3,843 research outputs found

    Cytosolic thioredoxin reductase 1 is required for correct disulfide formation in the ER

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    Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway

    Structure-Function Analysis of Diacylglycerol Acyltransferase Sequences from 70 Organisms

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    <p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obesity and related diseases. The objective of this analysis was to identify conserved sequence motifs and amino acid residues for better understanding of the structure-function relationship of these important enzymes.</p> <p>Results</p> <p>117 DGAT sequences from 70 organisms including plants, animals, fungi and human are obtained from database search using tung tree DGATs. Phylogenetic analysis separates these proteins into DGAT1 and DGAT2 subfamilies. These DGATs are integral membrane proteins with more than 40% of the total amino acid residues being hydrophobic. They have similar properties and amino acid composition except that DGAT1s are approximately 20 kDa larger than DGAT2s. DGAT1s and DGAT2s have 41 and 16 completely conserved amino acid residues, respectively, although only two of them are shared by all DGATs. These residues are distributed in 7 and 6 sequence blocks for DGAT1s and DGAT2s, respectively, and located at the carboxyl termini, suggesting the location of the catalytic domains. These conserved sequence blocks do not contain the putative neutral lipid-binding domain, mitochondrial targeting signal, or ER retrieval motif. The importance of conserved residues has been demonstrated by site-directed and natural mutants.</p> <p>Conclusions</p> <p>This study has identified conserved sequence motifs and amino acid residues in all 117 DGATs and the two subfamilies. None of the completely conserved residues in DGAT1s and DGAT2s is present in recently reported isoforms in the multiple sequences alignment, raising an important question how proteins with completely different amino acid sequences could perform the same biochemical reaction. The sequence analysis should facilitate studying the structure-function relationship of DGATs with the ultimate goal to identify critical amino acid residues for engineering superb enzymes in metabolic engineering and selecting enzyme inhibitors in therapeutic application for obesity and related diseases.</p

    Resting-state EEG power and coherence vary between migraine phases

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    © 2016, The Author(s). Background: Migraine is characterized by a series of phases (inter-ictal, pre-ictal, ictal, and post-ictal). It is of great interest whether resting-state electroencephalography (EEG) is differentiable between these phases. Methods: We compared resting-state EEG energy intensity and effective connectivity in different migraine phases using EEG power and coherence analyses in patients with migraine without aura as compared with healthy controls (HCs). EEG power and isolated effective coherence of delta (1–3.5 Hz), theta (4–7.5 Hz), alpha (8–12.5 Hz), and beta (13–30 Hz) bands were calculated in the frontal, central, temporal, parietal, and occipital regions. Results: Fifty patients with episodic migraine (1–5 headache days/month) and 20 HCs completed the study. Patients were classified into inter-ictal, pre-ictal, ictal, and post-ictal phases (n = 22, 12, 8, 8, respectively), using 36-h criteria. Compared to HCs, inter-ictal and ictal patients, but not pre- or post-ictal patients, had lower EEG power and coherence, except for a higher effective connectivity in fronto-occipital network in inter-ictal patients (p <.05). Compared to data obtained from the inter-ictal group, EEG power and coherence were increased in the pre-ictal group, with the exception of a lower effective connectivity in fronto-occipital network (p <.05). Inter-ictal and ictal patients had decreased EEG power and coherence relative to HCs, which were “normalized” in the pre-ictal or post-ictal groups. Conclusion: Resting-state EEG power density and effective connectivity differ between migraine phases and provide an insight into the complex neurophysiology of migraine

    Near-Infrared Super Resolution Imaging with Metallic Nanoshell Particle Chain Array

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    We propose a near-infrared super resolution imaging system without a lens or a mirror but with an array of metallic nanoshell particle chain. The imaging array can plasmonically transfer the near-field components of dipole sources in the incoherent and coherent manners and the super resolution images can be reconstructed in the output plane. By tunning the parameters of the metallic nanoshell particle, the plasmon resonance band of the isolate nanoshell particle red-shifts to the near-infrared region. The near-infrared super resolution images are obtained subsequently. We calculate the field intensity distribution at the different planes of imaging process using the finite element method and find that the array has super resolution imaging capability at near-infrared wavelengths. We also show that the image formation highly depends on the coherence of the dipole sources and the image-array distance.Comment: 15 pages, 6 figure

    Electron Transport in Very Clean, As-Grown Suspended Carbon Nanotubes

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    Single walled carbon nanotubes (SWNT) have displayed a wealth of quantum transport phenomena thus far. Defect free, unperturbed SWNTs with wellbehaved or tunable metal contacts are important to probing the intrinsic electrical properties of nanotubes. Meeting these conditions experimentally is nontrivial due to numerous disorder and randomizing factors. Here we show that ~ 1 um long fully suspended SWNTs grown-in-place between metal contacts afford SWNT devices exhibiting well-defined characteristics over much wider energy ranges than nanotubes pinned on substrates. Various low temperature transport regimes in true-metallic, small and large bandgap semiconducting nanotubes are observed including quantum states shell-filling, -splitting and -crossing in magnetic fields for medium conductance devices. The clean transport data reveals a correlation between the contact junction resistance and the various transport regimes in SWNT devices. Further, we show that electrical transport data can be used to probe the band structures of nanotubes including nonlinear band dispersion.Comment: Nature Materials, in pres

    Attention wins over sensory attenuation in a sound detection task

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    'Sensory attenuation', i.e., reduced neural responses to self-induced compared to externally generated stimuli, is a well-established phenomenon. However, very few studies directly compared sensory attenuation with attention effect, which leads to increased neural responses. In this study, we brought sensory attenuation and attention together in a behavioural auditory detection task, where both effects were quantitatively measured and compared. The classic auditory attention effect of facilitating detection performance was replicated. When attention and sensory attenuation were both present, attentional facilitation decreased but remained significant. The results are discussed in the light of current theories of sensory attenuation

    Quantum anti-Zeno effect without wave function reduction

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    We study the measurement-induced enhancement of the spontaneous decay (called quantum anti-Zeno effect) for a two-level subsystem, where measurements are treated as couplings between the excited state and an auxiliary state rather than the von Neumann's wave function reduction. The photon radiated in a fast decay of the atom, from the auxiliary state to the excited state, triggers a quasi-measurement, as opposed to a projection measurement. Our use of the term "quasi-measurement" refers to a "coupling-based measurement". Such frequent quasi-measurements result in an exponential decay of the survival probability of atomic initial state with a photon emission following each quasi-measurement. Our calculations show that the effective decay rate is of the same form as the one based on projection measurements. What is more important, the survival probability of the atomic initial state which is obtained by tracing over all the photon states is equivalent to the survival probability of the atomic initial state with a photon emission following each quasi-measurement to the order under consideration. That is because the contributions from those states with photon number less than the number of quasi-measurements originate from higher-order processes.Comment: 7 pages, 3 figure

    A hybrid model for identity obfuscation by face replacement

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    As more and more personal photos are shared and tagged in social media, avoiding privacy risks such as unintended recognition becomes increasingly challenging. We propose a new hybrid approach to obfuscate identities in photos by head replacement. Our approach combines state of the art parametric face synthesis with latest advances in Generative Adversarial Networks (GAN) for data-driven image synthesis. On the one hand, the parametric part of our method gives us control over the facial parameters and allows for explicit manipulation of the identity. On the other hand, the data-driven aspects allow for adding fine details and overall realism as well as seamless blending into the scene context. In our experiments, we show highly realistic output of our system that improves over the previous state of the art in obfuscation rate while preserving a higher similarity to the original image content
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