41 research outputs found

    Effects of Starvation on Brain Short Neuropeptide F-1, -2, and -3 Levels and Short Neuropeptide F Receptor Expression Levels of the Silkworm, Bombyx mori

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    In our previous report, we demonstrated the possibility that various regulatory neuropeptides influence feeding behavior in the silkworm, Bombyx mori. Among these feeding-related neuropeptides, short neuropeptide F (sNPF) exhibited feeding-accelerating activity when injected into B. mori larvae. Like other insect sNPFs, the deduced amino acid sequence of the cDNA encoding the sNPF precursor appears to produce multiple sNPF and sNPF-related peptides in B. mori. The presence of three sNPFs, sNPF-1, sNPF-2, and sNPF-3, in the brain of B. mori larvae was confirmed by direct MALDI-TOF mass spectrometric profiling. In addition, all three sNPFs are present in other larval ganglia. The presence of sNPF mRNA in the central nervous system (CNS) was also confirmed by Reverse transcription-polymerase chain reaction. Semi-quantitative analyses of sNPFs in the larval brain using matrix-assisted laser desorption ionization time-of-flight mass spectrometry further revealed that brain sNPF levels decrease in response to starvation, and that they recover with the resumption of feeding. These data suggest that sNPFs were depleted by the starvation process. Furthermore, food deprivation decreased the transcriptional levels of the sNPF receptor (BNGR-A10) in the brain and CNS, suggesting that the sNPF system is dependent on the feeding state of the insect and that the sNPF system may be linked to locomotor activity associated with foraging behavior. Since the injection of sNPFs accelerated the onset of feeding in B. mori larvae, we concluded that sNPFs are strongly related to feeding behavior. In addition, semi-quantitative MS analyses revealed that allatostatin, which is present in the larval brain, is also reduced in response to starvation, whereas the peptide level of Bommyosuppressin was not affected by different feeding states

    Utility of robot‐assisted radical cystectomy with intracorporeal urinary diversion for muscle‐invasive bladder cancer

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    Radical cystectomy remains the gold standard for treatment of muscle‐invasive bladder cancer. Robot‐assisted radical cystectomy has technical advantages over laparoscopic radical cystectomy and has emerged as an alternative to open radical cystectomy. Despite the advancements in robotic surgery, experience with total intracorporeal reconstruction of urinary diversion remains limited. Most surgeons have carried out the hybrid approach of robot‐assisted radical cystectomy and extracorporeal reconstruction of urinary diversion, as intracorporeal reconstruction of urinary diversion remains technically challenging. However, intracorporeal reconstruction of urinary diversion might potentially proffer additional benefits, such as decreased fluid loss, reduction in estimated blood loss and a quicker return of bowel function. The adoption of intracorporeal ileal neobladder reconstruction has hitherto been limited to high‐volume academic institutions. In the present review, we compare the totally intracorporeal robot‐assisted radical cystectomy approach with open radical cystectomy and robot‐assisted radical cystectomy + extracorporeal reconstruction of urinary diversion in muscle‐invasive bladder cancer patients

    Intravenous cyclophosphamide treatment for systemic lupus erythematosus with severe autonomic disorders confirmed by head-up tilt table test: A case series

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    Autonomic disorders are common in patients with systemic lupus erythematosus (SLE), but the therapeutic strategy and methods for evaluating the effects of therapy have not been established. We describe the three cases of SLE patients who developed severe autonomic disorders as demonstrated by the head-up tilt table test (HUT). All three patients were treated by intensive immunosuppressive treatments including intravenous cyclophosphamide (IVCY); their HUT results all became negative. Our cases suggest that IVCY treatment can be a good therapeutic option for severe autonomic disorders in SLE patients. The HUT is a useful objective method for the diagnosis of and the evaluation of longitudinal therapeutic effects on autonomic disorders in SLE patients with orthostatic intolerance

    Time-resolved serial femtosecond crystallography reveals early structural changes in channelrhodopsin

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    X線自由電子レーザーを用いて、光照射によるチャネルロドプシンの構造変化の過程を捉えることに成功. 京都大学プレスリリース. 2021-03-26.Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore

    Light-induced structural changes and the site of O=O bond formation in PSII caught by XFEL

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    Photosystem II (PSII) is a huge membrane-protein complex consisting of 20 different subunits with a total molecular mass of 350 kDa for a monomer. It catalyses light-driven water oxidation at its catalytic centre, the oxygen-evolving complex (OEC). The structure of PSII has been analysed at 1.9 Å resolution by synchrotron radiation X-rays, which revealed that the OEC is a Mn4CaO5 cluster organized in an asymmetric, 'distorted-chair' form. This structure was further analysed with femtosecond X-ray free electron lasers (XFEL), providing the 'radiation damage-free' structure. The mechanism of O=O bond formation, however, remains obscure owing to the lack of intermediate-state structures. Here we describe the structural changes in PSII induced by two-flash illumination at room temperature at a resolution of 2.35 Å using time-resolved serial femtosecond crystallography with an XFEL provided by the SPring-8 ångström compact free-electron laser. An isomorphous difference Fourier map between the two-flash and dark-adapted states revealed two areas of apparent changes: around the QB/non-haem iron and the Mn4CaO5 cluster. The changes around the QB/non-haem iron region reflected the electron and proton transfers induced by the two-flash illumination. In the region around the OEC, a water molecule located 3.5 Å from the Mn4CaO5 cluster disappeared from the map upon two-flash illumination. This reduced the distance between another water molecule and the oxygen atom O4, suggesting that proton transfer also occurred. Importantly, the two-flash-minus-dark isomorphous difference Fourier map showed an apparent positive peak around O5, a unique μ4-oxo-bridge located in the quasi-centre of Mn1 and Mn4 (refs 4,5). This suggests the insertion of a new oxygen atom (O6) close to O5, providing an O=O distance of 1.5 Å between these two oxygen atoms. This provides a mechanism for the O=O bond formation consistent with that proposed previousl

    Autoimmune Autonomic Neuropathy: From Pathogenesis to Diagnosis

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    Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates

    Mechanically-Sensitive Fluorochromism by Molecular Domino Transformation in a Schiff Base Crystal

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    The ability to make large changes in properties against small external stimuli is one of key factors in sensing materials. Molecular domino transformation, i.e. polymorphic transformation starting at a stimulated point and extending to the whole crystal, is an attractive phenomenon from this viewpoint. We recently found such a transformation in a crystal of 4-nitro-N-salicylideneaniline as one of Schiff bases. In this study, quantitative evaluations were conducted on a mechanical stimulus and emission properties in the transformation of the crystal. Our results demonstrate the potential applicability of the crystal to detection of even less than a few μN mechanical stimuli as an emission color change. A molecular level transformation mechanism revealed by microcrystal electron diffraction also contributes to future development of the transformation-based materials

    A Novel Square-Planar Ni(II) Complex with an AminoCarboxamidoDithiolato-Type Ligand as an Active-Site Model of NiSOD

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    To understand the role of the unique equatorial coordination environment at the active center in nickel superoxide dismutase (NiSOD), we prepared a novel Ni­(II) complex with an amino–carboxamido–dithiolato-type square-planar ligand (<b>1</b>, [Ni<sup>2+</sup>(L<sub>1</sub>)]<sup>−</sup>) as a model of the NiSOD active site. Complex <b>1</b> has a low-spin square-planar structure in all solvents. Interestingly, the absorption wavelength and ν­(CO) stretching vibrations of <b>1</b> are affected by solvents. This provides an indication that the carbonyl oxygens participate in hydrogen-bonding interactions with solvents. These interactions are reflected in the redox potentials; the peak potential of an anodic wave (<i>E</i> <sub>pa</sub>) values of Ni­(II)/Ni­(III) waves for <b>1</b> are shifted to a positive region for solvents with higher acceptor numbers. This indicates that the disproportionation of superoxide anion by NiSOD may be regulated by hydrogen-bonding interactions between the carboxamido carbonyl and electrophilic molecules through fine-tuning of the redox potential for optimal SOD activity. Interestingly, the <i>E</i> <sub>pa</sub> value of the Ni­(III)/Ni­(II) couple in <b>1</b> in water (+0.303 V vs normal hydrogen electrode (NHE)) is similar to that of NiSOD (+0.290 V vs NHE). We also investigated the superoxide-reducing and -oxidizing reactions of <b>1</b>. First, <b>1</b> reacts with superoxide to yield the superoxide-bound Ni­(II) species (UV–vis: 425, 525, and ∼650 nm; electron paramagnetic resonance (EPR) (4 K): <i>g</i> <sub>//</sub> = 2.21, <i>g</i> <sub>⊥</sub> = 2.01; resonance Raman: ν­(<sup>16</sup>O–<sup>16</sup>O)/ν­(<sup>18</sup>O–<sup>18</sup>O) = 1020/986 cm<sup>–1</sup>), which is then oxidized to Ni­(III) state only in the presence of both a proton and 1-methylimidazole, as evidenced by EPR spectra. Second, EPR spectra indicate that the oxidized complex of <b>1</b> with 1-methylimidazole at the axial site can be reduced by reaction with superoxide. The Ni­(III) complex with 1-methylimidazole at the axial site does not participate in any direct interaction with azide anion (p<i>K</i> <sub>a</sub> 4.65) added as mimic of superoxide (p<i>K</i> <sub>a</sub> 4.88). According to these data, we propose the superoxide disproportionation mechanism in superoxide-reducing and -oxidizing steps of NiSOD in both Ni­(II) and Ni­(III) states

    Data for "Mechanically-Sensitive Fluorochromism by Molecular Domino Transformation in a Schiff Base Crystal"

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    &lt;p&gt;The dataset contains input and output files of computational chemistry by Quantum ESPRESSO and Gaussian softwares conducted on two polymorphic crystal structures of 4-nitro-N-salicylideneaniline.&lt;/p&gt
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