Prostaglandin D2 Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine

PGD2, a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD2 contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD2 in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D2 (PGD2) 1 d before challenge with low-dose aerosolized antigen. Not only the numbers of eosinophils, lymphocytes, and macrophages but also the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid were higher in PGD2-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD2-pretreated mice than in control. Injection of anti-MDC antibody into PGD2-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cyto-kine production after antigen challenge. These results indicate that PGD2 accelerates Th2 type inflammation by induction of MDC. Our results suggest that this mechanism may play a key role in the development of human asthma and that MDC might be a target molecule for therapeutic intervention

Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst

The authors present a method for flattening SiC surfaces with Pt as a catalyst in HF solution. The mechanism for flattening SiC surfaces is discussed. The flattened 4H-SiC (0001) surface is composed of alternating wide and narrow terraces with single-bilayer-height steps, which are induced by the rate difference of the catalytic reactions between adjacent terraces. Scanning tunneling microscopy images reveal a 1×1 phase on the terraces. The 1×1 phase is composed of coexisting of F- and OH-terminated Si atoms, which originate from the polarization of the underlying Si-C bonds. © 2007 American Institute of Physics.Kenta Arima, Hideyuki Hara, et al. "Atomic-scale flattening of SiC surfaces by electroless chemical etching in HF solution with Pt catalyst", Appl. Phys. Lett. 90(20), 202106 (2007) https://doi.org/10.1063/1.2739084

Establishing seasonal and alert influenza thresholds in Cambodia using the WHO method: implications for effective utilization of influenza surveillance in the tropics and subtropics

Objective: To establish seasonal and alert thresholds and transmission intensity categories for influenza to provide timely triggers for preventive measures or upscaling control measures in Cambodia. Methods: Using Cambodia's influenza-like illness (ILI) and laboratory-confirmed influenza surveillance data from 2009 to 2015, three parameters were assessed to monitor influenza activity: the proportion of ILI patients among all outpatients, proportion of ILI samples positive for influenza and the product of the two. With these parameters, four threshold levels (seasonal, moderate, high and alert) were established and transmission intensity was categorized based on a World Health Organization alignment method. Parameters were compared against their respective thresholds. Results: Distinct seasonality was observed using the two parameters that incorporated laboratory data. Thresholds established using the composite parameter, combining syndromic and laboratory data, had the least number of false alarms in declaring season onset and were most useful in monitoring intensity. Unlike in temperate regions, the syndromic parameter was less useful in monitoring influenza activity or for setting thresholds. Conclusion: Influenza thresholds based on appropriate parameters have the potential to provide timely triggers for public health measures in a tropical country where monitoring and assessing influenza activity has been challenging. Based on these findings, the Ministry of Health plans to raise general awareness regarding influenza among the medical community and the general public. Our findings have important implications for countries in the tropics/subtropics and in resource-limited settings, and categorized transmission intensity can be used to assess severity of potential pandemic influenza as well as seasonal influenza

The Index of Exercise Tolerance in Heart Failure with Preserved Ejection Fraction is Gait Speed

Introduction: Exercise tolerance, an important factor affecting life prognosis and rehospitalization in patients with chronic heart failure, is a major outcome of cardiac rehabilitation. Heart failure with preserved ejection fraction (HFpEF) from reduced diastolic capacity has recently increased among patients with chronic heart failure. This study evaluated and clarified the factors indicating exercise tolerance in patients with HFpEF from various perspectives, including cardiac and skeletal muscle functions. Material and Methods: The subjects were 31 patients with HFpEF who underwent cardiac rehabilitation. Exercise tolerance was assessed using a 6-minute walking test. Physical function, physical activity, body composition test, baseline characteristics, blood data, and echocardiography results were extracted from medical records to identify the indicators of exercise tolerance. Results: Gait speed was significantly different in exercise tolerance for HFpEF patients (β=0.75, p<0.01). Unlike HFrEF, HFpEF were no significant differences in brain natriuretic peptide (BNP) levels and cardiac function. Conclusion: Gait speed is an indicator of exercise tolerance in HFpEF patients. However, its pathological course differs from HFrEF, indicating that it is poorly related to BNP, a biomarker for heart failure and cardiac function

Pressure-induced volumetric negative thermal expansion in CoZr2 superconductor

We investigate the thermal expansion and superconducting properties of a CuAl2-type (tetragonal) superconductor CoZr2 under high pressures. We perform high-pressure synchrotron X-ray diffraction in a pressure range of 2.9 GPa < P < 10.4 GPa and discover that CoZr2 exhibits volumetric negative thermal expansion under high pressures. Although the uniaxial positive thermal expansion (PTE) along the a-axis is observed under ambient pressure, that is suppressed by pressure, while the large uniaxial negative thermal expansion (NTE) along the c-axis is maintained under the pressure regime. As a result of a combination of the suppressed uniaxial PTE along the a-axis and uniaxial NTE along the c-axis, volumetric negative thermal expansion is achieved under high pressure in CoZr2. The mechanisms of volumetric NTE would be based on the flexible crystal structure caused by the soft Co-Co bond as seen in the iso-structural compound FeZr2, which exhibits uniaxial NTE along the c-axis. We also perform high-pressure electrical resistance measurements of CoZr2 to confirm the presence of superconductivity under the examined pressure regime in the range of 0.03 GPa < P < 41.9 GPa. We confirm the presence of superconductivity under all pressures and observe dome-like shape pressure dependence of superconducting transition temperature. Because of the coexistence of two phenomena, which are volumetric NTE and superconductivity, in CoZr2 under high pressure, the coexistence would be achievable under ambient pressure by tuning chemical compositions after our present observation.Comment: 22 pages, 7 figures, supporting informatio

Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau

Intracellular filamentous tau pathology is the defining feature of tauopathies, which form a subset of neurodegenerative diseases. We have analyzed pathological tau in Alzheimer’s disease, and in frontotemporal lobar degeneration associated with tauopathy to include cases with Pick bodies, corticobasal degeneration, progressive supranuclear palsy, and ones due to intronic mutations in MAPT. We found that the C-terminal band pattern of the pathological tau species is distinct for each disease. Immunoblot analysis of trypsin-resistant tau indicated that the different band patterns of the 7–18 kDa fragments in these diseases likely reflect different conformations of tau molecular species. Protein sequence and mass spectrometric analyses revealed the carboxyl-terminal region (residues 243–406) of tau comprises the protease-resistant core units of the tau aggregates, and the sequence lengths and precise regions involved are different among the diseases. These unique assembled tau cores may be used to classify and diagnose disease strains. Based on these results, we propose a new clinicopathological classification of tauopathies based on the biochemical properties of tau

Degradation of Mutant Protein Aggregates within the Endoplasmic Reticulum of Vasopressin Neurons

Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER

Bortezomib-cyclophosphamide-dexamethasone induction/consolidation and bortezomib maintenance for transplant-eligible newly diagnosed multiple myeloma: phase 2 multicenter trial

[Objectives:] We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). [Methods:] From 2013 to 2016, 42 patients with a median age of 58 (range 42–65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. [Results:] Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%−97.5%) and 62.6% (95% CI: 45.8%−75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. [Conclusion:] VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan