A mitotic SKAP isoform regulates spindle positioning at astral microtubule plus ends

The Astrin/SKAP complex plays important roles in mitotic chromosome alignment and centrosome integrity, but previous work found conflicting results for SKAP function. Here, we demonstrate that SKAP is expressed as two distinct isoforms in mammals: a longer, testis-specific isoform that was used for the previous studies in mitotic cells and a novel, shorter mitotic isoform. Unlike the long isoform, short SKAP rescues SKAP depletion in mitosis and displays robust microtubule plus-end tracking, including localization to astral microtubules. Eliminating SKAP microtubule binding results in severe chromosome segregation defects. In contrast, SKAP mutants specifically defective for plus-end tracking facilitate proper chromosome segregation but display spindle positioning defects. Cells lacking SKAP plus-end tracking have reduced Clasp1 localization at microtubule plus ends and display increased lateral microtubule contacts with the cell cortex, which we propose results in unbalanced dynein-dependent cortical pulling forces. Our work reveals an unappreciated role for the Astrin/SKAP complex as an astral microtubule mediator of mitotic spindle positioning.Leukemia & Lymphoma Society of America (Scholar Award)National Institute of General Medical Sciences (U.S.) (GM088313)American Cancer Society (121776

Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis

BACKGROUND: There are a number of different manifestations of pulmonary aspergillosis. This study aims to review the radiology, presentation, and histological features of lung nodules caused by Aspergillus spp. METHODS: Patients were identified from a cohort attending our specialist Chronic Pulmonary Aspergillosis clinic. Patients with cavitating lung lesions, with or without fibrosis and those with aspergillomas or a diagnosis of invasive aspergillosis were excluded. Demographic, laboratory, and clinical data and radiologic findings were recorded. RESULTS: Thirty-three patients with pulmonary nodules and diagnostic features of aspergillosis (histology and/or laboratory findings) were identified. Eighteen (54.5 %) were male, mean age 58 years (range 27–80 years). 19 (57.6 %) were former or current smokers. The median Charleston co-morbidity index was 3 (range 0–7). All complained of a least one of; dyspnoea, cough, haemoptysis, or weight loss. None reported fever. Ten patients (31 %) did not have an elevated Aspergillus IgG, and only 4 patients had elevated Aspergillus precipitins. Twelve patients (36 %) had a single nodule, six patients (18 %) had between 2 and 5 nodules, 2 (6 %) between 6 and 10 nodules and 13 (39 %) had more than 10 nodules. The mean size of the nodules was 21 mm, with a maximum size ranging between 5–50 mm. No nodules had cavitation radiographically. The upper lobes were most commonly involved. Histology was available for 18 patients and showed evidence of granulation tissue, fibrosis, and visualisation of fungal hyphae. CONCLUSION: Pulmonary nodules are a less common manifestation of aspergillosis in immunocompetent patients. Distinguishing these nodules from other lung pathology may be difficult on CT findings alone

Combined extracellular matrix cross-linking activity of the peroxidase MLT-7 and the dual oxidase BLI-3 is critical for post-embryonic viability in <i>Caenorhabditis elegans</i>

The nematode cuticle is a protective collagenous extracellular matrix that is modified, cross-linked, and processed by a number of key enzymes. This Ecdysozoan-specific structure is synthesized repeatedly and allows growth and development in a linked degradative and biosynthetic process known as molting. A targeted RNA interference screen using a cuticle collagen marker has been employed to identify components of the cuticle biosynthetic pathway. We have characterized an essential peroxidase, MoLT-7 (MLT-7), that is responsible for proper cuticle molting and re-synthesis. MLT-7 is an active, inhibitable peroxidase that is expressed in the cuticle-synthesizing hypodermis coincident with each larval molt. mlt-7 mutants show a range of body morphology defects, most notably molt, dumpy, and early larval stage arrest phenotypes that can all be complemented with a wild type copy of mlt-7. The cuticles of these mutants lacks di-tyrosine cross-links, becomes permeable to dye and accessible to tyrosine iodination, and have aberrant collagen protein expression patterns. Overexpression of MLT-7 causes mutant phenotypes further supporting its proposed enzymatic role. In combination with BLI-3, an H2O2-generating NADPH dual oxidase, MLT-7 is essential for post-embryonic development. Disruption of mlt-7, and particularly bli-3, via RNA interference also causes dramatic changes to the in vivo cross-linking patterns of the cuticle collagens DPY-13 and COL-12. This points toward a functionally cooperative relationship for these two hypodermally expressed proteins that is essential for collagen cross-linking and proper extracellular matrix formation

Strategies for Testing the Impact of Natural Flood Risk Management Measures

Natural Flood Management (NFM) is an approach that seeks to work with natural processes to enhance the flood regulating capacity of a catchment, whilst delivering a wide range of ecosystem services, from pollution assimilation to habitat creation and carbon storage. This chapter describes a tiered approach to NFM, commencing with strategic modelling to identify a range of NFM opportunities (tree-planting, distributed runoff attenuation features, and soil structure improvements), and their potential benefits, before engagement with catchment partners, and prioritisation of areas for more detailed hydrological modelling and uncertainty analysis. NFM measures pose some fundamental challenges in modelling their contribution to flood risk management because they are often highly distributed, can influence multiple catchment processes, and evidence for their effectiveness at the large scale is uncertain. This demands we model the ‘upstream’ in more detail so that we can assess the effectiveness of many small-scale changes at the large-scale. We demonstrate an approach to address these challenges employing the fast, high resolution, fully-distributed inundation model JFLOW, and visualisation of potential benefits in map form. These are used to engage catchment managers who can prioritise areas for potential deployment of NFM measures, where more detailed modelling may be targeted. We then demonstrate a framework applying the semi-distributed Dynamic TOPMODEL in which uncertainty plays an integral role in the decision-making process

Comparison of six Aspergillus-specific IgG assays for the diagnosis of chronic pulmonary aspergillosis (CPA)

Summary Objectives: Chronic pulmonary aspergillosis (CPA) is estimated to affect 3 million persons worldwide. Aspergillus-specific IgG is a key component in CPA diagnosis. We aimed to establish the optimal diagnostic cut offs for CPA and the comparative performance of six assays in this context. Methods: Sera from 241 patients with CPA and 100 healthy blood donors were tested using five Aspergillus-specific IgG assays plus precipitin testing using Microgen Aspergillus antigens. Optimal CPA diagnostic cut-offs were; ImmunoCAP 20 mg/L (96% sensitivity, 98% specificity), Immulite 10 mg/L (96% sensitivity, 98% specificity), Serion 35 U/ml (90% sensitivity, 98% specificity), Dynamiker 65 AU/ml (77% sensitivity, 97% specificity) and Genesis 20 U/ ml (75% sensitivity, 99% specificity). The precipitin test was 59% sensitive and 100% specific

Orbital dependent nucleonic pairing in the lightest known isotopes of tin

By studying the 109Xe-->105Te-->101Sn superallowed alpha-decay chain, we observe low-lying states in 101Sn, the one-neutron system outside doubly magic 100Sn. We find that the spins of the ground state (J = 7=2) and first excited state (J = 5=2) in 101Sn are reversed with respect to the traditional level ordering postulated for 103Sn and the heavier tin isotopes. Through simple arguments and state-of-the-art shell model calculations we explain this unexpected switch in terms of a transition from the single-particle regime to the collective mode in which orbital-dependent pairing correlations, dominate.Comment: 5 pages 3 figure

Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis.

BACKGROUND: The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda. METHODS: We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics. RESULTS: 10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24. CONCLUSION: These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis. TRIAL REGISTRATION: The SOUTH trial was registered prospectively. ClinicalTrials.gov Identifier: NCT01782950 ; Registration date: 4th February 2013; Last verified: 13th April 2015

First Evidence of Peat Domes in the Congo Basin using LiDAR from a fixed-wing drone

This work was funded by CongoPeat, a NERC Large Grant (NE/R016860/1) to S.L.L. and E.T.A.M. (UAV data collection, I.J.D. time), a NERC Open CASE Studentship to S.L.L., I.L. and G.D. and a Phillip Leverhulme Prize to S.L.L. (peat depths).The world’s most extensive tropical peatlands occur in the Cuvette Centrale depression in the Congo Basin, which stores 30.6 petagrams of carbon (95% CI, 6.3–46.8). Improving our understanding of the genesis, development and functioning of these under-studied peatlands requires knowledge of their topography and, in particular, whether the peat surface is domed, as this implies a rain-fed system. Here we use a laser altimeter mounted on an unmanned airborne vehicle (UAV) to measure peat surface elevation along two transects at the edges of a peatland, in the northern Republic of Congo, to centimetre accuracy and compare the results with an analysis of nearby satellite LiDAR data (ICESat and ICESat-2). The LiDAR elevations on both transects show an upward slope from the peatland edge, suggesting a surface elevation peak of around 1.8 m over ~20 km. While modest, this domed shape is consistent with the peatland being rainfed. In-situ peat depth measurements and our LiDAR results indicate that this peatland likely formed at least 10,000 years BP in a large shallow basin ~40 km wide and ~3 m deep.Publisher PDFPeer reviewe