Ratiometric Flapping Force Probe That Works in Polymer Gels

Polymer gels have recently attracted attention for their application in flexible devices, where mechanically robust gels are required. While there are many strategies to produce tough gels by suppressing nanoscale stress concentration on specific polymer chains, it is still challenging to directly verify the toughening mechanism at the molecular level. To solve this problem, the use of the flapping molecular force probe (FLAP) is promising because it can evaluate the nanoscale forces transmitted in the polymer chain network by ratiometric analysis of a stress-dependent dual fluorescence. A flexible conformational change of FLAP enables real-time and reversible responses to the nanoscale forces at the low force threshold, which is suitable for quantifying the percentage of the stressed polymer chains before structural damage. However, the previously reported FLAP only showed a negligible response in solvated environments because undesirable spontaneous planarization occurs in the excited state, even without mechanical force. Here, we have developed a new ratiometric force probe that functions in common organogels. Replacement of the anthraceneimide units in the flapping wings with pyreneimide units largely suppresses the excited-state planarization, leading to the force probe function under wet conditions. The FLAP-doped polyurethane organogel reversibly shows a dual-fluorescence response under sub-MPa compression. Moreover, the structurally modified FLAP is also advantageous in the wide dynamic range of its fluorescence response in solvent-free elastomers, enabling clearer ratiometric fluorescence imaging of the molecular-level stress concentration during crack growth in a stretched polyurethane film

Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type.

Amyloid aggregates found in the brain of patients with neurodegenerative diseases, including Alzheimer's and Parkinson's disease, are thought to spread to increasingly larger areas of the brain through a prion-like seeding mechanism. Not much is known about which cell surface receptors may be involved in the cell-to-cell transfer, but proteoglycans are of interest due to their well-known propensity to interact with amyloid aggregates. In this study, we investigated the involvement of plasma membrane-bound heparan and chondroitin sulfate proteoglycans in cellular uptake of aggregates consisting of α-synuclein, a protein forming amyloid aggregates in Parkinson's disease. We show, using a pH-sensitive probe, that internalization of α-synuclein amyloid fibrils in neuroblastoma cells is dependent on heparan sulfate, whereas internalization of smaller non-amyloid oligomers is not. We also show that α-synuclein fibril uptake in an oligodendrocyte-like cell line is equally dependent on heparan sulfate, while astrocyte- and microglia-like cell lines have other means to internalize the fibrils. In addition, we analyzed the interaction between the α-synuclein amyloid fibrils and heparan sulfate and show that overall sulfation of the heparan sulfate chains is more important than sulfation at particular sites along the chains

The “journal of functional morphology and kinesiology” journal club series: Highlights on recent papers in musculoskeletal disorders

© 2017 by the authors. We are glad to introduce the fourth Journal Club. This edition is focused on several relevant studies published in the last few years in the field of musculoskeletal disorders, chosen by our Editorial Board members. We hope to stimulate your curiosity in this field. The Editorial Board members wish you an inspiring lecture

骨孔内での腱骨移行部再生における力学的影響

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1549号, 学位授与年月日 : 平成14年12月31日, 学位授与大学 : 金沢大

Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study

<p>Abstract</p> <p>Background</p> <p>The amino-acid balance in cancer patients often differs from that in healthy individuals, because of metabolic changes. This study investigated the use of plasma amino-acid profiles as a novel marker for screening non-small-cell lung cancer (NSCLC) patients.</p> <p>Methods</p> <p>The amino-acid concentrations in venous blood samples from pre-treatment NSCLC patients (<it>n </it>= 141), and age-matched, gender-matched, and smoking status-matched controls (<it>n </it>= 423), were measured using liquid chromatography and mass spectrometry. The resultant study data set was subjected to multiple logistic regression analysis to identify amino acids related with NSCLC and construct the criteria for discriminating NSCLC patients from controls. A test data set derived from 162 patients and 3,917 controls was used to validate the stability of the constructed criteria.</p> <p>Results</p> <p>The plasma amino-acid profiles significantly differed between the NSCLC patients and the controls. The obtained model (including alanine, valine, isoleucine, histidine, tryptophan and ornithine concentrations) performed well, with an area under the curve of the receiver-operator characteristic curve (ROC_AUC) of >0.8, and allowed NSCLC patients and controls to be discriminated regardless of disease stage or histological type.</p> <p>Conclusions</p> <p>This study shows that plasma amino acid profiling will be a potential screening tool for NSCLC.</p

Perampanel Inhibits α‐Synuclein Transmission in Parkinson's Disease Models

パーキンソン病モデルへのペランパネルの有効性を確認 --パーキンソン病の進行抑制治療への期待--. 京都大学プレスリリース. 2021-04-05.[Background]: The intercellular transmission of pathogenic proteins plays a key role in the clinicopathological progression of neurodegenerative diseases. Previous studies have demonstrated that this uptake and release process is regulated by neuronal activity. [Objective]: The objective of this study was to examine the effect of perampanel, an antiepileptic drug, on α‐synuclein transmission in cultured cells and mouse models of Parkinson's disease.Methods: Mouse primary hippocampal neurons were transduced with α‐synuclein preformed fibrils to examine the effect of perampanel on the development of α‐synuclein pathology and its mechanisms of action. An α‐synuclein preformed fibril‐injected mouse model was used to validate the effect of oral administration of perampanel on the α‐synuclein pathology in vivo. [Results]: Perampanel inhibited the development of α‐synuclein pathology in mouse hippocampal neurons transduced with α‐synuclein preformed fibrils. Interestingly, perampanel blocked the neuronal uptake of α‐synuclein preformed fibrils by inhibiting macropinocytosis in a neuronal activity‐dependent manner. We confirmed that oral administration of perampanel ameliorated the development of α‐synuclein pathology in wild‐type mice inoculated with α‐synuclein preformed fibrils.[Conclusion]: Modulation of neuronal activity could be a promising therapeutic target for Parkinson's disease, and perampanel could be a novel disease‐modifying drug for Parkinson's disease

Impact of Gba2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)

Homozygous mutations in the lysosomal glucocerebrosidase gene, GBA1, cause Gaucher's disease (GD), while heterozygous mutations in GBA1 are a strong risk factor for Parkinson's disease (PD), whose pathological hallmark is intraneuronal α-synuclein (asyn) aggregates. We previously reported that gba1 knockout (KO) medaka exhibited glucosylceramide accumulation and neuronopathic GD phenotypes, including short lifespan, the dopaminergic and noradrenergic neuronal cell loss, microglial activation, and swimming abnormality, with asyn accumulation in the brains. A recent study reported that deletion of GBA2, non-lysosomal glucocerebrosidase, in a non-neuronopathic GD mouse model rescued its phenotypes. In the present study, we generated gba2 KO medaka and examined the effect of Gba2 deletion on the phenotypes of gba1 KO medaka. The Gba2 deletion in gba1 KO medaka resulted in the exacerbation of glucosylceramide accumulation and no improvement in neuronopathic GD pathological changes, asyn accumulation, or swimming abnormalities. Meanwhile, though gba2 KO medaka did not show any apparent phenotypes, biochemical analysis revealed asyn accumulation in the brains. gba2 KO medaka showed a trend towards an increase in sphingolipids in the brains, which is one of the possible causes of asyn accumulation. In conclusion, this study demonstrated that the deletion of Gba2 does not rescue the pathological changes or behavioral abnormalities of gba1 KO medaka, and GBA2 represents a novel factor affecting asyn accumulation in the brains

Development of ethnographic digital collections

Περιέχει το πλήρες κείμενοΟι λαογραφικές συλλογές αποτελούν πολύτιμη πηγή μελέτης, εξερεύνησης και αξιολόγησης των εθνικών στερεοτύπων των διαφόρων διαμερισμάτων μιας χώρας, δεδομένου ότι στις συλλογές είναι καταχωρημένα ανόθευτα και πηγαία τα εγχώρια εθνοχαρακτηριστικά τους. Κατά κύριο λόγο η λαογραφία αναφέρεται στους μύθους, τα τραγούδια, τη μουσική, τα έθιμα, τη χειροτεχνία, την ενδυμασία, την αρχιτεκτονική και την προφορική παράδοση μιας κοινότητας. Η ιδιαιτερότητα και η ποικιλία ενός τομέα όπως της λαογραφίας δικαιολογεί απόλυτα την ύπαρξη συλλογών και υπο-συλλογών σύνθετης δομής και σημασιολογίας, όπως αυτές που αναφέρουμε παραπάνω. Επομένως η ανάπτυξη ψηφιακών συλλογών απαιτεί τη διατήρηση των στοιχείων που χρειάζονται για: (α) την περιγραφή του περιεχομένου της κάθε συλλογής χωριστά και (β) τη σωστή απεικόνιση της δομής των αντικειμένων στο εσωτερικό αυτής. Στόχος της εργασίας αυτής είναι η παρουσίαση μιας μεθοδολογίας για την ανάπτυξη ενός περιγραφικού μοντέλου μεταδεδομένων για λαογραφικές συλλογές. Το μοντέλο θα αποτελέσει βασικό εργαλείο για την περιγραφή του ψηφιοποιημένου λαογραφικού υλικού, την πρόσβαση σε αυτό από κατανεμημένους χρήστες και φυσικά την επικοινωνία του με άλλα συστήματα. Επιπλέον θα συμβάλλει στη διασύνδεση σύνθετων συλλογών και των αντικειμένων που περιλαμβάνουν είτε σημασιολογικά, είτε χρονικά, είτε θεματικά είτε με οποιονδήποτε άλλο τρόπο απαιτεί η φύση των συλλογών και οι ανάγκες των χρηστών

Liver regeneration after portal vein embolization: comparison between absolute ethanol and N-butyl-cyanoacrylate in an in vivo rat model

PURPOSETo compare the effects of absolute ethanol (ethanol) and N-butyl-cyanoacrylate (NBCA) on non-embolized liver lobe regeneration in a rat model.METHODSTwenty-seven Sprague–Dawley rats underwent portal vein embolization (PVE) using ethanol:lipiodol, 1:1 (ethanol group, n = 11, 40.74%), NBCA:lipiodol, 1:1 (NBCA group, n = 11, 40.74%), or sham treatment (sham group, n = 5, 18.52%). The non-embolized and embolized lobe-to-whole liver weight ratios 14 days after PVE were compared among the groups (n = 5, 18.52%). The expressions of CD68 and Ki-67 and embolized-lobe necrotic area percentages one day after PVE were compared between the ethanol (n = 3, 11.11%) and NBCA (n = 3, 11.11%) groups.RESULTSThe non-embolized lobe-to-whole liver weight ratio after PVE was significantly higher in the NBCA group (n = 5, 33.33%) than in the ethanol group (n = 5, 33.33%) (84.28% ± 1.53% vs. 76.88% ± 4.12%, P = 0.029). The embolized lobe-to-whole liver weight ratio after PVE was significantly lower in the NBCA group than in the ethanol group (15.72% ± 1.53% vs. 23.12% ± 4.12%, P = 0.029). The proportions of CD68- and Ki-67-positive cells in the non-embolized lobe after PVE were significantly higher in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [60 (48–79) vs. 55 (37–70), P = 0.003; 1 (0–2) vs. 1 (0–2), P = 0.004]. The embolized-lobe necrotic area percentage after PVE was significantly larger in the NBCA group (n = 30, 50%) than in the ethanol group (n = 30, 50%) [29.46 (12.56–83.90%) vs. 16.34 (3.22–32.0%), P < 0.001].CONCLUSIONPVE with NBCA induced a larger necrotic area in the embolized lobe and promoted greater non-embolized liver lobe regeneration compared with PVE with ethanol