21 research outputs found

    The Living Together Arrangement: Social Work and the Lost Client

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    A recent research study suggests that persons living together outside of marriage do not view social work services as a potential source of help for problems brought into the living together arrangement, those common to all intimate long-range dyadic relationships or those directly related to choice of lifestyle. A multi-faceted approach is suggested which would aim at reaching this potential client group in a climate which will neither stigmatize or judge the alternate lifestyle or the persons who practice it

    An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis

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    Tuberculosis (TB), caused by infection with Mycobacterium tuberculosis (M. tuberculosis), is a major cause of morbidity and mortality worldwide and efforts to control TB are hampered by difficulties with diagnosis, prevention and treatment 1,2. Most people infected with M. tuberculosis remain asymptomatic, termed latent TB, with a 10% lifetime risk of developing active TB disease, but current tests cannot identify which individuals will develop disease 3. The immune response to M. tuberculosis is complex and incompletely characterized, hindering development of new diagnostics, therapies and vaccines 4,5. We identified a whole blood 393 transcript signature for active TB in intermediate and high burden settings, correlating with radiological extent of disease and reverting to that of healthy controls following treatment. A subset of latent TB patients had signatures similar to those in active TB patients. We also identified a specific 86-transcript signature that discriminated active TB from other inflammatory and infectious diseases. Modular and pathway analysis revealed that the TB signature was dominated by a neutrophil-driven interferon (IFN)-inducible gene profile, consisting of both IFN-γ and Type I IFNαβ signalling. Comparison with transcriptional signatures in purified cells and flow cytometric analysis, suggest that this TB signature reflects both changes in cellular composition and altered gene expression. Although an IFN signature was also observed in whole blood of patients with Systemic Lupus Erythematosus (SLE), their complete modular signature differed from TB with increased abundance of plasma cell transcripts. Our studies demonstrate a hitherto under-appreciated role of Type I IFNαβ signalling in TB pathogenesis, which has implications for vaccine and therapeutic development. Our study also provides a broad range of transcriptional biomarkers with potential as diagnostic and prognostic tools to combat the TB epidemic

    Trafficking through COPII Stabilises Cell Polarity and Drives Secretion during Drosophila Epidermal Differentiation

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    BACKGROUND: The differentiation of an extracellular matrix (ECM) at the apical side of epithelial cells implies massive polarised secretion and membrane trafficking. An epithelial cell is hence engaged in coordinating secretion and cell polarity for a correct and efficient ECM formation. PRINCIPAL FINDINGS: We are studying the molecular mechanisms that Drosophila tracheal and epidermal cells deploy to form their specific apical ECM during differentiation. In this work we demonstrate that the two genetically identified factors haunted and ghost are essential for polarity maintenance, membrane topology as well as for secretion of the tracheal luminal matrix and the cuticle. We show that they code for the Drosophila COPII vesicle-coating components Sec23 and Sec24, respectively, that organise vesicle transport from the ER to the Golgi apparatus. CONCLUSION: Taken together, epithelial differentiation during Drosophila embryogenesis is a concerted action of ECM formation, plasma membrane remodelling and maintenance of cell polarity that all three rely mainly, if not absolutely, on the canonical secretory pathway from the ER over the Golgi apparatus to the plasma membrane. Our results indicate that COPII vesicles constitute a central hub for these processes

    Steep reverse bed slope at the grounding line of the Weddell Sea sector in West Antarctica

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    The bed of the West Antarctic Ice Sheet is, in places, more than 1.5 km below sea level1, 2. It has been suggested that a positive ice-loss feedback may occur when an ice sheet’s grounding line retreats across a deepening bed1, 2, 3. Applied to the West Antarctic Ice Sheet, this process could potentially raise global sea level4 by more than 3 m. Hitherto, attention has focussed on changes at the Siple Coast5, 6, 7 and Amundsen Sea embayment8, 9, 10 sectors of West Antarctica. Here, we present radio-echo sounding information from the ice sheet’s third sector, the Weddell Sea embayment, that reveals a large subglacial basin immediately upstream of the grounding line. The reverse bed slope is steep, with about 400 m of decline over 40 km. The basin floor is smooth and flat, with little small-scale topography that would delay retreat, indicating that it has been covered with marine sediment5, 11 and was previously deglaciated. Upstream of the basin, well-defined glacially carved fjords with bars at their mouths testify to the position of a former ice margin about 200 km inland from the present margin. Evidence so far suggests that the Weddell Sea sector of the West Antarctic Ice Sheet has been stable, but in the light of our data we propose that the region could be near a physical threshold of substantial change
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