AMP N1-oxide, a unique compound of royal jelly, induces neurite outgrowth from PC12 cells via signaling by protein kinase A independent of that by mitogen-activated protein kinase

Earlier we identified adenosine monophosphate (AMP) N1-oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth (neuritegenesis) from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1-oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK) but also that of cAMP/calcium-response element-binding protein (CREB) in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1-oxide-induced neuritegenesis, whereas that of protein kinase A (PKA) by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1-oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N1-oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1-oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ

miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors

miR669a and miR669q inhibit postnatal cardiac progenitor differentiation by directly targeting the 3′UTR of MyoD

Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFκB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs

Development of 300 mW Background-Compensated Planar Absolute Radiometer Operating at Room Temperature

NIST’s C-series isoperibol calorimeters [1] operating at room temperature have been used as reference instruments in the laser power calibrations at NIST for over 50 years. These calorimeters operate from 100 μW to 300 mW with an expanded uncertainty of 0.86% (k = 2). Recently developed vertically aligned carbon-nanotube (VACNT) absorbers, with spectrally flat and hemispherical absorptance better than 99.95%, have enabled development of planar absolute bolometers with smaller size and significantly faster measurements compared to traditional laser calorimeters. In this work, we present the latest progress of the Planar Absolute Radiometer for Room Temperature (PARRoT) [2] currently under construction that will replace the old reference C-series calorimeters. PARRoT is based on the electrical power substitution method and it can measure laser powers up to 300 mW with a predicted expanded uncertainty better than 0.1% (k = 2). The radiometer is operated at room temperature and placed in a 15 cm cube vacuum chamber to minimize convection while still providing a compact and sturdy standard. The laser beam is transmitted to the absorber by an uncoated fused silica window with a 0.5° wedge assuring polarization independent laser power detection. PARRoT is background compensated by differential operation where the reference detector chip is driven by a constant DC power and the measuring detector chip is feedback controlled to follow the temperature of the reference detector chip. The closed loop operation makes the radiometer’s response linear across the operational power range. We have optimized the detector chip design by thermal modeling [2]. The modeled electro-optical inequivalence for a centered laser beam is 0.007% and the spatial non-uniformity is ±0.02% within 4 mm radius from the absorber’s center, meaning that PARRoT is not sensitive to small alignment offsets. PARRoT’s differential background compensation makes it insensitive to variations in background radiation. That combined with a compact design would allow it to be used as a radiance detector standard for field calibrations and atmospheric measurements outdoors or as a transfer standard between laboratories. Similar bolometers will be launched in a CubeSat satellite next year to measure total solar irradiance [3]. By changing a few resistance values in the electronics, by changing the detector chip’s heater resistance, and modifying the thermal conductance of the heat link design, the power range of PARRoT can be modified for different applications without compromising the accuracy. For example, reducing the heater resistance and increasing the heat link’s thermal conductance can extend the power range to 2 W. This enables, for instance, direct calibration of the 1 W laser beam power in LIGO (Laser Interferometer Gravitational-wave Observatory) with an expanded uncertainty of 0.1% (k = 2) which would be an order of magnitude improvement to its current calibration against NIST’s reference calorimeter via an integrating sphere transfer standard. Acknowledgements: Jenny and Antti Wihuri Foundation, Finland is acknowledged for the financial support of this research. 1. E. D. West et al., “A Reference Calorimeter for Laser Energy Measurements,” J. Res. Natl. Bur. Stand. (U. S.) 76A, 13–26 (1972). 2. A. Vaskuri et al., “Microfabricated bolometer based on a vertically aligned carbon nanotube absorber,” Proc. SPIE 11269, 1–12, Synthesis and Photonics of Nanoscale Materials XVII, 112690L (March 2020). 3. D. Harber et al., “Compact total irradiance monitor flight demonstration,” Proc. SPIE 11131, 1–8, CubeSats and SmallSats for Remote Sensing III, 111310D (August 2019)

Essential roles of Raf/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, YY1, and Ca2+ influx in growth arrest of human vascular smooth muscle cells by bilirubin

The biological effects of bilirubin, still poorly understood, are concentration-dependent ranging from cell protection to toxicity. Here we present data that at high nontoxic physiological concentrations, bilirubin inhibits growth of proliferating human coronary artery smooth muscle cells by three events. It impairs the activation of Raf/ERK/MAPK pathway and the cellular Raf and cyclin D1 content that results in retinoblastoma protein hypophosphorylation on amino acids S608 and S780. These events impede the release of YY1 to the nuclei and its availability to regulate the expression of genes and to support cellular proliferation. Moreover, altered calcium influx and calpain II protease activation leads to proteolytical degradation of transcription factor YY1. We conclude that in the serum-stimulated human vascular smooth muscle primary cell cultures, bilirubin favors growth arrest, and we propose that this activity is regulated by its interaction with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis.Wepropose that these activities together culminate in diminished 5 S and 45 S ribosomal RNA synthesis and cell growth arrest. The observations provide important mechanistic insight into the molecular mechanisms underlying the transition of human vascular smooth muscle cells from proliferative to contractile phenotype and the role of bilirubin in this transition