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The electric field effect in ferromagnetic semiconductors enables switching of the magnetization, which is a key technology for spintronic applications. We demonstrated electric field—induced ferromagnetism at room temperature in a magnetic oxide semiconductor, (Ti,Co)O 2 , by means of electric double-layer gating with high-density electron accumulation (>10 14 per square centimeter). By applying a gate voltage of a few volts, a low-carrier paramagnetic state was transformed into a high-carrier ferromagnetic state, thereby revealing the considerable role of electron carriers in high-temperature ferromagnetism and demonstrating a route to room-temperature semiconductor spintronics.

RNA metagenomic analysis of tissues from 4 wild-caught northern short-tailed shrews in Alabama, USA, revealed a novel henipavirus (family Paramyxoviridae). Phylogenetic analysis supported the placement of the virus within the shrew henipavirus clade, related to human-infecting shrewborne henipaviruses. Our study results highlight the presence of henipavirus infections in North America.

POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4 , was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B , which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B , but not OCT4 , was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo , and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo . POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.

. The fibulins are a family of secreted glycoproteins associated with basement membranes, elastic fibers, and other matrices. They are expressed in a variety of tissues. Association with these matrix structures is mediated by their ability to interact with many extracellular matrix constituents. The seven members of the family are defined by the presence of two structural modules, a tandem repeat of epidermal growth factor-like modules and a unique C-terminal fibulin-type module. They act not only as intermolecular bridges within the extracellular matrix to form supramolecular structures, but also as mediators for cellular processes and tissue remodeling. These important functions of fibulins in a wide range of biological processes have been shown in in vitro systems, gene knockout mice, and human genetic disorders. In this review, we describe the structure and function of these proteins and discuss the implication of fibulins in development and diseases.

Background: Frequency of FGFR2 amplification, its clinicopathological features, and the results of high-throughput screening assays in a large cohort of gastric clinical samples remain largely unclear. Methods: Drug sensitivity to a fibroblast growth factor receptor (FGFR) inhibitor was evaluated in vitro . The gene amplification of the FGFRs in formalin-fixed, paraffin-embedded (FFPE) gastric cancer tissues was determined by a real-time PCR-based copy number assay and fluorescence in situ hybridisation (FISH). Results: FGFR2 amplification confers hypersensitivity to FGFR inhibitor in gastric cancer cell lines. The copy number assay revealed that 4.1% (11 out of 267) of the gastric cancers harboured FGFR2 amplification. No amplification of the three other family members ( FGFR1 , 3 and 4 ) was detected. A FISH analysis was performed on 7 cases among 11 FGFR2 -amplified cases and showed that 6 of these 7 cases were highly amplified, while the remaining 1 had a relatively low grade of amplification. Although the difference was not significant, patients with FGFR2 amplification tended to exhibit a shorter overall survival period. Conclusion: FGFR2 amplification was observed in 4.1% of gastric cancers and our established PCR-based copy number assay could be a powerful tool for detecting FGFR2 amplification using FFPE samples. Our results strongly encourage the development of FGFR-targeted therapy for gastric cancers with FGFR2 amplification.

Genomic instability (GI) in cancer facilitates cancer evolution and is an exploitable target for therapy purposes. However, specific genes involved in cancer GI remain elusive. Causal genes for GI via expressions have not been comprehensively identified in colorectal cancers (CRCs). To fill the gap in knowledge, we developed a data mining strategy (Gene Expression to Copy Number Alterations; “GE-CNA”). Here we applied the GE-CNA approach to 592 TCGA CRC datasets, and identified 500 genes whose expression levels associate with CNA. Among these, 18 were survival-critical (i.e., expression levels correlate with significant differences in patients’ survival). Comparison with previous results indicated striking differences between lung adenocarcinoma and CRC: (a) less involvement of overexpression of mitotic genes in generating genomic instability in the colon and (b) the presence of CNA-suppressing pathways, including immune-surveillance, was only partly similar to those in the lung. Following 13 genes (TIGD6, TMED6, APOBEC3D, EP400NL, B3GNT4, ZNF683, FOXD4, FOXD4L1, PKIB, DDB2, MT1G, CLCN3, CAPS) were evaluated as potential drug development targets (hazard ratio [> 1.3 or < 0.5]). Identification of specific CRC genomic instability genes enables researchers to develop GI targeting approach. The new results suggest that the “targeting genomic instability and/or aneuploidy” approach must be tailored for specific organs.

In this study, we present a new granular rock-analogue material (GRAM) with a dynamic scaling suitable for the simulation of fault and fracture processes in analogue experiments. Dynamically scaled experiments allow the direct comparison of geometrical, kinematical and mechanical processes between model and nature. The geometrical scaling factor defines the model resolution, which depends on the density and cohesive strength ratios of model material and natural rocks. Granular materials such as quartz sands are ideal for the simulation of upper crustal deformation processes as a result of similar nonlinear deformation behaviour of granular flow and brittle rock deformation. We compared the geometrical scaling factor of common analogue materials applied in tectonic models, and identified a gap in model resolution corresponding to the outcrop and structural scale (1–100 m). The proposed GRAM is composed of quartz sand and hemihydrate powder and is suitable to form cohesive aggregates capable of deforming by tensile and shear failure under variable stress conditions. Based on dynamical shear tests, GRAM is characterized by a similar stress–strain curve as dry quartz sand, has a cohesive strength of 7.88 kPa and an average density of 1.36 g cm−3. The derived geometrical scaling factor is 1 cm in model = 10.65 m in nature. For a large-scale test, GRAM material was applied in strike-slip analogue experiments. Early results demonstrate the potential of GRAM to simulate fault and fracture processes, and their interaction in fault zones and damage zones during different stages of fault evolution in dynamically scaled analogue experiments.

An ABCB-type transporter, AmABCB1, was identified in a transcriptome from unfolding seedlings of A. mexicana by its amino acid sequence identity to previously characterized alkaloid transporters from Coptis japonica and Thalictrum minus. Expression analysis revealed mature seeds as its main location; meanwhile, in vitro assays in yeast cells showed that AmABCB1 had uptake and efflux activities for sanguinarine and berberine, respectively.

NK911 is a novel supramolecular nanocarrier designed for the enhanced delivery of doxorubicin (DXR) and is one of the successful polymer micelle systems to exhibit an efficient accumulation in solid tumours in mice. The purpose of this study was to define the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of NK911 and to evaluate its pharmacokinetic profile in man. NK911 was given intravenously to patients with solid tumours every 3 weeks using an infusion pump at a rate of 10 mg DXR equivalent min −1 . The starting dose was 6 mg DXR equivalent m −2 , and the dose was escalated according to the accelerated titration method. A total of 23 patients participated in this study. Neutropenia was the predominant haematological toxicity, and grade 3 or 4 neutropenia was observed at doses of 50 and 67 mg m −2 . Common nonhaematological toxicities were mild alopecia, stomatitis, and anorexia. In the dose identification part of the study, DLTs were observed at a dose of 67 mg m −2 (grade 4 neutropenia lasting more than 5 days). Thus, this dosage level was determined to be the MTD. Infusion-related reactions were not observed in any cases. The C 5 min and area under the concentration curve parameters of NK911 exhibited dose-dependent characteristics. Among the 23 patients, a partial response was obtained in one patient with metastatic pancreatic cancer. NK911 was well tolerated and produced only moderate nausea and vomiting at myelosuppressive dosages. The recommended phase II dose was determined to be 50 mg m −2 every 3 weeks.

Background:Osteosarcopenia is defined as osteoporosis combined with sarcopenia. Both osteoporosis and sarcopenia are risk factors for falls and fractures in healthy individuals1. The relationships of falls and fractures to osteosarcopenia in rheumatoid arthritis (RA) patients are unknown.Objectives:The synergistic effect of osteoporosis and sarcopenia and the impact of osteosarcopenia on falls and fractures in RA patients were investigated using four years of data from a longitudinal study.Methods:The data from a prospective, observational study (CHIKARA study: UMIN000023744) were examined. The patients were divided into four groups according to their baseline status: no sarcopenia and osteoporosis (SP-OP-); only sarcopenia (SP+OP-); only osteoporosis (SP-OP+); and both sarcopenia and osteoporosis (SP+OP+). Sarcopenia was diagnosed by the criteria of the Asia Working Group on Sarcopenia 20142. Patients with osteoporosis were defined as those having a therapeutic intervention for osteoporosis. The survival rate and Cox hazard ratio were analyzed using falls and fractures as endpoints, adjusted by age, sex, and body mass index.Results:A total of 100 RA patients (female 78%, mean age 66.1 years) were enrolled. The number of SP-OP-, SP+OP-, SP-OP+, and SP+OP+ patients was 45, 17, 27, and 11, respectively. Their baseline characteristics are shown in Table 1. A total of 35 patients had falls, and 19 patients had fractures during the four-year follow-up. The fall-free survival rate in the SP-OP-, SP+OP-, SP-OP+, and SP+OP+ groups was 75.6%, 64.7%, 51.9%, and 36.4%, respectively; that of the SP+OP+ group was significantly lower than that of the other groups (P=0.021) (Figure 1). The fracture-free survival rate in the SP-OP-, SP+OP-, SP-OP+, and SP+OP+ groups was 86.7%, 82.4%, 81.5%, and 54.5%, respectively. That of the SP+OP+ group was relatively lower than that of the other groups (P=0.121). The hazard ratio of falls was significantly increased in the SP+OP+ group by 3.32-fold (95%CI: 1.01-10.9) compared to that in the SP-OP- group, whereas that in the SP+OP- and SP-OP+ groups was 2.58-fold (95%CI: 0.75-8.8) and 2.29-fold (95%CI: 0.94-5.6) higher, respectively. There were no significant differences compared to the SP-OP- group. The hazard ratio of fractures in the SP+OP+ group was increased 2.73-fold (95%CI: 0.61-12.2) compared to that in the SP-OP- group.Table 1.Baseline characteristics of the four groupsSA-OP-SA+OP-SA-OP+SA+OP+P value*Female, %73.358.888.91000.027Age, years63 (49, 72)69 (60, 79)73 (64, 75)73 (65, 81)0.008Disease duration, years4.4 (1.0, 8.4)4.0 (1.3, 8.9)7.6 (1.5, 14.5)10.5 (3.2, 26.5)0.035DAS28-ESR3.14 (2.66, 3.70)3.55 (3.01, 4.65)3.93 (3.28, 4.63)3.53 (2.48, 3.89)0.01mHAQ0.25 (0, 0.375)0.375 (0.125, 0.875)0.375 (0.125, 0.875)0.5 (0.125, 0.875)0.065MTX, mg/week, rate (%)8.4 ± 2.9 (86.7)8.7 ± 3.5 (70.6)8.3 ± 2.8 (92.6)6.8 ± 1.0 (90.9)0.388Glucocorticoid, mg/day, rate (%)3.7 ± 1.9 (20.0)6.3 ± 1.8 (11.8)4.0 ± 1.7 (44.4)3.8 ± 1.8 (18.2)0.400Body mass index, kg/m223.4 ± 3.819.2 ± 2.321.7 ± 2.419.2 ± 2.0<0.001Data are shown as mean ± standard deviation (SD) or median (25th, 75th percentile).*: compared in four groups by Kruskal-Walls test.Figure 1.Fall-free survival rates of the four groups.[Figure omitted. See PDF]Conclusion:The survival rates with the endpoints of falls and fractures in RA patients with osteosarcopenia were lower during the four-year follow-up. In particular, the risk of falls increased with the synergistic effect of osteoporosis and sarcopenia in RA patients.References:[1]Dennison, E. M. et al. Fracture risk following intermission of osteoporosis therapy. Osteoporos Int 30, 1733-1743, doi:10.1007/s00198-019-05002-w (2019).[2]Chen, L. K. et al. Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc 15, 95-101, doi:10.1016/j.jamda.2013.11.025 (2014).Disclosure of Interests:None declared.