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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]

The problem of finite-time attitude-tracking control (ATC) for a rigid spacecraft subject to inertial uncertainties, external disturbances, actuator saturations and faults is addressed. First, a fast nonsingular terminal sliding mode (FNTSM) manifold is constructed to improve robustness. Second, the fuzzy logic system (FLS) is integrated into the manifold derivative to deal with the lumped unknown function. The specific assumptions about uncertainties in most of the existing achievements are no longer needed. Combining the FNTSM and fuzzy approximation techniques, an enhanced fault-tolerant control scheme is developed. Compared to almost all finite-time ATC results based on FLS or neural network, a new Proof line is proposed to prove that the approximation errors are finite-time stable instead of asymptotically stable. Therefore, the attitude controller presented herein guarantees the real finite-time stability in a complete sense. Finally, numerical experiments are conducted to verify the effectiveness of the solution, and comparisons with related works are displayed. • Assumptions on uncertainties in the existing achievements are abolished. • Finite-time stability of fuzzy approximation errors is proved via a new Proof line. • Norm approximation is exploited to reduce the parameters to be estimated online. • The attitude controller guarantees the finite-time stability in a complete sense. [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]

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]

In this paper, to improve the dynamic performance of DFIG-based WT, a NADRC technology is proposed. The proposed NADRC can actively estimate and compensate the plant internal dynamics and external disturbances in real time. Therefore, it improves the tracking performance of the rotor current without any overshoot and steady-state error, and enhances the fault ride-through capability of DFIG-based wind turbine. Compared with the proportional PI control, the proposed NADRC during grid fault can significantly suppress the peak values of stator and rotor currents and DC-link voltage, and decrease the oscillation time of electromagnetic torque. Moreover, the proposed NADRC has a characteristic of one-parameter tuning by using the parameterization technique of controller, and parameter tuning of NADRC is only determined by the rise time of the system step response. A series of simulations for various cases on a 1.5-MW DFIG-based wind turbine are implemented, and the results validate the stability of the proposed NADRC and the strong robustness against the plant internal dynamics and external disturbances. [ABSTRACT FROM AUTHOR]

This paper studies the issue of finite-time prescribed performance control for spacecraft attitude tracking with inertia perturbations, external disturbances, actuator saturations and faults. To the best of the authors' knowledge, limited results have been reported in the relevant literature, and how to achieve the prescribed performance attitude tracking within a preset time interval is still an open problem. A novel finite-time prescribed performance function (FTPPF) whose settling time can be arbitrarily preset is first proposed. With the FTPPF predefining the envelope of tracking-error trajectories, the original spacecraft model is transformed into a new error system. Based on the barrier Lyapunov function of converted errors, the attitude controller is derived via backstepping design. During the process, the fuzzy approximation is used to handle inertia perturbations and external disturbances, while the Nussbaum gain technique is adopted to compensate for the efficiency loss caused by actuator saturations and faults. Finally, a finite-time fault-tolerant control scheme that guarantees both transient and steady-state performances (e.g., the maximum overshoot, steady-state error, and settling time) is developed. To verify the effectiveness of the solution, numerical experiments involving comparisons with related achievements are performed. [ABSTRACT FROM AUTHOR]

Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP (mtGTP) metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP- but not ATP-specific succinyl-CoA synthetase (SCS) promotes reproductive longevity in Caenorhabditis elegans. We further identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion and reproductive longevity. Moreover, we discovered that bacterial inputs affect mtGTP levels and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mtGTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and identify mitochondrial fission induction as an effective strategy to improve reproductive health. [Display omitted] • Mitochondrial GTP-specific succinyl-CoA synthetase regulates reproductive longevity • Oocyte mitochondrial positioning influences reproductive health during aging • Mitochondrial fission in the oocyte promotes reproductive longevity • Bacterial vitamin B12 modulates reproductive aging via GTP succinyl-CoA synthetase Lee et al. identify a signaling nexus between mitochondrial GTP metabolism and mitochondrial dynamics in regulating C. elegans reproductive aging. They further demonstrate that bacterial metabolites act through this signaling mechanism to modulate the host's reproductive health during aging. [ABSTRACT FROM AUTHOR]

Background: The computational prediction of methylation levels at single CpG resolution is promising to explore the methylation levels of CpGs uncovered by existing array techniques, especially for the 450 K beadchip array data with huge reserves. General prediction models concentrate on improving the overall prediction accuracy for the bulk of CpG loci while neglecting whether each locus is precisely predicted. This leads to the limited application of the prediction results, especially when performing downstream analysis with high precision requirements. Results: Here we reported PretiMeth, a method for constructing precise prediction models for each single CpG locus. PretiMeth used a logistic regression algorithm to build a prediction model for each interested locus. Only one DNA methylation feature that shared the most similar methylation pattern with the CpG locus to be predicted was applied in the model. We found that PretiMeth outperformed other algorithms in the prediction accuracy, and kept robust across platforms and cell types. Furthermore, PretiMeth was applied to The Cancer Genome Atlas data (TCGA), the intensive analysis based on precise prediction results showed that several CpG loci and genes (differentially methylated between the tumor and normal samples) were worthy for further biological validation. Conclusion: The precise prediction of single CpG locus is important for both methylation array data expansion and downstream analysis of prediction results. PretiMeth achieved precise modeling for each CpG locus by using only one significant feature, which also suggested that our precise prediction models could be probably used for reference in the probe set design when the DNA methylation beadchip update. PretiMeth is provided as an open source tool via https://github.com/JxTang-bioinformatics/PretiMeth. [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]