Transforming growth factor-beta (beta 1, beta 2, and beta 3) gene expression and action during pubertal development of the seminiferous tubule: potential role at the onset of spermatogenesis

The potential role of transforming growth factor-beta (TGF beta) as a mediator of cell-cell interactions during the pubertal development of the seminiferous tubule was examined. Mesenchymal-derived peritubular cells and epithelial-like Sertoli cells were isolated from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of the multiple forms of TGF beta (TGF beta 1, -beta 2, and -beta 3) in whole testis and isolated somatic cell types was determined using a nuclease protection analysis. TGF beta 1 and TGF beta 2 mRNA expression was predominant in the immature testis and decreased at the onset of puberty. TGF beta 3 mRNA expression, the most abundant form of TGF beta present, peaked at an early pubertal stage, coincident with the initiation of spermatogenesis. Peritubular and Sertoli cells expressed each isoform of TGF beta during development. Peritubular cell mRNA expression of TGF beta 1, -beta 2, and -beta 3 decreased during pubertal development upon differentiation of this cell type. Sertoli cell expression of TGF beta 1 increased slightly and plateaued during pubertal development. TGF beta 2 mRNA expression was evident only in immature prepubertal Sertoli cells. Sertoli cell mRNA expression of TGF beta 3 increased transiently at the onset of puberty, corresponding with the peak of expression observed during the analysis of whole testicular development. Immunoblot analysis indicated that both cultured peritubular and Sertoli cells can produce the proteins for TGF beta 1, -beta 2, and -beta 3. Analysis of the hormonal regulation of TGF beta expression revealed that FSH caused a dramatic decrease in Sertoli cell TGF beta 2 expression while having no effect on TGF beta 1 or TGF beta 3 expression. Potential actions of TGF beta in the seminiferous tubule were also examined. TGF beta 1 inhibited TGF alpha-induced [3H]thymidine incorporation into peritubular cell DNA with cells from each developmental stage examined. TGF beta 1 had no effect on Sertoli cell proliferation. Previously, germinal cells have been shown to be responsive to TGF beta. This study demonstrates the potential of having a unique hormone-dependent pattern of TGF beta isoform expression during postnatal organ development. Observations demonstrate that the suppression of TGF beta 2 expression, in part in response to FSH, and the transient increase in TGF beta 3 expression correlate with the onset of puberty and the induction of spermatogenesis

Transforming growth factor-α and epidermal growth factor receptor gene expression and action during pubertal development of the seminiferous tubule

The potential role of transforming growth factor-alpha (TGF-alpha) as a mediator of cell-cell interactions in the growth and development of the testis was examined. Developing rat testes were collected, and preparations of mesenchymal-derived peritubular cells and epithelial-like Sertoli cells were isolated from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), in whole testis and isolated cell types was determined using a nuclease protection assay. TGF-alpha and EGFR gene expression were predominant early in testis development and decreased during pubertal development. TGF-alpha expression was greatest in prepubertal peritubular cells. Sertoli cell TGF-alpha expression remained relatively constant during development, with a slight decline at the later pubertal stages. EGFR gene expression was predominant in peritublar cells throughout development. A low level of EGFR expression was detected in Sertoli cells. Scatchard analysis confirmed the presence of high affinity receptors on peritubular cells; however, no functional receptors were detected on Sertoli cells from any stage of development examined. Interestingly, low-level EGFR gene expression was also detected in pachytene spermatocytes and round spermatids. TGF-alpha was found to stimulate [3H] thymidine incorporation into DNA and increase cellular proliferation of peritubular cells from each developmental stage, while having no effect on Sertoli cells. The in vivo physiological significance of TGF-alpha was evaluated in a line of transgenic mice which overexpress TGF-alpha in the mature testis. These transgenic animals had no abnormal testicular morphology or alterations in spermatogenesis. Observations demonstrate that gene expression of TGF-alpha and its receptor is high during early pubertal stages when somatic cell growth is predominant and low at late pubertal stages when somatic cell proliferation is reduced. TGF-alpha can act as an autocrine/paracrine mitogen for the mesenchymal-derived peritubular cell, while actions on the Sertoli cell population are not evident. The observation that spermatogenic cells express the EGFR gene, although the protein remains to be identified, implies that TGF-alpha may potentially mediate Sertoli-germinal cell interactions

Constructed Action in American Sign Language: A Look at Second Language Learners in a Second Modality

Constructed action is a cover term used in signed language linguistics to describe multi-functional constructions which encode perspective-taking and viewpoint. Within constructed action, viewpoint constructions serve to create discourse coherence by allowing signers to share perspectives and psychological states. Character, observer, and blended viewpoint constructions have been well documented in signed language literature in Deaf signers. However, little is known about hearing second language learners’ use of constructed action or about the acquisition and use of viewpoint constructions. We investigate the acquisition of viewpoint constructions in 11 college students acquiring American Sign Language (ASL) as a second language in a second modality (M2L2). Participants viewed video clips from the cartoon Canary Row and were asked to “retell the story as if you were telling it to a deaf friend”. We analyzed the signed narratives for time spent in character, observer, and blended viewpoints. Our results show that despite predictions of an overall increase in use of all types of viewpoint constructions, students varied in their time spent in observer and character viewpoints, while blended viewpoint was rarely observed. We frame our preliminary findings within the context of M2L2 learning, briefly discussing how gestural strategies used in multimodal speech-gesture constructions may influence learning trajectories

Mimotopes and Proteome Analyses Using Human Genomic and cDNA Epitope Phage Display

In the post-genomic era, validation of candidate gene targets frequently requires proteinbased strategies. Phage display is a powerful tool to define protein-protein interactions by generating peptide binders against target antigens. Epitope phage display libraries have the potential to enrich coding exon sequences from human genomic loci. We evaluated genomic and cDNA phage display strategies to identify genes in the 5q31 Interleukin gene cluster and to enrich cell surface receptor tyrosine kinase genes from a breast cancer cDNA library. A genomic display library containing 2 × 10 6 clones with exon-sized inserts was selected with antibodies specific for human Interleukin-4 (IL-4) and Interleukin-13. The library was enriched significantly after two selection rounds and DNA sequencing revealed unique clones. One clone matched a cognate IL-4 epitope; however, the majority of clone insert sequences corresponded to E. coli genomic DNA. These bacterial sequences act as ‘mimotopes’ (mimetic sequences of the true epitope), correspond to open reading frames, generate displayed peptides, and compete for binding during phage selection. The specificity of these mimotopes for IL-4 was confirmed by competition ELISA. Other E. coli mimotopes were generated using additional antibodies. Mimotopes for a receptor tyrosine kinase gene were also selected using a breast cancer SKBR-3 cDNA phage display library, screened against an anti-erbB2 monoclonal antibody. Identification of mimotopes in genomic and cDNA phage libraries is essential for phage display-based protein validation assays and two-hybrid phage approaches that examine protein-protein interactions. The predominance of E. coli mimotopes suggests that the E. coli genome may be useful to generate peptide diversity biased towards protein coding sequences

The Spitzer discovery of a galaxy with infrared emission solely due to AGN activity

We present a galaxy (SAGE1CJ053634.78-722658.5) at a redshift of 0.14 of which the IR is entirely dominated by emission associated with the AGN. We present the 5-37 um Spitzer/IRS spectrum and broad wavelength SED of SAGE1CJ053634, an IR point-source detected by Spitzer/SAGE (Meixner et al 2006). The source was observed in the SAGE-Spec program (Kemper et al., 2010) and was included to determine the nature of sources with deviant IR colours. The spectrum shows a redshifted (z=0.14+-0.005) silicate emission feature with an exceptionally high feature-to-continuum ratio and weak polycyclic aromatic hydrocarbon (PAH) bands. We compare the source with models of emission from dusty tori around AGNs from Nenkova et al. (2008). We present a diagnostic diagram that will help to identify similar sources based on Spitzer/MIPS and Herschel/PACS photometry. The SED of SAGE1CJ053634 is peculiar because it lacks far-IR emission and a clear stellar counterpart. We find that the SED and the IR spectrum can be understood as emission originating from the inner ~10 pc around an accreting black hole. There is no need to invoke emission from the host galaxy, either from the stars or from the interstellar medium, although a possible early-type host galaxy cannot be excluded based on the SED analysis. The hot dust around the accretion disk gives rise to a continuum, which peaks at 4 um, whereas the strong silicate features may arise from optically thin emission of dusty clouds within ~10 pc around the black hole. The weak PAH emission does not appear to be linked to star formation, as star formation templates strongly over-predict the measured far-IR flux levels. The SED of SAGE1CJ053634 is rare in the local universe but may be more common in the more distant universe. The conspicuous absence of host-galaxy IR emission places limits on the far-IR emission arising from the dusty torus alone.Comment: Accepted for publication in A&A, 7 pages, 6 figure

A catalogue of faint local radio AGN and the properties of their host galaxies

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2018 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.We present a catalogue of 2210 local ( z < 0.1) galaxies that contain faint active galactic nuclei (AGN). We select these objects by identifying galaxies that exhibit a significant excess in their radio luminosities, compared to what is expected from the observed levels of star formation activity in these systems. This is achieved by comparing the optical (spectroscopic) star formation rate (SFR) to the 1.4 GHz luminosity measured from the Faint Images of the Radio Sky at Twenty centimeters survey. The majority of the AGN identified in this study are fainter than those in previous work, such as in the Best and Heckman (2012) catalogue. We show that these faint AGN make a non-negligible contribution to the radio luminosity function at low luminosities (below 1022.5 W Hz−1), and host ∼13 per cent of the local radio luminosity budget. Their host galaxies are predominantly high stellar-mass systems (with a median stellar mass of 1011 M⊙), are found across a range of environments (but typically in denser environments than star-forming galaxies) and have early-type morphologies. This study demonstrates a general technique to identify AGN in galaxy populations where reliable optical SFRs can be extracted using spectro-photometry and where radio data are also available so that a radio excess can be measured. Our results also demonstrate that it is unsafe to infer SFRs from radio emission alone, even if bright AGN have been excluded from a sample, since there is a significant population of faint radio AGN that may contaminate the radio-derived SFRs.Peer reviewedFinal Published versio

The X-Ray Star Formation Story as Told by Lyman Break Galaxies in the 4 Ms CDF-S

We present results from deep X-ray stacking of {gt}4000 high-redshift galaxies from z {ap} 1 to 8 using the 4 Ms Chandra Deep Field-South data, the deepest X-ray survey of the extragalactic sky to date. The galaxy samples were selected using the Lyman break technique based primarily on recent Hubble Space Telescope ACS and WFC3 observations. Based on such high specific star formation rates (sSFRs): log SFR/M $_{*}$ {gt} -8.7, we expect that the observed properties of these Lyman break galaxies (LBGs) are dominated by young stellar populations. The X-ray emission in LBGs, eliminating individually detected X-ray sources (potential active galactic nucleus), is expected to be powered by X-ray binaries and hot gas. We find, for the first time, evidence of evolution in the X-ray/SFR relation. Based on X-ray stacking analyses for z {lt} 4 LBGs (covering ~{}90% of the universe's history), we find that the 2-10 keV X-ray luminosity evolves weakly with redshift (z) and SFR as log L $_X$ = 0.93log (1 + z) + 0.65log SFR + 39.80. By comparing our observations with sophisticated X-ray binary population synthesis models, we interpret that the redshift evolution of L $_X$/SFR is driven by metallicity evolution in high mass X-ray binaries, likely the dominant population in these high sSFR galaxies. We also compare these models with our observations of X-ray luminosity density (total 2-10 keV luminosity per Mpc$^{3}$) and find excellent agreement. While there are no significant stacked detections at z {gt}~{} 5, we use our upper limits from 5 {lt}~{} z {lt}~{} 8 LBGs to constrain the supermassive black hole accretion history of the universe around the epoch of reionization

Mid-infrared luminous quasars in the GOODS–Herschel fields: a large population of heavily obscured, Compton-thick quasars at z ≈ 2

We present the infrared (IR) and X-ray properties of a sample of 33 mid-IR luminous quasars (νL6 μm ≥ 6 × 1044 erg s−1) at redshift z ≈ 1–3, identified through detailed spectral energy distribution analyses of distant star-forming galaxies, using the deepest IR data from Spitzer and Herschel in the GOODS–Herschel fields. The aim is to constrain the fraction of obscured, and Compton-thick (CT, NH > 1.5 × 1024 cm−2) quasars at the peak era of nuclear and star formation activities. Despite being very bright in the mid-IR band, ≈30 per cent of these quasars are not detected in the extremely deep 2 and 4 Ms Chandra X-ray data available in these fields. X-ray spectral analysis of the detected sources reveals that the majority (≈67 per cent) are obscured by column densities NH > 1022 cm−2; this fraction reaches ≈80 per cent when including the X-ray-undetected sources (9 out of 33), which are likely to be the most heavily obscured, CT quasars. We constrain the fraction of CT quasars in our sample to be ≈24–48 per cent, and their space density to be Φ = (6.7 ± 2.2) × 10−6 Mpc−3. From the investigation of the quasar host galaxies in terms of star formation rates (SFRs) and morphological distortions, as a sign of galaxy mergers/interactions, we do not find any direct relation between SFRs and quasar luminosity or X-ray obscuration. On the other hand, there is tentative evidence that the most heavily obscured quasars have, on average, more disturbed morphologies than the unobscured/moderately obscured quasar hosts, which preferentially live in undisturbed systems. However, the fraction of quasars with disturbed morphology amongst the whole sample is ≈40 per cent, suggesting that galaxy mergers are not the main fuelling mechanism of quasars at z ≈ 2

Prevalence and risk of Down syndrome in monozygotic and dizygotic multiple pregnancies in Europe: implications for prenatal screening.

OBJECTIVE: To determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome. DESIGN: Population-based prevalence study based on EUROCAT congenital anomaly registries. SETTING: Eight European countries. POPULATION: 14.8 million births 1990-2009; 2.89% multiple births. METHODS: DS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases. MAIN OUTCOME MEASURES: Relative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome. STATISTICAL ANALYSIS: Poisson and logistic regression stratified for maternal age, country and time. RESULTS: Overall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]). CONCLUSIONS: The risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening