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The secreted protein Sonic Hedgehog (SHH) acts in graded fashion to pattern the dorsal-ventral axis of the vertebrate neural tube. This is a dynamic process in which increasing concentrations and durations of exposure to SHH generate neurons with successively more ventral identities. Interactions between the receiving cells and the graded signal underpin the mechanism of SHH action. In particular, negative feedback, involving proteins transcriptionally induced or repressed by SHH signaling, plays an essential role in shaping the graded readout. On one hand, negative feedback controls, in a noncell-autonomous manner, the distribution of SHH across the field of receiving cells. On the other, it acts cell-autonomously to convert different concentrations of SHH into distinct durations of intracellular signal transduction. Together, these mechanisms exemplify a strategy for morphogen interpretation, which we have termed temporal adaptation that relies on the continuous processing and refinement of the cellular response to the graded signal.
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http://dx.doi.org/10.1101/cshperspect.a002014 | DOI Listing |
ACS Synth Biol
September 2025
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85281, United States.
Cellular resource limitations create unintended interactions among synthetic gene circuit modules, compromising circuit modularity. This challenge is particularly pronounced in circuits with positive feedback, where uneven resource allocation can lead to Winner-Takes-All (WTA) behavior, favoring one module at the expense of others. In this study, we experimentally implemented a Negatively Competitive Regulatory (NCR) controller using CRISPR interference (CRISPRi) and evaluated its effectiveness in mitigating WTA behavior in two gene circuits: dual self-activation and cascading bistable switch.
View Article and Find Full Text PDFPsychol Res
September 2025
Berlin School of Mind and Brain & Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
The existence of free will has been called into question by Benjamin Libet's seminal experiment, who argued that our conscious decision is preceded by an unconscious decision reflected in the readiness potential (RP). Alternatively, it has been argue that the RP rather reflects a decision process in which different signals accumulate until they reach the intention threshold, at which point an agent experience their intention simultaneously. This raises the question what type of signal is accumulated given that no external information is provided.
View Article and Find Full Text PDFJ Chem Phys
September 2025
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
We study how protein condensates respond to a site of active RNA transcription (i.e., a gene promoter) due to electrostatic protein-RNA interactions.
View Article and Find Full Text PDFNew Phytol
September 2025
Institute of Plant Biochemistry and Cluster of Excellences on Plant Science (CEPLAS), Heinrich Heine University Düsseldorf, Faculty of Mathematics and Natural Sciences, Düsseldorf, 40225, Germany.
In mammals, blood sugar levels are tightly controlled by two hormones: insulin and glucagon. In flowering plants, a comparable regulatory mechanism exists, mediated by the sugar-signalling molecule trehalose 6-phosphate (Tre6P). Similar to insulin, Tre6P functions as a signal and negative feedback regulator of sucrose, the main transport sugar in vascular plants.
View Article and Find Full Text PDFJ Speech Lang Hear Res
September 2025
Department of Communication Sciences & Disorders, Montclair State University, Bloomfield, NJ.
Purpose: Residual speech sound disorder (RSSD) is a high-prevalence condition that can limit children's academic and social participation, with negative consequences for overall well-being. Previous studies have described visual biofeedback as a promising option for RSSD, but results have been inconclusive due to study design limitations and small sample sizes.
Method: In a preregistered randomized controlled trial, 108 children aged 9-15 years with RSSD affecting American English /ɹ/ were randomly assigned to receive treatment incorporating visual biofeedback (subdivided into ultrasound and visual-acoustic types) or a comparison condition of motor-based treatment consistent with current best practices in speech therapy.