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1.
Phys Rev Lett ; 132(8): 082501, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38457706

ABSTRACT

The structure and decay of the most neutron-rich beryllium isotope, ^{16}Be, has been investigated following proton knockout from a high-energy ^{17}B beam. Two relatively narrow resonances were observed for the first time, with energies of 0.84(3) and 2.15(5) MeV above the two-neutron decay threshold and widths of 0.32(8) and 0.95(15) MeV, respectively. These were assigned to be the ground (J^{π}=0^{+}) and first excited (2^{+}) state, with E_{x}=1.31(6) MeV. The mass excess of ^{16}Be was thus deduced to be 56.93(13) MeV, some 0.5 MeV more bound than the only previous measurement. Both states were observed to decay by direct two-neutron emission. Calculations incorporating the evolution of the wave function during the decay as a genuine three-body process reproduced the principal characteristics of the neutron-neutron energy spectra for both levels, indicating that the ground state exhibits a strong spatially compact dineutron component, while the 2^{+} level presents a far more diffuse neutron-neutron distribution.

2.
Phys Rev Lett ; 131(21): 212501, 2023 Nov 24.
Article in English | MEDLINE | ID: mdl-38072612

ABSTRACT

The cluster structure of the neutron-rich isotope ^{10}Be has been probed via the (p,pα) reaction at 150 MeV/nucleon in inverse kinematics and in quasifree conditions. The populated states of ^{6}He residues were investigated through missing mass spectroscopy. The triple differential cross section for the ground-state transition was extracted for quasifree angle pairs (θ_{p},θ_{α}) and compared to distorted-wave impulse approximation reaction calculations performed in a microscopic framework using successively the Tohsaki-Horiuchi-Schuck-Röpke product wave function and the wave function deduced from antisymmetrized molecular dynamics calculations. The remarkable agreement between calculated and measured cross sections in both shape and magnitude validates the molecular structure description of the ^{10}Be ground-state, configured as an α-α core with two valence neutrons occupying π-type molecular orbitals.

4.
Rev Sci Instrum ; 94(9)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37671952

ABSTRACT

A retroreflector array, composed of a cluster of small retroreflectors, is experimentally studied for application to a Michelson-type interferometer system in the fusion plasma experiment. Such a new-type reflector has the potential to be a vital and effective tool at a spatially limited location, such as on the vacuum chamber wall of plasma experimental devices. To investigate the effect of retroreflector array on the reflected beam properties, a tabletop experiment is performed with the retroreflector array composed of 4 mm corner-cube retroreflectors and with a 320-GHz (λ ∼ 0.937 mm) submillimeter wave source. An imaging camera is utilized to measure the submillimeter wave beam profile and is scanned perpendicularly to the beam propagation direction if necessary. The experimental result exhibits a diffraction effect on the reflected beam, resulting in the emergence of discrete peaks on the reflected beam profile, as predicted in the past numerical study; however, the most reflected beam power converges on the one reflected into the incident direction, resulting from a property as a retroreflector. Furthermore, the dependence of the reflected beam on the incident beam angle is characterized while fixing the detector position, and the retroreflection beam intensity is found to vary due to the diffraction effect. Such an undesired variation of beam intensity induced by the diffraction can be suppressed with a focusing lens placed in front of the detector in the practical application to an interferometer.

5.
Nature ; 620(7976): 965-970, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37648757

ABSTRACT

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

6.
J Neonatal Perinatal Med ; 16(2): 343-348, 2023.
Article in English | MEDLINE | ID: mdl-37182845

ABSTRACT

INTRODUCTION: Although breast milk is considered the optimal nutrition for infants, it is also the primary cause of postnatal cytomegalovirus (CMV) infection. Preterm infants with postnatal CMV infections are susceptible to a variety of life-threatening conditions. CASE SUMMARY: Twin male infants were delivered via emergency caesarian section at 27 weeks' gestation secondary to maternal complete uterine rupture. The Apgar scores at 1 and 5 min were 1 and 1 for the older twin (Twin A) and 0 and 3 for the younger twin (Twin B). Their birth weights were 1203 g (+ 0.65SD) and 495 g (- 3.79SD) respectively. On day 41, laboratory blood test results for Twin B showed a moderate elevation in C-reactive protein (CRP), thrombocytopenia. CMV quantitative polymerase chain reaction (qPCR) tests in Twin B's urine and blood as well as in the mother's breast milk were positive, but stored, dried umbilical cord CMV qPCR tests were negative. Twin B was diagnosed with a postnatal CMV infection secondary to infected breast milk and ganciclovir was commenced on day 52. Treatment was switched to valganciclovir at 74 days of age, but a negative CMV-DNA level in the blood was not achieved. Postnatal CMV infection in this infant led to an exacerbation of pre-existing bronchopulmonary dysplasia (BPD) and he demised at 182 days of age. CONCLUSION: Postnatal cytomegalovirus infections may lead to exacerbations of BPD. Early use of raw breast milk in preterm infants should be done with careful consideration of this potential complication.


Subject(s)
Bronchopulmonary Dysplasia , Cytomegalovirus Infections , Infant , Female , Pregnancy , Infant, Newborn , Male , Humans , Milk, Human , Infant, Extremely Low Birth Weight , Infant, Premature , Prospective Studies , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/drug therapy , Cytomegalovirus Infections/diagnosis , Cytomegalovirus , Infectious Disease Transmission, Vertical
7.
Phys Rev Lett ; 130(17): 172501, 2023 Apr 28.
Article in English | MEDLINE | ID: mdl-37172241

ABSTRACT

We report on the first proton-induced single proton- and neutron-removal reactions from the neutron-deficient ^{14}O nucleus with large Fermi-surface asymmetry S_{n}-S_{p}=18.6 MeV at ∼100 MeV/nucleon, a widely used energy regime for rare-isotope studies. The measured inclusive cross sections and parallel momentum distributions of the ^{13}N and ^{13}O residues are compared to the state-of-the-art reaction models, with nuclear structure inputs from many-body shell-model calculations. Our results provide the first quantitative contributions of multiple reaction mechanisms including the quasifree knockout, inelastic scattering, and nucleon transfer processes. It is shown that the inelastic scattering and nucleon transfer, usually neglected at such energy regime, contribute about 50% and 30% to the loosely bound proton and deeply bound neutron removal, respectively. These multiple reaction mechanisms should be considered in analyses of inclusive one-nucleon removal cross sections measured at intermediate energies for quantitative investigation of single-particle strengths and correlations in atomic nuclei.

8.
J Dent Res ; 102(3): 331-339, 2023 03.
Article in English | MEDLINE | ID: mdl-36529984

ABSTRACT

Periodontal disease is caused by dysbiosis of the dental biofilm and the host inflammatory response. Various pathogenic factors, such as proteases and lipopolysaccharides (LPSs) produced by bacteria, are involved in disease progression. Endotoxin tolerance is a function of myeloid cells, which sustain inflammation and promote tissue regeneration upon prolonged stimulation by endotoxins such as LPS. The role of endotoxin tolerance is gaining attention in various chronic inflammatory diseases, but its role in periodontal disease remains elusive. Oxidative stress, one of the major risk factors for periodontal disease, promotes disease progression through various mechanisms, of which only some are known. The effect of oxidative stress on endotoxin tolerance has not yet been studied, and we postulated that endotoxin tolerance regulation may be an additional mechanism through which oxidative stress influences periodontal disease. This study aimed to reveal the effect of oxidative stress on endotoxin tolerance and that of endotoxin tolerance on periodontitis progression. The effect of oxidative stress on endotoxin tolerance was analyzed in vitro using peritoneal macrophages of mice and hydrogen peroxide (H2O2). The results showed that oxidative stress inhibits endotoxin tolerance induced by Porphyromonas gingivalis LPS in macrophages, at least partially, by downregulating LPS-elicited negative regulators of Toll-like receptor (TLR) signaling. A novel oxidative stress mouse model was established using SMP30KO mice incapable of ascorbate biosynthesis. Using this model, we revealed that oxidative stress impairs endotoxin tolerance potential in macrophages in vivo. Furthermore, gingival expression of endotoxin tolerance-related genes and TLR signaling negative regulators was decreased, and symptoms of ligature-induced periodontitis were aggravated in the oxidative stress mouse model. Our findings suggest that oxidative stress may contribute to periodontitis progression through endotoxin tolerance inhibition.


Subject(s)
Lipopolysaccharides , Periodontitis , Humans , Lipopolysaccharides/pharmacology , Endotoxin Tolerance , Hydrogen Peroxide , Oxidative Stress , Disease Progression , Porphyromonas gingivalis
9.
Rev Sci Instrum ; 93(11): 113519, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36461432

ABSTRACT

A new 320 GHz solid-state source interferometer is installed in the Heliotron J helical device to explore the physics of high-density plasmas (ne > 2-3 × 1019 m-3, typically) realized with advanced fueling techniques. This interferometry system is of the Michelson type and is based on the heterodyne principle, with two independent solid-state sources that can deliver an output power of up to 50 mW. A high time resolution measurement of <1 µs can be derived by tuning the frequency of one source in the frequency range of 312-324 GHz on the new system, which can realize the fluctuation measurement. We successfully measured the line-averaged electron density in high-density plasma experiments. The measured density agreed well with a microwave interferometer measurement using a different viewing chord, demonstrating that the new system can be used for routine diagnostics of electron density in Heliotron J.

10.
J Physiol Anthropol ; 41(1): 41, 2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36514087

ABSTRACT

BACKGROUND: The ability to avoid obstacles efficiently and safely is important for older adults to prevent injuries from tripping and falling. It is important to find an optimal spatial margin between the body and an obstacle considering both safety and efficiency. One side of finding the optimal margin is to decrease the margin in terms of motor efficiency. In this study, we tested whether fingertip-contact intervention to obtain haptic feedback information to perceive the relationship between body and the environment could immediately improve spatial perception and collision avoidance behavior (an instantaneous effect). METHODS: Twenty-seven older adults (12 males and 15 females) participated in the experiment. In the intervention of the fingertip-contact group, they lightly touched the edge of a door with both fingertips while walking. The test task before and after the intervention involved grasping a horizontal bar and passing through a narrow opening. As dependent variables, we measured the spatial margin and the collision rate. RESULTS: The fingertip-contact group showed a significant decrease in the spatial margin after the intervention. On the other hand, there was no significant improvement in the collision rate after the intervention but rather a decrease only in the control group. CONCLUSION: The results obtained in this study indicate that touching obstacles with the fingertips had an instantaneous effect, leading to efficient movement learning, although a possible side effect of an increased collision rated was also found. The proposed intervention might promote an efficiency-based strategy due to learning the spatial relationship between the body and the environment, and it may suppress the excessive avoidance of older adults.


Subject(s)
Haptic Technology , Walking , Male , Female , Humans , Aged , Feedback , Touch , Movement
11.
Sci Rep ; 12(1): 14204, 2022 Aug 20.
Article in English | MEDLINE | ID: mdl-35987922

ABSTRACT

Understanding pellet ablation physics is crucial to realizing efficient fueling into a high temperature plasma for the steady state operation of ITER and future fusion reactors. Here we report the first observation of the formation of fluctuation structures in the pellet plasmoid during the pellet ablation process by a fast camera in a medium-sized fusion device, Heliotron J. The fluctuation has a normalized fluctuation level of ~ 15% and propagates around the moving pellet across the magnetic field. By comparing the fluctuation structures with the shape of magnetic field lines calculated with the field line tracing code, we successfully reconstruct the spatio-temporal structure of the fluctuations during the pellet ablation process. The fluctuations are located at the locations displaced toroidally from the pellet and propagate in the cross-field direction around the pellet axis along the field line, indicating a three-dimensional behavior and structure of fluctuations. The fluctuation would be driven by a strong inhomogeneity formed around the pellet and invoke the relaxation of the gradient through a cross-field transport induced by the fluctuations, which could affect the pellet ablation and pellet fueling processes. Such fluctuations can be ubiquitously present at the inhomogeneity formed around a pellet in the pellet ablation process in fusion devices.

12.
J Neuroinflammation ; 19(1): 188, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35841099

ABSTRACT

BACKGROUND: There is growing evidence that neuroinflammation may contribute to schizophrenia neuropathology. Elevated pro-inflammatory cytokines are evident in the midbrain from schizophrenia subjects, findings that are driven by a subgroup of patients, characterised as a "high inflammation" biotype. Cytokines trigger the release of antibodies, of which immunoglobulin G (IgG) is the most common. The level and function of IgG is regulated by its transporter (FcGRT) and by pro-inflammatory IgG receptors (including FcGR3A) in balance with the anti-inflammatory IgG receptor FcGR2B. Testing whether abnormalities in IgG activity contribute to the neuroinflammatory abnormalities schizophrenia patients, particularly those with elevated cytokines, may help identify novel treatment targets. METHODS: Post-mortem midbrain tissue from healthy controls and schizophrenia cases (n = 58 total) was used to determine the localisation and abundance of IgG and IgG transporters and receptors in the midbrain of healthy controls and schizophrenia patients. Protein levels of IgG and FcGRT were quantified using western blot, and gene transcript levels of FcGRT, FcGR3A and FcGR2B were assessed using qPCR. The distribution of IgG in the midbrain was assessed using immunohistochemistry and immunofluorescence. Results were compared between diagnostic (schizophrenia vs control) and inflammatory (high vs low inflammation) groups. RESULTS: We found that IgG and FcGRT protein abundance (relative to ß-actin) was unchanged in people with schizophrenia compared with controls irrespective of inflammatory subtype. In contrast, FcGRT and FcGR3A mRNA levels were elevated in the midbrain from "high inflammation" schizophrenia cases (FcGRT; p = 0.02, FcGR3A; p < 0.0001) in comparison to low-inflammation patients and healthy controls, while FcGR2B mRNA levels were unchanged. IgG immunoreactivity was evident in the midbrain, and approximately 24% of all individuals (control subjects and schizophrenia cases) showed diffusion of IgG from blood vessels into the brain. However, the intensity and distribution of IgG was comparable across schizophrenia cases and control subjects. CONCLUSION: These findings suggest that an increase in the pro-inflammatory Fcγ receptor FcGR3A, rather than an overall increase in IgG levels, contribute to midbrain neuroinflammation in schizophrenia patients. However, more precise information about IgG-Fcγ receptor interactions is needed to determine their potential role in schizophrenia neuropathology.


Subject(s)
Schizophrenia , Cytokines/metabolism , Humans , Immunoglobulin G , Inflammation , Mesencephalon/metabolism , RNA, Messenger , Receptors, IgG/genetics , Receptors, IgG/metabolism , Schizophrenia/metabolism
13.
Nature ; 606(7915): 678-682, 2022 06.
Article in English | MEDLINE | ID: mdl-35732764

ABSTRACT

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

14.
J Dent Res ; 101(8): 942-950, 2022 07.
Article in English | MEDLINE | ID: mdl-35238237

ABSTRACT

Mucin in saliva plays a critical role in the hydration and lubrication of the oral mucosa by retaining water molecules, and its impaired function may be associated with hyposalivation-independent xerostomia. Age-dependent effects on salivary gland function and rheological properties of secreted saliva are not fully understood as aging is a complex and multifactorial process. We aimed to evaluate age-related changes in the rheological properties of saliva and elucidate the underlying mechanism. We performed ex vivo submandibular gland (SMG) and sublingual gland (SLG) perfusion experiments to collect saliva from isolated glands of young (12 wk old) and aged (27 mo old) female C57BL/6J mice and investigate the rheological properties by determining the spinnbarkeit (viscoelasticity). While fluid secretion was comparable in SMG and SLG of both mice, spinnbarkeit showed a significant decrease in SLG saliva of aged mice than that of young mice. There were no significant differences in GalNAc concentration between young and aged SLG saliva. Liquid chromatography/tandem mass spectrometry analysis of SLG saliva revealed that (Hex)1 (HexNAc)1 (NeuAc)1 at m/z 793.31 was the most abundant O-glycan structure in SLG saliva commonly detected in both mice. Lectin staining of salivary gland tissue showed that SLG stained strongly with Maackia amurensis lectin II (MAL II) while Sambucus nigra agglutinin (SNA) stained little, if any, SLG. The messenger RNA expression of St3gal1 that encodes an α-2,3 sialic acid sialyltransferase SIAT4-A showed a decrease in SLG of aged mice, confirmed by a Western blot analysis. Lectin blot analysis in SLG saliva revealed that the relative signal intensity detected by MAL II was significantly lower in aged SLG. Our results suggest that spinnbarkeit decreases in SLG of aging mice due to downregulation of sialic acid linked to α-2,3 sialic acid sialyltransferase expression.


Subject(s)
Sublingual Gland , Xerostomia , Aging , Animals , Female , Lectins/metabolism , Mice , Mice, Inbred C57BL , N-Acetylneuraminic Acid/metabolism , Saliva/metabolism , Sialyltransferases , Submandibular Gland/metabolism , Xerostomia/metabolism
15.
Tech Coloproctol ; 26(2): 109-115, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34761314

ABSTRACT

BACKGROUND: Placing a transanal endoscopic rectal purse-string suture (taEPS) is the crucial first component of transanal total mesorectal excision (taTME). However, no structured training is available to improve the procedure-specific skills for taEPS. The aim of this study was to create a performance rubric to improve taEPS skills and provide preliminary evidence for its validity. METHODS: A performance rubric was created based on technical considerations for taEPS, identified by consulting with taTME surgical and performance assessment experts. Ten independent, blinded raters assessed 10 videotaped taEPS procedures of consecutive taTME cases, at National Cancer Center Hospital East (NCCHE), Chiba, Japan, in January 2018-March 2019 using the rubric and the Global Operative Assessment of Laparoscopic Skills (GOALS). Internal consistency and inter-rater reliabilities were calculated. Videotaped taEPS procedures were timed and assessed by the rubric. Correlation between rubric scores and suturing times were analyzed. RESULTS: The rubric consists of four items: loading the needle (LN), atraumatic needle passage (AP), planned suture path (PS), and overall performance (OA). Videotaped performances were graded on a 3-point Likert scale; scores were calculated as sums of the points. Cronbach's α for internal consistency was 0.713. Inter-rater reliabilities were LN: 0.73, AP: 0.76, PS: 0.71, and OA: 0.70. Rubric and GOALS scores were strongly correlated (r = 0.964, p < 0.001). In 112 consecutive taEPS performances, rubric scores were strongly correlated with suturing time (r = - 0.69, p < 0.001). Surgeons' experience with taTME was associated with rubric scores and suturing time. CONCLUSIONS: This study provides preliminary validation for the taEPS skill performance rubric. The rubric's structured training may facilitate skill acquisition by providing trainees with critical clinical considerations.


Subject(s)
Laparoscopy , Proctectomy , Rectal Neoplasms , Transanal Endoscopic Surgery , Humans , Laparoscopy/methods , Postoperative Complications/surgery , Rectal Neoplasms/surgery , Rectum/surgery , Sutures , Transanal Endoscopic Surgery/methods
16.
Phys Rev Lett ; 126(16): 162701, 2021 Apr 23.
Article in English | MEDLINE | ID: mdl-33961456

ABSTRACT

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

17.
Phys Rev Lett ; 126(8): 082501, 2021 Feb 26.
Article in English | MEDLINE | ID: mdl-33709737

ABSTRACT

A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.

18.
Clin Exp Immunol ; 204(2): 239-250, 2021 05.
Article in English | MEDLINE | ID: mdl-33555619

ABSTRACT

Humanized non-obese diabetic/severe combined immunodeficiency/interleukin-2 receptor-γ-null (NOD/SCID/IL2rγnull ) [humanized (huNSG)] mice engrafted with human hematopoietic cells have been used for investigations of the human immune system. However, the epigenetic features of the human regulatory T (Treg ) cells of huNSG mice have not been studied. The objective of this study was to clarify the characteristics of human Treg cells in huNSG mice, especially in terms of the epigenetic aspects. We compared the populations, inhibitory molecule expression and suppressive capacity of human Treg cells in spleens harvested from the huNSG mice 120 days after the engraftment of human umbilical cord blood CD34+ cells with human peripheral blood mononuclear cells (PBMCs). Histone modifications and enhancer of zeste homolog 2 (Ezh2), an H3K27 methyltransferase, of human Treg cells were quantified in huNSG mice and human PBMCs. The effect of Ezh2 inhibitor on human Treg cells exposed to interleukin (IL)-6 was also compared between them. Human Treg cells in the spleens of huNSG mice showed an increased proportion among CD4+ T cells, higher expressions of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor-related protein (GITR), a higher production of IL-10 and enhanced suppressive capacity when compared with those in human PBMCs. H3K27me3 and Ezh2 were specifically up-regulated in human Treg cells of huNSG mice in comparison with those of human PBMCs. The decrease in Treg cells induced by IL-6 exposure was attenuated in huNSG mice when compared with human PBMCs, while the difference between them was cancelled by addition of Ezh2 inhibitor. In conclusion, huNSG mice exhibit functionally augmented human Treg cells owing to enzymatic up-regulation of H3K27me3.


Subject(s)
Histones/immunology , T-Lymphocytes, Regulatory/immunology , Up-Regulation/immunology , Animals , CD4-Positive T-Lymphocytes/immunology , Cells, Cultured , Humans , Interleukin-6/immunology , Leukocytes, Mononuclear/immunology , Male , Mice , Mice, Inbred NOD , Mice, SCID
19.
Clin Exp Immunol ; 203(3): 385-399, 2021 03.
Article in English | MEDLINE | ID: mdl-33238047

ABSTRACT

The citrullinated inter-alpha-trypsin inhibitor heavy chain 4 (cit-ITIH4) was identified as its blood level was associated with the arthritis score in peptide glucose-6-phosphate-isomerase-induced arthritis (pGIA) mice and the disease activity in patients with rheumatoid arthritis (RA). This study aimed to clarify its citrullination pathway and function as related to neutrophils. In pGIA-afflicted joints, ITIH4 and cit-ITIH4 levels were examined by immunohistochemistry (IHC), immunoprecipitation (IP) and Western blotting (WB), while peptidylarginine deiminase (PAD) expression was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), IHC and immunofluorescent methods. The pGIA mice received anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibodies to deplete neutrophils and the expression of cit-ITIH4 was investigated by WB. The amounts of ITIH4 and cit-ITIH4 in synovial fluid (SF) from RA and osteoarthritis (OA) patients were examined by I.P. and W.B. Recombinant ITIH4 and cit-ITIH4 were incubated with sera from healthy volunteers before its chemotactic ability and C5a level were evaluated using Boyden's chamber assay and enzyme-linked immunosorbent assay (ELISA). During peak arthritic phase, ITIH4 and cit-ITIH4 were increased in joints while PAD4 was over-expressed, especially in the infiltrating neutrophils of pGIA mice. Levels of cit-ITIH4 in plasma and joints significantly decreased upon neutrophil depletion. ITIH4 was specifically citrullinated in SF from RA patients compared with OA patients. Native ITIH4 inhibited neutrophilic migration and decreased C5a levels, while cit-ITIH4 increased its migration and C5a levels significantly. Cit-ITIH4 is generated mainly in inflamed joints by neutrophils via PAD4. Citrullination of ITIH4 may change its function to up-regulate neutrophilic migration by activating the complement cascade, exacerbating arthritis.


Subject(s)
Arthritis, Experimental/immunology , Arthritis, Rheumatoid/immunology , Cell Movement/immunology , Joints/immunology , Neutrophils/immunology , Proteinase Inhibitory Proteins, Secretory/immunology , Adult , Aged , Animals , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/metabolism , Citrulline/immunology , Citrulline/metabolism , Female , Humans , Immunohistochemistry , Joints/metabolism , Male , Mice, Inbred DBA , Microscopy, Fluorescence , Middle Aged , Neutrophils/cytology , Proteinase Inhibitory Proteins, Secretory/metabolism , Young Adult
20.
Phys Rev Lett ; 124(21): 212503, 2020 May 29.
Article in English | MEDLINE | ID: mdl-32530691

ABSTRACT

The heaviest bound isotope of boron ^{19}B has been investigated using exclusive measurements of its Coulomb dissociation, into ^{17}B and two neutrons, in collisions with Pb at 220 MeV/nucleon. Enhanced electric dipole (E1) strength is observed just above the two-neutron decay threshold with an integrated E1 strength of B(E1)=1.64±0.06(stat)±0.12(sys) e^{2} fm^{2} for relative energies below 6 MeV. This feature, known as a soft E1 excitation, provides the first firm evidence that ^{19}B has a prominent two-neutron halo. Three-body calculations that reproduce the energy spectrum indicate that the valence neutrons have a significant s-wave configuration and exhibit a dineutronlike correlation.

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