Many chemotherapy treatments induce apoptosis or pyroptosis through BAK/BAX-dependent mitochondrial pathway. BAK/BAX activation causes the mitochondrial outer membrane permeabilization (MOMP), which induces the activation of pro-apoptotic caspase cascade. GSDME cleavage by the pro-apoptotic caspases determines whether chemotherapy drug treatments induce apoptosis or pyroptosis, however, its regulation mechanisms are not clear. In this study, we showed that TNFα+CHX and navitoclax-induced cancer cell pyroptosis through a BAK/BAX-caspase-3-GSDME signaling pathway. GSDME knockdown inhibited the pyroptosis, suggesting the essential role of GSDME in this process. Interestingly, GSDME was found to be palmitoylated on its C-terminal (GSDME-C) during chemotherapyinduced pyroptosis, while 2-bromopalmitate (2-BP) could inhibit the GSDME-C palmitoylation and chemotherapyinduced pyroptosis. Mutation of palmitoylation sites on GSDME also diminished the pyroptosis induced by chemotherapy drugs. Moreover, 2-BP treatment increased the interaction between GSDME-C and GSDME-N, providing a potential mechanism of this function. Further studies indicated several ZDHHC proteins including ZDHHC-2,7,11,15 could interact with and palmitoylate GSDME. Our findings offered new targets to achieve the transformation between chemotherapy-induced pyroptosis and apoptosis.
Ecology and biomechanics play central roles in the generation of phenotypic diversity. When unrelated taxa invade a similar ecological niche, biomechanical demands can drive convergent morphological transformations. Thus, examining convergence helps to elucidate the key catalysts of phenotypic change. Gliding mammals are often presented as a classic case of convergent evolution because they independently evolved in numerous clades, each possessing patagia ("wing" membranes) that generate lift during gliding. We use phylogenetic comparative methods to test whether the skeletal morphologies of the six clades of extant gliding mammals demonstrate convergence. Our results indicate that glider skeletons are convergent, with glider groups consistently evolving proportionally longer, more gracile limbs than arborealists, likely to increase patagial surface area. Nonetheless, we interpret gliders to represent incomplete convergence because (1) evolutionary model-fitting analyses do not indicate strong selective pressures for glider trait optima, (2) the three marsupial glider groups diverge rather than converge, and (3) the gliding groups remain separated in morphospace (rather than converging on a single morphotype), which is reflected by an unexpectedly high level of morphological disparity. That glider skeletons are morphologically diverse is further demonstrated by fossil gliders from the Mesozoic Era, which possess unique skeletal characteristics that are absent in extant gliders. Glider morphologies may be strongly influenced by factors such as body size and attachment location of patagia on the forelimb, which can vary among clades. Thus, convergence in gliders appears to be driven by a simple lengthening of the limbs, whereas additional skeletal traits reflect nuances of the gliding apparatus that are distinct among different evolutionary lineages. Our unexpected results add to growing evidence that incomplete convergence is prevalent in vertebrate clades, even among classic cases of convergence, and they highlight the importance of examining form-function relationships in light of phylogeny, biomechanics, and the fossil record. * This article corresponds to Quinn, B. L. 2020. Digest: Incomplete convergence drives formfunction relationship in gliders. Evolution.
Due to the limited energy of the sensor nodes, the unreasonable clustering routing algorithm will cause node premature death and low utilization of energy efficiency in wireless sensor network (WSN). In Adaptive Thresholdsensitive Energy Efficient Network (APTEEN), the assignments of the cluster head (CH) are much heavier than other nodes. The CH unbalanced energy dissipation between nodes that make them die prematurely. Ant colony algorithm can avoid this problem, so this paper presents a double cluster heads Adaptive Threshold-sensitive Energy Efficient Network based on ant colony (ADCAPTEEN). ADCAPTEEN optimizes the cluster head election method compared with APTEEN. It suggests that one master cluster head (MCH) and one vice cluster head (VCH) will be selected in each cluster. The double cluster heads (DCH) can co-work on data collection, fusion, transition, etc. To make routes more stable and energy efficient, this paper proposes a Multiple Adaptive Threshold-sensitive Energy Efficient Network based on Ant-colony (AMAPTEEN). It is the optimization of ADCAPTEEN. And CH selects intermediate node (IM_node) multiple times with ant colony algorithm per round in each cluster, and this way forms multiple route transmission data. Simulation in OPNET proves that compared with APTEEN, ADCAPTEEN reduces energy dissipation, improves node survival rate, and extends network life cycle. AMAPTEEN delays the time of node death, balances energy consumption, and extends network lifetime further operating in the same settings compared with ADCAPTEEN. The proposed two algorithms have good scalability, and they are suitable for large-scale network.
Many cellular stresses are transduced into apoptotic signals through modification or upregulation of the BH3-only subfamily of BCL2 proteins. Through direct or indirect mechanisms, these proteins activate BAK and BAX to permeabilize the mitochondrial outer membrane. While the BH3-only proteins BIM, PUMA, and tBID have been confirmed to directly activate BAK through its canonical BH3 binding groove, whether the BH3-only proteins BMF, HRK or BIK can directly activate BAK is less clear. Here we show that BMF and HRK bind and directly activate BAK. Through NMR studies, site-directed mutagenesis, and advanced molecular dynamics simulations, we also find that BAK activation by BMF and possibly HRK involves a previously unrecognized binding groove formed by BAK α4, α6, and α7 helices. Alterations in this groove decrease the ability of BMF and HRK to bind BAK, permeabilize membranes and induce apoptosis, suggesting a potential role for this BH3-binding site in BAK activation.
Sonic metamaterials have a wide range of applications in wave control and super-resolution imaging, and are favored for their several unique and advantageous properties. However, current double-negative sonic metamaterials have complex structures composed of various materials, which limits their design and application. Thus, we must produce double-negative features using a simple structure of one material. Because of their unique concave configurations and various resonances, star-shaped structures readily form band gaps and show superior material properties. In this study, we designed and simulated star-shaped single-phase metamaterials, considered ideal structures. Our numerical results suggest that these metamaterials have two band gaps as well as double-negative properties over specific frequency ranges. Moreover, we investigated how their band gap and double-negative properties depended on the concave angle.
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