Signaling via interleukin-4, receptor alpha chain is required for successful vaccination against schistosomiasis in BALB/c mice

Radiation-attenuated (RA) schistosome larvae are potent stimulators of innate immune responses at the skin site of exposure (pinna) that are likely to be important factors in the development of Th1-mediated protective immunity. In addition to causing an influx of neutrophils, macrophages, and dendritic cells (DCs) into the dermis, RA larvae induced a cascade of chemokine and cytokine secretion following in vitro culture of pinna biopsy samples. While macrophage inflammatory protein 1 and interleukin-1 (IL-1) were produced transiently within the first few days, the Th1-promoting cytokines IL-12 and IL-18 were secreted at high levels until at least day 14. Assay of C3H/HeJ mice confirmed that IL-12 secretion was not due to lipopolysaccharide contaminants binding Toll-like receptor 4. Significantly, IL-12 p40 secretion was sustained in pinnae from vaccinated mice but not in those from nonprotected infected mice. In contrast, IL-10 was produced from both vaccinated and infected mice. This cytokine regulates IL-12-associated dermal inflammation, since in vaccinated IL-10/ mice, pinna thickness was greatly increased concurrent with elevated levels of IL-12 p40. A significant number of IL-12 p40 cells were detected as emigrants from in vitro-cultured pinnae, and most were within a population of rare large granular cells that were Ia, consistent with their being antigen-presenting cells. Labeling of IL-12 cells for CD11c, CD205, CD8, CD11b, and F4/80 indicated that the majority were myeloid DCs, although a proportion were CD11c F4/80, suggesting that macrophages were an additional source of IL-12 in the skin

Flexible C : N ratio enhances metabolism of large phytoplankton when resource supply is intermittent

Abstract. Phytoplankton cell size influences particle sinking rate, food web interactions and biogeographical distributions. We present a model in which the uptake, storage and assimilation of nitrogen and carbon are explicitly resolved in different-sized phytoplankton cells. In the model, metabolism and cellular C : N ratio are influenced by the accumulation of carbon polymers such as carbohydrate and lipid, which is greatest when cells are nutrient starved, or exposed to high light. Allometric relations and empirical data sets are used to constrain the range of possible C : N, and indicate that larger cells can accumulate significantly more carbon storage compounds than smaller cells. When forced with extended periods of darkness combined with brief exposure to saturating irradiance, the model predicts organisms large enough to accumulate significant carbon reserves may on average synthesize protein and other functional apparatus up to five times faster than smaller organisms. The advantage of storage in terms of average daily protein synthesis rate is greatest when modeled organisms were previously nutrient starved, and carbon storage reservoirs saturated. Small organisms may therefore be at a disadvantage in terms of average daily growth rate in environments that involve prolonged periods of darkness and intermittent nutrient limitation. We suggest this mechanism is a significant constraint on phytoplankton C : N variability and cell size distribution in different oceanic regimes. </jats:p

1SXPS: A deep Swift X-ray Telescope point source catalog with light curves and spectra

We present the 1SXPS (Swift-XRT Point Source) catalog of 151,524 X-ray point-sources detected by the Swift-XRT in 8 years of operation. The catalog covers 1905 square degrees distributed approximately uniformly on the sky. We analyze the data in two ways. First we consider all observations individually, for which we have a typical sensitivity of ~3e-13 erg/cm2/s (0.3--10 keV). Then we co-add all data covering the same location on the sky: these images have a typical sensitivity of ~9e-14 erg/cm2/s (0.3--10 keV). Our sky coverage is nearly 2.5 times that of 3XMM-DR4, although the catalog is a factor of ~1.5 less sensitive. The median position error is 5.5" (90% confidence), including systematics. Our source detection method improves on that used in previous XRT catalogs and we report >68,000 new X-ray sources. The goals and observing strategy of the Swift satellite allow us to probe source variability on multiple timescales, and we find ~30,000 variable objects in our catalog. For every source we give positions, fluxes, time series (in four energy bands and two hardness ratios), estimates of the spectral properties, spectra and spectral fits for the brightest sources, and variability probabilities in multiple energy bands and timescales.Comment: 27 pages, 19 figures; accepted for publication in ApJS. The accompanying website, http://www.swift.ac.uk/1SXPS is live; the Vizier entry should be available shortl

Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia

Background: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. Principal Findings: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ) and the sex hormone medroxyprogesterone acetate (MPA) against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M) converged upon the increased synthesis and reduced metabolism of prostaglandin D2 (PGD2) resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Δ12,14 PGJ2 (15d-PGJ2). BEZ increased PGD2 synthesis via the generation of reactive oxygen species (ROS) and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ2 by inhibiting the PGD2 11β -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD2 to 9α11β-PGF2α. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. Significance: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML

What is the current state of debate around the use of contextualised admissions for undergraduate admissions? A review of the current stakeholder perspective

This is the author accepted manuscript. The final version is available from Taylor & Francis (Routledge) via the DOI in this record.Higher Education Institutions in England are an integral part of the government’s social mobility strategy. Contextualisation of undergraduate admissions decisions has emerged as a key tool towards progressing social mobility objectives. The present paper builds on our previous 2013 research by describing findings from 15 qualitative interviews with stakeholders in contextualised admissions. Stakeholders were drawn from government, non-governmental and third sector bodies including those representing the voice of schools and young people. We find that data challenges continue to be a main barrier to the application of contextual admissions. Respondents thought that more consistency and transparency between universities would be helpful to assist applicants and those who support them to better understand contextual data use in undergraduate admissions. Views are divided about whether differential admissions offers represent the most important application of contextual data. Respondents saw potential for using contextual data beyond admissions for supporting students at university and into further study or employment.The Access Projec

On the asymmetric zero-range in the rarefaction fan

We consider the one-dimensional asymmetric zero-range process starting from a step decreasing profile. In the hydrodynamic limit this initial condition leads to the rarefaction fan of the associated hydrodynamic equation. Under this initial condition and for totally asymmetric jumps, we show that the weighted sum of joint probabilities for second class particles sharing the same site is convergent and we compute its limit. For partially asymmetric jumps we derive the Law of Large Numbers for the position of a second class particle under the initial configuration in which all the positive sites are empty, all the negative sites are occupied with infinitely many first class particles and with a single second class particle at the origin. Moreover, we prove that among the infinite characteristics emanating from the position of the second class particle, this particle chooses randomly one of them. The randomness is given in terms of the weak solution of the hydrodynamic equation through some sort of renormalization function. By coupling the zero-range with the exclusion process we derive some limiting laws for more general initial conditions.Comment: 22 pages, to appear in Journal of Statistical Physic

EMDR to Treat Functional Neurological Disorder: A Review

Eye movement desensitization and reprocessing (EMDR) therapy is an established treatment for posttraumatic stress disorder (PTSD), but there is increasing evidence for its use beyond PTSD. EMDR can be effective at treating distressing memories not associated with PTSD, as well as somatic symptoms (like chronic pain), and as such could potentially be used as a treatment for patients with functional neurological disorder (FND). Searches were conducted for published peer-reviewed articles on the use of EMDR for FND. The databases selected and searched were Medline, Embase, Cochrane Library, CINAHL Plus, Web of Science, PsychINFO, PubMed, and Francine Shapiro Library. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Three relevant articles were found. The studies included are one case series and two case studies. Of the five participants included in the studies, four experienced functional non-epileptic attacks; and one experienced functional movement disorder. Four out of the five patients were successfully treated with EMDR. EMDR is potentially a useful treatment of FND, but further research, including controlled trials, is required. The authors propose that EMDR could be useful in treating patients with FND and comorbid PTSD, as well as patients without comorbid PTSD. We discuss the clinical implications and propose how EMDR could fit into the FND treatment pathway

Phytotoxicity and cytogenotoxicity of water and sediment of urban stream in bioassay with Lactuca sativa

The aim of this study was to evaluate the spatial and temporal influence of the phytotoxicity and cytogenotoxicity of water and sediment of urban stream on the germination and initial growth of Lactuca sativa. Samples were collected from water and sediment at five sites of the Pântano Stream (Alfenas, Minas Gerais) during the period from October 2010 to July 2011. The concentrations of the metals Cd, Pb and Zn were quantified. Moreover, phytotoxicity and cytogenotoxicity were tested with samples of water and aqueous extracts of sediments. The evaluated end points were the germination rate, root length, fresh and dry weight, mitotic index and frequency of chromosomal abnormalities. Higher levels of Cd and Pb were verified in water samples collected during the rainy months. Water and sediment showed phytotoxic effect on germination, fresh weight and dry weight of Lactuca sativa. Root length was stimulated and only samples of water reduced the mitotic index. Significant temporal variation related to rainfall was observed only for phytotoxicity tests.Objetivou-se, com este trabalho, avaliar a influência espacial e temporal da fitotoxicidade e da citogenotoxicidade da água e do sedimento de córrego urbano quanto às características germinativas e de crescimento inicial de Lactuca sativa. Amostras de água e de sedimento foram coletadas em 5 pontos do Córrego do Pântano (Alfenas, Minas Gerais), no período de outubro de 2010 a julho de 2011 e as concentrações dos metais Cd, Pb e Zn foram quantificadas. Os ensaios de fitotoxicidade e de citogenotoxicidade foram realizados com as amostras de água e extratos aquosos dos sedimentos. Os parâmetros avaliados foram taxa de germinação, comprimento de raízes, biomassa fresca e seca, índice mitótico e a frequência de anormalidades cromossômicas. Constataram-se maiores concentrações de Cd e Pb nas amostras de água coletadas nos meses com a ocorrência de precipitações pluviométricas. Água e sedimento apresentaram efeito fitotóxico sobre germinação, biomassa fresca e seca de Lactuca sativa. O comprimento de raízes foi estimulado e apenas as amostras de água reduziram o índice mitótico. Evidenciou-se, também, variação temporal significativa relacionada com o regime pluviométrico apenas para o teste de fitotoxicidade.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)UNIFAL Instituto de Ciências da NaturezaUNIFAL Instituto de Ciências ExatasUNIFESPUNIFESPSciEL