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Microtubules (MTs) are intrinsically dynamic polymers. In neurons, staggered individual microtubules form stable, polarized acentrosomal MT arrays spanning the axon and dendrite to support long-distance intracellular transport. How the stability and polarity of these arrays are maintained when individual MTs remain highly dynamic is still an open question. Here we visualize MT arrays in vivo in C. elegans neurons with single microtubule resolution. We find that the CRMP family homolog, UNC-33, is essential for the stability and polarity of MT arrays in neurites. In unc-33 mutants, MTs exhibit dramatically reduced rescue after catastrophe, develop gaps in coverage, and lose their polarity, leading to trafficking defects. UNC-33 is stably anchored on the cortical cytoskeleton and forms patch-like structures along the dendritic shaft. These discrete and stable UNC-33 patches concentrate free tubulins and correlate with MT rescue sites. In vitro , purified UNC-33 preferentially associates with MT tips and increases MT rescue frequency. Together, we propose that UNC-33 functions as a microtubule-associated protein (MAP) to promote individual MT rescue locally. Through this activity, UNC-33 prevents the loss of individual MTs, thereby maintaining the coverage and polarity of MT arrays throughout the lifetime of neurons.
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Previous studies on the clap-fling mechanism have predominantly focused on the initial downward and forward phases of flight in miniature insects, either during hovering or forward flight. However, this study presents the first comprehensive kinematic data of Coccinella septempunctata during climbing flight. It reveals, for the first time, that a clap-and-fling mechanism occurs during the initial upward and backward phase of the hind wings' motion. This discovery addresses the previously limited understanding of the clap-and-fling mechanism by demonstrating that, during the clap motion, the leading edges of beetle's wings come into proximity to form a figure-eight shape before rotating around their trailing edge to open into a "V" shape. By employing numerical solutions to solve Navier-Stokes (N-S) equations, we simulated both single hind wings' and double hind wings' aerodynamic conditions. Our findings demonstrate that this fling mechanism not only significantly enhances the lift coefficient by approximately 9.65% but also reduces the drag coefficient by about 1.7%, indicating an extension of the applicability range of this clap-and-fling mechanism beyond minute insect flight. Consequently, these insights into insect flight mechanics deepen our understanding of their biological characteristics and inspire advancements in robotics and biomimetics.
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Insulin-mechanistic target of rapamycin (mTOR) signaling drives anabolic growth during organismal development; its late-life dysregulation contributes to aging and limits lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here, we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin, INS-7, is drastically overproduced from early life and shortens lifespan in lpd-3 mutants. LPD-3 forms a bridge-like tunnel megaprotein to facilitate non-vesicular cellular lipid trafficking. Lipidomic profiling reveals increased hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1. Reducing the abundance of HYL-1, insulin receptor/DAF-2 or mTOR/LET-363, normalizes INS-7 levels and rescues the lifespan of lpd-3 mutants. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age. We propose that LPD-3 acts as a megaprotein brake for organismal aging and that its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Envejecimiento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Factores de Transcripción Forkhead/metabolismo , Insulina/metabolismo , Longevidad/fisiología , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The open-cathode forced-convection proton exchange membrane fuel cell has emerged as a viable option for portable energy sources. The forced-convection open-cathode mode, however, makes the cell's performance sensitive to changes in the cathode channel and fan parameters. In this study, small fuel cell stacks with varying cathode channel depths, widths, and width-rib ratios were assembled, and the effects of different cathode channel parameters and fan duty ratios on cell performance were investigated. The experimental results show that changing the cathode channel parameters has a significant impact on oxidant supply. When the channel width is increased, the cell performance increases first, then decreases. The cell performance decreases as the channel width-rib ratio increases. The performance of the cell improves as the cathode channel depth increases. Furthermore, the experimental results show that decreasing the duty ratio of the fan and using moderate heating improves cell performance.
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Insulin-mTOR signaling drives anabolic growth during organismal development, while its late-life dysregulation may detrimentally contribute to aging and limit lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin INS-7 is drastically over-produced in early life and shortens lifespan in lpd-3 mutants, a C. elegans model of human Alkuraya-Kucinskas syndrome. LPD-3 forms a bridge-like tunnel megaprotein to facilitate phospholipid trafficking to plasma membranes. Lipidomic profiling reveals increased abundance of hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1 (Homolog of Yeast Longevity). Reducing HYL-1 activity decreases INS-7 levels and rescues the lifespan of lpd-3 mutants through insulin receptor/DAF-2 and mTOR/LET-363. LPD3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age in wild type animals. We propose that LPD-3 acts as a megaprotein brake for aging and its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.
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Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through conserved homeostatic mechanisms. Here we report an exceptionally large and evolutionarily conserved protein LPD-3 in C. elegans that mediates lipid trafficking to confer cold resilience. We identify lpd-3 mutants in a mutagenesis screen for genetic suppressors of the lipid desaturase FAT-7. LPD-3 bridges the endoplasmic reticulum (ER) and plasma membranes (PM), forming a structurally predicted hydrophobic tunnel for lipid trafficking. lpd-3 mutants exhibit abnormal phospholipid distribution, diminished FAT-7 abundance, organismic vulnerability to cold, and are rescued by Lecithin comprising unsaturated phospholipids. Deficient lpd-3 homologues in Zebrafish and mammalian cells cause defects similar to those observed in C. elegans. As mutations in BLTP1, the human orthologue of lpd-3, cause Alkuraya-Kucinskas syndrome, LPD-3 family proteins may serve as evolutionarily conserved highway bridges critical for ER-associated non-vesicular lipid trafficking and resilience to cold stress in eukaryotic cells.
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Caenorhabditis elegans , Pez Cebra , Animales , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Fosfolípidos/metabolismo , Retículo Endoplásmico/metabolismo , Membrana Celular/metabolismo , Mamíferos/metabolismoRESUMEN
The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn2+ store, and excessive mitochondrial Zn2+ is linked to neurodegeneration. How mitochondria maintain their Zn2+ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn2+ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn2+ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn2+ exits from mitochondria and acts as an activation signal. In slc-30a9-deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk-Landau-Perez cerebrorenal syndrome where an SLC30A9 mutation was found.
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Proteínas de Transporte de Catión/farmacología , Proteínas de Ciclo Celular/farmacología , Mitocondrias/metabolismo , Factores de Transcripción/farmacología , Zinc/metabolismo , Animales , Axones/metabolismo , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/fisiología , Proteínas de Transporte de Catión/genética , Proteínas de Ciclo Celular/genética , Dendritas/metabolismo , Femenino , Técnicas de Inactivación de Genes , Células HeLa , Homeostasis , Humanos , Masculino , Potencial de la Membrana Mitocondrial , Mutación , Espermatozoides/fisiología , Factores de Transcripción/genéticaRESUMEN
The design of the anode flow field is critical for yielding better performance of micro direct methanol fuel cells (µDMFCs). In this work, the effect of different flow fields on cell performance was investigated by the simulation method. Compared with grid, parallel and double-serpentine flow fields, a single-serpentine flow field can better improve the mass transfer efficiency of methanol and the emission efficiency of the carbon dioxide by-product. The opening ratio and channel length also have important effects on the cell performance. The cells were manufactured using silicon-based micro-electro-mechanical system (MEMS) technologies and tested to verify the simulation results. The experimental results show that the single-serpentine flow field represents a higher peak power density (16.83 mWcm-2) than other flow fields. Moreover, the results show that an open ratio of 47.3% and a channel length of 63.5 mm are the optimal parameters for the single-serpentine flow field.
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Although the hybrid power system that combines a photovoltaic cell and a lithium-ion battery is increasingly mature and practical, long-lifetime auxiliary power will be still needed in severe weather conditions. A small-volume hydrogen-oxygen fuel cell system based on the hydrolysis of NaBH4 is designed. The fuel cell system contains a tiny hydrogen generator, a hydrogen cleaner, and a small fuel cell stack consisting of three units in series. The relationship between the amount of catalyst and output performance is discussed. The long-time discharging results indicate that the fuel cell system has high power capacity. The compact design allows the fuel cell system to integrate the structure with a photovoltaic cell and lithium-ion cell and forms a hybrid power system with a small package. The power management circuit for these power sources without logic devices is designed and tested. The control strategy selects the photovoltaic-battery subsystem as the primary power source, and the fuel cell subsystem works as the backup power source to handle the circumstance when the energy stored in the battery is exhausted. The test results show that the power management system could switch the power supply automatically and timely under various emergency conditions, and the output voltage remains stable all the time.
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A membrane electrode assembly (MEA) with a novel trilaminar-catalytic layered structure was designed and fabricated for a micro-direct methanol fuel cell (µ-DMFC). The trilaminar-catalytic layer comprises three porous layers. The medial layer has a lower porosity than the inner and outer layers. The simulation results predicted a lower water content and a higher oxygen concentration in the trilaminar-catalytic layer. The novel trilaminar-catalytic layer enhanced the back diffusion of water from the cathode to the anode, which reduces methanol crossover and improves oxygen mass transportation. The electrochemical results of the half-cell test indicate that the novel MEA has a greatly increased cathode polarization and a slightly increased anode polarization. Thus, this novel µ-DMFC structure has a higher power density and a longer discharging time, and hence may be used in portable systems.
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With the development of low-power technology in electronic devices, the wireless sensor network shows great potential in applications in health tracing and ocean monitoring. These scenarios usually contain abundant low-frequency vibration energy, which can be collected through appropriate energy conversion architecture; thus, the common issue of limited battery life in wireless sensor devices could be solved. Traditional energy-converting structures such as the cantilever-beam type or spring-mass type have the problem of high working frequency. In this work, an eccentric pendulum-based electromagnetic vibration energy harvester is designed, analyzed, and verified with the finite element analysis method. The pendulum that contains alternative distributed magnets in the outer side works as a rotor and has the advantages of a simple structure and low center frequency. The structure size is well scalable, and the optimal output performance can be obtained by optimizing the coil thickness and width for a given diameter of the energy harvester. The simulation results show that the energy harvester could work in ultra-low frequencies of 0.2-3.0 Hz. A full-scale prototype of the energy harvester is manufactured and tested. The center working frequency is 2.0 Hz with an average output power of 8.37 mW, which has potential for application in driving low-power wireless sensor nodes.
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Allomyrina dichotomahas a natural ultra-high flying ability and maneuverability. Especially its ability to fly flexibly in the air, makes it more adaptable to the harsh ecological environment. In this study, a bionic flapping-wing micro air vehicle (FMAV) is designed and fabricated by mimicking the flight mode ofA. dichotoma. Parametric design was employed for combining the airframe structure and flight characteristics analysis. To improve the transmission efficiency and compactness of the FMAV mechanisms, this study first analyses the body structure ofA. dichotoma, and then proposes a novel mechanism of FMAV based on its biological motion characteristics, the flight motion characteristics, and its musculoskeletal system. By optimizing the flapping-wing mechanism and mimicking the flying mechanism ofA. dichotoma, the large angle amplitude and the high-frequency flapping motion can be achieved to generate more aerodynamic force. Meanwhile, to improve the bionic effect and the wing performance of FMAV, the flexible deformation ofA. dichotomawings for each flapping period was observed by a high-speed camera. Furthermore, the bionic design of wings the prototype was carried out, therefore the wings can generate a high lift force in the flapping process. The experiment demonstrated that the aircraft can achieve a flapping angle of 160 degrees and 30 Hz flapping frequency. The attitude change of FMAV is realized by mimicking the movement for the change of attitude of theA. dichotoma, by changing the angle of attack of the wing, and executing the flight action of multiple degrees of freedom including pitch, roll and yaw. Finally, the aerodynamic experiment demonstrated that the prototype can offer 27.8 g lift and enough torque for altitude adjustment.
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Vuelo Animal , Alas de Animales , Animales , Fenómenos Biomecánicos , Biónica , Diseño de Equipo , Modelos BiológicosRESUMEN
INPP5K (SKIP) is an inositol 5-phosphatase that localizes in part to the endoplasmic reticulum (ER). We show that recruitment of INPP5K to the ER is mediated by ARL6IP1, which shares features of ER-shaping proteins. Like ARL6IP1, INPP5K is preferentially localized in ER tubules and enriched, relative to other ER resident proteins (Sec61ß, VAPB, and Sac1), in newly formed tubules that grow along microtubule tracks. Depletion of either INPP5K or ARL6IP1 results in the increase of ER sheets. In a convergent but independent study, a screen for mutations affecting the distribution of the ER network in dendrites of the PVD neurons of Caenorhabditis elegans led to the isolation of mutants in CIL-1, which encodes the INPP5K worm orthologue. The mutant phenotype was rescued by expression of wild type, but not of catalytically inactive CIL-1. Our results reveal an unexpected role of an ER localized polyphosphoinositide phosphatase in the fine control of ER network organization.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/enzimología , Dendritas/enzimología , Retículo Endoplásmico/enzimología , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Animales , Células COS , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Chlorocebus aethiops , Dendritas/genética , Retículo Endoplásmico/genética , Eliminación de Gen , Células HeLa , Humanos , Ratones , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/genéticaRESUMEN
Werner syndrome (WS) is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells (MSCs). This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, telomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN-deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.