Expression of VPAC1 in a murine model of allergic asthma

Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter of the inhibitory non-adrenergic non-cholinergic nervous system and influences the mammalian airway function in various ways. Hence known for bronchodilatory, immunomodulatory and mucus secretion modulating effects by interacting with the VIP receptors VPAC1 and VPAC2, it is discussed to be a promising target for pharmaceutical intervention in common diseases such as COPD and bronchial asthma. Here we examined the expression and transcriptional regulation of VPAC1 in the lungs of allergic mice using an ovalbumin (OVA) -induced model of allergic asthma. Mice were sensitized to OVA and challenged with an OVA aerosol. In parallel a control group was sham sensitized with saline. VPAC1 expression was examined using RT-PCR and real time-PCR studies were performed to quantify gene transcription. VPAC1 mRNA expression was detected in all samples of OVA-sensitized and challenged animals and control tissues. Further realtime analysis did not show significant differences at the transcriptional level. Although the present studies did not indicate a major transcriptional regulation of VPAC1 in states of allergic airway inflammation, immunomodulatory effects of VPAC1 might still be present due to regulations at the translational level

‘Oh motherland I pledge to thee…’ : a study into nationalism, gender and the representation of an imagined family within national anthems

In this paper we aim to join feminist critiques of nationalism, arguing that beyond understanding nations as imagined communities (Anderson 1983: 6), the symbolic construction of gender must also be considered in the formation of those communities. We argue that the metaphor of an ‘imagined family’ or ‘filial community’ is a more useful concept towards understanding the links between gender and nationhood in four ways as family relations: 1) provide a clear, hierarchical structure, 2) prescribe social roles and responsibilities, 3) are linked to positive affective connotations and 4) reify social phenomena as biologically determined. In order to empirically substantiate our claim, we will explore the prevalence and use of family metaphors in a key symbol of nationhood discourses of nationhood. Through a qualitative analysis of national anthems as ‘mnemonics of national identity’, we demonstrate the widespread presence of family metaphors, discussing how they reproduce ideas of family and gender. Finally, we discuss how the ‘imagined family’ as present in anthems and other forms of national representation could inform future studies of nationalism and national politics.PostprintPeer reviewe

Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.

The B cell adaptor protein (BCAP) is a multimodular regulator of inflammatory signaling in diverse immune system cells. BCAP couples TLR signaling to phosphoinositide metabolism and inhibits MyD88-directed signal transduction. BCAP is recruited to the TLR signalosome forming multitypic interactions with the MAL and MyD88 signaling adaptors. In this study, we show that indirect dimerization of BCAP TIR is required for negative regulation of TLR signaling. This regulation is mediated by a transcription factor Ig (TIG/IPT) domain, a fold found in the NF-κB family of transcription factors. We have solved the crystal structure of the BCAP TIG and find that it is most similar to that of early B cell factor 1 (EBF1). In both cases, the dimer is stabilized by a helix-loop-helix motif at the C terminus and interactions between the β-sheets of the Ig domains. BCAP is exclusively localized in the cytosol and is unable to bind DNA. Thus, the TIG domain is a promiscuous dimerization module that has been appropriated for a range of regulatory functions in gene expression and signal transduction

Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes

Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time-course of healing. Their comparison to cancer transcriptomes revealed that a resolution phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer

Assessing the impacts of the Deepwater Horizon oil spill: the National Status and Trends Program response; a summary report of coastal contamination

NOAA’s National Status and Trends Program (NS&T) collected oyster tissue and sediments for quantification of polycyclic aromatic hydrocarbons (PAHs) and petroleum associated metals before and after the landfall of oil from the Deepwater Horizon incident of 2010. These new pre- and post- landfall measurements were put into a historical context by comparing them to data collected in the region over three decades during Mussel Watch monitoring. Overall, the levels of PAHs in both sediment and oysters both pre- and post-landfall were within the range of historically observed values for the Gulf of Mexico. Some specific sites did have elevated PAH levels. While those locations generally correspond to areas in which oil reached coastal areas, it cannot be conclusively stated that the contamination is due to oiling from the Deepwater Horizon incident at these sites due to the survey nature of these sampling efforts. Instead, our data indicate locations along the coast where intensive investigation of hydrocarbon contamination should be undertaken. Post-spill concentrations of oil-related trace metals (V, Hg, Ni) were generally within historically observed ranges for a given site, however, nickel and vanadium were elevated at some sites including areas in Mississippi Sound and Galveston, Terrebonne, Mobile, Pensacola, and Apalachicola Bays. No oyster tissue metal body burden exceeded any of the United States Food and Drug Administration’s (FDA) shellfish permissible action levels for human consumption

Compendium of Total Ionizing Dose and Displacement Damage for Candidate Spacecraft Electronics for NASA

Vulnerability of a variety of candidate spacecraft electronics to total ionizing dose and displacement damage is studied. Devices tested include optoelectronics, digital, analog, linear, and hybrid devices

Recent Single Event Effects Compendium of Candidate Electronics for NASA Space Systems

We present the results of single event effects (SEE) testing and analysis investigating the effects of radiation on electronics. This paper is a summary of test results

Negative Regulation of TLR Signaling by BCAP Requires Dimerization of Its DBB Domain.

The B cell adaptor protein (BCAP) is a multimodular regulator of inflammatory signaling in diverse immune system cells. BCAP couples TLR signaling to phosphoinositide metabolism and inhibits MyD88-directed signal transduction. BCAP is recruited to the TLR signalosome forming multitypic interactions with the MAL and MyD88 signaling adaptors. In this study, we show that indirect dimerization of BCAP TIR is required for negative regulation of TLR signaling. This regulation is mediated by a transcription factor Ig (TIG/IPT) domain, a fold found in the NF-κB family of transcription factors. We have solved the crystal structure of the BCAP TIG and find that it is most similar to that of early B cell factor 1 (EBF1). In both cases, the dimer is stabilized by a helix-loop-helix motif at the C terminus and interactions between the β-sheets of the Ig domains. BCAP is exclusively localized in the cytosol and is unable to bind DNA. Thus, the TIG domain is a promiscuous dimerization module that has been appropriated for a range of regulatory functions in gene expression and signal transduction