1,720,972 research outputs found
The feeding and reproductive strategies of Acartidae in Southampton Water
SIGLEAvailable from British Library Document Supply Centre- DSC:DXN059943 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Photoperiod and temperature regulation of diapause egg production in Acartia bifilosa from Southampton Water
In Southampton Water the copepod Acartia bifilosa presents a diapause reproductive strategy, where there is a switch from subitaneous to diapause egg production around May, prior to the species' disappearance from the water column between June and October. The effect of temperature and photoperiod on the production of diapause eggs by A. bifilosa was studied in an attempt to determine the primary cues for its summer diapause. A parallel study on the effect of temperature on metabolic efficiency of A. bifilosa and the non-diapause species A. discaudata, defined by the species' 'scope for growth' (SfG), was examined as a potential, ultimate reason behind the diapause stage. Photoperiod was identified as the primary proximate cue that induced diapause in A. bifilosa, and this response was temperature-mediated. Diapause was triggered by a 13:11 h light:dark photoperiod (day length), corresponding to a late-April photoperiodic regime, and resting eggs were produced even at temperatures as low as 5°C. A very low number of diapause eggs were, however, also produced after 6 d at a 12:12 h light:dark photoperiod at elevated temperatures between 14 and 20°C, but the mean percentage produced was significantly less (p < 0.05) than under the longer day lengths. The ultimate cause of the over-summering strategy of A. bifilosa is currently unknown, but the SfG assay indicated that at 10°C, SfG was twice that at 20 or 5°C, and so it may diapause to avoid the higher temperatures in summer. This pattern contrasted with the SfG of A. discaudata, which suggested a simple, positive relationship with temperature. In the field, competition is greatly reduced in the winter months, so A. bifilosa has a better chance of survival, even with its lower SfG
Enfortumab vedotin with pembrolizumab for first-line treatment of unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy [ID6332]: a single technology appraisal
This report is a critique of the company’s submission (CS) to NICE from Astellas Pharma Ltd on the clinical effectiveness and cost effectiveness of enfortumab vedotin with pembrolizumab for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy. It identifies the strengths and weaknesses of the CS
The pathway of cross-presentation is influenced by the particle size of phagocytosed antigen
Cross-presentation is the presentation by MHC class I of antigenic peptides from exogenous proteins that have been internalised and processed by professional antigen presenting cells, eg. dendritic cells (DC). We have investigated the influence of particle size and antigen load on cross-presentation following antigen delivery on microspheres (MS). Cross-presentation from small particles (0.8 ?m) is sensitive to proteasome inhibition and the blockade of ER-resident MHC class I complex export, whereas cross-presentation from larger particles (aggregated clumps of 0.8 ?m MS) is resistant to these antagonists. This observation may have been overlooked previously, due to the heterogeneity of particle size and MS uptake in unsorted DC populations. Whilst larger particles carry more antigen, we show that antigen load does not influence the cross-presentation pathway utilised. Whereas early endosome autoantigen 1 (EEA1) could be observed in all phagosomes, we observed endoplasmic reticulum SNARE of 24 kDa (ERS24) and cathepsin S in association with 3.0 ?m and aggregated 0.8 ?m MS, but not individual 0.8 ?m MS. A potential mechanism underlying our observations may be the activation of ?-catenin by disruption of E-cadherin-mediated adhesion. Activated ?-catenin was detected in the cytoplasm of cells after phagocytosis of MS (highest levels for the largest particles). We propose that particle size can direct the use of different pathways for the cross-presentation of an identical antigen. Furthermore, these pathways have differing yields of MHC class I-peptide complexes, which is an important variable in designing vaccination strategies for maximal antigen expression and CD8(+) T cell priming
Viral antigen mediated NKp46 activation of NK cells results in tumor rejection via NK-DC crosstalk
Natural killer (NK) cells play a critical role in antitumor immunity, their activation being regulated through NK cell receptors. Although the endogenous ligands for these receptors are largely unknown, viral ligands have been identified. We investigated the ability of an activating NK receptor ligand derived from the mumps virus, haemagglutinin-neuraminidase (HN) to enhance NK activation against tumor cells. HN-expressing B16.OVA tumor cells induced stronger activation of NK cells compared with B16.OVA cells and also promoted dendritic cell (DC) activation toward a DC1 phenotype, in vitro. Moreover, incubation of DCs, NK cells and HN-expressing B16-OVA cells further enhanced NK cell activation through the NK-DC crosstalk, in a cell-to-cell contact- and IL-12-dependent fashion. Immunization of mice with HN-expressing B16-OVA cells resulted in > 85% survival rate after subsequent challenge with parental B16 or B16.OVA tumor cells. Tumor rejection was dependent on both NK and CD8+ T cells but not on CD4+ T cells, demonstrating induction of an effective adaptive immune response through innate immune cell activation. Our data indicate the potential of using robust NK cell activation, which through the NK-DC crosstalk stimulates effective antitumor responses, providing an alternate vaccine strategy
Efgartigimod for treating generalised myasthenia gravis: a single technology appraisal
This report is a critique of the company’s submission (CS) to NICE from argenx on the clinical effectiveness and cost effectiveness of efgartigimod (Vyvgart®) for treating generalised myasthenia gravis (gMG). It identifies the strengths and weaknesses of the CS
Nintedanib for treating idiopathic pulmonary fibrosis in people with a forced vital capacity above 80% predicted (part-review of technology appraisal guidance 379): a single technology appraisal
Darolutamide with androgen deprivation therapy and docetaxel for treating hormone-sensitive metastatic prostate cancer: a single technology appraisal
This report is a critique of the company’s submission (CS) to NICE from Bayer on the clinical effectiveness and cost effectiveness of darolutamide + docetaxel + androgen deprivation therapy (ADT) for treating metastatic hormone-sensitive prostate cancer (mHSPC). It identifies the strengths and weakness of the CS
Bimekizumab for treating active psoriatic arthritis: a single technology appraisal
This report is a critique of the company’s submission (CS) to NICE from UCB Pharma on the clinical effectiveness and cost effectiveness of bimekizumab for treating psoriatic arthritis. It identifies the strengths and weaknesses of the CS
Glofitamab with gemcitabine and oxaliplatin for treating relapsed or refractory diffuse large B-cell lymphoma: A Single Technology Appraisal
This report is a critique of the company’s submission (CS) to NICE from Roche on theclinical effectiveness and cost effectiveness of glofitamab in combination with gemcitabine and oxaliplatin for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL). It identifies the strengths and weaknesses of the CS
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