486 research outputs found
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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
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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
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 Ă
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
âmimotopesâ (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
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 = 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 /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) 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
PACS Evolutionary Probe (PEP) - A Herschel Key Program
Deep far-infrared photometric surveys studying galaxy evolution and the
nature of the cosmic infrared background are a key strength of the Herschel
mission. We describe the scientific motivation for the PACS Evolutionary Probe
(PEP) guaranteed time key program and its role in the complement of Herschel
surveys, and the field selection which includes popular multiwavelength fields
such as GOODS, COSMOS, Lockman Hole, ECDFS, EGS. We provide an account of the
observing strategies and data reduction methods used. An overview of first
science results illustrates the potential of PEP in providing calorimetric star
formation rates for high redshift galaxy populations, thus testing and
superseeding previous extrapolations from other wavelengths, and enabling a
wide range of galaxy evolution studies.Comment: 13 pages, 12 figures, accepted for publication in A&
Concurrent Supermassive Black Hole and Galazy Growth: Linking Environment and Nuclear Activity in Zeta Equals 2.23 H Alpha Emitters
We present results from an approximately equal 100 ks Chandra observation of the 2QZ Cluster 1004+00 structure at z = 2.23 (hereafter 2QZ Clus). 2QZ Clus was originally identified as an overdensity of four optically-selected QSOs at z = 2.23 within a 15 15 arcmin square region. Narrow-band imaging in the near-IR (within the K band) revealed that the structure contains an additional overdensity of 22 z = 2.23 H alpha-emitting galaxies (HAEs), resulting in 23 unique z = 2.23 HAEs/QSOs (22 within the Chandra field of view). Our Chandra observations reveal that three HAEs in addition to the four QSOs harbor powerfully accreting supermassive black holes (SMBHs), with 2-10 keV luminosities of approximately equal (8-60) 10(exp 43) erg s(exp1) and X-ray spectral slopes consistent with unobscured active galactic nucleus (AGN). Using a large comparison sample of 210 z = 2.23 HAEs in the Chandra-COSMOS field (C-COSMOS), we find suggestive evidence that the AGN fraction increases with local HAE galaxy density. The 2QZ Clus HAEs reside in a moderately overdense environment (a factor of approximately equal 2 times over the field), and after excluding optically-selected QSOs, we find that the AGN fraction is a factor of approximately equal 3.5(+3.8/ 2.2) times higher than C-COSMOS HAEs in similar environments. Using stacking analyses of the Chandra data and Herschel SPIRE observations at 250micrometers, we respectively estimate mean SMBH accretion rates ( M(BH)) and star formation rates (SFRs) for the 2QZ Clus and C-COSMOS samples. We find that the mean 2QZ Clus HAE stacked X-ray luminosity is QSO-like (L(210 keV) approximately equal [6-10] 10(exp 43) erg s(exp 1)), and the implied M(BH)/SFR approximately equal (1.6-3.2) 10(exp 3) is broadly consistent with the local M(BH)/Stellar Mass relation and z approximately equal 2 X-ray selected AGN. In contrast, the C-COSMOS HAEs are on average an order of magnitude less X-ray luminous and have M(BH)/SFR approximately equal (0.2-0.4) 10(exp 3), somewhat lower than the local MBH/M relation, but comparable to that found for z approximately equal 1-2 star-forming galaxies with similar mean X-ray luminosities. We estimate that a periodic QSO phase with duty cycle approximately 2%-8% would be sufficient to bring star-forming galaxies onto the local M(BH)/Stellar Mass relation. This duty cycle is broadly consistent with the observed C-COSMOS HAE AGN fraction (Approximately equal 0.4%-2.3%) for powerful AGN with LX approximately greater than 10(exp 44) erg s(exp 1). Future observations of 2QZ Clus will be needed to identify key factors responsible for driving the mutual growth of the SMBHs and galaxies
Bulge growth through disk instabilities in high-redshift galaxies
The role of disk instabilities, such as bars and spiral arms, and the
associated resonances, in growing bulges in the inner regions of disk galaxies
have long been studied in the low-redshift nearby Universe. There it has long
been probed observationally, in particular through peanut-shaped bulges. This
secular growth of bulges in modern disk galaxies is driven by weak,
non-axisymmetric instabilities: it mostly produces pseudo-bulges at slow rates
and with long star-formation timescales. Disk instabilities at high redshift
(z>1) in moderate-mass to massive galaxies (10^10 to a few 10^11 Msun of stars)
are very different from those found in modern spiral galaxies. High-redshift
disks are globally unstable and fragment into giant clumps containing 10^8-10^9
Msun of gas and stars each, which results in highly irregular galaxy
morphologies. The clumps and other features associated to the violent
instability drive disk evolution and bulge growth through various mechanisms,
on short timescales. The giant clumps can migrate inward and coalesce into the
bulge in a few 10^8 yr. The instability in the very turbulent media drives
intense gas inflows toward the bulge and nuclear region. Thick disks and
supermassive black holes can grow concurrently as a result of the violent
instability. This chapter reviews the properties of high-redshift disk
instabilities, the evolution of giant clumps and other features associated to
the instability, and the resulting growth of bulges and associated sub-galactic
components.Comment: 37 pages, 9 figures. Invited refereed review to appear in "Galactic
Bulges", E. Laurikainen, D. Gadotti, R. Peletier (eds.), Springe
The AGN content in luminous IR galaxies at z\sim2 from a global SED analysis including Herschel data
We use Herschel-PACS far-infrared data, combined with previous multi-band
information and mid-IR spectra, to properly account for the presence of an
active nucleus and constrain its energetic contribution in luminous infrared
(IR) sources at z\sim2. The sample is composed of 24 sources in the GOODS-South
field, with typical IR luminosity of 10^{12} Lo. Data from the 4 Ms Chandra
X-ray imaging in this field are also used to identify and characterize AGN
emission. We reproduce the observed spectral energy distribution (SED),
decomposed into a host-galaxy and an AGN component. A smooth-torus model for
circum-nuclear dust is used to account for the direct and re-processed
contribution from the AGN. We confirm that galaxies with typical
L_{8-1000um}\sim10^{12}Lo at z\sim2 are powered predominantly by
star-formation. An AGN component is present in nine objects (\sim35% of the
sample) at the 3sigma confidence level, but its contribution to the 8-1000 um
emission accounts for only \sim5% of the energy budget. The AGN contribution
rises to \sim23% over the 5-30 um range (in agreement with Spitzer IRS results)
and to \sim60% over the narrow 2-6 um range. The presence of an AGN is
confirmed by X-ray data for 3 (out of nine) sources, with X-ray spectral
analysis indicating the presence of significant absorption, i.e.
NH\sim10^{23}-10^{24} cm^{-2}. An additional source shows indications of
obscured AGN emission from X-ray data. The comparison between the
mid-IR--derived X-ray luminosities and those obtained from X-ray data suggests
that obscuration is likely present also in the remaining six sources that
harbour an AGN according to the SED-fitting analysis.Comment: 12 pages, including 5 figures. Accepted for publication in MNRA
Black Holes in the Early Universe
The existence of massive black holes was postulated in the sixties, when the
first quasars were discovered. In the late nineties their reality was proven
beyond doubt, in the Milky way and a handful nearby galaxies. Since then,
enormous theoretical and observational efforts have been made to understand the
astrophysics of massive black holes. We have discovered that some of the most
massive black holes known, weighing billions of solar masses, powered luminous
quasars within the first billion years of the Universe. The first massive black
holes must therefore have formed around the time the first stars and galaxies
formed. Dynamical evidence also indicates that black holes with masses of
millions to billions of solar masses ordinarily dwell in the centers of today's
galaxies. Massive black holes populate galaxy centers today, and shone as
quasars in the past; the quiescent black holes that we detect now in nearby
bulges are the dormant remnants of this fiery past. In this review we report on
basic, but critical, questions regarding the cosmological significance of
massive black holes. What physical mechanisms lead to the formation of the
first massive black holes? How massive were the initial massive black hole
seeds? When and where did they form? How is the growth of black holes linked to
that of their host galaxy? Answers to most of these questions are work in
progress, in the spirit of these Reports on Progress in Physics.Comment: Reports on Progress in Physics, in pres
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