RESUMO
Synthetic glucocorticoids (GC), such as dexamethasone, are extensively used to treat chronic inflammation and autoimmune disorders. However, long-term treatments are limited by various side effects, including muscle atrophy. GC activities are mediated by the glucocorticoid receptor (GR), that regulates target gene expression in various tissues in association with cell-specific co-regulators. Here we show that GR and the lysine-specific demethylase 1 (LSD1) interact in myofibers of male mice, and that LSD1 connects GR-bound enhancers with NRF1-associated promoters to stimulate target gene expression. In addition, we unravel that LSD1 demethylase activity is required for triggering starvation- and dexamethasone-induced skeletal muscle proteolysis in collaboration with GR. Importantly, inhibition of LSD1 circumvents muscle wasting induced by pharmacological levels of dexamethasone, without affecting their anti-inflammatory activities. Thus, our findings provide mechanistic insights into the muscle-specific GC activities, and highlight the therapeutic potential of targeting GR co-regulators to limit corticotherapy-induced side effects.
Assuntos
Dexametasona , Glucocorticoides , Histona Desmetilases , Músculo Esquelético , Atrofia Muscular , Receptores de Glucocorticoides , Animais , Masculino , Histona Desmetilases/metabolismo , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Glucocorticoides/farmacologia , Dexametasona/farmacologia , Receptores de Glucocorticoides/metabolismo , Camundongos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/tratamento farmacológico , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Camundongos Endogâmicos C57BL , Regulação da Expressão Gênica/efeitos dos fármacosRESUMO
As the need for higher data rates for communication increases, the terahertz (THz) band has drawn considerable attention. This spectral region promises a much wider bandwidth and the transmission of large amounts of data at high speeds. However, there are still challenges that need to be addressed before the THz telecommunications technology hits the consumer market. One of the recurring concerns is that THz radiation is greatly absorbed by atmospheric water-vapor. Although many studies have presented the attenuation of THz signals under different atmospheric conditions, these results analyze specific temperature or humidity values, leaving the need for a more comprehensive analysis over a wider range of climate conditions. In this work, we present the first study of the attenuation of THz radiation over a broad range of temperatures and humidity values. It is worth noticing that all of our measurements have been undertaken at atmospheric pressure unlike many previous studies where the pressure was not kept constant for various temperatures. Furthermore, we extend our analysis beyond the impact of absolute humidity on the bit error rate in THz communications. We also discuss the refractivity of the atmosphere, examining its variations across different temperatures and humidity levels. THz propagation is studied using two different measurement systems, a long-path THz time-domain spectrometer as well as a quasi-optic setup with vector network analyze. We also compare the results with the ITU-R P.676-13 propagation model. We conclude that the attenuation at the absorption peaks increases linearly with water content and has no dependence on the temperature, while the refractive index, away from absorption lines, namely at 300 GHz shows a sub-linear increase with humidity.
RESUMO
Terahertz (THz) radiation has shown enormous potential for non-destructive inspection in many contexts. Here, we present a method for imaging defects in chocolate bars that can be extended to many other materials. Our method requires only a continuous wave (CW) monochromatic source and detector at relatively low frequencies (280 GHz) corresponding to a relatively long wavelength of 1.1 mm. These components are used to construct a common-path configuration enabling the capturing of several images of THz radiation diffracted by the test object at different axial depths. The captured diffraction-rich images are used to constrain the associated phase retrieval problem enabling full access to the wave field, i.e., real amplitude and phase distributions. This allows full-field diffraction-limited phase-contrast imaging. Thus, we experimentally demonstrate the possibility of identifying contaminant particles with dimensions comparable to the wavelength.
Assuntos
Chocolate , Microscopia de Contraste de Fase , Radiação TerahertzRESUMO
In this contribution, we demonstrate the first referenceless measurement of a THz wavefront by means of shear-interferometry. The technique makes use of a transmissive Ronchi phase grating to generate the shear. We fabricated the grating by mechanical machining of high-density polyethylene. At the camera plane, the +1 and -1 diffraction orders are coherently superimposed, generating an interferogram. We can adjust the shear by selecting the period of the grating and the focal length of the imaging system. We can also alter the direction of the shear by rotating the grating. A gradient-based iterative algorithm is used to reconstruct the wavefront from a set of shear interferograms. The results presented in this study demonstrate the first step towards wavefield sensing in the terahertz band without using a reference wave.
RESUMO
We designed and tested a highly sensitive metasurface device based on free-standing complementary asymmetric split-ring resonators at terahertz frequencies. It is utilized for sensing a galactose film. We characterized the device using the induced red shift of a Fano resonance observed in the THz transmission. The sensor has a high sensitivity of 91.7 GHz/RIU due to a significant interaction between the galactose overlayer and the metasurface.