Estradiol Signaling at the Heart of Folliculogenesis: Its Potential Deregulation in Human Ovarian Pathologies

Estradiol (E2) is a major hormone controlling women fertility, in particular folliculogenesis. This steroid, which is locally produced by granulosa cells (GC) within ovarian follicles, controls the development and selection of dominant preovulatory follicles. E2 effects rely on a complex set of nuclear and extra-nuclear signal transduction pathways principally triggered by its nuclear receptors, ERα and ERβ. These transcription factors are differentially expressed within follicles, with ERβ being the predominant ER in GC. Several ERβ splice isoforms have been identified and display specific structural features, which greatly complicates the nature of ERβ-mediated E2 signaling. This review aims at providing a concise overview of the main actions of E2 during follicular growth, maturation, and selection in human. It also describes the current understanding of the various roles of ERβ splice isoforms, especially their influence on cell fate. We finally discuss how E2 signaling deregulation could participate in two ovarian pathogeneses characterized by either a follicular arrest, as in polycystic ovary syndrome, or an excess of GC survival and proliferation, leading to granulosa cell tumors. This review emphasizes the need for further research to better understand the molecular basis of E2 signaling throughout folliculogenesis and to improve the efficiency of ovarian-related disease therapies.

Counting-loss correction method based on dual-exponential impulse shaping

Under the condition of high counting rate, the phenomenon of nuclear pulse signal pile-up using a single exponential impulse shaping method is still very serious, and leads to a severe loss in counting rate. A real nuclear pulse signal can be expressed as a dual-exponential decay function with a certain rising edge. This paper proposes a new dual-exponential impulse shaping method and shows its deployment in hardware to test its performance. The signal of a high-performance silicon drift detector under high counting rate in an X-ray fluorescence spectrometer is obtained. The result of the experiment shows that the new method can effectively shorten the dead-time caused by nuclear signal pile-up and correct the counting rate.

Boron deficiency-induced root growth inhibition is mediated by brassinosteroid signalling regulation in Arabidopsis

ABSTRACTBrassinosteroid (BR) is a pivotal phytohormone involved in regulating root development. Boron (B) is an essential micronutrient for plant growth and development, and root growth of plants is rapidly inhibited under B deficiency condition, but the mechanisms are still elusive. Here, we demonstrate that BR plays crucial roles in these processes. We identify BR-related processes underlying B deficiency at the physiological, genetic, molecular/cell biological and transcriptome levels, and provide strong evidences that B deficiency can affect BR signalling, thereby altering root growth. RNA-sequencing analysis reveals a high co-regulation between BR-regulated genes and B deficiency-responsive genes. We found that low B negatively regulates BR signalling to control BR signalling-dependent root elongation, bes1-D exhibits insensitivity to low B stress, and bri1-301 mutants fails to respond to B depletion. Exogenous eBL application can rescue the inhibition of root growth under B deficiency condition, and application of BR biosynthesis inhibitor BRZ aggravates root growth inhibition of wild-type under B deficiency condition. B deficiency reduces the nuclear signal of BES1. We further found that B deficiency reduces the accumulation of brassinolide (BL) by reducing BR6ox1 and BR6ox2 mRNA level to down-regulate BR signalling and modulate root elongation. Altogether, our results uncover a role of BR signalling in root elongation under B deficiency.One-sentence summaryB deficiency reduces the accumulation of brassinolide by reducing BR6ox1 and BR6ox2 mRNA level to down-regulate BR signalling and modulate root elongation.

Nutritional Stress in Head and Neck Cancer Originating Cell Lines: The Sensitivity of the NRF2-NQO1 Axis

Nutritional stress disturbs the cellular redox-status, which is characterized by the increased generation of reactive oxygen species (ROS). The NRF2-NQO1 axis represents a protective mechanism against ROS. Its strength is cell type-specific. FaDu, Cal 27 and Detroit 562 cells differ with respect to basal NQO1 activity. These cells were grown for 48 hours in nutritional conditions (NC): (a) Low glucose–NC2, (b) no glucose, no glutamine–NC3, (c) no glucose with glutamine–NC4. After determining the viability, proliferation and ROS generation, NC2 and NC3 were chosen for further exploration. These conditions were also applied to IMR-90 fibroblasts. The transcripts/transcript variants of NRF2 and NQO1 were quantified and transcript variants were characterized. The proteins (NRF2, NQO1 and TP53) were analyzed by a western blot in both cellular fractions. Under NC2, the NRF2-NQO1 axis did not appear activated in the cancer cell lines. Under NC3, the NRF2-NQO1axis appeared slightly activated in Detroit 562. There are opposite trends with respect to TP53 nuclear signal when comparing Cal 27 and Detroit 562 to FaDu, under NC2 and NC3. The strong activation of the NRF2-NQO1 axis in IMR-90 resulted in an increased expression of catalytically deficient NQO1, due to NQO1*2/*2 polymorphism (rs1800566). The presented results call for a comprehensive exploration of the stress response in complex biological systems.

The Building of Pulsed NQR/NMR Spectrometer

<p>NQR spectrometer designed is composed of four modules; Transmitter, Probe, Receiver and computer controlled (FPGA &amp; Software) module containing frequency synthesizer, synchronous demodulator, pulse programmer and display. The function of the Transmitter module is to amplify the RF pulse sequence to about 200 W power level into the probe (50 Ohm) which is a parallel resonance circuit with a tapped capacitor. The probe excites the nucleus and picks-up the signal emitted from the nuclei. The nuclear signal at the same frequency as the excitation, which is typically in the range of a few microvolts is amplified, demodulated and filtered (1 kHz to 100 kHz) by receiver module. 14N NQR, 1H and 2H NMR signals are observed from the spectrometer.As the SNR of NQR signal is very low, NQR signal processing based on Adaptive Line Enhancement is presented.</p>

Disrupted TSH Receptor Expression in Female Mouse Lung Fibroblasts Alters Subcellular IGF-1 Receptor Distribution

A relationship between the actions of TSH and IGF-1 was first recognized several decades ago. The close physical and functional associations between their respective receptors (TSHR and IGF-1R) has been described more recently in thyroid epithelium and human orbital fibroblasts as has the noncanonical behavior of IGF-1R. Here we report studies conducted in lung fibroblasts from female wild-type C57/B6 (TSHR+/+) mice and their littermates in which TSHR has been knocked out (TSHR−/−). Flow cytometric analysis revealed that cell surface IGF-1R levels are substantially lower in TSHR−/− fibroblasts compared with TSHR+/+ fibroblasts. Confocal immunofluorescence microscopy revealed similar divergence with regard to both cytoplasmic and nuclear IGF-1R. Western blot analysis demonstrated both intact IGF-1R and receptor fragments in both cellular compartments. In contrast, IGF-1R mRNA levels were similar in fibroblasts from mice without and with intact TSHR expression. IGF-1 treatment of TSHR+/+ fibroblasts resulted in reduced nuclear and cytoplasmic staining for IGF-1Rα, whereas it enhanced the nuclear signal in TSHR−/− cells. In contrast, IGF-1 enhanced cytoplasmic IGF-1Rβ in TSHR−/− fibroblasts while increasing the nuclear signal in TSHR+/+ cells. These findings indicate the intimate relationship between TSHR and IGF-1R found earlier in human orbital fibroblasts also exists in mouse lung fibroblasts. Furthermore, the presence of TSHR in these fibroblasts influenced not only the levels of IGF-1R protein but also its subcellular distribution and response to IGF-1. They suggest that the mouse might serve as a suitable model for delineating the molecular mechanisms overarching these two receptors.