Effects of formaldehyde, as an indoor air pollutant, on the airway

ABSTRACTHomes are being built to be more airtight because of demands for energy conservation in recent years. At the same time, recognition of numerous sources of formaldehyde in indoor environments has increased concerns about health hazards from this pollutant. Formaldehyde has been shown to cause and exacerbate asthmatic symptoms. In addition, the effects of formaldehyde on the airway are proportional to the concentration and duration of exposure and are greater in inflamed than in healthy airways. Formaldehyde may induce features of airway inflammation associated with asthma, such as epithelial disruption, microvascular leakage and increased airway secretions. Exposure to this chemical may facilitate IgE sensitization to a variety of allergens, as well as producing IgE-mediated allergic responses to itself. Thus, avoidance of formaldehyde exposure may reduce the incidence and severity of asthma, although the ability of low concentrations of formaldehyde to trigger mechanisms contributing to asthmatic symptoms is still debated. Setting appropriate exposure limits for formaldehyde as an indoor environmental pollutant requires further quantitative and predictive evaluation of its health effects

The shielding effect of HTS power cable based on E-J power law

A method for analysing the current distribution in high-T/sub c/ superconducting (HTS) power cable is examined by the aid of the novel use of anisotropic conductivity and 3-D finite element method considering E-J power law characteristic. The detailed current distribution in the cable is illustrated and the shielding effect of HTS shield layer with intervals is also examined. It is shown that AC losses in shield layer with intervals are increased when the interval between wires becomes large

Dram1 regulates DNA damage-induced alternative autophagy

Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy

Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

Role of PERK in mitochondrial function

Mitochondria play a central role in the function of brown adipocytes (BAs). Although mitochondrial biogenesis, which is indispensable for thermogenesis, is regulated by coordination between nuclear DNA transcription and mitochondrial DNA transcription, the molecular mechanisms of mitochondrial development during BA differentiation are largely unknown. Here, we show the importance of the ER-resident sensor PKR-like ER kinase (PERK) in the mitochondrial thermogenesis of brown adipose tissue. During BA differentiation, PERK is physiologically phosphorylated independently of the ER stress. This PERK phosphorylation induces transcriptional activation by GA-binding protein transcription factor α subunit (GABPα), which is required for mitochondrial inner membrane protein biogenesis, and this novel role of PERK is involved in maintaining the body temperatures of mice during cold exposure. Our findings demonstrate that mitochondrial development regulated by the PERK–GABPα axis is indispensable for thermogenesis in brown adipose tissue

Autophagy controls centrosome number by degrading Cep63

Centrosome number is associated with the chromosome segregation and genomic stability. The ubiquitin–proteasome system is considered to be the main regulator of centrosome number. However, here we show that autophagy also regulates the number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The autophagic regulation of centrosome number is dependent on a centrosomal protein of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that are engulfed and digested by autophagy in wild-type cells, and that the upregulation of Cep63 increases centrosome number. Cep63 is recruited to autophagosomes via interaction with p62, a molecule crucial for selective autophagy. In vivo, hematopoietic cells from autophagy-deficient and p62−/− mice also contained multiple centrosomes. These results indicate that autophagy controls centrosome number by degrading Cep63

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

High Energy Particle Measurements during Long Discharge in LHD

The spatial resolved energy spectra can be observed during a long discharge of NBI plasma bycontinuously scanning the neutral particle analyzer. In these discharges, the plasmas are initiated by the ECH heating, after that NBI#2 (Co-injection) sustains the plasma during 40-60 seconds. The scanned pitch angle is from 44 degrees to 74 degrees. The injected neutral beam (hydrogen) energy of NBI#2 is only 130 keV because the original ion source polarity is negative. The shape of spectra is almost similar from 44 degrees to 53 degrees. However the spectra from 55 degrees are strongly varied. It reflects the injection pitch angle of the beam according to the simulation (53 degrees ot R* = 3.75 m in simulation). The beam keeps the pitch angle at incidence until the beam energy becomes to the energy, which the pitch angle scattering is occurred by the energy loss due to the electron collision. The low flux region can be observed around 10-15 keV, which is 15 times of the electron temperature. The energy region may be equal to the energy at which the pitch angle scattering is occurred. At the energy, the particle is scattered by the collision with the plasma ions and some of particles may run away from the plasma because they have a possibility to enter the loss cone. According to the simulation, the loss cone can be expected at the 10 keV with the small angular dependence. The depth of the loss cone is deep at the small pitch angle. The hollow in the spectrum may be concluded to be the loss cone as the tendency is almost agreed with the experimental result

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix