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Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity. [ABSTRACT FROM AUTHOR]

In this paper, the problem of finite-time attitude-tracking control for a rigid spacecraft is addressed. Uncertainties including unknown inertial parameters, external disturbances, actuator failures and saturation constraints are considered. Firstly, a smooth function which is different from the common saturation treatment is presented to deal with the actuator constraints. Secondly, a fast non-singular terminal sliding mode (FNTSM) manifold composed of tracking errors is constructed. To estimate the unknown function in the sliding surface derivative, Chebyshev neural network (CNN) is introduced and thus the strict assumptions on uncertainties in many related works are abolished. By designing the CNN adaptive laws, a new fault-tolerant control scheme is proposed such that the attitude tracking can be achieved within a limited time interval. Compared with the existing CNN-based achievements with finite-time convergence, the approximation errors are proved to be finite-time stable instead of uniformly ultimately bounded (UUB). Finally, simulation experiments are conducted to demonstrate the satisfactory tracking performance of the attitude controller. [ABSTRACT FROM AUTHOR]

This paper provides a new solution for the finite‐time attitude maneuvers of rigid spacecraft. Uncertainties involving unknown inertial parameters, external disturbances and actuator failures are taken into account. With an effort to achieve attitude tracking despite the impact of uncertainties, a non‐singular terminal sliding mode (NTSM) manifold consisting of attitude errors and angular velocity errors is first constructed. After that, a simple but efficient adaptive updating law is derived to estimate the upper bound of the lumped unknown function in the derivative of sliding surface. Combining NTSM technology and pure adaptive control, a chattering‐free fault‐tolerant controller is presented. The premise assumptions on uncertainties in most of the existing achievements are eliminated, which makes the controller less constrained and more practical. The rigorous proof of finite‐time stability is provided and the convergent regions of tracking errors are explicitly expressed. Finally, numerical simulation is conducted to verify the effectiveness of the proposed control scheme and the comparison experiments with relevant literature demonstrate the satisfactory performances. [ABSTRACT FROM AUTHOR]

Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus through physical proximity and functional interaction. In response to external and internal stimuli, lysosomes actively adjust their distribution between peripheral and perinuclear regions and modulate lysosome–nucleus signaling pathways; in turn, the nucleus fine-tunes lysosomal biogenesis and functions through transcriptional controls. Changes in coordination between these two essential organelles are associated with metabolic disorders, neurodegenerative diseases, and aging. In this review, we address recent advances in lysosome–nucleus communication by multi-tiered regulatory mechanisms and discuss how these regulations couple metabolic inputs with organellar motility, cellular signaling, and transcriptional network. Lysosomal–nuclear communication coordinates lysosomal positioning, metabolism, and signaling with nuclear transcription to support fundamental cellular activities. Lysosomal positioning between peripheral and perinuclear regions is subject to cooperative regulation in response to metabolic stimuli and contributes to lysosomal functions and signaling. Retrograde transport of chaperone proteins and transcription factors from the lysosome to the nucleus is actively regulated by metabolic signaling. Nuclear transcriptional networks comprise a variety of different transcription factors that act independently or coordinately to fine tune lysosomal-autophagic gene expression. [ABSTRACT FROM AUTHOR]

Summary: In this article, the problem of finite‐time attitude‐tracking control for rigid spacecraft is addressed. Uncertainties caused by external disturbances, unknown inertial matrix, actuator failures, and saturation constraints are tackled simultaneously. First, a smooth function that is more qualified to approximate the standard saturation characteristics is presented to deal with the actuator saturation constraints. Second, a fast nonsingular terminal sliding mode (FNTSM) manifold is constructed as a foundation of controllers design. By incorporating the fuzzy logic system into FNTSM technique, a less demanding solution of coping with model uncertainties is provided because the requirement of a prior knowledge of unknown inertial parameters and external disturbances in many existing achievements is removed. To reduce the number of parameters to be estimated, the norm approximation approach is exploited. Subsequently, an antichattering attitude controller is presented such that all the tracking errors converge into arbitrary small domains around the origin in finite time. The result is further extended to obtain a fault‐tolerant controller against completely failed actuators. Finally, numerical simulation is conducted to verify the effectiveness of the proposed control scheme and comparison with relevant literature demonstrates its high performance. Furthermore, an experiment for the large satellite Hubble Space Telescope is carried out to validate the practical feasibility. [ABSTRACT FROM AUTHOR]

Summary Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription. HES in turn upregulates SEC activity, forming an unexpected self-reinforcing feedback loop with SEC. SEC inactivation leads to neuroblast loss, whereas its forced activation results in neural progenitor dedifferentiation and tumorigenesis. Our studies unveil an SEC-mediated intracellular amplifier mechanism in ensuring robustness and precision in stem cell fate commitment and provide mechanistic explanation for the highly frequent association of SEC overactivation with human cancers. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are specialized sentinel and APCs coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed Ags, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states. TLR activation by a lipopeptide globally reshaped the cell-surface proteome of cDCs, with >100 proteins upregulated or downregulated. By simultaneously elevating positive regulators and reducing inhibitory signals across multiple protein families, the remodeling creates a cell-surface milieu promoting immune responses. Still, cDCs maintain the stimulatory-to-inhibitory balance by leveraging a distinct set of inhibitory molecules. This analysis thus uncovers the molecular complexity and plasticity of the cDC cell surface and provides a roadmap for understanding cDC activation and signaling., (Copyright © 2024 The Authors.)

Organismal aging involves functional declines in both somatic and reproductive tissues. Multiple strategies have been discovered to extend lifespan across species. However, how age-related molecular changes differ among various tissues and how those lifespan-extending strategies slow tissue aging in distinct manners remain unclear. Here we generated the transcriptomic Cell Atlas of Worm Aging (CAWA, http://mengwanglab.org/atlas ) of wild-type and long-lived strains. We discovered cell-specific, age-related molecular and functional signatures across all somatic and germ cell types. We developed transcriptomic aging clocks for different tissues and quantitatively determined how three different pro-longevity strategies slow tissue aging distinctively. Furthermore, through genome-wide profiling of alternative polyadenylation (APA) events in different tissues, we discovered cell-type-specific APA changes during aging and revealed how these changes are differentially affected by the pro-longevity strategies. Together, this study offers fundamental molecular insights into both somatic and reproductive aging and provides a valuable resource for in-depth understanding of the diversity of pro-longevity mechanisms., (© 2024. The Author(s).)

Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins associated with the lysosome mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked to longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using deep proteomic profiling, we systemically profiled lysosome-associated proteins linked with four different longevity mechanisms. We discovered the lysosomal recruitment of AMP-activated protein kinase and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we further elucidated lysosomal heterogeneity across tissues as well as the increased enrichment of the Ragulator complex on Cystinosin-positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity across multiple scales and provides resources for understanding the contribution of lysosomal protein dynamics to signal transduction, organelle crosstalk, and organism longevity., Competing Interests: YY, SG, YG, PH, QZ, JL, BJ, QZ, DS, MA, SJ, MW No competing interests declared, (© 2024, Yu, Gao, Guan et al.)

The correct establishment and maintenance of unidirectional Notch signaling are critical for the homeostasis of various stem cell lineages. However, the molecular mechanisms that prevent cell-autonomous ectopic Notch signaling activation and deleterious cell fate decisions remain unclear. Here we show that the retromer complex directly and specifically regulates Notch receptor retrograde trafficking in Drosophila neuroblast lineages to ensure the unidirectional Notch signaling from neural progenitors to neuroblasts. Notch polyubiquitination mediated by E3 ubiquitin ligase Itch/Su(dx) is inherently inefficient within neural progenitors, relying on retromer-mediated trafficking to avoid aberrant endosomal accumulation of Notch and cell-autonomous signaling activation. Upon retromer dysfunction, hypo-ubiquitinated Notch accumulates in Rab7 + enlarged endosomes, where it is ectopically processed and activated in a ligand-dependent manner, causing progenitor-originated tumorigenesis. Our results therefore unveil a safeguard mechanism whereby retromer retrieves potentially harmful Notch receptors in a timely manner to prevent aberrant Notch activation-induced neural progenitor dedifferentiation and brain tumor formation., Competing Interests: BL, CW, SG, RZ, RS, YL, YS No competing interests declared, (© 2018, Li et al.)