Efficiency of Organelle Capture by Microtubules as a Function of Centrosome Nucleation Capacity: General Theory and the Special Case of Polyspermia

Transport of organelles along microtubules is essential for the cell metabolism and morphogenesis. The presented analysis derives the probability that an organelle of a given size comes in contact with the microtubule aster. The question is asked how this measure of functionality of the microtubule aster is controlled by the centrosome. A quantitative model is developed to address this question. It is shown that for the given set of cellular parameters, such as size and total tubulin content, a centrosome nucleation capacity exists that maximizes the probability of the organelle capture. The developed general model is then applied to the capture of the female pronucleus by microtubules assembled on the sperm centrosome, following physiologically polyspermic fertilization. This application highlights an unintuitive reflection of nonlinearity of the nucleated polymerization of the cellular pool of tubulin. The prediction that the sperm centrosome should lower its nucleation capacity in the face of the competition from the other sperm is a stark illustration of the new optimality principle. Overall, the model calls attention to the capabilities of the centrosomal pathway of regulation of the transport-related functionality of the microtubule cytoskeleton. It establishes a quantitative and conceptual framework that can guide experiment design and interpretation

Régulation de la dynamique d'assemblage des microtubules (propriétés fonctionnelles du complexe stathmine / tubuline)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Leveraging Centric Data Federated Learning Using Blockchain For Integrity Assurance

Machine learning abilities have become a vital component for various solutions across industries, applications, and sectors. Many organizations seek to leverage AI-based solutions across their business services to unlock better efficiency and increase productivity. Problems, however, can arise if there is a lack of quality data for AI-model training, scalability, and maintenance. We propose a data-centric federated learning architecture leveraged by a public blockchain and smart contracts to overcome this significant issue. Our proposed solution provides a virtual public marketplace where developers, data scientists, and AI-engineer can publish their models and collaboratively create and access quality data for training. We enhance data quality and integrity through an incentive mechanism that rewards contributors for data contribution and verification. Those combined with the proposed framework helped increase with only one user simulation the training dataset with an average of 100 input daily and the model accuracy by approximately 4\%.Comment: Published at International Workshop on Trustable, Verifiable and Auditable Federated Learning in Conjunction with AAAI 2022 (FL-AAAI-22) https://federated-learning.org/fl-aaai-2022

Local axonal function of STAT3 rescues axon degeneration in the pmn model of motoneuron disease

Axonal maintenance, plasticity, and regeneration are influenced by signals from neighboring cells, in particular Schwann cells of the peripheral nervous system. Schwann cells produce neurotrophic factors, but the mechanisms by which ciliary neurotrophic factor (CNTF) and other neurotrophic molecules modify the axonal cytoskeleton are not well understood. In this paper, we show that activated signal transducer and activator of transcription-3 (STAT3), an intracellular mediator of the effects of CNTF and other neurotrophic cytokines, acts locally in axons of motoneurons to modify the tubulin cytoskeleton. Specifically, we show that activated STAT3 interacted with stathmin and inhibited its microtubule-destabilizing activity. Thus, ectopic CNTF-mediated activation of STAT3 restored axon elongation and maintenance in motoneurons from progressive motor neuronopathy mutant mice, a mouse model of motoneuron disease. This mechanism could also be relevant for other neurodegenerative diseases and provide a target for new therapies for axonal degeneration