The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory ...neurons as a central integrator of various nociceptive stimuli. However, several human skin cell populations are also now recognized to express TRPV1, but with unknown function. Exploiting the human hair follicle (HF) as a prototypic epithelial-mesenchymal interaction system, we have characterized the HF expression of TRPV1 in situ and have examined TRPV1 signaling in organ-cultured human scalp HF and outer root sheath (ORS) keratinocytes in vitro. TRPV1 immunoreactivity was confined to distinct epithelial compartments of the human HF, mainly to the ORS and hair matrix. In organ culture, TRPV1 activation by capsaicin resulted in a dose-dependent and TRPV1-specific inhibition of hair shaft elongation, suppression of proliferation, induction of apoptosis, premature HF regression (catagen), and up-regulation of intrafollicular transforming growth factor-beta(2). Cultured human ORS keratinocytes also expressed functional TRPV1, whose stimulation inhibited proliferation, induced apoptosis, elevated intracellular calcium concentration, up-regulated known endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), and down-regulated known hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor). These findings strongly support TRPV1 as a significant novel player in human hair growth control, underscore the physiological importance of TRPV1 in human skin beyond nociception, and identify TRPV1 as a promising, novel target for pharmacological manipulations of epithelial growth disorders.
Summary
Background Galanin is a trophic factor of the central and peripheral nervous system that shows widespread distribution in human skin. However, the exact localization and the role of galanin ...in the hair follicle (HF) remain to be clarified.
Objectives To characterize galanin expression in human scalp HFs and to examine the effects of galanin on normal human scalp HF growth in organ culture.
Methods Immunohistochemistry was performed on cryosections of human female scalp skin. Anagen HFs were microdissected and cultured up to 9 days and treated with 100 nmol L−1 galanin. Staining for Ki‐67, TUNEL and Masson–Fontana were used to analyse proliferation, apoptosis and hair cycle staging of the HFs. Functional effects of galanin were tested in serum‐free HF organ culture.
Results Galanin‐like immunoreactivity was detected in the outer root sheath (ORS) and inner root sheath. Additionally, galanin mRNA was detected in ORS keratinocytes and all HF samples tested. Galanin receptor transcripts (GalR2, GalR3) were also detected in selected samples. Galanin reduced proliferation of hair matrix keratinocytes in situ compared with vehicle‐treated controls, shortened the hair growth phase (anagen) in vitro and reduced hair shaft elongation. This was accompanied by the premature development of a catagen‐like morphology of galanin‐treated HFs.
Conclusions We present the first evidence that human HFs are both a source and a functionally relevant target of galanin. Due to its hair growth‐inhibitory properties in vitro, galanin application deserves further exploration as a potential new treatment strategy for unwanted hair growth (hirsutism, hypertrichosis).
KIC 8560861 (HD 183648) is a marginally eccentric (e = 0.05) eclipsing binary with an orbital period of Porb = 31.973 d, exhibiting mmag amplitude pulsations on time scales of a few days. We present ...the results of the complex analysis of high and medium-resolution spectroscopic data and Kepler Q0 – Q16 long cadence photometry.
The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 h on the protein kinase C (PKC) profiles, rates of proliferation and apoptosis in Jurkat cells and lymphocytes of 10 ...patients with systemic lupus erythematosus (SLE) and nine healthy subjects. The expressions of PKC proteins, the rates of proliferation and apoptosis were determined. The effects of BZ were different in the Jurkat and lupus T cells. Whereas BZ elevated the expression of PKC θ, δ and ξ isoenzymes in the Jurkat cells, it was unable to do that in the lupus T cells. BZ induced a dose‐dependent increase in the apoptosis of Jurkat cells, while decreased the proliferation. The same effect of BZ was observed on the apoptosis of lymphocytes both in SLE and healthy subjects at concentrations higher than the therapeutic dose. We conclude that BZ treatment in vitro was not able to restore the SLE‐specific defect (decrease) in the expression of PKC isoenzymes in the T cells as it was expected. This can be a limiting factor in the positive clinical effects of BZ in lupus.
Background and Purpose
Heat‐sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is ...well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are indispensable in the formation of the glomerular filtration barrier, we investigated the presence and function of Ca2+‐permeable TRPV1–4 channels in human podocyte cultures.
Experimental Approach
Expression of TRPV1–4 channels was investigated at protein (immunocytochemistry, Western blot) and mRNA (Q‐PCR) level in a conditionally immortalized human podocyte cell line. Channel function was assessed by measuring intracellular Ca2+ concentration using Flou‐4 Ca2+‐indicator dye and patch clamp electrophysiology upon applying various activators and inhibitors.
Key Results
Thermosensitive TRP channels were expressed in podocytes. The TRPV1‐specific agonists capsaicin and resiniferatoxin did not affect the intracellular Ca2+ concentration. Cannabidiol, an activator of TRPV2 and TRPV4 channels, induced moderate Ca2+‐influxes, inhibited by both tranilast and HC067047, blockers of TRPV2 and TRPV4 channels respectively. The TRPV4‐specific agonists GSK1016790A and 4α‐phorbol 12,13‐didecanoate induced robust Ca2+‐signals which were abolished by HC067047. Non‐specific agonists of TRPV3 channels induced marked Ca2+ transients. However, TRPV3 channel blockers, ruthenium red and isopentenyl diphosphate only partly inhibited the responses and TRPV3 silencing was ineffective suggesting remarkable off‐target effects of the compounds.
Conclusion and Implications
Our results indicate the functional presence of TRPV4 and other thermosensitive TRPV channels in human podocytes and raise the possibility of their involvement in the regulation of glomerular filtration barrier.
CHEOPS in-flight performance Fortier, A.; Simon, A. E.; Broeg, C. ...
Astronomy and astrophysics (Berlin),
7/2024, Letnik:
687
Journal Article
Recenzirano
Odprti dostop
Context . Since the discovery of the first exoplanet almost three decades ago, the number of known exoplanets has increased dramatically. By beginning of the 2000s it was clear that dedicated ...facilities to advance our studies in this field were needed. The CHaracterising ExOPlanet Satellite (CHEOPS) is a space telescope specifically designed to monitor transiting exoplanets orbiting bright stars. In September 2023, CHEOPS completed its nominal mission duration of 3.5 yr and remains in excellent operational conditions. As a testament to this, the mission has been extended until the end of 2026. Aims . Scientific and instrumental data have been collected throughout in-orbit commissioning and nominal operations, enabling a comprehensive analysis of the mission’s performance. In this article, we present the results of this analysis with a twofold goal. First, we aim to inform the scientific community about the present status of the mission and what can be expected as the instrument ages. Secondly, we intend for this publication to serve as a legacy document for future missions, providing insights and lessons learned from the successful operation of CHEOPS. Methods . To evaluate the instrument performance in flight, we developed a comprehensive monitoring and characterisation (M&C) programme. It consists of dedicated observations that allow us to characterise the instrument’s response and continuously monitor its behaviour. In addition to the standard collection of nominal science and housekeeping data, these observations provide valuable input for detecting, modelling, and correcting instrument systematics, discovering and addressing anomalies, and comparing the instrument’s actual performance with expectations. Results . The precision of the CHEOPS measurements has enabled the mission objectives to be met and exceeded. The satellite’s performance remains stable and reliable, ensuring accurate data collection throughout its operational life. Careful modelling of the instrumental systematics allows the data quality to be significantly improved during the light curve analysis phase, resulting in more precise scientific measurements. Conclusions . CHEOPS is compliant with the driving scientific requirements of the mission. Although visible, the ageing of the instrument has not affected the mission’s performance. The satellite’s capabilities remain robust, and we are confident that we will continue to acquire high-quality data during the mission extension.
Complex period variations of five W UMa type binaries (AB And, OO Aql, DK Cyg, V566 Oph, U Peg) were investigated by analyzing their O-C diagrams, and several common features were found. Four of the ...five systems show secular period variations at a constant rate on the order of parallel P sub(sec)/P parallel similar to 10 super(-7) yr super(-1). In the case of AB And, OO Aql, and U Peg a high-amplitude, nearly one-century long quasi-sinusoidal pattern was also found. It might be explained as light-time effect, or by some magnetic phenomena, although the mathematical, and consequently the physical, parameters of these fits are very problematic, as the obtained periods are very close to the length of the total data range. The most interesting feature of the studied O-C diagrams is a low amplitude ( similar to 2-4 x 10 super(-3) d) modulation with a period around 18-20 yr in four of the five cases. This phenomenon might be indirect evidence of some magnetic cycle in late-type overcontact binaries as an analog to the observed activity cycles in RS CVn systems.
The goal of the current study was to investigate the expression of transient receptor potential vanilloid-1 (TRPV1) on human in vitro differentiated monocyte-derived dendritic cells (DCs) and to ...dissect the corresponding role of TRPV1-signaling in DC-specific functions. TRPV1 expression was identified both at the protein and gene levels in human DCs. Moreover, the prototypic TRPV1 agonist capsaicin specifically (i.e. via TRPV1) and dose-dependently inhibited cytokine-induced DC differentiation, phagocytosis of bacteria, activation of DCs, and pro-inflammatory cytokine secretion. These data introduce TRPV1-coupled signaling as a novel player in human monocyte-derived DC biology with anti-inflammatory actions.
Asymmetric features in exoplanet transit light curves are often interpreted as a gravity darkening effect especially if there is spectroscopic evidence of a spin-orbit misalignment. Since other ...processes can also lead to light curve asymmetries this may lead to inaccurate gravity darkening parameters. Here we investigate the case of non-radial pulsations as possible sources of asymmetry and likely source of misinterpreted parameters through simulations. We obtained a series of simulated transit light curves of a hypothetical exoplanet-star system: a host star with no gravity darkening exhibiting small amplitude pulsations, and a typical hot Jupiter in a circular, edge-on orbit. A number of scenarios of pulsations of various amplitudes were considered, and a proper account of the obscuring effect of transits on all the surface intensity components was made. The magnitude of amplitude and phase modulations of nonradial pulsations during transits was also also investigated. We then fitted both a non-gravity-darkened, and a gravity-darkened, free spin-orbit axis model on the data. The Akaike and Bayesian Information Criteria were used for an objective selection of the most plausible model. We then explored the dependence of the parameter deviations on the pulsation properties, in order to identify configurations that can lead to falsely misaligned solutions. Low-amplitude pulsations in general do not affect the determination of the system parameters beyond their noise nature. However, frequencies close to multiples of the orbital frequency are found to cause distortions leading to solutions with a side tilted stellar rotational axis, they are therefore preferable to clean beforehand for the sake of a correct analysis. Additionally, for cases with higher-amplitude pulsations, it is recommended to pre-process and clean the pulsations before analysis.
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