Buurstout8992

Drosophila melanogaster is a useful and highly tractable model organism for understanding the molecular mechanisms of human diseases. We previously characterized a new dUbqn knockdown model that induces learning-memory and locomotive deficits mediated by impaired proteostasis. Although proteinopathies are the main causes of neurodegenerative diseases, limited information is currently available on the relationship between proteostasis and neurodegenerative-related behavioral perturbations, such as locomotion, wakefulness, and sexual activities. Thus, the present study aimed to elucidate the mechanisms by which dUbqn depletion which is known to cause proteinopathies, affects neurodegenerative-related behavioral perturbations. Pan-neuronal dUbqn-depleted flies showed significantly reduced evening activity along with altered pre- and postsynaptic structural NMJ's proteins by attenuating signals of Bruchpilot puncta and GluRIIA clustering. In addition, the neurochemical profiles of GABA, glutamate, dopamine, and serotonin were disturbed and these changes also affected courtship behaviors in dUbqn-depleted flies. Collectively, these results extend our understanding on how dUbqn depletion affects neurochemical regulation to drive behavioral disturbances that are generally found in the early stage of neurodegenerative diseases. Moreover, the present study may contribute a novel finding to the design of new agents that prevent disease progression or even treat diseases related to neurodegeneration.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.A helimagnet is a chiral magnet in which the direction of the magnetic moment spatially rotates in a plane perpendicular to the propagation vector. The sense of the rotation known as spin helicity is a robust degree of freedom of matter and may provide a new concept of magnetic memory if it can be electrically controlled and detected. Here we show that the helicity can be controlled by magnetic fields and electric currents in an itinerant helimagnet MnP. Second-harmonic resistivity measurements allow us to read out the controlled helicity. In contract to an insulating multiferroic magnet, in which spin rotation was shown to be controllable by an electric field, we achieve helicity manipulation by using an electric current in the conducting helimagnet. The controllability of the spin helicity may pave the way to new method of realizing magnetic memories based on the spin internal degrees of freedom.Drug-induced gingival overgrowth (DIGO) is recognized as a side effect of nifedipine (NIF); however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed miR-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells (GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2 (HMGA2) is the downstream target gene of miR-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that miR-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of miR-4651 and HMGA2 as therapeutic targets.The emerging resistance of crop pathogens to fungicides poses a challenge to food security and compels discovery of new antifungal compounds. Here, we show that mono-alkyl lipophilic cations (MALCs) inhibit oxidative phosphorylation by affecting NADH oxidation in the plant pathogens Zymoseptoria tritici, Ustilago maydis and Magnaporthe oryzae. One of these MALCs, consisting of a dimethylsulfonium moiety and a long alkyl chain (C18-SMe2+), also induces production of reactive oxygen species at the level of respiratory complex I, thus triggering fungal apoptosis. In addition, C18-SMe2+ activates innate plant defense. This multiple activity effectively protects cereals against Septoria tritici blotch and rice blast disease. C18-SMe2+ has low toxicity in Daphnia magna, and is not mutagenic or phytotoxic. Thus, MALCs hold potential as effective and non-toxic crop fungicides.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Tetraspanins play critical roles in various physiological processes, ranging from cell adhesion to virus infection. The members of the tetraspanin family have four membrane-spanning domains and short and large extracellular loops, and associate with a broad range of other functional proteins to exert cellular functions. Here we report the crystal structure of CD9 and the cryo-electron microscopic structure of CD9 in complex with its single membrane-spanning partner protein, EWI-2. The reversed cone-like molecular shape of CD9 generates membrane curvature in the crystalline lipid layers, which explains the CD9 localization in regions with high membrane curvature and its implications in membrane remodeling. The molecular interaction between CD9 and EWI-2 is mainly mediated through the small residues in the transmembrane region and protein/lipid interactions, whereas the fertilization assay revealed the critical involvement of the LEL region in the sperm-egg fusion, indicating the different dependency of each binding domain for other partner proteins.Escaping programmed cell death is a hallmark of cancer. NF-κB transcription factors are key regulator of cell survival and aberrant NF-κB signaling has been involved in the pathogenesis of most human malignancies. Although NF-κB is best known for its antiapoptotic role, other processes regulating the life/death balance, such as autophagy and necroptosis, seem to network with NF-κB. This review discusses how the reciprocal regulation of NF-κB, autophagy and programmed cell death affect cancer development and progression.Electron-phonon (e-ph) interactions are usually treated in the lowest order of perturbation theory. Here we derive next-to-leading order e-ph interactions, and compute from first principles the associated electron-two-phonon (2ph) scattering rates. The derivations involve Matsubara sums of two-loop Feynman diagrams, and the numerical calculations are challenging as they involve Brillouin zone integrals over two crystal momenta and depend critically on the intermediate state lifetimes. Using Monte Carlo integration together with a self-consistent update of the intermediate state lifetimes, we compute and converge the 2ph scattering rates, and analyze their energy and temperature dependence. We apply our method to GaAs, a weakly polar semiconductor with dominant optical-mode long-range e-ph interactions. We find that the 2ph scattering rates are as large as nearly half the value of the one-phonon rates, and that including the 2ph processes is necessary to accurately predict the electron mobility in GaAs from first principles.Optically-interfaced spins in the solid state are a promising platform for quantum technologies. A crucial component of these systems is high-fidelity, projective measurement of the spin state. Here, we demonstrate single-shot spin readout of a single rare earth ion qubit, Er3+, which is attractive for its telecom-wavelength optical transition and compatibility with silicon nanophotonic circuits. In previous work with laser-cooled atoms and ions, and solid-state defects, spin readout is accomplished using fluorescence on an optical cycling transition; however, Er3+ and other rare earth ions generally lack strong cycling transitions. We demonstrate that modifying the electromagnetic environment around the ion can increase the strength and cyclicity of the optical transition by several orders of magnitude, enabling single-shot quantum nondemolition readout of the ion's spin with 94.6% fidelity. We use this readout to probe coherent dynamics and relaxation of the spin.The viability of past, current and future devices for information technology hinges on their sensitivity to the presence of impurities. The latter can reshape extrinsic Hall effects or the efficiency of magnetoresistance effects, essential for spintronics, and lead to resistivity anomalies, the so-called Kondo effect. see more Here, we demonstrate that atomic defects enable highly efficient all-electrical detection of spin-swirling textures, in particular magnetic skyrmions, which are promising bit candidates in future spintronics devices. The concomitant impurity-driven alteration of the electronic structure and magnetic non-collinearity gives rise to a new spin-mixing magnetoresistance (XMRdefect). Taking advantage of the impurities-induced amplification of the bare transport signal, which depends on their chemical nature, a defect-enhanced XMR (DXMR) is proposed. Both XMR modes are systematised for 3d and 4d transition metal defects implanted at the vicinity of skyrmions generated in PdFe bilayer deposited on Ir(111). The ineluctability of impurities in devices promotes the implementation of defect-enabled XMR modes in reading architectures with immediate implications in magnetic storage technologies.Calorie-restricted (CR) diet has multiple beneficial effects on brain function. Here we report morphological and functional changes in hippocampal astrocytes in 3-months-old mice subjected to 1 month of the diet. Whole-cell patch-clamp recordings were performed in the CA1 stratum (str.) radiatum astrocytes of hippocampal slices. The cells were also loaded with fluorescent dye through the patch pipette. CR did not affect the number of astrocytic branches but increased the volume fraction (VF) of distal perisynaptic astrocytic leaflets. The astrocyte growth did not lead to a decrease in the cell input resistance, which may be attributed to a decrease in astrocyte coupling through the gap junctions. Western blotting revealed a decrease in the expression of Cx43 but not Cx30. Immunocytochemical analysis demonstrated a decrease in the density and size of Cx43 clusters. Cx30 cluster density did not change, while their size increased in the vicinity of astrocytic soma. CR shortened K+ and glutamate transporter currents in astrocytes in response to 5 × 50 Hz Schaffer collateral stimulation. However, no change in the expression of astrocytic glutamate transporter 1 (GLT-1) was observed, while the level of glutamine synthetase (GS) decreased. These findings suggest that enhanced enwrapping of synapses by the astrocytic leaflets reduces glutamate and K+ spillover. Reduced spillover led to a decreased contribution of extrasynaptic N2B containing N-methyl-D-aspartate receptors (NMDARs) to the tail of burst-induced EPSCs. The magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. This enhancement was abolished by N2B-NMDARs antagonist. Our findings suggest that astrocytic morphofunctional remodeling is responsible for enhanced synaptic plasticity, which provides a basis for improved learning and memory reported after CR.