Crystal Structure of the Caenorhabditis elegans Apoptosome Reveals an Octameric Assembly of CED-4

SummaryThe CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death in Caenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How the CED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystal structure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organized as a tetramer of an asymmetric dimer via a previously unreported interface among AAA+ ATPases. These eight CED-4 molecules form a funnel-shaped structure. The mature CED-3 protease is monomeric in solution and forms an active holoenzyme with the CED-4 apoptosome, within which the protease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosome appears to bind only two, not eight, molecules of mature CED-3. The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA+ ATPases and suggests a mechanism for the activation of CED-3

Prescribed Performance Control for Two-axis Optronic Stabilized Platform

Aiming at improving the tracking and stabilizing performance of two-axis optronic stabilized platform with Stribeck friction and uncertain velocity disturbance, a prescribed performance control strategy with unknown initial errors is designed. By designing a new performance function, the limit of traditional prescribed control that the initial error has to be known accurately is broken through. The strategy possesses strong robustness against unknown disturbance, and the state error is restrained to a predefined arbitrary small residual. It is guaranteed that the closed-loop system is uniformly ultimately bounded. The simulation results demonstrate the effectiveness of proposed strategy

Squid ink polysaccharide reduces cyclophosphamide-induced testicular damage via Nrf2/ARE activation pathway in mice

Objective(s):Cyclophosphamide (CP) toxicity on testis was hampered by squid ink polysaccharide (SIP) via restoration of antioxidant ability in our previous investigations. This study investigated roles of Nrf2/ARE signal pathway in testis of treated mice. Materials and Methods: Male Kunming mice were employed to undergo treatment with SIP and/or CP. Protein levels of Nrf2, keap-1, histone deacetylase 2 (HDAC2), quinone oxidoreductase 1 (NQO-1), and heme oxygenase 1 (HO-1) and phosphorylation level of protein kinase C (PKC) in testis were evaluated by Western blotting. Results: Data showed that SIP elevated expressions of NQO-1 and HO-1 genes, two downstream target molecules of Nrf2, via activating Nrf2 to play preventive roles on CP-treated testis, and further discovered that upstream regulators of Nrf2, keap-1, HDAC2, and PKC, were concerned with the regulation of Nrf2. Conclusion: These results suggest that SIP could effectively weaken CP-associated testicular damage via Nrf2/ARE signal pathway

Prescribed Performance Control for Two-axis Optronic Stabilized Platform

Aiming at improving the tracking and stabilizing performance of two-axis optronic stabilized platform with Stribeck friction and uncertain velocity disturbance, a prescribed performance control strategy with unknown initial errors is designed. By designing a new performance function, the limit of traditional prescribed control that the initial error has to be known accurately is broken through. The strategy possesses strong robustness against unknown disturbance, and the state error is restrained to a predefined arbitrary small residual. It is guaranteed that the closed-loop system is uniformly ultimately bounded. The simulation results demonstrate the effectiveness of proposed strategy

Systematical assessment of digit ratio in a female masculinization disease: polycystic ovary syndrome

BackgroundIn recent years, the right ratio of 2nd and 4th digit length (2D:4D) is regarded as an anatomical marker of prenatal testosterone exposure. Polycystic ovary syndrome (PCOS) is a female masculinized disease and is determined by prenatal testosterone exposure. Whether the ratio in the right hand of PCOS women is reduced or not compared with non-PCOS women is under debate. To further investigate the relationship between PCOS and digit ratio, we systematically measured all the digit ratios.MethodsWe recruited 34 non-PCOS women, 116 PCOS women, and 40 men and systematically measured all the ratios of digit length (2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, and 4D:5D) of right hands and left hands.ResultsLeft 2D:3D, 2D:4D, and 2D:5D in men were significantly lower than those in non-PCOS women. Significantly lower digit ratios of left 2D:3D and 2D:4D were observed in PCOS compared with non-PCOS women. In the subgroup analysis, the left ratio of digit length in 2D:3D and 2D:5D of the hyperandrogenism subgroup was lower than that of the non-hyperandrogenism subgroup without statistical significance. The logistic regression model of PCOS revealed that 2D:3D, 2D:4D, 2D:5D, and 3D:4D of left hands were statistically related to the diagnosis of PCOS among all the digit ratios.ConclusionNot only 2D:4D but also other digit ratios, such as 2D:3D and 2D:5D, are a marker of prenatal testosterone exposure and may be an anatomical marker of PCOS. The majority of these significant differences included left 2D, with the following order: non-PCOS women > PCOS women > men

Hybrid Ginseng‐derived Extracellular Vesicles‐Like Particles with Autologous Tumor Cell Membrane for Personalized Vaccination to Inhibit Tumor Recurrence and Metastasis

Abstract Personalized cancer vaccines based on resected tumors from patients is promising to address tumor heterogeneity to inhibit tumor recurrence or metastasis. However, it remains challenge to elicit immune activation due to the weak immunogenicity of autologous tumor antigens. Here, a hybrid membrane cancer vaccine is successfully constructed by membrane fusion to enhance adaptive immune response and amplify personalized immunotherapy, which formed a codelivery system for autologous tumor antigens and immune adjuvants. Briefly, the functional hybrid vesicles (HM‐NPs) are formed by hybridizing ginseng‐derived extracellular vesicles‐like particles (G‐EVLPs) with the membrane originated from the resected autologous tumors. The introduction of G‐EVLPs can enhance the phagocytosis of autologous tumor antigens by dendritic cells (DCs) and facilitate DCs maturation through TLR4, ultimately activating tumor‐specific cytotoxic T lymphocytes (CTLs). HM‐NPs can indeed strengthen specific immune responses to suppress tumors recurrence and metastasis including subcutaneous tumors and orthotopic tumors. Furthermore, a long‐term immune protection can be obtained after vaccinating with HM‐NPs, and prolonging the survival of animals. Overall, this personalized hybrid autologous tumor vaccine based on G‐EVLPs provides the possibility of mitigating tumor recurrence and metastasis after surgery while maintaining good biocompatibility

Data from: Foraging responses of sheep to plant spatial micro-patterns can cause diverse associational effects of focal plant at individual and population levels

1. Multiple-scale foraging decisions by large herbivores can cause associational effects of focal plant individuals neighbored with different species. Spatial micro-patterns between the focal plant and its neighboring species within patches can affect herbivore foraging selectivity at within- and between-patch scale, which may consequently lead to associational plant effects occurring at both plant individual and population levels. However, these associational effects have not been explored together in the plant-herbivore interaction studies. 2. We aim to evaluate how plant spatial micro-pattern within different quality patches mediate herbivore foraging selectivity, thereby affecting the associational effects of focal plant individuals and population. 3. Using sheep as the model herbivore and a medium preferred species as the focal plant, we conducted a manipulative experiment by allowing sheep grazing freely among three different quality patches, each of which consisted of preferred, un-preferred and focal plant species with different abundances forming spatially aggregated or dispersed micro-patterns. 4. Results showed that, compared with the aggregated plant micro-pattern, dispersed plant micro-patterns within different quality patches increased sheep within-patch selectivity, and caused diverse associational effects of focal plant individuals. Focal plant individuals experienced neighbor contrast defense (i.e. got protection in the high quality patch) and associational defense (i.e. got protection in the low quality patch), respectively, when plants dispersedly distributed in the low and high quality patch. Focal plant individuals simultaneously experienced associational susceptibility (i.e. got damage in the high quality patch) and neighbor contrast susceptibility (i.e. got damage in the low quality patch) when plants dispersedly distributed in the medium quality patch. Furthermore, dispersed plant micro-patterns reduced sheep foraging selectivity between patches, and led to a lower consumption of focal plant population compared with the aggregated plant micro-pattern. 5. Herbivore adopt different within- and between-patch foraging decisions to maintain a high intake of the preferred species in response to various plant micro-patterns, and consequently cause diverse associational effects of both focal plant individuals and population. These associational effects have important implications for understanding the species coexistence and plant community assembly in the grazing ecosystems