Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null ...mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. The molecular mechanisms by which TMEM38B mutations cause OI are unknown. We identified 3 probands with recessive defects in TMEM38B. TRIC-B protein is undetectable in proband fibroblasts and osteoblasts, although reduced TMEM38B transcripts are present. TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability. Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery. The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps. Collagen helical lysine hydroxylation is reduced, while telopeptide hydroxylation is increased, despite increased LH1 and decreased Ca2+-dependent FKBP65, respectively. Although PDI levels are maintained, procollagen chain assembly is delayed in proband cells. The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen. Lower-stability forms of collagen that elude proteasomal degradation are not incorporated into extracellular matrix, which contains only normal stability collagen, resulting in matrix insufficiency. These data support a role for TRIC-B in intracellular Ca2+ homeostasis, and demonstrate that absence of TMEM38B causes OI by dysregulation of calcium flux kinetics in the ER, impacting multiple collagen-specific chaperones and modifying enzymes.
We exploit the deep and extended far-IR data sets (at 70, 100 and 160 μm) of the Herschel Guaranteed Time Observation (GTO) PACS Evolutionary Probe (PEP) Survey, in combination with the Herschel ...Multi-tiered Extragalactic Survey data at 250, 350 and 500 μm, to derive the evolution of the rest-frame 35-, 60-, 90- and total infrared (IR) luminosity functions (LFs) up to z ∼ 4. We detect very strong luminosity evolution for the total IR LF (L
IR ∝ (1 + z)3.55 ± 0.10 up to z ∼ 2, and ∝ (1 + z)1.62 ± 0.51 at 2 < z 4) combined with a density evolution (∝(1 + z)−0.57 ± 0.22 up to z ∼ 1 and ∝ (1 + z)−3.92 ± 0.34 at 1 < z 4). In agreement with previous findings, the IR luminosity density (ρIR) increases steeply to z ∼ 1, then flattens between z ∼ 1 and z ∼ 3 to decrease at z 3. Galaxies with different spectral energy distributions, masses and specific star formation rates (SFRs) evolve in very different ways and this large and deep statistical sample is the first one allowing us to separately study the different evolutionary behaviours of the individual IR populations contributing to ρIR. Galaxies occupying the well-established SFR-stellar mass main sequence (MS) are found to dominate both the total IR LF and ρIR at all redshifts, with the contribution from off-MS sources (≥0.6 dex above MS) being nearly constant (∼20 per cent of the total ρIR) and showing no significant signs of increase with increasing z over the whole 0.8 < z < 2.2 range. Sources with mass in the range 10 ≤ log(M/M) ≤ 11 are found to dominate the total IR LF, with more massive galaxies prevailing at the bright end of the high-z ( 2) LF. A two-fold evolutionary scheme for IR galaxies is envisaged: on the one hand, a starburst-dominated phase in which the Super Massive Black Holes (SMBH) grows and is obscured by dust (possibly triggered by a major merging event), is followed by an AGN-dominated phase, then evolving towards a local elliptical. On the other hand, moderately star-forming galaxies containing a low-luminosity AGN have various properties suggesting they are good candidates for systems in a transition phase preceding the formation of steady spiral galaxies.
ABSTRACT Local starbursts have a higher efficiency of converting gas into stars, as compared to typical star-forming galaxies at a given stellar mass, possibly indicative of different modes of star ...formation. With the peak epoch of galaxy formation occurring at z > 1, it remains to be established whether such an efficient mode of star formation is occurring at high redshift. To address this issue, we measure the molecular gas content of seven high-redshift (z ∼ 1.6) starburst galaxies with the Atacama Large Millimeter/submillimeter Array and IRAM/Plateau de Bure Interferometer. Our targets are selected from the sample of Herschel far-infrared-detected galaxies having star formation rates (∼300-800 M yr−1) elevated ( 4×) above the star-forming main sequence (MS) and included in the FMOS-COSMOS near-infrared spectroscopic survey of star-forming galaxies at z ∼ 1.6 with Subaru. We detect CO emission in all cases at high levels of significance, indicative of high gas fractions (∼30%-50%). Even more compelling, we firmly establish with a clean and systematic selection that starbursts, identified as MS outliers, at high redshift generally have a lower ratio of CO to total infrared luminosity as compared to typical MS star-forming galaxies, although with a smaller offset than expected based on past studies of local starbursts. We put forward a hypothesis that there exists a continuous increase in star formation efficiency with elevation from the MS with galaxy mergers as a possible physical driver. Along with a heightened star formation efficiency, our high-redshift sample is similar in other respects to local starbursts, such as being metal rich and having a higher ionization state of the interstellar medium.
In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. ...The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose-response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.
Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon ...nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.
Twenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17 months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms.
These data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT.
Abstract
We present deep ALMA CO(5−4) observations of a main-sequence, clumpy galaxy at z = 1.5 in the HUDF. Thanks to the ∼0
${^{\prime\prime}_{.}}$
5 resolution of the ALMA data, we can link ...stellar population properties to the CO(5−4) emission on scales of a few kiloparsec. We detect strong CO(5−4) emission from the nuclear region of the galaxy, consistent with the observed L
IR–
$L^{\prime }_{\rm CO(5-4)}$
correlation and indicating ongoing nuclear star formation. The CO(5−4) gas component appears more concentrated than other star formation tracers or the dust distribution in this galaxy. We discuss possible implications of this difference in terms of star formation efficiency and mass build-up at the galaxy centre. Conversely, we do not detect any CO(5−4) emission from the UV-bright clumps. This might imply that clumps have a high star formation efficiency (although they do not display unusually high specific star formation rates) and are not entirely gas dominated, with gas fractions no larger than that of their host galaxy (∼50 per cent). Stellar feedback and disc instability torques funnelling gas towards the galaxy centre could contribute to the relatively low gas content. Alternatively, clumps could fall in a more standard star formation efficiency regime if their actual star formation rates are lower than generally assumed. We find that clump star formation rates derived with several different, plausible methods can vary by up to an order of magnitude. The lowest estimates would be compatible with a CO(5−4) non-detection even for main-sequence like values of star formation efficiency and gas content.
Using a mass-limited sample of 24 mu m detected, star-forming galaxies at 0.5 < z < 1.3, we study the mass-star formation rate (SFR) correlation and its tightness. The correlation is well defined ...(sigma = 0.28 dex) for disk galaxies (n sub(Sersic) < 1.5), while more bulge-dominated objects often have lower specific SFRs (sSFRs). For disk galaxies, a much tighter correlation (sigma = 0.19 dex) is obtained if the rest-frame H-band luminosity is used instead of stellar mass derived from multi-color photometry. The sSFR correlates strongly with rest-frame optical colors (hence luminosity-weighted stellar age) and also with clumpiness (which likely reflects the molecular gas fraction). This implies that most of the observed scatter is real, despite its low level, and not dominated by random measurement errors. After correcting for these differential effects a remarkably small dispersion remains (sigma = 0.14 dex), suggesting that measurement errors in mass or SFR are <, ~0.10 dex, excluding systematic uncertainties. Measurement errors in stellar masses, the thickening of the correlation due to real sSFR variations, and varying completeness with stellar mass, can spuriously bias the derived slope to lower values due to the finite range over which observables (mass and SFR) are available. When accounting for these effects, the intrinsic slope for the main sequence for disk galaxies gets closer to unity.
Atacama Large Millimeter/submillimeter Array (ALMA) measurements for 93 Herschel-selected galaxies at 1.1 ≤ z ≤ 1.7 in COSMOS reveal a sizable (>29%) population with compact star formation (SF) ...sizes, lying on average >×3.6 below the optical stellar mass (M )-size relation of disks. This sample widely spans the star-forming main sequence (MS), having 108 ≤ M ≤ 1011.5 M and 20 ≤ star formation rate (SFR) ≤ 680 M yr−1. The 32 size measurements and 61 upper limits are measured on ALMA images that combine observations of CO(5-4), CO(4-3), CO(2-1), and λobs ∼ 1.1-1.3 mm continuum, all tracing the star-forming molecular gas. These compact galaxies have instead normally extended Kband sizes, suggesting strong specific SFR gradients. Compact galaxies comprise the 50 18% of MS galaxies at M > 1011M . This is not expected in standard bimodal scenarios, where MS galaxies are mostly steadily growing extended disks. We suggest that compact MS objects are early post-starburst galaxies in which the merger-driven boost of SF has subsided. They retain their compact SF size until either further gas accretion restores premerger galaxy-wide SF, or until becoming quenched. The fraction of merger-affected SF inside the MS seems thus larger than anticipated and might reach ∼50% at the highest M . The presence of large galaxies above the MS demonstrates an overall poor correlation between galaxy SF size and specific SFR.
We present Atacama Large Millimetre Array and Atacama Compact Array observations of the Sunyaev-Zel’dovich effect in the z = 2 galaxy cluster Cl J1449+0856, an X-ray-detected progenitor of typical ...massive clusters in the present day Universe. While in a cleaned but otherwise untouched 92 GHz map of this cluster little to no negative signal is visible, careful subtraction of known sub-millimetre emitters in the uv plane reveals a decrement at 5σ significance. The total signal is −190 ± 36 μJy, with a peak offset by 5″–9″ (∼50 kpc) from both the X-ray centroid and the still-forming brightest cluster galaxy. A comparison of the recovered uv-amplitude profile of the decrement with different pressure models allows us to derive total mass constraints consistent with the ∼6 × 1013M⊙ estimated from X-ray data. Moreover, we find no strong evidence for a deviation of the pressure profile with respect to local galaxy clusters, although a slight tension at small-to-intermediate spatial scales suggests a flattened central profile, opposite to that seen in a cool core and possibly an AGN-related effect. This analysis of the lowest mass single SZ detection so far illustrates the importance of interferometers when observing the SZ effect in high-redshift clusters, the cores of which cannot be considered quiescent, such that careful subtraction of galaxy emission is necessary.
To better constrain the physical mechanisms driving star formation, we present the first systematic study of the radio continuum size evolution of star-forming galaxies (SFGs) over the redshift range ...0.35 < z < 2.25. We use the VLA COSMOS 3 GHz map (noise rms = 2.3 μJy beam−1, θbeam = 0.75 arcsec) to construct a mass-complete sample of 3184 radio-selected SFGs that reside on and above the main sequence (MS) of SFGs. We constrain the overall extent of star formation activity in galaxies by applying a 2D Gaussian model to their radio continuum emission. Extensive Monte Carlo simulations are used to validate the robustness of our measurements and characterize the selection function. We find no clear dependence between the radio size and stellar mass, M⋆, of SFGs with 10.5 ≲ log(M⋆/M⊙) ≲ 11.5. Our analysis suggests that MS galaxies are preferentially extended, while SFGs above the MS are always compact. The median effective radius of SFGs on (above) the MS of Reff = 1.5 ± 0.2 (1.0 ± 0.2) kpc remains nearly constant with cosmic time; a parametrization of the form Reff ∝ (1 + z)α yields a shallow slope of only α = −0.26 ± 0.08 (0.12 ± 0.14) for SFGs on (above) the MS. The size of the stellar component of galaxies is larger than the extent of the radio continuum emission by a factor ∼2 (1.3) at z = 0.5 (2), indicating star formation is enhanced at small radii. The galactic-averaged star formation rate surface density (ΣSFR) scales with the distance to the MS, except for a fraction of MS galaxies (≲10%) that harbor starburst-like ΣSFR. These “hidden” starbursts might have experienced a compaction phase due to disk instability and/or a merger-driven burst of star formation, which may or may not significantly offset a galaxy from the MS. We thus propose to use ΣSFR and distance to the MS in conjunction to better identify the galaxy population undergoing a starbursting phase.
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