Keck Spectroscopy of Faint 3 < z < 7 Lyman Break Galaxies: III. The Mean Ultraviolet Spectrum at z=4

We present and discuss the mean rest-frame ultraviolet spectrum for a sample of 81 Lyman Break Galaxies (LBGs) selected to be B-band dropouts with a mean redshift of z=3.9 and apparent magnitudes z_AB<26. Most of the individual spectra are drawn from our ongoing survey in the GOODS fields with the Keck DEIMOS spectrograph, and we have augmented our sample with published data taken with FORS2 on the VLT. In general we find similar trends in the spectral diagnostics to those found in the earlier, more extensive survey of LBGs at z=3 undertaken by Shapley et al (2003). Specifically, we find low-ionization absorption lines which trace the presence of neutral outflowing gas are weaker in galaxies with stronger Lyman-alpha emission, bluer UV spectral slopes, lower stellar masses, lower UV luminosities and smaller half-light radii. This is consistent with a physical picture whereby star formation drives outflows of neutral gas which scatters Lyman-alpha and gives rise to strong low-ionization absorption lines, while increasing the stellar mass, size, metallicity, and dust content of galaxies. Typical galaxies are thus expected to have stronger Lyman-alpha emission and weaker low-ionization absorption at earlier times (higher redshifts). Indeed, our mean spectrum at z=4 shows somewhat weaker low-ionization absorption lines than at z=3 and available data at higher redshift indicates a rapid decrease in low-ionization absorption strength with redshift. We argue that the reduced low-ionization absorption is likely caused by a decrease in the covering fraction and/or velocity range of outflowing neutral gas at earlier epochs. Our continuing survey will enable us to extend these diagnostics more reliably to higher redshift and determine the implications for the escape fraction of ionizing photons which governs the role of early galaxies in cosmic reionization. [Abridged]Comment: 17 pages, 12 figures, submitted to ApJ. Comments welcom

The teneurin C-terminal domain possesses nuclease activity and is apoptogenic.

Teneurins are type 2 transmembrane proteins expressed by developing neurons during periods of synaptogenesis and apoptosis. Neurons expressing teneurin-1 synapse with other teneurin-1-expressing neurons, and neurons expressing teneurin-2 synapse with other teneurin-2-expressing neurons. Knockdowns and mutations of teneurins lead to abnormal neuronal connections, but the mechanisms underlying teneurin action remain unknown. Teneurins appear to have evolved via horizontal gene transfer from prokaryotic proteins involved in bacterial self-recognition. The bacterial teneurin-like proteins contain a cytotoxic C-terminal domain that is encapsulated in a tyrosine-aspartic acid repeat barrel. Teneurins are likely to be organized in the same way, but it is unclear if the C-terminal domains of teneurins have cytotoxic properties. Here we show that expression of teneurin C-terminal domains or the addition of purified teneurin C-terminal domains leads to an increase in apoptosis in vitro The C-terminal domains of teneurins are most similar to bacterial nucleases, and purified C-terminal domains of teneurins linearize pcDNA3 and hydrolyze mitochondrial DNA. We hypothesize that yet to be identified stimuli lead to the release of the encapsulated teneurin C-terminal domain into the intersynaptic region, resulting in programmed cell death or the disruption of mitochondrial DNA and the subsequent pruning of inappropriate contacts

Revisiting the Tenascins: Exploitable as Cancer Targets?

For their full manifestation, tumors require support from the surrounding tumor microenvironment (TME), which includes a specific extracellular matrix (ECM), vasculature, and a variety of non-malignant host cells. Together, these components form a tumor-permissive niche that significantly differs from physiological conditions. While the TME helps to promote tumor progression, its special composition also provides potential targets for anti-cancer therapy. Targeting tumor-specific ECM molecules and stromal cells or disrupting aberrant mesenchyme-cancer communications might normalize the TME and improve cancer treatment outcome. The tenascins are a family of large, multifunctional extracellular glycoproteins consisting of four members. Although each have been described to be expressed in the ECM surrounding cancer cells, tenascin-C and tenascin-W are currently the most promising candidates for exploitability and clinical use as they are highly expressed in various tumor stroma with relatively low abundance in healthy tissues. Here, we review what is known about expression of all four tenascin family members in tumors, followed by a more thorough discussion on tenascin-C and tenascin-W focusing on their oncogenic functions and their potential as diagnostic and/or targetable molecules for anti-cancer treatment purposes

Teneurins: Domain Architecture, Evolutionary Origins, and Patterns of Expression

Disruption of teneurin expression results in abnormal neural networks, but just how teneurins support the development of the central nervous system remains an area of active research. This review summarizes some of what we know about the functions of the various domains of teneurins, the possible evolution of teneurins from a bacterial toxin, and the intriguing patterns of teneurin expression. Teneurins are a family of type-2 transmembrane proteins. The N-terminal intracellular domain can be processed and localized to the nucleus, but the significance of this nuclear localization is unknown. The extracellular domain of teneurins is largely composed of tyrosine-aspartic acid repeats that fold into a hollow barrel, and the C-terminal domains of teneurins are stuffed, and least partly, into the barrel. A 6-bladed beta-propeller is found at the other end of the barrel. The same arrangement—6-bladed beta-propeller, tyrosine-aspartic acid repeat barrel, and the C-terminal domain inside the barrel—is seen in toxic proteins from bacteria, and there is evidence that teneurins may have evolved from a gene encoding a prokaryotic toxin via horizontal gene transfer into an ancestral choanoflagellate. Patterns of teneurin expression are often, but not always, complementary. In the central nervous system, where teneurins are best studied, interconnected populations of neurons often express the same teneurin. For example, in the chicken embryo neurons forming the tectofugal pathway express teneurin-1, whereas neurons forming the thalamofugal pathway express teneurin-2. In Drosophila melanogaster, Caenorhabditis elegans, zebrafish and mice, misexpression or knocking out teneurin expression leads to abnormal connections in the neural networks that normally express the relevant teneurin. Teneurins are also expressed in non-neuronal tissue during development, and in at least some regions the patterns of non-neuronal expression are also complementary. The function of teneurins outside the nervous system remains unclear

Teneurin-1 is expressed in interconnected regions of the developing brain and is processed in vivo

<p>Abstract</p> <p>Background</p> <p>Teneurins are a unique family of transmembrane proteins conserved from <it>C. elegans </it>and <it>D. melanogaster </it>to mammals. In vertebrates there are four paralogs (teneurin-1 to -4), all of which are expressed prominently in the developing central nervous system.</p> <p>Results</p> <p>Analysis of teneurin-1 expression in the developing chick brain by in situ hybridization and immunohistochemistry defined a unique, distinct expression pattern in interconnected regions of the brain. Moreover we found complementary patterns of teneurin-1 and-2 expression in many parts of the brain, including the retina, optic tectum, olfactory bulb, and cerebellum as well as in brain nuclei involved in processing of sensory information. Based on these expression patterns, we suspect a role for teneurins in neuronal connectivity.</p> <p>In contrast to the cell-surface staining of the antibody against the extracellular domain, an antibody recognizing the intracellular domain revealed nuclear staining in subpopulations of neurons and in undifferentiated mesenchyme. Western blot analysis of brain lysates showed the presence of N-terminal fragments of teneurin-1 containing the intracellular domain indicating that proteolytic processing occurs. Finally, the teneurin-1 intracellular domain was found to contain a nuclear localization signal, which is required for nuclear localization in transfected cells.</p> <p>Conclusion</p> <p>Teneurin-1 and -2 are expressed by distinct interconnected populations of neurons in the developing central nervous system. Our data support the hypothesis that teneurins can be proteolytically processed leading to the release of the intracellular domain and its translocation to the nucleus.</p

Keck Spectroscopy of Gravitationally Lensed z=4 Galaxies: Improved Constraints on the Escape Fraction of Ionizing Photons

The fraction of ionizing photons that escape from young star-forming galaxies is one of the largest uncertainties in determining the role of galaxies in cosmic reionization. Yet traditional techniques for measuring this fraction are inapplicable at the redshifts of interest due to foreground screening by the Lyman alpha forest. In an earlier study, we demonstrated a reduction in the equivalent width of low-ionization absorption lines in composite spectra of Lyman break galaxies at z=4 compared to similar measures at z=3. This might imply a lower covering fraction of neutral gas and hence an increase with redshift in the escape fraction of ionizing photons. However, our spectral resolution was inadequate to differentiate between several alternative explanations, including changes with redshift in the outflow kinematics. Here we present higher quality spectra of 3 gravitationally lensed Lyman break galaxies at z=4 with a spectral resolution sufficient to break this degeneracy of interpretation. We present a method for deriving the covering fraction of low-ionization gas as a function of outflow velocity and compare the results with similar quality data taken for galaxies at lower redshift. We find a significant trend of lower covering fractions of low-ionization gas for galaxies with strong \Lya emission. In combination with the demographic trends of \Lya emission with redshift from our earlier work, our results provide new evidence for a reduction in the average H I covering fraction, and hence an increase in the escape fraction of ionizing radiation from Lyman break galaxies, with redshift.Comment: submitted to Ap

The Expression and Possible Functions of Tenascin-W During Development and Disease

Tenascins are a family of multifunctional glycoproteins found in the extracellular matrix of chordates. Two of the tenascins, tenascin-C and tenascin-W, form hexabrachions. In this review, we describe the discovery and domain architecture of tenascin-W, its evolution and patterns of expression during embryogenesis and in tumors, and its effects on cells in culture. In avian and mammalian embryos tenascin-W is primarily expressed at sites of osteogenesis, and in the adult tenascin-W is abundant in certain stem cell niches. In primary cultures of osteoblasts tenascin-W promotes cell migration, the formation of mineralized foci and increases alkaline phosphatase activity. Tenascin-W is also prominent in many solid tumors, yet it is missing from the extracellular matrix of most adult tissues. This makes it a potential candidate for use as a marker of tumor stroma and a target for anti-cancer therapies

Computational Study of the Ro-Vibrational Spectrum of CO-CO₂

An accurate ab initio ground-state intermolecular potential energy surface (PES) was determined for the CO-CO2 van der Waals dimer. The Lanczos algorithm was used to compute rovibrational energies on this PES. For both the C-in and O-in T-shaped isomers, the fundamental transition frequencies agree well with previous experimental results. We confirm that the in-plane states previously observed are geared states. In addition, we have computed and assigned many other vibrational states. The rotational constants we determine from J = 1 energy levels agree well with their experimental counterparts. Planar and out-of-plane cuts of some of the wavefunctions we compute are quite different, indicating strong coupling between the bend and torsional modes. Because the stable isomers are T-shaped, vibration along the out-of-plane coordinates is very floppy. In CO-CO2, when the molecule is out-of-plane, interconversion of the isomers is possible, but the barrier height is higher than the in-plane geared barrier height

Spectroscopy of CASSOWARY gravitationally-lensed galaxies in SDSS: characterisation of an extremely bright reionization-era analog at z=1.42z=1.42

We present new observations of sixteen bright ($r=19-21$) gravitationally lensed galaxies at $z\simeq 1-3$ selected from the CASSOWARY survey. Included in our sample is the $z=1.42$ galaxy CSWA-141, one of the brightest known reionization-era analogs at high redshift (g=20.5), with a large sSFR (31.2 Gyr$^{-1}$) and an [OIII]+H$\beta$ equivalent width (EW$_{\rm{[OIII]+H\beta}}$=730~\r{A}) that is nearly identical to the average value expected at $z\simeq 7-8$. In this paper, we investigate the rest-frame UV nebular line emission in our sample with the goal of understanding the factors that regulate strong CIII] emission. Whereas most of the sources in our sample show weak UV line emission, we find elevated CIII] in the spectrum of CSWA-141 (EW$_{\rm{CIII]}}$=4.6$\pm1.9$~\r{A}) together with detections of other prominent emission lines (OIII], Si III], Fe II$^\star$, Mg II). We compare the rest-optical line properties of high redshift galaxies with strong and weak CIII] emission, and find that systems with the strongest UV line emission tend to have young stellar populations and nebular gas that is moderately metal-poor and highly ionized, consistent with trends seen at low and high redshift. The brightness of CSWA-141 enables detailed investigation of the extreme emission line galaxies which become common at $z>6$. We find that gas traced by the CIII] doublet likely probes higher densities than that traced by [OII] and [SII]. Characterisation of the spectrally resolved Mg II emission line and several low ionization absorption lines suggests neutral gas around the young stars is likely optically thin, potentially facilitating the escape of ionizing radiation.Comment: 20 pages, 9 figures, Accepted for publication in MNRA