Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin.

While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target

Standoff Detection of Solid Traces by Single-Beam Nonlinear Raman Spectroscopy Using Shaped Femtosecond Pulses

We demonstrate a single-beam, standoff (>10m) coherent anti-Stokes Raman scattering spectroscopy (CARS) of various materials, including trace amounts of explosives and nitrate samples, under ambient light conditions. The multiplex measurement of characteristic molecular vibrations with <20cm-1 spectral resolution is carried out using a single broadband (>550cm-1) phase-shaped femtosecond laser pulse. We exploit the strong nonresonant background signal for amplification of the weak backscattered resonant CARS signal by using a homodyne detection scheme. This facilitates a simple, highly sensitive single-beam spectroscopic technique, with a potential for hazardous materials standoff detection applications

Potential barrier height at the grain boundaries of a poly-silicon nanowire

We present measurements of the potential barrier height and its dependence on grain size in poly-silicon nanowire (P-SiNW) arrays. Measurements conducted using Kelvin probe force microscopy coupled with electrostatic simulations, enabled us also to extract the density of the grain boundary interface states and their energy distribution. In addition it was shown that the barrier height scales with the grain size as the square of the grain radius

Rosiglitazone and Pioglitazone Alter Aromatase Kinetic Properties in Human Granulosa Cells

We have previously reported that, in human granulosa cells, thiazolidinediones rosiglitazone and pioglitazone inhibit estrogen synthesis by interfering with androgen binding to aromatase, without an effect on aromatase mRNA or protein expression. In the current paper, we explore the effects of rosiglitazone and pioglitazone on the aromatase enzyme kinetic properties in human granulosa cells. The cells were incubated with various concentrations of testosterone or androstenedione, with or without rosiglitazone or pioglitazone. Estradiol and estrone concentrations in the conditioned tissue culture medium were measured by radioimmunoassay or immunosorbent assay. When testosterone was used as substrate, rosiglitazone or pioglitazone inhibited the Vmax by 35% (P < 0.001) and 24% (P < 0.001), respectively. When androstenedione was used as substrate, both rosiglitazone or pioglitazone inhibited Vmax by 13% (P < 0.007). We conclude that rosiglitazone or pioglitazone has no effect on Km but inhibits Vmax of aromatase in human granulosa cells, therefore, acting as noncompetitive inhibitors

Ultrasensitive hydrogen detection by electrostatically formed silicon nanowire decorated by palladium nanoparticles

Developing high performance hydrogen (H_{2}) sensors is of utmost importance to facilitate the safe usage of H_{2} as the alternative source of clean and renewable energy. We present an ultra-sensitive H_{2} sensor operating in air and based on electrostatically formed nanowire (EFN) sensor decorated by palladium nanoparticles (Pd NPs). By appropriate tuning of the various gate voltages of the EFN, an extremely high sensor response of ∼2 × 10^{6} % (0.8 % H_{2} exposure) and a sensitivity of ∼400 % ppm^{−1} is obtained at room temperature (20 ± 2 °C). This sensor outperforms, to the best of our knowledge, most of the reported resistive and field effect transistor (FET) based H^{2} sensors. The EFN power consumption varies from few pW to ∼436 nW at maximum current operation thus enabling ultra-low power usage at room temperature. In addition, the sensor exhibits fast response and recovery times, retains good sensing performances even at 50 % relative humidity (RH) and exhibits reproducibility over time. Combining Pd NPs with the unique features of the EFN platform makes Pd-EFN a versatile, robust, low power, rapid, and highly sensitive H_{2} sensor

Photon assisted Levy flights of minority carriers in n-InP

We study the photoluminescence spectra of n-doped InP bulk wafers, both in the reflection and the transmission geometries relative to the excitation beam. From the observed spectra we estimate the spatial distribution of minority carriers allowing for the spectral filtering due to re-absorption of luminescence in the wafer. This distribution unambiguously demonstrates a non-exponential drop-off with distance from the excitation region. Such a behavior evidences an anomalous photon-assisted transport of minority carriers enhanced owing to the high quantum efficiency of emission. It is shown that the transport conforms very well to the so-called Levy-flights process corresponding to a peculiar random walk that does not reduce to diffusion. The index gamma of the Levy flights distribution is found to be in the range gamma = 0.64 to 0.79, depending on the doping. Thus, we propose the high-efficiency direct-gap semiconductors as a remarkable laboratory system for studying the anomalous transport.Comment: 12 pages, 9 figure

Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency from Molecular Mechanisms to Clinical Manifestations

Fragile X syndrome (FXS), is caused by a loss-of-function mutation in the FMR1 gene located on the X-chromosome, which leads to the most common cause of inherited intellectual disability in males and the leading single-gene defect associated with autism. A full mutation (FM) is represented by more than 200 CGG repeats within the FMR1 gene, resulting in FXS. A FM is inherited from women carrying a FM or a premutation (PM; 55–200 CGG repeats) allele. PM is associated with phenotypes distinct from those associated with FM. Some manifestations of the PM are unique; fragile-X-associated tremor/ataxia syndrome (FXTAS), and fragile-X-associated primary ovarian insufficiency (FXPOI), while others tend to be non-specific such as intellectual disability. In addition, women carrying a PM may suffer from subfertility or infertility. There is a need to elucidate whether the impairment of ovarian function found in PM carriers arises during the primordial germ cell (PGC) development stage, or due to a rapidly diminishing oocyte pool throughout life or even both. Due to the possibility of expansion into a FM in the next generation, and other ramifications, carrying a PM can have an enormous impact on one’s life; therefore, preconception counseling for couples carrying the PM is of paramount importance. In this review, we will elaborate on the clinical manifestations in female PM carriers and propose the definition of fragile-X-associated diminished ovarian reserve (FXDOR), then we will review recent scientific findings regarding possible mechanisms leading to FXDOR and FXPOI. Lastly, we will discuss counseling, preventative measures and interventions available for women carrying a PM regarding different aspects of their reproductive life, fertility treatment, pregnancy, prenatal testing, contraception and fertility preservation options

Red Ginseng Extract Facilitates the Early Differentiation of Human Embryonic Stem Cells into Mesendoderm Lineage

Human embryonic stem cells (hESCs) have capacities to self-renew and differentiate into all cell types in vitro. Red ginseng (RG) is known to have a wide range of pharmacological effects in vivo; however, the reports on its effects on hESCs are few. In this paper, we tried to demonstrate the effects of RG on the proliferation and differentiation of hESCs. Undifferentiated hESCs, embryoid bodies (EBs), and hESC-derived cardiac progenitors (CPs) were treated with RG extract at 0.125, 0.25, and 0.5 mg/mL. After treatment of undifferentiated hESCs from day 2 to day 6 of culture, BrdU labeling showed that RG treatment increased the proliferation of hESCs, and the expression of Oct4 and Nanog was increased in RG-treated group. To find out the effects of RG on early differentiation stage cells, EBs were treated with RG extract for 10 days and attached for further differentiation. Immunostaining for three germ layer markers showed that RG treatment increased the expressions of Brachyury and HNF3β on EBs. Also, RG treatment increased the expression of Brachyury in early-stage and of Nkx2.5 in late-stage hESC-derived CPs. These results demonstrate facilitating effects of RG extract on the proliferation and early differentiation of hESC