We present new measurements of the cosmic cold molecular gas evolution out to redshift 6 based on systematic mining of the Atacama Large Millimeter/submillimeter Array (ALMA) public archive in the ...COSMOS deep field (A3COSMOS). Our A3COSMOS data set contains ∼700 galaxies (0.3 z 6) with high-confidence ALMA detections in the (sub)millimeter continuum and multiwavelength spectral energy distributions. Multiple gas mass calibration methods are compared, and biases in band conversions (from observed ALMA wavelength to rest-frame Rayleigh-Jeans tail continuum) have been tested. Combining our A3COSMOS sample with ∼1000 CO-observed galaxies at 0 z 4 (75% at z < 0.1), we parameterize galaxies' molecular gas depletion time ( ) and molecular gas to stellar mass ratio ( ) each as a function of the stellar mass ( ), offset from the star-forming main sequence ( ) and cosmic age (or redshift). Our proposed functional form provides a statistically better fit to current data (than functional forms in the literature) and implies a "downsizing" effect (i.e., more-massive galaxies evolve earlier than less-massive ones) and "mass quenching" (gas consumption slows down with cosmic time for massive galaxies but speeds up for low-mass ones). Adopting galaxy stellar mass functions and applying our function for gas mass calculation, we for the first time infer the cosmic cold molecular gas density evolution out to redshift 6 and find agreement with CO blind surveys as well as semianalytic modeling. These together provide a coherent picture of cold molecular gas, star formation rate, and stellar mass evolution in galaxies across cosmic time.
During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic ...viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
We present results on the dust attenuation of galaxies at redshift ∼3–6 by studying the relationship between the UV spectral slope (βUV) and the infrared excess (IRX; L
IR/L
UV) using ...Atacama Large Millimeter/submillimeter Array (ALMA) far-infrared continuum observations. Our study is based on a sample of 67 massive, star-forming galaxies with a median mass of M
* ∼ 1010.7 M
⊙ spanning a redshift range z = 2.6–3.7 (median z = 3.2) that were observed with ALMA at
$\lambda _{\text{rest}}=300\,{\rm \mu m}$
. Both the individual ALMA detections (41 sources) and stacks including all galaxies show the IRX–βUV relationship at z ∼ 3 is mostly consistent with that of local starburst galaxies on average. However, we find evidence for a large dispersion around the mean relationship by up to ±0.5 dex. Nevertheless, the locally calibrated dust correction factors based on the IRX–βUV relation are on average applicable to main-sequence z ∼ 3 galaxies. This does not appear to be the case at even higher redshifts, however. Using public ALMA observations of z ∼ 4–6 galaxies we find evidence for a significant evolution in the IRX–βUV and the IRX–M
* relations beyond z ∼ 3 towards lower IRX values. We discuss several caveats that could affect these results, including the assumed dust temperature. ALMA observations of larger z > 3 galaxy sample spanning a wide range of physical parameters (e.g. lower stellar mass) will be important to investigate this intriguing redshift evolution further.
Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide ...better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.
ABSTRACT
We present an analysis of the dust attenuation of star-forming galaxies at z = 2.5–4.0 through the relationship between the UV spectral slope (β), stellar mass (M*), and the infrared excess ...(IRX = LIR/LUV) based on far-infrared continuum observations from the Atacama Large Millimeter/sub-millimeter Array (ALMA). Our study exploits the full ALMA archive over the COSMOS field processed by the A3COSMOS team, which includes an unprecedented sample of ∼1500 galaxies at z ∼ 3 as primary or secondary targets in ALMA band 6 or 7 observations with a median continuum sensitivity of 126 $\rm {\mu Jy\, beam}^{-1}$ (1σ). The detection rate is highly mass dependent, decreasing drastically below log (M*/M⊙) = 10.5. The detected galaxies show that the IRX–β relationship of massive (log M*/M⊙ > 10) main-sequence galaxies at z = 2.5–4.0 is consistent with that of local galaxies, while starbursts are generally offset by $\sim 0.5\, {\rm dex}$ to larger IRX values. At the low-mass end, we derive upper limits on the infrared luminosities through stacking of the ALMA data. The combined IRX–M* relation at $\rm {log\, ({\it M}_{\ast }/\mathrm{M}_{\odot })\gt 9}$ exhibits a significantly steeper slope than reported in previous studies at similar redshifts, implying little dust obscuration at log M*/M⊙ < 10. However, our results are consistent with earlier measurements at z ∼ 5.5, indicating a potential redshift evolution between z ∼ 2 and z ∼ 6. Deeper observations targeting low-mass galaxies will be required to confirm this finding.
Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson's disease. Although impulse control disorders are conceptualized as lying ...within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson's disease patients with impulse control disorders. We describe results of a 11C raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson's disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson's disease patients may provide a model into the pathophysiology of this disorder.
Cell proliferation and apoptosis are paralleled by altered regulation of ion channels that play an active part in the signaling of those fundamental cellular mechanisms. Cell proliferation must--at ...some time point--increase cell volume and apoptosis is typically paralleled by cell shrinkage. Cell volume changes require the participation of ion transport across the cell membrane, including appropriate activity of Cl- and K+ channels. Besides regulating cytosolic Cl- activity, osmolyte flux and, thus, cell volume, most Cl- channels allow HCO3- exit and cytosolic acidification, which inhibits cell proliferation and favors apoptosis. K+ exit through K+ channels may decrease intracellular K+ concentration, which in turn favors apoptotic cell death. K+ channel activity further maintains the cell membrane potential, a critical determinant of Ca2+ entry through Ca2+ channels. Cytosolic Ca2+ may trigger mechanisms required for cell proliferation and stimulate enzymes executing apoptosis. The switch between cell proliferation and apoptosis apparently depends on the magnitude and temporal organization of Ca2+ entry and on the functional state of the cell. Due to complex interaction with other signaling pathways, a given ion channel may play a dual role in both cell proliferation and apoptosis. Thus, specific ion channel blockers may abrogate both fundamental cellular mechanisms, depending on cell type, regulatory environment and condition of the cell. Clearly, considerable further experimental effort is required to fully understand the complex interplay between ion channels, cell proliferation and apoptosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inactivation of β-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of
Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by ...decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of β-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that β-catenin together with TCF proteins regulates osteoblast expression of
Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that β-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Regulatory T cells (Tregs) are crucial for the maintenance of immunological self-tolerance and their absence or dysfunction can lead to autoimmunity. However, the molecular pathways that govern Treg ...biology remain obscure. In this study, we show that the nuclear factor-κB signalling mediator mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an important novel regulator of both Tregs originating in the thymus ('natural' or nTregs) and Tregs induced to differentiate from naive thymocyte helper (Th) cells in the periphery ('induced' or iTregs). Our examination of mice deficient for MALT1 revealed that these mutants have a reduced number of total Tregs. In young Malt1
mice, nTregs are totally absent and iTreg are diminished in the periphery. Interestingly, total Treg numbers increase in older Malt1
mice as well as in Malt1
mice subjected to experimentally induced inflammation. iTregs isolated from WT and Malt1
mice were indistinguishable with respect to their ability to suppress the activities of effector T cells, but Malt1
iTregs expressed higher levels of Toll-like receptor (TLR) 2. Treatment of WT and Malt1
Th cells in vitro with the TLR2 ligand Pam3Cys strongly enhanced the induction and proliferation of Malt1
iTregs. Our data suggest that MALT1 supports nTreg development in the thymus but suppresses iTreg induction in the periphery during inflammation. Our data position MALT1 as a key molecule that contributes to immune tolerance at steady-state while facilitating immune reactivity under stress conditions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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