Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption

AbstractThe biological role of phosphatidylinositol (PI)-3 kinase was examined in osteoclast-like multinucleated cells (OCLs) formed in co-cultures of mouse osteoblastic cells and bone marrow cells. The expression of PI-3 kinase in OCLs was confirmed by Western blot analysis. Wortmannin (WT), a specific inhibitor of PI-3 kinase, inhibited PI-3 kinase activity in OCLs both in vitro and in vivo. WT also inhibited pit-forming activity on dentine slices and disrupted a ringed structure of F-actin-containing dots (an actin ring) in OCLs in a dose-dependent manner. The inhibitory profiles of WT for pit and actin ring formation were similar to that for PI-3 kinase activity in OCLs. Electron microscopic analysis revealed that OCLs treated with WT did not form ruffled borders. Instead, numerous electron lucent vacuoles of differing sizes were found throughout the cytoplasm. These results suggest that PI-3 kinase is important in osteoclastic bone resorption

Measurement of the 6Li(e,e'p) reaction cross sections at low momentum transfer

The triple differential cross sections for the 6Li(e,e'p) reaction have been measured in the excitation energy region from 27 to 46 MeV in a search for evidence of the giant dipole resonance (GDR) in 6Li. The cross sections have no distinct structures in this energy region, and decrease smoothly with the energy transfer. Angular distributions are different from those expected with the GDR. Protons are emitted strongly in the momentum-transfer direction. The data are well reproduced by a DWIA calculation assuming a direct proton knockout process.Comment: 19 pages, 7 figures, revised text, to be published in Nucl. Phys.

Crystal structure of (1R,2R)-trans-1,2-cyclohexanedicarhoxylic acid-(R)- 1-phenylethylamine salt

金沢大学大学院自然科学研究科先端機能物質金沢大学工学

Regular pulse checks for patients with non-cardioembolic stroke in rehabilitation hospitals to improve recognition and detection of atrial fibrillation (the ESCORT study): protocol for a prospective multicenter observational study

BackgroundCryptogenic stroke (CS) are heterogeneous in origin; however, most CS are embolic mechanism. Paroxysmal atrial fibrillation (AF) is suspected to be a major type of CS that leads to severe cerebral infarction without anticoagulant use. Therefore, the identification of AF is vital in patients with CS. However, patients are often unaware of AF because they have no symptoms, and AF may not be detected on an electrocardiogram (ECG) or Holter ECG on admission. After patients with stroke are treated in the acute phase, they are promptly transferred to a rehabilitation hospital for functional recovery. Once the patient is transferred to a hospital, a few attempts are made to detect AF. In addition, rehabilitation therapists are considered to have insufficient awareness of the possibility of undiagnosed AF.ObjectiveThis study aimed to increase the understanding of the importance of AF detection in patients with ischemic stroke among therapists in rehabilitation hospitals and to investigate whether regular pulse screening can aid in the detection of AF. If AF was detected, we determined the rate and timing of AF detection and identified the patient characteristics.MethodsThis multicenter prospective observational study aimed to detect AF in patients with non-cardiac stroke at rehabilitation hospitals. Therapists performed pulse checks before, during, and after rehabilitation. If arrhythmia or tachycardia was detected, an ECG was performed, and the physician checked for AF. If the patient complained of chest symptoms, electrocardiography (ECG) was performed to check for AF. We investigated the characteristics, laboratory data, cognitive status, complications, such as stroke recurrence, and functional outcomes of patients with AF.ResultsThe study is in the enrollment phase. Recruitment began in September 2022 and will end in August 2023. Patients have provided written informed consent. The main results have been submitted for publication in your journal.ConclusionThe findings of this study will help identify patients with AF in rehabilitation hospitals and improve awareness among therapists

Comparative analysis of facial morphology between Okinawa Islanders and mainland Japanese using three-dimensional images.

OBJECTIVES: Differences in facial height and breadth between Okinawa Islanders and mainland Japanese have been reported in previous craniometric and somatometric studies. This study using three-dimensional (3D) images aimed to identify more detailed characteristics of facial morphology in each population. METHODS: Using a hand-held 3D scanner, we obtained 60 facial surface images each from Okinawa Islanders and mainland Japanese. Twenty-one landmarks were plotted on a computer and 27 measurements of distances and angles between the landmarks were taken. Statistical analyses such as t test, principal component analysis (PCA), regression analysis, and discriminant analysis were performed to identify sex and regional differences, the patterns of facial features, factors explaining the facial patterns, and other features. RESULTS: Okinawa Islanders showed lower facial and nasal heights than mainland Japanese. Furthermore, we identified larger protrusions of the glabella and nasal root in Okinawa Islanders than in mainland Japanese. In the PCA, we observed components of facial shape patterns. These components mainly represented facial size (PC1), facial depth (PC2), the prominence of the glabella and nasal root (PC3), and facial breadth (PC4). We identified that the population difference is strongly associated with PC3. CONCLUSIONS: This study quantitatively identified differences in the facial morphology between Okinawa Islanders and mainland Japanese using 3D digital images, with special emphases on the differences in the nasal height and the prominence of the glabella and nasal root

Novel calmodulin mutations associated with congenital arrhythmia susceptibility.

BACKGROUND: Genetic predisposition to life-threatening cardiac arrhythmias such as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. METHODS AND RESULTS: We used conventional and next-generation sequencing approaches, including exome analysis, in genotype-negative LQTS probands. We identified 5 novel de novo missense mutations in CALM2 in 3 subjects with LQTS (p.N98S, p.N98I, p.D134H) and 2 subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1 to 9 years. Three of 5 probands had cardiac arrest and 1 of these subjects did not survive. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of 5 probands responded to β-blocker therapy, whereas 1 subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within Ca(2+)-binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced Ca(2+)-binding affinity. CONCLUSIONS: CALM2 mutations can be associated with LQTS and with overlapping features of LQTS and CPVT

Sensitive and label-free biosensing of RNA with predicted secondary structures by a triplex affinity capture method

A novel biosensing approach for the label-free detection of nucleic acid sequences of short and large lengths has been implemented, with special emphasis on targeting RNA sequences with secondary structures. The approach is based on selecting 8-aminoadenine-modified parallel-stranded DNA tail-clamps as affinity bioreceptors. These receptors have the ability of creating a stable triplex-stranded helix at neutral pH upon hybridization with the nucleic acid target. A surface plasmon resonance biosensor has been used for the detection. With this strategy, we have detected short DNA sequences (32-mer) and purified RNA (103-mer) at the femtomol level in a few minutes in an easy and level-free way. This approach is particularly suitable for the detection of RNA molecules with predicted secondary structures, reaching a limit of detection of 50 fmol without any label or amplification steps. Our methodology has shown a marked enhancement for the detection (18% for short DNA and 54% for RNA), when compared with the conventional duplex approach, highlighting the large difficulty of the duplex approach to detect nucleic acid sequences, especially those exhibiting stable secondary structures. We believe that our strategy could be of great interest to the RNA field