We report on the detection of two series of harmonically related doublets in IRC +10216. From the observed frequencies, the rotational constant of the first series is B = 1380.888 MHz and that of the ...second series is B = 1381.512 MHz. The two series correspond to two species with a 2Σ electronic ground state. After considering all possible candidates, and based on quantum chemical calculations, the first series is assigned to MgC3N and the second to MgC4H. For the latter species, optical spectroscopy measurements support its identification. Unlike diatomic metal-containing molecules, the line profiles of the two new molecules indicate that they are formed in the outer layers of the envelope, as occurs for MgNC and other polyatomic metal-cyanides. We also confirm the detection of MgCCH that was previously reported from the observation of two doublets. The relative abundance of MgC3N with respect to MgNC is close to one while that of MgC4H relative to MgCCH is about ten. The synthesis of these magnesium cyanides and acetylides in IRC +10216 can be explained in terms of a two-step process initiated by the radiative association of Mg+ with large cyanopolyynes and polyynes followed by the dissociative recombination of the ionic complexes.
Summary
Electron tomography methods using the conventional transmission electron microscope have been widely used to investigate the three‐dimensional distribution patterns of various cellular ...structures including microtubules in neurites. Because the penetrating power of electrons depends on the section thickness and accelerating voltage, conventional TEM, having acceleration voltages up to 200 kV, is limited to sample thicknesses of 0.2 µm or less. In this paper, we show that the ultra‐high voltage electron microscope (UHVEM), employing acceleration voltages of higher than 1000 kV (1 MV), allowed distinct reconstruction of the three‐dimensional array of microtubules in a 0.7‐µm‐thick neurite section. The detailed structure of microtubules was more clearly reconstructed from a 0.7‐µm‐thick section at an accelerating voltage of 1 MV compared with a 1.0 µm section at 2 MV. Furthermore, the entire distribution of each microtubule in a neurite could be reconstructed from serial‐section UHVEM tomography. Application of optimised UHVEM tomography will provide new insights, bridging the gap between the structure and function of widely‐distributed cellular organelles such as microtubules for neurite outgrowth.
Lay Description
An optimal 3D visualisation of microtubule cytoskeleton using ultra‐high voltage electron microscopy tomography
The ultra‐high voltage electron microscope (UHVEM) is able to visualise a micrometre‐thick specimen at nanoscale spatial resolution because of the high‐energy electron beam penetrating such a specimen. In this study, we determined the optimal conditions necessary for microtubule cytoskeleton imaging within 0.7‐µm‐thick section using a combination with UHVEM and electron tomography method. Our approach provides excellent 3D information about the complex arrangement of the individual microtubule filaments that make up the microtubule network.
Summary
Background
In extramammary Paget disease (EMPD), Paget cells are sometimes detected outside the clinical border (subclinical extension). However, the spreading pattern of Paget cells in ...subclinical extension remains unclear. In addition, the macroscopic appearances of lesions accompanied by subclinical extension are totally unknown.
Objectives
To characterize the spreading pattern of Paget cells as well as the macroscopic appearance of lesions of EMPD with subclinical extension.
Methods
Nineteen patients with primary anogenital EMPD underwent mapping biopsies and excisional surgeries; biopsy samples were then taken at the periphery of well‐demarcated lesions. Samples were transparentized and subjected to whole‐mount immunostaining with anticytokeratin 7 antibody to label Paget cells. The histological border was evaluated in three dimensions by two‐photon microscopy. The shape and location of the histological border were compared with those of the clinical border.
Results
In 21 samples taken at the lesion where subclinical extension was not shown by mapping biopsy, the shape and location of the histological border were almost identical to those of the clinical border. However, two samples exhibited small foci of Paget cells outside the clinical border, showing subclinically extended satellite lesions. In the two samples taken at the lesions where subclinical extension was shown by mapping biopsy, a continuous arrangement of Paget cells extending beyond the clinical border was identified. Subclinically extended Paget cells were detected solely outside hypopigmented patches with erythema.
Conclusions
In EMPD, at least two patterns of subclinical extension exist: continuous and satellite lesions. Subclinical extension might exist preferentially outside hypopigmented patches with erythema.
What's already known about this topic?
Paget cells in extramammary Paget disease often spread beyond the clinical border, which is referred to as subclinical extension.
The spreading pattern of the subclinically extended Paget cells remains unclear.
There are no reports on the macroscopic appearances of lesions accompanied by subclinical extension.
What does this study add?
Three‐dimensional analysis by whole‐mount immunostaining revealed two spreading patterns of Paget cells in subclinical extension.
Paget cells formed either small satellite lesions or continuous lesions forming a polygonal margin.
All subclinically extended Paget cells were detected outside hypopigmented patches with erythema.
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Linked Comment: Hatta. Br J Dermatol 2017; 177:18–19
Summary
Background
Sublingual immunotherapy (SLIT) has proven to be safe and efficient for the treatment of type I allergies. However, the mechanisms underlying allergen transportation within the ...sublingual compartment, the localization of antigens, and the identities of the cells responsible for this immunization remain incompletely understood.
Objective
In this study, we focused on the sublingual ductal system and analysed the localization and transportation of antigens after their sublingual application.
Methods
In mice given adjuvant‐free antigens sublingually, tissues were removed at 0, 0.5, 1, or 2 h after the application and subjected to immunohistochemistry. Cells isolated from the sublingual duct and mucosa were analysed by flow cytometry.
Results
Substantial immunoreactivity to ovalbumin (OVA) was evident in sublingual ductal epithelial cells at 30 min and 1 h after sublingual administration of OVA, but it had disappeared at 2 h. The ductal epithelial cells incorporated not only OVA, but also particulate antigens such as latex or silica beads and microbes. MHC class II (MHCII)+ antigen‐presenting cells (APCs) were located around the sublingual ductal system, and MHCII+ cells were co‐localized with, and around, antigen‐incorporated sublingual duct cells. CD11b+ CD11c− cells were present among CD45+ MHCII+ cells at greater frequency in the sublingual duct than in the sublingual mucosa, and they were the main contributors to the incorporation of OVA in vitro.
Conclusions and Clinical Relevance
This study reveals that sublingual antigens can be transported across sublingual ductal epithelial cells to the ductal APCs. If the system is the same in humans as in mice, the ductal APCs may prove to be important target cells for SLIT.
This study investigated the effectiveness of treatment with Janus kinase (JAK) inhibitors in rheumatoid arthritis (RA) assessed by ultrasonography (US) activity, and the influence of patient ...characteristics and previous treatments.
This prospective study assessed 60 treatment initiations among 53 Japanese patients diagnosed with RA who underwent treatment with JAK inhibitors during June 2013 to February 2020. Of the 53 patients, seven patients were enrolled in duplicate because they were treated with two different JAK inhibitors at different periods. For each case, the improvement rate on the power Doppler (PD) score was assessed at 6 month follow-up. Median improvement rate of PD score was used to classify cases as either US responders or non-responders, and patient characteristics were compared between the two groups.
All indicators of clinical disease activity and US activity showed a significant improvement at 3 months compared with baseline. Although the JAK inhibitor-cycler group and the interleukin-6 (IL-6) inhibitor inadequate response (IR) group tended to show a later improvement for US activity, all indicators of clinical disease activity and US activity showed a significant improvement at 6 months compared with baseline for both groups. Multivariate analysis showed that concomitant methotrexate use and an IR to the previous biologic or targeted-synthetic disease-modifying anti-rheumatic drug (b/tsDMARD) treatment were independently and significantly associated with US responders.
Use of a JAK inhibitor in combination with methotrexate and an absence of IR to any previous b/tsDMARDs demonstrated superior effectiveness for patients with RA.
Nitriles constitute almost 15% of the molecules observed in the interstellar medium (ISM), surprisingly only two dinitriles have been detected in the ISM so far. The lack of astronomical detections ...for dinitriles may be partly explained by the absence of laboratory rotational spectroscopic data.
Our goal is to investigate the rotational spectrum of glutaronitrile, N≡C-CH
-CH
-CH
-C≡N, in order to allow its possible detection in the ISM.
The rotational spectrum of glutaronitrile was measured using two different experimental setups. A Fourier transform microwave spectrometer was employed to observe the supersonic jet rotational spectrum of glutaronitrile between 6 and 20 GHz. In addition, the mmW spectrum was observed in the frequency range 72-116.5 GHz using a broadband millimetre-wave spectrometer based on radio astronomy receivers with fast Fourier transform backends. The spectral searches were supported by high-level ab initio calculations.
A total of 111 rotational transitions with maximum values of
and
quantum numbers 54 and 18, respectively, were measured for the
conformer of glutaronitrile. The analysis allowed us to accurately determine the rotational, nuclear quadrupole coupling, quartic and sextic centrifugal distortion constants. These rotational parameters were employed to search for glutaronitrile in the cold and warm molecular clouds Orion KL, Sgr B2(N), B1-b and TMC-1, using the spectral surveys captured by IRAM 30m at 3mm. Glutaronitrile was not detected, and the upper limits' column densities were derived. Those are a factor of 1.5 and 5 lower than those obtained for the total column densities of the analogous succinonitrile in Orion KL and Sgr B2, respectively.
Summary
Docetaxel and paclitaxel are widely used in the treatment of various malignant neoplasms. Taxane‐induced sclerosis is dose‐dependent and usually not generalized. Little information on the ...pathogenesis of scleroderma is currently available. Here, we report a case of generalized scleroderma and a case of early‐stage oedematous sclerosis, both of which presented with intense versican deposits after administration of taxane for angiosarcoma.
What's already known about this topic?
Taxane‐induced sclerosis occurs dose dependently; however, little information on the pathogenesis of scleroderma is currently available.
What does this study add?
We analysed collagen type I, hyaluronan and versican, and revealed that administration of taxane increased the amount of versican, which led to oedema and sclerosis in our patients.
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