout). Missing elements in a pathway connecting the activator or initiator and target can also be inferred from a null pathway result. The value of this static network analysis tool is illustrated by the predication from pathFinder analysis of a novel cyclic AMP-dependent, protein kinase A-independent signaling pathway in neuroendocrine cells, which has been experimentally confirmed.
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http://dx.doi.org/10.1126/scisignal.131pt4 | DOI Listing |
Commun Biol
September 2025
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.
Neuronal development and function are orchestrated by a plethora of regulatory mechanisms that control the abundance, localization, interactions, and function of proteins. A key role in this regard is assumed by post-translational protein modifications (PTMs). While some PTM types, such as phosphorylation or ubiquitination, have been explored comprehensively, PTMs involving ubiquitin-like modifiers (Ubls) have remained comparably enigmatic (Ubls).
View Article and Find Full Text PDFSci Rep
September 2025
Laboratory of Animal Morphology, Department of Animal Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya, 464-8601, Aichi, Japan.
During early pregnancy in mice, leukemia inhibitory factor (LIF) regulates embryo implantation by activating the JAK/STAT3 signaling pathway. The STAT3 pathway has been recognized to play a critical role in embryo implantation; however, it remains unclear whether STAT3 activation alone is sufficient to induce implantation. In this study, we investigated the effects of RO8191, a potential STAT3 activator, on embryo implantation through a series of studies with different mouse models.
View Article and Find Full Text PDFNat Commun
September 2025
Institute of Neurosciences and Medicine, Brain & Behaviour (INM-7), Research Centre Juelich; Wilhelm-Johnen-Straße 1, Juelich, Germany.
Autism is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition ratio is discussed as a pathomechanism but in-vivo evidence of disturbed neurotransmission underlying functional alterations remains scarce. We compare local resting-state brain activity and neurotransmitter co-localizations between autism (N = 405, N = 395) and neurotypical controls (N = 473, N = 474) in two independent cohorts and correlate them with excitation-inhibition changes induced by glutamatergic (ketamine) and GABAergic (midazolam) medication.
View Article and Find Full Text PDFNat Commun
September 2025
Shanghai Yao Yuan Biotechnology Ltd (Drug Farm), Shanghai, China.
ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 potently inhibits human ALPK1 (IC = 1.
View Article and Find Full Text PDFPlant Physiol Biochem
September 2025
Shanxi Normal University, Taiyuan, 030000, PR China.
Suaeda salsa(S.salsa) is a promising halophytic species for vegetation restoration in highly saline-alkali soils. Carboxylated single-walled carbon nanotubes (COOH-SWCNTs) have emerged as potential agents for modulating plant responses to abiotic stress.
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