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Our results provide a model for high dose-dependent chemoresistance in neuroblastoma cells that could enable a patient-dependent chemotherapy screening strategy.Mitochondria are key organelles inside the cell that house a wide range of molecular pathways involved in energy metabolism, ions homeostasis, and cell death. Several databases characterize the different mitochondrial aspects and thus support basic and clinical research. Here we present MitopatHs, a web-based data set that allows navigating among the biochemical signaling pathways (PatHs) of human (H) mitochondria (Mito). MitopatHs is designed to visualize and comprehend virtually all types of pathways in two complementary ways a logical view, where the sequence of biochemical reactions is presented as logical deductions, and an intuitive graphical visualization, which enables the examination and the analysis of each step of the pathway. MitopatHs is a manually curated, open access and collaborative tool, whose goal is to enable the visualization and comprehension of complicated molecular routes in an easy and fast way.Glycosylation is a fundamental post-translational modification of proteins that boosts their structural diversity providing subtle and specialized biological properties and functions. All those genetic diseases due to a defective glycan biosynthesis and attachment to the nascent glycoproteins fall within the wide area of congenital disorders of glycosylation (CDG), mostly causing multisystem involvement. In the present paper, we detailed the unique serum N-glycosylation of a CDG-candidate patient with an unexplained neurological phenotype and liver adenomatosis harboring a recurrent pathogenic HNF1α variant. Serum transferrin isoelectric focusing showed a surprising N-glycosylation pattern consisting on hyposialylation, as well as remarkable hypersialylation. Mass spectrometry-based glycomic analyses of individual serum glycoproteins enabled to unveil hypersialylated complex N-glycans comprising up to two sialic acids per antenna. Further advanced MS analysis showed the additional sialic acid is bonded through an α2-6 linkage to the peripheral N-acetylglucosamine residue.Neuroblastoma is a highly heterogeneous embryonal solid tumor of the sympathetic nervous system. As some tumors can be treated to undergo differentiation, investigating this process can guide differentiation-based therapies of neuroblastoma. Here, we studied the role of E3 ubiquitin ligases Cbl and Cbl-b in regulation of long-term signaling responses associated with extracellular signal-regulated kinase phosphorylation and neurite outgrowth, a morphological marker of neuroblastoma cell differentiation. Using quantitative mass spectrometry (MS)-based proteomics, we analyzed how the neuroblastoma cell line proteome, phosphoproteome, and ubiquitylome were affected by Cbl and Cbl-b depletion. To quantitatively assess neurite outgrowth, we developed a high-throughput microscopy assay that was applied in combination with inhibitor studies to pinpoint signaling underlying neurite outgrowth and to functionally validate proteins identified in the MS data sets. Using this combined approach, we identified a role for SHP-2 and CDK16 in Cbl/Cbl-b-dependent regulation of extracellular signal-regulated kinase phosphorylation and neurite outgrowth, highlighting their involvement in neuroblastoma cell differentiation.Triboelectric nanogenerator (TENG) is regarded as an equally important mechanical energy harvesting technology as electromagnetic generator (EMG). Here, the input mechanical torques and energy conversion efficiencies of the rotating EMG and TENG are systematically measured, respectively. At constant rotation rates, the input mechanical torque of EMG is balanced by the friction resisting torque and electromagnetic resisting torque, which increases with the increasing rotation rate due to Ampere force. While the input mechanical torque of TENG is balanced by the friction resisting torque and electrostatic resisting torque, which is nearly constant at different rotation rates. The energy conversion efficiency of EMG increases with the increasing input mechanical power, while that of the TENG remains nearly constant. Compared with the EMG, the TENG has a higher conversion efficiency at a low input mechanical power, which demonstrates a remarkable merit of the TENG for efficiently harvesting weak ambient mechanical energy.Somitogenesis is often described using the clock-and-wavefront (CW) model, which does not explain how molecular signaling rearranges the pre-somitic mesoderm (PSM) cells into somites. Our scanning electron microscopy analysis of chicken embryos reveals a caudally-progressing epithelialization front in the dorsal PSM that precedes somite formation. Signs of apical constriction and tissue segmentation appear in this layer 3-4 somite lengths caudal to the last-formed somite. TH5427 We propose a mechanical instability model in which a steady increase of apical contractility leads to periodic failure of adhesion junctions within the dorsal PSM and positions the future inter-somite boundaries. This model produces spatially periodic segments whose size depends on the speed of the activation front of contraction (F), and the buildup rate of contractility (Λ). The Λ/F ratio determines whether this mechanism produces spatially and temporally regular or irregular segments, and whether segment size increases with the front speed.In modern society, the natural drive to behave impulsively in order to obtain rewards must often be curbed. A continued failure to do so is associated with a range of outcomes including drug abuse, pathological gambling, and obesity. Here, we used virtual reality technology to investigate whether spatial proximity to rewards has the power to exacerbate the drive to behave impulsively toward them. We embedded two behavioral tasks measuring distinct forms of impulsive behavior, impulsive action, and impulsive choice, within an environment rendered in virtual reality. Participants responded to three-dimensional cues representing food rewards located in either near or far space. Bayesian analyses revealed that participants were significantly less able to stop motor actions when rewarding cues were near compared with when they were far. Since factors normally associated with proximity were controlled for, these results suggest that proximity plays a distinctive role in driving impulsive actions for rewards.