Androgen and estrogen receptor expression in the developing human penis and clitoris.

To better understand how the human fetal penis and clitoris grows and remodels, we undertook an investigation to define active areas of cellular proliferation and programmed cell death spatially and temporally during development of human fetal external genitalia from the indifferent stage (8 weeks) to 18 weeks of gestation. Fifty normal human fetal penile and clitoral specimens were examined using macroscopic imaging, scanning electron microscopy and immunohistochemical localization for the cellular proliferation and apoptotic markers, Ki67 and Caspase-3. A number of hot spots of cellular proliferation characterized by Ki67 localization are present in the penis and clitoris especially early in development, most notably in the corporal body, glans, remodeling glanular urethra, the urethral plate, the roof of the urethral groove and the fully formed penile urethra. The 12-fold increase in penile length over 10 weeks of growth from 8 to 18 weeks of gestation based on Ki67 labelling appears to be driven by cellular proliferation in the corporal body and glans. Throughout all ages in both the developing penis and clitoris Ki67 labeling was consistently elevated in the ventral epidermis and ventral mesenchyme relative to the dorsal counterparts. This finding is consistent with the intense morphogenetic activity/remodeling in the ventral half of the genital tubercle in both sexes involving formation of the urethral/vestibular plates, canalization of the urethral/vestibular plates and fusion of the urethral folds to form the penile urethra. Areas of reduced or absent Ki67 staining include the urethral fold epithelium that fuses to form the penile tubular urethra. In contrast, the urethral fold mesenchyme is positive for Ki67. Apoptosis was rarely noted in the developing penis and clitoris; the only area of minimal Caspase-3 localization was in the epithelium of the ventral epithelial glanular channel remodeling

Controlling mixed conductivity in Na 1/2 Bi 1/2 TiO 3 using A-site non-stoichiometry and Nb-donor doping

Precise control of electronic and/or ionic conductivity in electroceramics is crucial to achieve the desired functional properties as well as to improve manufacturing practices. We recently reported the conventional piezoelectric material Na1/2Bi1/2TiO3 (NBT) can be tuned into a novel oxide-ion conductor with an oxide-ion transport number (tion) > 0.9 by creating bismuth and oxygen vacancies. A small Bi-excess in the nominal starting composition (Na0.50Bi0.50+xTiO3+3x/2, x = 0.01) or Nb-donor doping (Na0.50Bi0.50Ti1−yNbyO3+y/2, 0.005 ≤ y ≤ 0.030) can reduce significantly the electrical conductivity to create dielectric behaviour by filling oxygen vacancies and suppressing oxide ion conduction (tion ≤ 0.10). Here we show a further increase in the starting Bi-excess content (0.02 ≤ x ≤ 0.10) reintroduces significant levels of oxide-ion conductivity and increases tion ∼ 0.4–0.6 to create mixed ionic/electronic behaviour. The switch from insulating to mixed conducting behaviour for x > 0.01 is linked to the presence of Bi-rich secondary phases and we discuss possible explanations for this effect. Mixed conducting behaviour with tion ∼ 0.5–0.6 can also be achieved with lower levels of Nb-doping (y ∼ 0.003) due to incomplete filling of oxygen vacancies without the presence of secondary phases. NBT can now be compositionally tailored to exhibit three types of electrical behaviour; Type I (oxide-ion conductor); Type II (mixed ionic-electronic conductor); Type III (insulator) and these results reveal an approach to fine-tune tion in NBT from near unity to zero. In addition to developing new oxide-ion and now mixed ionic/electronic NBT-based conductors, this flexibility in control of oxygen vacancies allows fine-tuning of both the dielectric/piezoelectric properties and design manufacturing practices for NBT-based multilayer piezoelectric devices

Canalization of the Vestibular Plate in the Absence of Urethral Fusion Characterizes Development of the Human Clitoris: The Single Zipper Hypothesis.

PurposeWe characterized the early gestation development of the female external genitalia using optical projection tomography to visualize anatomical structures at high resolution.Materials and methodsFirst and early second trimester human female fetal external genitalia were collected with consent after voluntary termination. Specimens labeled with anti-E-Cadherin antibody underwent analysis with optical projection tomography. Histological sections were immunostained for androgen receptor, 5α-reductase, Ki67 for proliferation and Caspase 3 for apoptosis.ResultsThree-dimensional reconstructions demonstrated proximal to distal canalization of the epithelial vestibular plate and formation of a vestibular groove, which remained open. Ki67 was observed throughout with greatest density in the dorsal vestibular plate at the level of the opening groove. Staining for Caspase 3 was minimal in all sections. Androgen receptor staining was seen throughout the mesenchyme and in the apical epithelium of the dorsal vestibular groove. Throughout the epithelium and epidermis 5α-reductase staining was observed.ConclusionsEarly development of the external genitalia in the female is analogous to that in the male, demonstrating a similar opening zipper driving canalization of the vestibular plate with localized epithelial proliferation in the absence of significant apoptosis. Thus we hypothesize that the mechanism underlying the opening zipper must be androgen independent and the absence of androgen driven urethral fusion characterizes the normal development of the human clitoris

Imaging the developing human external and internal urogenital organs with light sheet fluorescence microscopy.

Technological advances in three-dimensional (3D) reconstruction techniques have previously enabled paradigm shifts in our understanding of human embryonic and fetal development. Light sheet fluorescence microscopy (LSFM) is a recently-developed technique that uses thin planes of light to optically section whole-mount cleared and immunolabeled biologic specimens. The advent of commercially-available light sheet microscopes has facilitated a new generation of research into protein localization and tissue dynamics at extremely high resolution. Our group has applied LSFM to study developing human fetal external genitalia, internal genitalia and kidneys. This review describes LSFM and presents our group's technique for preparing, clearing, immunostaining and imaging human fetal urogenital specimens. We then present light sheet images and videos of each element of the developing human urogenital system. To the extent of our knowledge, the work conducted by our laboratory represents the first description of a method for performing LSFM on the full human urogenital system during the embryonic and fetal periods

The influence of excess K2O on the electrical properties of (K,Na)1/2Bi1/2TiO3 ceramics

The solid solution (KxNa0.50-x)Bi0.50TiO3 (KNBT) between Na1/2Bi1/2TiO3 (NBT) and K1/2Bi1/2TiO3 (KBT) has been extensively researched as a candidate lead-free piezoelectric material because of its relatively high Curie temperature and good piezoelectric properties, especially near the morphotropic phase boundary (MPB) at x ~ 0.10 (20 mol% KBT). Here we show low levels of excess K2O in the starting compositions, i.e. (Ky+0.03Na0.50-y)Bi0.50TiO3.015 (y-series), can significantly change the conduction mechanism and electrical properties compared to a nominally stoichiometric KNBT series (KxNa0.50-x)Bi0.50TiO3 (x-series). Impedance Spectroscopy measurements reveal significantly higher bulk conductivity (σb) values for y ≥ 0.10 samples (activation energy, Ea, ≤ 0.95 eV) compared to the corresponding x-series samples which possess band-gap type electronic conduction (Ea ~ 1.26 to 1.85 eV). The largest difference in electrical properties occurs close to the MPB composition (20 mol% KBT) where y = 0.10 ceramics possess b (at 300 oC) that is 4 orders of magnitude higher than x = 0.10 and the oxide-ion transport number in the former is ~ 0.70 – 0.75 compared to < 0.05 in the latter (between 600 and 800 oC). The effect of excess K2O can be rationalised on the basis of the (K + Na):Bi ratio in the starting composition prior to ceramic processing. This demonstrates the electrical properties of KNBT to be sensitive to low levels of A-site nonstoichiometry and indicates excess K2O in KNBT starting compositions to compensate for volatilisation can lead to undesirable high dielectric loss and leakage currents at elevated temperatures

Effects of gamma-tocopherol supplementation on thrombotic risk factors

Objective: The antioxidant activity of vitamin E is derived primarily from alpha-tocopherol (&alpha;-T) and gammatocopherol (&gamma;-T). Results of epidemiological studies have demonstrated an inverse relationship between vitamin E intake and coronary disease. However, the results of clinical trials using &alpha;-T are equivocal. We determined the effect of 5 weeks of 100 mg/d or 200 mg/d &gamma;-T supplementation on thrombotic markers such as platelet reactivity, lipid profile and the inflammation marker C-reactive protein (CRP). Methods and results: Fourteen healthy subjects consumed 100 mg/day while 13 consumed 200 mg/d of &gamma;-T and 12 received placebo (soybean capsules with less than 5 mg/d &gamma;-T) in a double-blinded parallel study design. Fasting pre and post dose blood samples were analysed. Blood &gamma;-T concentrations increased significantly (p&lt;0.05) relative to dose during the intervention period. Both groups receiving active ingredients showed significantly lower platelet activation after supplementation (p&lt;0.05). Subjects consuming 100 mg/d &gamma;-T had significantly decreased LDL cholesterol, platelet aggregation and mean platelet volume (MPV) (p&lt;0.05). Little effect of &gamma;-T was observed on other parameters. Conclusions: These data suggest that &gamma;-T&nbsp; supplementation may have a permissive role in decreasing the risk ofthrombotic events by improving lipid profile and reducing platelet activity.<br /

Structure–property relationships in (1 − x)BaTiO3–xBiGdO3 ceramics

(1 − x)BaTiO3–xBiGdO3 ceramics were prepared by the solid state reaction method. X-ray diffraction and Raman spectroscopy indicate a maximum co-solubility of Bi/Gd in BaTiO3 at x = 0.10 with a change of symmetry from tetragonal to pseudo-cubic at x = 0.08. Backscattered electron images, however, reveal the presence of a secondary phase in x ≥ 0.06. The dielectric behaviour evolves continuously with x from a classical ferroelectric to a typical relaxor and this transition is accompanied by a shift in the permittivity maxima towards lower temperatures. The presence of two dielectric anomalies for x ≥ 0.06 is associated with residual core–shell structures, as revealed by transmission electron microscopy. The dielectric anomaly associated with the core regions remains at ∼120 °C, whereas the other anomaly decreases continuously towards lower temperature with x. This study shows that chemical equilibrium is much more difficult to achieve than in other (1 − x)BaTiO3–xBi[Me]O3 systems, where Me is Yb or Sc

“It’s an opportunity to get opportunities”: A brief report on the working lives of individuals with intellectual and developmental disabilities during the Covid-19 pandemic

The Covid-19 pandemic has impacted countless individuals, including those who experience intellectual and developmental disabilities (IDD). Even amid a pandemic, for many individuals, working continues to be a critically important aspect of their life, providing opportunities to accomplish their desired quality of life. Currently, limitations exist to understanding both the working lives of individuals with IDD, but also how individuals with IDD make meaning from their work during a pandemic. Using a psychology of working theory (PWT; Blustein, 2006), this research brief summarizes a qualitative study on the working experiences of individuals with IDD. This study included interviews with six adults with IDD across the United States. The purpose of the study was to gather data on how individuals with IDD were impacted by the Covid-19 pandemic and to establish an understanding of work through the PWT framework. Qualitative content analysis was used to examine data collected from interviews to identify emergent themes from the work lives of those interviewed. Results indicate that the pandemic impacted individuals work to varying degrees, including reduced hours and loss of jobs. The pandemic also impacted their personal lives, limiting opportunities for social gatherings with families or activities such as Special Olympics. All participants confirmed the application of the PWT taxonomy as a good fit to describe their working experiences. Specifically, participants were still self-determined and motivated to work during the pandemic, yet their social connections were negatively impacted. Lastly, we briefly discuss the concept of dignity of risk and additional practices to support individuals with IDD as they continue to work