A Mid-Infrared Study of the Class 0 Cluster in LDN 1448

We present ground-based mid-infrared observations of Class 0 protostars in LDN 1448. Of the five known protostars in this cloud, we detected two, L1448N:A and L1448C, at 12.5, 17.9, 20.8, and 24.5 microns, and a third, L1448 IRS 2, at 24.5 microns. We present high-resolution images of the detected sources, and photometry or upper limits for all five Class 0 sources in this cloud. With these data, we are able to augment existing spectral energy distributions (SEDs) for all five objects and place them on an evolutionary status diagram.Comment: Accepted by the Astronomical Journal; 26 pages, 9 figure

The haematopoietic GTPase RhoH modulates IL3 signalling through regulation of STAT activity and IL3 receptor expression

<p>Abstract</p> <p>Background</p> <p>RhoH is a constitutively active member of the family of Rho GTPases. Its expression is restricted to the haematopoietic lineage, where it serves as a positive regulator for T cell selection and mast cell function and as a negative regulator for growth-related functions in other lineages. Here, we examined the activation of signal transducer and activator of transcription (STAT) proteins in response to stimulation with interleukin 3 (IL3).</p> <p>Results</p> <p>Using the murine IL3-dependent cell line BaF3 we investigated the influence of RhoH protein expression levels on IL3-mediated cellular responses. RhoH overexpressing cells showed lower sensitivity to IL3 and decreased STAT5 activation. SiRNA-mediated repression of <it>RhoH </it>gene expression led to an increase in proliferation and STAT5 activity which correlated with an increased number of IL3 receptor α chain molecules, also known as CD123, expressed at the cell surface. Interestingly, these findings could be reproduced using human THP-1 cells as a model system for acute myeloid leukaemia, where low RhoH levels are known to be an unfavourable prognostic marker. Overexpression of RhoH on the other hand caused an induction of STAT1 activity and western blot analysis revealed that activated STAT1 is phosphorylated on Tyr701. STAT1 is known to induce apoptosis or cell cycle arrest and we detected an upregulation of cyclin-dependent kinase inhibitors (CDKI) <it>p21^Cip1</it>and <it>p27^Kip1</it>in RhoH overexpressing BaF3 cells.</p> <p>Conclusions</p> <p>We propose that RhoH functions as a negative regulator for IL3-induced signals through modulation of the JAK-STAT pathway. High levels of RhoH allow the IL3-dependent activation of STAT1 causing decreased proliferation through upregulation of <it>p21^Cip1</it>and <it>p27^Kip1</it>. Low RhoH levels on the other hand led to an upregulation of IL3-dependent cell growth, STAT5 activity and an increase of CD123 surface expression, linking RhoH to a CD123/STAT5 phenotype that has been described in AML patients.</p

Submillimeter Observations of the Ultraluminous BAL Quasar APM 08279+5255

With an inferred bolometric luminosity of 5\times10^{15}{\rm \lsun}, the recently identified z=3.87, broad absorption line quasar APM 08279+5255 is apparently the most luminous object currently known. As half of its prodigious emission occurs in the infrared, APM 08279+5255 also represents the most extreme example of an Ultraluminous Infrared Galaxy. Here, we present new submillimeter observations of this phenomenal object; while indicating that a vast quantity of dust is present, these data prove to be incompatible with current models of emission mechanisms and reprocessing in ultraluminous systems. The influence of gravitational lensing upon these models is considered and we find that while the emission from the central continuum emitting region may be significantly enhanced, lensing induced magnification cannot easily reconcile the models with observations. We conclude that further modeling, including the effects of any differential magnification is required to explain the observed emission from APM 08279+5255.Comment: 12 Pages with Two figures. Accepted for publication in the Astrophysical Journal Letter

High Mass Star Formation. II. The Mass Function of Submillimeter Clumps in M17

We have mapped an approximately 5.5 by 5.5 pc portion of the M17 massive star-forming region in both 850 and 450 micron dust continuum emission using the Submillimeter Common-User Bolometer Array (SCUBA) on the James Clerk Maxwell Telescope (JCMT). The maps reveal more than 100 dusty clumps with deconvolved linear sizes of 0.05--0.2 pc and masses of 0.8--120 solar masses, most of which are not associated with known mid-infrared point sources. Fitting the clump mass function with a double power law gives a mean power law exponent of alpha_high = -2.4 +/- 0.3 for the high-mass power law, consistent with the exponent of the Salpeter stellar mass function. We show that a lognormal clump mass distribution with a peak at about 4 solar masses produces as good a fit to the clump mass function as does a double power law. This 4 solar mass peak mass is well above the peak masses of both the stellar initial mass function and the mass function of clumps in low-mass star-forming regions. Despite the difference in intrinsic mass scale, the shape of the M17 clump mass function appears to be consistent with the shape of the core mass function in low-mass star-forming regions. Thus, we suggest that the clump mass function in high-mass star-forming regions may be a scaled-up version of that in low-mass regions, instead of its extension to higher masses.Comment: 33 pages, 6 figures, 3 tables. Accepted for publication in the Astrophysical Journa

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1–occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation

GluN2B and GluN2D NMDARs dominate synaptic responses in the adult spinal cord

The composition of the postsynaptic ionotropic receptors that receive presynaptically released transmitter is critical not only for transducing and integrating electrical signals but also for coordinating downstream biochemical signaling pathways. At glutamatergic synapses in the adult CNS an overwhelming body of evidence indicates that the NMDA receptor (NMDAR) component of synaptic responses is dominated by NMDARs containing the GluN2A subunit, while NMDARs containing GluN2B, GluN2C, or GluN2D play minor roles in synaptic transmission. Here, we discovered NMDAR-mediated synaptic responses with characteristics not described elsewhere in the adult CNS. We found that GluN2A-containing receptors contribute little to synaptic NMDAR responses while GluN2B dominates at synapses of lamina I neurons in the adult spinal cord. In addition, we provide evidence for a GluN2D-mediated synaptic NMDAR component in adult lamina I neurons. Strikingly, the charge transfer mediated by GluN2D far exceeds that of GluN2A and is comparable to that of GluN2B. Lamina I forms a disti

Optical Sensor for Diverse Organic Vapors at ppm Concentration Ranges

A broadly responsive optical organic vapor sensor is described that responds to low concentrations of organic vapors without significant interference from water vapor. Responses to several classes of organic vapors are highlighted, and trends within classes are presented. The relationship between molecular properties (vapor pressure, boiling point, polarizability, and refractive index) and sensor response are discussed

Potentiation of Synaptic GluN2B NMDAR Currents by Fyn Kinase Is Gated through BDNF-Mediated Disinhibition in Spinal Pain Processing

In chronic pain states, the neurotrophin brain-derived neurotrophic factor (BDNF) transforms the output of lamina I spinal neurons by decreasing synaptic inhibition. Pain hypersensitivity also depends on N-methyl-D-aspartate receptors (NMDARs) and Src-family kinases, but the locus of NMDAR dysregulation remains unknown. Here, we show that NMDAR-mediated currents at lamina I synapses are potentiated in a peripheral nerve injury model of neuropa

Mantle deformation beneath the Chicxulub impact crater

Accepted versio

Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study

Background: Tissue MicroArray technology aims to perform immunohistochemical staining on hundreds of different tissue samples simultaneously. It allows faster analysis, considerably reducing costs incurred in staining. A time consuming phase of the methodology is the selection of tissue areas within paraffin blocks: no utilities have been developed for the identification of areas to be punched from the donor block and assembled in the recipient block.Results: The presented work supports, in the specific case of a primary subtype of breast cancer (tubular breast cancer), the semi-automatic discrimination and localization between normal and pathological regions within the tissues. The diagnosis is performed by analysing specific morphological features of the sample such as the absence of a double layer of cells around the lumen and the decay of a regular glands-and-lobules structure. These features are analysed using an algorithm which performs the extraction of morphological parameters from images and compares them to experimentally validated threshold values. Results are satisfactory since in most of the cases the automatic diagnosis matches the response of the pathologists. In particular, on a total of 1296 sub-images showing normal and pathological areas of breast specimens, algorithm accuracy, sensitivity and specificity are respectively 89%, 84% and 94%.Conclusions: The proposed work is a first attempt to demonstrate that automation in the Tissue MicroArray field is feasible and it can represent an important tool for scientists to cope with this high-throughput technique