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1.
Phys Rev E ; 109(3-1): 034604, 2024 Mar.
Article En | MEDLINE | ID: mdl-38632748

Because of its plasticity, a densely packed colloidal suspension, called a paste, remembers directions of its motion, such as vibration and flow. When it dries, primary desiccation cracks propagate in a direction perpendicular to the direction of its vibrational motion and parallel to the direction of its flow motion, which are memory effects of paste. Application of an oscillatory shear strain to a paste using a rheometer reveals that the transition from memory of vibration to that of flow is induced when the amplitude of the oscillatory shear strain exceeds a threshold value. Findings also demonstrate that oscillatory motion is unnecessary, i.e., merely a large shear deformation is sufficient for the memory of flow. Therefore, only oscillatory shear strain with a small amplitude is necessary for memory of vibration; large shear deformation is sufficient for memory of flow.

2.
Proc Jpn Acad Ser B Phys Biol Sci ; 98(6): 227-282, 2022.
Article En | MEDLINE | ID: mdl-35691845

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10's of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation.


Meteoroids , Solar System , Water
3.
Cureus ; 14(3): e22791, 2022 Mar.
Article En | MEDLINE | ID: mdl-35371855

It is well known that acute myeloid leukemia (AML) is characterized by lethargy, fever, pallor, and purpura. In children, however, skeletal symptoms may be present at onset in rare cases, and such cases tend to be misdiagnosed as osteomyelitis or septic arthritis. To distinguish acute leukemia from osteomyelitis or bone tumor, the utility of magnetic resonance imaging (MRI) has been discussed. We present a pediatric case of AML in which the initial manifestation was pain in a single bone, and the diagnosis was aided by bone marrow examination and MRI. A one-year-old male with AML presented with left humeral bone pain and intermittent fever. T1-weighted magnetic resonance imaging (T1WI) revealed diffuse low signal intensity in the bone marrow adjacent to the localized musculoskeletal symptoms. Despite a lack of blasts in the peripheral blood, the histopathological features of the bone focus suggested the need for an iliac crest bone marrow biopsy to obtain a definitive diagnosis. After the diagnosis of AML, the patient received induction and consolidation chemotherapy. He is currently alive in remission after a post-diagnosis follow-up of 36 months. To date, only seven pediatric cases of AML with skeletal symptoms at initial presentation have been reported, including the present one. In three cases, the skeletal lesion was observed at a single site, and the initial misdiagnosis was discitis, septic arthritis, or acute osteomyelitis. We suggest that AML should be considered as a differential diagnosis in children presenting with treatment-resistant single skeletal lesions. Not only MRI but also bone biopsy can yield diagnostically important information.

4.
Bioorg Med Chem ; 61: 116728, 2022 05 01.
Article En | MEDLINE | ID: mdl-35395514

We have developed a series of attenuated cationic amphiphilic lytic (ACAL) peptides that can efficiently bring immunoglobulin G (IgG) and other functional proteins into cells. Delivery is generally achieved through the coadministration of ACAL peptides with cargo proteins. However, conjugation of ACAL peptides with cargos may be a promising approach for in vivo application to link in vivo outcomes of ACAL peptides and cargos. This study describes the creation of a new cell-permeable ACAL peptide, L17ER4. L17E is an optimized prototype of ACAL peptides previously developed in our laboratory for efficient delivery of IgGs into cells. Delivery was improved by functionalizing L17E with a tetra-arginine (R4) tag. Compared to the use of R8, a representative cell-penetrating peptide with high intracellular delivery efficacy, conjugation with L17ER4 afforded approximately four-fold higher cellular uptake of model small-molecule cargos (fluorescein isothiocyanate and HiBiT peptide). L17ER4 was also able to deliver proteins to cells. Fused with L17ER4, Cre recombinase was delivered into cells. Intracerebroventricular injection of Cre-L17ER4 into green red reporter mice, R26GRR, led to significant in vivo gene recombination in ependymal cells, suggesting that L17ER4 may be used as a cell-penetrating peptide for delivering protein therapeutics into cells in vivo.


Cell-Penetrating Peptides , Animals , Cations , Cell-Penetrating Peptides/chemistry , Mice
5.
Angew Chem Int Ed Engl ; 60(36): 19804-19812, 2021 09 01.
Article En | MEDLINE | ID: mdl-34114295

Fc region binding peptide conjugated with attenuated cationic amphiphilic lytic peptide L17E trimer [FcB(L17E)3 ] was designed for immunoglobulin G (IgG) delivery into cells. Particle-like liquid droplets were generated by mixing Alexa Fluor 488 labeled IgG (Alexa488-IgG) with FcB(L17E)3 . Droplet contact with the cellular membrane led to spontaneous influx and distribution of Alexa488-IgG throughout cells in serum containing medium. Involvement of cellular machinery accompanied by actin polymerization and membrane ruffling was suggested for the translocation. Alexa488-IgG negative charges were crucial in liquid droplet formation with positively charged FcB(L17E)3 . Binding of IgG to FcB(L17E)3 may not be necessary. Successful intracellular delivery of Alexa Fluor 594-labeled anti-nuclear pore complex antibody and anti-mCherry-nanobody tagged with supernegatively charged green fluorescence protein allowed binding to cellular targets in the presence of FcB(L17E)3 .


Cytosol/metabolism , Immunoglobulin G/metabolism , Peptides/metabolism , Surface-Active Agents/metabolism , Cations/chemistry , Cations/metabolism , Cytosol/chemistry , Humans , Immunoglobulin G/chemistry , Molecular Structure , Particle Size , Peptides/chemistry , Surface-Active Agents/chemistry
6.
Bioorg Med Chem Lett ; 40: 127925, 2021 05 15.
Article En | MEDLINE | ID: mdl-33705909

Our research group has been studying the design of intracellular delivery peptides based on cationic lytic peptides. By placing negatively charged amino acids on potentially hydrophobic faces of the peptides, membrane lytic activity is attenuated on the cell surface, whereas it recovers in endosomes, enabling cytosolic delivery of proteins including antibodies. These lytic peptides generally contain multiple lysines, facilitating cell surface interaction and membrane perturbation. This study evaluated the effect of lysine-to-homoarginine substitution using HAad as a model delivery peptide. The resulting peptide had a comparable or better delivery efficacy for Cre recombinase, antibodies, and the Cas9/sgRNA complex with one-quarter of the concentration of HAad, implying that a subtle structural difference can affect delivery activity.


Drug Carriers/chemistry , Endosomes/metabolism , Homoarginine/chemistry , Intracellular Membranes/metabolism , Peptides/chemistry , Amino Acid Sequence , CRISPR-Associated Protein 9/pharmacology , Dextrans/chemistry , Drug Carriers/toxicity , Drug Liberation , Fluoresceins/chemistry , Fluorescent Dyes/chemistry , HeLa Cells , Humans , Immunoglobulin G/pharmacology , Integrases/pharmacology , Liposomes/chemistry , Peptides/toxicity , RNA, Guide, Kinetoplastida/pharmacology , Sulfonic Acids/chemistry
7.
Mod Rheumatol Case Rep ; 4(2): 272-277, 2020 07.
Article En | MEDLINE | ID: mdl-33087001

Arthralgia is a well-known complication of cutaneous polyarteritis nodosa (CPN). However, few cases of destructive arthritis with CPN resulting in chronic pain and disability have been documented. Here we report a case of CPN associated with destructive arthritis of the right foot, accompanied by seronegative arthritis in the right ankle, for which orthopaedic surgery was necessary. X-ray and computed tomography revealed progressive joint destruction in the right talonavicular joint, and magnetic resonance imaging demonstrated severe synovitis of the right talocrural joint. When the talonavicular joint was opened, we observed marked synovitis and a defect in the cartilage that had expanded within the joint. Although mild cartilage degeneration was observed in the talocrural joint, arthroscopic observation revealed no massive defect on the articulated surface. Arthrodesis and arthroscopic synovectomy yielded a good midterm clinical outcome, indicating that surgical intervention was useful for the treatment for destructive arthritis with CPN. Rheumatologists and orthopaedic surgeons should be aware of potential complications such as destructive arthritis when treating patients with CPN.


Polyarteritis Nodosa/surgery , Arthrodesis/methods , Arthroscopy/methods , Disease Management , Humans , Polyarteritis Nodosa/diagnosis , Synovectomy/methods , Treatment Outcome
8.
Bioorg Med Chem Lett ; 30(17): 127362, 2020 09 01.
Article En | MEDLINE | ID: mdl-32738963

Intracellular delivery of biomacromolecules is a challenging research field in chemical biology and drug delivery. We previously reported a peptide named L17E, which successfully delivered functional proteins, including antibodies, into cells. However, relatively high concentrations of L17E and proteins are needed. In this study, we prepared dimers of L17E and its analog L17E/Q21E. Dimerization of L17E increased cytotoxicity leading to reduced intracellular delivery compared with L17E. On the other hand, the dimers of the L17E analog, L17E/Q21E, especially when tethered at the N-termini, yielded a comparable level of intracellular delivery with L17E at decreased amounts of delivery peptides and cargoes.


Cytosol/metabolism , Peptides/metabolism , Amino Acid Sequence , Antibodies/chemistry , Antibodies/metabolism , Dimerization , Drug Carriers/chemistry , Fluorescent Dyes/chemistry , HeLa Cells , Humans , Microscopy, Confocal , Peptides/chemistry
9.
Angew Chem Int Ed Engl ; 59(45): 19990-19998, 2020 11 02.
Article En | MEDLINE | ID: mdl-32557993

Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into the cytosol are desired to achieve successful delivery. Focusing on compositional differences between the cell and endosomal membranes and the pH decrease within endosomes, we designed the lipid-sensitive and pH-responsive endosome-lytic peptide HAad. This peptide contains aminoadipic acid (Aad) residues, which serve as a safety catch for preferential permeabilization of endosomal membranes over cell membranes, and His-to-Ala substitutions enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was supported by model studies using large unilamellar vesicles (LUVs) and by increased intracellular delivery of biomacromolecules (including antibodies) into live cells. Cerebral ventricle injection of Cre recombinase with HAad led to Cre/loxP recombination in a mouse model, thus demonstrating potential applicability of HAad in vivo.


Endosomes/metabolism , Peptides/metabolism , Cell Membrane/metabolism , Endocytosis , HeLa Cells , Humans , Hydrophobic and Hydrophilic Interactions
10.
Acta Crystallogr D Struct Biol ; 74(Pt 8): 787-791, 2018 Aug 01.
Article En | MEDLINE | ID: mdl-30082514

To improve the sensitivity of hydrogen detection using neutrons, a proton-polarization technique together with a high-pressure cooling method is necessary. The highest pressure (200 MPa) used in the experiment described here enabled relatively large protein crystals to be cooled without any cryoprotectants while retaining the protein structure, and it was confirmed that high-pressure-cooled crystals diffracted to nearly the same resolution as flash-cooled small crystals soaked with cryoprotectants. Dynamic nuclear polarization was used as a proton-polarization technique for protein crystals, and ∼300 mg polycrystalline protein doped with TEMPOL gave a maximum proton polarization of 22.3% at a temperature of 0.5 K in a 2.5 T magnetic field.


Cold Temperature , Crystallography/methods , Hydrogen/chemistry , Neutron Diffraction/methods , Proteins/chemistry , Cyclic N-Oxides , Electron Spin Resonance Spectroscopy , Muramidase/chemistry , Pressure , Spin Labels
11.
Orthopedics ; 40(5): e911-e914, 2017 Sep 01.
Article En | MEDLINE | ID: mdl-28585994

Removal of orthopedic implants may sometimes be difficult because of ongrowth of new bone. Titanium screws can become encased or stripped during the process of initial open reduction and internal fixation or at the time of hardware removal. Difficulty in removing screws from a locking plate is particularly well-known. Two patients with tibial and femoral diaphyseal fractures were treated using a locking plate or an intramedullary nail. However, after fracture healing, it was difficult to remove the locking screw or reconstruction screws because of damage to the heads. The stripped reconstruction screw was successfully removed employing the authors' so-called parallel planes technique. In this method, a high-speed diamond-tipped burr is applied to opposite sides of the screw head to form 2 parallel faces located slightly away from the recess of the screw head. The 2 faces can then be grasped solidly with locking pliers, allowing removal of the implant by unscrewing it with a gentle upward pulling action. The locking plate was cut from the plate edge to the edge of the screw hole. While making these radial cuts in the plates, the authors were careful not to extend the blade into the screw head. After removal of the locking plate from the screw, the authors were able to extract the jammed screw uneventfully using this technique. This technique can be performed without difficulty and does not require a special device. It is a useful option for extraction of damaged screws. [Orthopedics. 2017; 40(5):e911-e914.].


Bone Screws , Device Removal/methods , Fracture Fixation, Internal/instrumentation , Aged , Bone Plates , Equipment Failure , Female , Femoral Fractures/surgery , Fracture Fixation, Internal/methods , Humans , Male , Open Fracture Reduction/instrumentation , Open Fracture Reduction/methods , Surgical Instruments , Tibial Fractures/surgery , Titanium , Young Adult
12.
Mod Rheumatol ; 27(3): 417-424, 2017 May.
Article En | MEDLINE | ID: mdl-27550190

OBJECTIVES: Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA. METHODS: Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12 NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up. RESULTS: The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p = 0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p = 0.0027, 0.0017 and p < 0.0001, respectively). Stepwise regression analysis showed that talar subsidence was an independent predictor of a worse JSSF score in the NA group (F = 10.3). CONCLUSIONS: The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA.


Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement, Ankle/adverse effects , Postoperative Complications/epidemiology , Adult , Aged , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Arthroplasty, Replacement, Ankle/methods , Female , Humans , Male , Middle Aged , Radiography , Reoperation/statistics & numerical data , Treatment Outcome
13.
PLoS One ; 10(8): e0136611, 2015.
Article En | MEDLINE | ID: mdl-26317770

OBJECTIVE: To investigate clinical and radiological differences between joint destruction in the wrist and the feet in patients with RA. METHODS: A cross-sectional clinical study was conducted in an RA cohort at a single institution. Clinical data included age, sex and duration of disease. Laboratory data included sero-positivity for anti-cyclic citrullinated peptide (CCP) antibody and RF. Radiological measurements included Larsen grades and the modified Sharp/van der Heijde method (SHS) for the hands/wrists and the feet. Statistical analyses were performed using the Kruskal-Wallis H-test, a dummy variable linear regression model and multivariate logistic regression analysis with 95% confidence interval and odds ratios. RESULTS: A total of 405 patients were enrolled, and 314 patients were analysed in this study. The duration of disease in the foot-dominant group was significantly less than that in the wrist-dominant group. When patients were subdivided by duration of disease, the Larsen grade of the feet was significantly higher than that of the wrist in the first quadrant subgroup, but this was reversed with increasing duration of disease. Anti-CCP status was a significant predictive factor for joint destruction in the wrist but not in the feet, while RF status was not predictive in either the wrist or the feet. CONCLUSIONS: Joint destruction in the feet started earlier than in the wrist, but the latter progresses faster with increasing duration of disease. Anti-CCP status predicts joint destruction in the wrist better than in the feet.


Arthritis, Rheumatoid/blood , Foot Joints/diagnostic imaging , Wrist Joint/diagnostic imaging , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/diagnostic imaging , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Radiography
14.
J Spinal Disord Tech ; 28(5): E270-6, 2015 Jun.
Article En | MEDLINE | ID: mdl-23381185

STUDY DESIGN: A retrospective study of 58 patients undergoing cantilever transforaminal lumbar interbody fusion (c-TLIF). OBJECTIVES: To evaluate morphologic changes in the intervertebral foramen (IVF) on the side contralateral to spacer insertion in patients undergoing c-TLIF using plain x-ray films and computed tomography scan. SUMMARY OF BACKGROUND DATA: The morphologic changes in the contralateral lumbar foramen in c-TLIF using unilateral insertion of spacers have not been well studied. MATERIALS AND METHODS: Fifty-eight consecutive patients with lumbar dysplastic changes or degenerative disk diseases underwent c-TLIF using 96 kidney-type spacers with local bone grafts. Radiographic findings (sagittal disk angle), computed tomography scan findings (coronal disk angle, disk height, foraminal height (FH), foraminal width, and cross-sectional area of IVF in contralateral lumbar foramen) were compared between preoperative period and 6 months after surgery. The correlations between contralateral lumbar foraminal dimensions and disk height, sagittal disk angle, and coronal disk angle were analyzed. RESULTS: After c-TLIF, sagittal angle, disk height, FH, foraminal width, and cross-sectional area of the IVF were significantly increased. Increase in posterior disk height showed a positive correlation with increases in FH, foraminal width, and cross-sectional area of IVF (r=0.235-0.511). However, the increase in sagittal disk angle showed a negative correlation with changes in foraminal width and cross-sectional area of IVF (r=-0.256 to -0.206). CONCLUSIONS: Lumbar foraminal dimensions on the side contralateral to spacer insertion increased significantly after c-TLIF, suggesting that c-TLIF enables indirect decompression of the contralateral nerve root. Although increase in posterior disk height was shown to be an important factor to increase contralateral foraminal size, segmental lordosis was a risk factor for a decrease in contralateral foraminal size.


Internal Fixators , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Spinal Fusion/instrumentation , Adult , Aged , Anatomy, Cross-Sectional , Female , Humans , Intervertebral Disc/diagnostic imaging , Lordosis/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Risk Factors , Spinal Nerve Roots/diagnostic imaging , Tomography, X-Ray Computed
15.
Clin Rheumatol ; 32(5): 721-5, 2013 May.
Article En | MEDLINE | ID: mdl-23478907

We report a 61-year-old woman with rheumatoid arthritis (RA: Steinblocker stage III, class 3) who developed severe swelling and neuropathy of the right lower limb caused by an iliopectineal bursa associated with destruction of the hip joint. Physical examination revealed an inguinal mass and groin pain. X-ray examination indicated destruction of the hip joint. Contrast-enhanced computed tomography showed the bursa connected with the hip joint and a markedly compressed external iliac vein among the inguinal ligament, pubis, and bursa. The patient underwent partial synovial resection and total hip arthroplasty for recovery of hip function, and this led to successful resolution of the symptoms and bursa. We present the characteristic images from this case and review all previously reported cases of RA iliopsoas bursitis causing leg swelling or neuropathy, and summarize the background. Since this lesion may cause various symptoms, clinical awareness that iliopsoas bursitis may present with unique clinical symptoms may aid correct diagnosis.


Bursa, Synovial/pathology , Bursitis/diagnosis , Edema/diagnosis , Polyneuropathies/diagnosis , Arthritis, Rheumatoid/complications , Arthroplasty, Replacement, Hip , Bursitis/pathology , Contrast Media/pharmacology , Diagnosis, Differential , Edema/pathology , Female , Groin/pathology , Hip Joint/pathology , Humans , Iliac Vein/pathology , Lower Extremity/pathology , Middle Aged , Polyneuropathies/pathology , Tomography, X-Ray Computed
16.
J Spinal Disord Tech ; 26(5): E177-82, 2013 Jul.
Article En | MEDLINE | ID: mdl-23381186

STUDY DESIGN: In vivo measurement of lumbar foramen using computed tomography and an axial loading device in healthy young subjects. OBJECTIVE: To investigate the effects of axial loading on the morphology of the lumbar foramen in vivo. SUMMARY OF BACKGROUND DATA: In vitro studies have shown morphologic changes in the lumbar foramen in response to axial loading. The effects of axial loading on foraminal dimensions in vivo, however, are poorly understood. MATERIALS AND METHODS: The study population consisted of 12 asymptomatic healthy young volunteers [6 men and 6 women; age range, 22-34 y (mean, 27 y)]. Lumbar computed tomography images were compared with and without axial loading using a compression device (DynaWell), and differences in disk height (DH), foraminal height (FH), foraminal width (FW), and the cross-sectional area (CSA) of the intervertebral foramen (IVF) were determined. RESULTS: During axial loading, the FHs at L1/L2, L2/L3, L3/L4, and L4/L5 each decreased significantly (P<0.01 each), by 4.0%, 6.6%, 6.6%, and 5.1%, respectively. Maximum FW decreased significantly (P<0.05 each) at L2/L3 (7.2%) and L3/L4 (5.7%), and increased significantly (P<0.05) at L5/S1 (8.9%). The CSAs of the IVF decreased significantly (P<0.01 each) at L2/L3 (10.8%) and L3/L4 (10.7%) and increased significantly (P<0.01) at L5/S1 (23.3%). Changes in FH, maximum and minimum FW, and CSA of the IVF significantly (P<0.01) correlated with change in posterior DH. CONCLUSIONS: FH, FW, and CSA of the IVF, except for L5/S1, decreased significantly during axial loading. Changes in posterior DH correlated well with the changes in foraminal dimensions.


Compressive Strength/physiology , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/physiology , Tomography, X-Ray Computed/methods , Weight-Bearing/physiology , Adult , Female , Humans , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/physiology , Male , Young Adult
17.
Science ; 323(5916): 900-5, 2009 Feb 13.
Article En | MEDLINE | ID: mdl-19213911

The farside gravity field of the Moon is improved from the tracking data of the Selenological and Engineering Explorer (SELENE) via a relay subsatellite. The new gravity field model reveals that the farside has negative anomaly rings unlike positive anomalies on the nearside. Several basins have large central gravity highs, likely due to super-isostatic, dynamic uplift of the mantle. Other basins with highs are associated with mare fill, implying basalt eruption facilitated by developed faults. Basin topography and mantle uplift on the farside are supported by a rigid lithosphere, whereas basins on the nearside deformed substantially with eruption. Variable styles of compensation on the near- and farsides suggest that reheating and weakening of the lithosphere on the nearside was more extensive than previously considered.

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