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Restrictive cardiomyopathy (RCM) is a rare disease characterized by increased ventricular stiffness and preserved ventricular contraction. Various sarcomere gene variants are known to cause RCM; however, more than a half of patients do not harbor such pathogenic variants. We recently demonstrated that cardiac fibroblasts (CFs) play important roles in inhibiting the diastolic function of cardiomyocytes via humoral factors and direct cell–cell contact regardless of sarcomere gene mutations. However, the mechanical properties of CFs that are crucial for intercellular communication and the cardiomyocyte microenvironment remain less understood. In this study, we evaluated the rheological properties of CFs derived from pediatric patients with RCM and healthy control CFs via atomic force microscopy. Then, we estimated the cellular modulus scale factor related to the cell stiffness, fluidity, and Newtonian viscosity of single cells based on the single power-law rheology model and analyzed the comprehensive gene expression profiles via RNA-sequencing. RCM-derived CFs showed significantly higher stiffness and viscosity and lower fluidity compared to healthy control CFs. Furthermore, RNA-sequencing revealed that the signaling pathways associated with cytoskeleton elements were affected in RCM CFs; specifically, cytoskeletal actin-associated genes ( ACTN1 , ACTA2 , and PALLD ) were highly expressed in RCM CFs, whereas several tubulin genes ( TUBB3 , TUBB , TUBA1C , and TUBA1B ) were down-regulated. These results implies that the signaling pathways associated with cytoskeletal elements alter the rheological properties of RCM CFs, particularly those related to CF–cardiomyocyte interactions, thereby leading to diastolic cardiac dysfunction in RCM.

Restrictive cardiomyopathy (RCM) is a rare disease characterized by increased ventricular stiffness and preserved ventricular contraction. Various sarcomere gene variants are known to cause RCM; however, more than a half of patients do not harbor such pathogenic variants. We recently demonstrated that cardiac fibroblasts (CFs) play important roles in inhibiting the diastolic function of cardiomyocytes via humoral factors and direct cell-cell contact regardless of sarcomere gene mutations. However, the mechanical properties of CFs that are crucial for intercellular communication and the cardiomyocyte microenvironment remain less understood. In this study, we evaluated the rheological properties of CFs derived from pediatric patients with RCM and healthy control CFs via atomic force microscopy. Then, we estimated the cellular modulus scale factor related to the cell stiffness, fluidity, and Newtonian viscosity of single cells based on the single power-law rheology model and analyzed the comprehensive gene expression profiles via RNA-sequencing. RCM-derived CFs showed significantly higher stiffness and viscosity and lower fluidity compared to healthy control CFs. Furthermore, RNA-sequencing revealed that the signaling pathways associated with cytoskeleton elements were affected in RCM CFs; specifically, cytoskeletal actin-associated genes (ACTN1, ACTA2, and PALLD) were highly expressed in RCM CFs, whereas several tubulin genes (TUBB3, TUBB, TUBA1C, and TUBA1B) were down-regulated. These results implies that the signaling pathways associated with cytoskeletal elements alter the rheological properties of RCM CFs, particularly those related to CF-cardiomyocyte interactions, thereby leading to diastolic cardiac dysfunction in RCM.

Background: Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated. Methods: ADCC, CDC and anoikis assays in combination with C2-74 and an anticancer drug (5-fluorouracil or cisplatin) were investigated using tumor cell lines (MKN-45, MKN-74 and KATO III). In the anoikis assay, other human anti-CEA Abs and mouse anti-CEA-related cell adhesion molecule 6 Abs were also investigated using HLC-1 cells. Results: Additive cytotoxicity was observed when the anticancer drug and C2-74 on tumor cells were combined in the CDC assays, whereas in the anoikis assay, no such additive effect was observed. Anti-CEA-related cell adhesion molecule 6 Abs, but not anti-CEA Abs, accelerated anoikis in HLC-1 cells. Conclusion: A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells.

Background This study aimed to evaluate the association of COVID-19 preventive behavior and job-related stress with sleep quality among healthcare workers (HCWs). We conducted a cross-sectional survey using a questionnaire at the National Center of Neurology and Psychiatry, Tokyo, Japan. Methods A total of 586 participants who completed the questionnaire were eligible for the study. The Pittsburgh Sleep Quality Index was used to evaluate sleep quality. We examined the level of engagement between poor sleep and COVID-19-related infection preventive behaviors, such as avoiding closed spaces, crowded places, and close contact (three Cs), a distance of at least one meter from others, wearing a face mask regularly, washing hands regularly, and working remotely, as well as job-related stress in the work environment, exposure to patients, potential risk of infection, fear of infecting others, need for social confinement, and financial instability. We conducted a hierarchical logistic regression analysis to examine the relationship between poor sleep and COVID-19 preventive behavior, job-related stress, and other covariates, including age, sex, and the Kessler Psychological Distress Scale (K6), which was used to measure non-specific psychological distress. Results Poor sleep was observed in 223 (38.1%) participants. Adherence to COVID-19 preventive measures was relatively high: 84.1% of participants answered “always” for wearing a face mask regularly and 83.4% for washing hands regularly. In the multivariate logistic regression analysis, stress in the work environment (odds ratio [OR] = 2.09, 95% confidence interval [CI], 1.37–3.20; p  < 0.001), financial instability (OR = 1.73, 95% CI, 1.12–2.67; p  < 0.05), and low adherence to working remotely (OR = 1.65, 95% CI, 1.06–2.57; p  < 0.05) were independently and significantly associated with poor sleep after controlling for the covariates. Conclusions One year into the COVID-19 pandemic, the poor sleep rates of HCWs remained high. These results emphasize the need to protect HCWs from work environment stress and financial concerns.

We have successfully determined the internuclear distance of I 2 molecules in an alignment laser field by applying our molecular structure determination methodology to an I 2 p X-ray photoelectron diffraction profile observed with femtosecond X-ray free electron laser pulses. Using this methodology, we have found that the internuclear distance of the sample I 2 molecules in an alignment Nd:YAG laser field of 6 × 10 11  W/cm 2 is elongated by from 0.18 to 0.30 Å “in average” relatively to the equilibrium internuclear distance of 2.666 Å. Thus, the present experiment constitutes a critical step towards the goal of femtosecond imaging of chemical reactions and opens a new direction for the study of ultrafast chemical reaction in the gas phase.

We report on the measurement of deep inner-shell 2 p X-ray photoelectron diffraction (XPD) patterns from laser-aligned I 2 molecules using X-ray free-electron laser (XFEL) pulses. The XPD patterns of the I 2 molecules, aligned parallel to the polarization vector of the XFEL, were well matched with our theoretical calculations. Further, we propose a criterion for applying our molecular-structure-determination methodology to the experimental XPD data. In turn, we have demonstrated that this approach is a significant step toward the time-resolved imaging of molecular structures.

We performed time-resolved photoelectron spectroscopy of valence orbitals of aligned CO2 molecules using the femtosecond soft x-ray free-electron laser and the synchronized near-infrared laser. By properly ordering the individual single-shot ion images, we successfully obtained the photoelectron angular distributions (PADs) of the CO2 molecules aligned in the laboratory frame (LF). The simulations using the dipole matrix elements due to the time dependent density functional theory calculations well reproduce the experimental PADs by considering the axis distributions of the molecules. The simulations further suggest that, when the degrees of alignment can be increased up to 〈 cos 2 θ 〉 > 0.8 , the molecular geometries during photochemical reactions can be extracted from the measured LFPADs once the accurate matrix elements are given by the calculations.

Xtend is a soft X-ray imaging telescope developed for the X-Ray Imaging and Spectroscopy Mission (XRISM). XRISM is scheduled to be launched in the Japanese fiscal year 2022. Xtend consists of the Soft X-ray Imager (SXI), an X-ray CCD camera, and the X-ray Mirror Assembly (XMA), a thin-foil-nested conically approximated Wolter-I optics. The SXI uses the P-channel, back-illuminated type CCD with an imaging area size of 31 mm on a side. The four CCD chips are arranged in a 2\\(\\times\\)2 grid and can be cooled down to \\(-120\\) \\(^{\\circ}\\)C with a single-stage Stirling cooler. The XMA nests thin aluminum foils coated with gold in a confocal way with an outer diameter of 45~cm. A pre-collimator is installed in front of the X-ray mirror for the reduction of the stray light. Combining the SXI and XMA with a focal length of 5.6m, a field of view of \\(38^{\\prime}\\times38^{\\prime}\\) over the energy range from 0.4 to 13 keV is realized. We have completed the fabrication of the flight model of both SXI and XMA. The performance verification has been successfully conducted in a series of sub-system level tests. We also carried out on-ground calibration measurements and the data analysis is ongoing.

In this multi-messenger astronomy era, all the observational probes are improving their sensitivities and overall performance. The Focusing on Relativistic universe and Cosmic Evolution (FORCE) mission, the product of a JAXA/NASA collaboration, will reach a 10 times higher sensitivity in the hard X-ray band (\\(E >\\) 10~keV) in comparison with any previous hard X-ray missions, and provide simultaneous soft X-ray coverage. FORCE aims to be launched in the early 2030s, providing a perfect hard X-ray complement to the ESA flagship mission Athena. FORCE will be the most powerful X-ray probe for discovering obscured/hidden black holes and studying high energy particle acceleration in our Universe and will address how relativistic processes in the universe are realized and how these affect cosmic evolution. FORCE, which will operate over 1--79 keV, is equipped with two identical pairs of supermirrors and wideband X-ray imagers. The mirror and imager are connected by a high mechanical stiffness extensible optical bench with alignment monitor systems with a focal length of 12~m. A light-weight silicon mirror with multi-layer coating realizes a high angular resolution of \\(<15''\\) in half-power diameter in the broad bandpass. The imager is a hybrid of a brand-new SOI-CMOS silicon-pixel detector and a CdTe detector responsible for the softer and harder energy bands, respectively. FORCE will play an essential role in the multi-messenger astronomy in the 2030s with its broadband X-ray sensitivity.