Large format heterodyne arrays for observing far-infrared lines with SOFIA

In the wavelength regime between 60 and 300 microns there are a number of atomic and molecular emission lines that are key diagnostic probes of the interstellar medium. These include transitions of [CII], [NII], [OI], HD, H_2D^+, OH, CO, and H_2O, some of which are among the brightest global and local far-infrared lines in the Galaxy. In Giant Molecular Clouds (GMCs), evolved star envelopes, and planetary nebulae, these emission lines can be extended over many arc minutes and possess complicated, often self absorbed, line profiles. High spectral resolution (R > 10^5) observations of these lines at sub-arcminute angular resolution are crucial to understanding the complicated interplay between the interstellar medium and the stars that form from it. This feedback is central to all theories of galactic evolution. Large format heterodyne array receivers can provide the spectral resolution and spatial coverage to probe these lines over extended regions. The advent of large format (~100 pixel) spectroscopic imaging cameras in the far-infrared (FIR) will fundamentally change the way astronomy is performed in this important wavelength regime. While the possibility of such instruments has been discussed for more than two decades, only recently have advances in mixer and local oscillator technology, device fabrication, micromachining, and digital signal processing made the construction of such instruments tractable. These technologies can be implemented to construct a sensitive, flexible, heterodyne array facility instrument for SOFIA. The instrument concept for StratoSTAR: Stratospheric Submm/THz Array Receiver includes a common user mounting, control system, IF processor, spectrometer, and cryogenic system. The cryogenic system will be designed to accept a frontend insert. The frontend insert and associated local oscillator system/relay optics would be provided by individual user groups and reflect their scientific interests. Rapid technology development in this field makes SOFIA the ideal platform to operate such a modular, continuously evolving instrument

High-field impurity magneto-optics of Si:Se

Contains fulltext : 130582.pdf (publisher's version ) (Open Access

Detection of OD towards the low-mass protostar IRAS 16293-2422 [Letter]

Context. Although water is an essential and widespread molecule in star-forming regions, its chemical formation pathways are still not very well constrained. Observing the level of deuterium fractionation of OH, a radical involved in the water chemical network, is a promising way to infer its chemical origin. Aims. We aim at understanding the formation mechanisms of water by investigating the origin of its deuterium fractionation. This can be achieved by observing the abundance of OD towards the low-mass protostar IRAS 16293−2422, where the HDO distribution is already known. Methods. Using the GREAT receiver on board SOFIA, we observed the ground-state OD transition at 1391.5 GHz towards the low-mass protostar IRAS 16293−2422. We also present the detection of the HDO 111-000 line using the APEX telescope. We compare the OD/HDO abundance ratio inferred from these observations with the predictions of chemical models. Results. The OD line is detected in absorption towards the source continuum. This is the first detection of OD outside the solar system. The SOFIA observation, coupled to the observation of the HDO 111-000 line, provides an estimate of the abundance ratio OD/HDO ~ 17–90 in the gas where the absorption takes place. This value is fairly high compared with model predictions. This may be reconciled if reprocessing in the gas by means of the dissociative recombination of H2DO+ further fractionates OH with respect to water. Conclusions. The present observation demonstrates the capability of the SOFIA/GREAT instrument to detect the ground transition of OD towards star-forming regions in a frequency range that was not accessible before. Dissociative recombination of H2DO+ may play an important role in setting a high OD abundance. Measuring the branching ratios of this reaction in the laboratory will be of great value for chemical models

Enhanced Transferrin Receptor Expression by Proinflammatory Cytokines in Enterocytes as a Means for Local Delivery of Drugs to Inflamed Gut Mucosa

Therapeutic intervention in inflammatory bowel diseases (IBDs) is often associated with adverse effects related to drug distribution into non-diseased tissues, a situation which attracts a rational design of a targeted treatment confined to the inflamed mucosa. Upon activation of immune cells, transferrin receptor (TfR) expression increases at their surface. Because TfR is expressed in all cell types we hypothesized that its cell surface levels are regulated also in enterocytes. We, therefore, compared TfR expression in healthy and inflamed human colonic mucosa, as well as healthy and inflamed colonic mucosa of the DNBS-induced rat model. TfR expression was elevated in the colonic mucosa of IBD patients in both the basolateral and apical membranes of the enterocytes. Increased TfR expression was also observed in colonocytes of the induced colitis rats. To explore the underlying mechanism CaCo-2 cells were treated with various proinflammatory cytokines, which increased both TfR expression and transferrin cellular uptake in a mechanism that did not involve hyper proliferation. These findings were then exploited for the design of targetable carrier towards inflamed regions of the colon. Anti-TfR antibodies were conjugated to nano-liposomes. As expected, iron-starved Caco-2 cells internalized anti-TfR immunoliposomes better than controls. Ex vivo binding studies to inflamed mucosa showed that the anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of non-specific immunoliposomes. It is concluded that targeting mucosal inflammation can be accomplished by nano-liposomes decorated with anti-TfR due to inflammation-dependent, apical, elevated expression of the receptor

Structural analysis of haemoglobin binding by HpuA from the Neisseriaceae family

The Neisseriaceae family of bacteria causes a range of diseases including meningitis, septicaemia, gonorrhoea and endocarditis, and extracts haem from haemoglobin as an important iron source within the iron-limited environment of its human host. Herein we report crystal structures of apo- and haemoglobin-bound HpuA, an essential component of this haem import system. The interface involves long loops on the bacterial receptor that present hydrophobic side chains for packing against the surface of haemoglobin. Interestingly, our structural and biochemical analyses of Kingella denitrificans and Neisseria gonorrhoeae HpuA mutants, although validating the interactions observed in the crystal structure, show how Neisseriaceae have the fascinating ability to diversify functional sequences and yet retain the haemoglobin binding function. Our results present the first description of HpuA’s role in direct binding of haemoglobin

Mathematical modeling of the dynamic storage of iron in ferritin

<p>Abstract</p> <p>Background</p> <p>Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content.</p> <p>Results</p> <p>Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated <it>in vitro </it>with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded.</p> <p>Conclusions</p> <p>The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.</p

New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathway function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to Golgi membranes. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion, and opens stimulating perspectives for the use of our platform in physiological and pathological contexts.Includes Wellcome Trust, MRC and H202